WorldWideScience

Sample records for biological disease modifying

  1. Biological response modifiers and their potential use in the treatment of inflammatory skin diseases

    DEFF Research Database (Denmark)

    Villadsen, Louise S; Skov, Lone; Baadsgaard, Ole

    2003-01-01

    and fewer side-effects than the current systemic therapies now used for severe psoriasis, contact dermatitis and atopic dermatitis. In the pathogenesis of inflammatory skin diseases, the immune system plays a pivotal role, and this is where biological response modifiers such as monoclonal antibodies......In recent years, a more detailed understanding of the pathogenesis of several inflammatory skin diseases, combined with the developments within biotechnology, has made it possible to design more selective response modifiers. Biological response modifiers hold the potential for greater effectiveness......, recombinant cytokines, or fusion proteins may be effective. Several biological response modifiers have already shown positive results in phase II/III clinical trials in skin diseases, and many new biological response modifiers are in progress....

  2. Searching for disease-modifying drugs in AD: can we combine neuropsychological tools with biological markers?

    Science.gov (United States)

    Caraci, Filippo; Castellano, Sabrina; Salomone, Salvatore; Drago, Filippo; Bosco, Paolo; Di Nuovo, Santo

    2014-02-01

    Drug discovery efforts in Alzheimer's disease (AD) have been directed in the last ten years to develop "disease-modifying drugs" able to exert neuroprotective effects in an early phase of AD pathogenesis. Unfortunately several candidate disease-modifying drugs have failed in Phase III clinical trials conducted in mild to moderate AD for different methodological difficulties, such as the time course of treatment in relation to development of disease as well as the appropriate use of validated biological and neuropsychological markers. Mild cognitive impairment (MCI) has been considered a precursor of AD. Much effort is now directed to identify the most appropriate and sensitive markers which can predict the progression from MCI to AD, such as neuroimaging markers (e.g. hippocampal atrophy and amyloid positron emission tomography imaging), cerebrospinal fluid markers (i.e. association of elevated tau with low levels of amyloid β -peptide(1-42) and neuropsychological markers (i.e. episodic memory deficits and executive dysfunction). Recent studies demonstrate that the combination of these different biomarkers significantly increases the chance to predict the conversion into AD within 24 months. These biomarkers will be essential in the future to analyze clinical efficacy of disease-modifying drugs in MCI patients at high risk to develop AD. In the present review we analyze recent evidence on the combination of neuropsychological and biological markers in AD as a new tool to track disease progression in early AD as well as the response to disease-modifying drugs. PMID:24040795

  3. Implications of Rheumatic Disease and Biological Response-Modifying Agents in Plastic Surgery.

    Science.gov (United States)

    Tsai, David M; Borah, Gregory L

    2015-12-01

    The preoperative evaluation for any reconstructive or aesthetic procedure requires a detailed history of existing medical conditions and current home medications. The prevalence of rheumatic diseases such as rheumatoid arthritis, gout, and psoriasis is high, but the impact of these chronic illnesses on surgical outcome and the side effects of the powerful medications used for treatment are often underappreciated. In this review, the authors highlight key perioperative considerations specific to rheumatologic diseases and their associated pharmacologic therapies. In particular, the authors discuss the perioperative management of biological response-modifying agents, which have largely become the new standard of therapy for many rheumatic diseases. The literature reveals three key perioperative concerns with biological therapy for rheumatic disease: infection, wound healing delays, and disease flare. However, data on specific perioperative complications are lacking, and it remains controversial whether withholding biological therapy before surgery is of benefit. The risk of these adverse events is influenced by several factors: age, sex, class of biological agent, duration of exposure, dosage, onset and severity of disease, and type of surgical procedure. Overall, it remains best to develop an individualized plan. In younger patients with recent onset of biological therapy, it is reasonable to withhold therapy based on 3 to 5 half-lives of the specific agent. In older patients with a substantial history of rheumatic disease, the decision to discontinue therapy must be weighed and decided carefully in conjunction with the rheumatologist. PMID:26595025

  4. Ten years of publicly funded biological disease-modifying antirheumatic drugs in Australia.

    Science.gov (United States)

    Hopkins, Ashley M; Proudman, Susanna M; Vitry, Agnes I; Sorich, Michael J; Cleland, Leslie G; Wiese, Michael D

    2016-02-01

    Biological disease-modifying antirheumatic drugs (bDMARDs) for rheumatoid arthritis (RA) treatment were among the first high-cost medicines to be subsidised in Australia. High-cost medicines pose several challenges to the Australian National Medicines Policy, which aims to provide timely access to effective medicines at a cost individuals and the community can afford. Thus, novel restriction criteria were developed to encourage cost-effective use of bDMARDs. Government expenditure on bDMARD subsidies for RA treatment grew to about $383 million in 2014. Evidence that initiation and continuation criteria for bDMARDs meet usually applied cost-benefit criteria is lacking. The combined expenditure on tocilizumab, certolizumab pegol and golimumab (added to the Australian Government's Pharmaceutical Benefits Scheme in 2010) was $93 million in 2014, which is 210% over the initial estimate. Present and future challenges with regard to bDMARDs for RA and other high-cost drugs include improved expenditure predictions, monitoring of cost-effectiveness in relation to actual use and strategic development, regulation and use of biosimilars. Ten years of documentation on clinical and laboratory findings indicating eligibility to initiate and continue on bDMARDs remains un-used. These data represent an untapped opportunity to promote quality of use of bDMARDs and biosimilars and to improve cost predictions for high-cost drugs. PMID:26821102

  5. Assessing the effectiveness of synthetic and biologic disease-modifying antirheumatic drugs in psoriatic arthritis – a systematic review

    Directory of Open Access Journals (Sweden)

    Kingsley GH

    2015-05-01

    Full Text Available Gabrielle H Kingsley, David L Scott Rheumatology Unit, Kings College London, London, UK Background: Psoriatic arthritis is an inflammatory arthritis the primary manifestations of which are locomotor and skin disease. Although a number of guidelines have been published citing strategies for reducing disease progression, the evidence base for disease-modifying agents is unclear. This forms the focus of this systematic review. Methods: The systematic review was undertaken according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2009 checklist. We selected randomized controlled trials (RCTs that looked at the impact of interventions with disease-modifying agents, either synthetic drugs or biologics on musculoskeletal outcomes, notably American College of Rheumatology 20 percent responders. Results were analyzed using Review Manager 5.1.6 (Cochrane Collaboration, Oxford, UK. Whilst our primary focus was on published trials, we also looked at new trials presented in abstract form in 2013–2014 that were not yet published to avoid omitting important and up-to-date information on developing treatments. Results: Our in-depth analysis included 28 trials overall enrolling 5,177 patients published between the 1980s and now as well as limited analysis of some studies in abstract form as described earlier. The most frequently available locomotor outcome measure was the American College of Rheumatology 20 percent responders. The risk ratio for achieving an American College of Rheumatology 20 percent responders response was positive in favor of treatment (risk ratio 2.30; 95% confidence interval 1.78–2.96; