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  1. Anti-tumour necrosis factor agent and liver injury: Literature review, recommendations for management

    PubMed Central

    Rossi, Roberta Elisa; Parisi, Ioanna; Despott, Edward John; Burroughs, Andrew Kenneth; O'Beirne, James; Conte, Dario; Hamilton, Mark Ian; Murray, Charles Daniel

    2014-01-01

    Abnormalities in liver function tests, including transient and self-limiting hypertransaminasemia, cholestatic disease and hepatitis, can develop during treatment with anti-tumour-necrosis-factor (TNF) therapy. The optimal management of liver injury related to anti-TNF therapy is still a matter of debate. Although some authors recommend discontinuing treatment in case of both a rise of alanine aminotransferase more than 5 times the upper limit of normal, or the occurrence of jaundice, there are no standard guidelines for the management of anti-TNF-related liver injury. Bibliographical searches were performed in PubMed, using the following key words: inflammatory bowel disease (IBD); TNF inhibitors; hypertransaminasemia; drug-related liver injury; infliximab. According to published data, elevation of transaminases in patients with IBD treated with anti-TNF is a common finding, but resolution appears to be the usual outcome. Anti-TNF agents seem to be safe with a low risk of causing severe drug-related liver injury. According to our centre experience, we found that hypertransaminasemia was a common, mainly self-limiting finding in our IBD cohort and was not correlated to infliximab treatment on both univariate and multivariate analyses. An algorithm for the management of liver impairment occurring during anti-TNF treatment is also proposed and this highlights the need of a multidisciplinary approach and suggests liver biopsy as a key-point in the management decision in case of severe rise of transaminases. However, hepatic injury is generally self-limiting and drug withdrawal seems to be an exception. PMID:25516646

  2. Interaction of thalidomide, phthalimide analogues of thalidomide and pentoxifylline with the anti-tumour agent 5,6-dimethylxanthenone-4-acetic acid: concomitant reduction of serum tumour necrosis factor-alpha and enhancement of anti-tumour activity.

    PubMed Central

    Ching, L. M.; Browne, W. L.; Tchernegovski, R.; Gregory, T.; Baguley, B. C.; Palmer, B. D.

    1998-01-01

    DMXAA (5,6-dimethylxanthenone-4-acetic acid), a novel anti-tumour agent currently undergoing clinical evaluation, appears to mediate its anti-tumour effects through immune modulation and the production of the cytokine tumour necrosis factor-alpha (TNF). Our previous studies have shown that thalidomide, a potent inhibitor of TNF biosynthesis that has numerous biological effects, including inhibition of tumour angiogenesis, unexpectedly augments the anti-tumour response in mice to DMXAA. We show here that thalidomide (100 mg kg(-1)) has no effect when administered with inactive doses of DMXAA, and that it must be given simultaneously with an active dose of DMXAA to have its maximum potentiating effect on the growth of the murine Colon 38 adenocarcinoma. To address the issue of whether inhibition of serum TNF production is important for potentiation of anti-tumour activity, we have tested three potent analogues of thalidomide. All three analogues, when co-administered with DMXAA to mice at doses lower than those used with thalidomide, inhibited TNF production and were effective in potentiating the anti-tumour activity of DMXAA against transplanted Colon 38 tumours. One of the analogues, N-phenethyltetrafluorophthalimide, was 1000-fold more potent than thalidomide and at a dose of 0.1 mg kg(-1) in combination with DMXAA (30 mg kg(-1)) cured 100% of mice, compared with 67% for the group treated with DMXAA alone. We also tested pentoxifylline and found it to suppress TNF production in response to DMXAA and to potentiate the anti-tumour effect of DMXAA. The results are compatible with the hypothesis that pharmacological reduction of serum TNF levels might benefit the anti-tumour effects of DMXAA and suggest new strategies for therapy using this agent. PMID:9703279

  3. Molecular design of hybrid tumour necrosis factor alpha with polyethylene glycol increases its anti-tumour potency.

    PubMed Central

    Tsutsumi, Y.; Kihira, T.; Tsunoda, S.; Kanamori, T.; Nakagawa, S.; Mayumi, T.

    1995-01-01

    This study was conducted to increase the anti-tumour potency and reduce the toxic side-effects of tumour necrosis factor alpha (TNF-alpha). Natural human TNF-alpha was chemically conjugated with monomethoxy polyethylene glycol (PEG) using succinimidyl coupling of lysine amino groups of TNF-alpha. The number-average molecular weight of PEG-modified TNF-alpha (PEG-TNF-alpha) increased with an increase in the reaction time and the initial molar ratio of PEG relative to TNF-alpha. The resulting modified TNF-alpha was separated into fractions of various molecular weights. The specific activity of separated PEG-TNF-alpha s relative to that of native TNF-alpha gradually decreased with an increase in the degree of PEG modification, but the plasma half-life was drastically increased with the increase in molecular weight of modified TNF-alpha. PEG-TNF-alpha s, in which 29% and 56% of lysine residues were coupled to PEG, had anti-tumour activity approximately 4 and 100 times greater than unmodified TNF-alpha in the murine Meth-A fibrosarcoma model. Extensive PEG modification did not increase its in vivo activity. A high dose of unmodified TNF-alpha induced toxic side-effects, but these were not observed with the modified TNF-alpha s. Optimal PEG modification of TNF-alpha markedly increased its bioavailability and may facilitate its potential anti-tumour therapeutic use. PMID:7734321

  4. Elevation of serum KL-6 in patients with psoriasis treated with anti-tumour necrosis factor-α therapy.

    PubMed

    Higashi, Y; Tada, K; Shimokawa, M; Kawai, K; Kanekura, T

    2016-01-01

    We report three patients with psoriasis whose serum level of Krebs Von Den Lungen (KL)-6 increased during therapy with anti-tumour necrosis factor (TNF)-α. A diagnosis of early-phase or subclinical interstitial pneumonia was made in two patients, and their KL-6 level decreased after anti-TNF-α discontinuation. The rise in KL-6 in the other patient was attributed to methotrexate. We propose that serum KL-6 should be monitored routinely in patients treated with anti-TNF agents. PMID:25557847

  5. Evolution of collagen arthritis in mice is arrested by treatment with anti-tumour necrosis factor (TNF) antibody or a recombinant soluble TNF receptor.

    PubMed Central

    Piguet, P F; Grau, G E; Vesin, C; Loetscher, H; Gentz, R; Lesslauer, W

    1992-01-01

    Immunization of DBA/1 mice with type II collagen within complete Freund's adjuvant leads to arthritis, lasting more than 3 months. Injection of anti-tumour necrosis factor (TNF) IgG, 2 and 3 weeks after immunization prevented the development of arthritis in the following months. This treatment had no effect when started 2 months after induction of the disease. A soluble form of the human recombinant TNF receptor type-beta (rsTNFR-beta), continuously infused at a rate of 20 micrograms/day during the second and third week after immunization, also had a long-term protective effect. Anti-TNF antibody had no effect upon the production of anti-type II collagen antibodies. These results indicate that TNF is critically involved in an early phase of this arthritis. Images Figure 1 Figure 2 PMID:1337334

  6. Biosimilars in immune-mediated inflammatory diseases: initial lessons from the first approved biosimilar anti-tumour necrosis factor monoclonal antibody.

    PubMed

    Isaacs, J D; Cutolo, M; Keystone, E C; Park, W; Braun, J

    2016-01-01

    The introduction of targeted biological therapies has revolutionised the management of immune-mediated inflammatory diseases (IMIDs) such as rheumatoid arthritis, ankylosing spondylitis, psoriasis and inflammatory bowel disease. Following treatment with these therapies, many patients experience significant improvements in different aspects of their disease, including symptoms, work productivity and other outcomes relevant for individuals and society. However, due to the complexity of biological drug development and manufacturing processes, the costs of these therapies are relatively high. Indeed, the financial burden on healthcare systems due to biological therapies is considerable and lack of patient access to effective treatment remains a concern in many parts of the world. As many reference biological therapies have now reached or are near to patent expiry, a number of 'biosimilar' drugs have been developed for use in various clinical settings, and some of these drugs are already in use in several countries. While the potential pharmacoeconomic benefits of cost-effective biosimilars seem clear, several issues have been raised regarding, for example, the definition of biosimilarity and the validity of indication extrapolation, as well as the 'switchability' and relative immunogenicity of biosimilars and their reference drugs. In this review, these issues will be discussed with reference to CT-P13, a biosimilar of the anti-tumour necrosis factor monoclonal antibody infliximab, which is approved in Europe and elsewhere for the treatment of various IMIDs. Other important issues, including those related to data collection during nonclinical and clinical development of biosimilars, are also discussed. PMID:26403380

  7. Risk of skin and soft tissue infections (including shingles) in patients exposed to anti-tumour necrosis factor therapy: results from the British Society for Rheumatology Biologics Register

    PubMed Central

    Galloway, James B; Mercer, Louise K; Moseley, Alison; Dixon, William G; Ustianowski, Andrew P; Helbert, Matthew; Watson, Kath D; Lunt, Mark; Hyrich, Kimme L; Symmons, Deborah PM

    2013-01-01

    Introduction Anti-tumour necrosis factor (TNF) therapy is a mainstay of treatment in rheumatoid arthritis (RA). In 2001, BSRBR was established to evaluate the safety of these agents. This paper addresses the safety of anti-TNF therapy in RA with specific reference to serious skin and soft tissue infections (SSSI) and shingles. Methods A cohort of anti-TNF-treated patients was recruited alongside a comparator group with active RA treated with non-biological disease-modifying antirheumatic drugs (nbDMARD). 11 881 anti-TNF and 3673 nbDMARD patients were analysed. Follow-up was by 6-monthly questionnaires to patients and clinicians. Analyses considered SSSI and shingles separately. Incidence rates (IR) were calculated and then compared using survival analyses. Results The crude IR for SSSI were: anti-TNF 1.6/100 patient-years (95% CI 1.4 to 1.8); nbDMARD 0.7/100 patient-years (95% CI 0.5 to 1.0) and shingles: anti-TNF 1.6/100 patient-years (95% CI 1.3 to 2.0); nbDMARD 0.8/100 patient-years (95% CI 0.6 to 1.1). Adjusted HR were SSSI 1.4 (95% CI 0.9 to 2.4), shingles 1.8 (95% CI 1.2 to 2.8). For SSSI, no significant differences were seen between anti-TNF agents. For shingles, the lowest risk was observed for adalimumab (adjusted HR vs nbDMARD) 1.5 (95% CI 1.1 to 2.0) and highest for infliximab (HR 2.2; 95% CI 1.4 to 3.4)). Conclusion A significantly increased risk of shingles was observed in the anti-TNF-treated cohort. The risk of SSSI tended towards being greater with anti-TNF treatment but was not statistically significant. As with any observational dataset cause and effect cannot be established with certainty as residual confounding may remain. This finding would support the evaluation of zoster vaccination in this population. PMID:22532633

  8. Anti-inflammatory effects of systemic anti-tumour necrosis factor α treatment in human/murine SCID arthritis

    PubMed Central

    Schadlich, H.; Ermann, J.; Biskop, M.; Falk, W.; Sperling, F.; Jungel, A.; Lehmann, J.; Emmrich, F.; Sack, U.

    1999-01-01

    OBJECTIVES—To evaluate in vivo the contribution of tumour necrosis factor α (TNFα) to the chimeric transfer model of human rheumatoid arthritis synovial membrane into SCID mice (hu/mu SCID arthritis), systemic anti-TNFα treatment was performed and the clinical, serological, and histopathological effects of this treatment assessed.
METHODS—Animals were treated with the rat-antimouse TNFα monoclonal antibody V1q, starting on day 1 after hu/mu engraftment, twice weekly for 12 weeks. Joint swelling, serum concentrations of human and murine interleukin 6 (IL6), and serum amyloid P (SAP) were measured. Histopathological and immunohistochemical analyses of the joints were also performed at the end of treatment.
RESULTS—Neutralisation of murine TNFα induced the following effects: (a) reduction of extent and duration of the acute arthritis phase, with significant reduction of joint swelling at two weeks; (b) decrease of murine SAP concentrations after the first antibody administration; and (c) increase of murine IL6 in the serum. At the end of treatment, there was a significant reduction of the inflammatory infiltration in the engrafted joints. Because of the mild degree of joint erosion, no treatment effects could be demonstrated on the destructive process.
CONCLUSION—In the lymphocyte independent hu/mu SCID arthritis, anti-TNFα treatment reduces local and systemic signs of inflammation.

 PMID:10381487

  9. Anti tumour necrosis-α therapy increases the number of FOXP3+ regulatory T cells in children affected by Crohn's disease

    PubMed Central

    Ricciardelli, Ida; Lindley, Keith J; Londei, Marco; Quaratino, Sonia

    2008-01-01

    Crohn's disease (CD) is a chronic inflammatory disease of the gastrointestinal tract. Its pathogenesis is not completely understood, though the prevailing model is that the intestinal flora drives a strong intestinal T helper 1 (Th1)/Th17 type immune response and inflammation in the genetically susceptible host. This leads to overly aggressive T-cell responses to normal bacteria causing tissue damage. Intestinal homeostasis and maintenance of tolerance to harmless antigens in the intestine has been shown to be maintained by CD4+ CD25+ T regulatory cells (Treg) in animal models of inflammatory bowel diseases. Here we investigated whether Infliximab, a chimeric monoclonal antibody directed against tumour necrosis factor (TNF)-α shown to be highly effective in the treatment of CD, has any effect on mucosal CD4+ CD25+ (FOXP3+) Tregs. Colonic mucosal biopsies from children with active Crohn's disease treated in vivo with Infliximab and controls were analysed to determine FOXP3 expression by immunofluorescence and reverse transcription–polymerase chain reaction. We observed that FOXP3+ T cells were significantly reduced in mucosa of CD patients with active disease compared with controls and restored to normal following Infliximab treatment. The frequency of FOXP3+ cells and mRNA expression was significantly increased in CD mucosa from patients treated in vivo with Infliximab compared with CD patients treated with conventional therapies. In conclusion, we show that Infliximab treatment does not solely neutralize soluble TNF-α, but also affects activation and possibly expansion of mucosal regulatory T cells. We suggest that anti TNF-α immunotherapy can also restore mucosal homeostasis in Crohn's disease. PMID:18422560

  10. Rheumatoid arthritis, anti-tumour necrosis factor treatment, and risk of squamous cell and basal cell skin cancer: cohort study based on nationwide prospectively recorded data from Sweden

    PubMed Central

    Simard, Julia F; Asker Hagelberg, Charlotte; Askling, Johan

    2016-01-01

    Objective To investigate the risk of squamous cell and basal cell skin cancer in patients with rheumatoid arthritis naive to biologic drugs, in patients starting tumour necrosis factor (TNF) inhibitor treatment, and in the general population. Design Population based cohort study. Setting Nationwide data from Sweden. Participants Cohort of patients with rheumatoid arthritis naive to biologics (n=46 409), cohort of patients with rheumatoid arthritis starting TNF inhibitor treatment as first biologic in 1998-2012 (n=12 558), and matched general population comparator cohort, identified through national quality of care and health registers. Main outcome measure Hazard ratio of first in situ or invasive squamous cell skin cancer (1998-2012) and first basal cell cancer (2004-12). Results For basal cell cancer, the hazard ratio was 1.22 (95% confidence interval 1.07 to 1.41) comparing biologics-naive rheumatoid arthritis patients with the general population and 1.14 (0.98 to 1.33; 236 v 1587 events) comparing TNF inhibitor treated patients with biologics-naive patients. For squamous cell cancer, the hazard ratio was 1.88 (1.74 to 2.03) comparing biologics-naive rheumatoid arthritis patients with the general population and 1.30 (1.10 to 1.55; 191 v 847 events) comparing TNF inhibitors with biologics-naive patients; the latter translated to an annual number needed to harm in the order of 1600. Among people with a history of squamous cell or basal cell cancer, TNF inhibitors did not further increase risks. Conclusion A small to moderately increased risk of basal cell cancer was seen in biologics-naive rheumatoid arthritis patients, with no further effect of TNF inhibitors. For squamous cell cancer, the risk was nearly doubled in biologics-naive patients, with a further 30% increase in risk among patients treated with TNF inhibitors; this translates to one additional case for every 1600 years of treatment experience, assuming that this association reflected causality

  11. Polymorphisms within the human leucocyte antigen-E gene and their associations with susceptibility to rheumatoid arthritis as well as clinical outcome of anti-tumour necrosis factor therapy.

    PubMed

    Iwaszko, M; Świerkot, J; Kolossa, K; Jeka, S; Wiland, P; Bogunia-Kubik, K

    2015-12-01

    Involvement of the non-classical human leucocyte antigen-E (HLA-E) in both innate and acquired immune response suggests its possible role in development of autoimmune pathologies. This study was undertaken to investigate relationships between the HLA-E gene single nucleotide polymorphisms (SNPs) and a risk of rheumatoid arthritis (RA), as well as to evaluate a potential of these polymorphisms to modulate clinical outcome of anti-tumour necrosis factor (TNF) treatment in female patients. A total of 223 female patients with RA receiving anti-TNF biological therapy and 134 female healthy subjects were enrolled into the study. Genotypings for two SNPs within the HLA-E gene (rs1264457 HLA-E*01:01/01:03; rs1059510 HLA-E*01:03:01/01:03:02) were performed using a polymerase chain reaction (PCR) amplification employing LightSNiP assays. Clinical response was evaluated according to the European League Against Rheumatism (EULAR) criteria at 12 and 24 weeks after initiation of the therapy. The frequency of the HLA-E*01:01/01:01 genotype was decreased significantly in RA patients in comparison to controls (P = 0.031). The presence of the HLA-E*01:01/01:01 genotype in patients correlated with better EULAR response after 12 weeks of anti-TNF treatment, while 01:03 allele carriers were generally unresponsive to the treatment (P = 0.014). The HLA-E*01:03/01:03 genotype was also over-represented among non-responding patients in comparison to HLA-E*01:01/01:01 homozygotes (P = 0.021). With respect to the HLA-E rs1059510 variation, a better response after 12 weeks was observed more frequently in patients carrying the HLA-E*01:03:01/01:03:01 genotype than other genotypes (P = 0.009). The results derived from this study imply that HLA-E polymorphisms may influence RA susceptibility and affect clinical outcome of anti-TNF therapy in female RA patients. PMID:26307125

  12. Rewiring macrophages for anti-tumour immunity.

    PubMed

    Lee, Yunqin; Biswas, Subhra K

    2016-06-28

    Tumour-associated macrophages facilitate cancer progression, but whether they can be reprogrammed to elicit an anti-tumour response remains unclear. Deletion of the microRNA-processing enzyme Dicer is now shown to rewire macrophages to an anti-tumour mode, leading to an enhanced response to immunotherapy and inhibition of tumour progression. PMID:27350442

  13. Photodynamic therapy and anti-tumour immunity

    PubMed Central

    Castano, Ana P.; Mroz, Pawel; Hamblin, Michael R.

    2010-01-01

    Photodynamic therapy (PDT) uses non-toxic photosensitizers and harmless visible light in combination with oxygen to produce cytotoxic reactive oxygen species that kill malignant cells by apoptosis and/or necrosis, shut down the tumour microvasculature and stimulate the host immune system. In contrast to surgery, radiotherapy and chemotherapy that are mostly immunosuppressive, PDT causes acute inflammation, expression of heat-shock proteins, invasion and infiltration of the tumour by leukocytes, and might increase the presentation of tumour-derived antigens to T cells. PMID:16794636

  14. MicroRNAs Involved in Anti-Tumour Immunity

    PubMed Central

    Yu, Hong W. H.; Sze, Daniel M. Y.; Cho, William C. S.

    2013-01-01

    MicroRNAs (miRNAs) are a category of small RNAs that constitute a new layer of complexity to gene regulation within the cell, which has provided new perspectives in understanding cancer biology. The deregulation of miRNAs contributes critically to the development and pathophysiology of a number of cancers. miRNAs have been found to participate in cell transformation and multiplication by acting as tumour oncogenes or suppressors; therefore, harnessing miRNAs may provide promising cancer therapeutics. Another major function of miRNAs is their activity as critical regulatory vehicles eliciting important regulatory processes in anti-tumour immunity through their influence on the development, differentiation and activation of various immune cells of both innate and adaptive immunity. This review aims to summarise recent findings focusing on the regulatory mechanisms of the development, differentiation, and proliferative aspects of the major immune populations by a diverse profile of miRNAs and may enrich our current understanding of the involvement of miRNAs in anti-tumour immunity. PMID:23478435

  15. The anti-tumour effects of zoledronic acid

    PubMed Central

    Zekri, Jamal; Mansour, Maged; Karim, Syed Mustafa

    2014-01-01

    Bone is the most common site for metastasis in patients with solid tumours. Bisphosphonates are an effective treatment for preventing skeletal related events and preserving quality of life in these patients. Zoledronic acid (ZA) is the most potent osteoclast inhibitor and is licensed for the treatment of bone metastases. Clodronate and pamidronate are also licensed for this indication. In addition, ZA has been demonstrated to exhibit antitumour effect. Direct and indirect mechanisms of anti-tumour effect have been postulated and at many times proven. Evidence exists that ZA antitumour effect is mediated through inhibition of tumour cells proliferation, induction of apoptosis, synergistic/additive to inhibitory effect of cytotoxic agents, inhibition of angiogenesis, decrease tumour cells adhesion to bone, decrease tumour cells invasion and migration, disorganization of cell cytoskeleton and activation of specific cellular antitumour immune response. There is also clinical evidence from clinical trials that ZA improved long term survival outcome in cancer patients with and without bone metastases. In this review we highlight the preclinical and clinical studies investigating the antitumour effect of bisphosphonates with particular reference to ZA. PMID:26909294

  16. Regression of Sweet's syndrome associated with Crohn's disease after anti-Tumour Necrosis Factor therapy.

    PubMed

    Rahier, J F; Lion, L; Dewit, O; Lambert, M

    2005-01-01

    The association of inflammatory bowel disease and acute febrile neutrophilic dermatitis (Sweet's syndrome) has infrequently been reported in the literature. We describe the case of a 41-year-old Caucasian woman with ileo- anal Crohn's disease who presented simultaneously an erythema nodosum and a Sweet's syndrome. A dramatic regression of the cutaneous lesions was observed after infliximab treatment, indicating that this therapy might be useful for both Crohn's disease and Sweet's syndrome. PMID:16268426

  17. Goshajinkigan reduces oxaliplatin-induced peripheral neuropathy without affecting anti-tumour efficacy in rodents.

    PubMed

    Ushio, Soichiro; Egashira, Nobuaki; Sada, Hikaru; Kawashiri, Takehiro; Shirahama, Masafumi; Masuguchi, Ken; Oishi, Ryozo

    2012-06-01

    Oxaliplatin is a key drug in the treatment of colorectal cancer, but it causes acute and chronic neuropathies in patients. Goshajinkigan (GJG) is a Kampo medicine that is used for the treatments of several neurological symptoms including pain and numbness. More recently, GJG has been reported to prevent the oxaliplatin-induced peripheral neuropathy in clinical studies. No experimental study, however, has been conducted to date to determine the effect of GJG on pain behaviour in a rat model of oxaliplatin-induced neuropathy. Moreover, the impact on the anti-tumour effect of oxaliplatin remains unknown. In the present study, we examined the effects of GJG on the peripheral neuropathy and anti-tumour activity of oxaliplatin in rodents. Repeated administration of oxaliplatin caused cold hyperalgesia from days 3 to 37 and mechanical allodynia from days 21 to 28. Repeated administration of GJG prevented the oxaliplatin-induced cold hyperalgesia but not mechanical allodynia and axonal degeneration in rat sciatic nerve. Single administration of GJG reduced both cold hyperalgesia and mechanical allodynia after the development of neuropathy. In addition, GJG did not affect the anti-tumour effect of oxaliplatin in the tumour cells or tumour cells-implanted mice. These results suggest that GJG relieves the oxaliplatin-induced cold hyperalgesia and mechanical allodynia without affecting anti-tumour activity of oxaliplatin, and, therefore, may be useful for the oxaliplatin-induced neuropathy in clinical practice. PMID:21907570

  18. Effects of nandrolone decanoate on the toxicity and anti-tumour action of CCNU and FU in murine tumours.

    PubMed Central

    Bibby, M. C.; Double, J. A.; Mughal, M. A.

    1981-01-01

    Pre-treatment with the anabolic steroid nandrolone decanoate (ND) increases the LD50 of 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU) and 5-Fluorouracil (FU) in NMRI mice. Administration of ND did not affect the anti-tumour action of CCNU against a transplantable mouse adenocarcinoma of the colon (MAC 13) or the anti-tumour action of FU against MAC 26. In both tumour lines ND had no significant effect on tumour growth. These data suggest that an increase in the anti-tumour selectivity of these agents may be produced by pre-treatment with ND. PMID:7295514

  19. Anti-tumour immunity in malignant melanoma assay by tube leucocyte adherence inhibition.

    PubMed Central

    Marti, J. H.; Thomson, D. M.

    1976-01-01

    Tumour antigen-induced inhibition of leucocyte adherence was modified for use in glass test tubes (Tube LAI assay) for the study of cell-mediated anti-tumour immunity to human malignant melanoma. Peripheral blood leucocytes (PBL) of 20 out of 25 patients (80%) with active malignant melanoma responded to an extract of malignant melanoma with LAI, whereas only 4-5% of 475 control subjects showed a response. The malignant melanoma patients reacted to both allogeneic and autologous extracts of malignant melanoma which indicates a common cross-reacting antigen. Malignant melanoma patients did not respond to unrelated tumour extracts. The LAI was mediated by PBL (monocytes) "armed" with cytophilic anti-tumour antibody specific for the sensitizing tumour antigen. The anti-tumour response of the malignant melanoma patients was dependent on the stage of the cancer, and 11 out of 13 Stage I patients had a positive NAI, whereas patients with disseminated cancer had decreased response. The diminished LAI in patients with large tumour burdens appeared to be the result of release of tumour antigen systemically. Also, surgery and chemotherapy depressed LAI. Although LAI was depressed after surgical excision of the cutaneous melanoma, most patients showed LAI 1-3 months later. Tumour-free melanoma patients monitored for one year by the Tube LAI assay showed a decline in their anti-tumour immunity 5-6 months after surgery. The NAI was low or negative after the 8th post-surgical month in tumour-free patients. Patients with residual malignant melanoma showed persistent or recurrent LAI after the 8th post-surgical month. LAI reactivity monitored after "curative" surgery for malignant melanoma may assist in determining whether the patient is tumour-free or has a recurrence. PMID:962991

  20. Which alkylglycerols from shark liver oil have anti-tumour activities?

    PubMed

    Deniau, Anne-Laure; Mosset, Paul; Le Bot, Damien; Legrand, Alain B

    2011-01-01

    Alkylglycerols (alkyl-Gro) are ether lipids abundant in shark liver oil (SLO), and oral SLO or alkyl-Gro mix from this source have several in vivo biological activities including stimulation of haematopoiesis an immunological defences, or anti-tumour and anti-metastasis activities in vivo. Composition of natural alkyl-Gro mix contains several alkyl-Gro varying by chain length and unsaturation, and individual anti-tumour activity of each molecule present in natural mix remained unknown. We synthesized six prominent constituents of natural alkyl-Gro mix, namely 12:0, 14:0 16:0, 18:0, 16:1 n-7, and 18:1 n-9 alkyl-Gro. Using an in vivo model of grafted tumour in mice (3LL cells), we studied and compared the oral anti-tumour and anti-metastasis activities of each of these 6 alkyl-Gro. 16:1 and 18:1 alkyl-Gro showed strong activity in reducing lung metastasis number, while saturated alkyl-Gro had weaker (16:0) or no (12:0, 14:0, 18:0) effect. Spleen weights at day 20 after graft were also measured and showed tremendous variations depending on the treatment. Tumour graft resulted in a raise in spleen weight in control group, this raise was nearly abolished in 16:1 and 18:1 alkyl-Gro-treated mice, and was reduced in 14:0 and 16:0 alkyl-Gro-treated mice. Conversely, 18:0 alkyl-Gro-treated mice showed spleen weigh raise as compared with untreated grafted mice. These new data demonstrate a prominent role of unsaturation in the anti-tumour activities of alkyl-Gro. PMID:20036307

  1. Fractionated Radiotherapy with 3 x 8 Gy Induces Systemic Anti-Tumour Responses and Abscopal Tumour Inhibition without Modulating the Humoral Anti-Tumour Response

    PubMed Central

    Habets, Thomas H. P. M.; Oth, Tammy; Houben, Ans W.; Huijskens, Mirelle J. A. J.; Senden-Gijsbers, Birgit L. M. G.; Schnijderberg, Melanie C. A.; Brans, Boudewijn; Dubois, Ludwig J.; Lambin, Philippe; De Saint-Hubert, Marijke; Germeraad, Wilfred T. V.; Tilanus, Marcel G. J.; Mottaghy, Felix M.

    2016-01-01

    Accumulating evidence indicates that fractionated radiotherapy (RT) can result in distant non-irradiated (abscopal) tumour regression. Although preclinical studies indicate the importance of T cells in this infrequent phenomenon, these studies do not preclude that other immune mechanisms exhibit an addition role in the abscopal effect. We therefore addressed the question whether in addition to T cell mediated responses also humoral anti-tumour responses are modulated after fractionated RT and whether systemic dendritic cell (DC) stimulation can enhance tumour-specific antibody production. We selected the 67NR mammary carcinoma model since this tumour showed spontaneous antibody production in all tumour-bearing mice. Fractionated RT to the primary tumour was associated with a survival benefit and a delayed growth of a non-irradiated (contralateral) secondary tumour. Notably, fractionated RT did not affect anti-tumour antibody titers and the composition of the immunoglobulin (Ig) isotypes. Likewise, we demonstrated that treatment of tumour-bearing Balb/C mice with DC stimulating growth factor Flt3-L did neither modulate the magnitude nor the composition of the humoral immune response. Finally, we evaluated the immune infiltrate and Ig isotype content of the tumour tissue using flow cytometry and found no differences between treatment groups that were indicative for local antibody production. In conclusion, we demonstrate that the 67NR mammary carcinoma in Balb/C mice is associated with a pre-existing antibody response. And, we show that in tumour-bearing Balb/C mice with abscopal tumour regression such pre-existing antibody responses are not altered upon fractionated RT and/or DC stimulation with Flt3-L. Our research indicates that evaluating the humoral immune response in the setting of abscopal tumour regression is not invariably associated with therapeutic effects. PMID:27427766

  2. Anti-tumour effect of metformin in canine mammary gland tumour cells.

    PubMed

    Saeki, K; Watanabe, M; Tsuboi, M; Sugano, S; Yoshitake, R; Tanaka, Y; Ong, S M; Saito, T; Matsumoto, K; Fujita, N; Nishimura, R; Nakagawa, T

    2015-08-01

    Metformin is an oral hypoglycaemic drug used in type 2 diabetes. Its pharmacological activity reportedly involves mitochondrial respiratory complex I, and mitochondrial respiratory complex inhibitors have a strong inhibitory effect on the growth of metastatic canine mammary gland tumour (CMGT) cell lines. It is hypothesised that metformin has selective anti-tumour effects on metastatic CMGT cells. The aim of this study was to investigate the in vitro effect of metformin on cell growth, production of ATP and reactive oxygen species (ROS), and the AMP-activated protein kinase (AMPK) mammalian target of rapamycin (mTOR) pathway in two CMGT clonal cell lines with different metastatic potential. In addition, transcriptome analysis was used to determine cellular processes disrupted by metformin and in vivo anti-tumour effects were examined in a mouse xenograft model. Metformin inhibited CMGT cell growth in vitro, with the metastatic clone (CHMp-5b) displaying greater sensitivity. ATP depletion and ROS elevation were observed to a similar extent in the metastatic and non-metastatic (CHMp-13a) cell lines after metformin exposure. However, subsequent AMPK activation and mTOR pathway inhibition were prominent only in metformin-insensitive non-metastatic cells. Microarray analysis revealed inhibition of cell cycle progression by metformin treatment in CHMp-5b cells, which was further confirmed by Western blotting and cell cycle analysis. Additionally, metformin significantly suppressed tumour growth in xenografted metastatic CMGT cells. In conclusion, metformin exhibited an anti-tumour effect in metastatic CMGT cells through AMPK-independent cell cycle arrest. Its mechanism of action differed in the non-metastatic clone, where AMPK activation and mTOR inhibition were observed. PMID:25981932

  3. Stimulation of anti-tumour immunity in guinea-pigs by methanol extraction residue of BCG.

    PubMed Central

    Wainberg, M. A.; Deutsch, V.; Weiss, D. W.

    1976-01-01

    The immunoprophylactic effects of the methanol extraction residue (MER) of BCG were investigated in Strain 2 guinea-pigs injected with cells of the transplantable, diethylnitrosamine-induced, Line 10 hepatocarcinoma. Pretreatment with MER at times ranging from 18 to 182 days prior to tumour implantation protected approximately 40% of guinea-pigs from progressive neoplastic disease. In addition, MER-treated animals developed specific cell-mediated anti-tumour immunity both more rapidly and at higher levels than did non-MER-treated tumour-bearing controls. It was not possible, however, to prognosticate from the results of such laboratory studies to the outcome of immunoprophylaxis. PMID:187207

  4. Raloxifene Inhibits NF-kB Pathway and Potentiates Anti-Tumour Activity of Cisplatin with Simultaneous Reduction in its Nephrotoxictiy.

    PubMed

    Jamdade, Vinayak Sudhir; Mundhe, Nitin A; Kumar, Parveen; Tadla, Venkatesh; Lahkar, Mangala

    2016-01-01

    Cisplatin induced nephrotoxicity is the chief obstacle in the use of cisplatin as chemotherapeutic agent. However, it remains as most widely employed anticancer agent to treat various solid tumours like head-neck, testicular, ovarian and mammary gland cancer. Raloxifene is claimed to be potent anti-inflammatory as well as anti-cancer agent. The present study was carried out to explore the effect of pre-treatment of raloxifene on cisplatin induced nephrotoxicity and its anti-tumour activity in 7, 12 dimethyl benz [a] anthracene induced mammary tumour in animal model. Renal damage was accessed by measuring serum level of creatinine, blood urea nitrogen and albumin whereas systemic inflammation was accessed by measuring level of pro-inflammatory cytokines like tumour necrosis factor alpha (TNF-α), interleukin 6 (IL-6), interleukin 10 (IL-10) and nuclear factor kappa B (NFκB). Moreover, assessment of tumour reduction was done by measuring tumour volume and percentage tumour reduction. A single dose of cisplatin (7.5 mg/kg) resulted in significant increase in serum creatinine, blood urea nitrogen, NF-kB, TNF-α and IL-6 levels along with decrease in albumin and IL-10 levels. However, there were no significant changes in raloxifene (8 mg/kg) treated group. Pre-treatment of raloxifene (8 mg/kg) caused marked decrease in serum creatinine, blood urea nitrogen, TNF-α and IL-6 levels whereas increase in albumin and IL-10 levels. However, pre-treatment of raloxifene showed maximum tumour reduction as compared to cisplatin and raloxifene treated groups. The present study demonstrates that raloxifene potentiates anti-tumour activity of cisplatin with simultaneous reduction in its nephrotoxicity, and this effect is attributed to its direct anti-inflammatory activity. PMID:26439246

  5. Anti-tumour synergy of cytotoxic chemotherapy and anti-CD40 plus CpG-ODN immunotherapy through repolarization of tumour-associated macrophages

    PubMed Central

    Buhtoiarov, Ilia N; Sondel, Paul M; Wigginton, Jon M; Buhtoiarova, Tatiana N; Yanke, Eric M; Mahvi, David A; Rakhmilevich, Alexander L

    2011-01-01

    We studied the effectiveness of monoclonal anti-CD40 + cytosine–phosphate–guanosine-containing oligodeoxynucleotide 1826 (CpG-ODN) immunotherapy (IT) in mice treated with multidrug chemotherapy (CT) consisting of vincristine, cyclophosphamide and doxorubicin. Combining CT with IT led to synergistic anti-tumour effects in C57BL/6 mice with established B16 melanoma or 9464D neuroblastoma. CT suppressed the functions of T cells and natural killer (NK) cells, but primed naïve peritoneal macrophages (Mφ) to in vitro stimulation with lipopolysaccharide (LPS), resulting in augmented nitric oxide (NO) production. IT, given after CT, did not restore the responsiveness of T cells and NK cells, but further activated Mφ to secrete NO, interferon-γ (IFN-γ) and interleukin (IL)-12p40 and to suppress the proliferation of tumour cells in vitro. These functional changes were accompanied by immunophenotype alterations on Mφ, including the up-regulation of Gr-1. CD11b+F4/80+Mφ comprised the major population of B16 tumour-infiltrating leucocytes. CT + IT treatment up-regulated molecules associated with the M1 effector Mφ phenotype [CD40, CD80, CD86, major histocompatibility complex (MHC) class II, IFN-γ, tumour necrosis factor-α (TNF-α) and IL-12] and down-regulated molecules associated with the M2 inhibitory Mφ phenotype (IL-4Rα, B7-H1, IL-4 and IL-10) on the tumour-associated Mφ compared with untreated controls. Together, the results show that CT and anti-CD40 + CpG-ODN IT synergize in the induction of anti-tumour effects which are associated with the phenotypic repolarization of tumour-associated Mφ. PMID:21039467

  6. CD169 identifies an anti-tumour macrophage subpopulation in human hepatocellular carcinoma.

    PubMed

    Zhang, Yi; Li, Jin-Qing; Jiang, Ze-Zhou; Li, Lian; Wu, Yan; Zheng, Limin

    2016-06-01

    Macrophages are a major component of most solid tumours and can exert both anti- and pro-tumourigenic functions. Although the immunosuppressive/pro-tumour roles of macrophages have been widely examined, significantly less is known about macrophage subpopulations that have potential anti-tumour properties in humans. In the present study, a population of CD169(+) macrophages with relatively high expression levels of HLA-DR and CD86 was identified in human hepatocellular carcinoma tissues. The frequency of CD169-expressing macrophages within cancer nests was significantly lower than that found in paired non-tumour areas. In vitro experiments revealed that in the presence of anti-CD3 stimulation, CD169(+) macrophages could significantly enhance the proliferation, cytotoxicity, and cytokine production capacity of CD8(+) T cells in a CD169 molecule-dependent manner. Autocrine TGF-β produced by tumour-stimulated macrophages was involved in the down-regulation of CD169 expression on these cells. Moreover, the accumulation of CD169(+) macrophages in tumour tissues was negatively associated with disease progression and predicted favourable survival in hepatocellular carcinoma patients, which was in contrast to the trend observed for total CD68(+) macrophages. Therefore, CD169 might act as a co-stimulatory molecule for cytotoxic T-cell activation, and could define a population of tumour-infiltrating macrophages with potential anti-tumour properties in human hepatocellular carcinoma tissues. Copyright © 2016 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. PMID:27174787

  7. Anti-tumour promoting activity of diphenylmethyl selenocyanate against two-stage mouse skin carcinogenesis.

    PubMed

    Das, Rajat Kumar; Bhattacharya, Sudin

    2005-01-01

    Epidemiological, clinical and experimental evidence collectively suggests that Se in different inorganic and organic forms provides a potential cancer chemopreventive agent, active against several types of cancer. It can exert preventive activity in all the three stages of cancer: initiation, promotion and progression. Literature reports revealed that organoselenocyanates have more potential as chemopreventive agents than inorganic forms due to their lower toxicity. In our previous report we showed chemopreventive efficacy of diphenylmethyl selenocyanate during the initiation and pre- plus post-initiation phases of skin and colon carcinogenesis process. The present study was undertaken to explore the anti-tumour promoting activity of diphenylmethyl selenocyanate in a 7,12-dimethylbenz (a) anthracene (DMBA)-croton oil two-stage skin carcinogenesis model. The results obtained showed significant (p<0.01) reduction of the incidence and number of skin papillomas, precancerous skin lesions, along with significant (p<0.01) elevation of phase II detoxifying enzymes (GST, Catalase and SOD) and inhibition of lipid peroxidation in liver and skin. Thus, the present data strongly suggest that diphenylmethyl selenocyanate also has the potential to act as anti-tumour promoter agent in a two-stage skin carcinogenesis mouse model, pointing to possible general efficacy. PMID:16101330

  8. Polyphenolic compounds with anti-tumour potential from Corchorus olitorius (L.) Tiliaceae, a Nigerian leaf vegetable.

    PubMed

    Taiwo, Bamigboye J; Taiwo, Grace O; Olubiyi, Olujide O; Fatokun, Amos A

    2016-08-01

    Chromatographic fractionation of the methanolic extract of Corchorus olitorius (L.) (Tiliaceae), on silica gel yielded two polyphenolic compounds. The structures of the compounds were elucidated as Methyl-1,4,5-tri-O-caffeoyl quinate and trans-3-(4-Hydroxy-3-methoxyphenyl)acrylic anhydride, based on extensive use of spectroscopic techniques such as (1)H and (13)C NMR, DEPT and 2D NMR experiments (COSY, HSQC, HMBC), IR and MS. To establish an initial proof-of-concept for the biological relevance of these compounds, their cytotoxicity against the cancer cell lines HeLa, HL460 and PC3, which might indicate their anti-tumour potential, was assessed. The compounds when tested at a range of concentrations up to 1.6mM were found to possess mild cytotoxic activity which was significant against HeLa cells at ⩾800μM. The trans-3-(4-Hydroxy-3-methoxyl phenyl)acrylic anhydride was found to be related to curcumin, a compound known to have anti-cancer activity. Docking of each of the two compounds and also of curcumin into some molecular targets implicated in tumourigenesis revealed that the three compounds had binding affinities that were superior to those obtained for the co-crystallized inhibitors of metalloproteinase-9, fibroblast growth factor receptor 2 (FGFR2) and epidermal growth factor receptor (EGFR). The plant Corchorus olitorius therefore represents a potential source of natural 'lead' compounds with anti-tumour potential. PMID:27381082

  9. Bortezomib-induced pro-inflammatory macrophages as a potential factor limiting anti-tumour efficacy.

    PubMed

    Beyar-Katz, Ofrat; Magidey, Ksenia; Ben-Tsedek, Neta; Alishekevitz, Dror; Timaner, Michael; Miller, Valeria; Lindzen, Moshit; Yarden, Yosef; Avivi, Irit; Shaked, Yuval

    2016-07-01

    Multiple myeloma (MM) is a chronic progressive malignancy of plasma cells. Although treatment with the novel proteasome inhibitor, bortezomib, significantly improves patient survival, some patients fail to respond due to the development of de novo resistance. We have previously shown that cytotoxic drugs can induce pro-tumorigenic host-mediated effects which contribute to tumour re-growth and metastasis, and thus limit anti-tumour efficacy. However, such effects and their impact on tumour cell aggressiveness have not been investigated using cytostatic agents such as bortezomib. Here we show that plasma from bortezomib-treated mice significantly increases migration, viability and proliferation of MM cells in vitro, compared to plasma from vehicle treated mice. In vivo, bortezomib induces the mobilization of pro-angiogenic bone marrow cells. Furthermore, mice treated with bortezomib and subsequently were used as recipients for an injection of MM cells succumb to MM earlier than mice treated with the vehicle. We show that bortezomib promotes pro-inflammatory macrophages which account for MM cell aggressiveness, an effect which is partially mediated by interleukin-16. Accordingly, co-inoculation of MM cells with pro-inflammatory macrophages from bortezomib-treated mice accelerates MM disease progression. Taken together, our results suggest that, in addition to the known effective anti-tumour activity of bortezomib, host-driven pro-tumorigenic effects generated in response to treatment can promote MM aggressiveness, and thus may contribute to the overall limited efficacy. Copyright © 2016 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. PMID:27037906

  10. Salmonella enterica serovar Typhimurium immunotherapy for B-cell lymphoma induces broad anti-tumour immunity with therapeutic effect

    PubMed Central

    Grille, Sofía; Moreno, María; Bascuas, Thais; Marqués, Juan M; Muñoz, Natalia; Lens, Daniela; Chabalgoity, Jose A

    2014-01-01

    Despite the efficacy of current immune-chemotherapy for treatment of B-cell non-Hodgkin lymphoma, a substantial proportion of patients relapse, highlighting the need for new therapeutic modalities. The use of live microorganisms to develop anti-tumoural therapies has evolved since Coley's toxin and is now receiving renewed attention. Salmonella Typhimurium has been shown to be highly effective as an anti-tumour agent in many solid cancer models, but it has not been used in haemato-oncology. Here, we report that intra-tumoural administration of LVR01 (attenuated S. Typhimurium strain with safety profile) elicits local and systemic anti-tumour immunity, resulting in extended survival in a lymphoma model. LVR01 induces intra-tumoural recruitment of neutrophils and activated CD8+ T cells, as well as increasing the natural killer cell activation status. Furthermore, a systemic specific anti-tumour response with a clear T helper type 1 profile was observed. This approach is an alternative therapeutic strategy for lymphoma patients that could be easily moved into clinical trials. PMID:24834964

  11. Anti-tumour strategies aiming to target tumour-associated macrophages

    PubMed Central

    Tang, Xiaoqiang; Mo, Chunfen; Wang, Yongsheng; Wei, Dandan; Xiao, Hengyi

    2013-01-01

    Tumour-associated macrophages (TAMs) represent a predominant population of inflammatory cells that present in solid tumours. TAMs are mostly characterized as alternatively activated M2-like macrophages and are known to orchestrate nearly all stages of tumour progression. Experimental investigations indicate that TAMs contribute to drug-resistance and radio-protective effects, and clinical evidence shows that an elevated number of TAMs and their M2 profile are correlated with therapy failure and poor prognosis in cancer patients. Recently, many studies on TAM-targeted strategies have made significant progress and some pilot works have achieved encouraging results. Among these, connections between some anti-tumour drugs and their influence on TAMs have been suggested. In this review, we will summarize recent advances in TAM-targeted strategies for tumour therapy. Based on the proposed mechanisms, those strategies are grouped into four categories: (i) inhibiting macrophage recruitment; (ii) suppressing TAM survival; (iii) enhancing M1-like tumoricidal activity of TAMs; (iv) blocking M2-like tumour-promoting activity of TAMs. It is desired that further attention be drawn to this research field and more effort be made to promote TAM-targeted tumour therapy. PMID:23113570

  12. Targeting ALCAM in the cryo-treated tumour microenvironment successfully induces systemic anti-tumour immunity.

    PubMed

    Kudo-Saito, Chie; Fuwa, Takafumi; Kawakami, Yutaka

    2016-07-01

    Cryoablative treatment has been widely used for treating cancer. However, the therapeutic efficacies are still controversial. The molecular mechanisms of the cryo-induced immune responses, particularly underlying the ineffectiveness, remain to be fully elucidated. In this study, we identified a new molecular mechanism involved in the cryo failure. We used cryo-ineffective metastatic tumour models that murine melanoma B16-F10 cells were subcutaneously and intravenously implanted into C57BL/6 mice. When the subcutaneous tumours were treated cryoablation on day 7 after tumour implantation, cells expressing activated leucocyte cell adhesion molecule (ALCAM/CD166) were significantly expanded not only locally in the treated tumours but also systemically in spleen and bone marrow of the mice. The cryo-induced ALCAM(+) cells including CD45(-) mesenchymal stem/stromal cells, CD11b(+)Gr1(+) myeloid-derived suppressor cells, and CD4(+)Foxp3(+) regulatory T cells significantly suppressed interferon γ production and cytotoxicity of tumour-specific CD8(+) T cells via ALCAM expressed in these cells. This suggests that systemic expansion of the ALCAM(+) cells negatively switches host-immune directivity to the tumour-supportive mode. Intratumoural injection with anti-ALCAM blocking monoclonal antibody (mAb) following the cryo treatment systemically induced tumour-specific CD8(+) T cells with higher cytotoxic activities, resulting in suppression of tumour growth and metastasis in the cryo-resistant tumour models. These suggest that expansion of ALCAM(+) cells is a determinant of limiting the cryo efficacy. Further combination with an immune checkpoint inhibitor anti-CTLA4 mAb optimized the anti-tumour efficacy of the dual-combination therapy. Targeting ALCAM may be a promising strategy for overcoming the cryo ineffectiveness leading to the better practical use of cryoablation in clinical treatment of cancer. PMID:27208904

  13. Systemic anti-tumour effects of local thermally sensitive liposome therapy

    PubMed Central

    Viglianti, Benjamin L.; Dewhirst, Mark W.; Boruta, R.J.; Park, Ji-Young; Landon, Chelsea; Fontanella, Andrew N.; Guo, Jing; Manzoor, Ashley; Hofmann, Christina L.; Palmer, Gregory M.

    2015-01-01

    Purpose There were two primary objectives of this study: (1) to determine whether treatment of a tumour site with systemically administered thermally sensitive liposomes and local hyperthermia (HT) for triggered release would have dual anti-tumour effect on the primary heated tumour as well as an unheated secondary tumour in a distant site, and (2) to determine the ability of non-invasive optical spectroscopy to predict treatment outcome. The optical end points studied included drug levels, metabolic markers flavin adenine dinucleotide (FAD), nicotinamide adenine dinucleotide phosphate (NAD(P)H), and physiological markers (total haemoglobin (Hb) and Hb oxygen saturation) before and after treatment. Materials and methods Mice were inoculated with SKOV3 human ovarian carcinoma in both hind legs. One tumour was selected for local hyperthermia and subsequent systemic treatment. There were four treatment groups: control, DOXIL® (non-thermally sensitive liposomes containing doxorubicin), and two different thermally sensitive liposome formulations containing doxorubicin. Optical spectroscopy was performed prior to therapy, immediately after treatment, and 6, 12, and 24 h post therapy. Results Tumour growth delay was seen with DOXIL and the thermally sensitive liposomes in the tumours that were heated, similar to previous studies. Tumour growth delay was also seen in the opposing tumour in the thermally sensitive liposome-treated groups. Optical spectroscopy demonstrated correlation between growth delay, doxorubicin (DOX) levels, and changes of NAD(P)H from baseline levels. Hb and Hb saturation were not correlated with growth delay. Discussion The study demonstrated that thermally sensitive liposomes affect the primary heated tumour as well as systemic efficacy. Non-invasive optical spectroscopy methods were shown to be useful in predicting efficacy at early time points post-treatment. PMID:25164143

  14. Regulation of local and metastatic host-mediated anti-tumour mechanisms by l-selectin and intercellular adhesion molecule-1

    PubMed Central

    Yamada, M; Yanaba, K; Hasegawa, M; Matsushita, Y; Horikawa, M; Komura, K; Matsushita, T; Kawasuji, A; Fujita, T; Takehara, K; Steeber, D A; Tedder, T F; Sato, S

    2006-01-01

    Malignant melanoma is often accompanied by a host response of inflammatory cell infiltration that is highly regulated by multiple adhesion molecules. To assess the role of adhesion molecules, including l-selectin and intercellular adhesion molecule-1 (ICAM-1), in this process, subcutaneous primary growth and metastasis to the lung of B16 melanoma cells not expressing l-selectin, ICAM-1 or their ligands were examined in mice lacking l-selectin, ICAM-1 or both. Primary subcutaneous growth of B16 melanoma was augmented by loss of l-selectin, ICAM-1 or both, while pulmonary metastasis was enhanced by the loss of l-selectin or combined loss of l-selectin and ICAM-1. In both situations, the combined loss of l-selectin and ICAM-1 exhibited the greatest effect. This enhancement was associated generally with a reduced accumulation of natural killer (NK) cells, CD4+ T cells and CD8+ T cells and also with a diminished release of interferon (IFN)-γ and tumour necrosis factor (TNF)-α but not interleukin (IL)-6. Cytotoxicity against melanoma was not defective by the absence of ICAM-1, l-selectin or both, suggesting that the enhancement of tumour growth and metastasis caused by the loss of adhesion molecules results from an impaired migration of effector cells into the tissue rather than from a suppression of the cytotoxic response. The results indicate that l-selectin and ICAM-1 contribute co-operatively to the anti-tumour reaction by regulating lymphocyte infiltration to the tumour. PMID:16412045

  15. Induction of anti-tumour lymphocytes in cancer patients after brief exposure to supernatants from cultures of anti-CD3-stimulated allogeneic lymphocytes.

    PubMed Central

    Baxevanis, C. N.; Tsiatas, M. L.; Cacoullos, N. T.; Spanakos, G.; Liacos, C.; Missitzis, I.; Papadhimitriou, S. I.; Papamichail, M.

    1997-01-01

    The present study investigated the ability of supernatants collected from cultures of healthy donor-derived peripheral blood mononuclear cells (HD-PBMCs) stimulated with anti-CD3 monoclonal antibody (MAb) (allogeneic CD3 supernatants; ACD3S) to induce, upon brief exposure, tumour-reactive cytotoxic lymphocytes in cancer patients' PBMCs. ACD3S enhanced natural killer (NK) and lymphokine-activated killer (LAK) cell-mediated cytotoxicity. ACD3S contained increased levels of interleukins (IL) 1, 2, 6, 7 and 12, as well as of granulocyte-macrophage colony-stimulating factor (GM-CSF), gamma-interferon (IFN-gamma) and tumour necrosis factor-alpha (TNF-alpha). MAbs against these cytokines significantly reduced the ACD3S-induced cytotoxicity. ACD3S-induced cytotoxicity was not inhibited by anti-CD4, CD8 and MHC class I MAbs, but was markedly reduced in the presence of MAb against CD18. In contrast to HD-PBMC, ACD3S derived from cancer patients' lymphocytes exhibited lower levels of the above-mentioned cytokines and exerted reduced biological activity. In conclusion, ACD3S are able to activate, upon short-term incubation, tumour-reactive lymphocytes from cancer patients' PBMCs that lyse a variety of tumour targets, including autologous tumours. ACD3S contain high levels of certain cytokines that positively influence the induction of autologous tumour-reactive lymphocytes. Such supernatants can be collected easily from healthy donors and stored until use in clinical trials for adoptive cellular therapy of cancer. They may also be indicated in the construction of cytokine cocktails that have the ability to induce anti-tumour cytotoxicity. PMID:9376269

  16. Anti-tumour promoting activity and antioxidant properties of girinimbine isolated from the stem bark of Murraya koenigii S.

    PubMed

    Kok, Yih Yih; Mooi, Lim Yang; Ahmad, Kartini; Sukari, Mohd Aspollah; Mat, Nashriyah; Rahmani, Mawardi; Ali, Abdul Manaf

    2012-01-01

    Girinimbine, a carbazole alkaloid isolated from the stem bark of Murraya koenigii was tested for the in vitro anti-tumour promoting and antioxidant activities. Anti-tumour promoting activity was determined by assaying the capability of this compound to inhibit the expression of early antigen of Epstein-Barr virus (EA-EBV) in Raji cells that was induced by the tumour promoter, phorbol 12-myristate 13-acetate. The concentration of this compound that gave an inhibition rate at fifty percent was 6.0 µg/mL and was not cytotoxic to the cells. Immunoblotting analysis of the expression of EA-EBV showed that girinimbine was able to suppress restricted early antigen (EA-R). However, diffused early antigen (EA-D) was partially suppressed when used at 32.0 µg/mL. Girinimbine exhibited a very strong antioxidant activity as compared to a-tocopherol and was able to inhibit superoxide generation in the 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced differentiated premyelocytic HL-60 cells more than 95%, when treated with the compound at 5.3 and 26.3 µg/mL, respectively. However girinimbine failed to scavenge the stable diphenyl picryl hydrazyl (DPPH)-free radical. PMID:22522395

  17. Matrix metalloproteinases inhibition promotes the polyfunctionality of human natural killer cells in therapeutic antibody-based anti-tumour immunotherapy.

    PubMed

    Zhou, Q; Gil-Krzewska, A; Peruzzi, G; Borrego, F

    2013-07-01

    Activation of human natural killer (NK) cells is associated with the cleavage of CD16 from the cell surface, a process mediated by matrix metalloproteinases (MMPs). In this report, we examined whether inhibition of MMPs would lead to improved NK cell antibody-dependent cell-mediated cytotoxicity (ADCC) function. Using an in-vitro ADCC assay, we tested the anti-tumour function of NK cells with three different therapeutic monoclonal antibodies (mAbs) in the presence of MMPs inhibitor GM6001 or its control. Loss of CD16 was observed when NK cells were co-cultured with tumour targets in the presence of specific anti-tumour antibodies, and was found particularly on the majority of degranulating NK responding cells. Treatment with MMPs inhibitors not only prevented CD16 down-regulation, but improved the quality of the responding cells significantly, as shown by an increase in the percentage of polyfunctional NK cells that are capable of both producing cytokines and degranulation. Furthermore, MMPs inhibition resulted in augmented and sustained CD16-mediated signalling, as shown by increased tyrosine phosphorylation of CD3ζ and other downstream signalling intermediates, which may account for the improved NK cell function. Collectively, our results provide a foundation for combining MMPs inhibitors and therapeutic mAbs in new clinical trials for cancer treatment. PMID:23607800

  18. Anti-tumour immune effect of oral administration of Lactobacillus plantarum to CT26 tumour-bearing mice.

    PubMed

    Hu, Jingtao; Wang, Chunfeng; Ye, Liping; Yang, Wentao; Huang, Haibin; Meng, Fei; Shi, Shaohua; Ding, Zhuang

    2015-06-01

    Colorectal cancer (CRC) is one of the most prevalent forms of cancer that shows a high mortality and increasing incidence. There are numerous successful treatment options for CRC, including surgery, chemotherapy, radiotherapy and immunotherapy; however, their side effects and limitations are considerable. Probiotics may be an effective strategy for preventing and inhibiting tumour growth through stimulation of host innate and adaptive immunity. We investigated and compared potential anti-tumour immune responses induced by two isolated Lactobacillus strains, Lactobacillus plantarum A and Lactobacillus rhamnosus b, by pre-inoculating mice with lactobacilli for 14 days. Subsequently, subcutaneous and orthotopic intestinal tumours were generated in the pre-inoculated mice using CT26 murine adenocarcinoma cells and were assessed for response against the tumour. Our results indicated that oral administration with L. plantarum inhibited CT26 cell growth in BALB/c mice and prolonged the survival time of tumour-bearing mice compared with mice administered L. rhamnosus. L. plantarum produced protective immunity against the challenge with CT26 cells by increasing the effector functions of CD8+ and natural killer (NK) cell infiltration into tumour tissue, up-regulation of IFN-gamma (but not IL-4 or IL-17) production, and promotion of Th1-type CD4+ T differentiation. Consequently, our results suggest that L. plantarum can enhance the anti-tumour immune response and delay tumour formation. PMID:25963256

  19. Design, characterization and anti-tumour cytotoxicity of a panel of recombinant, mammalian ribonuclease-based immunotoxins.

    PubMed Central

    Deonarain, M. P.; Epenetos, A. A.

    1998-01-01

    Bovine seminal ribonuclease (BSRNase) is an unusual member of the ribonuclease superfamily, because of its remarkable anti-tumour and immunosuppressive properties. We describe here the construction, expression, purification and characterization of a panel of six immunotoxins based upon this enzyme and show that we can increase its anti-tumour activity by over 2 x 10(4)-fold. This is achieved by improving tumour cell targeting using a single-chain Fv (scFv) directed against the oncofetal antigen placental alkaline phosphatase. As well as the simple scFv-BSRNase fusion protein, we have constructed five other derivatives with additional peptides designed to improve folding and intracellular trafficking and delivery. We find that the molecule most cytotoxic to antigen (PLAP)-positive cells in vitro is one that contains a C-terminal 'KDEL' endoplasmic reticulum retention signal and a peptide sequence derived from diphtheria toxin. All these molecules are produced in Escherichia coli (E. coli) as insoluble inclusion bodies and require extensive in vitro processing to recover antigen binding and ribonuclease activity. Despite incomplete ribonuclease activity and quaternary assembly, these molecules are promising reagents for specific chemotherapy of cancer and are potentially less harmful and immunogenic than current immunotoxins. Images Figure 2 PMID:9484808

  20. Anti-tumour/metastasis effects of the potassium-sparing diuretic amiloride: an orally active anti-cancer drug waiting for its call-of-duty?

    PubMed

    Matthews, Hayden; Ranson, Marie; Kelso, Michael J

    2011-11-01

    Amiloride.HCl is clinically used as an oral potassium-sparing diuretic, but multiple studies in biochemical, cellular and animal models have shown that the drug also possesses anti-tumour and anti-metastasis activities. The additional effects appear to arise through inhibition of two discrete targets: (i) the sodium-hydrogen exchanger 1 (NHE1), a membrane protein responsible for the characteristically low extracellular pH of tumours and (ii) the urokinase-type plasminogen activator (uPA), a serine protease mediator of cell migration, invasion and metastasis and well-known marker of poor prognosis in cancer. This mini-review summarises for the first time the reported anti-tumour/metastasis effects of amiloride in experimental models, discusses the putative molecular mechanisms responsible for these effects and concludes by commenting on the pros and cons of trialling amiloride or one of its structural analogues as potential new anti-tumour/metastasis drugs. PMID:21544803

  1. Heat shock protein derived from a non-autologous tumour can be used as an anti-tumour vaccine

    PubMed Central

    Casey, David G; Lysaght, Joanne; James, Tharappel; Bateman, Andrew; Melcher, Alan A; Todryk, Stephen M

    2003-01-01

    Antigenic cross-reactivity between certain tumours has allowed the development of more widely applicable, major histocompatibility complex-disparate (allogeneic) whole-cell vaccines. This principle should also allow heat shock proteins (hsp) derived from certain tumours (and carrying cross-reactive antigens) to be used as vaccines to generate anti-tumour immunity in a range of cancer patients. Here, hsp70 derived from gp70-antigen+ B16 melanoma generated cytotoxic-T-lymphocyte-mediated immune protection in BALB/c mice against challenge with gp70-antigen+ CT26 colorectal tumour cells. Using ovalbumin as a model tumour antigen, it is shown that hsp70 enhances peptide re-presentation by dendritic cells via class I over equimolar whole ovalbumin antigen. However, while transfection of tumour cells with inducible hsp70 increases hsp yield from tumours, it does not enhance antigen recognition via purified hsp70 nor via whole cells or their lysate. PMID:12941147

  2. Bp44mT: an orally active iron chelator of the thiosemicarbazone class with potent anti-tumour efficacy

    PubMed Central

    Yu, Y; Rahmanto, Y Suryo; Richardson, DR

    2012-01-01

    BACKGROUND AND PURPOSE Our previous studies demonstrated that a thiosemicarbazone iron chelator (di-2-pyridylketone-4,4-dimethyl-3-thiosemicarbazone; Dp44mT) possesses potent and selective anti-cancer activity but led to cardiotoxicity at non-optimal doses. In this study, we examined the in vivo anti-tumour efficacy and tolerability of a new-generation 2-benzoylpyridine thiosemicarbazone iron chelator (2-benzoylpyridine-4,4-dimethyl-3-thiosemicarbazone; Bp44mT) administered via the oral or i.v. routes. EXPERIMENTAL APPROACH BpT chelators were tested in vitro against human lung cancer cells (DMS-53) and in vivo in DMS-53 tumour xenografts in mice. The toxicity of Bp44mT in vivo and its effects on the expression of iron-regulated molecules involved in growth and cell cycle control were investigated. KEY RESULTS Administration of Bp44mT by either route resulted in marked dose-dependent inhibition of tumour growth. When administered at 50 mg·kg−1 via oral gavage three times per week for 23 days, the net xenograft growth was inhibited by 75%, compared with vehicle-treated mice. Toxicological examination showed reversible alterations including slight reduction of RBC count, with a decrease of liver and splenic iron levels, which confirmed iron chelation in vivo. Importantly, in contrast to Dp44mT, the chelator-treated mice did not show cardiac histological abnormalities. There was also no significant weight loss in mice, suggesting oral administration of Bp44mT was well tolerated. CONCLUSIONS AND IMPLICATIONS This is the first study to show that Bp44mT can be given orally with potent anti-tumour efficacy. Oral administration of a novel and effective chemotherapeutic agent provides the benefits of convenience for chronic dosing regimens. PMID:21658021

  3. The anti-tumour agent lonidamine is a potent inhibitor of the mitochondrial pyruvate carrier and plasma membrane monocarboxylate transporters.

    PubMed

    Nancolas, Bethany; Guo, Lili; Zhou, Rong; Nath, Kavindra; Nelson, David S; Leeper, Dennis B; Blair, Ian A; Glickson, Jerry D; Halestrap, Andrew P

    2016-04-01

    Lonidamine (LND) is an anti-tumour drug particularly effective at selectively sensitizing tumours to chemotherapy, hyperthermia and radiotherapy, although its precise mode of action remains unclear. It has been reported to perturb the bioenergetics of cells by inhibiting glycolysis and mitochondrial respiration, whereas indirect evidence suggests it may also inhibitL-lactic acid efflux from cells mediated by members of the proton-linked monocarboxylate transporter (MCT) family and also pyruvate uptake into the mitochondria by the mitochondrial pyruvate carrier (MPC). In the present study, we test these possibilities directly. We demonstrate that LND potently inhibits MPC activity in isolated rat liver mitochondria (Ki2.5 μM) and co-operatively inhibitsL-lactate transport by MCT1, MCT2 and MCT4 expressed inXenopus laevisoocytes withK0.5and Hill coefficient values of 36-40 μM and 1.65-1.85 respectively. In rat heart mitochondria LND inhibited the MPC with similar potency and uncoupled oxidation of pyruvate was inhibited more effectively (IC50∼ 7 μM) than other substrates including glutamate (IC50∼ 20 μM). In isolated DB-1 melanoma cells 1-10 μM LND increasedL-lactate output, consistent with MPC inhibition, but higher concentrations (150 μM) decreasedL-lactate output whereas increasing intracellular [L-lactate] > 5-fold, consistent with MCT inhibition. We conclude that MPC inhibition is the most sensitive anti-tumour target for LND, with additional inhibitory effects on MCT-mediatedL-lactic acid efflux and glutamine/glutamate oxidation. Together these actions can account for published data on the selective tumour effects of LND onL-lactate, intracellular pH (pHi) and ATP levels that can be partially mimicked by the established MPC and MCT inhibitor α-cyano-4-hydroxycinnamate (CHC). PMID:26831515

  4. The anti-tumour agent lonidamine is a potent inhibitor of the mitochondrial pyruvate carrier and plasma membrane monocarboxylate transporters

    PubMed Central

    Nancolas, Bethany; Guo, Lili; Zhou, Rong; Nath, Kavindra; Nelson, David S.; Leeper, Dennis B.; Blair, Ian A.; Glickson, Jerry D.; Halestrap, Andrew P.

    2016-01-01

    Lonidamine (LND) is an anti-tumour drug particularly effective at selectively sensitising tumours to chemotherapy, hyperthermia and radiotherapy, although its precise mode of action remains unclear. It has been reported to perturb the bioenergetics of cells by inhibiting glycolysis and mitochondrial respiration, while indirect evidence suggests it may also inhibit L-lactic acid efflux from cells mediated by members of the proton-linked monocarboxylate transporter (MCT) family and also pyruvate uptake into the mitochondria by the mitochondrial pyruvate carrier (MPC). Here we test these possibilities directly. We demonstrate that LND potently inhibits MPC activity in isolated rat liver mitochondria (Ki 2.5 μM) and cooperatively inhibits L-lactate transport by MCT1, MCT2 and MCT4 expressed in Xenopus laevis oocytes with K0.5 and Hill Coefficient values of 36–40 μM and 1.65–1.85. In rat heart mitochondria LND inhibited the MPC with similar potency and uncoupled oxidation of pyruvate was inhibited more effectively (IC50 ~7 μM) than other substrates including glutamate (IC50 ~20 μM). In isolated DB-1 melanoma cells 1–10 μM LND increased L-lactate output, consistent with MPC inhibition, but higher concentrations (150 μM) decreased L-lactate output while increasing intracellular [L-lactate] > five-fold, consistent with MCT inhibition. We conclude that MPC inhibition is the most sensitive anti-tumour target for LND, with additional inhibitory effects on MCT-mediated L-lactic acid efflux and glutamine/glutamate oxidation. Together these actions can account for published data on the selective tumour effects of LND on L-lactate, intracellular pH (pHi) and ATP levels that can be partially mimicked by the established MPC and MCT inhibitor α-cyano-4-hydroxycinnamate. PMID:26831515

  5. Infliximab therapy balances regulatory T cells, tumour necrosis factor receptor 2 (TNFR2) expression and soluble TNFR2 in sarcoidosis.

    PubMed

    Verwoerd, A; Hijdra, D; Vorselaars, A D M; Crommelin, H A; van Moorsel, C H M; Grutters, J C; Claessen, A M E

    2016-08-01

    Sarcoidosis is a systemic granulomatous disease of unknown aetiology that most commonly affects the lungs. Although elevated levels of regulatory T cells (Tregs ) have been reported, the extent to which they play a role in sarcoidosis pathogenesis remains unclear. Tumour necrosis factor (TNF) is thought to be one of the driving forces behind granuloma formation, illustrated by the efficacy of infliximab in severe sarcoidosis. Tregs express TNF receptor 2 (TNFR2) highly. Here, we examined the influence of infliximab therapy on Tregs and (soluble) TNFR2 levels in sarcoidosis, and correlated these with response to therapy. We observed that relative frequencies of Tregs were significantly higher in patients (n = 54) compared to healthy controls (n = 26; median 6·73 versus 4·36%; P < 0·001) and decreased following therapy (4·95; P < 0·001). Baseline TNFR2 expression on Tregs was increased significantly in patients versus controls (99·4 versus 96·2%; P = 0·031), and also in responders to therapy versus non-responders (99·6 versus 97·3%; P = 0·012). Furthermore, baseline soluble TNFR2 (sTNFR2) was higher in responders than in non-responders (mean 174 versus 107 pg/ml; P = 0·015). After treatment, responders showed a significant reduction in sTNFR2 levels in peripheral blood (-44·7 pg/ml; P < 0·001), in contrast to non-responders (+3·59 pg/ml). Our results demonstrated that Treg frequencies and TNFR2 expression on Tregs are increased in sarcoidosis, followed by a decline during infliximab therapy, suggesting a pathophysiological role of this T cell subset. Interestingly, sTNFR2 levels at baseline differed significantly between responders and non-responders, making it a potential marker in predicting which patients might benefit from infliximab. PMID:27158798

  6. miR-22 has a potent anti-tumour role with therapeutic potential in acute myeloid leukaemia.

    PubMed

    Jiang, Xi; Hu, Chao; Arnovitz, Stephen; Bugno, Jason; Yu, Miao; Zuo, Zhixiang; Chen, Ping; Huang, Hao; Ulrich, Bryan; Gurbuxani, Sandeep; Weng, Hengyou; Strong, Jennifer; Wang, Yungui; Li, Yuanyuan; Salat, Justin; Li, Shenglai; Elkahloun, Abdel G; Yang, Yang; Neilly, Mary Beth; Larson, Richard A; Le Beau, Michelle M; Herold, Tobias; Bohlander, Stefan K; Liu, Paul P; Zhang, Jiwang; Li, Zejuan; He, Chuan; Jin, Jie; Hong, Seungpyo; Chen, Jianjun

    2016-01-01

    MicroRNAs are subject to precise regulation and have key roles in tumorigenesis. In contrast to the oncogenic role of miR-22 reported in myelodysplastic syndrome (MDS) and breast cancer, here we show that miR-22 is an essential anti-tumour gatekeeper in de novo acute myeloid leukaemia (AML) where it is significantly downregulated. Forced expression of miR-22 significantly suppresses leukaemic cell viability and growth in vitro, and substantially inhibits leukaemia development and maintenance in vivo. Mechanistically, miR-22 targets multiple oncogenes, including CRTC1, FLT3 and MYCBP, and thus represses the CREB and MYC pathways. The downregulation of miR-22 in AML is caused by TET1/GFI1/EZH2/SIN3A-mediated epigenetic repression and/or DNA copy-number loss. Furthermore, nanoparticles carrying miR-22 oligos significantly inhibit leukaemia progression in vivo. Together, our study uncovers a TET1/GFI1/EZH2/SIN3A/miR-22/CREB-MYC signalling circuit and thereby provides insights into epigenetic/genetic mechanisms underlying the pathogenesis of AML, and also highlights the clinical potential of miR-22-based AML therapy. PMID:27116251

  7. Dihydro-β-agarofuran sesquiterpenes from celastraceae species as anti-tumour-promoting agents: Structure-activity relationship.

    PubMed

    Núñez, Marvin J; Jiménez, Ignacio A; Mendoza, Cristina R; Chavez-Sifontes, Marvin; Martinez, Morena L; Ichiishi, Eiichiro; Tokuda, Ryo; Tokuda, Harukuni; Bazzocchi, Isabel L

    2016-03-23

    Inhibition of tumour promotion in multistage chemical carcinogenesis is considered a promising strategy for cancer chemoprevention. In an ongoing investigation of bioactive secondary metabolites from Celastraceae species, five new dihydro-β-agarofuran sesquiterpenes (1-5), named Chiapens A-E, and seventeen known ones, were isolated from Maytenus chiapensis. Their structures were elucidated by extensive NMR spectroscopic and mass spectrometric techniques, and their absolute configurations were determined by circular dichroism studies, chemical correlations and biogenic means. The isolated compounds, along with twenty known sesquiterpenes, previously isolated from Zinowiewia costaricensis, have been tested for their inhibitory effects on Epstein-Barr virus early antigen (EBV-EA) activation induced by 12-O-tetradecanoylphorpol-13-acetate (TPA). Thirty three compounds from this series showed stronger effects than that of β-carotene, the reference inhibitor. The structure-activity relationship (SAR) analysis revealed that the type of substituent, in particular at the C-1 position of the sesquiterpene scaffold, was able to modulate the anti-tumour promoting activity. Compounds 3, 6, and 33 showed significant effects in an in vivo two-stage mouse-skin carcinogenesis model. PMID:26854381

  8. Anti-tumour activity of photodynamic therapy in combination with mitomycin C in nude mice with human colon adenocarcinoma.

    PubMed Central

    Ma, L. W.; Moan, J.; Steen, H. B.; Iani, V.

    1995-01-01

    The interaction of photodynamic therapy (PDT) and a chemotherapeutic drug, mitomycin C (MMC), was investigated using WiDr human colon adenocarcinoma tumours implanted on Balb/c athymic nude mice. The WiDr tumours were treated with PDT alone, MMC alone or with both. It was found that the combined treatment produced a greater retardation in the growth of the WiDr tumour than monotherapy with MMC or PDT. The synergistic effect was especially prominent when PDT was used in combination with a low dose of MMC (1 mg kg-1), since treatment of 1 mg kg-1 MMC alone had no effect on the tumour. The anti-tumour activity of PDT was found to be increased with MMC of 5 mg kg-1. The response of normal skin on mice feet to PDT slightly greater when PDT was combined with 5 mg kg-1 MMC than when PDT was applied alone, while no detectable additional effect on skin photosensitivity was observed when PDT was combined with 1 mg kg-1 MMC. An enhanced uptake of Photofrin in tumours was found 12 h and 24 h after administration of MMC. The effect of MMC on the cell cycle distribution of cell dissociated directly from the tumours was studied. The results suggest that the increased susceptibility to photoinactivation of Photofrin-sensitised tumours may be due to MMC-induced accumulation of the tumour cells in S-phase. PMID:7734319

  9. A G-quadruplex-binding compound showing anti-tumour activity in an in vivo model for pancreatic cancer

    PubMed Central

    Ohnmacht, Stephan A; Marchetti, Chiara; Gunaratnam, Mekala; Besser, Rachael J; Haider, Shozeb M; Di Vita, Gloria; Lowe, Helen L; Mellinas-Gomez, Maria; Diocou, Seckou; Robson, Mathew; Šponer, Jiri; Islam, Barira; Barbara Pedley, R; Hartley, John A; Neidle, Stephen

    2015-01-01

    We report here that a tetra-substituted naphthalene-diimide derivative (MM41) has significant in vivo anti-tumour activity against the MIA PaCa-2 pancreatic cancer xenograft model. IV administration with a twice-weekly 15 mg/kg dose produces ca 80% tumour growth decrease in a group of tumour-bearing animals. Two animals survived tumour-free after 279 days. High levels of MM41 are rapidly transported into cell nuclei and were found to accumulate in the tumour. MM41 is a quadruplex-interactive compound which binds strongly to the quadruplexes encoded in the promoter sequences of the BCL-2 and k-RAS genes, both of which are dis-regulated in many human pancreatic cancers. Levels of BCL-2 were reduced by ca 40% in tumours from MM41-treated animals relative to controls, consistent with BCL-2 being a target for MM41. Molecular modelling suggests that MM41 binds to a BCL-2 quadruplex in a manner resembling that previously observed in co-crystal structures with human telomeric quadruplexes. This supports the concept that MM41 (and by implication other quadruplex-targeting small molecules) can bind to quadruplex-forming promoter regions in a number of genes and down-regulate their transcription. We suggest that quadruplexes within those master genes that are up-regulated drivers for particular cancers, may be selective targets for compounds such as MM41. PMID:26077929

  10. A G-quadruplex-binding compound showing anti-tumour activity in an in vivo model for pancreatic cancer.

    PubMed

    Ohnmacht, Stephan A; Marchetti, Chiara; Gunaratnam, Mekala; Besser, Rachael J; Haider, Shozeb M; Di Vita, Gloria; Lowe, Helen L; Mellinas-Gomez, Maria; Diocou, Seckou; Robson, Mathew; Šponer, Jiri; Islam, Barira; Pedley, R Barbara; Hartley, John A; Neidle, Stephen

    2015-01-01

    We report here that a tetra-substituted naphthalene-diimide derivative (MM41) has significant in vivo anti-tumour activity against the MIA PaCa-2 pancreatic cancer xenograft model. IV administration with a twice-weekly 15 mg/kg dose produces ca 80% tumour growth decrease in a group of tumour-bearing animals. Two animals survived tumour-free after 279 days. High levels of MM41 are rapidly transported into cell nuclei and were found to accumulate in the tumour. MM41 is a quadruplex-interactive compound which binds strongly to the quadruplexes encoded in the promoter sequences of the BCL-2 and k-RAS genes, both of which are dis-regulated in many human pancreatic cancers. Levels of BCL-2 were reduced by ca 40% in tumours from MM41-treated animals relative to controls, consistent with BCL-2 being a target for MM41. Molecular modelling suggests that MM41 binds to a BCL-2 quadruplex in a manner resembling that previously observed in co-crystal structures with human telomeric quadruplexes. This supports the concept that MM41 (and by implication other quadruplex-targeting small molecules) can bind to quadruplex-forming promoter regions in a number of genes and down-regulate their transcription. We suggest that quadruplexes within those master genes that are up-regulated drivers for particular cancers, may be selective targets for compounds such as MM41. PMID:26077929

  11. The potential effect of patulin on mice bearing melanoma cells: an anti-tumour or carcinogenic effect?

    PubMed

    Boussabbeh, Manel; Ben Salem, Intidhar; Rjiba-Touati, Karima; Bouyahya, Chedy; Neffati, Fadwa; Najjar, Mohamed Fadhel; Bacha, Hassen; Abid-Essefi, Salwa

    2016-05-01

    Mycotoxins are bioactive compounds that are noxious to human. Their effects on oncogenesis have been satisfactorily elucidated, and some of mycotoxins have been classified as carcinogenic to humans. Nevertheless, patulin (PAT) is considered by the International Agency of Research on Cancer as 'not carcinogenic to humans'. The present study was designed to understand the effect of this mycotoxin on melanoma cells (B16F10) by measuring cell proliferation and assessing the anti-tumour effect in vivo in Balb/c mice. Our results revealed that intraperitoneally administration of PAT for 20 days significantly induces tumour regression in B16F10 cell-implanted mice. This effect was evidenced by the activation of apoptosis which is supported by the increase in p53 and Bax expressions, the downregulation of the protein levels of Bcl2, and the increase in caspase-3 activity. Moreover, systemic toxicity analysis demonstrated that there is no potential toxicity following PAT treatment unlike untreated melanoma mice which suffer from anaemia, inflammation and liver dysfunction. Remarkably, this is the first published report demonstrating the therapeutic efficacy of PAT in vivo models. PMID:26619846

  12. Suppression of microRNA activity amplifies IFN-γ-induced macrophage activation and promotes anti-tumour immunity.

    PubMed

    Baer, Caroline; Squadrito, Mario Leonardo; Laoui, Damya; Thompson, Danielle; Hansen, Sarah K; Kiialainen, Anna; Hoves, Sabine; Ries, Carola H; Ooi, Chia-Huey; De Palma, Michele

    2016-07-01

    Tumour-associated macrophages (TAMs) largely express an alternatively activated (or M2) phenotype, which entails immunosuppressive and tumour-promoting capabilities. Reprogramming TAMs towards a classically activated (M1) phenotype may thwart tumour-associated immunosuppression and unleash anti-tumour immunity. Here we show that conditional deletion of the microRNA (miRNA)-processing enzyme DICER in macrophages prompts M1-like TAM programming, characterized by hyperactive IFN-γ/STAT1 signalling. This rewiring abated the immunosuppressive capacity of TAMs and fostered the recruitment of activated cytotoxic T lymphocytes (CTLs) to the tumours. CTL-derived IFN-γ exacerbated M1 polarization of Dicer1-deficient TAMs and inhibited tumour growth. Remarkably, DICER deficiency in TAMs negated the anti-tumoral effects of macrophage depletion by anti-CSF1R antibodies, and enabled complete tumour eradication by PD1 checkpoint blockade or CD40 agonistic antibodies. Finally, genetic rescue of Let-7 miRNA activity in Dicer1-deficient TAMs partly restored their M2-like phenotype and decreased tumour-infiltrating CTLs. These findings suggest that DICER/Let-7 activity opposes IFN-γ-induced, immunostimulatory M1-like TAM activation, with potential therapeutic implications. PMID:27295554

  13. Multi-Scale Modeling Predicts a Balance of Tumor Necrosis Factor-α and Interleukin-10 Controls the Granuloma Environment during Mycobacterium tuberculosis Infection

    PubMed Central

    Cilfone, Nicholas A.; Perry, Cory R.; Kirschner, Denise E.; Linderman, Jennifer J.

    2013-01-01

    Interleukin-10 (IL-10) and tumor necrosis factor-α (TNF-α) are key anti- and pro-inflammatory mediators elicited during the host immune response to Mycobacterium tuberculosis (Mtb). Understanding the opposing effects of these mediators is difficult due to the complexity of processes acting across different spatial (molecular, cellular, and tissue) and temporal (seconds to years) scales. We take an in silico approach and use multi-scale agent based modeling of the immune response to Mtb, including molecular scale details for both TNF-α and IL-10. Our model predicts that IL-10 is necessary to modulate macrophage activation levels and to prevent host-induced tissue damage in a granuloma, an aggregate of cells that forms in response to Mtb. We show that TNF-α and IL-10 parameters related to synthesis, signaling, and spatial distribution processes control concentrations of TNF-α and IL-10 in a granuloma and determine infection outcome in the long-term. We devise an overall measure of granuloma function based on three metrics – total bacterial load, macrophage activation levels, and apoptosis of resting macrophages – and use this metric to demonstrate a balance of TNF-α and IL-10 concentrations is essential to Mtb infection control, within a single granuloma, with minimal host-induced tissue damage. Our findings suggest that a balance of TNF-α and IL-10 defines a granuloma environment that may be beneficial for both host and pathogen, but perturbing the balance could be used as a novel therapeutic strategy to modulate infection outcomes. PMID:23869227

  14. Therapeutic effects of date fruits (Phoenix dactylifera) in the prevention of diseases via modulation of anti-inflammatory, anti-oxidant and anti-tumour activity

    PubMed Central

    Rahmani, Arshad H; Aly, Salah M; Ali, Habeeb; Babiker, Ali Y; Srikar, Sauda; khan, Amjad A

    2014-01-01

    The current mode of treatment of various diseases based on synthetic drugs is expensive, alters genetic and metabolic pathways and also shows adverse side effects. Thus, safe and effective approach is needed to prevent the diseases development and progression. In this vista, Natural products are good remedy in the treatment/management of diseases and they are affordable and effective without any adverse effects. Dates are main fruit in the Arabian Peninsula and are considered to be one of the most significant commercial crops and also have been documented in Holy Quran and modern scientific literatures. Earlier studies have shown that constituents of dates act as potent antioxidant, anti-tumour as well as anti-inflammatory, provide a suitable alternative therapy in various diseases cure. In this review, dates fruits has medicinal value are summarized in terms of therapeutic implications in the diseases control through anti-oxidant, anti-inflammatory, anti-tumour and ant-diabetic effect. PMID:24753740

  15. PG545, a dual heparanase and angiogenesis inhibitor, induces potent anti-tumour and anti-metastatic efficacy in preclinical models

    PubMed Central

    Dredge, K; Hammond, E; Handley, P; Gonda, T J; Smith, M T; Vincent, C; Brandt, R; Ferro, V; Bytheway, I

    2011-01-01

    Background: PG545 is a heparan sulfate (HS) mimetic that inhibits tumour angiogenesis by sequestering angiogenic growth factors in the extracellular matrix (ECM), thus limiting subsequent binding to receptors. Importantly, PG545 also inhibits heparanase, the only endoglycosidase which cleaves HS chains in the ECM. The aim of the study was to assess PG545 in various solid tumour and metastasis models. Methods: The anti-angiogenic, anti-tumour and anti-metastatic properties of PG545 were assessed using in vivo angiogenesis, solid tumour and metastasis models. Pharmacokinetic (PK) data were also generated in tumour-bearing mice to gain an understanding of optimal dosing schedules and regimens. Results: PG545 was shown to inhibit angiogenesis in vivo and induce anti-tumour or anti-metastatic effects in murine models of breast, prostate, liver, lung, colon, head and neck cancers and melanoma. Enhanced anti-tumour activity was also noted when used in combination with sorafenib in a liver cancer model. PK data revealed that the half-life of PG545 was relatively long, with pharmacologically relevant concentrations of radiolabeled PG545 observed in liver tumours. Conclusion: PG545 is a new anti-angiogenic clinical candidate for cancer therapy. The anti-metastatic property of PG545, likely due to the inhibition of heparanase, may prove to be a critical attribute as the compound enters phase I clinical trials. PMID:21285983

  16. Anti-tumour-promoting and thermal-induced protein denaturation inhibitory activities of β-sitosterol and lupeol isolated from Diospyros lotus L.

    PubMed

    Rauf, Abdur; Uddin, Ghias; Khan, Haroon; Raza, Muslim; Zafar, Muhammad; Tokuda, Harukuni

    2016-01-01

    In this study, the anti-tumour-promoting and thermal-induced protein denaturation inhibitory activities of β-sitosterol (1) and lupeol (2), isolated from Diospyros lotus L., were explored. Compound 1 showed a marked concentration-dependent inhibition against 12-O-tetradecanoylphorbol-13-acetate (20 ng/32 pmol)-induced Epstein-Barr virus early antigen activation in Raji cells with IC50 of 270 μg/ml, without significant toxicity (70% viability). Compound 2 showed significant anti-tumour-promoting effect with IC50 of 412 μg/ml, without significant toxicity (60% viability). In heat-induced protein denaturation assay, compound 1 exhibited a concentration-dependent attenuation with a maximum effect of 73.5% at 500 μg/ml with EC50 of 117 μg/ml, while compound 2 exhibited a maximum effect of 59.2% at 500 μg/ml with EC50 of 355 μg/ml. Moreover, in silico docking studies against the phosphoinositide 3-kinase enzyme also show the inhibitory potency of these compounds. In short, both the compounds exhibited a marked anti-tumour-promoting and potent inhibitory effect on thermal-induced protein denaturation. PMID:26134930

  17. BALANCE

    DOEpatents

    Carmichael, H.

    1953-01-01

    A torsional-type analytical balance designed to arrive at its equilibrium point more quickly than previous balances is described. In order to prevent external heat sources creating air currents inside the balance casing that would reiard the attainment of equilibrium conditions, a relatively thick casing shaped as an inverted U is placed over the load support arms and the balance beam. This casing is of a metal of good thernnal conductivity characteristics, such as copper or aluminum, in order that heat applied to one portion of the balance is quickly conducted to all other sensitive areas, thus effectively preventing the fornnation of air currents caused by unequal heating of the balance.

  18. Anti-tumour effects of lanreotide for pancreatic and intestinal neuroendocrine tumours: the CLARINET open-label extension study

    PubMed Central

    Caplin, Martyn E; Pavel, Marianne; Ćwikła, Jarosław B; Phan, Alexandria T; Raderer, Markus; Sedláčková, Eva; Cadiot, Guillaume; Wolin, Edward M; Capdevila, Jaume; Wall, Lucy; Rindi, Guido; Langley, Alison; Martinez, Séverine; Gomez-Panzani, Edda; Ruszniewski, Philippe

    2016-01-01

    In the CLARINET study, lanreotide Autogel (depot in USA) significantly prolonged progression-free survival (PFS) in patients with metastatic pancreatic/intestinal neuroendocrine tumours (NETs). We report long-term safety and additional efficacy data from the open-label extension (OLE). Patients with metastatic grade 1/2 (Ki-67 ≤10%) non-functioning NET and documented baseline tumour-progression status received lanreotide Autogel 120 mg (n=101) or placebo (n=103) for 96 weeks or until death/progressive disease (PD) in CLARINET study. Patients with stable disease (SD) at core study end (lanreotide/placebo) or PD (placebo only) continued or switched to lanreotide in the OLE. In total, 88 patients (previously: lanreotide, n=41; placebo, n=47) participated: 38% had pancreatic, 39% midgut and 23% other/unknown primary tumours. Patients continuing lanreotide reported fewer adverse events (AEs) (all and treatment-related) during OLE than core study. Placebo-to-lanreotide switch patients reported similar AE rates in OLE and core studies, except more diarrhoea was considered treatment-related in OLE (overall diarrhoea unchanged). Median lanreotide PFS (core study randomisation to PD in core/OLE; n=101) was 32.8 months (95% CI: 30.9, 68.0). A sensitivity analysis, addressing potential selection bias by assuming that patients with SD on lanreotide in the core study and not entering the OLE (n=13) had PD 24 weeks after last core assessment, found median PFS remaining consistent: 30.8 months (95% CI: 30.0, 31.3). Median time to further PD after placebo-to-lanreotide switch (n=32) was 14.0 months (10.1; not reached). This OLE study suggests long-term treatment with lanreotide Autogel 120 mg maintained favourable safety/tolerability. CLARINET OLE data also provide new evidence of lanreotide anti-tumour benefits in indolent and progressive pancreatic/intestinal NETs. PMID:26743120

  19. Galactosylated streptavidin for improved clearance of biotinylated intact and F(ab')2 fragments of an anti-tumour antibody.

    PubMed Central

    Marshall, D.; Pedley, R. B.; Melton, R. G.; Boden, J. A.; Boden, R.; Begent, R. H.

    1995-01-01

    Persistence of high levels of radiolabelled antibody in the circulation is a major limitation of radioimmunotherapy. Biotinylation of the radiolabelled anti-tumour antibody followed by administration of streptavidin is known to give much improved tumour to blood ratios as the radioantibody is complexed and subsequently cleared via the reticuloendothelial system, although prolonged splenic uptake is a problem. We have investigated the effect on the clearance pattern and tumour localisation of a 125I-labelled biotinylated anti-CEA antibody (A5B7) after administration of a galactosylated form of streptavidin (gal-streptavidin) in nude mice bearing a human colon carcinoma xenograft. Fifteen minutes to 1 h after gal-streptavidin administration the complexes were cleared via the liver alone (as opposed to liver and spleen after native streptavidin). Twenty-four hours after administration of gal-streptavidin, the tumour to blood ratio for biotinylated A5B7 IgG increased from 2.9 to 13.2 and for biotinylated F(ab')2 fragments an increase from 4.9 to 33.2 was achieved. The reduction in tumour accumulation of F(ab')2 24 h after injection of the clearing agent was less than that seen with intact antibody. Injection of asialofetuin inhibited clearance, confirming that removal of the gal-streptavidin-biotinylated antibody complexes from the blood was via the asialoglycoprotein receptor on liver hepatocytes. Therefore, galactosylation of the streptavidin clearing agent allows rapid removal of radiolabelled biotinylated antibodies via the liver asialoglycoprotein receptor, as opposed to the reticuloendothelial system. Images Figure 5 Figure 6 Figure 7 PMID:7529526

  20. Anti-tumour effects of lanreotide for pancreatic and intestinal neuroendocrine tumours: the CLARINET open-label extension study.

    PubMed

    Caplin, Martyn E; Pavel, Marianne; Ćwikła, Jarosław B; Phan, Alexandria T; Raderer, Markus; Sedláčková, Eva; Cadiot, Guillaume; Wolin, Edward M; Capdevila, Jaume; Wall, Lucy; Rindi, Guido; Langley, Alison; Martinez, Séverine; Gomez-Panzani, Edda; Ruszniewski, Philippe

    2016-03-01

    In the CLARINET study, lanreotide Autogel (depot in USA) significantly prolonged progression-free survival (PFS) in patients with metastatic pancreatic/intestinal neuroendocrine tumours (NETs). We report long-term safety and additional efficacy data from the open-label extension (OLE). Patients with metastatic grade 1/2 (Ki-67 ≤ 10%) non-functioning NET and documented baseline tumour-progression status received lanreotide Autogel 120 mg (n = 101) or placebo (n = 103) for 96 weeks or until death/progressive disease (PD) in CLARINET study. Patients with stable disease (SD) at core study end (lanreotide/placebo) or PD (placebo only) continued or switched to lanreotide in the OLE. In total, 88 patients (previously: lanreotide, n = 41; placebo, n = 47) participated: 38% had pancreatic, 39% midgut and 23% other/unknown primary tumours. Patients continuing lanreotide reported fewer adverse events (AEs) (all and treatment-related) during OLE than core study. Placebo-to-lanreotide switch patients reported similar AE rates in OLE and core studies, except more diarrhoea was considered treatment-related in OLE (overall diarrhoea unchanged). Median lanreotide PFS (core study randomisation to PD in core/OLE; n=101) was 32.8 months (95% CI: 30.9, 68.0). A sensitivity analysis, addressing potential selection bias by assuming that patients with SD on lanreotide in the core study and not entering the OLE (n=13) had PD 24 weeks after last core assessment, found median PFS remaining consistent: 30.8 months (95% CI: 30.0, 31.3). Median time to further PD after placebo-to-lanreotide switch (n=32) was 14.0 months (10.1; not reached). This OLE study suggests long-term treatment with lanreotide Autogel 120 mg maintained favourable safety/tolerability. CLARINET OLE data also provide new evidence of lanreotide anti-tumour benefits in indolent and progressive pancreatic/intestinal NETs. PMID:26743120

  1. Persistence with anti-tumour necrosis factor therapies in patients with psoriatic arthritis: observational study from the British Society of Rheumatology Biologics Register

    PubMed Central

    Saad, Amr A; Ashcroft, Darren M; Watson, Kath D; Hyrich, Kimme L; Noyce, Peter R; Symmons, Deborah PM

    2009-01-01

    Introduction Anti-TNF therapies represent a breakthrough in the treatment of severe psoriatic arthritis. However, little is known about long-term drug persistence with these treatments in patients with psoriatic arthritis in routine clinical practice. The aim of this study was to assess persistence with first-course and second-course treatment with anti-TNF agents in a prospective cohort of psoriatic arthritis patients and to identify factors associated with and reasons for drug discontinuation. Methods A total of 566 patients with psoriatic arthritis were registered with the British Society for Rheumatology Biologics Register (first anti-TNF agent: etanercept, n = 316; infliximab, n = 162; and adalimumab, n = 88). Treating physicians completed 6-monthly follow-up questionnaires detailing changes to anti-TNF therapies. Persistence with treatment was examined using Kaplan–Meier survival analysis. Reasons for withdrawal were classified as due to inefficacy, adverse events or other reasons. Univariate and multivariate Cox proportional hazard models were developed to examine potential predictors of withdrawals due to inefficacy or adverse events, using a range of demographic, baseline disease-specific and therapeutic variables. Results At baseline, the mean (standard deviation) age of patients was 45.7 (11.1) years, 53% were female and the mean disease duration was 12.4 (8.7) years. Persistence data were available for a mean (standard deviation) follow-up of 2.3 (0.9) person-years. In total, 422 patients had completed at least 12 months of follow-up, 75.5% of whom remained on their first anti-TNF drug while 9.5% discontinued due to inefficacy, 10.0% due to adverse events and 5.0% due to other reasons. During the period of follow-up, 178 patients received a second anti-TNF therapy. The survivor function on second anti-TNF for switchers was 74% at 12 months. Conclusions Psoriatic arthritis patients show high persistence rates with both initial and second anti-TNF therapies. PMID:19356232

  2. Induction of DT-diaphorase by 1,2-dithiole-3-thiones in human tumour and normal cells and effect on anti-tumour activity of bioreductive agents.

    PubMed Central

    Doherty, G. P.; Leith, M. K.; Wang, X.; Curphey, T. J.; Begleiter, A.

    1998-01-01

    DT-diaphorase is a two-electron-reducing enzyme that is an important activator of bioreductive anti-tumour agents, such as mitomycin C (MMC) and EO9, and is inducible by many compounds, including 1,2-dithiole-3-thiones (D3Ts). We showed previously that D3T selectively increased DT-diaphorase activity in mouse lymphoma cells compared with normal mouse marrow cells, and also increased MMC or EO9 cytotoxic activity in the lymphoma cells with only minor effects in the marrow cells. In this study, we found that D3T significantly increased DT-diaphorase activity in 28 of 38 human tumour cell lines representing ten tissue types with no obvious relationships between the tumour type, or the base level of DT-diaphorase activity, and the ability of D3T to increase the enzyme activity. Induction of DT-diaphorase activity in human tumour cell lines by 12 D3T analogues varied markedly with the D3T structure. D3T also increased DT-diaphorase activity in normal human bone marrow and kidney cells but the increases were small in these cells. In addition, D3T increased the level of enzyme activity in normal human lung cells. Pretreatment of human tumour cells with D3T analogues significantly increased the cytotoxic activity of MMC or EO9 in these cells, and the level of enhancement of anti-tumour activity paralleled the level of DT-diaphorase induction. In contrast, D3T did not effect the toxicity of EO9 in normal kidney cells. These results demonstrate that D3T analogues can increase DT-diaphorase activity in a wide variety of human tumour cells and that this effect can enhance the anti-tumour activity of the bioreductive agents MMC and EO9. PMID:9579829

  3. Therapeutic effect of interleukin 12 on mouse haemangiosarcomas is not associated with an increased anti-tumour cytotoxic T-lymphocyte activity.

    PubMed Central

    Vizler, C.; Rosato, A.; Calderazzo, F.; Quintieri, L.; Fruscella, P.; Wainstok de Calmanovici, R.; Mantovani, A.; Vecchi, A.; Zanovello, P.; Collavo, D.

    1998-01-01

    In syngeneic mice, the H5V polyoma middle-T oncogene-transformed endothelioma cell line induces Kaposi's sarcoma-like cavernous haemangiomas that regress transiently, probably because of an anti-tumour immune response, but eventually grow progressively and kill the host. To evaluate the generation of tumour-specific cytotoxic T lymphocytes (CTLs), spleen cells of tumour-bearing mice were restimulated with irradiated H5V cells in mixed leucocyte-tumour cell cultures. Tumour-specific CTLs were demonstrable only when low numbers of H5V stimulator cells were used (<1 H5V cell per 50 splenocytes). We found that H5V cells secrete immunosuppressive mediators because CTL generation was blocked when H5V cells culture supernatants were added to allogeneic mixed leucocyte cultures. As numerous tumour-derived immunosuppressive mediators may interfere with interleukin 12 (IL-12) production, we tested whether IL-12 treatment of the tumour-bearing mice would augment their immune response and thus suppress tumour growth. Indeed, IL-12 inhibited tumour growth and prevented mortality, but did not increase anti-H5V CTL generation either in vitro or in vivo. Moreover, the anti-tumour activity in IL-12-treated mice was abrogated by anti-interferon (IFN)-gamma monoclonal antibody (MAb) co-administration. These results strongly suggest that the anti-tumour effect of IL-12 is principally mediated by IFN-gamma release that in turn blocks H5V cell proliferation and induces the release of factors that suppress angiogenesis. PMID:9484826

  4. Effects of structural variations in synthetic glycolipids upon mitogenicity for spleen lymphocytes, adjuvancy for humoral immune response and on anti-tumour potential.

    PubMed

    Nigam, V N; Bonaventure, J; Chopra, C; Brailovsky, C A

    1982-11-01

    Synthetic glycolipids prepared by esterification of various sugars and sorbitol, and containing various numbers of saturated or unsaturated fatty acid residues as well as bacterial lipid A and lipopolysaccharide, were tested for mitogenicity of splenic cells of Fischer rats and Swiss mice and for the augmentation of humoral immune response against sheep red blood cells in these species. Subsequently a few of the humoral immune-response-enhancing glycolipids were compared with non-enhancers in their anti-tumour activity against 13762 rat mammary carcinoma in inbred Fischer 344 rats and Ehrlich tumour in Swiss mice. They were given systemically after tumour inoculation and intratumourally in squalene and Tween emulsion after intradermal MAC tumour development. It was observed that certain structural characteristics in glycolipids with respect to the type of sugar, the type and number of fatty-acid residues were needed for their adjuvant action of the humoral arm of the immune response. Although humoral immune-response enhancers were somewhat superior to non-enhancers in their anti-tumour activity, the correlation coefficient demonstrated a lack of significant concordance. It is concluded that glycolipids selected for their ability to augment humoral immune responses against standard antigens need not be suspect as tumour-enhancers on the grounds that they would elicit blocking antibodies in vivo against tumour-associated antigens. PMID:6756461

  5. Inhibition of indoleamine 2,3-dioxygenase activity enhances the anti-tumour effects of a Toll-like receptor 7 agonist in an established cancer model

    PubMed Central

    Ito, Hiroyasu; Ando, Tatsuya; Arioka, Yuko; Saito, Kuniaki; Seishima, Mitsuru

    2015-01-01

    Toll-like receptor (TLR) agonists have been shown to have anti-tumour activity in basic research and clinical studies. However, TLR agonist monotherapy does not sufficiently eliminate tumours. Activation of the innate immune response by TLR agonists is effective at driving adaptive immunity via interleukin-12 (IL-12) or IL-1, but is counteracted by the simultaneous induction of immunosuppressive cytokines and other molecules, including IL-10, transforming growth factor-β, and indoleamine 2,3-dioxygenase (IDO). In the present study, we evaluated the anti-cancer effect of the TLR7 agonist, imiquimod (IMQ), in the absence of IDO activity. The administration of IMQ in IDO knockout (KO) mice inoculated with tumour cells significantly suppressed tumour progression compared with that in wild-type (WT) mice, and improved the survival rate. Moreover, injection with IMQ enhanced the tumour antigen-specific T helper type 1 response in IDO-KO mice with tumours. Combination therapy with IMQ and an IDO inhibitor also significantly inhibited tumour growth. Our results indicated that the enhancement of IDO expression with TLR agonists in cancer treatment might impair host anti-tumour immunity while the inhibition of IDO could enhance the therapeutic efficacy of TLR agonists via the increase of T helper type 1 immune response. PMID:25322876

  6. The anti-tumour effects of the prodrugs N-l-leucyl-doxorubicin and vinblastine-isoleucinate in human ovarian cancer xenografts.

    PubMed Central

    Boven, E.; Hendriks, H. R.; Erkelens, C. A.; Pinedo, H. M.

    1992-01-01

    N-l-leucyl-doxorubicin and vinblastine-isoleucinate can be considered as relatively non-toxic prodrugs from doxorubicin and vinblastine, respectively. A comparative analysis was carried out of the anti-tumour activity of the four compounds as well as vintriptol in four human ovarian cancer xenografts different in histology, growth rate and chemosensitivity. Injections were given i.v. weekly twice into mice bearing well-established s.c. tumours. At equitoxic doses, the amount of drug administered for N-l-leucyl-doxorubicin and vinblastine-isoleucinate was respectively 3-fold and 2-fold higher than the doses of the parent compound. N-l-leucyl-doxorubicin induced a growth inhibition > 50% in three out of four human ovarian cancer lines. The anti-tumour effects obtained were significantly better (P < 0.01) than in the case of doxorubicin. Vinblastine-isoleucinate studied in two of these lines could induce a growth inhibition of > 50%. This prodrug appeared slightly less effective than vinblastine. Insignificant growth inhibition (< 50%) was obtained by vintriptol. PMID:1457343

  7. Balancing

    NASA Astrophysics Data System (ADS)

    Harteveld, Casper

    At many occasions we are asked to achieve a “balance” in our lives: when it comes, for example, to work and food. Balancing is crucial in game design as well as many have pointed out. In games with a meaningful purpose, however, balancing is remarkably different. It involves the balancing of three different worlds, the worlds of Reality, Meaning, and Play. From the experience of designing Levee Patroller, I observed that different types of tensions can come into existence that require balancing. It is possible to conceive of within-worlds dilemmas, between-worlds dilemmas, and trilemmas. The first, the within-world dilemmas, only take place within one of the worlds. We can think, for example, of a user interface problem which just relates to the world of Play. The second, the between-worlds dilemmas, have to do with a tension in which two worlds are predominantly involved. Choosing between a cartoon or a realistic style concerns, for instance, a tension between Reality and Play. Finally, the trilemmas are those in which all three worlds play an important role. For each of the types of tensions, I will give in this level a concrete example from the development of Levee Patroller. Although these examples come from just one game, I think the examples can be exemplary for other game development projects as they may represent stereotypical tensions. Therefore, to achieve harmony in any of these forthcoming games, it is worthwhile to study the struggles we had to deal with.

  8. Simultaneous blockade of programmed death 1 and vascular endothelial growth factor receptor 2 (VEGFR2) induces synergistic anti-tumour effect in vivo

    PubMed Central

    Yasuda, S; Sho, M; Yamato, I; Yoshiji, H; Wakatsuki, K; Nishiwada, S; Yagita, H; Nakajima, Y

    2013-01-01

    Recent basic and clinical studies have shown that the programmed death ligand (PD-L)/PD-1 pathway has a significant role in tumour immunity, and its blockade has a therapeutic potential against several human cancers. We hypothesized that anti-angiogeneic treatment might augment the efficacy of PD-1 blockade. To this end, we evaluated combining the blockade of PD-1 and vascular endothelial growth factor receptor 2 (VEGFR2) in a murine cancer model using Colon-26 adenocarcinoma. Interestingly, simultaneous treatment with anti-PD-1 and anti-VEGFR2 monoclonal antibodies (mAbs) inhibited tumour growth synergistically in vivo without overt toxicity. Blocking VEGFR2 inhibited tumour neovascularization significantly, as demonstrated by the reduced number of microvessels, while PD-1 blockade had no impact on tumour angiogenesis. PD-1 blockade might promote T cell infiltration into tumours and significantly enhanced local immune activation, as shown by the up-regulation of several proinflammatory cytokine expressions. Importantly, VEGFR2 blockade did not interfere with T cell infiltration and immunological activation induced by PD-1 blockade. In conclusion, simultaneous blockade of PD-1 and VEGFR2 induced a synergistic in-vivo anti-tumour effect, possibly through different mechanisms that might not be mutually exclusive. This unique therapeutic strategy may hold significant promise for future clinical application. PMID:23600839

  9. Effector lymphocyte-induced lymph node-like vasculature enables naive T-cell entry into tumours and enhanced anti-tumour immunity.

    PubMed

    Peske, J David; Thompson, Elizabeth D; Gemta, Lelisa; Baylis, Richard A; Fu, Yang-Xin; Engelhard, Victor H

    2015-01-01

    The presence of lymph node (LN)-like vasculature in tumours, characterized by expression of peripheral node addressin and chemokine CCL21, is correlated with T-cell infiltration and positive prognosis in breast cancer and melanoma patients. However, mechanisms controlling the development of LN-like vasculature and how it might contribute to a beneficial outcome for cancer patients are unknown. Here we demonstrate that LN-like vasculature is present in murine models of melanoma and lung carcinoma. It enables infiltration by naive T cells that significantly delay tumour outgrowth after intratumoral activation. Development of this vasculature is controlled by a mechanism involving effector CD8 T cells and NK cells that secrete LTα3 and IFNγ. LN-like vasculature is also associated with organized aggregates of B lymphocytes and gp38(+) fibroblasts, which resemble tertiary lymphoid organs that develop in models of chronic inflammation. These results establish LN-like vasculature as both a consequence of and key contributor to anti-tumour immunity. PMID:25968334

  10. Effects of opioids on immunologic parameters that are relevant to anti-tumour immune potential in patients with cancer: a systematic literature review

    PubMed Central

    Boland, J W; McWilliams, K; Ahmedzai, S H; Pockley, A G

    2014-01-01

    Background: The immune system has a central role in controlling cancer, and factors that influence protective antitumour immunity could therefore have a significant impact on the course of malignant disease. Opioids are essential for the management of cancer pain, and preclinical studies indicate that opioids have the potential to influence these tumour immune surveillance mechanisms. The aim of this systematic literature review is to evaluate the clinical effects of opioids on the immune system of patients with cancer. Methods: A systematic search of Ovid MEDLINE (PubMed) and Embase, Cochrane database and Web of Knowledge for clinical studies, which evaluated the effects of opioids on the immune system in patients with cancer, was performed. Results: Five human studies, which have assessed the effects of opioids on the immune system in patients with cancer, were identified. Although all of these evaluated the effect of morphine on immunologic end points in patients with cancer, none measured the clinical effects. Conclusions: Evidence from preclinical, healthy volunteer and surgical models suggests that different opioids variably influence protective anti-tumour immunity; however, actual data derived from cancer populations are inconclusive and definitive recommendations cannot be made. Appropriately designed and powered studies assessing clinical outcomes of opioid use in people with cancer are therefore required to inform oncologists and others involved in cancer care about the rational use of opioids in this patient group. PMID:25025960

  11. Depletion of Regulatory T Cells Induces High Numbers of Dendritic Cells and Unmasks a Subset of Anti-Tumour CD8+CD11c+ PD-1lo Effector T Cells.

    PubMed

    Goudin, Nicolas; Chappert, Pascal; Mégret, Jérome; Gross, David-Alexandre; Rocha, Benedita; Azogui, Orly

    2016-01-01

    Natural regulatory T (Treg) cells interfere with multiple functions, which are crucial for the development of strong anti-tumour responses. In a model of 4T1 mammary carcinoma, depletion of CD25+Tregs results in tumour regression in Balb/c mice, but the mechanisms underlying this process are not fully understood. Here, we show that partial Treg depletion leads to the generation of a particular effector CD8 T cell subset expressing CD11c and low level of PD-1 in tumour draining lymph nodes. These cells have the capacity to migrate into the tumour, to kill DCs, and to locally regulate the anti-tumour response. These events are concordant with a substantial increase in CD11b+ resident dendritic cells (DCs) subsets in draining lymph nodes followed by CD8+ DCs. These results indicate that Treg depletion leads to tumour regression by unmasking an increase of DC subsets as a part of a program that optimizes the microenvironment by orchestrating the activation, amplification, and migration of high numbers of fully differentiated CD8+CD11c+PD1lo effector T cells to the tumour sites. They also indicate that a critical pattern of DC subsets correlates with the evolution of the anti-tumour response and provide a template for Treg depletion and DC-based therapy. PMID:27341421

  12. Depletion of Regulatory T Cells Induces High Numbers of Dendritic Cells and Unmasks a Subset of Anti-Tumour CD8+CD11c+ PD-1lo Effector T Cells

    PubMed Central

    Goudin, Nicolas; Chappert, Pascal; Mégret, Jérome; Gross, David-Alexandre; Rocha, Benedita

    2016-01-01

    Natural regulatory T (Treg) cells interfere with multiple functions, which are crucial for the development of strong anti-tumour responses. In a model of 4T1 mammary carcinoma, depletion of CD25+Tregs results in tumour regression in Balb/c mice, but the mechanisms underlying this process are not fully understood. Here, we show that partial Treg depletion leads to the generation of a particular effector CD8 T cell subset expressing CD11c and low level of PD-1 in tumour draining lymph nodes. These cells have the capacity to migrate into the tumour, to kill DCs, and to locally regulate the anti-tumour response. These events are concordant with a substantial increase in CD11b+ resident dendritic cells (DCs) subsets in draining lymph nodes followed by CD8+ DCs. These results indicate that Treg depletion leads to tumour regression by unmasking an increase of DC subsets as a part of a program that optimizes the microenvironment by orchestrating the activation, amplification, and migration of high numbers of fully differentiated CD8+CD11c+PD1lo effector T cells to the tumour sites. They also indicate that a critical pattern of DC subsets correlates with the evolution of the anti-tumour response and provide a template for Treg depletion and DC-based therapy. PMID:27341421

  13. Growth arrest vs direct cytotoxicity and the importance of molecular structure for the in vitro anti-tumour activity of ether lipids.

    PubMed Central

    Lohmeyer, M.; Workman, P.

    1995-01-01

    A panel of 25 different lipid agents was evaluated for in vitro activity against HT29 human colon carcinoma and HL60 promyelocytic leukaemia cells by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The structure-activity relationships seen with this series, including those for four sets of positional or stereoisomers, indicate that specific receptor proteins are unlikely as targets for anti-tumour lipid (ATL) action. Additional data confirm the lack of involvement of the platelet-activating factor receptor in particular and suggest that metabolic stability is a most important determinant of ATL activity. More detailed studies, with 1-O-octadecyl-2-O-methyl-rac-glycero-3-phosphocholine (ET18-OCH3) and (+/-)-2-(Hydroxy[tetrahydro-2-(octadecyloxy)methylfuran-2- yl]methoxyphosphinyloxy)-N,N,N,-trimethylethaniminium hydroxide (SRI 62-834), suggest three different modes of activity, depending on drug concentration and exposure time. Low doses of up to 5 microM in standard serum-containing medium cause population growth arrest after prolonged exposure. Growth arrest was associated with a leaky G2/M block as determined by flow cytometry. These effects are reversible. Intermediate concentrations (5-40 microM) were cytotoxic, causing a net reduction in cell numbers after 2-3 days. At even higher concentrations, all lipids caused rapid, direct membrane lysis. When the clonogenic assay was used to assess the effects of ATLs, most agents reduced colony formation at concentrations above 5 microM. However, some compounds proved stimulatory at nanomolar concentrations, suggesting that they might possess mitogenic properties. These results, particularly those concerning the concentration and time dependence, may be relevant to current clinical trials with ether lipids. PMID:7640206

  14. Pharmacokinetics, pharmacological and anti-tumour effects of the specific anti-oestrogen ICI 182780 in women with advanced breast cancer.

    PubMed Central

    Howell, A.; DeFriend, D. J.; Robertson, J. F.; Blamey, R. W.; Anderson, L.; Anderson, E.; Sutcliffe, F. A.; Walton, P.

    1996-01-01

    We have assessed the pharmacokinetics, pharmacological and anti-tumour effects of the specific steroidal anti-oestrogen ICI 182780 in 19 patients with advanced breast cancer resistant to tamoxifen. The agent was administered as a monthly depot intramuscular injection. Peak levels of ICI 182780 occurred a median of 8-9 days after dosing and then declined but were above the projected therapeutic threshold at day 28. Cmax during the first month was 10.5 ng/ml-1 and during the sixth month was 12.6 ng ml-1. The AUCs were 140.5 and 206.8 ng day ml-1 on the first and sixth month of dosing respectively, suggesting some drug accumulation. Luteinising hormone (LH) and follicle-stimulating hormone (FSH) levels rose after withdrawal of tamoxifen and then plateaued, suggesting no effect of ICI 182780 on the pituitary-hypothalamic axis. There were no significant changes in serum levels of prolactin, sex hormone-binding globulin (SHBG) or lipids. Side-effects were infrequent. Hot-flushes and sweats were not induced and there was no apparent effect of treatment upon the endometrium or vagina. Thirteen (69%) patients responded (seven had partial responses and six showed "no change' responses) to ICI 182780, after progression on tamoxifen, for a median duration of 25 months. Thus ICI 182780, given by monthly depot injection, and at the drug levels described, is an active second-line anti-oestrogen without apparent negative effects on the liver, brain or genital tract and warrants further evaluation in patients with advanced breast cancer. PMID:8688341

  15. The structure-dependent toxicity, pharmacokinetics and anti-tumour activity of HPMA copolymer conjugates in the treatment of solid tumours and leukaemia.

    PubMed

    Tomalova, Barbora; Sirova, Milada; Rossmann, Pavel; Pola, Robert; Strohalm, Jiri; Chytil, Petr; Cerny, Viktor; Tomala, Jakub; Kabesova, Martina; Rihova, Blanka; Ulbrich, Karel; Etrych, Tomas; Kovar, Marek

    2016-02-10

    Polymer drug carriers that are based on N-(2-hydroxypropyl)methacrylamide (HPMA) copolymers have been widely used in the development and synthesis of high-molecular-weight (HMW) drug delivery systems for cancer therapy. In this study, we compared linear (Mw ~27kDa, Rh ~4nm) and non-degradable star (Mw ~250kDa, Rh ~13nm) HPMA copolymer conjugates bearing anthracycline antibiotic doxorubicin (DOX) bound via pH-sensitive hydrazone bond. We determined the in vitro and in vivo toxicity of both conjugates and their maximum tolerated dose (MTD). We also compared their anti-tumour activity in mouse B-cell leukaemia (BCL1) and a mouse T-cell lymphoma (EL4) model. We found that MTD was higher for the linear conjugate (85mgDOX/kg) and lower for the star conjugate (22.5mgDOX/kg). An evaluation of the intestinal barrier integrity using FITC-dextran as a gut permeability tracer proved that no pathology was caused by the MTD of either conjugate. However, free DOX showed some damage to the gut barrier. The therapy of BCL1 leukaemia by both of the polymeric conjugates using the MTD or its fraction (i.e., equitoxic dosage) showed better results in the case of the star conjugate. On the other hand, treatment of EL4 lymphoma seemed to be more efficient when the linear conjugate was used. We suppose that the anti-cancer treatment of solid tumours and leukaemias requires different types of drug conjugates. We hypothesise that the most suitable HPMA copolymer-DOX conjugate for the treatment of solid tumours should have an HMW structure with increased Rh that would be stable for three to four days after the conjugate administration and then rapidly disintegrate in the short polymer chains, which are excretable from the body by glomerular filtration. On the other hand, the treatment of leukaemia requires a drug conjugate with a long circulation half-life. This would provide an active drug, whilst slowly degrading to excretable fragments. PMID:26708020

  16. Paradoxical effects of tumour necrosis factor-α in adjuvant-induced arthritis

    PubMed Central

    Williams, Richard O

    2008-01-01

    Anti-tumour necrosis factor (TNF)α therapy is highly effective in rheumatoid arthritis and it is surprising, therefore, that a recent study showed that intraperitoneal administration of recombinant TNFα reduced the severity of adjuvant-induced arthritis and decreased IFNγ expression in cultured draining lymph node cells. Furthermore, in untreated arthritic rats, maximal TNFα expression in draining lymph node cells coincided with spontaneous disease remission, suggesting a role for endogenous TNFα in recovery from arthritis. If confirmed in further studies, these findings suggest that, in addition to its well-established pro-inflammatory properties, TNFα may also play a disease-limiting role in this model of rheumatoid arthritis by suppressing effector T cell responses. PMID:18564403

  17. Renal papillary necrosis

    MedlinePlus

    ... your provider. Alternative Names Necrosis - renal papillae; Renal medullary necrosis Images Kidney anatomy Kidney - blood and urine flow References Ruggenenti P, Cravedi P, Remuzzi G. Microvascular and macrovascular diseases of the kidney. In: Taal MW, Chertow GM, ...

  18. X-Ray Structure and In Vitro Anti-Tumoural Activity of the Dimeric Bis[(2-Phenyl-1,2-Dicarba-Closo-Dodecaborane-1-Carboxylato)-Di-n-Butyltin] Oxide

    PubMed Central

    Tiekink, Edward R. T.; Bouhdid, Abdeslam; Willem, Rudolph; Bregadze, Vladimir I.; Ermanson, Lidia V.; Glazun, Sergey A.

    1997-01-01

    X-ray diffraction studies reveal the structure of {[(2-C6H5-1,2-C2B10H10-1-COO)Bu2Sn]2O}2, 1, to conform to the common motif found for {[(R′COO)R2Sn]2O}2 compounds. The dimer features a central Bu2Sn2O2 unit (two-fold symmetry) with the two Bu2Sn groups being linked via bridging oxygen atoms, each of which also carries an exocyclic Bu2Sn moiety. The two pairs of exo- and endo-cyclic tin atoms are each linked via an almost symmetrically bridging carboxylate ligand and the two remaining ligands coordinate an exocyclic tin atom only, in the monodentate mode. The in vitro anti-tumour activity of 1, determined against a variety of cell lines, is compared with those of the corresponding 2-methylcarboranylacetate, derivative 2, and with clinically used compounds. PMID:18475772

  19. Pro-inflammatory cytokine/chemokine production by reovirus treated melanoma cells is PKR/NF-κB mediated and supports innate and adaptive anti-tumour immune priming

    PubMed Central

    2011-01-01

    Background As well as inducing direct oncolysis, reovirus treatment of melanoma is associated with activation of innate and adaptive anti-tumour immune responses. Results Here we characterise the effects of conditioned media from reovirus-infected, dying human melanoma cells (reoTCM), in the absence of live virus, to address the immune bystander potential of reovirus therapy. In addition to RANTES, IL-8, MIP-1α and MIP-1β, reovirus-infected melanoma cells secreted eotaxin, IP-10 and the type 1 interferon IFN-β. To address the mechanisms responsible for the inflammatory composition of reoTCM, we show that IL-8 and IFN-β secretion by reovirus-infected melanoma cells was associated with activation of NF-κB and decreased by pre-treatment with small molecule inhibitors of NF-κB and PKR; specific siRNA-mediated knockdown further confirmed a role for PKR. This pro-inflammatory milieu induced a chemotactic response in isolated natural killer (NK) cells, dendritic cells (DC) and anti-melanoma cytotoxic T cells (CTL). Following culture in reoTCM, NK cells upregulated CD69 expression and acquired greater lytic potential against tumour targets. Furthermore, melanoma cell-loaded DC cultured in reoTCM were more effective at priming adaptive anti-tumour immunity. Conclusions These data demonstrate that the PKR- and NF-κB-dependent induction of pro-inflammatory molecules that accompanies reovirus-mediated killing can recruit and activate innate and adaptive effector cells, thus potentially altering the tumour microenvironment to support bystander immune-mediated therapy as well as direct viral oncolysis. PMID:21338484

  20. Fat Necrosis and Oil Cysts

    MedlinePlus

    ... Previous Topic Granular cell tumors Next Topic Mastitis Fat necrosis and oil cysts Fat necrosis happens when ... lumpy area if it becomes bothersome. How do fat necrosis and oil cysts affect your risk for ...

  1. Renal papillary necrosis

    MedlinePlus

    ... renal papillary necrosis, especially after taking over-the-counter pain medicines ... diabetes or sickle cell anemia may reduce your risk. To prevent renal ... over-the-counter pain relievers. Do not take more than the ...

  2. [Acute retinal necrosis].

    PubMed

    Lucke, K; Reinking, U; el-Hifnawi, E; Dennin, R H; Laqua, H

    1988-12-01

    The authors report on three patients with acute retinal necrosis who were treated with the virostatic agent Acyclovir and who underwent vitreoretinal surgery with silicone oil filling for total retinal detachment. In two eyes the retina was reattached, but useful vision was only preserved in one patient. Titers from blood and the vitreous, as well as microscopic findings in retinal biopsies, support the view that the necrosis is caused by a herpes simplex virus infection. After therapy with Acyclovir was instituted no further progression on the necrosis was observed. However, the development of retinal detachment could not be prevented. Early diagnosis and antiviral therapy are essential to improve the otherwise poor prognosis in this rare syndrome. PMID:3221657

  3. Anti-tumour and anti-metastatic activity of 3-(P-Chlorophenyl)-2,3-Dihydro-3-Hydroxythiazolo (3,2-A)-Benzimidazole-2-acetic acid (WY-13,876).

    PubMed Central

    Fenichel, R. L.; Gregory, F. J.; Alburn, H. E.

    1976-01-01

    Extensive investigation of 3-(p-chlorophenyl)-2,3-dihydro-3-hydroxythiazolo(3,2-alpha)-benzimidazole-2-acetic acid (Wy-13,876) in BDF1 mice implanted with Lewis lung tumour has shown that it is an effective anti-tumour and anti-metastatic agent. In vitro examination using HEp-2 human epidermal tumour cells has indicated that Wy-13,876 is not cytotoxic. When mice implanted with Lewis lung tumour and treated with Wy-13,876 are also injected with anti-thymocyte serum, an increase in lung metastases is observed suggesting that thymocyte activity is involved in the drug's mechanism of action. An increase in peripheral T lymphocytes observed in rats 18 h after a single oral dose of Wy-13,876 further supports this possibility. When Wy-13,876 is given to tumour -bearing mice in combination with low, ineffective doses of 5-fluorouracil or cyclophosphamide, further reduction of primary tumour growth is observed. PMID:1083737

  4. The anti-tumour efficacy of human recombinant interleukin 2. Correlation between sensitivity of tumours to the cytolytic effect of LAK cells in vitro and their susceptibility to interleukin 2 immunotherapy in vivo.

    PubMed

    Bubeník, J; Indrová, M

    1987-01-01

    Experiments were designed to test what percentage of experimental MC-induced murine sarcomas were sensitive to the local tumour inhibitory effect of IL-2 and whether any correlation existed between the sensitivity of these sarcomas to the immunotherapeutic effect of IL-2 and their susceptibility to the cytolytic effect of IL-2-activated killer cells. It was found that the sensitivity of MC-induced sarcomas to local IL-2 immunotherapy was a general phenomenon. Repeated peri-tumoural injections of RIL-2 inhibited the growth of five (MC11, MC13, MC14, MC15, MC16) out of six sarcomas in syngeneic mice. The sixth murine sarcoma (MC12) was found to be resistant to the tumour inhibitory effect of IL-2. Similarly, five (MC11, MC13, MC14, MC15, MC16) out of six murine sarcoma cell lines were sensitive to the cytolytic effect of IL-2-activated syngeneic killer spleen cells when examined in vitro, whereas the sixth (MC12) sarcoma cell line was resistant. These results suggest that LAK cells represent the effector cell mechanism responsible for the anti-tumour efficacy of local IL-2 immunotherapy and that in vitro testing of sensitivity to the LAK cell-mediated cytolysis may be used to detect tumours responding to IL-2 immunotherapy in vivo. PMID:3496154

  5. Subcutaneous encapsulated fat necrosis.

    PubMed

    Aydin, Dogu; Berg, Jais O

    2016-04-01

    We have described subcutaneous encapsulated fat necrosis, which is benign, usually asymptomatic and underreported. Images have only been published on two earlier occasions, in which the necrotic nodules appear "pearly" than the cloudy yellow surface in present case. The presented image may help future surgeons to establish the diagnosis peroperatively. PMID:27099753

  6. In vitro and in vivo anti-tumour effects of MPT0B014, a novel derivative aroylquinoline, and in combination with erlotinib in human non-small-cell lung cancer cells

    PubMed Central

    Tsai, An-Chi; Pai, Hui-Chen; Wang, Chih-Ya; Liou, Jing-Ping; Teng, Che-Ming; Wang, Jing-Chi; Pan, Shiow-Lin

    2014-01-01

    BACKGROUND AND PURPOSE The purpose of the current study was to assess a novel anti-cancer drug, MPT0B014, which is not a substrate for the P-glycoprotein (P-gp) transporter, alone and in combination with erlotinib, against human non-small cell lung cancer (NSCLC). EXPERIMENTAL APPROACH Cytotoxicity in human NSCLC cell lines was assessed by sulforhodamine B and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assays. Cell cycle phase distributions were estimated with FACScan flow cytometry. Protein expression was detected by Western blotting analysis. Efflux of rhodamine 123 or calcein-acetoxymethylester was used to study the P-gp profile. The A549 xenograft model in mice was used to assess in vivo anti-tumour activity. KEY RESULTS MPT0B014 showed potent anti-proliferative activity against A549, H1299 and H226 cells. It induced G2/M arrest with down-regulation of Cdc (Tyr15) and Cdc25C, and up-regulation of cyclin B1, phospho-Cdc2 (Thr161) and Aurora A/B. P-gp-overexpressing National Cancer Institute/Adriamycin-Resistant cells were also sensitive to B014. B014-induced loss of Mcl-1 was accompanied by activation of caspases-3, -7, -8 and -9, and initiation of apoptosis. B014 in combination with erlotinib caused significant tumour inhibition in vitro and in vivo. CONCLUSIONS AND IMPLICATIONS MPT0B014 exerted cytotoxicity against human NSCLC cell lines with little susceptibility to P-gp. Combined with the EGF receptor inhibitor, erlotinib, MPT0B014 exerted significant growth inhibition of A549 cells both in vitro and in vivo. B014 could be useful as an anti-cancer agent. PMID:24116948

  7. Metabolic characteristics of 13-cis-retinoic acid (isotretinoin) and anti-tumour activity of the 13-cis-retinoic acid metabolite 4-oxo-13-cis-retinoic acid in neuroblastoma

    PubMed Central

    Sonawane, Poonam; Cho, Hwang Eui; Tagde, Ashujit; Verlekar, Dattesh; Yu, Alice L; Reynolds, C Patrick; Kang, Min H

    2014-01-01

    Background and Purpose Isotretinoin (13-cis-retinoic acid; 13-cRA) is a differentiation inducer used to treat minimal residual disease after myeloablative therapy for high-risk neuroblastoma. However, more than 40% of children develop recurrent disease during or after 13-cRA treatment. The plasma concentrations of 13-cRA in earlier studies were considered subtherapeutic while 4-oxo-13-cis-RA (4-oxo-13-cRA), a metabolite of 13-cRA considered by some investigators as inactive, were greater than threefold higher than 13-cRA. We sought to define the metabolic pathways of 13-cRA and investigated the anti-tumour activity of its major metabolite, 4-oxo-13-cRA. Experimental Approach Effects of 13-cRA and 4-oxo-13-cRA on human neuroblastoma cell lines were assessed by DIMSCAN and flow cytometry for cell proliferation, MYCN down-regulation by reverse transcription PCR and immunoblotting, and neurite outgrowth by confocal microscopy. 13-cRA metabolism was determined using tandem MS in human liver microsomes and in patient samples. Key Results Six major metabolites of 13-cRA were identified in patient samples. Of these, 4-oxo-13-cRA was the most abundant, and 4-oxo-13-cRA glucuronide was also detected at a higher level in patients. CYP3A4 was shown to play a major role in catalysing 13-cRA to 4-oxo-13-cRA. In human neuroblastoma cell lines, 4-oxo-13-cRA and 13-cRA were equi-effective at inducing neurite outgrowth, inhibiting proliferation, decreasing MYCN mRNA and protein, and increasing the expression of retinoic acid receptor-β mRNA and protein levels. Conclusions and Implications We showed that 4-oxo-13-cRA is as active as 13-cRA against neuroblastoma cell lines. Plasma levels of both 13-cRA and 4-oxo-13-cRA should be evaluated in pharmacokinetic studies of isotretinoin in neuroblastoma. PMID:25039756

  8. Walled-off pancreatic necrosis.

    PubMed

    Ramia, J M; de la Plaza, R; Quiñones-Sampedro, J E; Ramiro, C; Veguillas, P; García-Parreño, J

    2012-05-01

    Acute severe pancreatitits may be complicated by the development of 'walled-off pancreatic necrosis' (WOPN), which is characterised by a mixture of solid components and fluids on imaging studies as a consequence of organised pancreatic tissue necrosis. We present here an overview of the definition, clinical features, and diagnostic and therapeutic management of this clinical condition, which is mostly based on consensus as adequate clinical trials are lacking. PMID:22641624

  9. Balance Problems

    MedlinePlus

    ... version of this page please turn Javascript on. Balance Problems About Balance Problems Have you ever felt dizzy, lightheaded, or ... dizziness problem during the past year. Why Good Balance is Important Having good balance means being able ...

  10. [Renal ultrasound in fat necrosis].

    PubMed

    Tizki, S; Lasry, F; Elftoiki, F Z; Hadj Khalifa, H; Itri, M; Khadir, K; Benchikhi, H

    2013-07-01

    Subcutaneous fat necrosis is an uncommon disease that may be complicated with potentially fatal hypercalcemia or with nephrocalcinosis. We report on the case of a patient with a history of significant perinatal asphyxia, hospitalized for a urinary tract infection. Lesions of subcutaneous fat necrosis were noted, with asymptomatic hypercalcemia at 3.9mmol/L. A renal ultrasound was performed and showed echogenic medullary pyramids bilaterally, consistent with nephrocalcinosis and left nephrolithiasis. The treatment of hypercalcemia included hyperhydration, a diuretic and corticosteroids. Progression was characterized by the total regression of skin lesions and normalization of serum calcium. Hypercalcemia is a rare complication of subcutaneous fat necrosis. It develops within days to weeks after the appearance of skin lesions. Nephrocalcinosis appears after several weeks or months. Hypercalcemia must be treated in due time to avoid the impact on the kidney. PMID:23726682

  11. Widespread marrow necrosis during pregnancy

    SciTech Connect

    Knickerbocker, W.J.; Quenville, N.F.

    1982-11-01

    Recently, a 22-year-old Caucasian female was referred to our Hospital two days post-partum. She had been feeling unwell during the last few days of her pregnancy and complained of multiple aches and pains, worst in the abdomen and lower back. Her admission platelet count was severely depressed and a bone biopsy showed extensive marrow necrosis with viable bony trabeculae. There was no evidence of vasculitis, vascular thrombosis, or malignancy. Widespread marrow necrosis in pregnancy followed by recovery, to our knowledge, has not been previously reported.

  12. Black Anal Canal: Acute Necrosis

    PubMed Central

    Martins, Catarina; Gonçalves, Cláudia; Alves, Paulo; Gil, Inês; Canhoto, Manuela; Silva, Filipe; Cotrim, Isabel; Amado, Cristina; Eliseu, Liliana; Vasconcelos, Helena

    2016-01-01

    Acute ischemia of the rectum or anal canal resulting in necrosis is extremely uncommon because both the rectum and the anal canal have excellent blood supplies. We present a case with spontaneous necrosis of the anal canal without rectal involvement. Surgical debridement was accomplished, and the recovery was uneventful. The patient was elderly, with probable atherosclerotic arterial disease, and presented with hypotension. Due to the lack of other precipitating factors, the hypoperfusion hypothesis seems to be the most suitable in this case. To the best of our knowledge, no similar cases have been reported in the literature on this subject.

  13. Balance Problems

    MedlinePlus

    ... our e-newsletter! Aging & Health A to Z Balance Problems Basic Facts & Information What are Balance Problems? Having good balance means being able to ... Only then can you “keep your balance.” Why Balance is Important Your feelings of dizziness may last ...

  14. Balance Problems

    MedlinePlus

    ... it could be a sign of a balance problem. Balance problems can make you feel unsteady or as if ... related injuries, such as hip fracture. Some balance problems are due to problems in the inner ear. ...

  15. Balance Problems

    MedlinePlus

    ... often, it could be a sign of a balance problem. Balance problems can make you feel unsteady or as ... fall-related injuries, such as hip fracture. Some balance problems are due to problems in the inner ...

  16. Acute Esophageal Necrosis: An Update

    PubMed Central

    Inayat, Faisal; Hurairah, Abu; Virk, Hafeez Ul Hassan

    2016-01-01

    Acute esophageal necrosis (AEN) or “black esophagus” is a rare clinical entity with an unclear etiology. It is diagnosed at upper gastrointestinal endoscopy with the presence of strikingly black necrotic esophagus. The treatment is primarily medical, but the prognosis is generally poor due to advanced age and comorbid illnesses in patients who develop AEN. Herein, we discussed the implications of poor glycemic control in regards with AEN and undertook a literature review of this rare diagnosis. PMID:27583242

  17. [Talus necrosis and its treatment].

    PubMed

    Trauth, J; Bläsius, K

    1988-08-01

    Aetiopathogenesis of the necrosis of the talus has not yet been definitely clarified, and neither has that of the other aseptic necroses. We were able to study the aetiopathogenesis, course of the disease and therapy in 20 of our own patients by follow-up; two of these developed necrosis of the talus in both feet. We definitely excluded patients suffering from osteochondrosis dissecans. Even though fracture of the talus is on the whole relatively rare, it remains the most frequent cause of necrosis of the talus. We also found talonecrosis after surgical correction of clubfoot, after Sudeck's disease (Sudeck-Leriche syndrome, Sudeck's atrophy or dystrophy), suppurative arthritis of the ankle joint, subtalar luxation and haematogenic osteomyelitis. Only few patients required surgery. In most cases a special boot constructed for arthrodesis patients proved sufficient. Each patient developed arthrodesis to a different degree. Depending upon the complaints and stiffening of the ankle joint or of the talo-calcanonavicular joint, the capacity of the patients to be gainfully employed was reduced by an amount between 20 and 30 per cent. PMID:2905578

  18. Cerebral radiation necrosis in pediatric patients.

    PubMed

    Plimpton, S Reed; Stence, Nicholas; Hemenway, Molly; Hankinson, Todd C; Foreman, Nicholas; Liu, Arthur K

    2015-02-01

    Radiation necrosis is a well-described toxicity following radiation therapy in the brain. There is little data regarding the incidence of radiation necrosis in pediatric patients. We retrospectively reviewed our experience with 101 children with solid brain tumors. Radiation necrosis was diagnosed by examination of magnetic resonance imaging. Median follow-up for all patients was 13 months (range 3-51). Radiation necrosis occurred in 5% (5/101) of cases with a median time to onset of 1.2 months. In three of these children, the child was symptomatic, requiring management with steroids and bevacizumab. Radiation necrosis did not correlate with the administration of chemotherapy, age at treatment, or planning treatment volume. Our experience with pediatric patients treated with radiotherapy for solid brain tumor suggests that children may have an increased likelihood to develop radiation necrosis compared to adults. PMID:23647507

  19. Acute oesophageal necrosis (black oesophagus).

    PubMed

    Galtés, Ignasi; Gallego, María Ángeles; Esgueva, Raquel; Martin-Fumadó, Carles

    2016-03-01

    A 54-year-old man was admitted to hospital after being found unconscious in his home. He had a history of alcoholism, multiple drug addictions, and type I diabetes mellitus. At admission, he had hyperglycaemia (550 mg/dL) with glucosuria and ketone bodies in the urine, along with septic shock refractory to bilateral alveolar infiltrates and severe respiratory failure. The patient died 24 hours post admission due to multiple organ failure, with diabetic ketoacidosis decompensated by possible respiratory infection in a patient with polytoxicomania. The autopsy confirmed the presence of acute bilateral bronchopneumonia, chronic pancreatitis, severe hepatic steatosis, and generalized congestive changes. At the oesophagus, acute oesophageal necrosis was evident. PMID:26949146

  20. Thermal inactivation of infectious hematopoietic necrosis and infectious pancreatic necrosis virus

    USGS Publications Warehouse

    Gosting, L.; Gould, R.W.

    1981-01-01

    A plaque assay was used to follow the inactivation kinetics of infectious hematopoietic necrosis virus and infectious pancreatic necrosis virus in cell culture media at various temperatures. Inactivation of infectious hematopoietic necrosis virus in a visceral organ slurry was compared with that in culture media.

  1. Prediction of pancreatic necrosis by dynamic pancreatography.

    PubMed Central

    Bradley, E L; Murphy, F; Ferguson, C

    1989-01-01

    Parenchymal necrosis has recently been recognized as the principal determinant of the incidence of secondary infection in acute pancreatitis. Because secondary infection of pancreatic necrosis accounts for more than 80% of all deaths from acute pancreatitis, a method for determining the presence or absence of parenchymal necrosis would offer considerable prognostic and therapeutic information. Thirty seven patients with unequivocal acute pancreatitis and five normal controls were prospectively studied with intravenous bolus, contrast-enhanced computed tomography (dynamic pancreatography). In the absence of pancreatic necrosis, there were no significant differences in parenchymal enhancement between any of the following patient groups: controls (5), uncomplicated pancreatitis (20), pancreatic abscess (7), or peripancreatic necrosis (4)(p less than 0.05). On the other hand, pancreatic parenchymal enhancement was significantly reduced or absent in all six patients with segmental or diffuse pancreatic necrosis (p less than 0.05). Postcontrast pancreatic parenchymal enhancement was also found to be inversely correlated with the number of Ranson signs (p less than 0.001). Dynamic pancreatography offers prognostic information and is a safe and reliable technique for predicting the presence or absence of pancreatic parenchymal necrosis. Images Figs. 1A and B. Figs. 3A and B. Figs. 4A and B. Fig. 5. Figs. 6A and B. Fig. 7. PMID:2802834

  2. Balancing Acts

    MedlinePlus

    ... a new type of balance therapy using computerized, virtual reality. UPMC associate professor Susan Whitney, Ph.D., developed ... a virtual grocery store in the university's Medical Virtual Reality Center. Patients walk on a treadmill and safely ...

  3. Balancing Acts

    MedlinePlus

    ... Current Issue Past Issues Special Section: Focus on Communication Balancing Acts Past Issues / Fall 2008 Table of ... from the National Institute on Deafness and Other Communication Disorders (NIDCD). It involves simulated trips down the ...

  4. Cortical necrosis in a renal transplant

    SciTech Connect

    Blumhardt, R.; Growcock, G.; Lasher, J.C.

    1983-07-01

    The /sup 99m/Tc-DTPA renogram is a well extabished noninvasive method for evaluating and following transplanted kidneys. The examination is useful in distinguishing rejection from acute tubular necrosis as well as demonstrating several less common complications such as vascular occlusion, urinary extravasation, obstruction, and lymphocele. A previously unreported condition involving a transplant kidney (i.e., renal cortical necrosis) is described which was diagnosed with renal scintigraphy in combination with sonography.

  5. Experimental Papillary Necrosis of the Kidney

    PubMed Central

    Wyllie, R. G.; Hill, G. S.; Murray, G.; Ramsden, P. W.; Heptinstall, R. H.

    1972-01-01

    Reserpine is able to exert a pronounced inhibitory effect on the development of papillary necrosis following the administration of bromoethylamine hydrobromide to the rat. This inhibitory effect has been observed using light microscopy, histochemistry, indigo carmine excretion and urine output. These observations suggest that vasoconstriction may play a significant role in the pathogenesis of papillary necrosis, but the evidence for this is incomplete. ImagesFig 1Fig 2Fig 3Fig 4Fig 5Fig 6 PMID:4114974

  6. [Palatal necrosis in children. Case report].

    PubMed

    Sancho, M A; Parri, F J; Raigosa, J M; Lerena, J; Cacéres, F; Muñoz, M E

    2006-04-01

    Palate necrosis as a consequence of palate infection it's an exceptional condition about there's not too much references at literature. We present a case of a 6 months old child who present a palatal necrosis after a supurative medial otitis that involved hard and soft palate, with positive culture for Pseudomona aeruginosa causing a almost complete absence of the palate that simulate a bilateral palatal cleft. PMID:16846136

  7. Imaging Tumor Necrosis with Ferumoxytol

    PubMed Central

    Aghighi, Maryam; Golovko, Daniel; Ansari, Celina; Marina, Neyssa M.; Pisani, Laura; Kurlander, Lonnie; Klenk, Christopher; Bhaumik, Srabani; Wendland, Michael; Daldrup-Link, Heike E.

    2015-01-01

    showed similar findings with high T1 signal in areas of tumor necrosis and low signal in areas of intracellularly compartmentalized iron. Conclusion Differential T1- and T2-enhancement patterns of USPIO in tumors enable conclusions about their intracellular and extracellular location. This information can be used to characterize the composition of the tumor microenvironment. PMID:26569397

  8. Balance System

    NASA Technical Reports Server (NTRS)

    1988-01-01

    TherEx Inc.'s AT-1 Computerized Ataxiameter precisely evaluates posture and balance disturbances that commonly accompany neurological and musculoskeletal disorders. Complete system includes two-strain gauged footplates, signal conditioning circuitry, a computer monitor, printer and a stand-alone tiltable balance platform. AT-1 serves as assessment tool, treatment monitor, and rehabilitation training device. It allows clinician to document quantitatively the outcome of treatment and analyze data over time to develop outcome standards for several classifications of patients. It can evaluate specifically the effects of surgery, drug treatment, physical therapy or prosthetic devices.

  9. Serine racemase: a key player in apoptosis and necrosis

    PubMed Central

    Canu, Nadia; Ciotti, Maria Teresa; Pollegioni, Loredano

    2014-01-01

    A fine balance between cell survival and cell death is required to sculpt the nervous system during development. However, an excess of cell death can occur following trauma, exposure to neurotoxins or alcohol, and some developmental and neurodegenerative diseases, such as Alzheimer's disease (AD). N-Methyl-D-aspartate receptors (NMDARs) support synaptic plasticity and survival of many neuronal populations whereas inappropriate activation may promote various forms of cell death, apoptosis, and necrosis representing the two extremes of a continuum of cell death processes both “in vitro” and “in vivo.” Hence, by identifying the switches controlling pro-survival vs. apoptosis and apoptosis vs. pro-excitotoxic outcome of NMDAR stimulation, NMDAR modulators could be developed that selectively block the cell death enhancing pro-survival signaling or synaptic plasticity mediated by NMDAR. Among these modulators, a role is emerging for the enzyme serine racemase (SR) that synthesizes D-serine, a key co-agonist with glutamate at NMDAR. This review summarizes the experimental evidence from “in vitro” neuronal cultures—with special emphasis on cerebellar granule neurons (CGNs)—and “in vivo” models of neurodegeneration, where the dual role of the SR/D-serine pathway as a master regulator of apoptosis and the apoptosis-necrosis shift will be discussed. PMID:24795622

  10. Balancing Eggs

    ERIC Educational Resources Information Center

    Mills, Allan

    2014-01-01

    Theory predicts that an egg-shaped body should rest in stable equilibrium when on its side, balance vertically in metastable equilibrium on its broad end and be completely unstable on its narrow end. A homogeneous solid egg made from wood, clay or plastic behaves in this way, but a real egg will not stand on either end. It is shown that this…

  11. Renal Papillary Necrosis: Role of Radiology

    PubMed Central

    Pandya, Vaidehi K.

    2016-01-01

    Renal Papillary Necrosis (RPN) is idefined as Ischemic necrobiosis of the papilla in the medulla of the kidneys. Variety of etiological factors are recognized which cause papillary necrosis, such as analgesic nephropathy, diabetes mellitus, urinary obstruction and sickle cell haemoglobinopathy. The early diagnosis of RPN is important to improve prognosis and reduce morbidity. Radiological Imaging offers early diagnosis and can guide prompt treatment of papillary necrosis and can minimize a decline in renal function. Here we report three cases of RPN with typical imaging findings. One of them was diabetic and hypertensive female with recurrent Urinary tract Infections and other was a male with no known co-morbidity. Both of them were diagnosed to have renal papillary necrosis on CT scan and were managed operatively and conservatively, respectively. Third case was a healthy female being investigated to be renal donor for her son. Here RPN was an incidental finding and was treated conservatively. Thus CT scan could detect it pre-operatively and complications due to transplantation of a kidney with papillary necrosis were avoided. So, we want to emphasize the importance of Radiology, particularly CT scanning in detection of RPN and to guide early and prompt treatment. PMID:26894147

  12. Hyperglycemia Increases Susceptibility to Ischemic Necrosis

    PubMed Central

    Lévigne, D.; Tobalem, M.; Modarressi, A.; Pittet-Cuénod, B.

    2013-01-01

    Diabetic patients are at risk for spontaneous foot ulcers, chronic wounds, infections, and tissue necrosis. Current theories suggest that the development and progression of diabetic foot ulcers are mainly caused by arteriosclerosis and peripheral neuropathy. Tissue necrosis plays a primordial role in the progression of diabetic foot ulcers but the underlying mechanisms are poorly understood. The aim of the present study was to investigate the effects of hyperglycemia per se on the susceptibility of ischemic tissue to necrosis, using a critical ischemic hind limb animal model. We inflicted the same degree of ischemia in both euglycemic and streptozotocin-induced hyperglycemic rats by resecting the external iliac, the femoral, and the saphenous arteries. Postoperative laser Doppler flowmetry of the ischemic feet showed the same degree of reduction in skin perfusion in both hyperglycemic and euglycemic animals. Nevertheless, we found a significantly higher rate of limb necrosis in hyperglycemic rats compared to euglycemic rats (71% versus 29%, resp.). In this study, we revealed that hyperglycemia per se increases the susceptibility to limb necrosis in ischemic conditions. Our results may help to better understand the physiopathology of progressive diabetic wounds and underline the importance of strict glycemic control in patients with critical limb ischemia. PMID:23509730

  13. Anti - tumour activity of an ayurvedic oil preparation.

    PubMed

    Panikar, K R; Bhanumathy, P; Raghunath, P N

    1986-10-01

    An ayurvedic oil preparation containing flowers of ixora coccinea and cortus sativum was subjected to an animal experimentation to find out how far it is efficient in preventing the development of Dalton's lymphoma as solid tumour. The oil was applied after injecting the cells and we found it could retard the development of tumour and arrest further development of already formed tumour. PMID:22557556

  14. Balance (or Vestibular) Rehabilitation

    MedlinePlus

    ... for the Public / Hearing and Balance Balance (or Vestibular) Rehabilitation Audiologic (hearing), balance, and medical diagnostic tests help indicate whether you are a candidate for vestibular (balance) rehabilitation. Vestibular rehabilitation is an individualized balance ...

  15. Balanced Can

    NASA Astrophysics Data System (ADS)

    Shakerin, Said

    2013-12-01

    The ordinary 12-oz beverage cans in the figures below are not held up with any props or glue. The bottom of such cans is stepped at its circumference for better stacking. When this kind of can is tilted, as shown in Fig. 1, the outside corners of the step touch the surface beneath, providing an effective contact about 1 cm wide. Because the contact is relatively wide and the geometry is symmetrical, it is easy to balance an empty can by simply adding an appropriate amount of water so that the overall center of mass is located directly above the contact. In fact, any amount of water between about 40 and 210 mL will work. A computational animation of this trick by Sijia Liang and Bruce Atwood that shows center of mass as a function of amount of added water is available at http://demonstrations.wolfram.com. Once there, search "balancing can."

  16. Cortical laminar necrosis following myocardial infarction.

    PubMed

    Lattanzi, Simona; Silvestrini, Mauro; Provinciali, Leandro

    2016-01-01

    The cortical laminar necrosis (CLN) is a permanent injury characterized by the selective delayed necrosis of the cerebral cortex, mainly of the third layer, and usually greater in the depths and sides of the sulci than over the crest of the gyri. The damage involves all cellular components - either neurons, glia cells and blood vessels - and results in a focal cortical band of pan-necrosis detectable in late sub-acute or chronic stages of reduced energy supply to the brain. The CLN has been described in different conditions as hypoxia, hypoglycemia and status epilepticus. At brain CT or MR scans it appears with pathognomonic highly hyperdense or T1-hyperintense lesions following the gyral anatomy of the cerebral cortex. We reported a case of CLN associated to myocardial infarct and discussed the underlying mechanisms. PMID:27375142

  17. Airplane Balance

    NASA Technical Reports Server (NTRS)

    Huguet, L

    1921-01-01

    The authors argue that the center of gravity has a preponderating influence on the longitudinal stability of an airplane in flight, but that manufacturers, although aware of this influence, are still content to apply empirical rules to the balancing of their airplanes instead of conducting wind tunnel tests. The author examines the following points: 1) longitudinal stability, in flight, of a glider with coinciding centers; 2) the influence exercised on the stability of flight by the position of the axis of thrust with respect to the center of gravity and the whole of the glider; 3) the stability on the ground before taking off, and the influence of the position of the landing gear. 4) the influence of the elements of the glider on the balance, the possibility of sometimes correcting defective balance, and the valuable information given on this point by wind tunnel tests; 5) and a brief examination of the equilibrium of power in horizontal flight, where the conditions of stability peculiar to this kind of flight are added to previously existing conditions of the stability of the glider, and interfere in fixing the safety limits of certain evolutions.

  18. [Digital necrosis in hand by uncommon mechanism].

    PubMed

    Leroux, Maria Bibiana; Lashak, Celina; Mazzurco, Martin

    2013-07-01

    A 43-year-old, non-smoking man presented with acute ischemic lesions of his left hand. He had been taking beta-blockers for his arterial hypertension. The day before the occurrence of these acute lesions, he self medicated with a drug containing ergotamine and caffeine because of a headache. About one hour after mild trauma to the hand, he noticed intense cyanosis accompanied by severe pain in the fingers that progressed to digital necrosis. Hematological tests, hand radiography, echo Doppler, and nailfold videocapillaroscopy were performed. Digital necrosis owing to an unusual combination of ischemic mechanisms is assumed. PMID:24010508

  19. Risk of tuberculosis is higher with anti-tumor necrosis factor monoclonal antibody therapy than with soluble tumor necrosis factor receptor therapy: The three-year prospective French Research Axed on Tolerance of Biotherapies registry

    PubMed Central

    Tubach, Florence; Salmon, Dominique; Ravaud, Philippe; Allanore, Yannick; Goupille, Philippe; Bréban, Maxime; Pallot-Prades, Béatrice; Pouplin, Sophie; Sacchi, Antoinette; Chichemanian, Rose Marie; Bretagne, Stéphane; Emilie, Dominique; Lemann, Marc; Lorthololary, Olivier; Mariette, Xavier

    2009-01-01

    Background Tuberculosis (TB) is associated with anti-tumour necrosis factor (TNF) therapy but whether it is drug-specific remains a concern. Our objective was to describe cases of tuberculosis associated with anti-TNF therapy, identify risk factors and estimate the incidence. Methods An incidence study with the French population as reference and a case-control analysis. We collected, for 3 years, cases of TB among French patients receiving anti-TNF therapy, whatever the indication, with two controls treated with anti-TNF agents per case. Results We collected 69 cases of TB in patients treated for rheumatoid arthritis (n=40), spondylarthropathies (n=18), inflammatory colitis (n=9), psoriasis (n=1) and Behçet’s disease (n=1) treated with infliximab (n=36), adalimumab (n=28) and etanercept (n=5). None of the cases had received correct chemoprophylaxis treatment. The sex and age-adjusted incidence rate of TB was 116.7 per 100,000 patient-years. The SIR was 12.2 (95% confidence interval 9.7–15.5) and was higher for therapy with infliximab and adalimumab than for that with etanercept: 18.6 (13.4–25.8) and 29.3 (20.2–42.4) versus 1.8 (0.7–4.3), respectively. In the case-control analysis, the exposure to infliximab or adalimumab versus etanercept was an independent risk factor for TB: odds ratio=13.3 (2.6–69.0) and 17.1 (3.6–80.6), respectively. Other risk factors were age, the first year of anti-TNF treatment, and being born in an endemic area. Conclusions The risk of TB is higher for patients receiving monoclonal-antibody than soluble-receptor anti-TNF therapy. The increased risk with early anti-TNF treatment and the absence of correct chemoprophylaxis treatment favours the reactivation of latent TB. PMID:19565495

  20. Epinephrine Injection Associated Scrotal Skin Necrosis

    PubMed Central

    Gul, Murat; Kaynar, Mehmet; Sekmenli, Tamer; Ciftci, Ilhan; Goktas, Serdar

    2015-01-01

    Male circumcision is among the most frequent surgical interventions throughout history. Although considered as a minor intervention, it may have complications ranging from insignificant to catastrophic. These complications can be attributed to the surgical procedure and anesthesia. In this report we present two cases of scrotal skin necrosis after lidocaine with epinephrine injection using subcutaneous ring block technique prior to circumcision. PMID:26185706

  1. Pythium Root Rot (and Feeder Root Necrosis)

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Pythium species cause a number of diseases on corn. Among the Pythium diseases, root rot presents the least conspicuous aboveground symptoms. Broadly defined, root rot also includes feeder root necrosis. At least 16 species of Pythium are known to cause root rot of corn. These include P. acanthicu...

  2. Pancreatography after recovery from massive pancreatic necrosis.

    PubMed

    Howard, J M; Wagner, S M

    1989-01-01

    Massive retroperitoneal necrosis may follow life-threatening acute pancreatitis. At delayed operation, the surgeon may not be able to delineate dead pancreas from dead adipose tissue. The question arises: has "gloved hand" debridement resulted in pancreatectomy? The histologists report only "necrotic debris, of uncertain origin." To obtain objective data, pancreatography was performed in 13 patients, 10 weeks to 23 months after onset of massive pancreatic necrosis. Each patient had required delayed laparotomy for debridement and external drainage at some earlier stage of their illness. Pancreatography was correlated with the clinical assessment of diabetes and steatorrhea. Except in specific cases involving internal fistulae, pancreatography has not been previously reported in such patients. The results demonstrate that the main pancreatic duct usually maintained its normal length and configuration. Necrosis or stricture of the main duct, if it occurred, was more likely to be followed by diabetes. Steatorrhea was clinically detected in a single patient only. The necrotic tissue, up to several kilograms in wet weight, is largely dead adipose tissue. The pancreas, especially its head, is resistant to necrosis, much more resistant than is the retroperitoneal fat. PMID:2910213

  3. Shaft balancing

    DOEpatents

    Irwin, John A.

    1979-01-01

    A gas turbine engine has an internal drive shaft including one end connected to a driven load and an opposite end connected to a turbine wheel and wherein the shaft has an in situ adjustable balance system near the critical center of a bearing span for the shaft including two 360.degree. rings piloted on the outer diameter of the shaft at a point accessible through an internal engine panel; each of the rings has a small amount of material removed from its periphery whereby both of the rings are precisely unbalanced an equivalent amount; the rings are locked circumferentially together by radial serrations thereon; numbered tangs on the outside diameter of each ring identify the circumferential location of unbalance once the rings are locked together; an aft ring of the pair of rings has a spline on its inside diameter that mates with a like spline on the shaft to lock the entire assembly together.

  4. Regulated necrosis and its implications in toxicology.

    PubMed

    Aki, Toshihiko; Funakoshi, Takeshi; Uemura, Koichi

    2015-07-01

    Recent research developments have revealed that caspase-dependent apoptosis is not the sole form of regulated cell death. Caspase-independent, but genetically regulated, forms of cell death include pyroptosis, necroptosis, parthanatos, and the recently discovered ferroptosis and autosis. Importantly, regulated necrosis can be modulated by small molecule inhibitors/activators, confirming the cell autonomous mechanism of these forms of cell death. The success of small molecule-mediated manipulation of regulated necrosis has produced great changes in the field of cell death research, and has also brought about significant changes in the fields of pharmacology as well as toxicology. In this review, we intend to summarize the modes of regulated cell death other than apoptosis, and discuss their implications in toxicology. PMID:25865964

  5. Giant cell arteritis presenting as scalp necrosis.

    PubMed

    Maidana, Daniel E; Muñoz, Silvia; Acebes, Xènia; Llatjós, Roger; Jucglà, Anna; Alvarez, Alba

    2011-01-01

    The differential of scalp ulceration in older patients should include several causes, such as herpes zoster, irritant contact dermatitis, ulcerated skin tumors, postirradiation ulcers, microbial infections, pyoderma gangrenosum, and giant cell arteritis. Scalp necrosis associated with giant cell arteritis was first described in the 1940s. The presence of this dermatological sign within giant cell arteritis represents a severity marker of this disease, with a higher mean age at diagnosis, an elevated risk of vision loss and tongue gangrene, as well as overall higher mortality rates, in comparison to patients not presenting this manifestation. Even though scalp necrosis due to giant cell arteritis is exceptional, a high level of suspicion must be held for this clinical finding, in order to initiate prompt and proper treatment and avoid blindness. PMID:21789466

  6. New cancer therapies and jaw necrosis.

    PubMed

    Patel, V; Kelleher, M; Sproat, C; Kwok, J; McGurk, M

    2015-09-11

    Osteonecrosis of the jaw (ONJ) has a number of causes, the most familiar being radiation or bisphosphonate induced. Various other novel anti-neoplastic and bone-targeting therapies that can also cause jaw necrosis have recently become available. This has led to the suggested acronym MRONJ for medication-related osteonecrosis of the jaw. This article summarises the available information on these drugs and their implications for the dental surgeon. PMID:26361116

  7. Uterine Necrosis Associated with Fusobacterium necrophorum Infection

    PubMed Central

    Widelock, T.; Elkattah, R.; Gibbs, S.; Mashak, Z.; Mohling, S.; DePasquale, S.

    2015-01-01

    Fusobacterium necrophorum is infrequently implicated as a pathogenic organism. When pathogenic, the typical clinical presentation is that of pharyngitis, cervical adenopathy, and unilateral thrombophlebitis of the internal jugular vein. Infections caused by Fusobacterium necrophorum within the fields of obstetrics and gynecology have been infrequently reported. We describe a 19-year-old woman who underwent a cesarean delivery complicated by sepsis and purulent uterine necrosis secondary to Fusobacterium necrophorum infection. PMID:26000185

  8. Idiopathic incus necrosis: Analysis of 4 cases.

    PubMed

    Kansu, Leyla; Yilmaz, Ismail; Akdogan, Volkan; Avci, Suat; Ozluoglu, Levent

    2013-02-01

    We evaluated ossicular chain reconstruction in patients with idiopathic incus necrosis who have conductive hearing loss and an intact ear drum. The study included four patients (3 women and 1 man; the ages of the patients were 22, 31, 35, and 56 years, respectively) with unilateral conductive hearing loss, no history of chronic serous otitis media, an intact ear drum, normal middle ear mucosa, and necrosis of the long processes of the incus. On preoperative pure tone audiometry, air-bone gaps were 24, 25, 38, and 33 dB. Bilateral tympanometry and temporal bone computed tomography results were normal. All 4 patients underwent an exploratory tympanotomy. During the operation, the mucosa of the middle ear was normal, with a mobile stapes foot plate and malleus. No evidence of any granulation tissue was found; however, necrosis of the incus long processes was seen. For ossicular reconstruction, we used tragal cartilage between the incus and the stapes in 1 patient; in the other 3 patients, glass ionomer bone cement was used (an interposition cartilage graft also was used in the patients who received the glass ionomer bone cement). In all patients, air-bone gaps under 20 dB were established in the first year after surgery. In the ossicular disorders within the middle ear, the incus is the most commonly affected ossicle. While, the most common cause of these disorders is chronic otitis media, it may be idiopathic rarely. Several ossicular reconstruction techniques have been used to repair incudostapedial discontinuity. PMID:23460219

  9. Ketoconazole attenuates radiation-induction of tumor necrosis factor

    SciTech Connect

    Hallahan, D.E.; Virudachalam, S.; Kufe, D.W.; Weichselbaum, R.R.

    1994-07-01

    Previous work has demonstrated that inhibitors of phospholipase A2 attenuate ionizing radiation-induced arachidonic acid production, protein kinase C activation, and prevent subsequent induction of the tumor necrosis factor gene. Because arachidonic acid contributes to radiation-induced tumor necrosis factor expression, the authors analyzed the effects of agents which alter arachidonate metabolism on the regulation of this gene. Phospholipase A2 inhibitors quinicrine, bromphenyl bromide, and pentoxyfylline or the inhibitor of lipoxygenase (ketoconazole) or the inhibitor of cycloxygenase (indomethacine) were added to cell culture 1 h prior to irradiation. Radiation-induced tumor necrosis factor gene expression was attenuated by each of the phospholipase A2 inhibitors (quinicrine, bromphenylbromide, and pentoxyfylline). Furthermore, ketoconazole attenuated X ray induced tumor necrosis factor gene expression. Conversely, indomethacin enhanced tumor necrosis factor expression following irradiation. The finding that radiation-induced tumor necrosis factor gene expression was attenuated by ketoconazole suggests that the lipoxygenase pathway participates in signal transduction preceding tumor necrosis factor induction. Enhancement of tumor necrosis factor expression by indomethacin following irradiation suggests that prostaglandins produced by cyclooxygenase act as negative regulators of tumor necrosis factor expression. Inhibitors of tumor necrosis factor induction ameliorate acute and subacute sequelae of radiotherapy. The authors propose therefore, that ketoconazole may reduce acute radiation sequelae such as mucositis and esophagitis through a reduction in tumor necrosis factor induction or inhibition of phospholipase A2 in addition to its antifungal activity. 25 refs., 2 figs.

  10. Tracheal necrosis with surgical emphysema following thyroidectomy.

    PubMed

    Chauhan, A; Ganguly, M; Saidha, N; Gulia, P

    2009-01-01

    Tracheal necrosis after thyroidectomy is an extremely rare event with only a few published reports. We present a case of a 65-year-old male who developed rapidly progressive surgical emphysema of face and upper thorax on the seventh day following total thyroidectomy. Prompt surgical exploration of neck revealed a tracheal rent at the level of the second tracheal ring. This hole was then refashioned into a formal tracheostomy. Patient had an eventful recovery. Tracheostomy was closed by the 14th day. The complication was probably related to tracheal injury sustained due to electro-coagulation and subsequent secondary infection. PMID:19884745

  11. Mechanisms of Acetaminophen-Induced Liver Necrosis

    PubMed Central

    Roberts, Dean W.; James, Laura P.

    2010-01-01

    Although considered safe at therapeutic doses, at higher doses, acetaminophen produces a centrilobular hepatic necrosis that can be fatal. Acetaminophen poisoning accounts for approximately one-half of all cases of acute liver failure in the United States and Great Britain today. The mechanism occurs by a complex sequence of events. These events include: (1) CYP metabolism to a reactive metabolite which depletes glutathione and covalently binds to proteins; (2) loss of glutathione with an increased formation of reactive oxygen and nitrogen species in hepatocytes undergoing necrotic changes; (3) increased oxidative stress, associated with alterations in calcium homeostasis and initiation of signal transduction responses, causing mitochondrial permeability transition; (4) mitochondrial permeability transition occurring with additional oxidative stress, loss of mitochondrial membrane potential, and loss of the ability of the mitochondria to synthesize ATP; and (5) loss of ATP which leads to necrosis. Associated with these essential events there appear to be a number of inflammatory mediators such as certain cytokines and chemokines that can modify the toxicity. Some have been shown to alter oxidative stress, but the relationship of these modulators to other critical mechanistic events has not been well delineated. In addition, existing data support the involvement of cytokines, chemokines, and growth factors in the initiation of regenerative processes leading to the reestablishment of hepatic structure and function. PMID:20020268

  12. Bilateral putaminal necrosis and bronopol toxicity.

    PubMed

    Trivisano, Marina; Carapelle, Elena; Martino, Tommaso; Specchio, Luigi Maria

    2015-01-01

    Among alcohols, methanol intoxication is the most frequently associated with cerebral toxicity, causing retinal damage and putaminal necrosis. This consequence is believed to be due to the transformation of methanol into formic acid. We describe the case of a patient who presented with acute impairment of consciousness and tetraparesis after she had been drinking several bottles of a topical antiseptic solution (Lysoform Medical) containing 2-bromo-2-nitro-1,3-propandiol (bronopol) among excipients, in order to lose weight during previous months. Moreover, she had been on a strict slimming diet. Soon after admission, a severe respiratory and metabolic impairment became rapidly evident, requiring an intensive care unit admission. Cerebral MRI showed the presence of bilateral putaminal necrosis. She recovered in 10 days, surprisingly, without any evident clinical neurological signs. Methanol, also bronopol, when diluted in aqueous solution, at warm temperature and/or higher pH, may release formaldehyde, which is converted into formic acid, a basal ganglia toxic compound. PMID:25697297

  13. Necrosis Avidity: A Newly Discovered Feature of Hypericin and its Preclinical Applications in Necrosis Imaging

    PubMed Central

    Jiang, Binghu; Wang, Jichen; Ni, Yicheng; Chen, Feng

    2013-01-01

    Hypericin has been widely studied as a potent photosensitizer for photodynamic therapy in both preclinical and clinical settings. Recently, hypericin has also been discovered to have a specific avidity for necrotic tissue. This affinity is also observed in a series of radiolabeled derivatives of hypericin, including [123I]iodohypericin, [124I]iodohypericin, and [131I]iodohypericin. Hypericin, along with other necrosis-avid contrast agents, has been investigated for use in noninvasively targeting necrotic tissues in numerous disorders. Potential clinical applications of hypericin include the identification of acute myocardial infarction, evaluation of tissue viability, assessment of therapeutic responses to treatments, and interventional procedures for solid tumors. The mechanisms of necrosis avidity in hypericin remain to be fully elucidated, although several hypotheses have been suggested. In particular, it has been proposed that the necrosis avidity of hypericin is compound specific; for instance, cholesterol, phosphatidylserine, or phosphatidylethanolamine components in the phospholipid bilayer of cellular membranes may be the major targets for its observed selectivity. Further investigations are needed to identify the specific binding moiety that is responsible for the necrosis avidity of hypericin. PMID:24052807

  14. The interplay between regulated necrosis and bacterial infection.

    PubMed

    Blériot, Camille; Lecuit, Marc

    2016-06-01

    Necrosis has long been considered as a passive event resulting from a cell extrinsic stimulus, such as pathogen infection. Recent advances have refined this view and it is now well established that necrosis is tightly regulated at the cell level. Regulated necrosis can occur in the context of host-pathogen interactions, and can either participate in the control of infection or favor it. Here, we review the two main pathways implicated so far in bacteria-associated regulated necrosis: caspase 1-dependent pyroptosis and RIPK1/RIPK3-dependent necroptosis. We present how these pathways are modulated in the context of infection by a series of model bacterial pathogens. PMID:27048818

  15. Quantitation of Acute Necrosis After Experimental Myocardial Infarction

    PubMed Central

    Yeap, Xin-Yi; Dehn, Shirley; Adelman, Jeremy; Lipsitz, Jeremy; Thorp, Edward B.

    2016-01-01

    Myocardial infarction (MI) is death and necrosis of myocardial tissue secondary to ischemia. MI is associated with adverse cardiac remodeling, progressive heart chamber dilation, ventricular wall thinning, and loss of cardiac function. Myocardial necrosis can be experimentally induced in rodents to simulate human MI by surgical occlusion of coronary arteries. When induced in knockout or transgenic mice, this model is useful for the identification of molecular modulators of cell death, cardiac remodeling, and preclinical therapeutic potential. Herein we outline in tandem, methods for microsurgical ligation of the left anterior descending artery followed by quantitation of myocardial necrosis. Necrosis is quantified after staining the heart with triphenyltetrazolium chloride. PMID:23733573

  16. Mitochondria-targeted antioxidants do not prevent tumour necrosis factor-induced necrosis of L929 cells.

    PubMed

    Jarvis, Reagan M; Göttert, Jana; Murphy, Michael P; Ledgerwood, Elizabeth C

    2007-09-01

    Mitochondrial production of reactive oxygen species (ROS) is widely reported as a central effector during TNF-induced necrosis. The effect of a family of mitochondria-targeted antioxidants on TNF-induced necrosis of L929 cells was studied. While the commonly used lipid-soluble antioxidant BHA effectively protected cells from TNF-induced necrosis, the mitochondria-targeted antioxidants MitoQ(3), MitoQ(5), MitoQ(10) and MitoPBN had no effect on TNF-induced necrosis. Since BHA also acts as an uncoupler of mitochondrial membrane potential, two additional uncouplers were tested. FCCP and CCCP both provided dose-dependent inhibition of TNF-induced necrosis. In conclusion, the generation of mitochondrial ROS may not be necessary for TNF-induced necrosis. Instead, these results suggest alternative mitochondrial functions, such as a respiration-dependent process, are critical for necrotic death. PMID:17729122

  17. A Question of Balance

    ERIC Educational Resources Information Center

    Claxton, David B.; Troy, Maridy; Dupree, Sarah

    2006-01-01

    Most authorities consider balance to be a component of skill-related physical fitness. Balance, however, is directly related to health, especially for older adults. Falls are a leading cause of injury and death among the elderly. Improved balance can help reduce falls and contribute to older people remaining physically active. Balance is a…

  18. Improve Your Balance

    MedlinePlus

    ... My Go4Life Get Free Stuff Be a Partner Balance Improve Your Balance Each year, more than 2 million older Americans ... types of exercise — endurance , strength , balance, and flexibility . Balance Stand on One Foot Heel-to-Toe Walk ...

  19. Balance in Assessment

    ERIC Educational Resources Information Center

    White, Richard

    2007-01-01

    The review by Black and Wiliam of national systems makes clear the complexity of assessment, and identifies important issues. One of these is "balance": balance between local and central responsibilities, balance between the weights given to various purposes of schooling, balance between weights for various functions of assessment, and balance…

  20. Dynamic balance improvement program

    NASA Technical Reports Server (NTRS)

    Butner, M. F.

    1983-01-01

    The reduction of residual unbalance in the space shuttle main engine (SSME) high pressure turbopump rotors was addressed. Elastic rotor response to unbalance and balancing requirements, multiplane and in housing balancing, and balance related rotor design considerations were assessed. Recommendations are made for near term improvement of the SSME balancing and for future study and development efforts.

  1. Severe Hepatic Necrosis Associated with Methyldopa

    PubMed Central

    Cameron, Ian A.; Achord, James L.; Bartee, Harry

    1981-01-01

    Family physicians should carefully follow their patients receiving methyldopa for liver toxicity. Methyldopa is commonly used in treating hypertension and its hepatotoxic potential is frequently overlooked. This point is illustrated in the following case report involving a 45-year-old black female. The patient had been receiving oral methyldopa for 7.5 months prior to hospitalization for control of severe hypertension. Methyldopa was discontinued on her second hospital day when her liver tests were found to be abnormal. She developed progressive liver failure and lapsed into hepatic coma. Subsequently, her liver biopsy showed severe hepatic necrosis. She slowly improved with medical management. Her liver tests returned to normal; she resumed work and at 14 months follow up her liver biopsy showed no evidence of chronic active liver disease. Monitoring for methyldopa toxicity as outlined in this article could have prevented this costly and near lethal side effect. ImagesFig. 1Fig. 2 PMID:21289717

  2. Eosinophilic Gastritis Presenting as Tissue Necrosis

    PubMed Central

    Jo, Yong Min; Jang, Jin Seok; Han, Seung Hee; Kang, Sang Hyun; Kim, Woo Jae; Jeong, Jin Sook

    2015-01-01

    Eosinophilic gastroenteritis is very rare disorder that is characterized by eosinophilic infiltration of the gastrointestinal tract in the absence of any definite causes of eosinophilia. It is associated with various clinical gastrointestinal manifestations, and depends on the involved layer and site. We report a case of eosinophilic gastritis presenting with severe necrosis. The symptoms disappeared immediately after beginning steroid treatment, and the eosinophil count decreased to the reference range. The patient showed eosinophilic gastritis characterized by necrotic change such as necrotizing gastritis. It is a unique presentation of eosinophilic gastritis. To the best of our knowledge, no case of eosinophilic gastritis characterized by necrotic change such as necrotizing gastritis has been previously reported in Korea. PMID:26668805

  3. United Kingdom nationwide study of avascular necrosis of the jaws including bisphosphonate-related necrosis.

    PubMed

    Rogers, S N; Palmer, N O A; Lowe, D; Randall, C

    2015-02-01

    We aimed to record all new patients who presented to departments of oral surgery, oral medicine, and oral and maxillofacial surgery, and to dental hospitals in the UK, with avascular necrosis of the jaws including bisphosphonate-related necrosis (BRONJ) over a 2-year period (1 June 2009-31 May 2011). They were eligible irrespective of age, cause, or coexisting conditions. Data on incidence, clinical characteristics, risk factors, and coexisting conditions were collected. A total of 383 cases were registered: 369 were described as BRONJ, 5 as avascular necrosis, and 9 were unknown. Bisphosphonates had been given orally in 207 (56%), intravenously in 125 (34%), both orally and intravenously in 27 (7%), and was unknown in 9 (2%); one had been given denosumab. The main risk factor was dental extraction, and the mandible was commonly affected. The median duration of administration until onset of BRONJ was 3 years in those treated intravenously and 4 years in those treated orally. Levels of engagement with the study varied between regions, and extrapolation from the 2 most involved (Merseyside and Northern Ireland) found around 8.2-12.8 cases/million/year, which is 508-793 patients/year across the UK. To our knowledge this is one of the first studies to estimate national rates of BRONJ. It confirms that the risk and incidence are low. With changes in trends for antiresorptive bone medication, and increasing numbers of elderly people, it would be useful to repeat the registration in the future. PMID:25497376

  4. Coagulopathy and encephalopathy in a dog with acute hepatic necrosis.

    PubMed

    Strombeck, D R; Krum, S; Rogers, Q

    1976-10-15

    Disseminated intravascular coagulation developed secondary to hepatic necrosis in a 5-year-old Saint Bernard. Although the coagulopathy responded to treatment with heparin, the dog died from the combined effects of gastric hemorrhage and encephalopathy, both of which are complications of hepatic necrosis. PMID:977448

  5. Peripancreatic fat necrosis worsens acute pancreatitis independent of pancreatic necrosis via unsaturated fatty acids increased in human pancreatic necrosis collections

    PubMed Central

    Noel, Pawan; Patel, Krutika; Durgampudi, Chandra; Trivedi, Ram N; de Oliveira, Cristiane; Crowell, Michael D; Pannala, Rahul; Lee, Kenneth; Brand, Randall; Chennat, Jennifer; Slivka, Adam; Papachristou, Georgios I; Khalid, Asif; Whitcomb, David C; DeLany, James P; Cline, Rachel A; Acharya, Chathur; Jaligama, Deepthi; Murad, Faris M; Yadav, Dhiraj; Navina, Sarah; Singh, Vijay P

    2016-01-01

    Background and aims Peripancreatic fat necrosis occurs frequently in necrotising pancreatitis. Distinguishing markers from mediators of severe acute pancreatitis (SAP) is important since targeting mediators may improve outcomes. We evaluated potential agents in human pancreatic necrotic collections (NCs), pseudocysts (PCs) and pancreatic cystic neoplasms and used pancreatic acini, peripheral blood mononuclear cells (PBMC) and an acute pancreatitis (AP) model to determine SAP mediators. Methods We measured acinar and PBMC injury induced by agents increased in NCs and PCs. Outcomes of caerulein pancreatitis were studied in lean rats coadministered interleukin (IL)-1β and keratinocyte chemoattractant/growth-regulated oncogene, triolein alone or with the lipase inhibitor orlistat. Results NCs had higher fatty acids, IL-8 and IL-1β versus other fluids. Lipolysis of unsaturated triglyceride and resulting unsaturated fatty acids (UFA) oleic and linoleic acids induced necro-apoptosis at less than half the concentration in NCs but other agents did not do so at more than two times these concentrations. Cytokine coadministration resulted in higher pancreatic and lung inflammation than caerulein alone, but only triolein coadministration caused peripancreatic fat stranding, higher cytokines, UFAs, multisystem organ failure (MSOF) and mortality in 97% animals, which were prevented by orlistat. Conclusions UFAs, IL-1β and IL-8 are elevated in NCs. However, UFAs generated via peripancreatic fat lipolysis causes worse inflammation and MSOF, converting mild AP to SAP. PMID:25500204

  6. [Programmed necrosis: a new target for
ischemia reperfusion injury].

    PubMed

    Li, Xiaojing; Ming, Yingzi; Niu, Ying; Liu, Qianwen; Ye, Qifa

    2016-07-01

    Recent years, the researchers have found a new type of cell death, referred to programmed necrosis or necroptosis, which involves the death receptor and the ligand binds and is initiated under the inhibition of apoptosis pathway. Programmed necrosis possesses the morphological features of typical necrosis accompanied by inflammation. The receptor interacting protein kinase 1/3(RIPK1/3) can be inhibited by the specific inhibitors, such as necrostatin-1. RIPK1/3 could regulate programmed necrosis and play a key role in the process. The significance of programmed necrosis in ischemia-reperfusion injury (IRI) has been attracted great attention at present. Simultaneously, a series of studies have found it also involves in the IRI of heart, kidney, brain and retina. PMID:27592584

  7. Pathophysiology, Diagnosis, and Treatment of Radiation Necrosis in the Brain

    PubMed Central

    MIYATAKE, Shin-Ichi; NONOGUCHI, Noasuke; FURUSE, Motomasa; YORITSUNE, Erina; MIYATA, Tomo; KAWABATA, Shinji; KUROIWA, Toshihiko

    2015-01-01

    New radiation modalities have made it possible to prolong the survival of individuals with malignant brain tumors, but symptomatic radiation necrosis becomes a serious problem that can negatively affect a patient’s quality of life through severe and lifelong effects. Here we review the relevant literature and introduce our original concept of the pathophysiology of brain radiation necrosis following the treatment of brain, head, and neck tumors. Regarding the pathophysiology of radiation necrosis, we introduce two major hypotheses: glial cell damage or vascular damage. For the differential diagnosis of radiation necrosis and tumor recurrence, we focus on the role of positron emission tomography. Finally, in accord with our hypothesis regarding the pathophysiology, we describe the promising effects of the anti-vascular endothelial growth factor antibody bevacizumab on symptomatic radiation necrosis in the brain. PMID:25744350

  8. Plasma intestinal alkaline phosphatase isoenzymes in neonates with bowel necrosis.

    PubMed Central

    McLachlan, R; Coakley, J; Murton, L; Campbell, N

    1993-01-01

    AIM--To determine if the intestinal isoenzymes of alkaline phosphatase (ALP) are biochemical markers of bowel necrosis in neonates. METHODS--Plasma ALP isoenzymes were measured in 22 babies with bowel necrosis, histologically confirmed, and in 22 matched controls. The isoenzymes were also measured in 16 infants with signs of necrotising enterocolitis, who recovered without histological confirmation of bowel necrosis. The isoenzymes were separated by polyacrylamide gel electrophoresis. Auxiliary tests for identification included neuraminidase digestion and treatment with monoclonal and polyclonal antiplacental antibodies. RESULTS--Intestinal ALP was detected in 16 infants with bowel necrosis--13 had fetal intestinal ALP (FI-ALP) and three had adult intestinal ALP (AI-ALP). FI-ALP was detected in nine of the controls. In the babies with bowel necrosis intestinal ALP was found over all gestations, but in the controls only in those less than 34 weeks. The percentages of total ALP activity due to intestinal ALP were significantly higher in those with bowel necrosis compared with matched controls (p = 0.028). In babies of all gestations diagnostic sensitivity for the presence of intestinal ALP as a marker of bowel necrosis was 73% and diagnostic specificity 59%. In babies greater than 34 weeks' gestation, diagnostic sensitivity fell to 60% but the test became completely specific. In two babies FI-ALP increased from zero/trace to high activity coincident with the episode of bowel necrosis. In 16 babies with signs of necrotising enterocolitis but unconfirmed bowel necrosis FI-ALP was detected in four. CONCLUSION--Intestinal ALP seems to be released into the circulation in some babies with bowel necrosis, but its detection does not have the diagnostic sensitivity and specificity to be a reliable biochemical marker of the condition. Images PMID:8157755

  9. Immunization with viral antigens: infectious haematopoietic necrosis.

    PubMed

    Winton, J R

    1997-01-01

    Infectious haematopoietic necrosis (IHN) is one of the most important viral diseases of salmonids, especially among juvenile fish where losses can be high. For over 20 years, researchers have tested a variety of preparations for control of IHN. Early vaccines consisted of killed virus and were effective when delivered by injection, but too costly to be practical on a large scale. Attenuated vaccines were developed by serial passage in cell culture and by monoclonal antibody selection. These offered excellent protection and were cost-effective, but residual virulence and uncertainty about their effects on other aquatic species made them poor candidates for licensing. Subunit vaccines using part of the IHNV glycoprotein gene cloned into E. coli or into an attenuated strain of A. salmonicida have been tested, appeared safe and were inexpensive. These vaccines were reported to provide some protection when delivered by immersion. Information on the location of antigenic sites on the glycoprotein led to trials using synthetic peptides, but these did not seem to be economically viable. Recently, plasmid vectors encoding the glycoprotein gene under control of a cytomegalovirus promoter were developed for genetic immunization. The constructs were highly protective when delivered by injection, but a more practical delivery system is needed. Thus, while several vaccine strategies have been tried in order to stimulate specific immunity against IHN, more research is needed to develop a commercially viable product for control of this important disease. PMID:9270850

  10. Pyelo-ureteral necrosis after renal transplantation.

    PubMed

    Spasovski, Goce B; Masin-Spasovska, Jelka; Stavridis, Sotir; Saiti, Skender; Lekovski, Ljupco

    2008-01-01

    Because of the limited chance of receiving a kidney transplant (for several well-known reasons), a lot of desperate dialysis patients procure an unrelated donor kidney transplant against all medical advice. This type of renal paid transplantation is associated with many surgical complications and invasive opportunistic infections that increase the morbidity and mortality in this group of transplant recipients. In this report, we describe a case of a 22-year-old girl with a segmental infarction of the graft lower pole and a complete pyelo-ureteral necrosis as a consequence of some vascular damage, complicated by a pathohistological finding of an invasive candidiasis. Despite the successful surgical pyelovesical anastomosis and the good recovery of the patient and the kidney, long-term prognosis remains poor. The lack of information from the transplanting center regarding both donor and recipient and the associated, unacceptable risks on the graft and patient survival in unrelated, paid transplant recipients reinforce the standpoint that this practice should be abandoned. PMID:18204913

  11. [An infected necrosis of the chin].

    PubMed

    Muller, B S; van Goor, H F; Rosenberg, A J W P

    2016-07-01

    A 51-year-old man was referred by his dentist to a maxillofacial surgeon with complaints of illness and pain in the mandible, associated with a rapidly expanding area of black gingiva and mucosa surrounding the lower front teeth. Clinically and radiographically there was evidence of an infected necrosis of the chin and floor of mouth. Following debridement at the operating room, the patient was treated at the intensive care unit for septic shock leading to prolonged hospitalisation. Investigation of the bone marrow did not provide an explanation for pancytopenia or the severity of the illness. In addition, genetic investigation of thiopurine S-methyltransferase gene showed no mutations. This gene codes for an identically named protein enzyme that contributes in the metabolising of the medicine azathioprine, used daily for an autoimmune disease. A combination of the use of azathioprine, a folic acid deficiency and sepsis led to this exceptional course of illness. Therapeutic intervention consisted of surgical debridement and treatment of the bacteraemia. Afterwards several corrective surgeries were necessary to restore oral functions. PMID:27430038

  12. Clinical studies with tumour necrosis factor.

    PubMed

    Spriggs, D R; Sherman, M L; Frei, E; Kufe, D W

    1987-01-01

    The mechanism of tumour necrosis factor (TNF) cytotoxicity remains unknown. The in vivo antitumour effects of TNF may be related to direct cytotoxicity, immunomodulatory effects or endothelial effects on tumour vasculature. Phase I and early Phase II clinical trials of human recombinant TNF are under way in Japan, the USA, the UK and Germany. The maximum Phase II dose for TNF has not been established. The clinical toxicity of TNF is generally similar to that of other biological agents. Systemic toxicity, including fever, chills, anorexia and nausea, has been seen in most patients treated with TNF and has not been clearly related to dose. Other toxicities have included liver function abnormalities, hypotension, transient neurological changes and haematological abnormalities. Few clinical responses have been reported but organized Phase II testing remains to be completed. Combination trials with interferons have recently been initiated. Phase II efficacy studies of TNF as a single agent and in combination are needed for an assessment of the value of this agent in cancer therapy. PMID:3330011

  13. Skylab water balance analysis

    NASA Technical Reports Server (NTRS)

    Leonard, J. I.

    1977-01-01

    The water balance of the Skylab crew was analyzed. Evaporative water loss using a whole body input/output balance equation, water, body tissue, and energy balance was analyzed. The approach utilizes the results of several major Skylab medical experiments. Subsystems were designed for the use of the software necessary for the analysis. A partitional water balance that graphically depicts the changes due to water intake is presented. The energy balance analysis determines the net available energy to the individual crewman during any period. The balances produce a visual description of the total change of a particular body component during the course of the mission. The information is salvaged from metabolic balance data if certain techniques are used to reduce errors inherent in the balance method.

  14. What is balance?

    PubMed

    Pollock, A S; Durward, B R; Rowe, P J; Paul, J P

    2000-08-01

    Balance is a term frequently used by health professionals working in a wide variety of clinical specialities. There is no universally accepted definition of human balance, or related terms. This article identifies mechanical definitions of balance and introduces clinical definitions of balance and postural control. Postural control is defined as the act of maintaining, achieving or restoring a state of balance during any posture or activity. Postural control strategies may be either predictive or reactive, and may involve either a fixed-support or a change-in-support response. Clinical tests of balance assess different components of balance ability. Health professionals should select clinical assessments based on a sound knowledge and understanding of the classification of balance and postural control strategies. PMID:10945424

  15. Polarization-balanced beamsplitter

    DOEpatents

    Decker, D.E.

    1998-02-17

    A beamsplitter assembly is disclosed that includes several beamsplitter cubes arranged to define a plurality of polarization-balanced light paths. Each polarization-balanced light path contains one or more balanced pairs of light paths, where each balanced pair of light paths includes either two transmission light paths with orthogonal polarization effects or two reflection light paths with orthogonal polarization effects. The orthogonal pairing of said transmission and reflection light paths cancels polarization effects otherwise caused by beamsplitting. 10 figs.

  16. Polarization-balanced beamsplitter

    DOEpatents

    Decker, Derek E.

    1998-01-01

    A beamsplitter assembly that includes several beamsplitter cubes arranged to define a plurality of polarization-balanced light paths. Each polarization-balanced light path contains one or more balanced pairs of light paths, where each balanced pair of light paths includes either two transmission light paths with orthogonal polarization effects or two reflection light paths with orthogonal polarization effects. The orthogonal pairing of said transmission and reflection light paths cancels polarization effects otherwise caused by beamsplitting.

  17. Early growth response 1 regulates glucose deprivation-induced necrosis

    PubMed Central

    JEON, HYUN MIN; LEE, SU YEON; JU, MIN KYUNG; KIM, CHO HEE; PARK, HYE GYEONG; KANG, HO SUNG

    2013-01-01

    Necrosis is commonly found in the core region of solid tumours due to metabolic stress such as hypoxia and glucose deprivation (GD) resulting from insufficient vascularization. Necrosis promotes tumour growth and development by releasing the tumour-promoting cytokine high mobility group box 1 (HMGB1); however, the molecular mechanism underlying necrotic cell death remains largely unknown. In this study, we show that early growth response 1 (Egr-1) is induced in a reactive oxygen species (ROS)-dependent manner by GD in several cell lines such as A549, MDA-MB-231 and HepG2 cells that exhibit necrosis upon GD. We found that Egr-1 short hairpin RNA (shRNA) prevented GD-induced necrosis and HMGB1 release. Necrosis-inhibiting activity of Egr-1 shRNA was also seen in multicellular tumour spheroids (MTSs), an in vitro tumour model system. In contrast, Egr-1 overexpression appeared to make tumour cells more susceptible to GD-induced necrosis. Finally, Egr-1 shRNA suppressed the growth of MTSs. These findings demonstrate that Egr-1 is implicated in GD-induced necrosis and tumour progression. PMID:23152075

  18. Wind Tunnel Balances

    NASA Technical Reports Server (NTRS)

    Warner, Edward P; Norton, F H

    1920-01-01

    Report embodies a description of the balance designed and constructed for the use of the National Advisory Committee for Aeronautics at Langley Field, and also deals with the theory of sensitivity of balances and with the errors to which wind tunnel balances of various types are subject.

  19. Coaching for Balance.

    ERIC Educational Resources Information Center

    Larson, Bonnie

    2001-01-01

    Discusses coaching for balance the integration of the whole self: physical (body), intellectual (mind), spiritual (soul), and emotional (heart). Offers four ways to identify problems and tell whether someone is out of balance and four coaching techniques for creating balance. (Contains 11 references.) (JOW)

  20. Challenges With the Diagnosis and Treatment of Cerebral Radiation Necrosis

    SciTech Connect

    Chao, Samuel T.; Ahluwalia, Manmeet S.; Barnett, Gene H.; Stevens, Glen H.J.; Murphy, Erin S.; Stockham, Abigail L.; Shiue, Kevin; Suh, John H.

    2013-11-01

    The incidence of radiation necrosis has increased secondary to greater use of combined modality therapy for brain tumors and stereotactic radiosurgery. Given that its characteristics on standard imaging are no different that tumor recurrence, it is difficult to diagnose without use of more sophisticated imaging and nuclear medicine scans, although the accuracy of such scans is controversial. Historically, treatment had been limited to steroids, hyperbaric oxygen, anticoagulants, and surgical resection. A recent prospective randomized study has confirmed the efficacy of bevacizumab in treating radiation necrosis. Novel therapies include using focused interstitial laser thermal therapy. This article will review the diagnosis and treatment of radiation necrosis.

  1. Anti-necrosis potential of polyphenols against snake venoms.

    PubMed

    Leanpolchareanchai, Jiraporn; Pithayanukul, Pimolpan; Bavovada, Rapepol

    2009-01-01

    Polyphenols from the extracts of Areca catechu L. and Quercus infectoria Oliv. inhibited phospholipase A(2), proteases, hyaluronidase and L-amino acid oxidase of Naja naja kaouthia Lesson (NK) and Calloselasma rhodostoma Kuhl (CR) venoms by in vitro tests. Both extracts inhibited the hemorrhagic activity of CR venom and the dermonecrotic activity of NK venom by in vivo tests. The inhibitory activity of plant polyphenols against local tissue necrosis induced by snake venoms may be caused by inhibition of inflammatory reactions, hemorrhage, and necrosis. The result implies the therapeutic potential of plant polyphenols against necrosis in snakebite victims. PMID:19874222

  2. Practical quantification of necrosis in histological whole-slide images.

    PubMed

    Homeyer, André; Schenk, Andrea; Arlt, Janine; Dahmen, Uta; Dirsch, Olaf; Hahn, Horst K

    2013-06-01

    Since the histological quantification of necrosis is a common task in medical research and practice, we evaluate different image analysis methods for quantifying necrosis in whole-slide images. In a practical usage scenario, we assess the impact of different classification algorithms and feature sets on both accuracy and computation time. We show how a well-chosen combination of multiresolution features and an efficient postprocessing step enables the accurate quantification necrosis in gigapixel images in less than a minute. The results are general enough to be applied to other areas of histological image analysis as well. PMID:23796718

  3. Incus and stapes necrosis associated with diabetes mellitus.

    PubMed

    Tüz, M; Doğru, H; Yasan, H; Döner, F; Yariktaş, M

    2006-07-01

    Chronic otitis media is often associated with ossicular defects, the most frequent being necrosis of the long process of incus. Except for infection and cholesteatoma; trauma and local pressure by chorda tympani are uncommon causes leading to incus erosion. In the literature, no case of incus necrosis has been reported associated with type II diabetes mellitus (DM). A patient is presented in this report with incus and stapes suprastructure necrosis and associated type II DM who was admitted to the out-patient clinic with complaints of conductive hearing loss. PMID:16834796

  4. Reconceptualizing balance: attributes associated with balance performance.

    PubMed

    Thomas, Julia C; Odonkor, Charles; Griffith, Laura; Holt, Nicole; Percac-Lima, Sanja; Leveille, Suzanne; Ni, Pensheng; Latham, Nancy K; Jette, Alan M; Bean, Jonathan F

    2014-09-01

    Balance tests are commonly used to screen for impairments that put older adults at risk for falls. The purpose of this study was to determine the attributes that were associated with balance performance as measured by the Frailty and Injuries: Cooperative Studies of Intervention Techniques (FICSIT) balance test. This study was a cross-sectional secondary analysis of baseline data from a longitudinal cohort study, the Boston Rehabilitative Impairment Study of the Elderly (Boston RISE). Boston RISE was performed in an outpatient rehabilitation research center and evaluated Boston area primary care patients aged 65 to 96 (N=364) with self-reported difficulty or task-modification climbing a flight of stairs or walking 1/2 of a mile. The outcome measure was standing balance as measured by the FICSIT-4 balance assessment. Other measures included: self-efficacy, pain, depression, executive function, vision, sensory loss, reaction time, kyphosis, leg range of motion, trunk extensor muscle endurance, leg strength and leg velocity at peak power. Participants were 67% female, had an average age of 76.5 (±7.0) years, an average of 4.1 (±2.0) chronic conditions, and an average FICSIT-4 score of 6.7 (±2.2) out of 9. After adjusting for age and gender, attributes significantly associated with balance performance were falls self-efficacy, trunk extensor muscle endurance, sensory loss, and leg velocity at peak power. FICSIT-4 balance performance is associated with a number of behavioral and physiologic attributes, many of which are amenable to rehabilitative treatment. Our findings support a consideration of balance as multidimensional activity as proposed by the current International Classification of Functioning, Disability, and Health (ICF) model. PMID:24952097

  5. Post-facelift flap necrosis treatment using charged polystyrene microspheres

    PubMed Central

    Weissman, Oren; Farber, Nimrod; Remer, Eric; Tessone, Ariel; Trivizki, Omer; Bank, Jonathan; Winkler, Eyal; Zilinsky, Isaac; Haik, Josef

    2013-01-01

    BACKGROUND: Flap necrosis following facial rhytidectomy constitutes a vexing and grievous complication to the patient and the surgeon. Treatment modalities that can expedite wound healing and re-epithelialization rates are highly desired. OBJECTIVES: To assess wound healing and re-epithelialization rates of open wounds following postrhytidectomy flap necrosis treated with commercially available charged polystyrene microspheres (Polyheal-1, Polyheal Ltd, Israel). METHODS: Flap necrosis following rhytidectomy with open wounds in three female patients were treated using dressings soaked with Polyheal-1. Wound closure rates were documented. RESULTS: The wounds demonstrated both accelerated granulation tissue formation and rapid re-epithelialization rates. No complications or side effects were encountered. CONCLUSIONS: Charged polystyrene microspheres may offer a new and efficacious way to treat open wounds due to flap necrosis following facial rhytidectomy. Further research with larger patient numbers is still needed to verify these findings. PMID:24431937

  6. Skin and Neourethral Necrosis in Staged Hypospadias Repair

    PubMed Central

    Mahdavi, Alireza; Sarafi, Mehdi

    2016-01-01

    Complications in hypospadias surgery are not uncommon however penile skin or flap necrosis is rarely reported. Ischemia of the flap or graft is a major complication in two stage repair of hypospadias. A 2-year old boy with proximal penile hypospadias, operated earlier for chordee correction and urethral plate formation with a preputial flap, presented for stage 2 repair. Ten days after surgery patient developed skin and neourethral necrosis. Early debridement was done followed by coverage with scrotal flaps. PMID:27398320

  7. Skin and Neourethral Necrosis in Staged Hypospadias Repair.

    PubMed

    Mirshemirani, Alireza; Mahdavi, Alireza; Sarafi, Mehdi

    2016-01-01

    Complications in hypospadias surgery are not uncommon however penile skin or flap necrosis is rarely reported. Ischemia of the flap or graft is a major complication in two stage repair of hypospadias. A 2-year old boy with proximal penile hypospadias, operated earlier for chordee correction and urethral plate formation with a preputial flap, presented for stage 2 repair. Ten days after surgery patient developed skin and neourethral necrosis. Early debridement was done followed by coverage with scrotal flaps. PMID:27398320

  8. Robotic cystogastrostomy and debridement of walled-off pancreatic necrosis.

    PubMed

    Nassour, Ibrahim; Ramzan, Zeeshan; Kukreja, Sachin

    2016-09-01

    Walled-off pancreatic necrosis is a known complication of acute pancreatitis and requires intervention if symptomatic or complicated. Laparoscopic cystogastrostomy as a minimally invasive surgical intervention has been well-described in surgical literature but data on a robotic approach is limited. Here we report a case of robotic cystogastrostomy and debridement of walled-off pancreatic necrosis in a patient with a history of severe biliary pancreatitis. PMID:27039191

  9. Cyclophilin D regulates necrosis, but not apoptosis, of murine eosinophils.

    PubMed

    Zhu, Xiang; Hogan, Simon P; Molkentin, Jeffery D; Zimmermann, Nives

    2016-04-15

    Eosinophil degranulation and clusters of free extracellular granules are frequently observed in diverse diseases, including atopic dermatitis, nasal polyposis, and eosinophilic esophagitis. Whether these intact granules are released by necrosis or a biochemically mediated cytolysis remains unknown. Recently, a peptidyl-prolyl isomerase located within the mitochondrial matrix, cyclophilin D (PPIF), was shown to regulate necrotic, but not apoptotic, cell death in vitro in fibroblasts, hepatocytes, and cardiomyocytes. Whether cyclophilin D regulates necrosis in hematopoietic cells such as eosinophils remains unknown. We used PPIF-deficient (Ppif(-/-)) mice to test whether cyclophilin D is required for regulating eosinophil necrosis. PPIF deficiency did not affect eosinophil development or maturation at baseline. After in vitro ionomycin or H2O2 treatment, Ppif(-/-) eosinophils were significantly protected from Ca(2+) overload- or oxidative stress-induced necrosis. Additionally, Ppif(-/-) eosinophils demonstrated significantly decreased necrosis, but not apoptosis, in response to Siglec-F cross-linking, a stimulus associated with eosinophil-mediated processes in vitro and in vivo. When treated with apoptosis inducers, Ppif(+/+) and Ppif(-/-) eosinophils exhibited no significant difference in apoptosis or secondary necrosis. Finally, in a dextran sodium sulfate-induced colitis model, although levels of colitogenic cytokines and eosinophil-selective chemokines were comparable between Ppif(+/+) and Ppif(-/-) mice, the latter exhibited decreased clinical outcomes. This correlated with significantly reduced eosinophil cytolysis in the colon. Collectively, our present studies demonstrate that murine eosinophil necrosis is regulated in vitro and in vivo by cyclophilin D, at least in part, thus providing new insight into the mechanism of eosinophil necrosis and release of free extracellular granules in eosinophil-associated diseases. PMID:26893161

  10. Identifying Balance in a Balanced Scorecard System

    ERIC Educational Resources Information Center

    Aravamudhan, Suhanya; Kamalanabhan, T. J.

    2007-01-01

    In recent years, strategic management concepts seem to be gaining greater attention from the academicians and the practitioner's alike. Balanced Scorecard (BSC) concept is one such management concepts that has spread in worldwide business and consulting communities. The BSC translates mission and vision statements into a comprehensive set of…

  11. Programmed necrosis in the Cross Talk of Cell Death and Inflammation

    PubMed Central

    Chan, Francis Ka-Ming; Luz, Nivea Farias; Moriwaki, Kenta

    2015-01-01

    Cell proliferation and cell death are integral elements in maintaining homeostatic balance in metazoans. Disease pathologies ensue when these processes are disturbed. A plethora of evidence indicates that malfunction of cell death can lead to inflammation, autoimmunity or immuno-deficiency. Programmed necrosis or necroptosis is a form of non-apoptotic cell death driven by the receptor interacting protein kinase 3 (RIPK3) and its substrate mixed lineage kinase domain-like (MLKL). RIPK3 partners with its upstream adaptors RIPK1, TRIF or DAI to signal for necroptosis in response to death receptor or toll-like receptor stimulation, pathogen infection, or sterile cell injury. Necroptosis promotes inflammation through leakage of cellular contents from damaged plasma membrane. Intriguingly, many of the signal adaptors of necroptosis have dual functions in innate immune signaling. This unique signature illustrates the cooperative nature of necroptosis and innate inflammatory signaling pathways in managing cell and organismal stresses from pathogen infection and sterile tissue injury. PMID:25493335

  12. Judicial Checks and Balances

    ERIC Educational Resources Information Center

    La Porta, Rafael; Lopez-de-Silanes, Florencio; Pop-Eleches, Cristian; Shleifer, Andrei

    2004-01-01

    In the Anglo-American constitutional tradition, judicial checks and balances are often seen as crucial guarantees of freedom. Hayek distinguishes two ways in which the judiciary provides such checks and balances: judicial independence and constitutional review. We create a new database of constitutional rules in 71 countries that reflect these…

  13. Inevitability of Balance Restoration

    PubMed Central

    2010-01-01

    Prolonged imbalance between input and output of any element in a living organism is incompatible with life. The duration of imbalance varies, but eventually balance is achieved. This rule applies to any quantifiable element in a compartment of finite capacity. Transient discrepancies occur regularly, but given sufficient time, balance is always achieved, because permanent imbalance is impossible, and the mechanism for eventual restoration of balance is foolproof. The kidney is a central player for balance restoration of fluid and electrolytes, but the smartness of the kidney is not the reason for perfect balance. The kidney merely accelerates the process. The most crucial element of the control system is that discrepancy between intake and output inevitably leads to a change in total content of the element in the system, and uncorrected balance has a cumulative effect on the overall content of the element. In a living organism, the speed of restoration of balance depends on the permissible duration of imbalance without death or severe disability. The three main factors that influence the speed of balance restoration are: magnitude of flux, basal store, and capacity for additional storage. For most electrolytes, total capacity is such that a substantial discrepancy is not possible for more than a week or two. Most control mechanisms correct abnormality partially. The infinite gain control mechanism is unique in that abnormality is completely corrected upon completion of compensation. PMID:21468193

  14. Chemical Equation Balancing.

    ERIC Educational Resources Information Center

    Blakley, G. R.

    1982-01-01

    Reviews mathematical techniques for solving systems of homogeneous linear equations and demonstrates that the algebraic method of balancing chemical equations is a matter of solving a system of homogeneous linear equations. FORTRAN programs using this matrix method to chemical equation balancing are available from the author. (JN)

  15. Leadership: A Balancing Act

    ERIC Educational Resources Information Center

    Hines, Thomas E.

    2011-01-01

    Maintaining balance in leadership can be difficult because balance is affected by the personality, strengths, and attitudes of the leader as well as the complicated environment within and outside the community college itself. This article explores what being a leader at the community college means, what the threats are to effective leadership, and…

  16. The Technology Balance Beam

    ERIC Educational Resources Information Center

    Coulson, Eddie K.

    2006-01-01

    "The Technology Balance Beam" is designed to question the role of technology within school districts. This case study chronicles a typical school district in relation to the school district's implementation of technology beginning in the 1995-1996 school year. The fundamental question that this scenario raises is, What is the balance between…

  17. A Balance of Power?

    ERIC Educational Resources Information Center

    Mosey, Edward

    1991-01-01

    The booming economy of the Pacific Northwest region promotes the dilemma of balancing the need for increased electrical power with the desire to maintain that region's unspoiled natural environment. Pertinent factors discussed within the balance equation are population trends, economic considerations, industrial power requirements, and…

  18. Balanced Literacy Instruction.

    ERIC Educational Resources Information Center

    Pressley, Michael; Roehrig, Alysia; Bogner, Kristen; Raphael, Lisa M.; Dolezal, Sara

    2002-01-01

    This article reviews the evidence for balanced literacy instruction in the elementary years. The case is made that the balanced instructional model is particularly appropriate and beneficial for students who have initial difficulties in learning to read and write. Key features of successful reading instruction programs are described. (Contains…

  19. Apoptosis, oncosis, and necrosis. An overview of cell death.

    PubMed Central

    Majno, G.; Joris, I.

    1995-01-01

    The historical development of the cell death concept is reviewed, with special attention to the origin of the terms necrosis, coagulation necrosis, autolysis, physiological cell death, programmed cell death, chromatolysis (the first name of apoptosis in 1914), karyorhexis, karyolysis, and cell suicide, of which there are three forms: by lysosomes, by free radicals, and by a genetic mechanism (apoptosis). Some of the typical features of apoptosis are discussed, such as budding (as opposed to blebbing and zeiosis) and the inflammatory response. For cell death not by apoptosis the most satisfactory term is accidental cell death. Necrosis is commonly used but it is not appropriate, because it does not indicate a form of cell death but refers to changes secondary to cell death by any mechanism, including apoptosis. Abundant data are available on one form of accidental cell death, namely ischemic cell death, which can be considered an entity of its own, caused by failure of the ionic pumps of the plasma membrane. Because ischemic cell death (in known models) is accompanied by swelling, the name oncosis is proposed for this condition. The term oncosis (derived from ónkos, meaning swelling) was proposed in 1910 by von Reckling-hausen precisely to mean cell death with swelling. Oncosis leads to necrosis with karyolysis and stands in contrast to apoptosis, which leads to necrosis with karyorhexis and cell shrinkage. Images Figure 1 Figure 2 Figure 3 Figure 5 Figure 6 Figure 7 Figure 8 PMID:7856735

  20. Computed tomography predictors of hepatocellular carcinoma tumour necrosis after chemoembolization

    PubMed Central

    Bryant, Mary K; Dorn, David P; Zarzour, Jessica; Smith, J Kevin; Redden, David T; Saddekni, Souheil; Aal, Ahmed Kamel Abdel; Gray, Stephen H; Eckhoff, Devin E; DuBay, Derek A

    2014-01-01

    Background Radiographical features associated with a favourable response to trans-arterial chemoembolization (TACE) are poorly defined for patients with hepatocellular carcinoma (HCC). Methods From 2008 to 2012, all first TACE interventions for HCC performed at the University of Alabama at Birmingham (UAB) were retrospectively reviewed. Only patients with a pre-TACE and a post-TACE computed tomography (CT) scan were included in the analyses (n = 115). HCC tumour response to TACE was quantified via the the modified Response Evaluation Criteria in Solid Tumors (mRECIST) criteria. Univariate and multivariable analyses were constructed. Results The index HCC tumours experienced a > 90% or complete tumour necrosis in 59/115 (51%) of patients after the first TACE intervention. On univariate analysis, smaller tumour size, peripheral tumour location and arterial enhancement were associated with a > 90% or complete tumour necrosis, whereas, only smaller tumour size [odds ratio (OR) 0.62; 95% confidence interval (CI) 0.48, 0.81] and peripheral location (OR 6.91; 95% CI 1.75, 27.29) were significant on multivariable analysis. There was a trend towards improved survival in the patients that experienced a > 90% or complete tumour necrosis (P = 0.08). Conclusions Peripherally located smaller HCC tumours are most likely to experience a > 90% or complete tumour necrosis after TACE. Surprisingly, arterial-phase enhancement and portal venous-phase washout were not significantly predictive of TACE-induced tumour necrosis. The TACE response was not statistically associated with improved survival. PMID:23980917

  1. The Extracellular Matrix Regulates Granuloma Necrosis in Tuberculosis.

    PubMed

    Al Shammari, Basim; Shiomi, Takayuki; Tezera, Liku; Bielecka, Magdalena K; Workman, Victoria; Sathyamoorthy, Tarangini; Mauri, Francesco; Jayasinghe, Suwan N; Robertson, Brian D; D'Armiento, Jeanine; Friedland, Jon S; Elkington, Paul T

    2015-08-01

    A central tenet of tuberculosis pathogenesis is that caseous necrosis leads to extracellular matrix destruction and bacterial transmission. We reconsider the underlying mechanism of tuberculosis pathology and demonstrate that collagen destruction may be a critical initial event, causing caseous necrosis as opposed to resulting from it. In human tuberculosis granulomas, regions of extracellular matrix destruction map to areas of caseous necrosis. In mice, transgenic expression of human matrix metalloproteinase 1 causes caseous necrosis, the pathological hallmark of human tuberculosis. Collagen destruction is the principal pathological difference between humanised mice and wild-type mice with tuberculosis, whereas the release of proinflammatory cytokines does not differ, demonstrating that collagen breakdown may lead to cell death and caseation. To investigate this hypothesis, we developed a 3-dimensional cell culture model of tuberculosis granuloma formation, using bioelectrospray technology. Collagen improved survival of Mycobacterium tuberculosis-infected cells analyzed on the basis of a lactate dehydrogenase release assay, propidium iodide staining, and measurement of the total number of viable cells. Taken together, these findings suggest that collagen destruction is an initial event in tuberculosis immunopathology, leading to caseous necrosis and compromising the immune response, revealing a previously unappreciated role for the extracellular matrix in regulating the host-pathogen interaction. PMID:25676469

  2. Effect of bevacizumab on radiation necrosis of the brain

    SciTech Connect

    Gonzalez, Javier; Kumar, Ashok J.; Conrad, Charles A.; Levin, Victor A. . E-mail: vlevin@mdanderson.org

    2007-02-01

    Purpose: Because blocking vascular endothelial growth factor (VEGF) from reaching leaky capillaries is a logical strategy for the treatment of radiation necrosis, we reasoned that bevacizumab might be an effective treatment of radiation necrosis. Patients and Methods: Fifteen patients with malignant brain tumors were treated with bevacizumab or bevacizumab combination for their tumor on either a 5 mg/kg/2-week or 7.5 mg/kg/3-week schedule. Radiation necrosis was diagnosed in 8 of these patients on the basis of magnetic resonance imaging (MRI) and biopsy. MRI studies were obtained before treatment and at 6-week to 8-week intervals. Results: Of the 8 patients with radiation necrosis, posttreatment MRI performed an average of 8.1 weeks after the start of bevacizumab therapy showed a reduction in all 8 patients in both the MRI fluid-attenuated inversion-recovery (FLAIR) abnormalities and T1-weighted post-Gd-contrast abnormalities. The average area change in the T1-weighted post-Gd-contrast abnormalities was 48% ({+-}22 SD), and the average change in the FLAIR images was 60% ({+-}18 SD). The average reduction in daily dexamethasone requirements was 8.6 mg ({+-}3.6). Conclusion: Bevacizumab, alone and in combination with other agents, can reduce radiation necrosis by decreasing capillary leakage and the associated brain edema. Our findings will need to be confirmed in a randomized trial to determine the optimal duration of treatment.

  3. Active balance system and vibration balanced machine

    NASA Technical Reports Server (NTRS)

    Qiu, Songgang (Inventor); Augenblick, John E. (Inventor); Peterson, Allen A. (Inventor); White, Maurice A. (Inventor)

    2005-01-01

    An active balance system is provided for counterbalancing vibrations of an axially reciprocating machine. The balance system includes a support member, a flexure assembly, a counterbalance mass, and a linear motor or an actuator. The support member is configured for attachment to the machine. The flexure assembly includes at least one flat spring having connections along a central portion and an outer peripheral portion. One of the central portion and the outer peripheral portion is fixedly mounted to the support member. The counterbalance mass is fixedly carried by the flexure assembly along another of the central portion and the outer peripheral portion. The linear motor has one of a stator and a mover fixedly mounted to the support member and another of the stator and the mover fixedly mounted to the counterbalance mass. The linear motor is operative to axially reciprocate the counterbalance mass.

  4. Chemical regulation of signaling pathways to programmed necrosis.

    PubMed

    Bae, Ji Hyun; Shim, Jung-Hyun; Cho, Young Sik

    2014-06-01

    Necroptosis is an active and well-orchestrated necrosis, distinctive from apoptosis in microscopic structure, and biochemical and molecular features. Unlike apoptosis-undergoing cells, which are removed by macrophage or neighboring cells, necrotic cell death releases danger signals and provokes inflammation, and further a severe damage to neighbor tissue. A regulated necrosis, termed as necroptosis or programmed necrosis, is emerging as a new paradigm of cell death that can be activated when apoptotic machinery is genetically or pathogenically defective. It plays biological significances in pathogenesis of a variety of inflammatory diseases as well as in a beneficial innate immune defense mechanism. This review highlights the identification of hits against necroptosis, and comprehensive approaches to discovery of small molecules that regulate necroptotic cell death. Also, the signaling molecular mechanism of necroptosis and future clinical uses of necroptosis inhibitor will be described in brief. PMID:24715577

  5. Scintigraphic study of propylthiouracil induced submassive hepatic necrosis.

    PubMed

    Singh, A; Thakur, R

    1995-02-01

    Drug induced hepatitis is a rare complication of thiourea antithyroid drugs. In some patients, the hepatotoxicity may be severe and lead to submassive hepatic necrosis (SHN). Submassive hepatic necrosis is a potentially fatal complication which is usually recognized on the liver biopsy and histological examination or autopsy. In the case presented here, SHN was identified on Tc-99m SC liver images. Sharply defined intrahepatic photopenic abnormalities without significant colloid shift were noted. SPECT images were most remarkable and exhibited extensive liver necrosis. Resolution of hepatic abnormalities correlated with clinical and biochemical resolution of SHN. In patients with propylthiouracil hepatotoxicity, serial liver SPECT images with Tc-99m SC appear helpful for the diagnosis and follow up of SHN and, in an appropriate clinical context, may obviate the need for liver biopsy. PMID:7720304

  6. Conjunctival Necrosis and Scleritis Following Subtenon Triamcinolone Acetonide Injection

    PubMed Central

    Eslampour, Alireza; Abrishami, Mojtaba; Tafaghodi, Somaye

    2013-01-01

    The present study aims to report a case of conjunctival necrosis and scleritis due to a subtenon injection of triamcinolone acetonate. A 15-year-old boy received a subtenon injection of triamcinolone acetonate after a pars plana vitrectomy due to an intraocular foreign body. Seven days later, conjunctival necrosis and scleritis appeared at the site of injection. No improvement was seen after seven days of conservative treatment, and necrotic tissue debridement was performed. Within one week the conjunctiva cleared. Conjunctival necrosis and scleritis are rare complications of periocular corticosteroid injections, but an early diagnosis can be very valuable. Improper dosage and injection site of corticosteroids with insufficient prophylactic antibiotics are predisposing factors. If conservative treatment is not sufficient, debridement should be considered as a potential critical treatment option. PMID:24396585

  7. [Treatment of early stage avascular necrosis of the femoral head].

    PubMed

    Zhu, He-Yu; Zhu, Bing

    2012-07-01

    Avascular necrosis is a progressively devastating disease and primarily affects weight-bearing joints. The hip is the most commonly affected joint. In early stage, nonoperative (including pharmacologic intervention and biophysical treatments) and operative modalities for protecting hip joint have become the main therapeutic methods. However there is still no satisfied mothod with reasonable effect. According to the treatment of the avascular necrosis of the femoral head of the pre-collapse stage, core decompression with modification of technique is still one of the safest and most commonly employed procedures. Recently there have been attempts to enhance the effect of core decompression with use of various growth and differentiation factors. Which is the hot spot of current research. Early diagnosis is the key to the treatment of the avascular necrosis of the femoral head. Comprehensive treatment which is based on the core decompression is still the main treatment of today. PMID:23116002

  8. Contemporary management of infected necrosis complicating severe acute pancreatitis

    PubMed Central

    Jamdar, Saurabh; Siriwardena, Ajith K

    2006-01-01

    Pancreatic necrosis complicating severe acute pancreatitis is a challenging scenario in contemporary critical care practice; it requires multidisciplinary care in a setting where there is a relatively limited evidence base to support decision making. This commentary provides a concise overview of current management of patients with infected necrosis, focusing on detection, the role of pharmacologic intervention, and the timing and nature of surgical interventions. Fine-needle aspiration of necrosis remains the mainstay for establishment of infection. Pharmacological intervention includes antibiotic therapy as an adjunct to surgical debridement/drainage and, more recently, drotrecogin alfa. Specific concerns remain regarding the suitability of drotrecogin alfa in this setting. Early surgical intervention is unhelpful; surgery is indicated when there is strong evidence for infection of necrotic tissue, with the current trend being toward 'less drastic' surgical interventions. PMID:16356213

  9. Cannabinoids act as necrosis-inducing factors in Cannabis sativa

    PubMed Central

    Shoyama, Yoshinari; Sugawa, Chitomi; Tanaka, Hiroyuki

    2008-01-01

    Cannabis sativa is well known to produce unique secondary metabolites called cannabinoids. We recently discovered that Cannabis leaves induce cell death by secreting tetrahydrocannabinolic acid (THCA) into leaf tissues. Examinations using isolated Cannabis mitochondria demonstrated that THCA causes mitochondrial permeability transition (MPT) though opening of MPT pores, resulting in mitochondrial dysfunction (the important feature of necrosis). Although Ca2+ is known to cause opening of animal MPT pores, THCA directly opened Cannabis MPT pores in the absence of Ca2+. Based on these results, we conclude that THCA has the ability to induce necrosis though MPT in Cannabis leaves, independently of Ca2+. We confirmed that other cannabinoids (cannabidiolic acid and cannabigerolic acid) also have MPT-inducing activity similar to that of THCA. Moreover, mitochondria of plants which do not produce cannabinoids were shown to induce MPT by THCA treatment, thus suggesting that many higher plants may have systems to cause THCA-dependent necrosis. PMID:19704450

  10. Cannabinoids act as necrosis-inducing factors in Cannabis sativa.

    PubMed

    Shoyama, Yoshinari; Sugawa, Chitomi; Tanaka, Hiroyuki; Morimoto, Satoshi

    2008-12-01

    Cannabis sativa is well known to produce unique secondary metabolites called cannabinoids. We recently discovered that Cannabis leaves induce cell death by secreting tetrahydrocannabinolic acid (THCA) into leaf tissues. Examinations using isolated Cannabis mitochondria demonstrated that THCA causes mitochondrial permeability transition (MPT) though opening of MPT pores, resulting in mitochondrial dysfunction (the important feature of necrosis). Although Ca(2+) is known to cause opening of animal MPT pores, THCA directly opened Cannabis MPT pores in the absence of Ca(2+). Based on these results, we conclude that THCA has the ability to induce necrosis though MPT in Cannabis leaves, independently of Ca(2+). We confirmed that other cannabinoids (cannabidiolic acid and cannabigerolic acid) also have MPT-inducing activity similar to that of THCA. Moreover, mitochondria of plants which do not produce cannabinoids were shown to induce MPT by THCA treatment, thus suggesting that many higher plants may have systems to cause THCA-dependent necrosis. PMID:19704450

  11. Flap Necrosis after Palatoplasty in Patients with Cleft Palate

    PubMed Central

    Rossell-Perry, Percy

    2015-01-01

    Palatal necrosis after palatoplasty in patients with cleft palate is a rare but significant problem encountered by any cleft surgeon. Few studies have addressed this disastrous complication and the prevalence of this problem remains unknown. Failure of a palatal flap may be attributed to different factors like kinking or section of the pedicle, anatomical variations, tension, vascular thrombosis, type of cleft, used surgical technique, surgeon's experience, infection, and malnutrition. Palatal flap necrosis can be prevented through identification of the risk factors and a careful surgical planning should be done before any palatoplasty. Management of severe fistulas observed as a consequence of palatal flap necrosis is a big challenge for any cleft surgeon. Different techniques as facial artery flaps, tongue flaps, and microvascular flaps have been described with this purpose. This review article discusses the current status of this serious complication in patients with cleft palate. PMID:26273624

  12. Load Balancing Scientific Applications

    SciTech Connect

    Pearce, Olga Tkachyshyn

    2014-12-01

    The largest supercomputers have millions of independent processors, and concurrency levels are rapidly increasing. For ideal efficiency, developers of the simulations that run on these machines must ensure that computational work is evenly balanced among processors. Assigning work evenly is challenging because many large modern parallel codes simulate behavior of physical systems that evolve over time, and their workloads change over time. Furthermore, the cost of imbalanced load increases with scale because most large-scale scientific simulations today use a Single Program Multiple Data (SPMD) parallel programming model, and an increasing number of processors will wait for the slowest one at the synchronization points. To address load imbalance, many large-scale parallel applications use dynamic load balance algorithms to redistribute work evenly. The research objective of this dissertation is to develop methods to decide when and how to load balance the application, and to balance it effectively and affordably. We measure and evaluate the computational load of the application, and develop strategies to decide when and how to correct the imbalance. Depending on the simulation, a fast, local load balance algorithm may be suitable, or a more sophisticated and expensive algorithm may be required. We developed a model for comparison of load balance algorithms for a specific state of the simulation that enables the selection of a balancing algorithm that will minimize overall runtime.

  13. A new geographic and host record for infectious pancreatic necrosis

    USGS Publications Warehouse

    Parisot, T.J.; Yasutake, W.T.; Bressler, V.

    1963-01-01

    The occurrence of infectious pancreatic necrosis in rainbow trout (Salmo gairdneri), brook trout (Salvelinus fontinalis), and cutthroat trout (Salmo clarki) has been experimentally authenticated for the first time in the western United States. The cutthroat trout represents a new host. Brook trout fin tissue culture inoculated with bacteria-free filtrate from the diseased fish tissue showed marked degenerative changes after 24 hours. Chinook salmon (Oncorhynchus tshawytscha), kokanee (O. nerka), and silver salmon (O. kisutch) were not susceptible to the virus when inoculated. Histologically, extensive pancreatic necrosis was observed in the original and experimental materials, but striated muscle hyalinization was detected only in the original material.

  14. A question of balance

    SciTech Connect

    Cook, G.; Brown, H.; Strawn, N.

    1996-12-31

    Nature seeks a balance. The global carbon cycle, in which carbon is exchanged between the atmosphere, biosphere, and oceans through natural processes such as absorption, photosynthesis, and respiration, is one of those balances. This constant exchange promotes an equilibrium in which atmospheric carbon dioxide is keep relatively steady over long periods of time. For the last 10,000 years, up to the 19th century, the global carbon cycle has maintained atmospheric concentrations of carbon dioxide between 260 and 290 ppm. This article discusses the disturbance of the balance, how ethanol fuels address the carbon dioxide imbalance, and a bioethanol strategy.

  15. Consideration of Dynamical Balances

    NASA Technical Reports Server (NTRS)

    Errico, Ronald M.

    2015-01-01

    The quasi-balance of extra-tropical tropospheric dynamics is a fundamental aspect of nature. If an atmospheric analysis does not reflect such balance sufficiently well, the subsequent forecast will exhibit unrealistic behavior associated with spurious fast-propagating gravity waves. Even if these eventually damp, they can create poor background fields for a subsequent analysis or interact with moist physics to create spurious precipitation. The nature of this problem will be described along with the reasons for atmospheric balance and techniques for mitigating imbalances. Attention will be focused on fundamental issues rather than on recipes for various techniques.

  16. Balance Evaluation Systems

    NASA Technical Reports Server (NTRS)

    1996-01-01

    NeuroCom's Balance Master is a system to assess and then retrain patients with balance and mobility problems and is used in several medical centers. NeuroCom received assistance in research and funding from NASA, and incorporated technology from testing mechanisms for astronauts after shuttle flights. The EquiTest and Balance Master Systems are computerized posturography machines that measure patient responses to movement of a platform on which the subject is standing or sitting, then provide assessments of the patient's postural alignment and stability.

  17. Errors in potassium balance

    SciTech Connect

    Forbes, G.B.; Lantigua, R.; Amatruda, J.M.; Lockwood, D.H.

    1981-01-01

    Six overweight adult subjects given a low calorie diet containing adequate amounts of nitrogen but subnormal amounts of potassium (K) were observed on the Clinical Research Center for periods of 29 to 40 days. Metabolic balance of potassium was measured together with frequent assays of total body K by /sup 40/K counting. Metabolic K balance underestimated body K losses by 11 to 87% (average 43%): the intersubject variability is such as to preclude the use of a single correction value for unmeasured losses in K balance studies.

  18. Mars Balance Challenge

    NASA Video Gallery

    The Challenge is to develop ideas for how NASA can turn available entry, descent, and landing balance mass on a future Mars mission into a scientific or technological payload. Proposed concepts sho...

  19. The Balanced Literacy Diet.

    ERIC Educational Resources Information Center

    Willows, Dale

    2002-01-01

    Describes professional development program in Ontario school district to improve student reading and writing skills. Program used food-pyramid concepts to help teacher learn to provide a balanced and flexible approach to literacy instruction based on student needs. (PKP)

  20. The Balancing Act

    SciTech Connect

    Fowler, Kimberly M.

    2008-05-01

    This essay is being proposed as part of a book titled: "Motherhood: The Elephant in the Laboratory." It offers professional and personal advice on how to balance working in the research field with a family life.

  1. Fluid and Electrolyte Balance

    MedlinePlus

    ... They are in your blood, urine and body fluids. Maintaining the right balance of electrolytes helps your ... them from the foods you eat and the fluids you drink. Levels of electrolytes in your body ...

  2. Balance Function Disorders

    NASA Technical Reports Server (NTRS)

    1991-01-01

    Researchers at the Balance Function Laboratory and Clinic at the Minneapolis (MN) Neuroscience Institute on the Abbot Northwestern Hospital Campus are using a rotational chair (technically a "sinusoidal harmonic acceleration system") originally developed by NASA to investigate vestibular (inner ear) function in weightlessness to diagnose and treat patients with balance function disorders. Manufactured by ICS Medical Corporation, Schaumberg, IL, the chair system turns a patient and monitors his or her responses to rotational stimulation.

  3. Exercise to Improve Your Balance

    MedlinePlus

    ... nia.nih.gov/Go4Life Exercise to Improve Your Balance Having good balance is important for many everyday activities, such as ... fracture of the arm, hand, ankle, or hip. Balance exercises can help you prevent falls and avoid ...

  4. Greenland Ice Sheet Mass Balance

    NASA Technical Reports Server (NTRS)

    Reeh, N.

    1984-01-01

    Mass balance equation for glaciers; areal distribution and ice volumes; estimates of actual mass balance; loss by calving of icebergs; hydrological budget for Greenland; and temporal variations of Greenland mass balance are examined.

  5. Energy Balance and Obesity

    PubMed Central

    Hill, James O.; Wyatt, Holly R.; Peters, John C.

    2012-01-01

    This paper describes the interplay among energy intake, energy expenditure and body energy stores and illustrates how an understanding of energy balance can help develop strategies to reduce obesity. First, reducing obesity will require modifying both energy intake and energy expenditure and not simply focusing on either alone. Food restriction alone will not be effective in reducing obesity if human physiology is biased toward achieving energy balance at a high energy flux (i.e. at a high level of energy intake and expenditure). In previous environments a high energy flux was achieved with a high level of physical activity but in today's sedentary environment it is increasingly achieved through weight gain. Matching energy intake to a high level of energy expenditure will likely be more a more feasible strategy for most people to maintain a healthy weight than restricting food intake to meet a low level of energy expenditure. Second, from an energy balance point of view we are likely to be more successful in preventing excessive weight gain than in treating obesity. This is because the energy balance system shows much stronger opposition to weight loss than to weight gain. While large behavior changes are needed to produce and maintain reductions in body weight, small behavior changes may be sufficient to prevent excessive weight gain. In conclusion, the concept of energy balance combined with an understanding of how the body achieves balance may be a useful framework in helping develop strategies to reduce obesity rates. PMID:22753534

  6. STABILITY OF INTERNAL HEAT NECROSIS IN TETRAPLOID X DIPLOID POTATOES

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Internal heat necrosis (IHN) is a severe physiological disorder of tubers, characterized by brown spots that first appear towards the apical end of the tuber parenchyma, although most of the parenchyma tissue is involved in severe cases. 'Atlantic' is the predominant potato (Solanum tuberosum L.) c...

  7. Avascular necrosis of the hip in multiple epiphyseal dysplasia

    SciTech Connect

    Mackenzie, W.G.; Bassett, G.S.; Mandell, G.A.; Scott, C.I. Jr. )

    1989-11-01

    We observed radiographic changes of avascular necrosis (AVN) of the capital femoral epiphysis in 9 hips of 11 patients with multiple epiphyseal dysplasia (MED). Plain roentgenography, bone scintigraphy, and magnetic resonance imaging (MRI) studies all revealed characteristic asymmetric changes in the presence of AVN superimposed on dysplastic femoral heads.

  8. Comparison of Types of Cell Death: Apoptosis and Necrosis.

    ERIC Educational Resources Information Center

    Manning, Francis; Zuzel, Katherine

    2003-01-01

    Cell death is an essential factor in many biological processes including development. Discusses two types of cell death: (1) necrosis (induced by sodium azide); and (2) apoptosis (induced by sodium chromate). Illustrates key features that differ between these two types of cells death including loss of membrane integrity and internucleosomal DNA…

  9. QTL mapping of internal heat necrosis in tetraploid potato

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Internal heat necrosis (IHN) is a physiological disorder of potato tubers. We developed a linkage map of tetraploid potato using AFLP and SSR markers, and mapped QTL for mean severity and percent incidence of IHN. Phentypic data indicated that the distribution of IHN is skewed toward resistance. Lat...

  10. Avascular necrosis of the distal pole of the scaphoid

    PubMed Central

    Tokyay, Abbas; Gunal, Izge

    2015-01-01

    Abstract Avascular necrosis (AVN) of the scaphoid predominantly occurs in the proximal pole. Review of the literature revealed only six cases and all are suspect due to the lack of either MRI investigation or investigation of bleeding preoperatively. We report four new cases and one of them appears to be a real distal pole AVN of the scaphoid in the literature.

  11. Watt and joule balances

    NASA Astrophysics Data System (ADS)

    Robinson, Ian A.

    2014-04-01

    The time is fast approaching when the SI unit of mass will cease to be based on a single material artefact and will instead be based upon the defined value of a fundamental constant—the Planck constant—h . This change requires that techniques exist both to determine the appropriate value to be assigned to the constant, and to measure mass in terms of the redefined unit. It is important to ensure that these techniques are accurate and reliable to allow full advantage to be taken of the stability and universality provided by the new definition and to guarantee the continuity of the world's mass measurements, which can affect the measurement of many other quantities such as energy and force. Up to now, efforts to provide the basis for such a redefinition of the kilogram were mainly concerned with resolving the discrepancies between individual implementations of the two principal techniques: the x-ray crystal density (XRCD) method [1] and the watt and joule balance methods which are the subject of this special issue. The first three papers report results from the NRC and NIST watt balance groups and the NIM joule balance group. The result from the NRC (formerly the NPL Mk II) watt balance is the first to be reported with a relative standard uncertainty below 2 × 10-8 and the NIST result has a relative standard uncertainty below 5 × 10-8. Both results are shown in figure 1 along with some previous results; the result from the NIM group is not shown on the plot but has a relative uncertainty of 8.9 × 10-6 and is consistent with all the results shown. The Consultative Committee for Mass and Related Quantities (CCM) in its meeting in 2013 produced a resolution [2] which set out the requirements for the number, type and quality of results intended to support the redefinition of the kilogram and required that there should be agreement between them. These results from NRC, NIST and the IAC may be considered to meet these requirements and are likely to be widely debated

  12. Cavendish Balance Automation

    NASA Technical Reports Server (NTRS)

    Thompson, Bryan

    2000-01-01

    This is the final report for a project carried out to modify a manual commercial Cavendish Balance for automated use in cryostat. The scope of this project was to modify an off-the-shelf manually operated Cavendish Balance to allow for automated operation for periods of hours or days in cryostat. The purpose of this modification was to allow the balance to be used in the study of effects of superconducting materials on the local gravitational field strength to determine if the strength of gravitational fields can be reduced. A Cavendish Balance was chosen because it is a fairly simple piece of equipment for measuring gravity, one the least accurately known and least understood physical constants. The principle activities that occurred under this purchase order were: (1) All the components necessary to hold and automate the Cavendish Balance in a cryostat were designed. Engineering drawings were made of custom parts to be fabricated, other off-the-shelf parts were procured; (2) Software was written in LabView to control the automation process via a stepper motor controller and stepper motor, and to collect data from the balance during testing; (3)Software was written to take the data collected from the Cavendish Balance and reduce it to give a value for the gravitational constant; (4) The components of the system were assembled and fitted to a cryostat. Also the LabView hardware including the control computer, stepper motor driver, data collection boards, and necessary cabling were assembled; and (5) The system was operated for a number of periods, data collected, and reduced to give an average value for the gravitational constant.

  13. Automatic force balance calibration system

    NASA Technical Reports Server (NTRS)

    Ferris, Alice T. (Inventor)

    1996-01-01

    A system for automatically calibrating force balances is provided. The invention uses a reference balance aligned with the balance being calibrated to provide superior accuracy while minimizing the time required to complete the calibration. The reference balance and the test balance are rigidly attached together with closely aligned moment centers. Loads placed on the system equally effect each balance, and the differences in the readings of the two balances can be used to generate the calibration matrix for the test balance. Since the accuracy of the test calibration is determined by the accuracy of the reference balance and current technology allows for reference balances to be calibrated to within .+-.0.05%, the entire system has an accuracy of a .+-.0.2%. The entire apparatus is relatively small and can be mounted on a movable base for easy transport between test locations. The system can also accept a wide variety of reference balances, thus allowing calibration under diverse load and size requirements.

  14. Automatic force balance calibration system

    NASA Astrophysics Data System (ADS)

    Ferris, Alice T.

    1995-05-01

    A system for automatically calibrating force balances is provided. The invention uses a reference balance aligned with the balance being calibrated to provide superior accuracy while minimizing the time required to complete the calibration. The reference balance and the test balance are rigidly attached together with closely aligned moment centers. Loads placed on the system equally effect each balance, and the differences in the readings of the two balances can be used to generate the calibration matrix for the test balance. Since the accuracy of the test calibration is determined by the accuracy of the reference balance and current technology allows for reference balances to be calibrated to within +/-0.05% the entire system has an accuracy of +/-0.2%. The entire apparatus is relatively small and can be mounted on a movable base for easy transport between test locations. The system can also accept a wide variety of reference balances, thus allowing calibration under diverse load and size requirements.

  15. First report of soybean vein necrosis disease caused by soybean vein necrosis-associated virus in Wisconsin and Iowa

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Several viral diseases of soybean (Glycine max) have been previously identified in the north-central U.S. soybean production area, which includes Wisconsin and Iowa (Hartman et al., 1999). In September 2012, soybean plants with symptoms similar to those reported for soybean vein necrosis disease (SV...

  16. The cryogenic balance design and balance calibration methods

    NASA Astrophysics Data System (ADS)

    Ewald, B.; Polanski, L.; Graewe, E.

    1992-07-01

    The current status of a program aimed at the development of a cryogenic balance for the European Transonic Wind Tunnel is reviewed. In particular, attention is given to the cryogenic balance design philosophy, mechanical balance design, reliability and accuracy, cryogenic balance calibration concept, and the concept of an automatic calibration machine. It is shown that the use of the automatic calibration machine will improve the accuracy of calibration while reducing the man power and time required for balance calibration.

  17. Extraordinary hall balance

    PubMed Central

    Zhang, S. L.; Liu, Y.; Collins-McIntyre, L. J.; Hesjedal, T.; Zhang, J. Y.; Wang, S. G.; Yu, G. H.

    2013-01-01

    Magnetoresistance (MR) effects are at the heart of modern information technology. However, future progress of giant and tunnelling MR based storage and logic devices is limited by the usable MR ratios of currently about 200% at room-temperature. Colossal MR structures, on the other hand, achieve their high MR ratios of up to 106% only at low temperatures and high magnetic fields. We introduce the extraordinary Hall balance (EHB) and demonstrate room-temperature MR ratios in excess of 31,000%. The new device concept exploits the extraordinary Hall effect in two separated ferromagnetic layers with perpendicular anisotropy in which the Hall voltages can be configured to be carefully balanced or tipped out of balance. Reprogrammable logic and memory is realised using a single EHB element. PACS numbers: 85.75.Nn,85.70.Kh,72.15.Gd,75.60.Ej. PMID:23804036

  18. Vibration balanced miniature loudspeaker

    NASA Astrophysics Data System (ADS)

    Schafer, David E.; Jiles, Mekell; Miller, Thomas E.; Thompson, Stephen C.

    2002-11-01

    The vibration that is generated by the receiver (loudspeaker) in a hearing aid can be a cause of feedback oscillation. Oscillation can occur if the microphone senses the receiver vibration at sufficient amplitude and appropriate phase. Feedback oscillation from this and other causes is a major problem for those who manufacture, prescribe, and use hearing aids. The receivers normally used in hearing aids are of the balanced armature-type that has a significant moving mass. The reaction force from this moving mass is the source of the vibration. A modification of the balanced armature transducer has been developed that balances the vibration of its internal parts in a way that significantly reduces the vibration force transmitted outside of the receiver case. This transducer design concept, and some of its early prototype test data will be shown. The data indicate that it should be possible to manufacture transducers that generate less vibration than equivalent present models by 15-30 dB.

  19. Multidimensional spectral load balancing

    SciTech Connect

    Hendrickson, B.; Leland, R.

    1993-01-01

    We describe an algorithm for the static load balancing of scientific computations that generalizes and improves upon spectral bisection. Through a novel use of multiple eigenvectors, our new spectral algorithm can divide a computation into 4 or 8 pieces at once. These multidimensional spectral partitioning algorithms generate balanced partitions that have lower communication overhead and are less expensive to compute than those produced by spectral bisection. In addition, they automatically work to minimize message contention on a hypercube or mesh architecture. These spectral partitions are further improved by a multidimensional generalization of the Kernighan-Lin graph partitioning algorithm. Results on several computational grids are given and compared with other popular methods.

  20. Rotary and Magnus balances

    NASA Technical Reports Server (NTRS)

    Malcolm, G. N.

    1981-01-01

    Two wind tunnel techniques for determining part of the aerodynamic information required to describe the dynamic bahavior of various types of vehicles in flight are described. Force and moment measurements are determined with a rotary-balance apparatus in a coning motion and with a Magnus balance in a high-speed spinning motion. Coning motion is pertinent to both aircraft and missiles, and spinning is important for spin stabilized missiles. Basic principles of both techniques are described, and specific examples of each type of apparatus are presented. Typical experimental results are also discussed.

  1. Breast necrosis induced by the use of coumadin: case report and review of literature

    PubMed Central

    Ejzenberg, Dani; Neusquen, Lucienne Pereira Del Grossi; Rolnik, Daniel Lorber; Lozinsky, Adriana Chebar; Piato, José Roberto Morales

    2015-01-01

    The coumadin-induced skin necrosis is rare and occurs more frequently in the breasts, thighs and buttocks. We describe the first case of coumadin necrosis of the breast in Brazil in a 62-year-old patient. PMID:26018146

  2. [APOPTOSIS AND NECROSIS OF CIRCULATING NEUTROPHILS IN PATIENTS WHILE HIGH RISK OF POSTOPERAIVE PERITONITIS OCCURRENCE].

    PubMed

    Sheyko, V D; Sytnik, D A; Shkurupiy, O O

    2015-11-01

    Processes of apoptosis and necrosis of peripheral neutrophils were investigated in 43 patients, operated on for an acute abdominal organs diseases on the first and fourth postoperative days. Changes of apoptosis and necrosis processes in peripheral neutrophils in dynamics were established. Unfavorable course of early postoperative period in patients with initial high and average risk of postoperative peritonitis occurrence was accompanied by shift in necrosis/apoptosis ratio towards necrosis of peripheral neutrophils. PMID:26939426

  3. Bilateral talus fracture dislocation: is avascular necrosis inevitable?

    PubMed Central

    Balaji G, Gopisankar; Arockiaraj, Justin

    2014-01-01

    Bilateral simultaneous fracture dislocation of the talus is a very rare injury. It occurs usually following high-velocity injuries. We report a 45-year-old man who presented with bilateral talar fracture dislocation following a heavy stone falling on him. On his right side, he had open talus dislocation with lateral process fracture and on his left side he had closed talar neck fracture dislocation. He underwent immediate debridement and external fixator application for his right side and open reduction and internal fixation for his left talus. At the end of 34 months’ follow-up, he was able to walk up to 2 km without pain. His ankle range of movements were restricted bilaterally. Radiographs revealed bilateral avascular necrosis with right side showing complete collapse. We present this case for its rare presentation of bilateral talar fracture dislocation with bilateral avascular necrosis with sequential radiographs. PMID:25155493

  4. The combination of breast necrosis and chylothorax following the OPCAB

    PubMed Central

    Sabzi, Feridoun; Yaghoubi, Alireza

    2016-01-01

    Due to long term patency, the internal mammary artery is considered as a conduit of choice for revascularization of the left anterior descending coronary artery. The internal mammary artery and its accessory branches in addition to perfusing the chest wall structures also contributes to supplying, part of the female breast arteries. In addition, due to the accompaniment of thoracic duct branches with the left internal mammary artery, harvesting may be associated with injury to these branches and contribute to chylothorax. We report a rare case of chylothorax and the breast necrosis following the coronary artery bypass grafting. The chylothorax was started in the second postoperative day and ceased gradually in the 12th day of operation. The breast necrosis appeared in the 3th weeks of operation with pain, and tenderness and black skin color change. The patient underwent total mastectomy in the 4th weeks of operation. PMID:27493707

  5. Progressive outer retinal necrosis-like retinitis in immunocompetent hosts.

    PubMed

    Chawla, Rohan; Tripathy, Koushik; Gogia, Varun; Venkatesh, Pradeep

    2016-01-01

    We describe two young immunocompetent women presenting with bilateral retinitis with outer retinal necrosis involving posterior pole with centrifugal spread and multifocal lesions simulating progressive outer retinal necrosis (PORN) like retinitis. Serology was negative for HIV and CD4 counts were normal; however, both women were on oral steroids at presentation for suspected autoimmune chorioretinitis. The retinitis in both eyes responded well to oral valaciclovir therapy. However, the eye with the more fulminant involvement developed retinal detachment with a loss of vision. Retinal atrophy was seen in the less involved eye with preservation of vision. Through these cases, we aim to describe a unique evolution of PORN-like retinitis in immunocompetent women, which was probably aggravated by a short-term immunosuppression secondary to oral steroids. PMID:27511757

  6. Progressive outer retinal necrosis: manifestation of human immunodeficiency virus infection.

    PubMed

    Lo, Phey Feng; Lim, Rongxuan; Antonakis, Serafeim N; Almeida, Goncalo C

    2015-01-01

    We present the case of a 54-year-old man who developed progressive outer retinal necrosis (PORN) as an initial manifestation of HIV infection without any significant risk factors for infection with HIV. PORN is usually found as a manifestation of known AIDS late in the disease. Our patient presented with transient visual loss followed by decrease in visual acuity and facial rash. Subsequent investigation revealed anterior chamber tap positive for varicella zoster virus (VZV), as well as HIV positivity, with an initial CD4 count of 48 cells/µL. Systemic and intravitreal antivirals against VZV, and highly active antiretroviral therapy against HIV were started, which halted further progression of retinal necrosis. This case highlights the importance of suspecting PORN where there is a rapidly progressive retinitis, and also testing the patient for HIV, so appropriate treatment can be started. PMID:25948844

  7. Inflammatory response and neuronal necrosis in rats with cerebral ischemia

    PubMed Central

    Wu, Lingfeng; Zhang, Kunnan; Hu, Guozhu; Yan, Haiyu; Xie, Chen; Wu, Xiaomu

    2014-01-01

    In the middle cerebral artery occlusion model of ischemic injury, inflammation primarily occurs in the infarct and peripheral zones. In the ischemic zone, neurons undergo necrosis and apoptosis, and a large number of reactive microglia are present. In the present study, we investigated the pathological changes in a rat model of middle cerebral artery occlusion. Neuronal necrosis appeared 12 hours after middle cerebral artery occlusion, and the peak of neuronal apoptosis appeared 4 to 6 days after middle cerebral artery occlusion. Inflammatory cytokines and microglia play a role in damage and repair after middle cerebral artery occlusion. Serum intercellular cell adhesion molecule-1 levels were positively correlated with the permeability of the blood-brain barrier. These findings indicate that intercellular cell adhesion molecule-1 may be involved in blood-brain barrier injury, microglial activation, and neuronal apoptosis. Inhibiting blood-brain barrier leakage may alleviate neuronal injury following ischemia. PMID:25422636

  8. Lovenox Induced Tissue Necrosis, a Case Report and Literature Review

    PubMed Central

    Issa, Abdelfatah Abou; Simman, Richard

    2015-01-01

    Lovenox is a trade name for Enoxaparin. It is a low molecular weight heparin (LMWH) and has other trade names like Clexane and Xaparin. It is an anticoagulant used to prevent and treat venous thromboembolism events (VTE) like deep vein thrombosis or pulmonary embolism, and is given as a subcutaneous injection. General speaking, the most common skin reactions as a result of enoxaparin use are: urticarial, ecchymosis, and even skin necrosis due to vasculitis. These side effects are usually located at the injection site. New studies have pointed out the side effect that could occur a distance from the site of Lovenox injection. In our case extensive skin and subcutaneous tissue necrosis developed at the abdominal wall injection site. PMID:26199895

  9. Lovenox Induced Tissue Necrosis, a Case Report and Literature Review.

    PubMed

    Issa, Abdelfatah Abou; Simman, Richard

    2013-12-01

    Lovenox is a trade name for Enoxaparin. It is a low molecular weight heparin (LMWH) and has other trade names like Clexane and Xaparin. It is an anticoagulant used to prevent and treat venous thromboembolism events (VTE) like deep vein thrombosis or pulmonary embolism, and is given as a subcutaneous injection. General speaking, the most common skin reactions as a result of enoxaparin use are: urticarial, ecchymosis, and even skin necrosis due to vasculitis. These side effects are usually located at the injection site. New studies have pointed out the side effect that could occur a distance from the site of Lovenox injection. In our case extensive skin and subcutaneous tissue necrosis developed at the abdominal wall injection site. PMID:26199895

  10. Tissue Necrosis Following Diode Laser-Assisted Transcanalicular Dacryocystorhinostomy

    PubMed Central

    McClintic, Scott M.; Yoon, Michael K.; Bidar, Maziar; Dutton, Jonathan J.; Vagefi, M. Reza; Kersten, Robert C.

    2012-01-01

    Advantages of transcanalicular laser-assisted dacryocystorhinostomy (TCDCR) over conventional external and endonasal dacryocystorhinostomy (DCR) have been purported to include decreased operating time, reduced morbidity, enhanced cosmesis, avoidance of general anesthesia, and a shorter recovery time. However, one case of skin necrosis has recently been reported to have occurred following diode laser-assisted TCDCR, and we now report three additional cases that were evaluated by the Ophthalmic Plastic Surgery services at the University of North Carolina and the University of California, San Francisco. Three patients developed full-thickness tissue necrosis over the medial canthus following TCDCR, and two of these patients experienced persistent tissue breakdown at the site following reconstructive repair. PMID:24807803

  11. Lives in the Balance.

    ERIC Educational Resources Information Center

    Our Children, 1997

    1997-01-01

    Changes in the workplace that would provide flexibility for working parents are slowly developing and receiving government, business, and societal attention. A sidebar, "Mother, Professional, Volunteer: One Woman's Balancing Act," presents an account of how one woman rearranged her professional life to enable her to do full-time parenting. (SM)

  12. Maintaining an Environmental Balance

    ERIC Educational Resources Information Center

    Environmental Science and Technology, 1976

    1976-01-01

    A recent conference of the National Environmental Development Association focused on the concepts of environment, energy and economy and underscored the necessity for balancing the critical needs embodied in these issues. Topics discussed included: nuclear energy and wastes, water pollution control, federal regulations, environmental technology…

  13. Balancing Chemical Equations.

    ERIC Educational Resources Information Center

    Savoy, L. G.

    1988-01-01

    Describes a study of students' ability to balance equations. Answers to a test on this topic were analyzed to determine the level of understanding and processes used by the students. Presented is a method to teach this skill to high school chemistry students. (CW)

  14. The Heider Balance:

    NASA Astrophysics Data System (ADS)

    Kułakowski, Krzysztof; Gawroński, Przemysław; Gronek, Piotr

    The Heider balance (HB) is investigated in a fully connected graph of N nodes. The links are described by a real symmetric array r (i, j), i, j =1, …, N. In a social group, nodes represent group members and links represent relations between them, positive (friendly) or negative (hostile). At the balanced state, r (i, j) r (j, k) r (k, i) > 0 for all the triads (i, j, k). As follows from the structure theorem of Cartwright and Harary, at this state the group is divided into two subgroups, with friendly internal relations and hostile relations between the subgroups. Here the system dynamics is proposed to be determined by a set of differential equations, ˙ r =rḑot r. The form of equations guarantees that once HB is reached, it persists. Also, for N =3 the dynamics reproduces properly the tendency of the system to the balanced state. The equations are solved numerically. Initially, r (i, j) are random numbers distributed around zero with a symmetric uniform distribution of unit width. Calculations up to N =500 show that HB is always reached. Time τ(N) to get the balanced state varies with the system size N as N-1/2. The spectrum of relations, initially narrow, gets very wide near HB. This means that the relations are strongly polarized. In our calculations, the relations are limited to a given range around zero. With this limitation, our results can be helpful in an interpretation of some statistical data.

  15. Regulation of Energy Balance.

    ERIC Educational Resources Information Center

    Bray, George A.

    1985-01-01

    Explains relationships between energy intake and expenditure focusing on the cellular, chemical and neural mechanisms involved in regulation of energy balance. Information is referenced specifically to conditions of obesity. (Physicians may earn continuing education credit by completing an appended test). (ML)

  16. A Balancing Act

    ERIC Educational Resources Information Center

    Lewis, Tamika; Mobley, Mary; Huttenlock, Daniel

    2013-01-01

    It's the season for the job hunt, whether one is looking for their first job or taking the next step along their career path. This article presents first-person accounts to see how teachers balance the rewards and challenges of working in different types of schools. Tamica Lewis, a third-grade teacher, states that faculty at her school is…

  17. Multidimensional spectral load balancing

    DOEpatents

    Hendrickson, Bruce A.; Leland, Robert W.

    1996-12-24

    A method of and apparatus for graph partitioning involving the use of a plurality of eigenvectors of the Laplacian matrix of the graph of the problem for which load balancing is desired. The invention is particularly useful for optimizing parallel computer processing of a problem and for minimizing total pathway lengths of integrated circuits in the design stage.

  18. Toward Balance in Translation.

    ERIC Educational Resources Information Center

    Costello, Nancy A.

    A study compared translations of biblical passages into different languages in Papua New Guinea. The study looked for evidence of balance between literal and free interpretation in translation style in the gospel of Mark, which is narrative and didactic material, in 12 languages, and the mainly hortatory genre in translations of 4 epistles:…

  19. [Acute hemorrhagic necrosis of the breast following treatment with Cumarin].

    PubMed

    Lüchtrath, H; Walkowsky, A

    1983-08-01

    A case of hemorrhagic necrosis of the breast is reported in a thirty-four year old woman who received Cumarin treatment for deep leg vein thrombosis and pulmonary embolism. It was necessary to remove the breast. The microscopic examination showed complete blockage of the vessels by fibrin thrombi in almost all veins. The cause of this venous thrombosis was explained as a Shwartzman-Sanarelli-Phenomenon. PMID:6555120

  20. Progressive Outer Retinal Necrosis and Immunosuppressive Therapy in Myasthenia Gravis

    PubMed Central

    Coisy, Solène; Ebran, Jean-Marc; Milea, Dan

    2014-01-01

    Introduction Progressive outer retinal necrosis (PORN) is a rare but devastating infectious retinitis associated with varicella zoster virus (VZV) and responsible for severe visual loss. Case Report A 59-year-old man treated for generalized myasthenia with oral azathioprine and prednisone presented with severe unilateral necrotizing retinitis. Polymerase chain reaction of the aqueous and vitreous humors was diagnostic for VZV PORN. Conclusion VZV PORN is a severe potential ocular complication of immunosuppression, prompting urgent diagnosis and appropriate treatment. PMID:24926266

  1. Disseminated intravascular coagulation and hepatocellular necrosis due to clove oil.

    PubMed

    Brown, S A; Biggerstaff, J; Savidge, G F

    1992-10-01

    We describe the case of a 2-year-old child who suffered from disseminated intravascular coagulation (DIC) and hepatocellular necrosis, following ingestion of clove oil. The patient was treated with heparin and fresh frozen plasma, and, following specific haemostasis assays, with appropriate coagulation factor and inhibitor concentrates. The case demonstrates how this approach can be successfully used in the management of DIC with coexisting liver failure. PMID:1450336

  2. [Avascular necrosis of the hip - diagnosis and treatment].

    PubMed

    Drescher, W; Pufe, T; Smeets, R; Eisenhart-Rothe, R V; Jäger, M; Tingart, M

    2011-04-01

    Femoral head necrosis is an ischaemic bone necrosis of traumatic or nontraumatic pathogenesis which can lead to hip joint destruction in young age. It is today the indication for 10 % of all the total hip joint replacements. Known aetiologies of nontraumatic femoral head necrosis are alcoholism, steroids, sickle cell anaemia, caisson, and Gaucher's disease. Further risk factors are chemotherapy, chronic inflammatory bowel disease, systemic lupus erythematosus, and multiple sclerosis, in which also steroids are involved. Gravidity is another risk factor, but still idiopathic pathogenesis is found. In diagnosis, the ARCO-classification of the Association for the Research of Osseous Circulation is essential. While stage 0 can only be found histologically, the reversible early stage 1 shows MR signal changes. In the irreversible early stage 2, first native x-ray changes are seen as lower radiolucency reflects new bone apposition on dead trabeculae. In stage 3, subchondral fracture follows, and in stage 4 secondary arthritis of the hip. Established therapy in stage 1 is core decompression, physiotherapy, and more and more also bisphosphonates. Sufficient data to support extracorporeal shock wave therapy are still lacking. Stem cell therapy seems to be a promising new therapy method in stage 2. In stage 2 and 3 mainly proximal femoral osteotomies and (non)vascularised bone transplantation are performed. In stage 4, depending on size and location of the necrotic zone and pathology of the adjacent bone, resurfacing or short stem hip arthroplasty can be performed. However, conventional THA is still golden standard. The problem and challenge, however, is the often young patient age in femoral head necrosis. Especially chemotherapy-associated osteonecrosis in leukaemia is found in patients in their second decade of life. Therefore, the hip should be preserved as long as possible. PMID:21469042

  3. Carrot yellow leaf virus Is Associated with Carrot Internal Necrosis

    PubMed Central

    Adams, Ian P.; Skelton, Anna; Macarthur, Roy; Hodges, Tobias; Hinds, Howard; Flint, Laura; Nath, Palash Deb; Boonham, Neil; Fox, Adrian

    2014-01-01

    Internal necrosis of carrot has been observed in UK carrots for at least 10 years, and has been anecdotally linked to virus infection. In the 2009 growing season some growers had up to 10% of yield with these symptoms. Traditional diagnostic methods are targeted towards specific pathogens. By using a metagenomic approach with high throughput sequencing technology, other, as yet unidentified causes of root necrosis were investigated. Additionally a statistical analysis has shown which viruses are most closely associated with disease symptoms. Carrot samples were collected from a crop exhibiting root necrosis (102 Affected: 99 Unaffected) and tested for the presence of the established carrot viruses: Carrot red leaf virus (CtRLV), Carrot mottle virus (CMoV), Carrot red leaf associated viral RNA (CtRLVaRNA) and Parsnip yellow fleck virus (PYFV). The presence of these viruses was not associated with symptomatic carrot roots either as single viruses or in combinations. A sub-sample of carrots of mixed symptom status was subjected to MiSeq sequencing. The results from these tests suggested Carrot yellow leaf virus (CYLV) was associated with symptomatic roots. Additionally a novel Torradovirus, a novel Closterovirus and two novel Betaflexiviradae related plant viruses were detected. A specific diagnostic test was designed for CYLV. Of the 102 affected carrots, 98% were positive for CYLV compared to 22% of the unaffected carrots. From these data we conclude that although we have yet to practically demonstrate a causal link, CYLV appears to be strongly associated with the presence of necrosis of carrots. PMID:25365290

  4. Necrosis and apoptosis in Trichinella spiralis-mediated tumour reduction

    PubMed Central

    Vasilev, Sasa; Ilic, Natasa; Gruden-Movsesijan, Alisa; Vasilijic, Sasa; Bosic, Martina

    2015-01-01

    It is known that infection with different pathogens, including helminths, can alter the progression of malignant or other diseases. We studied the effect of chronic Trichinella spiralis infection or muscle larvae excretory-secretory (ES L1) antigens on the malignant tumour growth in the mouse melanoma model system in vivo and in vitro. Our results confirmed that chronic infection with T. spiralis possesses the capacity to slow down the progression of tumour growth, resulting in an impressive reduction in tumour size. We found that the phenomenon could, at least partially, be related to a lower level of tumour necrosis compared to necrosis present in control animals with progressive malignancy course. An increased apoptotic potential among the low percentage of cells within the total tumour cell number in vivo was also observed. ES L1 antigen, as a parasitic product that is released during the chronic phase of infection, reduced the survival and slightly, but significantly increased the apoptosis level of melanoma cells in vitro. Our results imply that powerful Trichinella anti-malignance capacity does not rely only on necrosis and apoptosis but other mechanisms through which infection or parasite products manipulate the tumor establishment and expansion should be considered. PMID:26155183

  5. Cation dyshomeostasis and cardiomyocyte necrosis: the Fleckenstein hypothesis revisited

    PubMed Central

    Borkowski, Brian J.; Cheema, Yaser; Shahbaz, Atta U.; Bhattacharya, Syamal K.; Weber, Karl T.

    2011-01-01

    An ongoing loss of cardiomyocytes to apoptotic and necrotic cell death pathways contributes to the progressive nature of heart failure. The pathophysiological origins of necrotic cell loss relate to the neurohormonal activation that accompanies acute and chronic stressor states and which includes effector hormones of the adrenergic nervous system. Fifty years ago, Albrecht Fleckenstein and coworkers hypothesized the hyperadrenergic state, which accompanies such stressors, causes cardiomyocyte necrosis based on catecholamine-initiated excessive intracellular Ca2+ accumulation (EICA), and mitochondrial Ca2+ overloading in particular, in which the ensuing dysfunction and structural degeneration of these organelles leads to necrosis. In recent years, two downstream factors have been identified which, together with EICA, constitute a signal–transducer–effector pathway: (i) mitochondria-based induction of oxidative stress, in which the rate of reactive oxygen metabolite generation exceeds their rate of detoxification by endogenous antioxidant defences; and (ii) the opening of the mitochondrial inner membrane permeability transition pore (mPTP) followed by organellar swelling and degeneration. The pathogenesis of stress-related cardiomyopathy syndromes is likely related to this pathway. Other factors which can account for cytotoxicity in stressor states include: hypokalaemia; ionized hypocalcaemia and hypomagnesaemia with resultant elevations in parathyroid hormone serving as a potent mediator of EICA; and hypozincaemia with hyposelenaemia, which compromise antioxidant defences. Herein, we revisit the Fleckenstein hypothesis of EICA in leading to cardiomyocyte necrosis and the central role played by mitochondria. PMID:21398641

  6. Autophagy protects C. elegans against necrosis during Pseudomonas aeruginosa infection

    PubMed Central

    Zou, Cheng-Gang; Ma, Yi-Cheng; Dai, Li-Li; Zhang, Ke-Qin

    2014-01-01

    Autophagy, a conserved pathway that delivers intracellular materials into lysosomes for degradation, is involved in development, aging, and a variety of diseases. Accumulating evidence demonstrates that autophagy plays a protective role against infectious diseases by diminishing intracellular pathogens, including bacteria, viruses, and parasites. However, the mechanism by which autophagy regulates innate immunity remains largely unknown. Here, we show that autophagy is involved in host defense against a pathogenic bacterium Pseudomonas aeruginosa in the metazoan Caenorhabditis elegans. P. aeruginosa infection induces autophagy via a conserved extracellular signal-regulated kinase (ERK). Intriguingly, impairment of autophagy does not influence the intestinal accumulation of P. aeruginosa, but instead induces intestinal necrosis. Inhibition of necrosis results in the survival of autophagy-deficient worms after P. aeruginosa infection. These findings reveal a previously unidentified role for autophagy in protection against necrosis triggered by pathogenic bacteria in C. elegans and implicate that such a function of autophagy may be conserved through the inflammatory response in diverse organisms. PMID:25114220

  7. Cellular and molecular pathways to myocardial necrosis and replacement fibrosis

    PubMed Central

    Gandhi, Malay S.; Kamalov, German; Shahbaz, Atta U.; Bhattacharya, Syamal K.; Ahokas, Robert A.; Sun, Yao; Gerling, Ivan C.

    2010-01-01

    Fibrosis is a fundamental component of the adverse structural remodeling of myocardium present in the failing heart. Replacement fibrosis appears at sites of previous cardiomyocyte necrosis to preserve the structural integrity of the myocardium, but not without adverse functional consequences. The extensive nature of this microscopic scarring suggests cardiomyocyte necrosis is widespread and the loss of these contractile elements, combined with fibrous tissue deposition in the form of a stiff in-series and in-parallel elastic elements, contributes to the progressive failure of this normally efficient muscular pump. Cellular and molecular studies into the signal-transducer-effector pathway involved in cardiomyocyte necrosis have identified the crucial pathogenic role of intracellular Ca2+ overloading and subsequent induction of oxidative stress, predominantly confined within its mitochondria, to be followed by the opening of the mitochondrial permeability transition pore that leads to the destruction of these organelles and cells. It is now further recognized that Ca2+ overloading of cardiac myocytes and mitochondria serves as a prooxidant and which is counterbalanced by an intrinsically coupled Zn2+ entry serving as antioxidant. The prospect of raising antioxidant defenses by increasing intracellular Zn2+ with adjuvant nutriceuticals can, therefore, be preferentially exploited to uncouple this intrinsically coupled Ca2+–Zn2+ dyshomeostasis. Hence, novel yet simple cardioprotective strategies may be at hand that deserve to be further explored. PMID:20405318

  8. Radiation necrosis after treatment of solitary intracranial metastases

    SciTech Connect

    Sundaresan, N.; Galicich, J.H.; Deck, M.D.; Tomita, T.

    1981-03-01

    During the period from July 1977 to June 1980, 75 patients underwent the surgical excision of solitary brain metastases, and 61 of these patients received whole brain radiation. Three patients developed chronic radiation necrosis. In the 3 patients with necrosis, computed tomography suggested recurrent tumor; the histological diagnosis of necrosis only was obtained at operation in 2 of these patients and by autopsy in the third. Radiation damage resulted in the death of 1 patient, a chronic vegetative state in another, and severe neurological deficit in the third. An additional 4 patients had neurological complications probably related to radiation therapy. As the survival of such patients is prolonged by aggressive treatment, the incidence of radiation-induced complications is likely to increase. The optimal dose of radiation necessary to destroy microscopic foci of tumor after the surgical resection of a single brain metastasis is unknown. Because of the significant incidence of damage after radiation as currently delivered, studies using graded, lower doses are indicated.

  9. Identification of dirty necrosis in colorectal carcinoma based on multiphoton microscopy

    NASA Astrophysics Data System (ADS)

    Li, Lianhuang; Jiang, Weizhong; Yang, Yinghong; Chen, Zhifen; Feng, Changyin; Li, Hongsheng; Guan, Guoxian; Chen, Jianxin

    2014-06-01

    Dirty necrosis within glandular lumina is often considered as a characteristic of colorectal carcinomas (CRCs) that is a diagnostically useful feature of CRCs with DNA microsatellite instability (MSI). Multiphoton microscopy (MPM), which is based on the second-harmonic generation and two-photon excited fluorescence signals, was used to identify dirty necrosis. Our results demonstrated that MPM has the ability to exhibit the microstructure of dirty necrosis and the signal intensity as well as an emission spectrum that can help to differentiate dirty necrosis from cancer cells. These findings indicate that MPM may be helpful in distinguishing MSI colorectal carcinoma via the identification of dirty necrosis.

  10. Lunar Balance and Locomotion

    NASA Technical Reports Server (NTRS)

    Paloski, William H.

    2008-01-01

    Balance control and locomotor patterns were altered in Apollo crewmembers on the lunar surface, owing, presumably, to a combination of sensory-motor adaptation during transit and lunar surface operations, decreased environmental affordances associated with the reduced gravity, and restricted joint mobility as well as altered center-of-gravity caused by the EVA pressure suits. Dr. Paloski will discuss these factors, as well as the potential human and mission impacts of falls and malcoordination during planned lunar sortie and outpost missions. Learning objectives: What are the potential impacts of postural instabilities on the lunar surface? CME question: What factors affect balance control and gait stability on the moon? Answer: Sensory-motor adaptation to the lunar environment, reduced mechanical and visual affordances, and altered biomechanics caused by the EVA suit.

  11. Seismic offset balancing

    SciTech Connect

    Ross, C.P.; Beale, P.L.

    1994-01-01

    The ability to successfully predict lithology and fluid content from reflection seismic records using AVO techniques is contingent upon accurate pre-analysis conditioning of the seismic data. However, all too often, residual amplitude effects remain after the many offset-dependent processing steps are completed. Residual amplitude effects often represent a significant error when compared to the amplitude variation with offset (AVO) response that the authors are attempting to quantify. They propose a model-based, offset-dependent amplitude balancing method that attempts to correct for these residuals and other errors due to sub-optimal processing. Seismic offset balancing attempts to quantify the relationship between the offset response of back-ground seismic reflections and corresponding theoretical predictions for average lithologic interfaces thought to cause these background reflections. It is assumed that any deviation from the theoretical response is a result of residual processing phenomenon and/or suboptimal processing, and a simple offset-dependent scaling function is designed to correct for these differences. This function can then be applied to seismic data over both prospective and nonprospective zones within an area where the theoretical values are appropriate and the seismic characteristics are consistent. A conservative application of the above procedure results in an AVO response over both gas sands and wet sands that is much closer to theoretically expected values. A case history from the Gulf of Mexico Flexure Trend is presented as an example to demonstrate the offset balancing technique.

  12. Simple Cell Balance Circuit

    NASA Technical Reports Server (NTRS)

    Johnson, Steven D.; Byers, Jerry W.; Martin, James A.

    2012-01-01

    A method has been developed for continuous cell voltage balancing for rechargeable batteries (e.g. lithium ion batteries). A resistor divider chain is provided that generates a set of voltages representing the ideal cell voltage (the voltage of each cell should be as if the cells were perfectly balanced). An operational amplifier circuit with an added current buffer stage generates the ideal voltage with a very high degree of accuracy, using the concept of negative feedback. The ideal voltages are each connected to the corresponding cell through a current- limiting resistance. Over time, having the cell connected to the ideal voltage provides a balancing current that moves the cell voltage very close to that ideal level. In effect, it adjusts the current of each cell during charging, discharging, and standby periods to force the cell voltages to be equal to the ideal voltages generated by the resistor divider. The device also includes solid-state switches that disconnect the circuit from the battery so that it will not discharge the battery during storage. This solution requires relatively few parts and is, therefore, of lower cost and of increased reliability due to the fewer failure modes. Additionally, this design uses very little power. A preliminary model predicts a power usage of 0.18 W for an 8-cell battery. This approach is applicable to a wide range of battery capacities and voltages.

  13. Gait and balance disorders.

    PubMed

    Masdeu, Joseph C

    2016-01-01

    This chapter focuses on one of the most common types of neurologic disorders: altered walking. Walking impairment often reflects disease of the neurologic structures mediating gait, balance or, most often, both. These structures are distributed along the neuraxis. For this reason, this chapter is introduced by a brief description of the neurobiologic underpinning of walking, stressing information that is critical for imaging, namely, the anatomic representation of gait and balance mechanisms. This background is essential not only in order to direct the relevant imaging tools to the regions more likely to be affected but also to interpret correctly imaging findings that may not be related to the walking deficit object of clinical study. The chapter closes with a discussion on how to image some of the most frequent etiologies causing gait or balance impairment. However, it focuses on syndromes not already discussed in other chapters of this volume, such as Parkinson's disease and other movement disorders, already discussed in Chapter 48, or cerebellar ataxia, in Chapter 23, in the previous volume. As regards vascular disease, the spastic hemiplegia most characteristic of brain disease needs little discussion, while the less well-understood effects of microvascular disease are extensively reviewed here, together with the imaging approach. PMID:27430451

  14. Assessment of postural balance function.

    PubMed

    Kostiukow, Anna; Rostkowska, Elzbieta; Samborski, Włodzimierz

    2009-01-01

    Postural balance is defined as the ability to stand unassisted without falling. Examination of the patient's postural balance function is a difficult diagnostic task. Most of the balance tests used in medicine provide incomplete information on this coordination ability of the human body. The aim of this study was to review methods of assessment of the patient's postural balance function, including various tests used in medical diagnostics centers. PMID:20698188

  15. Percutaneous Catheter Drainage in Infected Pancreatitis Necrosis: a Systematic Review.

    PubMed

    Ke, Lichi; Li, Junhua; Hu, Peihong; Wang, Lianqun; Chen, Haiming; Zhu, Yaping

    2016-06-01

    The primary aim of this study was to present the outcomes of percutaneous catheter drainage (PCD) in patients with infected pancreatitis necrosis. A second aim was to focus on disease severity, catheter size, and additional surgical intervention. A literature search of the PubMed/MEDLINE/Cochrane Library (January 1998 to February 2015) databases was conducted. All randomized, non-randomized, and retrospective studies with data on PCD techniques and outcomes in patients with infected pancreatitis necrosis were included. Studies that reported data on PCD along with other interventions without the possibility to discriminate results specific to PCD were excluded. The main outcomes were mortality, major complications, and definitive successful treatment with percutaneous catheter drainage alone. Fifteen studies of 577 patients were included. There was only one randomized, controlled trial, and most others were retrospective case series. Organ failure before PCD occurred in 55.3 % of patients. With PCD alone, definitive successful treatment was 56.2 % of patients. Additional surgical intervention was required after PCD in 38.5 % of patients. The overall mortality rate was 18 % (104 of 577 patients). Complications occurred in 25.1 % of patients, and fistula was the most common complication. PCD is an efficient tool for treatment in the majority of patients with infected pancreatitis necrosis as the only intervention. Multiple organ failures before PCD are negative parameters for the outcome of the disease. Large catheters fail to prove to be more effective for draining necrotic tissue. However, in the extent of multi-morbid patients, to determine one single prognostic factor seems to be difficult. PMID:27358518

  16. Clinical Manifestation of Self-Limiting Acute Retinal Necrosis

    PubMed Central

    Brydak-Godowska, Joanna; Borkowski, Piotr; Szczepanik, Szymon; Moneta-Wielgoś, Joanna; Kęcik, Dariusz

    2014-01-01

    Background The purpose of this paper was to present a case series of self-limiting, peripheral acute retinal necrosis and to demonstrate efficacy of treatment with valacyclovir in patients resistant to acyclovir. The diagnosis was made on ophthalmoscopic examination and positive serum tests for herpes viruses. Material/Methods Ten patients (6F and 4M) aged 19–55 years were diagnosed and treated for self-limiting acute retinal necrosis (ARN). The following endpoints were reported: visual outcomes, clinical features, disease progression, treatment, and complications. Patients received only symptomatic treatment because they did not consent to vitreous puncture. Results Peripheral, mild retinitis was diagnosed in all eyes at baseline. Initially, all patients were treated with systemic acyclovir (800 mg, 5 times a day), prednisone (typically 40–60 mg/day), and aspirin in an outpatient setting. In 6 patients, treatment was discontinued at 6 months due to complete resolution of the inflammatory process. Four patients with immune deficiency showed signs and symptoms of chronic inflammation. Two patients did not respond to acyclovir (2 non-responders); however, those patients were successfully treated with valacyclovir. Complete resolution of inflammatory lesions was observed in 8 patients. In 2 patients, the disease progressed despite treatment – 1 female patient after kidney transplant who stopped the prescribed medications, and 1 male patient with SLE and antiphospholipid syndrome who experienced breakthrough symptoms on-treatment. He died due to cerebral venous sinus thrombosis. Neurological complications (encephalitis and meningitis) were observed in 2 female patients. Prophylactic laser photocoagulation was performed in 1 subject. Conclusions A series of cases of self-limiting acute retinal necrosis (ARN) is presented. This clinical form of ARN can resemble toxoplasmic retinitis in some cases. Oral antiviral medications provide an effective alternative to

  17. Diarachidonoylphosphoethanolamine induces necrosis/necroptosis of malignant pleural mesothelioma cells.

    PubMed

    Kaku, Yoshiko; Tsuchiya, Ayako; Kanno, Takeshi; Nakano, Takashi; Nishizaki, Tomoyuki

    2015-09-01

    The present study investigated 1,2-diarachidonoyl-sn-glycero-3-phosphoethanolamine (DAPE)-induced cell death in malignant pleural mesothelioma (MPM) cells. DAPE reduced cell viability in NCI-H28, NCI-H2052, NCI-H2452, and MSTO-211H MPM cell lines in a concentration (1-100μM)-dependent manner. In the flow cytometry using propidium iodide (PI) and annexin V (AV), DAPE significantly increased the population of PI-positive and AV-negative cells, corresponding to primary necrosis, and that of PI-positive and AV-positive cells, corresponding to late apoptosis/secondary necrosis, in NCI-H28 cells. DAPE-induced reduction of NCI-H28 cell viability was partially inhibited by necrostatin-1, an inhibitor of RIP1 kinase to induce necroptosis, or knocking-down RIP1. DAPE generated reactive oxygen species (ROS) followed by disruption of mitochondrial membrane potentials in NCI-H28 cells. DAPE-induced mitochondrial damage was attenuated by cyclosporin A, an inhibitor of cyclophilin D (CypD). DAPE did not affect expression and mitochondrial localization of p53 protein in NCI-H28 cells. DAPE significantly decreased intracellular ATP concentrations in NCI-H28 cells. Overall, the results of the present study indicate that DAPE induces necroptosis and necrosis of MPM cells; the former is mediated by RIP1 kinase and the latter is caused by generating ROS and opening CypD-dependent mitochondrial permeability transition pore, to reduce intracellular ATP concentrations. PMID:26004138

  18. Phosphorus Necrosis of the Jaw: A Present-day Study

    PubMed Central

    Hughes, J. P. W.; Baron, R.; Buckland, D. H.; Cooke, M. A.; Craig, J. D.; Duffield, D. P.; Grosart, A. W.; Parkes, P. W. J.; Porter, A.

    1962-01-01

    A historical note on the aetiology of phossy jaw shows that present-day knowledge is little greater than it was a century ago. The varied clinical course of the disease is described together with a report of 10 classical cases not previously reported. Six cases, not amounting to true necrosis but in which healing after dental extraction was delayed, and described, and mention is made of the noticeable differences in the oral state and appearances of tartar of healthy workmen exposed to phosphorus compared with healthy workmen not exposed. But no systematic differences of any kind were found in the incidence of general infections, fractures of bones, haematological findings, and biochemical studies of blood and urine in two groups of healthy men most exposed and least exposed to phosphorous in the same factory. An intensive study in hospital of a case of classical necrosis showed no departure from normal, except delayed healing following bone biopsy from the iliac crest, and a reversed polymorphonuclear/lymphocyte ratio. In the discussion the time of onset of necrosis after first exposure to phosphorus, clinical and radiological diagnosis, the organisms present, personal susceptibility, the appearance of the sequestra, and regeneration of bone are considered. An up-to-date note on prevention of the disease is given, although this has met with only partial success. Some persons are highly susceptible and, whilst complete protection is impossible in the light of our present knowledge, early diagnosis and modern treatment have robbed the disease of its terrible manifestations of Victorian times and turned it into a minor, although often uncomfortable complaint, with little or no resulting disability. Images PMID:14449812

  19. Cocaine hepatotoxicity: a study on the pathogenesis of periportal necrosis.

    PubMed Central

    Powell, C. J.; Charles, S. J.; Mullervy, J.

    1994-01-01

    Cocaine is reported to produce either periportal or mid-zonal necrosis in mice pretreated with the enzyme inducer phenobarbitone (James et al. 1987; Powell et al. 1991; Charles & Powell 1992). Dose-response and time course experiments were performed in phenobarbitone treated male DBA/2Ha mice to study the pathogenesis of this unusual cocaine induced lesion. An increase in the dose of cocaine from 60 to 90 or 120 mg/kg produced more extensive and severe periportal and linking portal damage and elevated plasma aspartate (AST) and alanine (ALT) aminotransferases in a dose dependent manner. Scattered hepatocyte degeneration began at the edge of the periportal region and was detectable by electron microscopy within 30 minutes of administration of 60 mg/kg of cocaine, with conspicuous disorganization of the endoplasmic reticulum being one of the earliest changes. Significant elevations of plasma AST and ALT were observed 3 hours after cocaine administration and were sustained for 12 hours, at which time progressive hepatocyte damage had developed into a network of confluent necrosis at the periphery of the periportal region. The rapidity of organelle derangement and subsequent cell death, and absence of any effect on total cytochrome P-450 or FAD-mono-oxygenase levels, appear to distinguish this periportal lesion from previous reports of cocaine induced centrilobular necrosis in non-enzyme induced mice, suggesting that the two types of damage may develop by different mechanisms. The observation that periportal lesions commence at the periphery of the periportal area, progressing portalwards with increasing dose and time, offers an explanation for the previously conflicting reports of cocaine induced mid-zonal and/or periportal lesions in phenobarbitone treated mice. Images Figure 1 Figure 3 Figure 4 PMID:7734331

  20. More on Chemical Reaction Balancing.

    ERIC Educational Resources Information Center

    Swinehart, D. F.

    1985-01-01

    A previous article stated that only the matrix method was powerful enough to balance a particular chemical equation. Shows how this equation can be balanced without using the matrix method. The approach taken involves writing partial mathematical reactions and redox half-reactions, and combining them to yield the final balanced reaction. (JN)

  1. Tumor necrosis factor inhibitors – state of knowledge

    PubMed Central

    Lis, Krzysztof; Kuzawińska, Olga

    2014-01-01

    Tumor necrosis factor (TNF) is considered a major proinflammatory cytokine, affecting various aspects of the immune reaction. All five TNF inhibitors currently available on the market (i.e., etanercept, infliximab, adalimumab, certolizumab and golimumab) are top sellers, although indicated only in autoimmune diseases, including rheumatoid arthritis, Crohn's disease and psoriasis. This article briefly discusses the background and place for TNF inhibitors in modern therapy. The main safety aspects of TNF inhibitor administration are described in particular, with special consideration of the available meta-analyses. Finally, perspectives on the next-generation TNF inhibitors and their use in the clinic are given. PMID:25624856

  2. Hypotensive hemorrhagic necrosis in basal ganglia and brainstem.

    PubMed

    Opeskin, K; Burke, M P

    2000-12-01

    Hypotensive hemorrhagic necrosis of the basal ganglia and brainstem has only occasionally been described. Three such cases are reported. Cardiac arrest had occurred in all cases, and it took at least 1 hour to restore adequate circulation. The patients remained comatose for 2 days to 2 weeks until death. Persistent hypotension causing ischemia in the distribution of deep perforating arteries is considered to have been the key underlying mechanism. Hemorrhage is thought to have been caused by extravasation of red blood cells through damaged blood vessels. PMID:11111807

  3. Emerging concepts in the management of acute retinal necrosis.

    PubMed

    Wong, Robert William; Jumper, J Michael; McDonald, H Richard; Johnson, Robert N; Fu, Arthur; Lujan, Brandon J; Cunningham, Emmett T

    2013-05-01

    Acute retinal necrosis (ARN), also known as Kirisawa-type uveitis, is an uncommon condition caused by infection of the retina by one of the herpes family of viruses, most typically varicella zoster virus or herpes simplex virus and less commonly cytomegalovirus. Clinical diagnosis can be challenging and is often aided by PCR-based analysis of ocular fluids. Treatment typically involves extended use of one or more antiviral agents. Long term retinal detachment risk is high. We review the literature on ARN and present an approach to the diagnosis and management of this serious condition. PMID:23235944

  4. Skin necrosis caused by prallethrin-A worldwide used insecticide.

    PubMed

    Botnariu, Gina; Birsan, Cristina; Podoleanu, Cristian; Moldovan, Cosmin; Stolnicu, Simona; Chiriac, Anca

    2016-04-01

    We report a case of necrosis caused by the use of prallethrin (mosquito repellent) on the skin in a 67-year-old diabetic female patient suffering from delusions of parasitosis. Cutaneous toxicity due to pyrethroids is less known or reported, despite well-documented pyrethroid poisoning involving the gastrointestinal, respiratory, cardiac, and nervous systems. Skin irritation has been described after acute accidental exposure but, as far as we know, no data have been published on the effects of pyrethroids when applied directly to the skin. PMID:26987111

  5. [Dystrophy and necrosis following radiotherapy for maxillary cancer (author's transl)].

    PubMed

    Bertoin, P; Dutou, L; Lacroze, M; Bailly, C

    1979-01-01

    About 10% of patients developed severe sequelae following radiotherapy, which had been associated with surgical treatment, even though they were, or appeared to be cured. Complications affected the skin and soft tissues (causing skin retraction, loss of substance, and sometimes trismus) and bone (necrosis required surgical treatment, and when there was associated cutaneous dystrophy, resulted in exposure of the bone and severe functional and esthetic problems). A critical study of the radiotherapeutic techniques used suggests that the dose given should be reduced, the fields modified, and Cobalt used in preference to electrons in most cases. PMID:288159

  6. BCG Induced Necrosis of the Entire Bladder Urothelium.

    PubMed

    Krönig, Malte; Jilg, Cordula; Burger, Dieter; Langer, Mathias; Timme-Bronsert, Sylvia; Werner, Martin; Wetterauer, Ulrich; Seemann, Wolfgang-Schultze

    2015-09-01

    Instillation therapy with attenuated tuberculosis bacteria (BCG) can significantly reduce rates of recurrence of non-muscle invasive bladder cancer. Local and systemic side effects such as dysuria, irritative voiding symptoms or partial bladder contracture and systemic inflammation were reported. A 75 year-old male patient with recurrent non muscle invasive bladder cancer developed necrosis of the entire bladder urothelium more than six years after BCG instillation immunotherapy. The resulting irritative voiding symptoms and low bladder capacity required radical cystectomy. BCG instillation can cause severe side effects, which develop gradually and eventually need radical surgical therapy such as cystectomy without tumor recurrence. PMID:26793538

  7. Digital necrosis with squamous cell carcinoma of the tonsil

    PubMed Central

    Warrier, Vinod; Ahmad, Ali; Alshatti, Yaqoub; Jafar, Ali

    2016-01-01

    Background Digital necrosis is a rare phenomenon of paraneoplastic syndrome associated with squamous cell carcinoma of the tonsil. Since 1965, more than 70 cases have been reported worldwide in the literature. Case report A 54-year-old male smoker presented with Raynaud’s phenomenon, proceeding to frank gangrene of the fingers. Working up the case finally pointed toward carcinoma of the tonsil as the underlying cause – a rare paraneoplastic manifestation. Conclusion No definite etiology has been found to be the cause of Raynaud’s phenomenon in this case of the squamous cell carcinoma of the tonsil. A brief discussion of the literature is also presented. PMID:27390535

  8. Supraspinatus Intramuscular Calcified Hematoma or Necrosis Associated with Tendon Tear

    PubMed Central

    Lädermann, Alexandre; Genevay, Muriel; Abrassart, Sophie; Schwitzguébel, Adrien Jean-Pierre

    2015-01-01

    Introduction. Rotator cuff intramuscular calcification is a rare condition usually caused by heterotopic ossification and myositis ossificans. Case Presentation. We describe a patient with voluminous calcified mass entrapped in supraspinatus muscle associated with corresponding tendon tear. Histological examination corresponded to a calcified hematoma or necrosis. Patient was surgically managed with open excision of the calcified hematoma and rotator cuff arthroscopic repair. At 6 months, supraspinatus muscle was healed, and functional outcome was good. Discussion and Conclusion. We hypothesized that supraspinatus intramuscular calcified hematoma was responsible for mechanical stress on the tendon. This association has never been described. PMID:26380138

  9. Myocardial steatosis and necrosis in atria and ventricles of rats given pyruvate dehydrogenase kinase inhibitors.

    PubMed

    Jones, Huw Bowen; Reens, Jaimini; Johnson, Elizabeth; Brocklehurst, Simon; Slater, Ian

    2014-12-01

    Pharmaceutical therapies for non-insulin-dependent diabetes mellitus (NIDDM) include plasma glucose lowering by enhancing glucose utilization. The mitochondrial pyruvate dehydrogenase (PDH) complex is important in controlling the balance between glucose and fatty acid substrate oxidation. Administration of pyruvate dehydrogenase kinase inhibitors (PDHKIs) to rats effectively lowers plasma glucose but results in myocardial steatosis that in some instances is associated primarily with atrial and to a lesser degree with ventricular pathology. Induction of myocardial steatosis is not dose-dependent, varies from minimal to moderate severity, and is either of multifocal or diffuse distribution. Ventricular histopathology was restricted to few myocardial degenerative fibers, while that in the atrium/atria was of either acute or chronic appearance with the former showing myocardial degeneration/necrosis, acute myocarditis, edema, endothelial activation (rounding up), endocarditis, and thrombosis associated with moderate myocardial steatosis and the latter with myocardial loss, replacement fibrosis, and no apparent or minimal association with steatosis. The evidence from these evaluations indicate that excessive intramyocardial accumulation of lipid may be either primarily adverse or represents an indicator of other adversely affected cellular processes. PMID:24742628

  10. Effects of osteoprotegerin, RANK and RANKL on bone destruction and collapse in avascular necrosis femoral head.

    PubMed

    Xiong, Ming-Yue; Liu, Li-Qiang; Liu, Shi-Qiong; Liu, Zhen-Hui; Gao, Hang-Fei

    2016-01-01

    Avascular necrosis of femoral head (AVFH) is a clinically recalcitrant disease of hip that leads to joint destruction. Osteoprotegerin (OPG), receptor activator of nuclear factor kappa-B (RANK) and RANK ligand (RANKL) regulates the balance, maturation and function of osteoclast and bone remodeling. This study aims to investigate molecular pathways which leads to AVN by studying expression profile of OPG, RANK and RANKL genes. Quantitative Real Time-PCR is used to evaluate mRNA expression of OPG, RANK and RANKL. mRNA and protein level in normal and necrotic tissue from 42 samples of ANFH specimens were analyzed. OPG and RANKL protein levels are estimated by western blotting. The results indicated that OPG mRNA levels are higher but not significantly different in necrotic tissue than that in normal tissue (P>0.05). Although expression of RANK and RANKL is significantly lower than that of OPG, RANK and RANKL mRNA levels are higher in necrotic tissue than normal tissue (P<0.05). Protein levels of OPG and RANKL show no significant difference. In conclusion, OPG, RANK and RANKL play important role in progress of bone remodeling in necrotic area and in disturbance of bone homeostasis, which might have an effect on bone destruction and subsequent collapse of hip joint. PMID:27508034

  11. Inverse regulation of human ERBB2 and epidermal growth factor receptors by tumor necrosis factor alpha.

    PubMed Central

    Kalthoff, H; Roeder, C; Gieseking, J; Humburg, I; Schmiegel, W

    1993-01-01

    Recombinant human tumor necrosis factor (TNF) alpha decreased the expression of ERBB2 mRNA by stimulating p55 TNF receptors of pancreatic tumor cells. This decrease contrasts with an increase in epidermal growth factor receptor (EGFR) mRNA. Both effects were selectively achieved by TNF-alpha or -beta, whereas interferon alpha or gamma or transforming growth factor beta showed no such effects. The inverse regulatory effects of TNF on ERBB2 and EGFR mRNA levels were evoked by different signaling pathways of p55 TNF receptors. The TNF-mediated ERBB2 mRNA decrease was followed by a reduction in protein. Four of five pancreatic tumor cell lines exhibited this down-regulation. This decrease of ERBB2 is a singular example of a modulation of this growth factor receptor by TNF. Overexpression of ERBB2 has been reported to cause resistance to TNF and other cytotoxic cytokines. In our study we show that the TNF-mediated down-regulation of ERBB2 in pancreatic tumor cells is accompanied by an increase in growth inhibition at low doses of TNF. The simultaneous alteration of the ERBB2/EGFR balance by TNF represents a striking model of cytokine receptor transregulation in the growth control of malignant pancreatic epithelial cells. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 Fig. 5 PMID:8105469

  12. Effects of osteoprotegerin, RANK and RANKL on bone destruction and collapse in avascular necrosis femoral head

    PubMed Central

    Xiong, Ming-Yue; Liu, Li-Qiang; Liu, Shi-Qiong; Liu, Zhen-Hui; Gao, Hang-Fei

    2016-01-01

    Avascular necrosis of femoral head (AVFH) is a clinically recalcitrant disease of hip that leads to joint destruction. Osteoprotegerin (OPG), receptor activator of nuclear factor kappa-B (RANK) and RANK ligand (RANKL) regulates the balance, maturation and function of osteoclast and bone remodeling. This study aims to investigate molecular pathways which leads to AVN by studying expression profile of OPG, RANK and RANKL genes. Quantitative Real Time-PCR is used to evaluate mRNA expression of OPG, RANK and RANKL. mRNA and protein level in normal and necrotic tissue from 42 samples of ANFH specimens were analyzed. OPG and RANKL protein levels are estimated by western blotting. The results indicated that OPG mRNA levels are higher but not significantly different in necrotic tissue than that in normal tissue (P>0.05). Although expression of RANK and RANKL is significantly lower than that of OPG, RANK and RANKL mRNA levels are higher in necrotic tissue than normal tissue (P<0.05). Protein levels of OPG and RANKL show no significant difference. In conclusion, OPG, RANK and RANKL play important role in progress of bone remodeling in necrotic area and in disturbance of bone homeostasis, which might have an effect on bone destruction and subsequent collapse of hip joint. PMID:27508034

  13. Lesson "Balance in Nature

    NASA Astrophysics Data System (ADS)

    Chapanova, V.

    2012-04-01

    Lesson "Balance in Nature" This simulation game-lesson (Balance in Nature) gives an opportunity for the students to show creativity, work independently, and to create models and ideas. It creates future-oriented thought connected to their experience, allowing them to propose solutions for global problems and personal responsibility for their activities. The class is divided in two teams. Each team chooses questions. 1. Question: Pollution in the environment. 2. Question: Care for nature and climate. The teams work on the chosen tasks. They make drafts, notes and formulate their solutions on small pieces of paper, explaining the impact on nature and society. They express their points of view using many different opinions. This generates alternative thoughts and results in creative solutions. With the new knowledge and positive behaviour defined, everybody realizes that they can do something positive towards nature and climate problems and the importance of individuals for solving global problems is evident. Our main goal is to recover the ecological balance, and everybody explains his or her own well-grounded opinions. In this work process the students obtain knowledge, skills and more responsible behaviour. This process, based on his or her own experience, dialogue and teamwork, helps the participant's self-development. Making the model "human↔ nature" expresses how human activities impact the natural Earth and how these impacts in turn affect society. Taking personal responsibility, we can reduce global warming and help the Earth. By helping nature we help ourselves. Teacher: Veselina Boycheva-Chapanova " Saint Patriarch Evtimii" Scholl Str. "Ivan Vazov"-19 Plovdiv Bulgaria

  14. Earth in the balance

    SciTech Connect

    Gore, A. Jr.

    1992-01-01

    Earth in the Balance is a lucid, scientifically grounded treatise on the global environments. The author's description of the world's water, air, and land use problems is clear, lively, and knowledgable. A major section of the book explores the psychological dimensions of global environmental problems. He attempts to synthesize ideas across many fields of thought. Gore offers a Global Marshall Plan - a worldwide strategic environment initiative that would help phase out older technologies and disseminate benign substitutes, change accounting methods so environmental costs are considered, and use education as a tool.

  15. Watt and joule balances

    NASA Astrophysics Data System (ADS)

    Robinson, Ian A.

    2014-04-01

    The time is fast approaching when the SI unit of mass will cease to be based on a single material artefact and will instead be based upon the defined value of a fundamental constant—the Planck constant—h . This change requires that techniques exist both to determine the appropriate value to be assigned to the constant, and to measure mass in terms of the redefined unit. It is important to ensure that these techniques are accurate and reliable to allow full advantage to be taken of the stability and universality provided by the new definition and to guarantee the continuity of the world's mass measurements, which can affect the measurement of many other quantities such as energy and force. Up to now, efforts to provide the basis for such a redefinition of the kilogram were mainly concerned with resolving the discrepancies between individual implementations of the two principal techniques: the x-ray crystal density (XRCD) method [1] and the watt and joule balance methods which are the subject of this special issue. The first three papers report results from the NRC and NIST watt balance groups and the NIM joule balance group. The result from the NRC (formerly the NPL Mk II) watt balance is the first to be reported with a relative standard uncertainty below 2 × 10-8 and the NIST result has a relative standard uncertainty below 5 × 10-8. Both results are shown in figure 1 along with some previous results; the result from the NIM group is not shown on the plot but has a relative uncertainty of 8.9 × 10-6 and is consistent with all the results shown. The Consultative Committee for Mass and Related Quantities (CCM) in its meeting in 2013 produced a resolution [2] which set out the requirements for the number, type and quality of results intended to support the redefinition of the kilogram and required that there should be agreement between them. These results from NRC, NIST and the IAC may be considered to meet these requirements and are likely to be widely debated

  16. Micromechanical Oscillating Mass Balance

    NASA Technical Reports Server (NTRS)

    Altemir, David A. (Inventor)

    1997-01-01

    A micromechanical oscillating mass balance and method adapted for measuring minute quantities of material deposited at a selected location, such as during a vapor deposition process. The invention comprises a vibratory composite beam which includes a dielectric layer sandwiched between two conductive layers. The beam is positioned in a magnetic field. An alternating current passes through one conductive layers, the beam oscillates, inducing an output current in the second conductive layer, which is analyzed to determine the resonant frequency of the beam. As material is deposited on the beam, the mass of the beam increases and the resonant frequency of the beam shifts, and the mass added is determined.

  17. Balancing innovation and evidence.

    PubMed

    Pilcher, Jobeth W

    2015-01-01

    Nurse educators are encouraged to use evidence to guide their teaching strategies. However, evidence is not always available. How can educators make decisions regarding strategies when data are limited or absent? Where do innovation and creativity fit? How can innovation be balanced with evidence? This article provides a discussion regarding other sources of evidence, such as extrapolations, theories and principles, and collective expertise. Readers are encouraged to review the options and then analyze how they might be applied to innovation in education. PMID:25790361

  18. Anti-tumour activity of two novel compounds in cisplatin-resistant testicular germ cell cancer

    PubMed Central

    Nitzsche, B; Gloesenkamp, C; Schrader, M; Hoffmann, B; Zengerling, F; Balabanov, S; Honecker, F; Höpfner, M

    2012-01-01

    Background: Resistance to cisplatin-based chemotherapy is associated with poor prognosis in testicular germ cell cancer, emphasising the need for new therapeutic approaches. In this respect, the therapeutic concept of anti-angiogenesis is of particular interest. In a previous study, we presented two novel anti-angiogenic compounds, HP-2 and HP-14, blocking the tyrosine kinase activity of angiogenic growth factor receptors, such as vascular endothelial growth factor receptor-2 (VEGFR-2), and related signalling pathways in testicular cancer. In this study, we investigated the efficacy of these new compounds in platinum-resistant testicular germ cell tumours (TGCTs), in vitro and in vivo. Methods and results: Drug-induced changes in cell proliferation of the cisplatin-sensitive TGCT cell line 2102EP and its cisplatin-resistant counterpart 2102EP-R, both expressing the VEGFR-2, were evaluated by crystal violet staining. Both compounds inhibited the growth of cisplatin-resistant TGCT cells in a dose-dependent manner. In combination experiments with cisplatin, HP-14 revealed additive growth-inhibitory effects in TGCT cells, irrespective of the level of cisplatin resistance. Anti-angiogenic effects of HP compounds were confirmed by tube formation assays with freshly isolated human umbilical vein endothelial cells. Using TGCT cells inoculated onto the chorioallantoic membrane of fertilised chicken eggs (chicken chorioallantoic membrane assay), the anti-angiogenic and anti-proliferative potency of the novel compounds was also demonstrated in vivo. Gene expression profiling revealed changes in the expression pattern of genes related to DNA damage detection and repair, as well as in chaperone function after treatment with both cisplatin and HP-14, alone or in combination. This suggests that HP-14 can revert the lost effectiveness of cisplatin in the resistant cells by altering the expression of critical genes. Conclusion: The novel compound HP-14 effectively inhibits the growth of cisplatin-resistant TGCT cells and suppresses tumour angiogenesis. Thus, HP-14 may be an interesting new agent that should be further explored for TGCT treatment, especially in TGCTs that are resistant to cisplatin. PMID:23169338

  19. Combined blockade of signalling pathways shows marked anti-tumour potential in phaeochromocytoma cell lines

    PubMed Central

    Nölting, Svenja; Garcia, Edwin; Alusi, Ghassan; Giubellino, Alessio; Pacak, Karel; Korbonits, Márta; Grossman, Ashley B

    2016-01-01

    Currently, there is no completely effective therapy available for metastatic phaeochromocytomas (PCCs) and paragangliomas. In this study, we explore new molecular targeted therapies for these tumours, using one more benign (mouse phaeochromocytoma cell (MPC)) and one more malignant (mouse tumour tissue (MTT)) mouse PCC cell line –both generated from heterozygous neurofibromin 1 knockout mice. Several PCC-promoting gene mutations have been associated with aberrant activation of PI3K/AKT, mTORC1 and RAS/RAF/ERK signalling. We therefore investigated different agents that interfere specifically with these pathways, including antagonism of the IGF1 receptor by NVP-AEW541. We found that NVP-AEW541 significantly reduced MPC and MTT cell viability at relatively high doses but led to a compensatory up-regulation of ERK and mTORC1 signalling at suboptimal doses while PI3K/AKT inhibition remained stable. We subsequently investigated the effect of the dual PI3K/mTORC1/2 inhibitor NVP-BEZ235, which led to a significant decrease of MPC and MTT cell viability at doses down to 50 nM but again increased ERK signalling. Accordingly, we next examined the combination of NVP-BEZ235 with the established agent lovastatin, as this has been described to inhibit ERK signalling. Lovastatin alone significantly reduced MPC and MTT cell viability at therapeutically relevant doses and inhibited both ERK and AKT signalling, but increased mTORC1/p70S6K signalling. Combination treatment with NVP-BEZ235 and lovastatin showed a significant additive effect in MPC and MTT cells and resulted in inhibition of both AKT and mTORC1/p70S6K signalling without ERK up-regulation. Simultaneous inhibition of PI3K/AKT, mTORC1/2 and ERK signalling suggests a novel therapeutic approach for malignant PCCs. PMID:22715163

  20. Melatonin potentiates the anti-tumour effect of pravastatin in rat mammary gland carcinoma model

    PubMed Central

    Orendáš, Peter; Kubatka, Peter; Bojková, Bianka; Kassayová, Monika; Kajo, Karol; Výbohová, Desanka; Kružliak, Peter; Péč, Martin; Adamkov, Marián; Kapinová, Andrea; Adamicová, Katarína; Sadloňová, Vladimíra; Chmelová, Martina; Stollárová, Nadežda

    2014-01-01

    Previous studies in the field of cancer research have suggested a possible role for statins in the reduction of risk in certain malignancies. The purpose of these studies was to examine the chemopreventive effects of pravastatin alone and in combination with pineal hormone melatonin in the N-methyl-N-nitrosourea-induced mammary carcinogenesis model. Pravastatin was given orally (1 00 mg/kg) and melatonin was added to the water (20 μg/ml). Chemoprevention began seven days prior to carcinogen administration and subsequently continued for 15 weeks until autopsy. At autopsy, mammary tumours were removed and prepared for histopathological and immunohistochemical analysis. Parameters of experimental carcinogenesis, mechanism of action (biomarkers of apoptosis, angiogenesis and proliferation) and side effects after long-term treatment in animals were assessed. Pravastatin alone suppressed tumour frequency by 20.5% and average tumour volume by 15% compared with controls. Combined administration of the drugs decreased tumour frequency by 69% and lengthened tumour latency by nine days compared with control animals. The ration between high and low grade carcinomas was apparently reduced in both treated groups. The analysis of carcinoma cells showed significant expression increase in caspase-3 and caspase-7 after pravastatin treatment; however, combined treatment even more pronounced increase in the expression of both caspases. Regarding VEGFR-2 expression, a small effect in carcinomas of both treated groups was found. In plasma metabolism evaluation, pravastatin alone significantly decreased levels of glucose and triacylglycerols. Our results suggest a mild anti-neoplastic effect of pravastatin in this rat mammary gland carcinoma model. Statins co-administered with other suitable drug (e.g. melatonin) should be further evaluated for tumour-preventive properties. PMID:25270735

  1. Enhanced anti-tumour effects of Vinca alkaloids given separately from cytostatic therapies

    PubMed Central

    Ehrhardt, H; Pannert, L; Pfeiffer, S; Wachter, F; Amtmann, E; Jeremias, I

    2013-01-01

    Background and Purpose In polychemotherapy protocols, that is for treatment of neuroblastoma and Ewing sarcoma, Vinca alkaloids and cell cycle-arresting drugs are usually administered on the same day. Here we studied whether this combination enables the optimal antitumour effects of Vinca alkaloids to be manifested. Experimental Approach Vinca alkaloids were tested in a preclinical mouse model in vivo and in vitro in combination with cell cycle-arresting drugs. Signalling pathways were characterized using RNA interference. Key Results In vitro, knockdown of cyclins significantly inhibited vincristine-induced cell death indicating, in accordance with previous findings, Vinca alkaloids require active cell cycling and M-phase transition for induction of cell death. In contrast, anthracyclines, irradiation and dexamethasone arrested the cell cycle and acted like cytostatic drugs. The combination of Vinca alkaloids with cytostatic therapeutics resulted in diminished cell death in 31 of 36 (86%) tumour cell lines. In a preclinical tumour model, anthracyclines significantly inhibited the antitumour effect of Vinca alkaloids in vivo. Antitumour effects of Vinca alkaloids in the presence of cytostatic drugs were restored by caffeine, which maintained active cell cycling, or by knockdown of p53, which prevented drug-induced cell cycle arrest. Therapeutically most important, optimal antitumour effects were obtained in vivo upon separating the application of Vinca alkaloids from cytostatic therapeutics. Conclusion and Implications Clinical trials are required to prove whether Vinca alkaloids act more efficiently in cancer patients if they are applied uncoupled from cytostatic therapies. On a conceptual level, our data suggest the implementation of polychemotherapy protocols based on molecular mechanisms of drug–drug interactions. Linked Article This article is commented on by Solary, pp 1555–1557 of this issue. To view this commentary visit http://dx.doi.org/10.1111/bph.12101 PMID:23186127

  2. Synthesis, analysis and biological evaluation of novel indolquinonecryptolepine analogues as potential anti-tumour agents.

    PubMed

    Le Gresley, A; Gudivaka, V; Carrington, S; Sinclair, A; Brown, J E

    2016-03-21

    A small library of cryptolepine analogues were synthesised incorporating halogens and/or nitrogen containing side chains to optimise their interaction with the sugar-phosphate backbone of DNA to give improved binding, interfering with topoisomerase II hence enhancing cytotoxicity. Cell viability, DNA binding and Topoisomerase II inhibition is discussed for these compounds. Fluorescence microscopy was used to investigate the uptake of the synthesised cryptolepines into the nucleus. We report the synthesis and anti-cancer biological evaluation of nine novel cryptolepine analogues, which have greater cytotoxicity than the parent compound and are important lead compounds in the development of novel potent and selective indoloquinone anti-neoplastic agents. PMID:26893255

  3. Preparation and Anti-Tumour Activity of Some Arylbismuth(III) Oxine Complexes.

    PubMed

    Smith, K A; Deacon, G B; Jackson, W R; Tiekink, E R; Rainone, S; Webster, L K

    1998-01-01

    New arylbismuth(lll) oxinates, PhBi(MeOx)(2), (p-MeC(6)H(4))Bi(Ox)(2), (p-MeC(6)H(4))Bi(MeOx)(2), (p-ClC(6)H(4))Bi(Ox)(2), and (p-ClC(6)H(4))Bi(MeOx)(2) (Ox(-) = quinolin-8-olate and MeOx(-)=2-methylquinolin-8-olate) have been prepared by reaction of the appropriate diarylbismuth chlorides with Na(Ox) or Na(MeOx) in the presence of 15-crown-5. An X-ray crystallographic study has shown PhBi(MeOx)(2) to be a five coordinate monomer with distorted square pyramidal stereochemistry. Chelating MeOx ligands have a cisoid arrangement in the square plane and the phenyl group is apical. The lattice is stabilised by significant pi-pi interactions between centrosymmetric molecules. A range of these complexes has been shown to have high in vitro biological activity (comparable with or better than cisplatin) against L1210 leukaemia, the corresponding cisplatin resistant line, and a human ovarian cell line, SKOV-3. However, initial in vivo testing against a solid mouse plasmacytoma (PC6) and P388 leukaemia has not revealed significant activity. PMID:18475861

  4. MPLA incorporation into DC-targeting glycoliposomes favours anti-tumour T cell responses.

    PubMed

    Boks, Martine A; Ambrosini, Martino; Bruijns, Sven C; Kalay, Hakan; van Bloois, Louis; Storm, Gert; Garcia-Vallejo, Juan J; van Kooyk, Yvette

    2015-10-28

    Dendritic cells (DC) are attractive targets for cancer immunotherapy as they initiate strong and long-lived tumour-specific T cell responses. DC can be effectively targeted in vivo with tumour antigens by using nanocarriers such as liposomes. Cross-presentation of tumour antigens is enhanced with strong adjuvants such as TLR ligands. However, often these adjuvants have off-target effects, and would benefit from a DC-specific targeting strategy, similar to the tumour antigen. The goal of this study was to develop a strategy for specifically targeting DC with tumour antigen and adjuvant by using glycoliposomes. We have generated liposomes containing the glycan Lewis(Le)(X) which is highly specific for the C-type lectin receptor DC-SIGN expressed by DC. Le(X)-modified liposomes were taken up by human monocyte-derived DC in a DC-SIGN-specific manner. As adjuvants we incorporated the TLR ligands Pam3CySK4, Poly I:C, MPLA and R848 into liposomes and compared their adjuvant capacity on DC. Incorporation of the TLR4 ligand MPLA into glycoliposomes induced DC maturation and production of pro-inflammatory cytokines, in a DC-SIGN-specific manner, and DC activation was comparable to administration of soluble MPLA. Incorporation of MPLA into glycoliposomes significantly enhanced antigen cross-presentation of the melanoma tumour antigen gp100280-288 peptide to CD8(+) T cells compared to non-glycosylated MPLA liposomes. Importantly, antigen cross-presentation of the gp100280-288 peptide was significantly higher using MPLA glycoliposomes compared to the co-administration of soluble MPLA with glycoliposomes. Taken together, our data demonstrates that specific targeting of a gp100 tumour antigen and the adjuvant MPLA to DC-SIGN-expressing DC enhances the uptake of peptide-containing liposomes, the activation of DC, and induces tumour antigen-specific CD8(+) T cell responses. These data demonstrate that adjuvant-containing glycoliposome-based vaccines targeting DC-SIGN(+) DC represent a powerful new approach for CD8(+) T cell activation. PMID:26151293

  5. MET is required for the recruitment of anti-tumoural neutrophils

    PubMed Central

    Finisguerra, Veronica; Di Conza, Giusy; Di Matteo, Mario; Serneels, Jens; Costa, Sandra; Thompson, A.A. Roger; Wauters, Els; Walmsley, Sarah; Prenen, Hans; Granot, Zvi; Casazza, Andrea; Mazzone, Massimiliano

    2015-01-01

    Mutations or amplification of the MET proto-oncogene are involved in the pathogenesis of several tumours1-4, which rely on the constitutive engagement of this pathway for their growth and survival1,5. However, MET is expressed not only by cancer cells but also by tumour-associated stromal cells although its precise role in this compartment is not well characterized6-11. Here, we show that MET is required for neutrophil chemoattraction and cytotoxicity in response to its ligand HGF. Met deletion in neutrophils enhances tumour growth and metastasis. This phenotype correlates with reduced neutrophil infiltration to both primary tumour and metastatic site. Similarly, Met is necessary for neutrophil transudation during colitis, skin rash or peritonitis. Mechanistically, Met is induced by tumour-derived TNF-α or other inflammatory stimuli in both mouse and human neutrophils. This induction is instrumental for neutrophil transmigration across an activated endothelium and iNOS production upon HGF stimulation. Consequently, HGF/MET-dependent nitric oxide release by neutrophils promotes cancer cell killing, which abates tumour growth and metastasis. Following systemic administration of a MET kinase inhibitor, we prove that the therapeutic benefit of MET targeting in cancer cells is partly countered by the pro-tumoural effect rising from MET blockade in neutrophils. Our work identifies an unprecedented role of MET in neutrophils, suggests a potential “Achilles’ heel” of MET-targeted therapies in cancer, and supports the rationale for evaluating anti-MET drugs in certain inflammatory diseases. PMID:25985180

  6. Glycolysis inhibition as a cancer treatment and its role in an anti-tumour immune response.

    PubMed

    Gill, Kheshwant S; Fernandes, Philana; O'Donovan, Tracey R; McKenna, Sharon L; Doddakula, Kishore K; Power, Derek G; Soden, Declan M; Forde, Patrick F

    2016-08-01

    Increased glycolysis is the main source of energy supply in cancer cells that use this metabolic pathway for ATP generation. Altered energy metabolism is a biochemical fingerprint of cancer cells that represents one of the "hallmarks of cancer". The immune system can prevent tumour growth by eliminating cancer cells but this editing process ultimately results in poorly immunogenic cells remaining allowing for unchallenged tumour growth. In this review we look at the glycolysis pathway as a target for cancer treatments. We also examine the interplay between the glycolysis modulation and the immune response as an anti-cancer therapy. PMID:27373814

  7. Mastectomy Weight and Tissue Expander Volume Predict Necrosis and Increased Costs Associated with Breast Reconstruction

    PubMed Central

    Yalanis, Georgia C.; Nag, Shayoni; Georgek, Jakob R.; Cooney, Carisa M.; Manahan, Michele A.; Rosson, Gedge D.

    2015-01-01

    Introduction: Impaired vascular perfusion in tissue expander (TE) breast reconstruction leads to mastectomy skin necrosis. We investigated factors and costs associated with skin necrosis in postmastectomy breast reconstruction. Methods: Retrospective review of 169 women with immediate TE placement following mastectomy between May 1, 2009 and May 31, 2013 was performed. Patient demographics, comorbidities, intraoperative, and postoperative outcomes were collected. Logistic regression analysis on individual variables was performed to determine the effects of tissue expander fill volume and mastectomy specimen weight on skin necrosis. Billing data was obtained to determine the financial burden associated with necrosis. Results: This study included 253 breast reconstructions with immediate TE placement from 169 women. Skin necrosis occurred in 20 flaps for 15 patients (8.9%). Patients with hypertension had 8 times higher odds of skin necrosis [odd ratio (OR), 8.10, P < 0.001]. Patients with TE intraoperative fill volumes >300 cm3 had 10 times higher odds of skin necrosis (OR, 10.66, P =0.010). Volumes >400 cm3 had 15 times higher odds of skin necrosis (OR, 15.56, P = 0.002). Mastectomy specimen weight was correlated with skin necrosis. Specimens >500 g had 10 times higher odds of necrosis and specimens >1000 g had 18 times higher odds of necrosis (OR, 10.03 and OR, 18.43; P =0.003 and P <0.001, respectively). Mastectomy skin necrosis was associated with a 50% increased inpatient charge. Conclusion: Mastectomy flap necrosis is associated with HTN, larger TE volumes and mastectomy specimen weights, resulting in increased inpatient charges. Conservative TE volumes should be considered for patients with hypertension and larger mastectomy specimens. PMID:26301139

  8. The role of tumour necrosis factor alpha and soluble tumour necrosis factor alpha receptors in the symptomatology of schizophrenia.

    PubMed

    Turhan, Levent; Batmaz, Sedat; Kocbiyik, Sibel; Soygur, Arif Haldun

    2016-07-01

    Background Immunological mechanisms may be responsible for the development and maintenance of schizophrenia symptoms. Aim The aim of this study is to measure tumour necrosis factor-alpha (TNF-α), soluble tumour necrosis factor-alpha receptor I (sTNF-αRI), and soluble tumour necrosis factor-alpha receptor II (sTNF-αRII) levels in patients with schizophrenia and healthy individuals, and to determine their relationship with the symptoms of schizophrenia. Methods Serum TNF-α, sTNF-αRI and sTNF-αRII levels were measured. The Positive and Negative Syndrome Scale (PANSS) was administered for patients with schizophrenia (n = 35), and the results were compared with healthy controls (n = 30). Hierarchical regression analyses were undertaken to predict the levels of TNF-α, sTNF-αRI and sTNF-αRII. Results No significant difference was observed in TNF-α levels, but sTNF-αRI and sTNF-αRII levels were lower in patients with schizophrenia. Serum sTNF-αRI and sTNF-αRII levels were found to be negatively correlated with the negative subscale score of the PANSS, and sTNF-αRI levels were also negatively correlated with the total score of the PANSS. Smoking, gender, body mass index were not correlated with TNF-α and sTNF-α receptor levels. Conclusions These results suggest that there may be a change in anti-inflammatory response in patients with schizophrenia due to sTNF-αRI and sTNF-αRII levels. The study also supports low levels of TNF activity in schizophrenia patients with negative symptoms. PMID:26754110

  9. X-ray-induced cell death: Apoptosis and necrosis

    SciTech Connect

    Nakano, Hisako; Shinohara, Kunio

    1994-10-01

    X-ray-induced cell death in MOLT-4N1, a subclone of MOLT-4 cells, and M10 cells was studied with respect to their modes of cell death, apoptosis and necrosis. MOLT-4N1 cells showed radiosensitivity similar to that of M10 cells, a radiosensitive mutant of L5178Y, as determined by the colony formation assay. Analysis of cell size demonstrated that MOLT-4N1 cells increased in size at an early stage after irradiation and then decreased to a size smaller than that of control cells, whereas the size of irradiated M10 cells increased continuously. Apoptosis detected by morphological changes and DNA ladder formation (the cleavage of DNA into oligonucleosomal fragments) occurred in X-irradiated MOLT-4N1 cells but not in M10 cells. Pulsed-field gel electrophoresis showed that the ladder formation involved an intermediate-sized DNA (about 20 kbp). Most of the DNA was detected at the origin in both methods of electrophoresis in the case of M10 cells, though a trace amount of ladder formation was observed. Heat treatment of M10 cells induced apoptosis within 30 min after treatment, in contrast to MOLT-4N1 cells. The results suggest that apoptosis and necrosis are induced by X rays in a manner which is dependent on the cell line irrespective of the capability of the cells to develop apoptosis. DNA fragmentation was the earliest change observed in the development of apoptosis. 27 refs., 8 figs., 1 tab.

  10. Infection Necrosis After an Extracorporeal Reduction of a Condyle Fracture.

    PubMed

    Hwang, Kun; Kim, Hyung Mook

    2016-05-01

    The authors experienced a patient of infection necrosis after an extracorporeal reduction of a condyle fracture and reconstructed it with an iliac bone graft.A 37-year-old man visited with a bilateral condyle fracture and a left para-symphyseal fracture. On the post-trauma third day, an intermaxillary fixation was applied using arch bars. On the post-trauma tenth day, an extracorporeal reduction was carried out. On postoperative day (POD) 7, the amount of the drain was 9 cc and the drain was removed. On POD 9, redness and a pus drain were observed on the operation site. On POD 18, growth of Streptococcus anginosus was observed in a thioglycolate broth. On POD 47, the infected condylar head was removed and reconstructed with an iliac bone graft. On the POD ninth week, the incisal opening was 24 mm.To prevent such infections, necrosis or absorption of reduced and a miniplate-fixed condyle head, the bony defect should be filled completely without exposing any medullary bone. Hematomas should be prevented using a large suction drain until the drain turns serous and eventually diminishes to zero. Finally, aseptic conditions are required in retrieving, assembling, and reinserting the extracorporeal reduced segment by changing the gloves and sufficient disinfectant irrigation. In case a pus discharge appears at the operation site, it would be wise to remove the fixed condyle, the infection source, and replace with healthy bone graft as soon as possible. PMID:27054427

  11. Gastric necrosis: A late complication of nissen fundoplication.

    PubMed

    Salinas, Javier; Georgiev, Tihomir; González-Sánchez, Juan Antonio; López-Ruiz, Elena; Rodríguez-Montes, José Antonio

    2014-09-27

    Gastric necrosis is a rare condition because of the rich blood supply and the extensive submucosal vascular network of the stomach. "Gas-bloat" syndrome is a well known Nissen fundoplication postoperative complication. It may cause severe gastric dilatation, but very rarely an ischemic compromise of the organ. Other factors, such as gastric outlet obstruction, may concur to cause an intraluminal pressure enough to blockade venous return and ultimately arterial blood supply and oxygen deliver, leading to ischaemia. We report a case of a 63-year-old women, who presented a total gastric necrosis following laparoscopic Nissen fundoplication and a pyloric phytobezoar which was the trigger event. No preexisting gastric motility disorders were present by the time of surgery, as demonstrated in the preoperative barium swallow, thus a poor mastication (patient needed no dentures) of a high fiber meal (cabbage) may have been predisposing factors for the development of a bezoar in an otherwise healthy women at the onset of old age. A total gastrectomy with esophagojejunostomy was performed and patient was discharged home after a 7-d hospital stay with no immediate complications. We also discuss some technical aspects of the procedure that might be important to reduce the incidence of this complication. PMID:25276288

  12. Necrosis of the femoral head after kidney transplantation.

    PubMed

    Lausten, G S; Lemser, T; Jensen, P K; Egfjord, M

    1998-12-01

    We reviewed the medical records of 750 patients (445 men, 305 women), who had received a kidney transplant during the period 1968-1995, for any sign of necrosis of the femoral head. For post-operative immunosuppression, 374 patients had received high-dose corticosteroids (average 12.5 g during the first year post-operatively), while 376 patients had received low-dose corticosteroids (average 6.5 g during the first year post-operatively) and cyclosporin A. Survival curves according to Kaplan and Meier (J Am Stat Ass 1958: 53: 457-481) were constructed. In the high-dose steroid group, 42/374 patients (11.2%) developed femoral head necrosis, at an average of 26.2 months post-transplantation. In the low-dose steroid group, only 19/376 (5.1%) patients developed this complication, at an average of 20.5 months post-transplantation. This difference in numbers of femoral head necroses was highly significant (p < 0.005). We conclude that steroid doses should be minimized whenever feasible in post-transplant immunosuppression therapy. PMID:9850453

  13. Carbendazim impends hepatic necrosis when combined with imazalil or cypermethrin.

    PubMed

    Dikić, Domagoj; Landeka, Irena; Knežević, Fabijan; Mojsović-Ćuić, Ana; Benković, Vesna; Horvat-Knežević, Anica; Lončar, Goran; Teparić, Renata; Rogić, Dunja

    2012-05-01

    Imazalil, cypermethrin and carbendazim are detected in plants for human nutrition. To explore whether their combinations, applied orally in low doses, would induce changes in metabolic patterns and hepatotoxicity, a subchronic in vivo experiment was conducted. Doses of 10mg/kg of imazalil (im) and cypermethrin (cy) and 20 mg/kg of carbendazim (car) and their combinations (im, 10 mg/kg+cy, 10mg/kg; im, 10mg/kg+car, 20mg/kg; car, 20 mg/kg + im, 10 mg/kg) were given to Swiss mice daily over 28 days. After 24 hr from the last dose, the relationships of cytotoxicity biomarkers were analysed: serum lactate dehydrogenase, aspartate transaminase, alanine transferase, amylase, alkaline phosphatase, creatine kinase, creatinine and total proteins. Individual pesticides showed different toxic potential (cy>im car) generally characterized by increase in enzyme activities. Histological analysis showed that cypermethrin, but not imazalil or carbendazim, alone can cause mild necrosis. Combinations generally caused decrease in the activity of enzymes, indicating liver damage. Low doses of carbendazim in combination with low doses of imazalil or cypermethrin caused very pronounced hepatic necrosis, more than any of the three individually applied pesticides or combination of imazalil and cypermethrin. In fruits and vegetables for human consumption, residues of these three pesticides and prolonged combined intake of low doses, which by themselves acutely would not cause any effect, may have similar hepatotoxic effects. PMID:22077925

  14. Epidemiological characteristics of infectious hematopoietic necrosis virus (IHNV): a review.

    PubMed

    Dixon, Peter; Paley, Richard; Alegria-Moran, Raul; Oidtmann, Birgit

    2016-01-01

    Infectious hematopoietic necrosis virus (IHNV, Rhabdoviridae), is the causative agent of infectious hematopoietic necrosis (IHN), a disease notifiable to the World Organisation for Animal Health, and various countries and trading areas (including the European Union). IHNV is an economically important pathogen causing clinical disease and mortalities in a wide variety of salmonid species, including the main salmonid species produced in aquaculture, Atlantic salmon (Salmo salar) and rainbow trout (Oncorhynchus mykiss). We reviewed the scientific literature on IHNV on a range of topics, including geographic distribution; host range; conditions required for infection and clinical disease; minimum infectious dose; subclinical infection; shedding of virus by infected fish; transmission via eggs; diagnostic tests; pathogen load and survival of IHNV in host tissues. This information is required for a range of purposes including import risk assessments; parameterisation of disease models; for surveillance planning; and evaluation of the chances of eradication of the pathogen to name just a few. The review focuses on issues that are of relevance for the European context, but many of the data summarised have relevance to IHN globally. Examples for application of the information is presented and data gaps highlighted. PMID:27287024

  15. Percentage tumor necrosis following chemotherapy in neuroblastoma correlates with MYCN status but not survival.

    PubMed

    Bomken, Simon; Davies, Beverley; Chong, Leeai; Cole, Michael; Wood, Katrina M; McDermott, Michael; Tweddle, Deborah A

    2011-03-01

    The percentage of chemotherapy-induced necrosis in primary tumors corresponds with outcome in several childhood malignancies, including high-risk metastatic diseases. In this retrospective pilot study, the authors assessed the importance of postchemotherapy necrosis in high-risk neuroblastoma with a histological and case notes review of surgically resected specimens. The authors reviewed all available histology of 31 high-risk neuroblastoma cases treated with COJEC (dose intensive etoposide and vincristine with either cyclophosphamide, cisplatin or carboplatin) or OPEC/OJEC (etoposide, vincristine and cyclophosphamide with alternating cisplatin [OPEC] or carboplatin [OJEC]) induction chemotherapy in 2 Children's Cancer & Leukaemia Group (CCLG) pediatric oncology centers. The percentage of postchemotherapy necrosis was assessed and compared with MYCN amplification status and overall survival. The median percentage of postchemotherapy tumor necrosis was 60%. MYCN status was available for 28 cases, of which 12 were amplified (43%). Survival in cases with ≥ 60% necrosis or ≥ 90% necrosis was not better than those with less necrosis, nor was percentage necrosis associated with survival using Cox regression. However, MYCN-amplified tumors showed a higher percentage of necrosis than non-MYCN-amplified tumors, 71.3% versus 37.2% (P = .006). This effect was not related to prechemotherapy necrosis and did not confer improved overall survival. Postchemotherapy tumor necrosis is higher in patients with MYCN amplification. In this study, postchemotherapy necrosis did not correlate with overall survival and should not lead to modification of postoperative treatment. However, these findings need to be confirmed in a larger prospective study of children with high-risk neuroblastoma. PMID:21214410

  16. RIP1 and RIP3 complex regulates radiation-induced programmed necrosis in glioblastoma.

    PubMed

    Das, Arabinda; McDonald, Daniel G; Dixon-Mah, Yaenette N; Jacqmin, Dustin J; Samant, Vikram N; Vandergrift, William A; Lindhorst, Scott M; Cachia, David; Varma, Abhay K; Vanek, Kenneth N; Banik, Naren L; Jenrette, Joseph M; Raizer, Jeffery J; Giglio, Pierre; Patel, Sunil J

    2016-06-01

    Radiation-induced necrosis (RN) is a relatively common side effect of radiation therapy for glioblastoma. However, the molecular mechanisms involved and the ways RN mechanisms differ from regulated cell death (apoptosis) are not well understood. Here, we compare the molecular mechanism of cell death (apoptosis or necrosis) of C6 glioma cells in both in vitro and in vivo (C6 othotopically allograft) models in response to low and high doses of X-ray radiation. Lower radiation doses were used to induce apoptosis, while high-dose levels were chosen to induce radiation necrosis. Our results demonstrate that active caspase-8 in this complex I induces apoptosis in response to low-dose radiation and inhibits necrosis by cleaving RIP1 and RI. When activation of caspase-8 was reduced at high doses of X-ray radiation, the RIP1/RIP3 necrosome complex II is formed. These complexes induce necrosis through the caspase-3-independent pathway mediated by calpain, cathepsin B/D, and apoptosis-inducing factor (AIF). AIF has a dual role in apoptosis and necrosis. At high doses, AIF promotes chromatinolysis and necrosis by interacting with histone H2AX. In addition, NF-κB, STAT-3, and HIF-1 play a crucial role in radiation-induced inflammatory responses embedded in a complex inflammatory network. Analysis of inflammatory markers in matched plasma and cerebrospinal fluid (CSF) isolated from in vivo specimens demonstrated the upregulation of chemokines and cytokines during the necrosis phase. Using RIP1/RIP3 kinase specific inhibitors (Nec-1, GSK'872), we also establish that the RIP1-RIP3 complex regulates programmed necrosis after either high-dose radiation or TNF-α-induced necrosis requires RIP1 and RIP3 kinases. Overall, our data shed new light on the relationship between RIP1/RIP3-mediated programmed necrosis and AIF-mediated caspase-independent programmed necrosis in glioblastoma. PMID:26684801

  17. Use of drug therapy to manage acute cutaneous necrosis of the skin.

    PubMed

    Wallace, Jill S; Hall, John C

    2010-04-01

    Acute cutaneous necrosis is defined as a sudden onset of gangrenous skin changes in the skin, associated with significant morbidity and mortality. The following diseases are included in this discussion: coumadin necrosis, heparin necrosis, brown recluse spider bite, necrotizing fasciitis, vasculitis, pyoderma gangrenosum, calciphylaxis, clotting abnormalities and embolic phenomena. The importance of early diagnosis, early distinction and early drug therapy or drug withdrawal must match the diagnosis for maximal preservation of the skin and underlying tissue. PMID:20514791

  18. Energy balance climate models

    NASA Technical Reports Server (NTRS)

    North, G. R.; Cahalan, R. F.; Coakley, J. A., Jr.

    1981-01-01

    An introductory survey of the global energy balance climate models is presented with an emphasis on analytical results. A sequence of increasingly complicated models involving ice cap and radiative feedback processes are solved, and the solutions and parameter sensitivities are studied. The model parameterizations are examined critically in light of many current uncertainties. A simple seasonal model is used to study the effects of changes in orbital elements on the temperature field. A linear stability theorem and a complete nonlinear stability analysis for the models are developed. Analytical solutions are also obtained for the linearized models driven by stochastic forcing elements. In this context the relation between natural fluctuation statistics and climate sensitivity is stressed.

  19. Balancing Family and Career

    NASA Astrophysics Data System (ADS)

    Andam, Aba Bentil; Dawson, Silvina Ponce; Horton, K. Renee; Sandow, Barbara

    2005-10-01

    In essentially all countries, responsibilities for child care, cooking, cleaning, and other homemaking tasks fall predominantly on the wife and mother. In addition, the childbearing years come during the period when a physicist must study hard, work long hours on research, and take temporary positions, often abroad. Thus, balancing family and career has long been one of the major barriers to women's participation in science and engineering fields, including physics. While many young women believe that they must choose between having children and having a science career, the fact is that the majority of women physicists in both developing and developed countries have successfully done both. This paper summarizes some ideas and recommendations raised in discussions, especially focused on easing the challenges of having children while in temporary jobs, returning to physics after a career break, the need for "family-friendly" working conditions, and the dual-career problem facing couples where both are scientists.

  20. Applications of balanced pairs

    NASA Astrophysics Data System (ADS)

    Li, HuanHuan; Wang, JunFu; Huang, ZhaoYong

    2016-05-01

    Let $(\\mathscr{X}$, $\\mathscr{Y})$ be a balanced pair in an abelian category. We first introduce the notion of cotorsion pairs relative to $(\\mathscr{X}$, $\\mathscr{Y})$, and then give some equivalent characterizations when a relative cotorsion pair is hereditary or perfect. We prove that if the $\\mathscr{X}$-resolution dimension of $\\mathscr{Y}$ (resp. $\\mathscr{Y}$-coresolution dimension of $\\mathscr{X}$) is finite, then the bounded homotopy category of $\\mathscr{Y}$ (resp. $\\mathscr{X}$) is contained in that of $\\mathscr{X}$ (resp. $\\mathscr{Y}$). As a consequence, we get that the right $\\mathscr{X}$-singularity category coincides with the left $\\mathscr{Y}$-singularity category if the $\\mathscr{X}$-resolution dimension of $\\mathscr{Y}$ and the $\\mathscr{Y}$-coresolution dimension of $\\mathscr{X}$ are finite.

  1. Skin friction balance

    NASA Technical Reports Server (NTRS)

    Ping, Tcheng (Inventor); Supplee, Frank H., Jr. (Inventor)

    1989-01-01

    A skin friction balance uses a parallel linkage mechanism to avoid inaccuracies in skin friction measurement attributable to off-center normal forces. The parallel linkage mechanism includes a stationary plate mounted in a cage, and an upper and lower movable plate which are linked to each other and to the stationary plate throught three vertical links. Flexure pivots are provided for pivotally connecting the links and the plates. A sensing element connected to the upper plate moves in response to skin friction, and the lower plate moves in the opposite direction of the upper plate. A force motor maintains a null position of the sensing element by exerting a restoring force in response to a signal generated by a linear variable differential transformer (LVDT).

  2. Energy balance in peridynamics.

    SciTech Connect

    Lehoucq, Richard B.; Silling, Stewart Andrew

    2010-09-01

    The peridynamic model of solid mechanics treats internal forces within a continuum through interactions across finite distances. These forces are determined through a constitutive model that, in the case of an elastic material, permits the strain energy density at a point to depend on the collective deformation of all the material within some finite distance of it. The forces between points are evaluated from the Frechet derivative of this strain energy density with respect to the deformation map. The resulting equation of motion is an integro-differential equation written in terms of these interparticle forces, rather than the traditional stress tensor field. Recent work on peridynamics has elucidated the energy balance in the presence of these long-range forces. We have derived the appropriate analogue of stress power, called absorbed power, that leads to a satisfactory definition of internal energy. This internal energy is additive, allowing us to meaningfully define an internal energy density field in the body. An expression for the local first law of thermodynamics within peridynamics combines this mechanical component, the absorbed power, with heat transport. The global statement of the energy balance over a subregion can be expressed in a form in which the mechanical and thermal terms contain only interactions between the interior of the subregion and the exterior, in a form anticipated by Noll in 1955. The local form of this first law within peridynamics, coupled with the second law as expressed in the Clausius-Duhem inequality, is amenable to the Coleman-Noll procedure for deriving restrictions on the constitutive model for thermomechanical response. Using an idea suggested by Fried in the context of systems of discrete particles, this procedure leads to a dissipation inequality for peridynamics that has a surprising form. It also leads to a thermodynamically consistent way to treat damage within the theory, shedding light on how damage, including the

  3. Ischaemic necrosis of the tongue as a rare complication of cardiogenic shock.

    PubMed

    Hulstaert, E; Roggeman, E; Beeckman, A-S; Moerman, M; Vanderstraeten, E; Rasquin, K; Monsaert, E; Baert, D; Dewint, P; Burvenich, P; Van Steenkiste, C

    2015-12-01

    Ischaemic necrosis of the tongue is an unusual clinical finding. In most cases it is associated with vasculitis, particularly giant cell arteritis (GCA). Other causes include profound cardiogenic shock. We report a case of tongue necrosis in an 81-year-old Caucasian woman. The patient was admitted to the intensive care unit (ICU) for cardiogenic shock. Swelling of the tongue was reported before intubation and evolved into tongue ischaemia and necrosis of the tip of the tongue. After surgical debridement the patient recovered. To our knowledge, this is the second report of a patient surviving tongue necrosis resulting from cardiogenic shock. PMID:26790554

  4. Anti-tumor necrosis factor-α therapy in uveitis.

    PubMed

    Cordero-Coma, Miguel; Sobrin, Lucia

    2015-01-01

    Since the first reported use in 2001 of an anti-tumor necrosis factor-alpha (TNF-α) agent, infliximab, for the treatment of uveitis, several new anti-TNF-α agents have emerged for the treatment of refractory noninfectious uveitides, although their use remains off-label in the US. These agents have demonstrated remarkable clinical antiinflammatory efficacy and a potential immunoregulatory role in selected uveitis patients, but it is currently unclear whether they can modify the natural history of disease. We review the rationale and clinical indications for this therapy, the differences between agents, how to manage dosing and intervals, and how to screen for and identify potential side effects. We also present a summary of the science behind the use of anti-TNF-α agents in ocular inflammation and the evidence for their efficacy. PMID:26164735

  5. Laser-induced fluorescence spectroscopy in tissue local necrosis detection

    NASA Astrophysics Data System (ADS)

    Cip, Ondrej; Buchta, Zdenek; Lesundak, Adam; Randula, Antonin; Mikel, Bretislav; Lazar, Josef; Veverkova, Lenka

    2014-03-01

    The recent effort leads to reliable imaging techniques which can help to a surgeon during operations. The fluorescence spectroscopy was selected as very useful online in vivo imaging method to organics and biological materials analysis. The presented work scopes to a laser induced fluorescence spectroscopy technique to detect tissue local necrosis in small intestine surgery. In first experiments, we tested tissue auto-fluorescence technique but a signal-to-noise ratio didn't express significant results. Then we applied a contrast dye - IndoCyanine Green (ICG) which absorbs and emits wavelengths in the near IR. We arranged the pilot experimental setup based on highly coherent extended cavity diode laser (ECDL) used for stimulating of some critical areas of the small intestine tissue with injected ICG dye. We demonstrated the distribution of the ICG exciter with the first file of shots of small intestine tissue of a rabbit that was captured by high sensitivity fluorescent cam.

  6. Phylogeography of infectious haematopoietic necrosis virus in North America

    USGS Publications Warehouse

    Kurath, Gael; Garver, Kyle A.; Troyer, Ryan M.; Emmenegger, Eveline J.; Einer-Jensen, Katja; Anderson, Eric D.

    2003-01-01

    Infectious hematopoietic necrosis virus (IHNV) is a rhabdoviral pathogen that infects wild and cultured salmonid fish throughout the Pacific Northwest of North America. IHNV causes severe epidemics in young fish and can cause disease or occur asymptomatically in adults. In a broad survey of 323 IHNV field isolates, sequence analysis of a 303 nucleotide variable region within the glycoprotein gene revealed a maximum nucleotide diversity of 8.6 %, indicating low genetic diversity overall for this virus. Phylogenetic analysis revealed three major virus genogroups, designated U, M and L, which varied in topography and geographical range. Intragenogroup genetic diversity measures indicated that the M genogroup had three- to fourfold more diversity than the other genogroups and suggested relatively rapid evolution of the M genogroup and stasis within the U genogroup. We speculate that factors influencing IHNV evolution may have included ocean migration ranges of their salmonid host populations and anthropogenic effects associated with fish culture.

  7. Progressive outer retinal necrosis in immunocompromised kidney allograft recipient.

    PubMed

    Turno-Kręcicka, A; Boratyńska, M; Tomczyk-Socha, M; Mazanowska, O

    2015-06-01

    Ocular complications in patients who underwent renal transplantation are attributed to side effects of the immunosuppressive regimen. Progressive outer retinal necrosis (PORN) syndrome is a clinical variant of necrotizing herpetic retinopathy and it occurs almost exclusively in patients with acquired immunodeficiency syndrome. We present a case of a human immunodeficiency virus-negative patient who underwent renal transplant and, after a few years, developed bilateral PORN associated with viral infections. Varicella zoster virus (VZV) and BK virus were identified by polymerase chain reaction from the vitreous fluid. It is unclear which of the viruses identified had the dominant role in the pathogenesis of PORN and other organ damage, or whether their actions were synergistic. Adequate antiviral immune surveillance, as well as pre-transplant vaccination against VZV, may reduce the incidence of VZV infection and its complications. PMID:25846017

  8. Viral erythrocytic necrosis: Chapter 2.2.7

    USGS Publications Warehouse

    Winton, James R.; Hershberger, Paul K.

    2014-01-01

    In spite of extensive efforts, the etiological agent of VEN has not been propagated in fish cell lines making its characterization difficult. However, transmission electron microscopy (TEM) of red blood cells from diseased fish convincingly demonstrates the presence of iridovirus-like particles that have been given the name erythrocytic necrosis virus (ENV). While the ENV virions in red blood cells of various species of fish from differing geographic locations may appear morphologically distinct (Smail 1982; Wolf 1988), at least one strain of ENV has now been partially sequenced, confirming it to be a member of the family Iridoviridae (Emmenegger et al. in press). However, the genetic relatedness of ENV from various fish hosts has not yet been investigated. 

  9. Antiviral selection in the management of acute retinal necrosis

    PubMed Central

    Tam, Patrick MK; Hooper, Claire Y; Lightman, Susan

    2010-01-01

    There is no consensus on the optimal antiviral regimen in the management of acute retinal necrosis, a disease caused by herpetic viruses with devastating consequences for the eye. The current gold standard is based on retrospective case series. Because the incidence of disease is low, few well-designed, randomized trials have evaluated treatment dosage and duration. Newer oral antiviral agents are emerging as alternatives to high-dose intravenous acyclovir, avoiding the need for inpatient intravenous treatment. Drug resistance is uncommon but may also be difficult to identify. Antiviral drugs have few side effects, but special attention needs to be paid to patients who have underlying renal disease, are pregnant or are immunocompromised. PMID:20169044

  10. Potential roles for tumour necrosis factor alpha during embryonic development.

    PubMed

    Wride, M A; Sanders, E J

    1995-01-01

    This paper reviews the evidence indicating possible roles for tumour necrosis factor-alpha (TNF alpha) in development. It is proposed that TNF alpha may have essentially three major roles during embryonic development, which may be analogous to its roles in the immune system and during inflammation: a role in programmed cell death; a role as a cellular growth and differentiation factor; and also a role in the remodelling of extracellular matrix, and the regulation of cell adhesion molecules and integrins. The concept of the existence of a cytokine array during embryogenesis, analogous to that occurring in inflammation, is discussed, as well as potential roles for TNF alpha in the induction of ubiquitin; protective mechanisms embryonic cells may employ against TNF alpha-mediated cytotoxicity; and a consideration of the role TNF alpha may play in a "free radical theory of development". PMID:7717528

  11. Role of Tumor Necrosis Factor Superfamily in Neuroinflammation and Autoimmunity

    PubMed Central

    Sonar, Sandip; Lal, Girdhari

    2015-01-01

    Tumor necrosis factor superfamily (TNFSF) molecules play an important role in the activation, proliferation, differentiation, and migration of immune cells into the central nervous system (CNS). Several TNF superfamily molecules are known to control alloimmunity, autoimmunity, and immunity. Development of transgenic and gene knockout animals, and monoclonal antibodies against TNFSF molecules have increased our understanding of individual receptor–ligand interactions, and their intracellular signaling during homeostasis and neuroinflammation. A strong clinical association has been observed between TNFSF members and CNS autoimmunity such as multiple sclerosis and also in its animal model experimental autoimmune encephalomyelitis. Therefore, they are promising targets for alternative therapeutic options to control autoimmunity. Although, TNFSF ligands are widely distributed and have diverse functions, we have restricted the discussions in this review to TNFSF receptor–ligand interactions and their role in the pathogenesis of neuroinflammation and CNS autoimmunity. PMID:26257732

  12. Gallbladder torsion with acute cholecystitis and gross necrosis

    PubMed Central

    Alkhalili, Eyas; Bencsath, Kalman

    2014-01-01

    A 92-year-old woman presented to the emergency department with a 2-week history of worsening right-sided abdominal pain. On examination she had right mid-abdominal tenderness. Laboratory studies demonstrated leukocytosis with normal liver function tests. A CT of the abdomen was remarkable for a large fluid collection in the right abdomen and no discernible gallbladder in the gallbladder fossa. An ultrasound confirmed the suspicion of a distended, floating gallbladder. The patient was taken to the operating room for laparoscopic cholecystectomy. The gallbladder was found to have volvulised in a counter -clockwise manner around its pedicle, with gross necrosis of the gallbladder. She underwent laparoscopic cholecystectomy. Pathological examination revealed acute necrotising calculus cholecystitis. PMID:24862426

  13. Tumor necrosis factor alpha polymorphism in heart failure/cardiomyopathy.

    PubMed

    Vadlamani, Lou; Iyengar, Srinivas

    2004-01-01

    Tumor necrosis factor a (TNF-alpha) is a proinflammatory cytokine that is produced by activated macrophages. It has been shown to stimulate the release of endothelial cytokines and NO, increase vascular permeability, decrease contractility, and induce a prothrombotic state. The most studied TNF-a gene mutation in heart disease is a gamma to alpha substitution, which occurs when 308 nucleotides move upstream from the transcription initiation site in the TNF promoter and has been associated with elevated levels of TNF-alpha. The TNF1 allele (wild type) contains gamma at this site, while the TNF2 allele has an alpha substitution at the site. The TNF2 allele is a more powerful transcriptional activator, therefore leading to higher TNF-alpha levels. Most of the studies to date have failed to conclusively show any link between the polymorphism and heart disease, both coronary artery disease and cardiomyopathy/heart failure. PMID:15591843

  14. [Fatal hepatic necrosis during treatment with sodium valproate].

    PubMed

    Miguil, M; Chlihi, A; Mjahed, K; Sarf, I; Moutawakkil, S; Benaguida, M

    1995-01-01

    The authors report a case of fatal hepatic failure in a 19-year old young man suffering from absence seizures and treated for two months with valproic acid (VPA). The duration of VPA therapy before onset of clinical manifestations was four weeks. The prodromal symptoms were weakness, anorexia, and vomiting, then in a few weeks occurred a jaundice and an hepatic encephalopathy leading to death. Among laboratory findings disturbance of liver tests and particularly depressed levels of clotting factors were observed. The histologic study of the liver showed an extended centrolobular necrosis associated with fatty change and fibrosis. The mechanism of this hepatic failure remains unknown. The seriousness of this complication necessitates to respect any contraindications. PMID:7583902

  15. Programmed necrosis in inflammation: Toward identification of the effector molecules.

    PubMed

    Wallach, David; Kang, Tae-Bong; Dillon, Christopher P; Green, Douglas R

    2016-04-01

    Until recently, programmed cell death was conceived of as a single set of molecular pathways. We now know of several distinct sets of death-inducing mechanisms that lead to differing cell-death processes. In one of them--apoptosis--the dying cell affects others minimally. In contrast, programmed necrotic cell death causes release of immunostimulatory intracellular components after cell-membrane rupture. Defining the in vivo relevance of necrotic death is hampered because the molecules initiating it [such as receptor-interacting protein kinase-1 (RIPK1), RIPK3, or caspase-1] also serve other functions. Proteins that participate in late events in two forms of programmed necrosis [mixed lineage kinase domain-like protein (MLKL) in necroptosis and gasdermin-D in pyroptosis] were recently discovered, bringing us closer to identifying molecules that strictly serve in death mediation, thereby providing probes for better assessing its role in inflammation. PMID:27034377

  16. Radar channel balancing with commutation

    SciTech Connect

    Doerry, Armin Walter

    2014-02-01

    When multiple channels are employed in a pulse-Doppler radar, achieving and maintaining balance between the channels is problematic. In some circumstances the channels may be commutated to achieve adequate balance. Commutation is the switching, trading, toggling, or multiplexing of the channels between signal paths. Commutation allows modulating the imbalance energy away from the balanced energy in Doppler, where it can be mitigated with filtering.

  17. Dynamic load balancing of applications

    DOEpatents

    Wheat, Stephen R.

    1997-01-01

    An application-level method for dynamically maintaining global load balance on a parallel computer, particularly on massively parallel MIMD computers. Global load balancing is achieved by overlapping neighborhoods of processors, where each neighborhood performs local load balancing. The method supports a large class of finite element and finite difference based applications and provides an automatic element management system to which applications are easily integrated.

  18. Dynamic load balancing of applications

    DOEpatents

    Wheat, S.R.

    1997-05-13

    An application-level method for dynamically maintaining global load balance on a parallel computer, particularly on massively parallel MIMD computers is disclosed. Global load balancing is achieved by overlapping neighborhoods of processors, where each neighborhood performs local load balancing. The method supports a large class of finite element and finite difference based applications and provides an automatic element management system to which applications are easily integrated. 13 figs.

  19. 14 CFR 23.421 - Balancing loads.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 14 Aeronautics and Space 1 2011-01-01 2011-01-01 false Balancing loads. 23.421 Section 23.421... Balancing Surfaces § 23.421 Balancing loads. (a) A horizontal surface balancing load is a load necessary to... balancing surfaces must be designed for the balancing loads occurring at any point on the limit...

  20. 14 CFR 23.421 - Balancing loads.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 14 Aeronautics and Space 1 2010-01-01 2010-01-01 false Balancing loads. 23.421 Section 23.421... Balancing Surfaces § 23.421 Balancing loads. (a) A horizontal surface balancing load is a load necessary to... balancing surfaces must be designed for the balancing loads occurring at any point on the limit...

  1. Libra: Scalable Load Balance Analysis

    SciTech Connect

    2009-09-16

    Libra is a tool for scalable analysis of load balance data from all processes in a parallel application. Libra contains an instrumentation module that collects model data from parallel applications and a parallel compression mechanism that uses distributed wavelet transforms to gather load balance model data in a scalable fashion. Data is output to files, and these files can be viewed in a GUI tool by Libra users. The GUI tool associates particular load balance data with regions for code, emabling users to view the load balance properties of distributed "slices" of their application code.

  2. Par Pond water balance

    SciTech Connect

    Hiergesell, R.A.; Dixon, K.L.

    1996-06-01

    A water budget for the Par Pond hydrologic system was established in order to estimate the rate of groundwater influx to Par Pond. This estimate will be used in modeling exercises to predict Par Pond reservoir elevation and spillway discharge in the scenario where Savannah River water is no longer pumped and discharged into Par Pond. The principal of conservation of mass was used to develop the water budget, where water inflow was set equal to water outflow. Components of the water budget were identified, and the flux associated with each was determined. The water budget was considered balanced when inflow and outflow summed to zero. The results of this study suggest that Par Pond gains water from the groundwater system in the upper reaches of the reservoir, but looses water to the groundwater system near the dam. The rate of flux of groundwater from the water table aquifer into Par Pond was determined to be 13 cfs. The rate of flux from Par Pond to the water table aquifer near the dam was determined to be 7 cfs.

  3. Balancing "we" and "me".

    PubMed

    Congdon, Christine; Flynn, Donna; Redman, Melanie

    2014-10-01

    The open office is the dominant form of workspace design for good reason: It fosters collaboration, promotes learning, and nurtures strong culture. But what most companies fail to realize is that collaboration has a natural rhythm that requires both interaction and private contemplation. Companies have been trying for decades to find the balance between public and private workspace that best supports collaboration. In 1980 52% of U.S. employees lacked workspaces where they could concentrate without distraction. In response, high-walled cubicles took over the corporate landscape. By the late 1990s, the tide had turned, and only 23% of employees wanted more privacy, and 50% wanted more access to other people. Ever since, firms have been beefing up spaces that support collaboration and shrinking areas for individual work. But the pendulum seems to have swung too far: Once again, people feel a pressing need for privacy, not only to do heads-down work but to cope with the intensity of work today. To address these needs, according to the authors, we have to rethink our assumptions about privacy. Traditionally defined in physical terms, privacy is now about the individual's ability to control information and stimulation. In this article, the authors examine workspace design through the new lens of privacy and offer insights on how to foster teamwork and solitude. PMID:25509575

  4. In the Balance:

    PubMed Central

    Weaver, Lawrence T.

    2010-01-01

    Summary The nineteenth century saw the incorporation of technology, such as the stethoscope, microscope, and thermometer, into clinical medicine. An instrument that has received less attention in the history of the role of technology in medicine is the weighing balance, or scale. Although not new to nineteenth-century medicine, it played an important part in the rise of the numerical method and its application to the development and shaping of pediatrics. This article explores the origin and development of the weighing of babies. During its clinical and scientific adoption, this simple procedure was refined and applied in a number of increasingly sophisticated and far-reaching ways: as a measure of the dimensions of the fetus and newborn, as an index of the viability of the newborn, as a means of estimating milk intake, as a way of distinguishing normality from abnormality, as a summary measure of infant health, and as an instrument of mass surveillance. In so doing it changed the way in which medical care was delivered to infants. PMID:20632732

  5. A balancing act for renewables

    NASA Astrophysics Data System (ADS)

    Elliott, David

    2016-01-01

    Energy storage will play a key role in increasing the use of variable energy sources. Nonetheless, storage is not the only balancing option and the overall design of power systems will incorporate a range of flexible generation, storage and grid-balancing options of different types and scales.

  6. Balancing Safety and Free Speech

    ERIC Educational Resources Information Center

    Hudson, David L., Jr.

    2004-01-01

    According to Jay Worona, general counsel for the New York State School Board Association, "Balancing safety and student constitutional rights is not easy. It has to be a careful balance. School officials must be prudent and not overreact. But one part of the equation has to be paramount. And safety should be the primary concern" (personal…

  7. Heat balance of the Earth

    NASA Technical Reports Server (NTRS)

    Budyko, M. I.; Berlyand, T. G.; Yefimova, N. A.; Zubenok, L. I.; Strokina, L. A.

    1980-01-01

    Results of improved calculations of the heat balance components of Earth's surface are reported for yearly average conditions. The technique used to determine the heat-balance components from land- and sea-based actinometric observations as well as from satellite data on the radiation balance of the Earth-atmosphere system is described, with special attention given to short-wavelength solar radiation on the continents, effective radiation from the land surface, the radiation balance of the ocean surface, heat expended by both evaporation from the ocean surface, and turbulent heat transfer between the ocean surface and the atmosphere. World maps of heat-balance components show yearly average values of total radiation, radiation balance, heat expended by evaporation, the turbulent heat flow between Earth's surface and atmosphere, and heat transfer between the ocean surface and underlying waters. The global surface heat balance is estimated along with global values of the various components and the heat-balance components for different latitude zones.

  8. The Balance-Scale Problem.

    ERIC Educational Resources Information Center

    Greenwood, Jay, Ed.

    1997-01-01

    Presents the reflections of students on a problem given in May, 1996 issue of this journal in order to share the thinking of middle school students. The problem concerned weighing on a double per balance if given a clump of clay, and a 20-gram and 50-gram balance. (ASK)

  9. Bladder Necrosis Associated with Placenta Accreta, Embolization, and Repair of Cystotomies

    PubMed Central

    Wu, Wayland J.; Smith, Arthur D.

    2015-01-01

    Abstract Bladder necrosis is an unusual and potentially devastating complication of embolization of the hypogastric arterial branches. The rich collateral blood supply makes this an extremely rare event. We present the case of a patient with bladder necrosis following placenta accreta that was treated with total abdominal hysterectomy and uterine artery embolization and cystotomy repairs.

  10. Analysis of risk and predictors of brain radiation necrosis after radiosurgery.

    PubMed

    Zhuang, Hongqing; Zheng, Yi; Wang, Junjie; Chang, Joe Y; Wang, Xiaoguang; Yuan, Zhiyong; Wang, Ping

    2016-02-16

    In this study, we examined the factors contributing to brain radiation necrosis and its predictors of patients treated with Cyberknife radiosurgery. A total of 94 patients with primary or metastatic brain tumours having been treated with Cyberknife radiotherapy from Sep. 2006 to Oct. 2011 were collected and retrospectively analyzed. Skull based tracking was used to deliver radiation to 104 target sites. and the prescribed radiation doses ranged from 1200 to 4500 cGy in 1 to 8 fractions with a 60% to 87% isodose line. Radiation necrosis was confirmed by imaging or pathological examination. Associations between cerebral radiation necrosis and factors including diabetes, cardio-cerebrovascular disease, target volume, isodose line, prescribed dosage, number of fractions, combination with whole brain radiation and biologically equivalent dose (BED) were determined by logistic regression. ROC curves were created to measure the predictive accuracy of influence factors and identify the threshold for brain radiation necrosis. Our results showed that radiation necrosis occurred in 12 targets (11.54%). Brain radiation necrosis was associated by BED, combination with whole brain radiotherapy, and fractions (areas under the ROC curves = 0.892±0.0335, 0.650±0.0717, and 0.712±0.0637 respectively). Among these factors, only BED had the capability to predict brain radiation necrosis, and the threshold dose was 7410 cGy. In conclusion, BED is the most effective predictor of brain radiation necrosis, with a dose of 7410 cGy being identified as the threshold. PMID:26675376

  11. Analysis of risk and predictors of brain radiation necrosis after radiosurgery

    PubMed Central

    Zhuang, Hongqing; Zheng, Yi; Wang, Junjie; Chang, Joe Y.; Wang, Xiaoguang; Yuan, Zhiyong; Wang, Ping

    2016-01-01

    In this study, we examined the factors contributing to brain radiation necrosis and its predictors of patients treated with Cyberknife radiosurgery. A total of 94 patients with primary or metastatic brain tumours having been treated with Cyberknife radiotherapy from Sep. 2006 to Oct. 2011 were collected and retrospectively analyzed. Skull based tracking was used to deliver radiation to 104 target sites. and the prescribed radiation doses ranged from 1200 to 4500 cGy in 1 to 8 fractions with a 60% to 87% isodose line. Radiation necrosis was confirmed by imaging or pathological examination. Associations between cerebral radiation necrosis and factors including diabetes, cardio-cerebrovascular disease, target volume, isodose line, prescribed dosage, number of fractions, combination with whole brain radiation and biologically equivalent dose (BED) were determined by logistic regression. ROC curves were created to measure the predictive accuracy of influence factors and identify the threshold for brain radiation necrosis. Our results showed that radiation necrosis occurred in 12 targets (11.54%). Brain radiation necrosis was associated by BED, combination with whole brain radiotherapy, and fractions (areas under the ROC curves = 0.892±0.0335, 0.650±0.0717, and 0.712±0.0637 respectively). Among these factors, only BED had the capability to predict brain radiation necrosis, and the threshold dose was 7410 cGy. In conclusion, BED is the most effective predictor of brain radiation necrosis, with a dose of 7410 cGy being identified as the threshold. PMID:26675376

  12. Acute retinal necrosis secondary to herpes simplex virus type 2 with preexisting chorioretinal scarring.

    PubMed

    Moesen, Ingemarie; Khemka, Sneh; Ayliffe, William

    2008-01-01

    Acute retinal necrosis in children is a devastating disease that requires early diagnosis and treatment. The authors describe a rarely reported case of bilateral acute retinal necrosis in a child caused by neonatal herpes simplex virus type 2, where the presence of previous chorioretinal scarring made diagnosis challenging. PMID:18286969

  13. A strain of Clover yellow vein virus that causes severe pod necrosis disease in snap bean

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Since 2000, the soybean aphid (Aphis glycines) has been associated with severe virus epidemics in snap bean (Phaseolus vulgaris) in the upper Midwestern states, New York, and Ontario, Canada. The causal agent of a disease causing severe mosaic, apical necrosis stunting and extensive pod necrosis wa...

  14. Pancreatic necrosis: results of necrosectomy, packing, and ultimate closure over drains.

    PubMed Central

    Branum, G; Galloway, J; Hirchowitz, W; Fendley, M; Hunter, J

    1998-01-01

    OBJECTIVE: The treatment of pancreatic necrosis at a tertiary referral center was reviewed to effect better patient outcome. SUMMARY BACKGROUND DATA: Pancreatic necrosis is a devastating disease that leads to death in 10% to 50% of cases. Infected necrosis is particularly deadly because 80% of deaths from necrosis are due to infection or its complications. Therapeutic strategies center on aggressive support of organ systems and prevention and treatment of infectious complications. METHODS: Records of all patients who underwent pancreatic necrosectomy from 1990 to 1996 at Emory University Hospital were reviewed. Patients with infected necrosis were debrided as soon as the diagnosis was made. Reoperation for completion necrosectomy with ultimate closure over lavage catheters was performed as necessary. RESULTS: Of the 244 patients admitted with acute pancreatitis in the study period, 50 underwent pancreatic debridement. The mean age was 52 years, and 74% of patients were transferred from other institutions. Eighty-four percent of patients had infected necrosis, and all patients underwent sequential debridement with eventual closure over drains. Organ failure occurred in 72% of cases, and the overall mortality rate was 12%. The mean length of stay was 54 days. CONCLUSIONS: The management of pancreatic necrosis demands the allocation of extensive resources. An aggressive operative strategy of multiple debridements with ultimate closure over drains can lead to a low mortality rate in patients with this complex disease, but the determination of when to explore patients with sterile necrosis remains difficult. PMID:9637550

  15. A balancing act: Physical balance, through arousal, influences size perception

    PubMed Central

    Geuss, Michael N.; Stefanucci, Jeanine K.; de Benedictis-Kessner, Justin; Stevens, Nicholas R.

    2012-01-01

    Previous research demonstrates that manipulating vision influences balance. Here, we question whether manipulating balance can influence vision and how it may influence vision, specifically the perception of width. In Experiment 1, participants estimated the width of beams while balanced and unbalanced. When unbalanced, participants judged the widths to be smaller. One possible explanation is that unbalanced participants did not view the stimulus as long as when balanced because they were focused on remaining balanced. In Experiment 2, we tested this notion by limiting viewing time. Experiment 2 replicated the findings of Experiment 1 but viewing time had no effect on width judgments. In Experiment 3, participants’ level of arousal was manipulated because the balancing task likely produced arousal. While jogging, participants judged the beams to be smaller. In Experiment 4, participants completed another arousing task (counting backward by 7s) that did not involve movement. Again, participants judged the beams to be smaller when aroused. Experiment 5a raised participants’ level of arousal before estimating the board widths (to control for potential dual-task effects) and found that heightened arousal still influenced perceived width of the boards. Collectively, heightened levels of arousal, caused by multiple manipulations (including balance), influenced perceived width. PMID:20952786

  16. [Brachial plexus compression from supraclavicular encapsulated fat necrosis. A case report].

    PubMed

    Domínguez-Páez, Miguel; de Miguel-Pueyo, Luis; Marín-Salido, Esteban José; Carrasco-Brenes, Antonio; Martín-Gallego, Alvaro; Arráez-Sánchez, Miguel Ángel

    2014-01-01

    We report the case of a 44-year-old male, lacking clinical history of previous illness, who had surgery at our hospital to treat a mass in the supraclavicular space. The patient presented with a 1-month progressive distal paresis of the left arm. The histo-pathological examination of the mass revealed an encapsulated fat necrosis. Fat necrosis is characterised by cystic architecture, encapsulation with fat necrosis within, and inflammatory infiltration of its walls. Neural structure compression secondary to this tumour mass is very rare. Fat necrosis is more frequent in the lower limbs, in areas exposed to trauma. This article is the first report of brachial plexus compression due to supraclavicular fat necrosis. PMID:24837841

  17. Thrombo-ischaemic pinnal necrosis associated with fenbendazole treatment in a dog.

    PubMed

    Nuttall, T J; Burrow, R; Fraser, I; Kipar, A

    2005-05-01

    An 11-week-old, female West Highland white terrier was presented with necrosis of the distal third of both pinnae. Haematology, biochemistry and urinalysis, Coombs test, antinuclear antibody and cold autoagglutinin antibody tests were normal. A drug reaction to fenbendazole was diagnosed. The necrotic ear tips were surgically removed. Histopathology revealed extensive coagulative necrosis of the epidermis and superficial to mid-dermis, a moderate interstitial neutrophilic infiltrate and complete thrombotic occlusion and necrosis of blood vessels. There was also endothelial cell activation and proliferation with endothelial cell cushions protruding into the vascular lumen. Immunohistochemistry for factor VIII-related antigen confirmed endothelial cell involvement. This case represents an unusual, drug-induced, thrombo-ischaemic necrosis of the pinnae. It is also, to the authors' knowledge, the first report of fenbendazole sensitivity in a dog. The histopathology is similar to previous cases of proliferative thrombovascular pinnal necrosis, suggesting that drug reactions should be considered in this condition. PMID:15909448

  18. Spontaneous and bilateral necrosis of the femoral head in a young experimental beagle dog

    PubMed Central

    Kobayashi, Ryosuke; Kurotaki, Tetsuro; Yamada, Naoaki; Kumabe, Shino; Doi, Takuya; Wako, Yumi; Tsuchitani, Minoru

    2015-01-01

    This report describes the pathological characterizations of a rare case of necrosis of the femoral head that was spontaneous, bilateral, avascular and nontraumatic. A 14-month-old beagle dog was presented with pain in the hind limbs. At necropsy, the articular surface in the bilateral femoral head was markedly irregular. There were no gross abnormalities other than in the hip joints. Microscopically, a wide range of trabecular bone necrosis localized in the subchondral area was observed in both femoral heads. In the right femoral head, fibrosis and proliferative vessels were noted in the subchondral area. The articular cartilage was thickened irregularly, but there was no evidence of cartilage necrosis. The bone marrow adjacent to the affected area showed severe depression. In the metaphysis, atrophic bone marrow, but not bone necrosis, was observed. This was a rare case of spontaneous necrosis of the femoral head in an experimental beagle dog. PMID:26028821

  19. Acquired-resistance of bevacizumab treatment for radiation brain necrosis: a case report

    PubMed Central

    Sun, Dayong; Bian, Jianliang; Chang, Joe Y.; Yuan, Zhiyong; Wang, Ping

    2016-01-01

    The case study reported on acquired bevacizumab resistance in one patient receiving re-treatment with bevacizumab following radiation brain necrosis progression after bevacizumab was discontinued. This case offers novel and additional insight for bevacizumab treatment. Low-dose bevacizumab is effective for radiation brain necrosis, and radiation brain necrosis may progress after bevacizumab discontinuation, whereas too many cycles of bevacizumab treatment may induce drug-resistance and re-treatment failure following the progression. Therefore, more rational administration for radiation brain necrosis with bevacizumab may include three aspects: short-course treatment, timely discontinuation upon obtaining satisfactory effects (to prevent long-term medication associated resistance) and re-treatment after brain necrosis progression. PMID:26933810

  20. Mechanisms balancing skeletal matrix synthesis and degradation.

    PubMed Central

    Blair, Harry C; Zaidi, Mone; Schlesinger, Paul H

    2002-01-01

    Bone is regulated by evolutionarily conserved signals that balance continuous differentiation of bone matrix-producing cells against apoptosis and matrix removal. This is continued from embryogenesis, where the skeleton differentiates as a solid mass and is shaped into separate bones by cell death and proteolysis. The two major tissues of the skeleton are avascular cartilage, with an extracellular matrix based on type II collagen and hydrophilic proteoglycans, and bone, a stronger and lighter material based on oriented type I collagen and hydroxyapatite. Both differentiate from the same mesenchymal stem cells. This differentiation is regulated by a family of related signals centred on bone morphogenic proteins. Fibroblast growth factors, Indian hedgehog and parathyroid hormone-related protein are important in determining the type of matrix and the relation of skeletal and non-skeletal structures. Removal of mineralized matrix involves apoptosis of matrix cells and differentiation of acid-secreting cells (osteoclasts) from macrophage precursors. Key regulators of matrix removal are signals in the tumour-necrosis-factor family. Osteoclasts dissolve bone by isolating a region of the matrix and secreting HCl and proteinases at that site. Successive cycles of removal and replacement allow growth, repair and remodelling. The signals for bone turnover are predominantly cell-membrane-associated, allowing very specific spatial regulation. In addition to its support function, bone is a reservoir of Ca2+, PO3-(4) and OH-. Secondary modulation of mineral secretion and bone degradation are mediated by humoral signals, including parathyroid hormone and vitamin D, as well as the cytokines that also regulate the underlying cell differentiation. PMID:12023876

  1. Searching for balanced development.

    PubMed

    Kulessa, M

    1987-08-01

    It is significant in China, as the day of 5 billion is commemorated, that the Government has shown its full committment to a family planning program that has been internationally acknowledged as one of the most successful efforts in the world today. Since 1979, the annual population growth rate in China has gone down from 2.7% to an annual average of around 1.2%. In fact, because China makes up more than 1/5 of the world's population, the overall growth rate achieved worldwide has been reduced to about 2%. This is heavily due to the achievements of the Chinese family planning program. Even as China has lowered its birthrate, its rate of agricultural production has rapidly risen. At present, China is doing well in grain production. Although the per capita income in China is still comparatively low, the country is able to feed its citizens, and the famines that used to be a big problem are now but a bad memory. As the close relationship between population and development is observed, there is some controversy about the effects and impact of family planning on development. The belief is held that the more people there are in this world, the more progress there will be because more brains, hands, and energy will be harnessed for development. As has also been noted, however, a person is not just head and hands--a person has a mouth to feed, as well. Thus, there is a need to balance the number of people with the resources of the society. If the rate of population growth outstrips economic and social production, then hunger and poverty will result, as the fruits of development will be eaten up too rapidly. PMID:12269159

  2. Bone necrosis and tumor induction following experimental intraoperative irradiation.

    PubMed

    Powers, B E; Gillette, E L; McChesney, S L; LeCouteur, R A; Withrow, S J

    1989-09-01

    The bone of the lumbar vertebrae of 153 dogs was examined 2 and 5 years after intraoperative irradiation (IORT), fractionated external beam irradiation (EBRT), or the combination. Groups of dogs received 15 to 55 Gy IORT only, 10 to 47.5 Gy IORT combined with 50 Gy EBRT in 2 Gy fractions or 60 to 80 Gy EBRT in 30 fractions. Six MeV electrons were used for IORT, and EBRT was done using photons from a 6 MV linear accelerator. The paraaortic region was irradiated and the ventral part of the lumbar vertebrae was in the 90% isodose level. Two years after irradiation, the dose causing significant bone necrosis as determined by at least 50% empty lacunae in the vertebral cortex was 38.2 Gy IORT alone and 32.5 Gy IORT combined with EBRT. Five years after irradiation, the dose causing 50% empty lacunae was 28.5 Gy IORT only and 14.4 Gy IORT combined with EBRT. The ED50 for lesions of the ventral vertebral artery was 21.7 Gy IORT only and 20.1 Gy IORT combined with 50 Gy EBRT 2 years after irradiation and 27.0 Gy IORT only and 20.0 Gy IORT combined with 50 Gy EBRT 5 years after irradiation. All lesions after EBRT only were mild. Eight dogs developed osteosarcomas 4 to 5 years after irradiation, one at 47.5 Gy IORT only and the remainder at 25.0 Gy IORT and above combined with 50 Gy EBRT. In conclusion, the extent of empty lacunae, indicating bone necrosis, was more severe 5 years after irradiation than after 2 years. The effect of 50 Gy EBRT in 2 Gy fractions was equivalent to about 6 Gy IORT 2 years after irradiation and to about 14 Gy 5 years after irradiation. Based on these estimates, IORT doses of 10 to 15 Gy have an effect 5 times or greater than the amount given in 2 Gy fractions. Osteosarcomas occurred in 21% of dogs which received doses greater than 25 Gy IORT. Doses of 15 to 20 Gy IORT in combination with 50 Gy EBRT in 2 Gy fractions may be near the tolerance level for late developing bone injury. PMID:2506159

  3. Work–Life Balance: History, Costs, and Budgeting for Balance

    PubMed Central

    Raja, Siva; Stein, Sharon L.

    2014-01-01

    The concept and difficulties of work–life balance are not unique to surgeons, but professional responsibilities make maintaining a work–life balance difficult. Consequences of being exclusively career focused include burn out, physical, and mental ailments. In addition, physician burn out may hinder optimal patient care and incur significant costs on health care in general. Assessing current uses of time, allocating goals catered to an individual surgeon, and continual self-assessment may help balance time, and ideally will help prevent burn out. PMID:25067921

  4. Tumor necrosis factor-alpha antagonists and neuropathy.

    PubMed

    Stübgen, Joerg-Patrick

    2008-03-01

    Tumor necrosis factor (TNF)-alpha plays an important role in many aspects of immune system development, immune-response regulation, and T-cell-mediated tissue injury. The evidence that TNF-alpha, released by autoreactive T cells and macrophages, may contribute to the pathogenesis of immune-mediated demyelinating neuropathies is reviewed. TNF-alpha antagonists (infliximab, etanercept, adalimumab) are indicated for the treatment of advanced inflammatory rheumatic and bowel disease, but these drugs can induce a range of autoimmune diseases that also attack the central and peripheral nervous systems. Case histories and series report on the association between anti-TNF-alpha treatment and various disorders of peripheral nerve such as Guillain-Barré syndrome, Miller Fisher syndrome, chronic inflammatory demyelinating polyneuropathy, multifocal motor neuropathy with conduction block, mononeuropathy multiplex, and axonal sensorimotor polyneuropathies. The proposed pathogeneses of TNF-alpha-associated neuropathies include both a T-cell and humoral immune attack against peripheral nerve myelin, vasculitis-induced nerve ischemia, and inhibition of signaling support for axons. Most neuropathies improve over a period of months by withdrawal of the TNF-alpha antagonist, with or without additional immune-modulating treatment. Preliminary observations suggest that TNF-alpha antagonists may be useful as an antigen-nonspecific treatment approach to immune-mediated neuropathies in patients with a poor response to, or intolerance of, standard therapies, but further studies are required. PMID:18041052

  5. Renal Papillary Necrosis Appearing as Bladder Cancer on Imaging

    PubMed Central

    Dagrosa, Lawrence M.; Gormley, Elizabeth Ann

    2016-01-01

    Abstract A 79-year-old woman with a history of diabetes mellitus and recurrent urinary tract infections (UTIs) presented with acute onset left lower quadrant pain, left-sided back pain, vomiting, and dysuria. Abdominopelvic CT scan revealed left hydroureteronephrosis to the level of the left ureterovesical junction (UVJ) where a bladder mass appeared to be obstructing the left ureteral orifice. The obstruction was ultimately found to be the result of a sloughed renal papilla lodged in the distal ureter, which created an inflammatory mass at the UVJ. Her history of diabetes and frequent UTIs likely predisposed her to the development of renal papillary necrosis (RPN) that resulted in sloughing of a renal papilla, distal ureteral obstruction with subsequent bladder inflammation that mimicked a bladder mass on imaging. RPN is a condition associated with many etiologies and likely represents a common final pathway of several diseases. Although several hypotheses exist, it is primarily thought to be ischemic in nature and is related to the underlying physiology of the renal papillae. We present a case of hydroureteronephrosis and bladder mass secondary to a sloughed renal papilla from RPN.

  6. Necrosis prediction of photodynamic therapy applied to skin disorders

    NASA Astrophysics Data System (ADS)

    Fanjul-Vélez, F.; Romanov, O. G.; López-Escobar, M.; Ortega-Quijano, N.; Arce-Diego, J. L.

    2009-02-01

    The great selectivity and the lack of side effects of Photodynamic Therapy make it more advantageous than radiotherapy or chemotherapy. The application of PDT to skin diseases is particularly appropriate, due to the accessibility of this tissue. Common disorders like nonmelanoma skin cancer, that includes basocelullar or squamous cell carcinomas, can be treated with PDT. Conventional procedures, like surgery or radiotherapy, are not so efficient and do not, in general, obtain the same favourable results. PDT in dermatology medical praxis uses fixed protocols depending on the photosensitizer and the optical source used. These protocols are usually provided by the photosensitizer laboratory, and every lesion is treated with the same parameters. In this work we present a photo-chemical model of PDT applied to skin disorders treated with topical photosensitizers. Optical propagation inside the tissue is calculated by means of a 3D diffusion equation, solved via a finite difference numerical method. The photosensitizer degradation or photobleaching is taken into account, as the drug looses efficiency with the irradiation time. With these data the necrosis area is estimated, so this model could be used as a predictive tool to adjust the optical power and exposition time for the particular disease under treatment.

  7. Tumor necrosis factor induced stimulation of granulopoiesis and radioprotection.

    PubMed

    Urbaschek, R; Männel, D N; Urbaschek, B

    1987-01-01

    Human recombinant tumor necrosis factor, TNF, was used to assess its ability to stimulate granulopoiesis and to protect mice against lethal irradiation, effects known to be inducable with TNF-rich postendotoxin serum from BCG infected mice (BCG/ET serum). Although the endotoxin contamination of this TNF preparation is extremely low its effects were compared in endotoxin low responder C3H/HeJ mice and susceptible NMRI mice. TNF is a potent inducer of serum colony stimulating activity, CSA, in both mouse strains. In peripheral blood a marked granulocytosis with a concomitant decrease in lymphocytes and monocytopenia occurs at 2 hours after injection of TNF. Moreover, TNF induces an increase in the number of splenic myelopoietic committed stem cells (GM-CFC, granulocyte-macrophage colony forming cells) determined five days after injection. The lethality rate, registered over 30 days after exposure to 660 cGy whole body X-irradiation is reduced to 40% in C3H/HeJ mice as compared to 75% in control animals. The reduction in lethality is observed both, when TNF was injected 24 hours before or after irradiation. In vitro, TNF significantly increases the number of colonies in the presence of CSA in bone marrow cultures. TNF per se does not effect colony growth. The studies reported here demonstrate that TNF is a myelopoiesis stimulating factor in mice which may be related to the reduction in lethality following whole body irradiation. PMID:3306175

  8. Colchicine prevents tumor necrosis factor-induced toxicity in vivo.

    PubMed Central

    Tiegs, G; Freudenberg, M A; Galanos, C; Wendel, A

    1992-01-01

    Tumor necrosis factor (TNF) toxicity was induced in vivo by intravenous administration of 15 micrograms of recombinant murine TNF-alpha per kg to galactosamine-sensitized mice. Within 8 h, the animals developed a fulminant hepatitis. Intravenous administration of 0.5 mg of colchicine per kg at 19 and 4 h prior to TNF challenge protected the animals against hepatitis. Lipopolysaccharide (LPS)-stimulated, bone marrow-derived macrophages from C3H/HeN mice released significant amounts of TNF in vitro. When such macrophages were intravenously given to LPS-resistant galactosamine-sensitized C3H/HeJ mice, these animals died within 24 h. Preincubation of these transferred macrophages with colchicine did not suppress the LPS-inducible TNF release from these cells. Concordantly, administration of macrophages exposed to colchicine in vitro resulted in full lethality. However, in vivo pretreatment of C3H/HeJ mice with colchicine 19 and 4 h prior to the transfer of LPS-stimulated macrophages prevented lethality. In LPS-responsive NMRI mice which had been protected against galactosamine-LPS-induced hepatitis by pretreatment with colchicine, TNF was still released into the blood. We conclude from our findings that the in vivo protection by colchicine is mediated by blocking TNF action on target cells while the effector cells of LPS toxicity, i.e., the macrophages, remain responsive. PMID:1563785

  9. Tumour necrosis factor alpha antibody protects against lethal meningococcaemia.

    PubMed

    Nassif, X; Mathison, J C; Wolfson, E; Koziol, J A; Ulevitch, R J; So, M

    1992-03-01

    Tumour necrosis factor alpha (TNF-alpha) has been shown to be the principal mediator of Gram-negative bacterial endotoxin-induced shock. Nevertheless, evidence suggests that TNF-alpha plays a beneficial role in controlling bacterial infections when multiplication of the microorganism is required to kill the host. Using an infant rat model of Neisseria meningitidis infection, we found that blood TNF-alpha concentration reaches a peak three hours after intraperitoneal injection of 3 x 10(6) bacteria. Thereafter, the level of TNF-alpha decreased and was undetectable six to eight hours after infection. A correlation was observed between the magnitude of initial TNF-alpha response and a fatal outcome. Pretreatment of the animals with polyclonal anti-TNF antiserum significantly reduced mortality relative to animals pretreated with control serum. However, pretreatment of animals with anti-TNF antibody did not alter the bacterial invasion of the cerebrospinal fluid. Injection of heat-killed bacteria did not cause death and induced lower TNF-alpha levels than the same number of live bacteria. This excludes the possibility that the role of TNF-alpha is to mediate a shock induced by the endotoxin component of the bacterial inoculum. These results indicate that TNF-alpha has a deleterious effect in this model of bacteraemia. Identification of the critical factors that determine the action of TNF-alpha during lethal bacteraemia will lead to a better understanding of these diseases and the development of appropriate therapeutic intervention. PMID:1552859

  10. Expression of Tumor Necrosis Factor in Human Acute Cardiac Rejection

    PubMed Central

    Arbustini, Eloisa; Grasso, Maurizia; Diegoli, Marta; Bramerio, Manuela; Foglieni, Andrea Scotti; Albertario, Marco; Martinelli, Luigi; Gavazzi, Antonello; Goggi, Claudio; Campana, Carlo; Vigano, Mario

    1991-01-01

    The authors performed an immunohistochemical study on expression of tumor necrosis factor alpha (TNFα) in endomyocardial biopsies from human cardiac allografts. TNFα immunoreactivity was found in 45% biopsies with mild acute rejection, in 83% biopsies with focal moderate rejection, in 80% biopsies with diffuse moderate rejection. Biopsies with absent rejection did not show immunoreactive cells. In mild rejection, positive cells were few and scanty monocytes and macrophages (MAC-387 and LN5 positive cells) and T lymphocytes (UCHL-1/CD45 RO positive cells) (up to 20% of all infiltrating cells). Expression of major histocompatibility complex (MHC) class II antigens on infiltrating and endothelial cells occurred earlier and independent of TNFα reactivity. Number of immunoreactive cells increased in moderate rejection (up to 50%). Immunoreactivity was also present in nonpigmented macrophages in part of the biopsies with resolving rejection (45%). The authors conclude that TNFα is expressed in acute cardiac rejection by immunologically activated inflammatory cells. Immunoreactive cells increase in number with increasing severity of the reaction. ImagesFigure 1Figure 2Figure 3Figure 4 PMID:1928295

  11. Tumour necrosis factor-alpha gene polymorphisms and Alzheimer's disease.

    PubMed

    Culpan, Doris; MacGowan, Sian H; Ford, Julia M; Nicoll, James A R; Griffin, W Sue; Dewar, Deborah; Cairns, Nigel J; Hughes, Anthony; Kehoe, Patrick G; Wilcock, Gordon K

    2003-10-16

    Recent findings suggest that production of pro-inflammatory cytokines, such as tumour necrosis factor-alpha (TNF-alpha), is increased in the brains of people with Alzheimer's disease (AD). We used direct sequencing methods on a section of the enhancer/promoter region and on a smaller fragment located 10.5 kb upstream of the TNF-alpha gene to respectively examine TNF-alpha polymorphisms and TNF-a and -b microsatellite alleles in a cohort of 235 post-mortem confirmed AD and 130 control cases. None of the TNF-alpha point mutations or microsatellite alleles investigated proved to be independent risk factors for AD. However, when -308/A, -238/G and TNF-a2 were examined as a 2-1-2 haplotype, we observed that the absence of that haplotype was significantly associated with AD (P = 0.014, Fisher's exact test) suggesting that the 2-1-2 haplotype may be protective against AD. PMID:12962917

  12. Constitutive synthesis of tumor necrosis factor in the thymus.

    PubMed Central

    Giroir, B P; Brown, T; Beutler, B

    1992-01-01

    Although tumor necrosis factor (TNF) is a major mediator of endotoxic shock, the normal function of TNF that has preserved this protein throughout mammalian evolution remains unknown. If the protein serves a role in normal development or homeostasis, it must be produced under physiologic conditions. To determine whether TNF secretion occurs in normal animals, and to define the tissue sources of the protein, we prepared a reporter construct in which the TNF coding sequence and introns are replaced by the chloramphenicol acetyltransferase (CAT) coding sequence. This construct was inserted into the murine genome, yielding 13 transgenic founders. Macrophages harvested from 4 of the transgenic lines expressed CAT activity after stimulation with Escherichia coli lipopolysaccharide in vitro. Each of these 4 transgenic lines also constitutively expressed CAT activity in the thymus but in no other tissue examined. Cultured thymocytes secrete TNF, as demonstrated both by cytotoxicity assays and by immunoprecipitation of radiolabeled thymic culture medium. CAT activity was associated with the thymic lymphocyte population and not with thymic macrophages or dendritic cells. CAT activity was present in thymic lymphocytes irrespective of CD4 or CD8 expression; T cells from the spleen, however, had no detectable CAT activity. The biosynthesis of TNF in the thymus of normal animals implies a role for this protein in the development or regulation of the immune response. Images PMID:1594585

  13. Tumor Necrosis Factor Superfamily in Innate Immunity and Inflammation

    PubMed Central

    Šedý, John; Bekiaris, Vasileios; Ware, Carl F.

    2015-01-01

    The tumor necrosis factor superfamily (TNFSF) and its corresponding receptor superfamily (TNFRSF) form communication pathways required for developmental, homeostatic, and stimulus-responsive processes in vivo. Although this receptor–ligand system operates between many different cell types and organ systems, many of these proteins play specific roles in immune system function. The TNFSF and TNFRSF proteins lymphotoxins, LIGHT (homologous to lymphotoxins, exhibits inducible expression, and competes with HSV glycoprotein D for herpes virus entry mediator [HVEM], a receptor expressed by T lymphocytes), lymphotoxin-β receptor (LT-βR), and HVEM are used by embryonic and adult innate lymphocytes to promote the development and homeostasis of lymphoid organs. Lymphotoxin-expressing innate-acting B cells construct microenvironments in lymphoid organs that restrict pathogen spread and initiate interferon defenses. Recent results illustrate how the communication networks formed among these cytokines and the coreceptors B and T lymphocyte attenuator (BTLA) and CD160 both inhibit and activate innate lymphoid cells (ILCs), innate γδ T cells, and natural killer (NK) cells. Understanding the role of TNFSF/TNFRSF and interacting proteins in innate cells will likely reveal avenues for future therapeutics for human disease. PMID:25524549

  14. Clostridium perfringens Delta-Toxin Induces Rapid Cell Necrosis

    PubMed Central

    Seike, Soshi; Miyamoto, Kazuaki; Kobayashi, Keiko; Takehara, Masaya; Nagahama, Masahiro

    2016-01-01

    Clostridium perfringens delta-toxin is a β-pore-forming toxin and a putative pathogenic agent of C. perfringens types B and C. However, the mechanism of cytotoxicity of delta-toxin remains unclear. Here, we investigated the mechanisms of cell death induced by delta-toxin in five cell lines (A549, A431, MDCK, Vero, and Caco-2). All cell lines were susceptible to delta-toxin. The toxin caused rapid ATP depletion and swelling of the cells. Delta-toxin bound and formed oligomers predominantly in plasma membrane lipid rafts. Destruction of the lipid rafts with methyl β-cyclodextrin inhibited delta-toxin-induced cytotoxicity and ATP depletion. Delta-toxin caused the release of carboxyfluorescein from sphingomyelin-cholesterol liposomes and formed oligomers; toxin binding to the liposomes declined with decreasing cholesterol content in the liposomes. Flow cytometric assays with annexin V and propidium iodide revealed that delta-toxin treatment induced an elevation in the population of annexin V-negative and propidium iodide-positive cells. Delta-toxin did not cause the fragmentation of DNA or caspase-3 activation. Furthermore, delta-toxin caused damage to mitochondrial membrane permeability and cytochrome c release. In the present study, we demonstrate that delta-toxin produces cytotoxic activity through necrosis. PMID:26807591

  15. Tumor necrosis factor superfamily in innate immunity and inflammation.

    PubMed

    Šedý, John; Bekiaris, Vasileios; Ware, Carl F

    2015-04-01

    The tumor necrosis factor superfamily (TNFSF) and its corresponding receptor superfamily (TNFRSF) form communication pathways required for developmental, homeostatic, and stimulus-responsive processes in vivo. Although this receptor-ligand system operates between many different cell types and organ systems, many of these proteins play specific roles in immune system function. The TNFSF and TNFRSF proteins lymphotoxins, LIGHT (homologous to lymphotoxins, exhibits inducible expression, and competes with HSV glycoprotein D for herpes virus entry mediator [HVEM], a receptor expressed by T lymphocytes), lymphotoxin-β receptor (LT-βR), and HVEM are used by embryonic and adult innate lymphocytes to promote the development and homeostasis of lymphoid organs. Lymphotoxin-expressing innate-acting B cells construct microenvironments in lymphoid organs that restrict pathogen spread and initiate interferon defenses. Recent results illustrate how the communication networks formed among these cytokines and the coreceptors B and T lymphocyte attenuator (BTLA) and CD160 both inhibit and activate innate lymphoid cells (ILCs), innate γδ T cells, and natural killer (NK) cells. Understanding the role of TNFSF/TNFRSF and interacting proteins in innate cells will likely reveal avenues for future therapeutics for human disease. PMID:25524549

  16. Apoptosis, paraptosis, necrosis, and cell regeneration in posttraumatic cerebral arteries.

    PubMed

    Danaila, L; Popescu, I; Pais, V; Riga, D; Riga, S; Pais, E

    2013-01-01

    This study is to understand the nature and functional significance of the activated cell death programs and rehabilitation signs during late vascular changes after brain injury. We used light and transmission electron microscopy to describe changes of cells within the vascular endothelium and tunica media of the cortical arteries four weeks after craniocerebral traumatism. Within tunica media of the posttraumatic damaged artery, apoptotic and paraptotic phenotypes were identified as well as some early ultrastructural signs of smooth muscle cells regeneration, these cell highlighting a remarkable degree of plasticity. Surprisingly, some endothelial cells showed an extensive rough endoplasmic reticulum development, whereas other endothelial cells showed typical necrosis. In conclusion, two groups of suicidal cells apoptotic and paraptotic cells were encountered in the same lesional vascular wall after neurotrauma, showing also signs of cell regeneration. The pathophysiologic significance of the coexisting double cell death programs and cell regeneration seems to be in relation with late cell survival, after arterial damage when some cells disappear and other cells try to survive undergoing reversible injury. PMID:23790779

  17. Tumor necrosis factor and cancer, buddies or foes?*

    PubMed Central

    WANG, Xia; LIN, Yong

    2008-01-01

    Tumor necrosis factor (TNF) is a multifunctional cytokine that plays important roles in diverse cellular events such as cell survival, proliferation, differentiation, and death. As a pro-inflammatory cytokine, TNF is secreted by inflammatory cells, which may be involved in inflammation-associated carcinogenesis. TNF exerts its biological functions through activating distinct signaling pathways such as nuclear factor κB (NF-κB) and c-Jun N-terminal kinase (JNK). NF-κB is a major cell survival signal that is anti-apoptotic while sustained JNK activation contributes to cell death. The crosstalk between the NF-κB and JNK is involved in determining cellular outcomes in response to TNF. In regard to cancer, TNF is a double-dealer. On one hand, TNF could be an endogenous tumor promoter, because TNF stimulates cancer cells’ growth, proliferation, invasion and metastasis, and tumor angiogenesis. On the other hand, TNF could be a cancer killer. The property of TNF in inducing cancer cell death renders it a potential cancer therapeutic, although much work is needed to reduce its toxicity for systematic TNF administration. Recent studies have focused on sensitizing cancer cells to TNF-induced apoptosis through inhibiting survival signals such as NF-κB, by combined therapy. In this article we provide an overview of the roles of TNF-induced signaling pathways in cancer biology with specific emphasis on carcinogenesis and cancer therapy. PMID:18954521

  18. Targeted Cancer Therapy with Tumor Necrosis Factor-Alpha

    PubMed Central

    Cai, Weibo; Kerner, Zachary J.; Hong, Hao; Sun, Jiangtao

    2013-01-01

    Tumor necrosis factor-alpha (TNF-α), a member of the TNF superfamily, was the first cytokine to be evaluated for cancer biotherapy. However, the clinical use of TNF-α is severely limited by its toxicity. Currently, TNF-α is administered only through locoregional drug delivery systems such as isolated limb perfusion and isolated hepatic perfusion. To reduce the systemic toxicity of TNF-α, various strategies have been explored over the last several decades. This review summarizes current state-of-the-art targeted cancer therapy using TNF-α. Passive targeting, cell-based therapy, gene therapy with inducible or tissue-specific promoters, targeted polymer-DNA complexes, tumor pre-targeting, antibody-TNF-α conjugate, scFv/TNF-α fusion proteins, and peptide/TNF-α fusion proteins have all been investigated to combat cancer. Many of these agents are already in advanced clinical trials. Molecular imaging, which can significantly speed up the drug development process, and nanomedicine, which can integrate both imaging and therapeutic components, has the potential to revolutionize future cancer patient management. Cooperative efforts from scientists within multiple disciplines, as well as close partnerships among many organizations/entities, are needed to quickly translate novel TNF-α-based therapeutics into clinical investigation. PMID:24115841

  19. Immunomagnetic reduction assay for nervous necrosis virus extracted from groupers.

    PubMed

    Lu, M W; Yang, S Y; Horng, H E; Yang, C C; Chieh, J J; Hong, Y W; Hong, C Y; Yang, H C; Wu, J L

    2012-04-01

    Nervous necrosis virus (NNV) is the cause of viral nervous disease, which is a serious constraint on production for grouper aquaculture. Real-time PCR is commonly used to detect and quantify NNV, has the disadvantages of being expensive and technically demanding. In this study, an immunomagnetic reduction (IMR) assay was developed as a rapid and cost-effective alternative to real-time PCR. This method used magnetic nanoparticles conjugated with antibodies specific for viral surface antigens to detect NNV in grouper tissue samples. The association of NNV with the antibody-conjugated magnetic particles resulted in a reduction in magnetic signal, which was strongly correlated with the concentration of NNV, as determined by real-time PCR. Grouper larvae were prepared for testing using a viral extraction buffer which provided a rapid, 15-min method of extracting viral antigens and had an extraction efficiency of higher than 80%. In addition, this study proposes using magnetic nanoparticles as labeling markers and as an assaying reagent for NNV. The magnetic nanoparticles are functionalized with antibodies against the viral surface of NNV and are able to associate specifically with NNV. The reduction of the magnetic signals comes from the association between magnetic particles and NNV, and relates to the concentration of NNV. The results show that the detected concentrations of NNV are highly correlated to those detected by real-time PCR. PMID:22335935

  20. Photosensitizer absorption coefficient modeling and necrosis prediction during Photodynamic Therapy.

    PubMed

    Salas-García, Irene; Fanjul-Vélez, Félix; Arce-Diego, José Luis

    2012-09-01

    The development of accurate predictive models for Photodynamic Therapy (PDT) has emerged as a valuable tool to adjust the current therapy dosimetry to get an optimal treatment response, and definitely to establish new personal protocols. Several attempts have been made in this way, although the influence of the photosensitizer depletion on the optical parameters has not been taken into account so far. We present a first approach to predict the spatio-temporal variation of the photosensitizer absorption coefficient during PDT applied to dermatological diseases, taking into account the photobleaching of a topical photosensitizer. This permits us to obtain the photons density absorbed by the photosensitizer molecules as the treatment progresses and to determine necrosis maps to estimate the short term therapeutic effects in the target tissue. The model presented also takes into account an inhomogeneous initial photosensitizer distribution, light propagation in biological media and the evolution of the molecular concentrations of different components involved in the photochemical reactions. The obtained results allow to investigate how the photosensitizer depletion during the photochemical reactions affects light absorption by the photosensitizer molecules as the optical radiation propagates through the target tissue, and estimate the necrotic tumor area progression under different treatment conditions. PMID:22704663

  1. Vaccinia Virus Induces Programmed Necrosis in Ovarian Cancer Cells

    PubMed Central

    Whilding, Lynsey M; Archibald, Kyra M; Kulbe, Hagen; Balkwill, Frances R; Öberg, Daniel; McNeish, Iain A

    2013-01-01

    The mechanisms by which oncolytic vaccinia virus induces tumor cell death are poorly understood. We have evaluated cell death pathways following infection of ovarian cancer cells with both wild-type and thymidine kinase-deleted (dTK) Lister strain vaccinia. We show that death does not rely upon classical apoptosis despite the appearances of some limited apoptotic features, including phosphatidylserine externalization and appearance of sub-G1 DNA populations. Vaccinia infection induces marked lipidation of LC3 proteins, but there is no general activation of the autophagic process and cell death does not rely upon autophagy induction. We show that vaccinia induces necrotic morphology on transmission electron microscopy, accompanied by marked by reductions in intracellular adenosine triphosphate, altered mitochondrial metabolism, and release of high mobility group box 1 (HMGB1) protein. This necrotic cell death appears regulated, as infection induces formation of a receptor interacting protein (RIP1)/caspase-8 complex. In addition, pharmacological inhibition of both RIP1 and substrates downstream of RIP1, including MLKL, significantly attenuate cell death. Blockade of TNF-α, however, does not alter virus efficacy, suggesting that necrosis does not result from autocrine cytokine release. Overall, these results show that, in ovarian cancer cells, vaccinia virus causes necrotic cell death that is mediated through a programmed series of events. PMID:23985697

  2. Protein expression strategies in Tobacco necrosis virus-D.

    PubMed

    Chkuaseli, Tamari; Newburn, Laura R; Bakhshinyan, David; White, K Andrew

    2015-12-01

    Tobacco necrosis virus (TNV-D) has a plus-strand RNA genome that is neither 5' capped nor 3' poly-adenylated. Instead, it utilizes a 3' cap-independent translational enhancer (3'CITE) located in its 3' untranslated region (UTR) for translation of its proteins. We have examined the protein expression strategies used by TNV-D and our results indicate that: (i) a base pairing interaction between conserved ACCA and UGGU motifs in the genomic 5'UTR and 3'CITE, respectively, is not required for efficient plant cell infection, (ii) similar potential 5'UTR-3'CITE interactions in the two viral subgenomic mRNAs are not needed for efficient translation of viral proteins in vitro, (iii) a small amount of capsid protein is translated from the viral genome by a largely 3'CITE-independent mechanism, (iv) the larger of two possible forms of capsid protein is efficiently translated, and (v) p7b is translated from subgenomic mRNA1 by a leaky scanning mechanism. PMID:26402375

  3. Lysophosphatidic acid induces necrosis and apoptosis in hippocampal neurons.

    PubMed

    Holtsberg, F W; Steiner, M R; Keller, J N; Mark, R J; Mattson, M P; Steiner, S M

    1998-01-01

    A diverse body of evidence indicates a role for the lipid biomediator lysophosphatidic acid (LPA) in the CNS. This study identifies and characterizes the induction of neuronal death by LPA. Treatment of cultured hippocampal neurons from embryonic rat brains with 50 microM LPA resulted in neuronal necrosis, as determined morphologically and by the release of lactate dehydrogenase. A concentration of LPA as low as 10 microM led to the release of lactate dehydrogenase. In contrast, treatment of neurons with 0.1 or 1.0 microM LPA resulted in apoptosis, as determined by chromatin condensation. In addition, neuronal death induced by 1 microM LPA was characterized as apoptotic on the basis of terminal dUTP nick end-labeling (TUNEL) staining, externalization of phosphatidylserine, and protection against chromatin condensation, TUNEL staining, and phosphatidylserine externalization by treatment with N-benzyloxycarbonyl-Val-Ala-Asp-fluoromethyl ketone, a broad-spectrum inhibitor of caspases, i.e., members of the interleukin-1beta converting enzyme family. Studies with antagonists of ionotropic glutamate receptors did not indicate a significant role for these receptors in apoptosis induced by 1 microM LPA. LPA (1 microM) also induced a decrease in mitochondrial membrane potential. Moreover, pretreatment of neurons with cyclosporin A protected against the LPA-induced decrease in mitochondrial membrane potential and neuronal apoptosis. Thus, LPA, at pathophysiological levels, can induce neuronal apoptosis and could thereby participate in neurodegenerative disorders. PMID:9422348

  4. Tumor necrosis factor drives increased splenic monopoiesis in old mice.

    PubMed

    Loukov, Dessi; Naidoo, Avee; Puchta, Alicja; Marin, Jorge L Arredondo; Bowdish, Dawn M E

    2016-07-01

    Aging is accompanied by changes in hematopoiesis and consequently in leukocyte phenotype and function. Although age-related changes in bone marrow hematopoiesis are fairly well documented, changes in extramedullary hematopoiesis are less well described. We observed that 18-22-mo-old mice had larger spleens than young controls and found that the enlargement was caused by increased monopoiesis. Because extramedullary hematopoiesis is often driven by inflammation, we hypothesized that the chronic, low-level inflammation that occurs with age is a causal agent in splenomegaly. To test this theory, we compared the number of monocytes in 18-mo-old tumor necrosis factor-knockout mice, which are protected from age-associated inflammation, and found that they did not have increased extramedullary monopoiesis. To determine whether increased splenic monopoiesis is caused by intrinsic changes in the myeloid precursors that occur with age or by the aging microenvironment, we created heterochronic bone marrow chimeras. Increased splenic monopoiesis occurred in old recipient mice, regardless of the age of the donor mouse, but not in young recipient mice, demonstrating that these cells respond to signals from the microenvironment. These data suggest that decreasing the inflammatory microenvironment with age would be an effective strategy for reducing inflammatory diseases propagated by cells of myeloid lineage, which increase in number with age. PMID:27037197

  5. Libra: Scalable Load Balance Analysis

    Energy Science and Technology Software Center (ESTSC)

    2009-09-16

    Libra is a tool for scalable analysis of load balance data from all processes in a parallel application. Libra contains an instrumentation module that collects model data from parallel applications and a parallel compression mechanism that uses distributed wavelet transforms to gather load balance model data in a scalable fashion. Data is output to files, and these files can be viewed in a GUI tool by Libra users. The GUI tool associates particular load balancemore » data with regions for code, emabling users to view the load balance properties of distributed "slices" of their application code.« less

  6. Survival of the salmonid viruses infectious hematopoietic necrosis (IHNV) and infectious pancreatic necrosis (IPNV) in ozonated, chlorinated, and Untreated waters

    USGS Publications Warehouse

    Wedemeyer, Gary A.; Nelson, Nancy C.; Smith, Cathy A.

    1978-01-01

    Ozone and chlorine inactivation curves were determined in three water types at 10 °C for the fish pathogenic viruses infectious hematopoietic necrosis (IHNV) and infectious pancreatic necrosis (IPNV). In phosphate-buffered, distilled water (PBDW) an ozone dose of 0.01 mg/L for 30 or 60 s inactivated IHNV or IPNV, respectively, suspended at a tissue culture 50% infective dose (TCID50) of 104–105/mL. In hard (120 mg/L as CaCO3) and soft water (30 mg/L) lake waters, an ozone application rate of 70 mg∙h−1∙L−1 for 10 min destroyed IHNV. IPNV inactivation in hard water required 90 mg∙O3∙h−1∙L−1 for 10 min but only a 30-s contact time in soft water. The IPNV was also somewhat more resistant to chlorine. In PBDW, a residual of 0.1 mg/L with contact times of 30 and 60 s, respectively, destroyed IHNV and IPNV. In soft lake water IHNV was destroyed within 5 min at 0.5 mg/L, while in hard water a 10-min contact time was required. For IPNV disinfection in soft water, 0.2 mg/L for 10 min was sufficient but this chlorine residual had essentially no effect on IPNV in hard water. Increasing this dose to 0.7 mg/L destroyed IPNV in hard water within 2 min. In untreated waters, IPNV was stable for at least 8 wk in either distilled, soft, or hard lake waters. However, IHNV survived only about 2 wk in distilled and 7 wk in the soft or hard lake waters. We suggest the serious consideration of ozone as a fish disease control agent. Key words: ozone, chlorine disinfection, fish pathogens, viruses

  7. Necrosis, and then stress induced necrosis-like cell death, but not apoptosis, should be the preferred cell death mode for chemotherapy: clearance of a few misconceptions

    PubMed Central

    Zhang, Ju; Lou, Xiaomin; Jin, Longyu; Zhou, Rongjia; Liu, Siqi; Xu, Ningzhi; Liao, D. Joshua

    2014-01-01

    Cell death overarches carcinogenesis and is a center of cancer researches, especially therapy studies. There have been many nomenclatures on cell death, but only three cell death modes are genuine, i.e. apoptosis, necrosis and stress-induced cell death (SICD). Like apoptosis, SICD is programmed. Like necrosis, SICD is a pathological event and may trigger regeneration and scar formation. Therefore, SICD has subtypes of stress-induced apoptosis-like cell death (SIaLCD) and stress-induced necrosis-like cell death (SInLCD). Whereas apoptosis removes redundant but healthy cells, SICD removes useful but ill or damaged cells. Many studies on cell death involve cancer tissues that resemble parasites in the host patients, which is a complicated system as it involves immune clearance of the alien cancer cells by the host. Cancer resembles an evolutionarily lower-level organism having a weaker apoptosis potential and poorer DNA repair mechanisms. Hence, targeting apoptosis for cancer therapy, i.e. killing via SIaLCD, will be less efficacious and more toxic. On the other hand, necrosis of cancer cells releases cellular debris and components to stimulate immune function, thus counteracting therapy-caused immune suppression and making necrosis better than SIaLCD for chemo drug development. PMID:25594039

  8. Accuracy of magnetic resonance spectroscopy in distinction between radiation necrosis and recurrence of brain tumors

    PubMed Central

    Anbarloui, Mousa Reza; Ghodsi, Seyed Mohammad; Khoshnevisan, Alireza; Khadivi, Masoud; Abdollahzadeh, Sina; Aoude, Ahmad; Naderi, Soheil; Najafi, Zeynab; Faghih-Jouibari, Morteza

    2015-01-01

    Background: Distinction between radiation necrosis and recurrence of intraparenchymal tumors is necessary to select the appropriate treatment, but it is often difficult based on imaging features alone. We developed an algorithm for analyzing magnetic resonance spectroscopy (MRS) findings and studied its accuracy in differentiation between radiation necrosis and tumor recurrence. Methods: Thirty-three patients with a history of intraparenchymal brain tumor resection and radiotherapy, which had developed new enhancing lesion were evaluated by MRS and subsequently underwent reoperation. Lesions with Choline (Cho)/N-acetyl aspartate (NAA) > 1.8 or Cho/Lipid > 1 were considered as tumor recurrence and the remaining as radiation necrosis. Finally, pre-perative MRS diagnoses were compared with histopathological report. Results: The histological diagnosis was recurrence in 25 patients and necrosis in 8 patients. Mean Cho/NAA in recurrent tumors was 2.72, but it was 1.46 in radiation necrosis (P < 0.01). Furthermore, Cho/Lipid was significantly higher in recurrent tumors (P < 0.01) with the mean of 2.78 in recurrent tumors and 0.6 in radiation necrosis. Sensitivity, specificity, and diagnostic accuracy of the algorithm for detecting tumor recurrence were 84%, 75% and 81%, respectively. Conclusion: MRS is a safe and informative tool for differentiating between tumor recurrence and radiation necrosis. PMID:25874054

  9. Bevacizumab as Therapy for Radiation Necrosis in Four Children With Pontine Gliomas

    SciTech Connect

    Liu, Arthur K.; Macy, Margaret E.; Foreman, Nicholas K.

    2009-11-15

    Purpose: Diffuse pontine gliomas are a pediatric brain tumor that is fatal in nearly all patients. Given the poor prognosis for patients with this tumor, their quality of life is very important. Radiation therapy provides some palliation, but can result in radiation necrosis and associated neurologic decline. The typical treatment for this necrosis is steroid therapy. Although the steroids are effective, they have numerous side effects that can often significantly compromise quality of life. Bevacizumab, an antibody against vascular endothelial growth factor, has been suggested as a treatment for radiation necrosis. We report on our initial experience with bevacizumab therapy for radiation necrosis in pediatric pontine gliomas. Materials and Methods: Four children with pontine gliomas treated at the Children's Hospital in Denver and the University of Colorado Denver developed evidence of radiation necrosis both clinically and on imaging. Those 4 children then received bevacizumab as a treatment for the radiation necrosis. We reviewed the clinical outcome and imaging findings. Results: After bevacizumab therapy, 3 children had significant clinical improvement and were able to discontinue steroid use. One child continued to decline, and, in retrospect, had disease progression, not radiation necrosis. In all cases, bevacizumab was well tolerated. Conclusions: In children with pontine gliomas, bevacizumab may provide both therapeutic benefit and diagnostic information. More formal evaluation of bevacizumab in these children is needed.

  10. Increased concentrations of tumour necrosis factor in "cachectic" patients with severe chronic heart failure.

    PubMed Central

    McMurray, J; Abdullah, I; Dargie, H J; Shapiro, D

    1991-01-01

    OBJECTIVE--To ascertain whether patients with cardiac failure and reduced body weight ("cardiac cachexia") have increased circulating concentrations of tumour necrosis factor (cachectin). DESIGN--Patients with cardiac failure were prospectively identified as "cachectic" (body fat less than 27% in men and less than 29% in women measured by skinfold thickness callipers) or "non-cachectic". Tumour necrosis factor was assayed blind to patient group. SETTING--Cardiology unit in a tertiary referral centre. PATIENTS--26 consecutive patients (10 women) (mean age 61) admitted for investigation or treatment of chronic heart failure. All were in New York Heart Association class III or IV. RESULTS--In nine of the 16 cachectic patients the concentration of tumour necrosis factor was increased (mean (SEM) 74 (20) pg/ml) compared with one of the 10 "non-cachectic" patients (22 pg/ml, p less than 0.001). Patients with a raised circulating concentration of tumour necrosis factor weighed significantly less (55.6 (3.5) kg) than those in whom the concentration of tumour necrosis factor was normal (69.0 (4.1) kg) (p = 0.02). CONCLUSIONS--Circulating concentrations of tumour necrosis factor were increased in a significant proportion of patients with chronic heart failure and low body weight. Tumour necrosis factor stimulates catabolism experimentally and it may be a factor in the weight loss seen in patients with "cardiac cachexia". PMID:1747295

  11. A novel role for the apoptosis inhibitor ARC in suppressing TNFα-induced regulated necrosis.

    PubMed

    Kung, G; Dai, P; Deng, L; Kitsis, R N

    2014-04-01

    TNFα signaling can promote apoptosis or a regulated form of necrosis. ARC (apoptosis repressor with CARD (caspase recruitment domain)) is an endogenous inhibitor of apoptosis that antagonizes both the extrinsic (death receptor) and intrinsic (mitochondrial/ER) apoptosis pathways. We discovered that ARC blocks not only apoptosis but also necrosis. TNFα-induced necrosis was abrogated by overexpression of wild-type ARC but not by a CARD mutant that is also defective for inhibition of apoptosis. Conversely, knockdown of ARC exacerbated TNFα-induced necrosis, an effect that was rescued by reconstitution with wild-type, but not CARD-defective, ARC. Similarly, depletion of ARC in vivo exacerbated necrosis caused by infection with vaccinia virus, which elicits severe tissue damage through this pathway, and sensitized mice to TNFα-induced systemic inflammatory response syndrome. The mechanism underlying these effects is an interaction of ARC with TNF receptor 1 that interferes with recruitment of RIP1, a critical mediator of TNFα-induced regulated necrosis. These findings extend the role of ARC from an apoptosis inhibitor to a regulator of the TNFα pathway and an inhibitor of TNFα-mediated regulated necrosis. PMID:24440909

  12. AICAR induces AMPK-independent programmed necrosis in prostate cancer cells.

    PubMed

    Guo, Feng; Liu, Shuang-Qing; Gao, Xing-Hua; Zhang, Long-Yang

    2016-05-27

    AICAR (5-Aminoimidazole-4-carboxamide riboside or acadesine) is an AMP-activated protein kinase (AMPK) agonist, which induces cytotoxic effect to several cancer cells. Its potential activity in prostate cancer cells and the underlying signaling mechanisms have not been extensively studied. Here, we showed that AICAR primarily induced programmed necrosis, but not apoptosis, in prostate cancer cells (LNCaP, PC-3 and PC-82 lines). AICAR's cytotoxicity to prostate cancer cells was largely attenuated by the necrosis inhibitor necrostatin-1. Mitochondrial protein cyclophilin-D (CYPD) is required for AICAR-induced programmed necrosis. CYPD inhibitors (cyclosporin A and sanglifehrin A) as well as CYPD shRNAs dramatically attenuated AICAR-induced prostate cancer cell necrosis and cytotoxicity. Notably, AICAR-induced cell necrosis appeared independent of AMPK, yet requiring reactive oxygen species (ROS) production. ROS scavengers (N-acetylcysteine and MnTBAP), but not AMPKα shRNAs, largely inhibited prostate cancer cell necrosis and cytotoxicity by AICAR. In summary, the results of the present study demonstrate mechanistic evidences that AMPK-independent programmed necrosis contributes to AICAR's cytotoxicity in prostate cancer cells. PMID:27103440

  13. On the relation of necrosis and inflammation to denaturation of proteins.

    PubMed

    OPIE, E L

    1962-03-01

    Necrosis of the skin was produced by the injection of measured quantities of electrolytes and of amino compounds into the dermis, and the relative ability of these substances to produce it was determined. Inflammation characterized by edema and accumulation of leucocytes accompanied necrosis. The ability of electrolytes to produce necrosis was found to increase with the valence of their basic ion, and in this respect was in accord with their ability to denature proteins. The quantity of different electrolytes needed to produce necrosis varied in the same order as the molar concentration of these electrolytes, that is isotonic with liver or kidney cells. Necrosis caused by amino compounds occurred with similar relation to the isotonicity of liver cells. In this as in other relations the cells acted as osmometers. The foregoing relations indicate that denaturation of proteins, necrosis of living tissue, and osmotic activity of liver or kidney cells are determined by molecular weight, valence, and ion-dissociation of electrolytes, that is, by the factors that determine the colligative properties of electrolytes. Agents such as turpentine, mustard, or croton oil and some halogen substitution compounds of methyl that are insoluble in water and soluble in lipoids have produced skin necrosis and inflammation. PMID:14482110

  14. Skylab water balance error analysis

    NASA Technical Reports Server (NTRS)

    Leonard, J. I.

    1977-01-01

    Estimates of the precision of the net water balance were obtained for the entire Skylab preflight and inflight phases as well as for the first two weeks of flight. Quantitative estimates of both total sampling errors and instrumentation errors were obtained. It was shown that measurement error is minimal in comparison to biological variability and little can be gained from improvement in analytical accuracy. In addition, a propagation of error analysis demonstrated that total water balance error could be accounted for almost entirely by the errors associated with body mass changes. Errors due to interaction between terms in the water balance equation (covariances) represented less than 10% of the total error. Overall, the analysis provides evidence that daily measurements of body water changes obtained from the indirect balance technique are reasonable, precise, and relaible. The method is not biased toward net retention or loss.

  15. How Our Balance System Works

    MedlinePlus

    ... from your eyes, the inner ear, and the sensory systems of the body (such as the skin, muscles, ... function? How are vision, the inner ear, and sensory systems impacting functional balance? Some of the tests of ...

  16. Improving Balance with Tai Chi

    MedlinePlus

    ... It emphasizes the intercon- nected nature of the body and mind (Figure 1), combining “physical movement, breathing techniques, and ... and focus. Figure 1. The interconnected nature of body and mind and concept of balance is symbolized by the ...

  17. Laboratory Workhorse: The Analytical Balance.

    ERIC Educational Resources Information Center

    Clark, Douglas W.

    1979-01-01

    This report explains the importance of various analytical balances in the water or wastewater laboratory. Stressed is the proper procedure for utilizing the equipment as well as the mechanics involved in its operation. (CS)

  18. Cautions Concerning Electronic Analytical Balances.

    ERIC Educational Resources Information Center

    Johnson, Bruce B.; Wells, John D.

    1986-01-01

    Cautions chemists to be wary of ferromagnetic samples (especially magnetized samples), stray electromagnetic radiation, dusty environments, and changing weather conditions. These and other conditions may alter readings obtained from electronic analytical balances. (JN)

  19. Aging: Balancing regeneration and cancer

    SciTech Connect

    Beausejour, Christian M.; Campisi, Judith

    2006-08-24

    The proliferation of cells must balance the longevity assured by tissue renewal against the risk of developing cancer. The tumor-suppressor protein p16{sup INK4a} seems to act at the pivot of this delicate equilibrium.

  20. Effects of tumor necrosis factor α-857C/T polymorphism on the expression of tumor necrosis factor α.

    PubMed

    Kimura, Koji; Takayanagi, Risa; Yokoyama, Haruko; Yamada, Yasuhiko

    2016-08-01

    It was reported that homozygosity for a lymphotoxin α (LTA) 1-1-1-1 haplotype (LTA NcoI-TNFc-aa13L-aa26) may identify subgroups with a poor response to infliximab in Crohn's disease patients. Previously, we found a genetic polymorphism that linked with the LTA 1-1-1-1 haplotype and noted that it was a tumor necrosis factor (TNF) α-857 T allele. To investigate the effects of the -857C/T (rs1799724) polymorphism on the expression of TNFα, we compared levels of transcriptional activity of the gene, mRNA, and protein of the TNFα. The change in transcriptional activity of the -857T allele was higher than that of the -857C allele. Furthermore, the accumulated transcriptional activity of the -857T allele was 1.3-fold higher than that of the -857C allele up to 48 h. The levels of mRNA and protein of the TNFα after stimulation were also shown to be significantly higher in -857C/T as compared to the -857C/C genotype. Our results suggested that TNFα promoter -857T is higher than -857C in the levels of transcriptional activity of the gene, mRNA, and protein of the TNFα. The differences in therapeutic effect of TNF inhibitors among individuals can be explained in part by the induction ability of TNFα via the -857C/T polymorphism. PMID:27307133

  1. Early embryonic and endometrial regulation of tumor necrosis factor and tumor necrosis factor receptor 2 in the cattle uterus.

    PubMed

    Correia-Álvarez, E; Gómez, E; Martín, D; Carrocera, S; Pérez, S; Peynot, N; Giraud-Delville, C; Caamaño, J N; Balseiro, A; Sandra, O; Duranthon, V; Muñoz, M

    2015-04-01

    Tumor necrosis factor (TNF) alpha likely mediates embryomaternal communication in mammals. In bovine, we have previously found that the uterine fluid of heifers that carried early embryos shows downregulation in the TNF and nuclear factor κB system. In this work, we assessed the expression of TNF and its receptor TNFR2 in the bovine endometrium and embryos during blastocyst development. Moreover, to explore the endometrial immune response to early embryos, we analyzed the number of CD45 leukocytes in the bovine endometrium. Day 8 endometrium and blastocyst recovered from animals after transfer of Day 5 embryos showed TNF and TNFR2 mRNA transcription and protein colocalization. The presence of embryos increased endometrial TNF and TNFR2 protein, whereas endometrial leukocytes decreased. Blastocysts exposed to the uterine tract had undetectable levels of TNF and lower levels of TNFR2 mRNA. These results suggest that the endometrium might lower the TNF concentration in the blastocyst by (1) regulating TNF secretion into the uterine fluid and (2) inducing decreased TNF and TNFR2 mRNA transcription in the embryo. Thus, TNF and TNFR2 might participate in early embryomaternal communication. PMID:25589228

  2. Walking (Gait), Balance, and Coordination Problems

    MedlinePlus

    ... tizanidine are generally effective in treating this symptom. Balance : Balance problems typically result in a swaying and “drunken” ... factors for falls are complex and include: poor balance and slowed walking reduced proprioception (the sensation of ...

  3. Form 6 - gas balancing agreement

    SciTech Connect

    Not Available

    1990-01-01

    In 1988, a special Committee of the Rocky Mountain Mineral Law Foundation undertook a project to draft a model from gas balancing agreement. This project was initiated at the request of a number of Foundation members who felt that a model form gas balancing agreement would facilitate the negotiation of operating agreement, since gas balancing issues had become sticking points in the process. The Committee was composed of attorneys representing a wide cross-section of the oil and gas industry including both major and independent oil companies, production companies with interstate pipeline affiliates, and private practitioners. The Committee attempted to address the more controversial issues in gas balancing with optional provisions in the Form. To facilitate the negotiation process, the number of optional provisions was minimized. This form may be used as an Appendix to the new A.A.P.L. Form 610-1989 Model Form Operating Agreement. This book includes provision of this Form which are: Ownership of gas production; Balancing of production accounts; Cash balancing upon depletion; Deliverability tests; Nominations; Statements; Payment of taxes; Operating expenses; Overproducing allowable; Payment of leasehold burdens; Operator's liability; Successors and assigns; Audits; Arbitration; and Operator's fees.

  4. [Brain MR perfusion and MR spectroscopy in differentiation of radiation necrosis from tumor recurrence (case report)].

    PubMed

    Tekşam, Mehmet; Kayahan, Esra Meltem; Yerli, Hasan; Ağildere, A Muhteşem

    2004-12-01

    It is not always possible to differentiate tumor recurrence from radiation necrosis using conventional MR images. In this report we present a case of pathologically proven radiation necrosis which appeared as nodular contrast enhancement on conventional MR images in a patient who was surgically treated for grade II astrocytoma 5 years ago. There were decreased choline, creatine and N-acetyl aspartate peaks and significantly increased lipid peak on multivoxel H1-MR spectroscopy while there was no significant perfusion increase on MR perfusion. These findings suggested changes secondary to radiation necrosis. PMID:15611913

  5. Complete Penile Necrosis in a Patient With Heparin-induced Thrombocytopenia: A Case Report*

    PubMed Central

    Blais, Anne-Sophie; Deschênes Rompré, Marie-Pier; Lacombe, Louis

    2014-01-01

    Penile necrosis is a rare condition that has been mostly described in association with diabetes mellitus and end-stage renal disease. We report an unusual case of acute penile necrosis because of heparin-induced thrombocytopenia. A 75-year-old man presented with acute renal failure and experienced cardiac complications during the hospitalization. The patient was treated twice with intravenous heparin. He developed symptoms of penile necrosis 4 days after the reintroduction of heparin. At that moment, the platelet count dropped by 61%, and the analysis of heparin-pf4 antibodies was positive for heparin-induced thrombocytopenia. The patient underwent a total penectomy and a perineal urethrostomy. PMID:26954936

  6. Forehead necrosis, one of the many facades of giant cell arteritis.

    PubMed

    Palmer, Vanessa Elizabeth; Young-Zvandasara, Tafadzwa; Vusirikala, Bharati

    2015-01-01

    Giant cell arteritis (GCA) is known to be a potentially blinding condition. Swift diagnosis can aid in preventing permanent visual loss and, more importantly, protect the contralateral eye. Classical symptoms include jaw claudication, myalgia and new-onset headache. We present two cases of GCA with scalp necrosis, a rare feature associated with this condition. In the first case, forehead necrosis preceded the visual symptoms by 2 days. In the second case it was noted a few weeks after the patient presented with profound unilateral loss of vision. Scalp necrosis is an important sign that should prompt those approached by these patients to consider GCA. PMID:25953578

  7. Tumor necrosis factor-alpha gene is not associated with obsessive-compulsive disorder.

    PubMed

    Zai, Gwyneth; Arnold, Paul D; Burroughs, Eliza; Richter, Margaret A; Kennedy, James L

    2006-02-01

    Dysregulation of the immune system has been suggested to play a role in the complex etiology of obsessive-compulsive disorder. In this context, tumor necrosis factor-alpha is considered an interesting candidate for genetic studies as overproduction of tumor necrosis factor-alpha, which may be genetically modulated, can exert neurotoxic effects and influence neural cell growth and proliferation. Moreover, the tumor necrosis factor-alpha gene is located on chromosome 6p21.3, a region that has been found to be weakly associated with obsessive-compulsive disorder in linkage studies. One functional polymorphism, G-308A, has been found within the gene. PMID:16395130

  8. Cutaneous necrosis in pregnancy secondary to activated protein C resistance in hereditary angioedema.

    PubMed

    Perkins, W; Downie, I; Keefe, M; Chisholm, M

    1995-04-01

    A 26-year-old woman with hereditary angineurotic oedema (HAE) presented at 22 weeks gestation with severe cutaneous necrosis similar to that seen in coumarin skin necrosis. Protein S deficiency secondary to HAE and pregnancy was postulated. Treatment with heparin, C1-inhibitor concentrates, systemic steroids and surgical debridement resulted in a successful outcome for both mother and child. Subsequent investigations revealed normal levels of protein C, antithrombin III, total protein S, free protein S but reduced function protein S activity with evidence of activated protein C resistance. Cutaneous necrosis has not been reported in associated with activated protein C resistance previously and the possible mechanisms are discussed. PMID:7745572

  9. Regulation of bitter taste responses by tumor necrosis factor.

    PubMed

    Feng, Pu; Jyotaki, Masafumi; Kim, Agnes; Chai, Jinghua; Simon, Nirvine; Zhou, Minliang; Bachmanov, Alexander A; Huang, Liquan; Wang, Hong

    2015-10-01

    Inflammatory cytokines are important regulators of metabolism and food intake. Over production of inflammatory cytokines during bacterial and viral infections leads to anorexia and reduced food intake. However, it remains unclear whether any inflammatory cytokines are involved in the regulation of taste reception, the sensory mechanism governing food intake. Previously, we showed that tumor necrosis factor (TNF), a potent proinflammatory cytokine, is preferentially expressed in a subset of taste bud cells. The level of TNF in taste cells can be further induced by inflammatory stimuli. To investigate whether TNF plays a role in regulating taste responses, in this study, we performed taste behavioral tests and gustatory nerve recordings in TNF knockout mice. Behavioral tests showed that TNF-deficient mice are significantly less sensitive to the bitter compound quinine than wild-type mice, while their responses to sweet, umami, salty, and sour compounds are comparable to those of wild-type controls. Furthermore, nerve recording experiments showed that the chorda tympani nerve in TNF knockout mice is much less responsive to bitter compounds than that in wild-type mice. Chorda tympani nerve responses to sweet, umami, salty, and sour compounds are similar between TNF knockout and wild-type mice, consistent with the results from behavioral tests. We further showed that taste bud cells express the two known TNF receptors TNFR1 and TNFR2 and, therefore, are potential targets of TNF. Together, our results suggest that TNF signaling preferentially modulates bitter taste responses. This mechanism may contribute to taste dysfunction, particularly taste distortion, associated with infections and some chronic inflammatory diseases. PMID:25911043

  10. Tumor necrosis factor-beta in human pregnancy and labor.

    PubMed

    Laham, N; Van Dunné, F; Abraham, L J; Farrugia, W; Bendtzen, K; Brennecke, S P; Rice, G E

    1997-04-01

    The aims of this study were to determine tumor necrosis factor-beta (TNF-beta) concentration profiles in peripheral venous plasma and amniotic fluid during pregnancy and at the time of labor and to characterise TNF-beta mRNA expression and TNF-beta release from human gestational tissues. In addition, we investigated the expression of TNF-beta binding protein, lymphotoxin-beta (LT-beta), in human gestational tissues. The mean (+/-S.E.M.) TNF-beta concentrations in maternal plasma (TIL, 78 +/- 12 pg/ml, n = 7 vs. TNIL, 304 +/- 88 pg/ml, n = 7) and amniotic fluid (TIL, 8 +/- 5 pg/ml, n = 6 vs. TNIL, 73 +/- 20 pg/ml, n = 20) were significantly (P < 0.05) decreased in association with term labor-onset (TIL) compared to term not-in-labor (TNIL). TNF-beta concentration in maternal plasma and amniotic fluid did not change significantly either with preterm labor (PIL), or during pregnancy. Group-matched comparison of maternal plasma and amniotic fluid TNF-beta concentrations demonstrated that amniotic fluid TNF-beta concentrations were 6-8 fold lower than maternal plasma TNF-beta concentrations. Furthermore, no detectable TNF-beta was secreted from cultured human amniotic, choriodecidual and placental explants. Although, TNF-beta mRNA was detected in amnion, choriodecidual and placenta, LT-beta was similarly expressed in these tissues, suggesting that TNF-beta may be cell membrane bound. These data demonstrate that TNF-beta is present at low levels within the intrauterine environment and may suggest that TNF-beta is specifically inhibited at the maternal-fetal interface. PMID:9185077

  11. Efficacy of certain disinfectants against infectious pancreatic necrosis virus

    USGS Publications Warehouse

    Elliott, Diane G.; Amend, Donald F.

    1978-01-01

    The virucidal properties of iodophor, chlorine (sodium hypochlorite), formalin, thimerosal (organic mercurial compound), malachite green, and acriflavine were tested on infectious pancreatic necrosis virus (IPNV). Iodine and chlorine showed good activity, but efficacy depended on the concentration of virus, the presence of organic matter (calf serum), and water pH. Water hardness (0-300 mg 1−1 as CaCO3) did not affect virucidal activity. In a 5 min exposure, 4 mg 1−1available iodine inactivated 103.9 TCID50 m1−1 IPNV but 16 mg 1−1 iodine were needed for inactivation of 106.3TCID50m1−1. The addition of 0-5% calf serum significantly reduced the iodine concentration and the virucidal activity. In comparison, 4 mg 1−1 chlorine were needed to inactivate 1046 TCID50 m1−1 IPNV in 5 min. However, the addition of 0-07 % serum greatly reduced the chlorine concentration and extended the virucidal contact time to 30 min or more. IPNV at 106.3 TCID60 m1−1 was not inactivated by exposures for 60 min to 0-2% formalin, 10 min to 0-2% thimerosal, 60 min to 5 mg 1−1 malachite green, or 20 min to 500 mg 1−1 acriflavine. However, acriflavine at 0-5 mg 1−1 in cell culture media prevented the development of cytopathology caused by IPNV and may be useful in the treatment of the disease.

  12. A third distinct tumor necrosis factor receptor of orthopoxviruses.

    PubMed

    Loparev, V N; Parsons, J M; Knight, J C; Panus, J F; Ray, C A; Buller, R M; Pickup, D J; Esposito, J J

    1998-03-31

    Cowpox virus Brighton red strain (CPV) contains a gene, crmD, which encodes a 320-aa tumor necrosis factor receptor (TNFR) of 44% and 22% identity, respectively, to the CPV TNFR-like proteins, cytokine response modifiers (crm) CrmB and CrmC. The crmD gene was interrupted in three other cowpox strains examined and absent in various other orthopoxviruses; however, four strains of ectromelia virus (ECT) examined contained an intact crmD (97% identity to CPV crmD) and lacked cognates of crmB and crmC. The protein, CrmD, contains a transport signal; a 151-aa cysteine-rich region with 21 cysteines that align with human TNFRII ligand-binding region cysteines; and C-terminal region sequences that are highly diverged from cellular TNFR C-terminal region sequences involved in signal transduction. Bacterial maltose-binding proteins containing the CPV or ECT CrmD cysteine-rich region bound TNF and lymphotoxin-alpha (LTalpha) and blocked their in vitro cytolytic activity. Secreted viral CrmD bound TNF and LTalpha and was detectable after the early stage of replication, using nonreducing conditions, as 60- to 70-kDa predominant and 90- to 250-kDa minor disulfide-linked complexes that were able to be reduced to a 46-kDa form and deglycosylated to a 38-kDa protein. Cells infected with CPV produced extremely low amounts of CrmD compared with ECT. Possessing up to three TNFRs, including CrmD, which is secreted as disulfide-linked complexes in varied amounts by CPV and ECT, likely enhances the dynamics of the immune modulating mechanisms of orthopoxviruses. PMID:9520445

  13. Treatment of rheumatoid arthritis with tumour necrosis factor inhibitors

    PubMed Central

    Mewar, Devesh; Wilson, Anthony G

    2011-01-01

    Advances in our understanding of the key mediators of chronic inflammation and tissue damage characteristic of rheumatoid arthritis (RA) have resulted in the development of novel therapies primarily targeting pro-inflammatory cytokines. Inhibitors of tumour necrosis factor (TNF) are the most widely used of the biological therapies at present with five different agents currently available; four are based on monoclonal anti-TNF antibodies and a soluble TNF receptor-Fc fusion protein. Long-term use of these molecules has proven to be highly effective in the majority of patients; however, around one-third have a suboptimal response potentially leading to further cartilage and bone damage, furthermore these agents are expensive compared with conventional therapies such as methotrexate. Many recent studies have attempted to identify therapeutic response biomarkers of TNF inhibitors which could be used to improve therapeutic targeting. The presence of rheumatoid factor and anti-cyclic citullinated protein antibodies, present in around 65% of RA patients, are associated with a poorer response to anti-TNF agents. Poorer response is also associated with levels of C-reactive protein and cartilage degradation product at initiation of treatment. Intriguingly, genetic studies of variants of TNF and of genes encoding members of the Toll-like receptors, nuclear factor-kappa B and p38 mitogen-activated protein kinase signalling families have been associated with response to individual anti-TNF agents. Continued advances in technologies such as ultra high throughput sequencing and proteomics should facilitate the discovery of additional biomarkers of response to anti-TNF resulting in improved disease control and quality of life for RA patients and reduced costs for healthcare funders. PMID:21039421

  14. EARLY DIVERSIFICATION OF THE TUMOR NECROSIS SUPERFAMILY IN TELEOSTS: GENOMIC CHARACTERIZATION AND EXPRESSION ANALYSIS

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Members of the tumor necrosis factor superfamily (TNFSF) are cytokines involved in diverse immunological and developmental pathways. Little is known about their evolution or expression in lower vertebrate species. Bioinformatic searches of available teleost databases including Zebrafish, Tetroadon...

  15. Acute esophageal necrosis occurring in a patient undergoing percutaneous coronary intervention.

    PubMed

    Kwon, Hyung-Jin; Park, Sang-Ho; Ahn, Ji-Hoon; Lee, Tae-Hoon; Lee, Chang-Kyun

    2014-05-01

    Acute esophageal necrosis is uncommon in the literature. Its etiology is unknown, although cardiovascular disease, hemodynamic compromise, gastric outlet obstruction, alcohol ingestion, hypoxemia, hypercoagulable state, infection, and trauma have all been suggested as possible causes. A 67-year-old female underwent a coronary angiography (CAG) for evaluation of chest pain. CAG findings showed coronary three-vessel disease. We planned percutaneous coronary intervention (PCI). Coronary arterial dissection during the PCI led to sudden hypotension. Six hours after the index procedure, the patient experienced a large amount of hematemesis. Emergency gastrofibroscopy was performed and showed mucosal necrosis with a huge adherent blood clot in the esophagus. After conservative treatment for 3 months, the esophageal lesion was completely improved. She was diagnosed with acute esophageal necrosis. We report herein a case of acute esophageal necrosis occurring in a patient undergoing percutaneous coronary intervention. PMID:24851074

  16. Herpesviral Hematopoietic Necrosis in Goldfish in Switzerland: Early Lesions in Clinically Normal Goldfish (Carassius auratus).

    PubMed

    Giovannini, S; Bergmann, S M; Keeling, C; Lany, C; Schütze, H; Schmidt-Posthaus, H

    2016-07-01

    Cyprinid herpesvirus 2 is a pathogen of goldfish, inducing a disease referred to as herpesviral hematopoietic necrosis. The disease is described so far in Japan, North America, Taiwan, Australia, the United Kingdom, and recently also Italy. Here the authors describe histologic lesions in clinically affected fish in comparison with clinically normal but virus DNA-positive goldfish in Switzerland. While necrosis or enhanced single-cell necrosis in the hematopoietic tissue in the pronephros or mesonephros was evident in dead and sick animals, in clinically normal goldfish, only single-cell necrosis was observed. Virus DNA was demonstrated in dead as well as clinically affected and subclinically infected goldfish by polymerase chain reaction and in situ hybridization. This study identifies the presence of goldfish herpesvirus in Switzerland and highlights the fact that the virus might be more widespread than assumed, as clinically normal goldfish can also carry cyprinid herpesvirus 2, showing histologically similar lesions but of lesser extent and severity. PMID:26553521

  17. Skin Flap Necrosis by Bone Marking with Methylene Blue in Cochlear Implantation.

    PubMed

    Kim, Yeon Hoo; Cho, Sung Il

    2015-09-01

    One of surgical complications in cochlear implantation is the necrosis of the skin flap above the receiver-stimulator coil. We present a case of 55-year-old woman who underwent cochlear implantation and developed a bluish skin necrosis due to bone marking. The planned position for the receiver-stimulator was marked using methylene blue through skin to bone. She did not undergo skin flap thinning and underwent successful implantation with complete electrode insertion. Few weeks postoperatively, the patient developed bluish discoloration with progressive thick, blue eschar formation and skin flap necrosis. She subsequently underwent wound debridement and skin flap closure. Cochlear explantation was not necessary. Timely diagnosis and management about this complication is necessary to prevent further skin breakdown and subsequent device extrusion. This report identifies the marking using methylene blue as another possible source of skin flap necrosis in cochlear implantation, and surgeons should be aware of this potential complication. PMID:26413579

  18. [Brain radiation necrosis after stereotactic radiotherapy of the resection cavity for intracranial metastases: analysis of the literature from four cases].

    PubMed

    Doré, M; Lefebvre, L; Delpon, G; Thillays, F

    2015-04-01

    Stereotactic hypofractionated radiotherapy after resection of brain metastasis is an alternative to whole brain radiotherapy. A high dose per fraction is associated with a risk of radiation necrosis. We present four cases of confirmed histological radiation necrosis. Differentiating recurrent tumour from radiation necrosis in this scenario is challenging. An enhancing area in magnetic resonance imaging (MRI) with a "cut bell pepper" appearance may suggest radiation necrosis. Advanced imaging modalities such as perfusion MR imaging and positron emission tomography can be useful. Dosimetric predictors of the occurrence of radiation necrosis after stereotactic hypofractionated radiotherapy are poorly understood and require prospective studies on larger cohorts. PMID:25573799

  19. Balancing act: the ultimate balance nutrition consulting center.

    PubMed

    Engle, L

    1998-11-01

    Nutritional issues often complicate health care but are very important in HIV treatment where diet can play a strong role in drug absorption and effectiveness. A Canadian company has started a for-fee nutritional counseling service called Ultimate Balance. The nutritionists at Ultimate Balance require medical disclosure and extensive telephone interviews with patients, and also review patients' cases and medications. The nutritional guidance provided is controversial, because it is funded by a company that produces nutritional supplements, and counselors sometimes recommend those supplements. A personal experience with the nutritional counseling service is described. Contact information is provided. PMID:11365979

  20. [Syncumar-induced necrosis following heparin-induced thrombocytopenia and thrombosis].

    PubMed

    Pósán, E; Adi, S; Szücs, G; Rigó, J; Boda, Z

    1995-04-30

    The authors describe the combined occurrence of heparin-induced thrombocytopenia and cumarin-induced skin necrosis, a rare condition that has not yet been reported in Hungary. The 69-year-old woman had received prophylactic heparin treatment prior to total hip arthroplasty. The first complication that the anticoagulant therapy brought about was serious thrombocytopenia paradoxically associated not with bleeding but with deep vein thrombosis. The latter necessitated coumarin therapy which resulted in severe skin necrosis. PMID:7739854

  1. Localized dose delivering by ion beam irradiation for experimental trial of establishing brain necrosis model.

    PubMed

    Takata, Takushi; Kondo, Natsuko; Sakurai, Yoshinori; Tanaka, Hiroki; Hasegawa, Takashi; Kume, Kyo; Suzuki, Minoru

    2015-11-01

    Localized dose delivery techniques to establish a brain radiation necrosis model are described. An irradiation field was designed by using accelerated protons or helium ions with a spread-out Bragg peak. Measurement of the designed field confirmed that a high dose can be confined to a local volume of an animal brain. The irradiation techniques described here are very useful for establishing a necrosis model without existence of extraneous complications. PMID:26454176

  2. [Intracardiac mass: Why not a liquefaction necrosis of a mitral annulus calcification?].

    PubMed

    Leddet, P; Couppié, P; De Poli, F; Uhry, S; Hanssen, M

    2015-11-01

    We report the case of an asymptomatic 70-year-old woman with a liquefaction necrosis of mitral annulus calcification. This mass was discovered incidentally during an echocardiographic examination. Additional treatment was not performed because liquefaction necrosis of mitral calcification usually has a benign prognosic. A scheduled clinical review with an echocardiographic examination and cardiac MRI was planified. The patient is actually healthy without any complication. PMID:26482628

  3. A case series of skin necrosis following use of non invasive ventilation pressure masks.

    PubMed

    Ahmad, Z; Venus, M; Kisku, W; Rayatt, S S

    2013-02-01

    Two cases of nasal skin necrosis secondary to pressure from the use of continuous positive airway pressure (CPAP) face masks are presented. Both developed skin necrosis as a result of wearing these masks over the nasal bridge. These cases highlight the need for clinical vigilance in application of CPAP masks, the need for monitoring the skin of the nose during CPAP use and the possible need for modifications in design to help prevent this serious complication. PMID:22432901

  4. Prevention of skin flap necrosis by a course of treatment with vasodilator drugs.

    PubMed

    Finseth, F; Adelberg, M G

    1978-05-01

    Large island skin flaps, comprising the entire abdominal covering in rats, were raised on one neurovascular pedicle in the groin. A standard area of necrosis was produced on the other side from the pedicle. However, when the animals were treated with certain vasodilator drugs for 15 days before and 7 days after the flaps were raised, there was little or no necrosis. The effect of the drug therapy was the same as a surgical delay. PMID:347479

  5. Hepatocellular carcinoma: IVIM diffusion quantification for prediction of tumor necrosis compared to enhancement ratios

    PubMed Central

    Kakite, Suguru; Dyvorne, Hadrien A.; Lee, Karen M.; Jajamovich, Guido H.; Knight-Greenfield, Ashley; Taouli, Bachir

    2015-01-01

    Purpose To correlate intra voxel incoherent motion (IVIM) diffusion parameters of liver parenchyma and hepatocellular carcinoma (HCC) with degree of liver/tumor enhancement and necrosis; and to assess the diagnostic performance of diffusion parameters vs. enhancement ratios (ER) for prediction of complete tumor necrosis. Patients and methods In this IRB approved HIPAA compliant study, we included 46 patients with HCC who underwent IVIM diffusion-weighted (DW) MRI in addition to routine sequences at 3.0 T. True diffusion coefficient (D), pseudo-diffusion coefficient (D*), perfusion fraction (PF) and apparent diffusion coefficient (ADC) were quantified in tumors and liver parenchyma. Tumor ER were calculated using contrast-enhanced imaging, and degree of tumor necrosis was assessed using post-contrast image subtraction. IVIM parameters and ER were compared between HCC and background liver and between necrotic and viable tumor components. ROC analysis for prediction of complete tumor necrosis was performed. Results 79 HCCs were assessed (mean size 2.5 cm). D, PF and ADC were significantly higher in HCC vs. liver (p < 0.0001). There were weak significant negative/positive correlations between D/PF and ER, and significant correlations between D/PF/ADC and tumor necrosis (for D, r 0.452, p < 0.001). Among diffusion parameters, D had the highest area under the curve (AUC 0.811) for predicting complete tumor necrosis. ER outperformed diffusion parameters for prediction of complete tumor necrosis (AUC > 0.95, p < 0.002). Conclusion D has a reasonable diagnostic performance for predicting complete tumor necrosis, however lower than that of contrast-enhanced imaging. PMID:27069971

  6. Tumor necrosis factor induces glomerular damage in the rabbit.

    PubMed Central

    Bertani, T.; Abbate, M.; Zoja, C.; Corna, D.; Perico, N.; Ghezzi, P.; Remuzzi, G.

    1989-01-01

    Tumor necrosis factor (TNF) is a polypeptide hormone produced by activated macrophages detectable in the circulation of experimental animals given endotoxin. Recent evidence strongly suggests that many of the deleterious effects of endotoxin in experimental animals are mediated by TNF. Because endotoxemia in experimental animals and humans is associated with glomerular damage the present investigation was designed to establish whether TNF directly induces glomerular functional and structural changes. Twenty-three rabbits were given human recombinant TNF at the doses of 0.08, 0.8, and 8.0 micrograms/kg/h as a continuous 5-hour intravenous infusion. Animals were killed at the end of the infusion. All rabbits given 0.8 and 8.0 micrograms/kg/h TNF developed anemia (Ht value decrease at 5 hours: 0.8 microgram/kg/h, 15%; 8.0 micrograms/kg/h, 16%); leukopenia (leukocyte count decrease at 5 hours: 0.8 micrograms/kg/h, 47%; 8.0 micrograms/kg/h, 59%); thrombocytopenia (platelet count decrease at 5 hours; 0.8 micrograms/kg/h, 45%; 8.0 micrograms/kg/h, 57%). Rabbits given 8.0 micrograms/kg/h also had renal failure (serum creatinine from 1.02 +/- 0.15 to 1.64 +/- 0.34 mg/dl). By light microscopy only occasional polymorphonuclear leukocytes in the glomerular capillaries were detectable in rabbits infused with 0.08 micrograms/kg/h TNF, whereas with 0.8 micrograms/kg/h TNF the presence of inflammatory cells in the glomerular capillaries was the prominent finding. With 8.0 micrograms/kg/h TNF beside leukocyte accumulation, fibrin was detected in the glomerular capillary lumens of two of eight animals. Electron microscopy found dose-dependent glomerular endothelial cell damage in animals given TNF with fibrinlike material in the capillary lumens. Glomerular changes induced by TNF were remarkably similar to those previously found in animals given endotoxin. Thus, TNF is likely to be the mediator of endotoxin-induced glomerular damage and can be regarded as a new mediator of

  7. Fast Neutron Induced Autophagy Leads To Necrosis In Glioblastoma Multiforme Cells

    NASA Astrophysics Data System (ADS)

    Yasui, Linda; Gladden, Samantha; Andorf, Christine; Kroc, Thomas

    2011-06-01

    Fast neutrons are highly effective at killing glioblastoma multiforme (GBM), U87 and U251 cells. The mode of cell death was investigated using transmission electron microscopy (TEM) to identify the fraction of irradiated U87 or U251 cells having morphological features of autophagy and/or necrosis. U87 or U251 cells were irradiated with 2 Gy fast neturons or 10 Gy γ rays. A majority of U87 and U251 cells exhibit features of cell death with autophagy after irradiation with either 10 Gy γ rays or 2 Gy fast neutrons. Very few γ irradiated cells had features of necrosis (U87 or U251 cell samples processed for TEM 1 day after 10 Gy γ irradiation). In contrast, a significant increase was observed in necrotic U87 and U251 cells irradiated with fast neutrons. These results show a greater percentage of cells exhibit morphological evidence of necrosis induced by a lower dose of fast neutron irradiation compared to γ irradiation. Also, the evidence of necrosis in fast neutron irradiated U87 and U251 cells occurs in a background of autophagy. Since autophagy is observed before necrosis, autophagy may play a role in signaling programmed necrosis in fast neutron irradiated U87 and U251 cells.

  8. Fast Neutron Induced Autophagy Leads To Necrosis In Glioblastoma Multiforme Cells

    SciTech Connect

    Yasui, Linda; Gladden, Samantha; Andorf, Christine; Kroc, Thomas

    2011-06-01

    Fast neutrons are highly effective at killing glioblastoma multiforme (GBM), U87 and U251 cells. The mode of cell death was investigated using transmission electron microscopy (TEM) to identify the fraction of irradiated U87 or U251 cells having morphological features of autophagy and/or necrosis. U87 or U251 cells were irradiated with 2 Gy fast neturons or 10 Gy {gamma} rays. A majority of U87 and U251 cells exhibit features of cell death with autophagy after irradiation with either 10 Gy {gamma} rays or 2 Gy fast neutrons. Very few {gamma} irradiated cells had features of necrosis (U87 or U251 cell samples processed for TEM 1 day after 10 Gy {gamma} irradiation). In contrast, a significant increase was observed in necrotic U87 and U251 cells irradiated with fast neutrons. These results show a greater percentage of cells exhibit morphological evidence of necrosis induced by a lower dose of fast neutron irradiation compared to {gamma} irradiation. Also, the evidence of necrosis in fast neutron irradiated U87 and U251 cells occurs in a background of autophagy. Since autophagy is observed before necrosis, autophagy may play a role in signaling programmed necrosis in fast neutron irradiated U87 and U251 cells.

  9. Response-driven imaging biomarkers for predicting radiation necrosis of the brain

    NASA Astrophysics Data System (ADS)

    Nazem Zadeh, Mohammad-Reza; Chapman, Christopher H.; Chenevert, Thomas; Lawrence, Theodore S.; Ten Haken, Randall K.; Tsien, Christina I.; Cao, Yue

    2014-05-01

    Radiation necrosis is an uncommon but severe adverse effect of brain radiation therapy (RT). Current predictive models based on radiation dose have limited accuracy. We aimed to identify early individual response biomarkers based upon diffusion tensor (DT) imaging and incorporated them into a response model for prediction of radiation necrosis. Twenty-nine patients with glioblastoma received six weeks of intensity modulated RT and concurrent temozolomide. Patients underwent DT-MRI scans before treatment, at three weeks during RT, and one, three, and six months after RT. Cases with radiation necrosis were classified based on generalized equivalent uniform dose (gEUD) of whole brain and DT index early changes in the corpus callosum and its substructures. Significant covariates were used to develop normal tissue complication probability models using binary logistic regression. Seven patients developed radiation necrosis. Percentage changes of radial diffusivity (RD) in the splenium at three weeks during RT and at six months after RT differed significantly between the patients with and without necrosis (p = 0.05 and p = 0.01). Percentage change of RD at three weeks during RT in the 30 Gy dose-volume of the splenium and brain gEUD combined yielded the best-fit logistic regression model. Our findings indicate that early individual response during the course of RT, assessed by radial diffusivity, has the potential to aid the prediction of delayed radiation necrosis, which could provide guidance in dose-escalation trials.

  10. Dependency of tissue necrosis on gelatin sponge particle size after canine hepatic artery embolization

    SciTech Connect

    Sonomura, Tetsuo; Yamada, Ryusaku; Kishi, Kazushi; Nishida, Norifumi; Yang, Ren J.; Sato, Morio

    1997-01-15

    Purpose. To determine the optimal size of gelatin sponge particles (GSPs) to produce maximum tumor necrosis with minimum side effects after canine hepatic artery embolization (HAE). Methods. GSPs were separated into four size ranges: A, up to 200 {mu}m (mean 152) as Gelfoam powder; B, 200-500 {mu}m (mean 336) as Gelfoam powder; C, 500-1000 {mu}m (mean 649) as Spongel; and D, 1000-2000 {mu}m (mean 1382) as Spongel. Three mongrel dogs were assigned randomly to HAE with each particle size. On day 7 after HAE, the livers were removed and subjected to pathological examination. Results. The mean volume of liver necrosis was 11% after embolization, with particle size A, 36.3% with B, 0% with C, and 1% with D. Coagulation necrosis was found in all livers with particles of sizes A and B, and in 1 of 6 with sizes C and D. Bile duct injury was found in five of six dogs with sizes A and B and in none with sizes C and D. Gallbladder necrosis was found in one dog with size B and pancreas necrosis in one with size A. Conclusion. GSPs of 500 {mu}m are considered optimally effective for tissue necrosis according to this model.

  11. Deletion of IL-33R attenuates VEGF expression and enhances necrosis in mammary carcinoma

    PubMed Central

    Pejnovic, Nada N.; Mitrovic, Slobodanka L. J.; Arsenijevic, Nebojsa N.; Simovic Markovic, Bojana J.; Lukic, Miodrag L.

    2016-01-01

    Interleukin-33 (IL-33)/IL-33 receptor (IL-33R, ST2) signaling pathway promotes mammary cancer growth and metastasis by inhibiting anti-tumor immunity. However, the role of IL-33/IL-33R axis in neoangiogenesis and tumor necrosis is not elucidated. Therefore, the aim of this study was to investigate the role of IL-33/IL-33R axis in mammary tumor necrosis. Deletion of IL-33R (ST2) gene in BALB/c mice enhanced tumor necrosis and attenuated tumor growth in 4T1 breast cancer model, which was associated with markedly decreased expression of vascular endothelial growth factor (VEGF) and IL-33 in mammary tumor cells. We next analyzed IL-33, IL-33R and VEGF expression and microvascular density (MVD) in breast tumors from 40 female patients with absent or present tumor necrosis. We found significantly higher expression of IL-33, IL-33R and VEGF in breast cancer tissues with absent tumor necrosis. Both, IL-33 and IL-33R expression correlated with VEGF expression in tumor cells. Further, VEGF expression positively correlated with MVD in perinecrotic zone. Taking together, our data indicate that IL-33/IL-33R pathway is critically involved in mammary tumor growth by facilitating expression of pro-angiogenic VEGF in tumor cells and attenuating tumor necrosis. These data add an unidentified mechanism by which IL-33/IL-33R axis facilitates tumor growth. PMID:26919112

  12. Effects of skeleton structure on necrosis targeting and clearance properties of radioiodinated dianthrones.

    PubMed

    Zhang, Dongjian; Jiang, Cuihua; Yang, Shengwei; Gao, Meng; Huang, Dejian; Wang, Xiaoning; Shao, Haibo; Feng, Yuanbo; Sun, Ziping; Ni, Yicheng; Zhang, Jian; Yin, Zhiqi

    2016-07-01

    Necrosis avid agents (NAAs) can be used for diagnose of necrosis-related diseases, evaluation of therapeutic responses and targeted therapeutics of tumor. In order to probe into the effects of molecular skeleton structure on necrosis targeting and clearance properties of radioiodinated dianthrones, four dianthrone compounds with the same substituents but different skeletal structures, namely Hypericin (Hyp), protohypericin (ProHyp), emodin dianthrone mesomer (ED-1) and emodin dianthrone raceme (ED-2) were synthesized and radioiodinated. Then radioiodinated dianthrones were evaluated in vitro for their necrosis avidity in A549 lung cancer cells untreated and treated with H2O2. Their biodistribution and pharmacokinetic properties were determined in rat models of induced necrosis. In vitro cell assay revealed that destruction of rigid skeleton structure dramatically reduced their necrosis targeting ability. Animal studies demonstrated that destruction of rigid skeleton structure dramatically reduced the necrotic tissue uptake and speed up the clearance from the most normal tissues for the studied compounds. Among these (131)I-dianthrones, (131)I-Hyp exhibited the highest uptake and persistent retention in necrotic tissues. Hepatic infarction could be clearly visualized by SPECT/CT using (131)I-Hyp as an imaging probe. The results suggest that the skeleton structure of Hyp is the lead structure for further structure optimization of this class of NAAs. PMID:26586010

  13. Response-driven Imaging Biomarkers for Predicting Radiation Necrosis of the Brain

    PubMed Central

    Nazem-Zadeh, Mohammad-Reza; Chapman, Christopher H.; Chenevert, Thomas; Lawrence, Theodore S.; Ten Haken, Randall K.; Tsien, Christina I.; Cao, Yue

    2014-01-01

    Purpose Radiation necrosis is an uncommon but severe adverse effect of brain radiation therapy. Current predictive models based on radiation dose have limited accuracy. We aimed to identify early individual response biomarkers based upon diffusion tensor (DT) imaging and incorporated them into a response model for prediction of radiation necrosis. Methods and Materials Twenty-nine patients with glioblastoma received six weeks of intensity modulated radiation therapy (RT) and concurrent temozolamide. Patients underwent DT-MRI scans before treatment, at three weeks during RT, and one, three, and six months after RT. Cases with radiation necrosis were classified based on generalized equivalent uniform dose (gEUD) of whole brain and DT index early changes in the corpus callosum and its substructures. Significant covariates were used to develop normal tissue complication probability models using binary logistic regression. Results Seven patients developed radiation necrosis. Percentage changes of radial diffusivity (RD) in the splenium at three weeks during RT and at six months after RT differed significantly between the patients with and without necrosis (p=0.05 and p=0.01). Percentage change of RD at three weeks during RT in the 30 Gy dose-volume of the splenium and brain gEUD combined yielded the best-fit logistic regression model. Conclusions Our findings indicate that early individual response during the course of RT, assessed by radial diffusivity, has the potential to aid in predicting delayed radiation necrosis, which could provide guidance in dose-escalation trials. PMID:24778364

  14. BALANCER: A Computer Program for Balancing Chemical Equations.

    ERIC Educational Resources Information Center

    Jones, R. David; Schwab, A. Paul

    1989-01-01

    Describes the theory and operation of a computer program which was written to balance chemical equations. Software consists of a compiled file of 46K for use under MS-DOS 2.0 or later on IBM PC or compatible computers. Additional specifications of courseware and availability information are included. (Author/RT)

  15. Decisional balance: Alcohol decisional balance intervention for heavy drinking undergraduates

    PubMed Central

    2015-01-01

    Background This study evaluated a decisional balance intervention among heavy drinking undergraduates and compared a non-weighted decisional balance proportion (DBP; Collins, Carey, & Otto, 2009) to a participant-weighted DBP with weights based on relative importance of items. We expected: 1) the intervention to decrease drinking compared to control; 2) the weighted intervention to be more effective compared to the non-weighted or control in reducing drinking; and 3) intervention efficacy to be moderated by initial DBP. Method Participants (N =162, Mean age = 24.37, SD = 6.81, 27% male) were randomly assigned to an alcohol intervention wherein they were either asked to assign weights of importance to pros and cons (weighted intervention), or not (non-weighted intervention), or to control. Participants completed web-based questionnaires at baseline and again during a one month follow-up assessment. Results Consistent with expectations, the non-weighted intervention was associated with reduced follow-up weekly drinking, and the weighted intervention was associated with reductions in drinking frequency. Results further indicated that initial decisional balance did not moderate intervention efficacy. Discussion Findings suggest that the decisional balance procedure can reduce drinking but there was not compelling evidence for the addition of weights. This study lays the groundwork for enhancing future interventions by increasing empirical knowledge of the role motivation plays in heavy alcohol use. PMID:26555004

  16. Heider balance in human networks

    NASA Astrophysics Data System (ADS)

    Gawroński, P.; Kułakowski, K.

    2005-07-01

    Recently, a continuous dynamics was proposed to simulate dynamics of interpersonal relations in a society represented by a fully connected graph. The final state of such a society was found to be identical with the so-called Heider balance (HB), where the society is divided into two mutually hostile groups. In the continuous model, a polarization of opinions was found in HB. Here we demonstrate that the polarization occurs also in Barabási-Albert networks, where the Heider balance is not necessarily present. In the second part of this work we demonstrate the results of our formalism, when applied to reference examples: the Southern women and the Zachary club.

  17. Current balancing for battery strings

    DOEpatents

    Galloway, James H.

    1985-01-01

    A battery plant is described which features magnetic circuit means for balancing the electrical current flow through a pluraliircuitbattery strings which are connected electrically in parallel. The magnetic circuit means is associated with the battery strings such that the conductors carrying the electrical current flow through each of the battery strings pass through the magnetic circuit means in directions which cause the electromagnetic fields of at least one predetermined pair of the conductors to oppose each other. In an alternative embodiment, a low voltage converter is associated with each of the battery strings for balancing the electrical current flow through the battery strings.

  18. 40 CFR 35.518 - Unexpended balances.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 1 2013-07-01 2013-07-01 false Unexpended balances. 35.518 Section 35... Unexpended balances. Subject to any relevant provisions of law, if a recipient's final Financial Status Report shows unexpended balances, the Regional Administrator will deobligate the unexpended balances...

  19. 40 CFR 35.518 - Unexpended balances.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 1 2010-07-01 2010-07-01 false Unexpended balances. 35.518 Section 35... Unexpended balances. Subject to any relevant provisions of law, if a recipient's final Financial Status Report shows unexpended balances, the Regional Administrator will deobligate the unexpended balances...

  20. 40 CFR 35.518 - Unexpended balances.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 1 2014-07-01 2014-07-01 false Unexpended balances. 35.518 Section 35... Unexpended balances. Subject to any relevant provisions of law, if a recipient's final Financial Status Report shows unexpended balances, the Regional Administrator will deobligate the unexpended balances...

  1. 40 CFR 35.118 - Unexpended balances.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 1 2013-07-01 2013-07-01 false Unexpended balances. 35.118 Section 35... balances. Subject to any relevant provisions of law, if a recipient's Financial Status Report shows unexpended balances, the Regional Administrator will deobligate the unexpended balances and make...

  2. 40 CFR 35.118 - Unexpended balances.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 1 2011-07-01 2011-07-01 false Unexpended balances. 35.118 Section 35... balances. Subject to any relevant provisions of law, if a recipient's Financial Status Report shows unexpended balances, the Regional Administrator will deobligate the unexpended balances and make...

  3. 40 CFR 35.118 - Unexpended balances.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 1 2010-07-01 2010-07-01 false Unexpended balances. 35.118 Section 35... balances. Subject to any relevant provisions of law, if a recipient's Financial Status Report shows unexpended balances, the Regional Administrator will deobligate the unexpended balances and make...

  4. 40 CFR 35.118 - Unexpended balances.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 1 2012-07-01 2012-07-01 false Unexpended balances. 35.118 Section 35... balances. Subject to any relevant provisions of law, if a recipient's Financial Status Report shows unexpended balances, the Regional Administrator will deobligate the unexpended balances and make...

  5. 40 CFR 35.118 - Unexpended balances.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 1 2014-07-01 2014-07-01 false Unexpended balances. 35.118 Section 35... balances. Subject to any relevant provisions of law, if a recipient's Financial Status Report shows unexpended balances, the Regional Administrator will deobligate the unexpended balances and make...

  6. 40 CFR 35.518 - Unexpended balances.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 1 2011-07-01 2011-07-01 false Unexpended balances. 35.518 Section 35... Unexpended balances. Subject to any relevant provisions of law, if a recipient's final Financial Status Report shows unexpended balances, the Regional Administrator will deobligate the unexpended balances...

  7. 40 CFR 35.518 - Unexpended balances.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 1 2012-07-01 2012-07-01 false Unexpended balances. 35.518 Section 35... Unexpended balances. Subject to any relevant provisions of law, if a recipient's final Financial Status Report shows unexpended balances, the Regional Administrator will deobligate the unexpended balances...

  8. Dose–Volume Relationships Associated With Temporal Lobe Radiation Necrosis After Skull Base Proton Beam Therapy

    SciTech Connect

    McDonald, Mark W.; Linton, Okechukwu R.; Calley, Cynthia S.J.

    2015-02-01

    Purpose: We evaluated patient and treatment parameters correlated with development of temporal lobe radiation necrosis. Methods and Materials: This was a retrospective analysis of a cohort of 66 patients treated for skull base chordoma, chondrosarcoma, adenoid cystic carcinoma, or sinonasal malignancies between 2005 and 2012, who had at least 6 months of clinical and radiographic follow-up. The median radiation dose was 75.6 Gy (relative biological effectiveness [RBE]). Analyzed factors included gender, age, hypertension, diabetes, smoking status, use of chemotherapy, and the absolute dose:volume data for both the right and left temporal lobes, considered separately. A generalized estimating equation (GEE) regression analysis evaluated potential predictors of radiation necrosis, and the median effective concentration (EC50) model estimated dose–volume parameters associated with radiation necrosis. Results: Median follow-up time was 31 months (range 6-96 months) and was 34 months in patients who were alive. The Kaplan-Meier estimate of overall survival at 3 years was 84.9%. The 3-year estimate of any grade temporal lobe radiation necrosis was 12.4%, and for grade 2 or higher radiation necrosis was 5.7%. On multivariate GEE, only dose–volume relationships were associated with the risk of radiation necrosis. In the EC50 model, all dose levels from 10 to 70 Gy (RBE) were highly correlated with radiation necrosis, with a 15% 3-year risk of any-grade temporal lobe radiation necrosis when the absolute volume of a temporal lobe receiving 60 Gy (RBE) (aV60) exceeded 5.5 cm{sup 3}, or aV70 > 1.7 cm{sup 3}. Conclusions: Dose–volume parameters are highly correlated with the risk of developing temporal lobe radiation necrosis. In this study the risk of radiation necrosis increased sharply when the temporal lobe aV60 exceeded 5.5 cm{sup 3} or aV70 > 1.7 cm{sup 3}. Treatment planning goals should include constraints on the volume of temporal lobes receiving

  9. Structural insights of homotypic interaction domains in the ligand-receptor signal transduction of tumor necrosis factor (TNF)

    PubMed Central

    Park, Young-Hoon; Jeong, Mi Suk; Jang, Se Bok

    2016-01-01

    Several members of tumor necrosis factor receptor (TNFR) superfamily that these members activate caspase-8 from death-inducing signaling complex (DISC) in TNF ligand-receptor signal transduction have been identified. In the extrinsic pathway, apoptotic signal transduction is induced in death domain (DD) superfamily; it consists of a hexahelical bundle that contains 80 amino acids. The DD superfamily includes about 100 members that belong to four subfamilies: death domain (DD), caspase recruitment domain (CARD), pyrin domain (PYD), and death effector domain (DED). This superfamily contains key building blocks: with these blocks, multimeric complexes are formed through homotypic interactions. Furthermore, each DD-binding event occurs exclusively. The DD superfamily regulates the balance between death and survival of cells. In this study, the structures, functions, and unique features of DD superfamily members are compared with their complexes. By elucidating structural insights of DD superfamily members, we investigate the interaction mechanisms of DD domains; these domains are involved in TNF ligand-receptor signaling. These DD superfamily members play a pivotal role in the development of more specific treatments of cancer. [BMB Reports 2016; 49(3): 159-166] PMID:26615973

  10. Gap Balanced Total Knee Arthroplasty

    MedlinePlus

    Gap Balanced Total Knee Arthroplasty – SIGMA® with AOX™ You must have Javascript enabled in your web browser. View Program Transcript Click Here to view the OR-Live, Inc. Privacy Policy and Legal Notice © 2010 OR-Live, Inc. All rights reserved.

  11. The Mean as Balance Point

    ERIC Educational Resources Information Center

    O'Dell, Robin S.

    2012-01-01

    There are two primary interpretations of the mean: as a leveler of data (Uccellini 1996, pp. 113-114) and as a balance point of a data set. Typically, both interpretations of the mean are ignored in elementary school and middle school curricula. They are replaced with a rote emphasis on calculation using the standard algorithm. When students are…

  12. A Balanced Higher Education System

    ERIC Educational Resources Information Center

    Brown, Roger

    2011-01-01

    This article explores what is meant by "a balanced higher education system". It argues that the Clarkian "triangle of coordination" (Clark, 1983) and the more recent model of Martinez and Richardson (2003) should be replaced by one that distinguishes between "self" and "collective" interests in both the academy and the wider society. Such a scheme…

  13. The Revenue vs. Service Balance

    ERIC Educational Resources Information Center

    Savarese, John

    2006-01-01

    Ten years ago, students at the University of Vermont (UVM) had to carry separate ID cards, meal cards, and athletic cards. Today, the single CATcard combines all of these functions, plus library privileges, an optional declining balance program called CAT$cratch, access to computer labs, use of vending machines without quarters, and even a ride on…

  14. Dual shell pressure balanced vessel

    DOEpatents

    Fassbender, Alexander G.

    1992-01-01

    A dual-wall pressure balanced vessel for processing high viscosity slurries at high temperatures and pressures having an outer pressure vessel and an inner vessel with an annular space between the vessels pressurized at a pressure slightly less than or equivalent to the pressure within the inner vessel.

  15. Dynamic balance in elite karateka.

    PubMed

    Zago, Matteo; Mapelli, Andrea; Shirai, Yuri Francesca; Ciprandi, Daniela; Lovecchio, Nicola; Galvani, Christel; Sforza, Chiarella

    2015-12-01

    In karate, balance control represents a key performance determinant. With the hypothesis that high-level athletes display advanced balance abilities, the purpose of the current study was to quantitatively investigate the motor strategies adopted by elite and non-elite karateka to maintain balance control in competition. The execution of traditional karate techniques (kihon) in two groups of elite Masters (n = 6, 31 ± 19 years) and non-elite Practitioners (n = 4, 25 ± 9 years) was compared assessing body center of mass (CoM) kinematics and other relevant parameters like step width and angular joint behavior. In the considered kihon sequence, normalized average CoM height was 8% lower (p < 0.05), while CoM displacement in the horizontal direction was significantly higher in Masters than in Practitioners (2.5 vs. 1.9 m, p < 0.05), as well as CoM average velocity and rms acceleration (p < 0.05). Step width was higher in Masters in more than half of the sequence steps (p < 0.05). Results suggest that elite karateka showed a refined dynamic balance control, obtained through the increase of the base of support and different maneuvers of lower limbs. The proposed method could be used to objectively detect talented karateka, to measure proficiency level and to assess training effectiveness. PMID:26499923

  16. Balancing Our Personal & Professional Lives.

    ERIC Educational Resources Information Center

    Amy, Chris; Smith, Becky F.

    1996-01-01

    Campus activities programmers are encouraged to balance roles by: remembering their time is valuable; accepting their own imperfection; saying "no" when necessary; taking care of themselves; learning to request help and delegate; giving best time and energy to what matters most; focusing on life's positives; developing support systems; keeping a…

  17. Learning from Balance Sheet Visualization

    ERIC Educational Resources Information Center

    Tanlamai, Uthai; Soongswang, Oranuj

    2011-01-01

    This exploratory study examines alternative visuals and their effect on the level of learning of balance sheet users. Executive and regular classes of graduate students majoring in information technology in business were asked to evaluate the extent of acceptance and enhanced capability of these alternative visuals toward their learning…

  18. Finding Balance in the Winds.

    ERIC Educational Resources Information Center

    Wilbur, Michael

    1999-01-01

    Describes the author's experience of and reflections concerning a group workshop facilitated by Michael Tlanusta Garrett of the Eastern Band of Cherokee. Provides information about the Native American teachings and traditions of the four winds, balance, and harmony, and discusses the use of self by group leaders as a powerful therapeutic and…

  19. Factors in a Balanced Project.

    ERIC Educational Resources Information Center

    Pickens, Diana

    Instructional projects are balanced when the pieces come together at one time with the concurrent approval of all interested parties. The physical analogy of a tripod can serve to illustrate the interaction among three dimensions of all projects: content, or what the course will contain; form, or what the course will look like; and process, or how…

  20. Off-Balance Sheet Financing.

    ERIC Educational Resources Information Center

    Adams, Matthew C.

    1998-01-01

    Examines off-balance sheet financing, the facilities use of outsourcing for selected needs, as a means of saving operational costs and using facility assets efficiently. Examples of using outside sources for energy supply and food services, as well as partnering with business for facility expansion are provided. Concluding comments address tax…

  1. Necrosis of lung epithelial cells during infection with Mycobacterium tuberculosis is preceded by cell permeation.

    PubMed

    Dobos, K M; Spotts, E A; Quinn, F D; King, C H

    2000-11-01

    Mycobacterium tuberculosis establishes infection, progresses towards disease, and is transmitted from the alveolus of the lung. However, the role of the alveolar epithelium in any of these pathogenic processes of tuberculosis is unclear. In this study, lung epithelial cells (A549) were used as a model in which to examine cytotoxicity during infection with either virulent or avirulent mycobacteria in order to further establish the role of the lung epithelium during tuberculosis. Infection of A549 cells with M. tuberculosis strains Erdman and CDC1551 demonstrated significant cell monolayer clearing, whereas infection with either Mycobacterium bovis BCG or Mycobacterium smegmatis LR222 did not. Clearing of M. tuberculosis-infected A549 cells correlated to necrosis, not apoptosis. Treatment of M. tuberculosis-infected A549 cells with streptomycin, but not cycloheximide, demonstrated a significant reduction in the necrosis of A549 cell monolayers. This mycobacterium-induced A549 necrosis did not correlate to higher levels of intracellular or extracellular growth by the mycobacteria during infection. Staining of infected cells with propidium iodide demonstrated that M. tuberculosis induced increased permeation of A549 cell membranes within 24 h postinfection. Quantitation of lactate dehydrogenase (LDH) release from infected cells further demonstrated that cell permeation was specific to M. tuberculosis infection and correlated to A549 cellular necrosis. Inactivated M. tuberculosis or its subcellular fractions did not result in A549 necrosis or LDH release. These studies demonstrate that lung epithelial cell cytotoxicity is specific to infection by virulent mycobacteria and is caused by cellular necrosis. This necrosis is not a direct correlate of mycobacterial growth or of the expression of host cell factors, but is preceded by permeation of the A549 cell membrane and requires infection with live bacilli. PMID:11035739

  2. Predisposing Factors of Liver Necrosis after Transcatheter Arterial Chemoembolization in Liver Metastases from Neuroendocrine Tumor

    SciTech Connect

    Joskin, Julien Baere, Thierry de; Auperin, Anne; Tselikas, Lambros Guiu, Boris Farouil, Geoffroy; Boige, Valérie Malka, David; Leboulleux, Sophie; Ducreux, Michel; Baudin, Eric; Deschamps, Frédéric

    2015-04-15

    PurposeTo investigate predictive factors for liver necrosis after transcatheter arterial chemoembolization (TACE) of neuroendocrine liver metastases.MethodsA total of 164 patients receiving 374 TACE were reviewed retrospectively to analyze predictive factors of liver necrosis. We analyzed patient age and sex; metastasis number and location; percentage of liver involvement; baseline liver function test; and pretreatment imaging abnormalities such as bile duct dilatation (BDD), portal vein narrowing (PVN), and portal vein thrombosis (PVT). We analyzed TACE technique such as Lipiodol or drug-eluting beads (DEB) as the drug’s vector; dose of chemotherapy; diameter of DEB; and number, frequency, and selectivity of TACE.ResultsLiver necrosis developed after 23 (6.1 %) of 374 TACE. In multivariate analysis, DEB > 300 μm in size induced more liver necrosis compared to Lipiodol (odds ratio [OR] 35.20; p < 0.0001) or with DEB < 300 μm in size (OR 19.95; p < 0.010). Pretreatment BDD (OR 119.64; p < 0.0001) and PVT (OR 9.83; p = 0.030) were predictive of liver necrosis. BDD or PVT responsible for liver necrosis were present before TACE in 59 % (13 of 22) and were induced by a previous TACE in 41 % (9 of 22) of cases.ConclusionDEB > 300 μm in size, BDD, and PVT are responsible for increased rate of liver necrosis after TACE. Careful analysis of BDD or PVT on pretreatment images as well as images taken between two courses can help avoid TACE complications.

  3. Avascular necrosis of bone after allogeneic bone marrow transplantation: clinical findings, incidence and risk factors.

    PubMed

    Socié, G; Sélimi, F; Sedel, L; Frija, J; Devergie, A; Esperou Bourdeau, H; Ribaud, P; Gluckman, E

    1994-03-01

    In the present study we describe the incidence, clinical course, and management of avascular necrosis of bone following allogeneic bone marrow transplantation, and identify risk factors related to its development. All patients developing avascular necrosis of bone after allogeneic bone marrow transplantation between January 1974 and September 1992 were included in the analysis and were studied using the Hôpital Saint Louis Bone Marrow Transplant Database and hospital records. 27/727 allogeneic transplant recipients developed avascular necrosis leading to an 8.1% incidence at 5 years, by product limit estimate, ranging from 5% to 11.2%. Symptoms developed 119-1747 d (median 398 d) after transplantation. In these 27 patients a total of 52 joints were affected (mean 1.92 per patient, range 1-7). The hip joint was most often affected (69% of patients). All patients had joint pain that led to diagnosis by means of standard radiographs with or without the help of technetium-99 scans and/or magnetic resonance imaging. All but three patients received steroid therapy for acute graft-versus-host disease. Among 10 factors tested, three were shown to be significantly linked to an increased risk for developing avascular necrosis by multivariate analysis: male gender (relative risk (RR) 4.72, P = 0.002), age older than 16 (RR = 3.87, P = 0.004), and acute graft-versus-host disease requiring steroid therapy (RR = 6.30, P = 0.0002). 10 patients (37%) required joint replacement within 19 months (range 2-42) following diagnosis of avascular necrosis. In conclusion, avascular necrosis of bone is a frequent late complication of allogeneic bone marrow transplantation causing significant morbidity and requiring replacement surgery in one-third of affected patients. In this 18-year single-centre survey, older age, male gender and steroid therapy given for acute graft-versus-host disease were shown to independently increase the risk of avascular necrosis of bone. PMID:8043445

  4. The Oncogenic MicroRNA miR-21 Promotes Regulated Necrosis in Mice

    PubMed Central

    Ma, Xiaodong; Conklin, Daniel J.; Li, Fenge; Dai, Zhongping; Hua, Xiang; Li, Yan; Xu-Monette, Zijun Y.; Young, Ken H.; Xiong, Wei; Wysoczynski, Marcin; Sithu, Srinivas D.; Srivastava, Sanjay; Bhatnagar, Aruni; Li, Yong

    2015-01-01

    MicroRNAs (miRNAs) regulate apoptosis, yet their role in regulated necrosis remains unknown. miR-21 is overexpressed in nearly all human cancer types and its role as an oncogene is suggested to largely depend on its anti-apoptotic action. Here we show that miR-21 is overexpressed in a murine model of acute pancreatitis, a pathologic condition involving RIP3-dependent regulated necrosis (necroptosis). Therefore, we investigate the role of miR-21 in acute pancreatitis injury and necroptosis. miR-21 deficiency protects against caerulein- or L-arginine-induced acute pancreatitis in mice. miR-21 inhibition using locked-nucleic-acid-modified oligonucleotide effectively reduces pancreatitis severity. miR-21 deletion is also protective in tumor necrosis factor-induced systemic inflammatory response syndrome. These data suggest that miRNAs are critical participants in necroptosis, and miR-21 enhances cellular necrosis by negatively regulating tumor suppressor genes associated with the death-receptor-mediated intrinsic apoptosis pathway and could be a therapeutic target for preventing pathologic necrosis. PMID:25990308

  5. Beethoven's renal disease based on his autopsy: a case of papillary necrosis.

    PubMed

    Schwarz, A

    1993-06-01

    The autopsy report of Ludwig van Beethoven written by Dr Johann Wagner in 1827 reveals that he had renal calculi that had not been diagnosed during his lifetime, together with perirenal fibrosis. The most comprehensive interpretation of this autopsy finding is that the regular calcareous deposits in every one of his renal calices represented calcified necrotic papillae. Severe urinary obstruction or diabetes as possible causes of papillary necrosis were not present. Analgesic abuse because of headaches, back pain, and attacks of rheumatism or gout may be presumed on the basis of Beethoven's uncontrolled way of taking medication. Salicin, a commonly used analgesic substance of that time (dried and powdered willow bark), is able to cause papillary necrosis. Perirenal fibrosis may be due to chronic infection or drug intake. Beethoven's other well-known diseases are deafness caused by otosclerosis of the inner ear, relapsing attacks of diarrhea as the symptoms of irritable bowel syndrome, and liver cirrhosis following viral hepatitis and chronic alcohol consumption. Liver cirrhosis also may cause papillary necrosis. In Beethoven's case, renal papillary necrosis was most probably the consequence of analgesic abuse together with decompensated liver cirrhosis. The autopsy report of Beethoven is the first case of papillary necrosis recorded in the literature. PMID:8503419

  6. A Novel Murine Model for Localized Radiation Necrosis and its Characterization Using Advanced Magnetic Resonance Imaging

    SciTech Connect

    Jost, Sarah C.; Hope, Andrew; Kiehl, Erich; Perry, Arie; Travers, Sarah; Garbow, Joel R.

    2009-10-01

    Purpose: To develop a murine model of radiation necrosis using fractionated, subtotal cranial irradiation; and to investigate the imaging signature of radiation-induced tissue damage using advanced magnetic resonance imaging techniques. Methods and Materials: Twenty-four mice each received 60 Gy of hemispheric (left) irradiation in 10 equal fractions. Magnetic resonance images at 4.7 T were subsequently collected using T1-, T2-, and diffusion sequences at selected time points after irradiation. After imaging, animals were killed and their brains fixed for correlative histologic analysis. Results: Contrast-enhanced T1- and T2-weighted magnetic resonance images at months 2, 3, and 4 showed changes consistent with progressive radiation necrosis. Quantitatively, mean diffusivity was significantly higher (mean = 0.86, 1.13, and 1.24 {mu}m{sup 2}/ms at 2, 3, and 4 months, respectively) in radiated brain, compared with contralateral untreated brain tissue (mean = 0.78, 0.82, and 0.83 {mu}m{sup 2}/ms) (p < 0.0001). Histology reflected changes typically seen in radiation necrosis. Conclusions: This murine model of radiation necrosis will facilitate investigation of imaging biomarkers that distinguish between radiation necrosis and tumor recurrence. In addition, this preclinical study supports clinical data suggesting that diffusion-weighted imaging may be helpful in answering this diagnostic question in clinical settings.

  7. Avascular necrosis of the femoral head at 2 years after pertrochanteric fracture surgery: Case report

    PubMed Central

    Deleanu, Bogdan; Prejbeanu, Radu; Vermesan, Dinu; Honcea, Lucian; Mioc, Mihail Lazar; Tsiridis, Eleftherios; Predescu, Vlad

    2015-01-01

    Introduction The avascular necrosis of the femoral head represents the death of bone tissue due to the lack of blood supply. The disease has a progressive evolution and left untreated leads to femoral head collapse and severe arthritis. Case presentation We present a case of a pertrochanteric fracture which has been successfully operated with a dynamic interlocking trochanteric gamma nail on the right hip. At 2 years after surgery the patient developed an incipient avascular necrosis of the femoral head. Despite the good positioning of the implant, we considered that the source of the pain was an intolerance of the implant, and thus we removed it. After implant removal, the patient was kept under observation and conservative treatment, to prevent further damage to the right hip and allow the healing to occur. At 6 months after the gamma nail was removed the X-rays revealed advanced avascular necrosis of the femoral head and secondary osteoarthritis on the right hip. The patient underwent surgery with an uncemented total hip arthroplasty. Discussion There are a few discussions regarding the avascular necrosis of the femoral head. These discussions may include the predisposing risk factors, the treatment of choice and the postoperative complications. Conclusion The avascular necrosis of the femoral head is a complication of pertrochanteric fractures that can not be foreseen or avoided. The optimal treatment in these cases is uncemented total hip arthroplasty. PMID:26900462

  8. Risk factors for mastectomy flap necrosis following immediate tissue expander breast reconstruction.

    PubMed

    Mlodinow, Alexei S; Fine, Neil A; Khavanin, Nima; Kim, John Y S

    2014-10-01

    Tissue expander placement is a mainstay of reconstructive surgery in the post-mastectomy patient. Necrosis of the native breast tissue is one of the most significant concerns in their post-operative care. The goal of this study is to elucidate factors that confer risk of this outcome. Chart review was conducted for a consecutive series of immediate tissue expander reconstructions by the two senior authors. Data was collected for several preoperative and intraoperative variables, as well as the outcome of mastectomy flap necrosis. Of the 1566 breasts that were examined, 135 (8.6%) experienced flap necrosis. The cohorts with and without flap necrosis were well matched. Those with the outcome of interest had significantly higher rates of switching to an autologous method of reconstruction (31.9% vs 6.2%, p < 0.001). Regression analysis revealed smoking status, increased age, tumescent mastectomy technique, and high (>66.67%) intraoperative tissue expander fill to confer increased risk of mastectomy flap necrosis. While smoking and older age are well-supported by the literature, tumescent technique and tissue expander fill are more novel points of discussion, which may serve as proxies for other issues. Awareness of these risk factors and their interplay will aid in clinical judgement and postoperative care of these patients. PMID:24495186

  9. Apoptosis and necrosis during the circadian cycle in the centipede midgut.

    PubMed

    Rost-Roszkowska, M M; Chajec, Ł; Vilimova, J; Tajovský, K

    2016-07-01

    Three types of cells have been distinguished in the midgut epithelium of two centipedes, Lithobius forficatus and Scolopendra cingulata: digestive, secretory, and regenerative cells. According to the results of our previous studies, we decided to analyze the relationship between apoptosis and necrosis in their midgut epithelium and circadian rhythms. Ultrastructural analysis showed that these processes proceed in a continuous manner that is independent of the circadian rhythm in L. forficatus, while in S. cingulata necrosis is activated at midnight. Additionally, the description of apoptosis and necrosis showed no differences between males and females of both species analyzed. At the beginning of apoptosis, the cell cytoplasm becomes electron-dense, apparently in response to shrinkage of the cell. Organelles such as the mitochondria, cisterns of endoplasmic reticulum transform and degenerate. Nuclei gradually assume lobular shapes before the apoptotic cell is discharged into the midgut lumen. During necrosis, however, the cytoplasm of the cell becomes electron-lucent, and the number of organelles decreases. While the digestive cells of about 10 % of L. forficatus contain rickettsia-like pathogens, the corresponding cells in S. cingulata are free of rickettsia. As a result, we can state that apoptosis in L. forficatus is presumably responsible for protecting the organism against infections, while in S. cingulata apoptosis is not associated with the elimination of pathogens. Necrosis is attributed to mechanical damage, and the activation of this process coincides with proliferation of the midgut regenerative cells at midnight in S. cingulata. PMID:26277351

  10. Correlation of MRI Biomarkers with Tumor Necrosis in Hras5 Tumor Xenograft in Athymic Rats

    PubMed Central

    Bradley, Daniel P; Tessier, Jean J; Ashton, Susan E; Waterton, John C; Wilson, Zena; Worthington, Philip L; Ryan, Anderson J

    2007-01-01

    Magnetic resonance imaging (MRI) can measure the effects of therapies targeting the tumor vasculature and has demonstrated that vascular-damaging agents (VDA) induce acute vascular shutdown in tumors in human and animal models. However, at subtherapeutic doses, blood flow may recover before the induction of significant levels of necrosis. We present the relationship between changes in MRI biomarkers and tumor necrosis. Multiple MRI measurements were taken at 4.7 T in athymic rats (n = 24) bearing 1.94 ± 0.2-cm3 subcutaneous Hras5 tumors (ATCC 41000) before and 24 hours after clinically relevant doses of the VDA, ZD6126 (0–10 mg/kg, i.v.). We measured effective transverse relaxation rate (R2*), initial area under the gadolinium concentration-time curve (IAUGC60/150), equivalent enhancing fractions (EHF60/150), time constant (Ktrans), proportion of hypoperfused voxels as estimated from fit failures in Ktrans analysis, and signal intensity (SI) in T2-weighted MRI (T2W). ZD6126 treatment induced > 90% dose-dependent tumor necrosis at 10 mg/kg; correspondingly, SI changes were evident from T2W MRI. Although R2* did not correlate, other MRI biomarkers significantly correlated with necrosis at doses of ≥ 5 mg/kg ZD6126. These data on Hras5 tumors suggest that the quantification of hypoperfused voxels might provide a useful biomarker of tumor necrosis. PMID:17534443

  11. Coumadin-induced skin necrosis in a 64 year-old female despite LMWH bridging therapy

    PubMed Central

    Kumar, Mehandar; Abrina, Vanessa Mae; Chittimireddy, Sasikala

    2012-01-01

    Summary Background: Coumadin is the standard oral anticoagulant used in a variety of clinical conditions. Coumadin inhibits the vitamin-K dependent gamma-carboxylation of coagulation factors II, VII, IX, X and the anticoagulant proteins C and S. Rarely, skin necrosis occurs when the resultant initial procoagulant state in the first few days of starting coumadin leads to thrombosis and formation of blood clots tin the dermal capillaries. This in turn causes skin necrosis due to interruption in blood supply to the skin. Case Report: We are presenting the case of a 64 year-old female admitted for acute respiratory distress secondary to newly-diagnosed pulmonary embolism. The patient was started on therapeutic doses of low molecular weight heparin (LMWH) and coumadin. After 5 days of treatment, the patient started complaining of pain and numbness in both upper extremities. Overnight, this rapidly progressed to manifest hemorrhagic bullae with necrotic areas. This was immediately recognized as coumadin-induced skin necrosis. Coumadin was stopped immediately. Vitamin K was administered and local wound care was provided. Therapeutic LMWH was continued. The skin lesions began to show improvement after 3 days. Conclusions: In coumadin-induced skin necrosis, the patient initially presents with pain and erythema, followed by petechial lesions which progress to become purpuric. Hemorrhagic bullae with necrosis and eschar formation may soon develop. Once it is suspected, coumadin should be stopped and the patient should be given Vitamin K and FFP to reverse the effects of coumadin. PMID:23569516

  12. The relevance of clinical balance assessment tools to differentiate balance deficits

    PubMed Central

    Mancini, Martina; Horak, Fay B

    2011-01-01

    Control of balance is complex and involves maintaining postures, facilitating movement, and recovering equilibrium. Balance control consists of controlling the body center of mass over its limits of stability. Clinical balance assessment can help assess fall risk and/or determine the underlying reasons for balance disorders. Most functional balance assessment scales assess fall risk and the need for balance rehabilitation but do not differentiate types of balance deficits. A system approach to clinical balance assessment can differentiate different kinds of balance disorders and a physiological approach can determine underlying sensorimotor mechanisms contributing to balance disorders. Objective measures of balance using computerized systems and wearable inertial sensors can bring more sensitive, specific and responsive balance testing to clinical practice. PMID:20485226

  13. Balance Dysfunction in Parkinson's Disease

    PubMed Central

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

    2015-01-01

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

  14. Energy balance in coronal funnels

    NASA Technical Reports Server (NTRS)

    Rabin, Douglas

    1991-01-01

    The energy balance in magnetic flux tubes is examined semianalytically for the case in which thermal conduction balances radiation or in which enthalpy transport occurs. Different values are considered for areal constriction, shape, length, and maximum temperature. The overall energy budget of the solar corona is not significantly affected by magnetic constriction. A bowl-shaped funnel with a constriction factor of 4 describes the empirical differential-emission measure for log-T values between approximately 5.3 and 6.0. Loop-scaling relationships are derived for the full range of models to illustrate the dependence of the constant of proportionality on the properties of the magnetic constriction. Constriction can reduce the total energy requirement of the funnel by a factor of 5 and not affect the differential emission in flow-dominated models.

  15. Balanced pressure gerotor fuel pump

    DOEpatents

    Raney, Michael Raymond; Maier, Eugen

    2004-08-03

    A gerotor pump for pressurizing gasoline fuel is capable of developing pressures up to 2.0 MPa with good mechanical and volumetric efficiency and satisfying the durability requirements for an automotive fuel pump. The pump has been designed with optimized clearances and by including features that promote the formation of lubricating films of pressurized fuel. Features of the improved pump include the use of a shadow port in the side plate opposite the outlet port to promote balancing of high fuel pressures on the opposite sides of the rotors. Inner and outer rotors have predetermined side clearances with the clearances of the outer rotor being greater than those of the inner rotor in order to promote fuel pressure balance on the sides of the outer rotor. Support of the inner rotor and a drive shaft on a single bushing with bearing sleeves maintains concentricity. Additional features are disclosed.

  16. Meridional energy balance of Jupiter

    NASA Technical Reports Server (NTRS)

    Pirraglia, J. A.

    1984-01-01

    The meridional energy balance of Jupiter is calculated from high spatial resolution observations by the Voyager 1 infrared spectrometer and radiometer. On a hemispheric scale Jupiter radiates thermal energy to space approximately uniform with latitude while solar energy absorption varies approximately as the solar angle. This implies internal adjustment to the solar energy with a larger contribution poleward of + or - 45 deg than in the equatorial zone. The internal flux is modulated by the major visible features of the zone and belt system but, unlike the hemispheric scale where increased internal flux is correlated with decreased solar absorption, on smaller scales the inverse occurs. The energy balance is very likely to be controlled by dynamics, but the relative influence of the upper atmosphere and the interior is not yet clear.

  17. Complete lives in the balance.

    PubMed

    Kerstein, Samuel J; Bognar, Greg

    2010-04-01

    The allocation of scarce health care resources such as flu treatment or organs for transplant presents stark problems of distributive justice. Persad, Wertheimer, and Emanuel have recently proposed a novel system for such allocation. Their "complete lives system" incorporates several principles, including ones that prescribe saving the most lives, preserving the most life-years, and giving priority to persons between 15 and 40 years old. This paper argues that the system lacks adequate moral foundations. Persad and colleagues' defense of giving priority to those between 15 and 40 leaves them open to the charge that they discriminate unfairly against children. Second, the paper contends that the complete lives system fails to provide meaningful practical guidance in central cases, since it contains no method for balancing its principles when they conflict. Finally, the paper proposes a new method for balancing principles of saving the most lives and maximizing life-years. PMID:20379920

  18. Balanced input-output assignment

    NASA Technical Reports Server (NTRS)

    Gawronski, W.; Hadaegh, F. Y.

    1989-01-01

    Actuator/sensor locations and balanced representations of linear systems are considered for a given set of controllability and observability grammians. The case of equally controlled and observed states is given special attention. The assignability of grammians is examined, and the conditions for their existence are presented, along with several algorithms for their determination. Although an arbitrary positive semidefinite matrix is not always assignable, the identity grammian is shown to be always assignable. The results are extended to the case of flexible structures.

  19. Constrained Allocation Flux Balance Analysis.

    PubMed

    Mori, Matteo; Hwa, Terence; Martin, Olivier C; De Martino, Andrea; Marinari, Enzo

    2016-06-01

    New experimental results on bacterial growth inspire a novel top-down approach to study cell metabolism, combining mass balance and proteomic constraints to extend and complement Flux Balance Analysis. We introduce here Constrained Allocation Flux Balance Analysis, CAFBA, in which the biosynthetic costs associated to growth are accounted for in an effective way through a single additional genome-wide constraint. Its roots lie in the experimentally observed pattern of proteome allocation for metabolic functions, allowing to bridge regulation and metabolism in a transparent way under the principle of growth-rate maximization. We provide a simple method to solve CAFBA efficiently and propose an "ensemble averaging" procedure to account for unknown protein costs. Applying this approach to modeling E. coli metabolism, we find that, as the growth rate increases, CAFBA solutions cross over from respiratory, growth-yield maximizing states (preferred at slow growth) to fermentative states with carbon overflow (preferred at fast growth). In addition, CAFBA allows for quantitatively accurate predictions on the rate of acetate excretion and growth yield based on only 3 parameters determined by empirical growth laws. PMID:27355325

  20. Momentum balance in wall jets

    NASA Astrophysics Data System (ADS)

    Johansson, T. Gunnar; Mehdi, Faraz; Naughton, Jonathan W.

    2012-11-01

    A plane wall jet experiment has been done to study its momentum balance. Two component laser Doppler anemometry was used to simultaneously measure the axial and wall-normal velocity components in 6 axial positions (x/H= 25, 50, 75, 100, 125 and 150) spanning from the wall all the way well into the ambient stagnant area. In this way not only the mean velocity components and Reynolds normal and shear stresses but also all their spatial derivatives were determined. In addition the wall shear stress was measured in all six axial positions using oil film interferometry. From these data all terms in the x-momentum equation, except the pressure term, could be evaluated. Later also the pressure was measured in the same profiles, and thereby also the pressure term was included in the balance. Contrary to common belief it was found that the pressure was not constant in the wall jet. The complete momentum balance is discussed and used to evaluate the roles played by the different contributing terms in different regions of the flow field in an effort to improve on our understanding of the mechanics of wall jets.

  1. Constrained Allocation Flux Balance Analysis

    PubMed Central

    Mori, Matteo; Hwa, Terence; Martin, Olivier C.

    2016-01-01

    New experimental results on bacterial growth inspire a novel top-down approach to study cell metabolism, combining mass balance and proteomic constraints to extend and complement Flux Balance Analysis. We introduce here Constrained Allocation Flux Balance Analysis, CAFBA, in which the biosynthetic costs associated to growth are accounted for in an effective way through a single additional genome-wide constraint. Its roots lie in the experimentally observed pattern of proteome allocation for metabolic functions, allowing to bridge regulation and metabolism in a transparent way under the principle of growth-rate maximization. We provide a simple method to solve CAFBA efficiently and propose an “ensemble averaging” procedure to account for unknown protein costs. Applying this approach to modeling E. coli metabolism, we find that, as the growth rate increases, CAFBA solutions cross over from respiratory, growth-yield maximizing states (preferred at slow growth) to fermentative states with carbon overflow (preferred at fast growth). In addition, CAFBA allows for quantitatively accurate predictions on the rate of acetate excretion and growth yield based on only 3 parameters determined by empirical growth laws. PMID:27355325

  2. Myxomatous stromal changes and necrosis of bone marrow--a retrospective study of 3 years.

    PubMed

    Gupta, Nalini; Kumar, Vijay; Varma, Neelam; Garewal, Gurjeevan; Das, Reena; Ahluwalia, Jasmina; Dash, Sumitra

    2004-07-01

    Myxomatous stromal changes and bone marrow necrosis (BMN) are uncommon histologic findings. These changes have been found in various conditions like disseminated carcinomatosis, postchemotherapy cases, chronic infections, infiltrative disorders of the marrow etc. The present study is a retrospective study of 3 years (Jan, 1999 to Dec. 2001) from Deptt. Of Hematology, Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh (India). During this period, 3740 bone marrow samples were examined. Myxomatous stromal changes and bone marrow necrosis were noted in 0.43% (16/3740) and 0.45% (17/3740) samples respectively. In addition to common causes of myxomatous stromal changes and bone marrow necrosis as described in the literature, this study highlights the association of these conditions with some of the rarer entities like hyperoxalosis, leishmaniasis, parvovirus induced marrow aplasia and cryptococcal infection. There is paucity of such associations in the literature. PMID:16295422

  3. Adrenocortical hemorrhagic necrosis: the role of catecholamines and retrograde medullary-cell embolism

    SciTech Connect

    Szabo, S.; McComb, D.J.; Kovacs, K.; Huettner, I.

    1981-10-01

    We investigated the pathogenesis of adrenal necrosis using animal models of the disease (induced by administration of acrylonitrile, cysteamine, or pyrazole) and human cases. Results of electron-microscopic and histochemical time-response studies with rat models revealed an early, retrograde embolization of medullary cells and cell fragments in the cortical capillaries that showed prominent endothelial injury. The experimental adrenal lesions were prevented by surgical removal of the medulla one month before administration of adrenocorticolytic chemicals, or by the administration of the alpha-adrenergic antagonist phenoxybenzamine hydrochloride. Histochemical staining for medullary (argyrophil) granules in human cases of adrenal necrosis demonstrated tissue fragments that stained positively for silver in vascular cortical spaces in nine of ten autopsy specimens and in all four surgical cases we reviewed. Thus, catecholamines released from the adrenal medulla and from the retrograde medullary emboli in the cortex may have a role in the pathogenesis of adrenocortical necrosis.

  4. Use of tumor necrosis factor (TNF) inhibitors in patients with HIV/AIDS.

    PubMed

    Gallitano, Stephanie M; McDermott, Laura; Brar, Kanwaljit; Lowenstein, Eve

    2016-05-01

    Patients with HIV and AIDS are living longer because of advancements in antiretroviral therapy. These patients are often susceptible to debilitating inflammatory disorders that are refractory to standard treatment. We discuss the relationship of tumor necrosis factor-alpha and HIV and then review 27 published cases of patients with HIV being treated with tumor necrosis factor-alpha inhibitors. This review is limited because no randomized controlled trials have been performed with this patient population. Regardless, we propose that reliable seropositive patients, who are adherent to medication regimens and frequent monitoring and have failed other treatment modalities, should be considered for treatment with tumor necrosis factor-alpha inhibitors. PMID:26774690

  5. Delayed-type Necrosis after Soft-tissue Augmentation with Hyaluronic Acid.

    PubMed

    Souza Felix Bravo, Bruna; Klotz De Almeida Balassiano, Laila; Roos Mariano Da Rocha, Camila; Barbosa De Sousa Padilha, Carolina; Martinezt Torrado, Carolina; Teixeira Da Silva, Roberta; Carlos Regazzi Avelleira, João

    2015-12-01

    The growing use of dermal fillers, specifically the use of hyaluronic acid, can be explained by their effectiveness and versatility as well as their favorable safety profiles. Nevertheless, early and late complications with varying levels of severity may occur. The incidence of complications is low and the majority of adverse events are mild (edema, erythema, and local ecchymosis) and of limited duration. However, more severe events, such as ischemia and necrosis, may occur. The symptoms of ischemia can occur immediately after the injection or several hours after the procedure. Here, the authors report three cases of necrosis after hyaluronic acid injection with the first symptoms presenting only several hours after the procedure. The patients were treated immediately after the diagnosis. The aim of this review is to communicate the possibility of the delayed-type presentation of necrosis, present the signs and symptoms that lead to early diagnosis, and review the treatment possibilities of this severe complication. PMID:26705447

  6. Experimental study on cheng zai wan for treatment of necrosis of the femoral head.

    PubMed

    Chen, Yanping; Huang, Keqin; Lang, Fengping; Huang, Yongxun; Huang, Hui; Huang, Hong; Zhou, Chongguang; Zhang, Wanqiang

    2003-12-01

    Cheng Zai Wan ([symbol: see text]), a Chinese herbal preparation was administrated in the two-leg rat model of aseptic necrosis of the femoral head established by taking prednisone acetate for a long period and the osteoporosis model rat by castration in order to explore the effects of the prescription on necrosis of the femoral head. The results showed that after treatment, the pitting on the surface of the femoral head disappeared, the reticular structure with filling cells was restored; the fat droplets in bone cells or cartilage cells of the femoral head were significantly reduced; sparse capillaries were improved, density and width of the bone trabecula were increased somewhat; bone mineral density, bone weight, bone strength and rigidity were significantly increased; and the low level of estrin was improved. It is suggested that Cheng Zai Wan has definite therapeutic effects on aseptic necrosis of the femoral head. PMID:14719304

  7. Delayed-type Necrosis after Soft-tissue Augmentation with Hyaluronic Acid

    PubMed Central

    Klotz De Almeida Balassiano, Laila; Roos Mariano Da Rocha, Camila; Barbosa De Sousa Padilha, Carolina; Martinezt Torrado, Carolina; Teixeira Da Silva, Roberta; Carlos Regazzi Avelleira, João

    2015-01-01

    The growing use of dermal fillers, specifically the use of hyaluronic acid, can be explained by their effectiveness and versatility as well as their favorable safety profiles. Nevertheless, early and late complications with varying levels of severity may occur. The incidence of complications is low and the majority of adverse events are mild (edema, erythema, and local ecchymosis) and of limited duration. However, more severe events, such as ischemia and necrosis, may occur. The symptoms of ischemia can occur immediately after the injection or several hours after the procedure. Here, the authors report three cases of necrosis after hyaluronic acid injection with the first symptoms presenting only several hours after the procedure. The patients were treated immediately after the diagnosis. The aim of this review is to communicate the possibility of the delayed-type presentation of necrosis, present the signs and symptoms that lead to early diagnosis, and review the treatment possibilities of this severe complication. PMID:26705447

  8. Binge Eating Leading to Acute Gastric Dilatation, Ischemic Necrosis and Rupture -A Case Report.

    PubMed

    Dewangan, Manish; Khare, Manish Kumar; Mishra, Sumanta; Marhual, Jogesh Chandra

    2016-03-01

    Acute gastric dilatation is a rarely encountered clinical scenario in our day to day practice. This is very rapidly progressing condition and can lead to ischemic necrosis and perforation/rupture of the stomach. It could be fatal if not timely intervened. We report such a case of a 17-year-old, otherwise healthy boy, who presented with pain and distension of abdomen following binge eating episode after 24 hours of prolonged fasting. On exploration, stomach was dilated with necrosis and perforation at fundus near greater curvature. He was managed with excision of all the devitalized area and primary repair with feeding jejunostomy. The case is presented due to its rarity. Acute gastric dilatation (AGD) leading to ischemic necrosis and perforation because of binge eating episode in an otherwise healthy person is an exceptional occurrence with only few cases reported in literature. The clinician should be aware of this condition for prompt and appropriate management. PMID:27134932

  9. A case of warfarin skin necrosis despite enoxaparin anticoagulation in a patient with protein S deficiency.

    PubMed

    Tai, Chau Y; Ierardi, Ralph; Alexander, James B

    2004-03-01

    Warfarin-induced skin necrosis is a rare complication associated with the use of oral anticoagulants. Most patients develop this at the initiation of therapy, often while still receiving intravenous unfractionated heparin (UFH). Recently, low-molecular-weight heparins (LMWHs) have gained wider use, providing an option for outpatient treatment of deep-vein thrombosis. The treatment protocols are similar to UFH, including the early initiation of oral anticoagulation with warfarin. A Medline search failed to reveal any cases of warfarin-induced skin necrosis while using a LMWH. We present a patient with protein S deficiency who developed warfarin skin necrosis despite appropriate anticoagulation with enoxaparin, and review the chemical and clinical difference between UFH and LMWH. PMID:15253263

  10. A genetic system involving superoxide causes F1 necrosis in wheat (T. aestivum L.).

    PubMed

    Khanna-Chopra, R; Dalal, M; Kumar, G P; Laloraya, M

    1998-07-30

    A genetic system in wheat is described in which F1 produced by crossing a drought tolerant cultivar C306 and high yielding cultivar WL711 exhibits leaf necrosis leading to the death of the plant. The mechanism underlying hybrid necrosis is not yet known. The hybrid exhibited a higher level of superoxide anion compared to the healthy leaves of parents at similar developmental stages. This increase in superoxide generation preceded necrotic lesion formation and displayed a gradient from the leaf tip to base. The leaf tip where necrotic lesions make their first appearance exhibited a higher level of superoxide compared to the base. Superoxide anion thus appears to play a vital role in necrosis of leaves in F1 hybrid. This genetic system can be a model system for understanding cell death in higher plants. PMID:9703992

  11. Binge Eating Leading to Acute Gastric Dilatation, Ischemic Necrosis and Rupture –A Case Report

    PubMed Central

    Khare, Manish Kumar; Mishra, Sumanta; Marhual, Jogesh Chandra

    2016-01-01

    Acute gastric dilatation is a rarely encountered clinical scenario in our day to day practice. This is very rapidly progressing condition and can lead to ischemic necrosis and perforation/rupture of the stomach. It could be fatal if not timely intervened. We report such a case of a 17-year-old, otherwise healthy boy, who presented with pain and distension of abdomen following binge eating episode after 24 hours of prolonged fasting. On exploration, stomach was dilated with necrosis and perforation at fundus near greater curvature. He was managed with excision of all the devitalized area and primary repair with feeding jejunostomy. The case is presented due to its rarity. Acute gastric dilatation (AGD) leading to ischemic necrosis and perforation because of binge eating episode in an otherwise healthy person is an exceptional occurrence with only few cases reported in literature. The clinician should be aware of this condition for prompt and appropriate management. PMID:27134932

  12. Segmental myofiber necrosis in myotonic dystrophy - An immunoperoxidase study of immunoglobulins in skeletal muscle.

    PubMed Central

    Silver, M. M.; Banerjee, D.; Hudson, A. J.

    1983-01-01

    Because serum immunoglobulin G levels are low in patients with myotonic dystrophy, it was hypothesized that it might be catabolized within abnormal muscle fibers. Accordingly, immunohistochemical stains for immunoglobulins were performed on muscle sections derived at biopsy or autopsy from patients with myotonic dystrophy, other forms of muscular dystrophy, nondystrophic muscle disease, or normal muscle. Positive staining for immunoglobulins was found only in necrotic segments of myofibers (in 7 of 19 dystrophic and 6 of 27 nondystrophic subjects), and it is believed that the staining was due to nonspecific diffusion. However, staining reactions distinguished between incipient necrosis and artifactual contraction bands and allowed us to study segmental myofiber necrosis, comparing its frequency in the various muscle diseases. Segmental myofiber necrosis was present in 4 of 16 cases of myotonic dystrophy. The relevance of this finding to the clinical and morphologic features of myotonic dystrophy is discussed. Images Figure 1 Figure 2 Figure 3 Figure 4 PMID:6351629

  13. Removal of displaced double flanged metal stent in walled-off necrosis by endoscopic ultrasonography

    PubMed Central

    Guo, Jintao; Liu, Zhijun; Sun, Siyu; Liu, Xiang; Wang, Sheng

    2016-01-01

    Endoscopic ultrasonography (EUS)-guided walled-off necrosis drainage using a double flanged metal stent was reported for satisfactory drainage and endoscopic necrosectomy. High complication rates related to stent migration are reported. This is the first report of the removal of a displaced, double flanged metal stent in walled-off necrosis by EUS. The patient was a 62-year-old male who was suffering from mild midepigastric abdominal pain. A double flanged metal stent had been placed in our endoscopy center 8 weeks before presentation. Computed tomography demonstrated complete resolution of the walled-off necrosis; however, the stent migrated into the cyst. We dislodged the stent using forceps with real-time endosonography. In conclusion, Follow-up is important for patients with a double flanged metal stent, specifically with regards to postprocedural stent migration. PMID:27080613

  14. Efficacy of virtual reality-based balance training versus the Biodex balance system training on the body balance of adults

    PubMed Central

    Ibrahim, Manal S.; Mattar, Ayman G.; Elhafez, Salam M.

    2016-01-01

    [Purpose] This study investigated efficacy of virtual reality (VR)-based balance training on enhancing balance and postural reactions of adults as a low-cost new modality compared to the established Biodex Balance System (BBS). [Subjects] Thirty normal adults of both genders were divided randomly into two equal-sized experimental groups of 15: BBS balance training and VR balance training. [Methods] The training programmes were conducted in 12 sessions, three 15-min sessions per week. The Nintendo® Wii Fit Plus (NWFP) and its balance board were used to train of the VR group. Each participant answered a questionnaire concerning usability, enjoyment, balance improvement, and fatigue at the end of the training programs. [Results] The study found a significant increase the measure of mean overall balance (OLB) in both groups. No significant difference was found between the groups, but a significant decrease in the mean balance-test time was found for both groups, with no significant difference between the two training methods. The VR programme was rated highly enjoyable by 81.8% of the group. [Conclusion] The Wii Fit Plus system with the balance board as a new VR balance-training technique, can be considered an effective and enjoyable tool for the training of adults’ body balance. PMID:26957722

  15. Efficacy of virtual reality-based balance training versus the Biodex balance system training on the body balance of adults.

    PubMed

    Ibrahim, Manal S; Mattar, Ayman G; Elhafez, Salam M

    2016-01-01

    [Purpose] This study investigated efficacy of virtual reality (VR)-based balance training on enhancing balance and postural reactions of adults as a low-cost new modality compared to the established Biodex Balance System (BBS). [Subjects] Thirty normal adults of both genders were divided randomly into two equal-sized experimental groups of 15: BBS balance training and VR balance training. [Methods] The training programmes were conducted in 12 sessions, three 15-min sessions per week. The Nintendo(®) Wii Fit Plus (NWFP) and its balance board were used to train of the VR group. Each participant answered a questionnaire concerning usability, enjoyment, balance improvement, and fatigue at the end of the training programs. [Results] The study found a significant increase the measure of mean overall balance (OLB) in both groups. No significant difference was found between the groups, but a significant decrease in the mean balance-test time was found for both groups, with no significant difference between the two training methods. The VR programme was rated highly enjoyable by 81.8% of the group. [Conclusion] The Wii Fit Plus system with the balance board as a new VR balance-training technique, can be considered an effective and enjoyable tool for the training of adults' body balance. PMID:26957722

  16. Dietary ergot alkaloids as a possible cause of tail necrosis in rabbits.

    PubMed

    Korn, A K; Gross, M; Usleber, E; Thom, N; Köhler, K; Erhardt, G

    2014-11-01

    This study describes the association between tail necrosis in rabbits and mycotoxins in rabbit feed. Clinical cases of tail necrosis were observed in 14 out of 103 rabbits kept in an outdoor group housing, fed with hay and a commercial pelleted feed. The observed clinical symptoms, alopecia, erosions, crusts and necrosis were restricted to the tail area and exclusively occurred in young rabbits aged 113 ± 20 days. Dermatological examination suggested that ischemia had caused necrosis. Analysis of blood samples showed an elevated level of creatine kinase. No weight loss occurred in affected rabbits. Trauma caused by injuries or technopathic lesions was also excluded. Histopathologically, the lesions were characterized by acute muscle fibre degeneration and chronic active dermatitis with granulation tissue formation. Necropsy of one rabbit revealed hepatocellular degeneration and necrosis as remarkable findings. Feed analysis for ergot alkaloids by enzyme immunoassays yielded a mean and maximum ergot alkaloid content of 410 ± 250 μg/kg and 1,700 μg/kg, respectively. Faeces of affected rabbits contained ergot alkaloids at levels up to 200 μg/kg. The mean and maximum dietary intake of total ergot alkaloids were 17 and 71 μg/kg bodyweight, respectively. Fusarium toxins (trichothecenes, zearalenone, fumonisins) were also found in the feed, but at levels which did not explain the observed effects. The results indicate that ergot alkaloids may have been the cause of tail necrosis, which is supported by literature data showing that rabbits are especially sensitive towards these toxins. PMID:25234267

  17. Detectable Subclinical Myocardial Necrosis Is Associated With Cardiovascular Risk in Stable Patients With Diabetes

    PubMed Central

    Tang, W.H. Wilson; Wu, Yuping; Britt, Earl B.; Iqbal, Naveed; Hazen, Stanley L.

    2013-01-01

    OBJECTIVE To investigate the relationship between different degrees of subclinical myocardial necrosis, glycemic control, and long-term adverse clinical outcomes within a stable patient population with diabetes mellitus. RESEARCH DESIGN AND METHODS We examined 1,275 stable patients with diabetes mellitus undergoing elective diagnostic coronary angiography with cardiac troponin I (cTnI) levels below the diagnostic cut-off for defining myocardial infarction (MI) (<0.03 ng/mL). The relationship of subclinical myocardial necrosis (cTnI 0.009–0.029 ng/mL) with incident major adverse cardiovascular events (MACE; defined as any death, MI, or stroke) over 3 years of follow-up was examined. RESULTS Subclinical myocardial necrosis was observed in 22% of patients. A strong association was observed between the magnitude of subclinical myocardial necrosis and risk of 3-year incident MACE (hazard ratio, 1.98; 95% confidence interval, 1.48–2.65; P < 0.001) and remained statistically significant even after adjustment for traditional risk factors, high-sensitivity C-reactive protein, and creatinine clearance. Only a weak correlation was observed between the presence of subclinical myocardial necrosis and either glycemic control (r = 0.06; P = 0.044 for hemoglobin A1c versus cTnI) or insulin resistance (r = 0.04; P = 0.094 for glucose-to-insulin ratio versus cTnI). CONCLUSIONS The presence of detectable subclinical myocardial necrosis in stable patients with diabetes mellitus is associated with heightened long-term risk for MACE, independent of traditional risk factors and glycemic control. PMID:23393213

  18. A GSK-3β Inhibitor Protects Against Radiation Necrosis in Mouse Brain

    SciTech Connect

    Jiang, Xiaoyu; Perez-Torres, Carlos J.; Thotala, Dinesh; Engelbach, John A.; Yuan, Liya; Cates, Jeremy; Gao, Feng; Drzymala, Robert E.; Rich, Keith M.; Schmidt, Robert E.; Ackerman, Joseph J.H.; Hallahan, Dennis E.; Garbow, Joel R.

    2014-07-15

    Purpose: To quantify the effectiveness of SB415286, a specific inhibitor of GSK-3β, as a neuroprotectant against radiation-induced central nervous system (brain) necrosis in a mouse model. Methods and Materials: Cohorts of mice were treated with SB415286 or dimethyl sulfoxide (DMSO) prior to irradiation with a single 45-Gy fraction targeted to the left hemisphere (brain) using a gamma knife machine. The onset and progression of radiation necrosis (RN) were monitored longitudinally by noninvasive in vivo small-animal magnetic resonance imaging (MRI) beginning 13 weeks postirradiation. MRI-derived necrotic volumes for SB415286- and DMSO-treated mice were compared. MRI results were supported by correlative histology. Results: Mice treated with SB415286 showed significant protection from radiation-induced necrosis, as determined by in vivo MRI with histologic validation. MRI-derived necrotic volumes were significantly smaller at all postirradiation time points in SB415286-treated animals. Although the irradiated hemispheres of the DMSO-treated mice demonstrated many of the classic histologic features of RN, including fibrinoid vascular necrosis, vascular telangiectasia, hemorrhage, and tissue loss, the irradiated hemispheres of the SB415286-treated mice consistently showed only minimal tissue damage. These studies confirmed that treatment with a GSK-3β inhibitor dramatically reduced delayed time-to-onset necrosis in irradiated brain. Conclusions: The unilateral cerebral hemispheric stereotactic radiation surgery mouse model in concert with longitudinal MRI monitoring provided a powerful platform for studying the onset and progression of RN and for developing and testing new neuroprotectants. Effectiveness of SB415286 as a neuroprotectant against necrosis motivates potential clinical trials of it or other GSK-3β inhibitors.

  19. Lipolysis of Visceral Adipocyte Triglyceride by Pancreatic Lipases Converts Mild Acute Pancreatitis to Severe Pancreatitis Independent of Necrosis and Inflammation

    PubMed Central

    Patel, Krutika; Trivedi, Ram N.; Durgampudi, Chandra; Noel, Pawan; Cline, Rachel A.; DeLany, James P.; Navina, Sarah; Singh, Vijay P.

    2016-01-01

    Visceral fat necrosis has been associated with severe acute pancreatitis (SAP) for over 100 years; however, its pathogenesis and role in SAP outcomes are poorly understood. Based on recent work suggesting that pancreatic fat lipolysis plays an important role in SAP, we evaluated the role of pancreatic lipases in SAP-associated visceral fat necrosis, the inflammatory response, local injury, and outcomes of acute pancreatitis (AP). For this, cerulein pancreatitis was induced in lean and obese mice, alone or with the lipase inhibitor orlistat and parameters of AP induction (serum amylase and lipase), fat necrosis, pancreatic necrosis, and multisystem organ failure, and inflammatory response were assessed. Pancreatic lipases were measured in fat necrosis and were overexpressed in 3T3-L1 cells. We noted obesity to convert mild cerulein AP to SAP with greater cytokines, unsaturated fatty acids (UFAs), and multisystem organ failure, and 100% mortality without affecting AP induction or pancreatic necrosis. Increased pancreatic lipase amounts and activity were noted in the extensive visceral fat necrosis of dying obese mice. Lipase inhibition reduced fat necrosis, UFAs, organ failure, and mortality but not the parameters of AP induction. Pancreatic lipase expression increased lipolysis in 3T3-L1 cells. We conclude that UFAs generated via lipolysis of visceral fat by pancreatic lipases convert mild AP to SAP independent of pancreatic necrosis and the inflammatory response. PMID:25579844

  20. Progressive Scleral Necrosis following I-125 Plaque Radiotherapy for Ciliochoroidal Melanoma with Protruding Extraocular Mass

    PubMed Central

    Hill, Jordan R.; Corrêa, Zélia M.

    2016-01-01

    Purpose The aim of this study was to describe the side effects of I-125 brachytherapy in the treatment of uveal melanoma. Methods This study was conducted as a case report. Results We report a case of scleral necrosis and protruding episcleral mass following the treatment of uveal melanoma with I-125 brachytherapy. Conclusions Scleral necrosis after plaque radiotherapy can clinically simulate tumor recurrence with extraocular extension. The management of uveal melanoma requires a careful clinical follow-up, weighing the implications of treatment morbidity and mortality. PMID:27239452

  1. Colonic Necrosis in a 4-Year-Old with Hyperlipidemic Acute Pancreatitis

    PubMed Central

    Patton, Tiffany J.; Sentongo, Timothy A.; Mak, Grace Z.; Kahn, Stacy A.

    2016-01-01

    Here we report the case of a 4-year-old male with severe acute pancreatitis due to hyperlipidemia, who presented with abdominal pain, metabolic abnormalities, and colonic necrosis. This colonic complication was secondary to the extension of a large peripancreatic fluid collection causing direct serosal autodigestion by pancreatic enzymes. Two weeks following the initial presentation, the peripancreatic fluid collection developed into a mature pancreatic pseudocyst, which was percutaneously drained. To our knowledge, this is the youngest documented pediatric case of colonic necrosis due to severe pancreatitis and the first descriptive pediatric case of a colonic complication due to hyperlipidemia-induced acute pancreatitis. PMID:26925282

  2. Treatment of glabella skin necrosis following injection of hyaluronic acid filler using platelet-rich plasma.

    PubMed

    Kang, Boo Kyoung; Kang, In Jung; Jeong, Ki Heon; Shin, Min Kyung

    2016-01-01

    Hyaluronic acid (HA) fillers have been widely used for soft-tissue augmentation. However, there can be various complications following HA filler injection. Skin necrosis is rare but one of the most disastrous side effects that, if not treated promptly and effectively, can result in permanent and potentially disfiguring scarring. Thus, early proper management is important. Herein we report a patient who experienced tissue necrosis of the glabellar area after receiving filler injections that was successfully treated using platelet-rich plasma and provide full follow-up clinical photographs. PMID:26052808

  3. Ischemic Necrosis of Upper Lip, and All Fingers and Toes After Norepinephrine Use.

    PubMed

    Shin, Jin Yong; Roh, Si-Gyun; Lee, Nae-Ho; Yang, Kyung-Moo

    2016-03-01

    A 68-year-old woman with necrosis of total finger, toe, and upper lip was requested by department of internal medicine. She was diagnosed with septic shock and treated with norepinephrine 10 days ago. Norepinephrine is an often-used medicine for normalizing blood pressure in septic shock patients. Norepinephrine stimulates adrenergic receptors, causing vasoconstriction and the rise of blood pressure. These peripheral vasoconstrictions sometimes lead to ischemic changes in end organs. In this case report, the authors describe ischemic necrosis of the upper lip and all fingers and toes after norepinephrine use in a patient in the intensive care unit. PMID:26854781

  4. SLC25A19 mutation as a cause of neuropathy and bilateral striatal necrosis.

    PubMed

    Spiegel, Ronen; Shaag, Avraham; Edvardson, Simon; Mandel, Hanna; Stepensky, Polina; Shalev, Stavit A; Horovitz, Yoseph; Pines, Ophry; Elpeleg, Orly

    2009-09-01

    Four patients, aged 7-20 years, suffered from recurrent episodes of flaccid paralysis and encephalopathy associated with bilateral striatal necrosis and chronic progressive polyneuropathy. Using homozygosity mapping, a pathogenic missense mutation in the SLC25A19 gene that encodes the mitochondrial thiamine pyrophosphate transporter was identified. An SLC25A19 mutation was previously reported in Amish congenital lethal microcephaly but the present patients' phenotype is markedly different, with normal head circumference, normal early childhood development, age-appropriate cognitive skills, and normal urinary organic acid profile. Determination of the SLC25A19 sequence should be considered in patients with bilateral striatal necrosis and progressive polyneuropathy. PMID:19798730

  5. Alcohol-Dependent Liver Cell Necrosis in vitro: A New Model

    NASA Astrophysics Data System (ADS)

    Schanne, Francis A. X.; Zucker, Amy H.; Farber, John L.; Rubin, Emanuel

    1981-04-01

    In alcoholic liver injury, necrosis is involved in the progression from benign fatty liver to alcoholic hepatitis and cirrhosis. However, there is no practical model of alcohol-dependent liver cell necrosis. The calcium-dependent killing of cultured rat hepatocytes by two different membrane-active hepatotoxins, galactosamine and phalloidin, is potentiated by ethyl alcohol. This indicates that some general physical effect of alcohol on cellular membranes renders cells susceptible to otherwise nonlethal injuries. The in vitro model described in this report may thus be used to search for a general mechanism underlying alcohol-related tissue injury.

  6. Intravascular gas in the transplanted kidney: a sign of extensive graft necrosis.

    PubMed

    Ishigami, Kousei; Olsen, Kim M; Hammet, Bradley K; Katz, Daniel A; Wu, You Min

    2004-04-01

    We encountered a case of transplanted kidney necrosis, with computed tomography (CT) demonstrating multiple areas of intravascular gas within the allograft. The intravascular gas represented air emboli from gas liberated from fermentation by gas-forming organisms in a perinephric abscess. Arterial bleeding accelerated by the wound infection and the resultant large perinephric hematoma caused renal infarction. Gas-forming infection of transplanted organs is associated with a poor graft outcome, which can present as a fulminant clinical course. Intravascular gas should be distinguished from collecting system gas because the former could represent extensive necrosis of the transplanted kidney. PMID:15290479

  7. Gluteal Necrosis and Lumbosacral Plexopathy in a Diabetic Patient after Renal Transplantation

    PubMed Central

    Asgari, M. A.; Masoumi, N.; Argani, H.

    2015-01-01

    A 34-year-old diabetic patient underwent a renal transplant which was complicated by right side lower extremity paresis and numbness with gluteal necrosis. The main reason was ligation of internal iliac artery of the same side as a result of extensive microvascular obstruction due to severe atheromatous plaque. This is a rare complication which is mostly reported in aneurysmal patients after bypass surgery. The gluteal necrosis is a serious complication which, as in our patient, resulted in patient's death in most of the reported cases. Because of catastrophic nature of this condition, identifying preventive measures is extremely important. PMID:26793402

  8. Dabigatran in the Treatment of Warfarin-Induced Skin Necrosis: A New Hope

    PubMed Central

    Bakoyiannis, Christos; Karaolanis, Georgios; Patelis, Nikolaos; Maskanakis, Anastasios; Tsaples, Georgios; Klonaris, Christos; Georgopoulos, Sotirios; Liakakos, Theodoros

    2016-01-01

    Warfarin-induced skin necrosis is an infrequent and well-recognized complication of warfarin treatment. The incidence was estimated between 0.01% and 0.1% whereas a paradoxal prothrombotic state that arises from warfarin therapy seems to be responsible for this life-threatening disease. To the best of our knowledge we present the first case of an old woman diagnosed with warfarin-induced skin necrosis, in whom novel oral anticoagulants and extensive surgical debridement were combined safely with excellent results. PMID:27110410

  9. Unilamellar liposomes modulate secretion of tumor necrosis factor by lipopolysaccharide-stimulated macrophages.

    PubMed Central

    Brisseau, G F; Kresta, A; Schouten, D; Bohnen, J M; Shek, P N; Fok, E; Rotstein, O D

    1994-01-01

    Liposomal encapsulation of antimicrobial agents has been used to improve drug delivery, particularly against intracellular pathogens. The effect of unilamellar liposomes on macrophage activation in response to Escherichia coli lipopolysaccharide was examined. Liposomes caused a dose- and time-dependent inhibition of tumor necrosis factor release by lipopolysaccharide-treated cells. The accumulation of tumor necrosis factor mRNA transcripts was unaffected, suggesting a posttranscriptional mechanism for this effect. However, induction of macrophage procoagulant activity was unaffected by liposomes, indicating a selective rather than a global inhibition. These data suggest that liposomes used for drug delivery may modulate the host response to infection. Images PMID:7872768

  10. TRAIL-induced programmed necrosis as a novel approach to eliminate tumor cells

    PubMed Central

    2014-01-01

    Background The cytokine TRAIL represents one of the most promising candidates for the apoptotic elimination of tumor cells, either alone or in combination therapies. However, its efficacy is often limited by intrinsic or acquired resistance of tumor cells to apoptosis. Programmed necrosis is an alternative, molecularly distinct mode of programmed cell death that is elicited by TRAIL under conditions when the classical apoptosis machinery fails or is actively inhibited. The potential of TRAIL-induced programmed necrosis in tumor therapy is, however, almost completely uncharacterized. We therefore investigated its impact on a panel of tumor cell lines of wide-ranging origin. Methods Cell death/viability was measured by flow cytometry/determination of intracellular ATP levels/crystal violet staining. Cell surface expression of TRAIL receptors was detected by flow cytometry, expression of proteins by Western blot. Ceramide levels were quantified by high-performance thin layer chromatography and densitometric analysis, clonogenic survival of cells was determined by crystal violet staining or by soft agarose cloning. Results TRAIL-induced programmed necrosis killed eight out of 14 tumor cell lines. Clonogenic survival was reduced in all sensitive and even one resistant cell lines tested. TRAIL synergized with chemotherapeutics in killing tumor cell lines by programmed necrosis, enhancing their effect in eight out of 10 tested tumor cell lines and in 41 out of 80 chemotherapeutic/TRAIL combinations. Susceptibility/resistance of the investigated tumor cell lines to programmed necrosis seems to primarily depend on expression of the pro-necrotic kinase RIPK3 rather than the related kinase RIPK1 or cell surface expression of TRAIL receptors. Furthermore, interference with production of the lipid ceramide protected all tested tumor cell lines. Conclusions Our study provides evidence that TRAIL-induced programmed necrosis represents a feasible approach for the elimination of

  11. Dissecting Cellulitis of the Scalp Responding to Intravenous Tumor Necrosis Factor-alpha Antagonist.

    PubMed

    Wollina, Uwe; Gemmeke, Astrid; Koch, André

    2012-04-01

    The authors present the case of a 30-year-old male patient with a severe and long-standing dissecting cellulitis of the scalp. The disease did not respond to conventional treatment, including oral antibiotics, isotretinoin, and prednisolone. Quality of life was significantly impaired. After introduction of anti-tumor necrosis factor-alpha treatment (infliximab), the malodorous discharge stopped, inflammation was reduced significantly, nodules became flat, and pain decreased. The treatment was well tolerated although he developed a temporary psoriasiform rash after the second intravenous infusion. In conclusion, anti-tumor necrosis factor-alpha treatment is a new therapeutic option in this severe and recalcitrant disorder. PMID:22708007

  12. PARTIAL NECROSIS OF THE LUNATE AFTER A TRANSLUNATE PALMAR PERILUNATE FRACTURE DISLOCATION

    PubMed Central

    AKANE, MAO; TATEBE, MASAHIRO; IYODA, KAZUHITO; OTA, KYOTARO; IWATSUKI, KATSUYUKI; YAMAMOTO, MICHIRO; HIRATA, HITOSHI

    2014-01-01

    ABSTRACT We present an extreme rare case of traumatic partial avascular necrosis of the lunate after palmar perilunate dislocation with lunate fracture. A 32-year-old female was injured by motorcycle accident with palmar perilunate fracture dislocation and lunate fracture. Scapholunate and lunotriquetrum dislocations were reduced and fixed temporarily. The torn dorsal ligament was repaired. Considering close observation with both arthroscopy and fluoroscopy, we decided not to conduct open reduction and internal fixation for the lunate. Partial avascular necrosis of the lunate appeared gradually in follow-up. PMID:25130008

  13. Classical syndromes in occupational medicine: phosphorus necrosis--a classical occupational disease

    SciTech Connect

    Felton, J.S.

    1982-01-01

    A disease nearly extinct in occupational health history is phosphorus necrosis, previously seen in near-epidemic proportions among workers making phosphorus-containing matches. Similar destructive lesions were encountered early in the 20th century among personnel fabricating fireworks. Through the diligent efforts of an economist and a supportive congressman, legislation was passed in 1912 placing a tax on phosphorus matches, and because of the fiscal burden resulting, a nontoxic substitute for elemental phosphorus was adopted by all manufacturers. Today phosphorus necrosis is extremely rare, but the former presence of the disease points up both apathy and courage in the identification and eradication of a remarkably disfiguring work-caused disease.

  14. Necrosis of the tail of pancreas following proximal splenic artery embolization.

    PubMed

    Talving, Peep; Rauk, Mariliis; Vipp, Liisa; Isand, Karl-Gunnar; Šamarin, Aleksandr; Põder, Kalle; Rätsep, Indrek; Saar, Sten

    2016-01-01

    The current case report presents a rare complication of a significant pancreatic tail necrosis following proximal splenic artery embolization in a 32-year-old male patient involved in a motorcycle accident. Proximal angiographic embolization of the splenic injury after trauma is a widely accepted method with excellent success rate; however, possible complications may occur and has been described in the literature. Nevertheless, only a few case reports pertinent to clinically significant pancreatic tail necrosis after the SAE has been reported. Thus, we add a case report to the scarce literature pertinent to this detrimental and rare complication. PMID:27177891

  15. Necrosis of the tail of pancreas following proximal splenic artery embolization

    PubMed Central

    Talving, Peep; Rauk, Mariliis; Vipp, Liisa; Isand, Karl-Gunnar; Šamarin, Aleksandr; Põder, Kalle; Rätsep, Indrek; Saar, Sten

    2016-01-01

    The current case report presents a rare complication of a significant pancreatic tail necrosis following proximal splenic artery embolization in a 32-year-old male patient involved in a motorcycle accident. Proximal angiographic embolization of the splenic injury after trauma is a widely accepted method with excellent success rate; however, possible complications may occur and has been described in the literature. Nevertheless, only a few case reports pertinent to clinically significant pancreatic tail necrosis after the SAE has been reported. Thus, we add a case report to the scarce literature pertinent to this detrimental and rare complication. PMID:27177891

  16. Colonic Necrosis in a 4-Year-Old with Hyperlipidemic Acute Pancreatitis.

    PubMed

    Patton, Tiffany J; Sentongo, Timothy A; Mak, Grace Z; Kahn, Stacy A

    2016-01-01

    Here we report the case of a 4-year-old male with severe acute pancreatitis due to hyperlipidemia, who presented with abdominal pain, metabolic abnormalities, and colonic necrosis. This colonic complication was secondary to the extension of a large peripancreatic fluid collection causing direct serosal autodigestion by pancreatic enzymes. Two weeks following the initial presentation, the peripancreatic fluid collection developed into a mature pancreatic pseudocyst, which was percutaneously drained. To our knowledge, this is the youngest documented pediatric case of colonic necrosis due to severe pancreatitis and the first descriptive pediatric case of a colonic complication due to hyperlipidemia-induced acute pancreatitis. PMID:26925282

  17. Warfarin-induced skin necrosis diagnosed on clinical grounds and treated with maggot debridement therapy

    PubMed Central

    Biscoe, Anna Louise; Bedlow, Alison

    2013-01-01

    A patient with a history of deep vein thrombosis presented with painful bruising and blistering on his left leg 7–10 days after warfarin treatment. A complicated 2-month treatment followed, where vasculitis was originally diagnosed from histological findings before the final diagnosis of warfarin-induced skin necrosis (WISN) was made on clinical grounds. Warfarin was stopped, reversed and low molecular weight heparin started but, the lesions had progressed to full thickness necrosis. This was originally treated with conventional surgical debridement before introducing maggot debridement therapy (MDT) in an effort to try to salvage the limb. PMID:23362073

  18. State of balance of the cryosphere

    NASA Technical Reports Server (NTRS)

    Van Der Veen, C. J.

    1991-01-01

    Available observations and mass balance estimates of the cryosphere are summarized. Problems discussed include mountain glaciers, the Greenland ice sheet, the Antarctic ice sheet, conventional glacier measurement techniques, and satellite applications in glacier mass balance studies. It is concluded that the interior part of the Greenland ice sheet is thickening or in near equilibrium. Estimates of the mass balance of the Antarctic ice sheet suggest that it is positive, although the error limits allow for a slightly negative balance.

  19. 2 CFR 200.98 - Unobligated balance.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 2 Grants and Agreements 1 2014-01-01 2014-01-01 false Unobligated balance. 200.98 Section 200.98... REQUIREMENTS FOR FEDERAL AWARDS Acronyms and Definitions Acronyms § 200.98 Unobligated balance. Unobligated balance means the amount of funds under a Federal award that the non-Federal entity has not obligated....

  20. Electronic Elections: A Balancing Act

    NASA Astrophysics Data System (ADS)

    Rezende, Pedro A. D.

    This article aims to share some major lessons learned from the pioneering experience in Brazil with the world's first full national implementation of universal electronic voting. Differing notions of security, and their "collateral entanglements", appear to play a key role and are contrasted in Brazil's pioneering electronic voting saga. After an introduction, we puzzle through what election security may mean. We elaborate on how technological innovations may affect the underlying risks, their nature, corrections and balance. Then we describe some ways in which innovations have been deployed and validated, and how the results are being perceived, before some closing remarks.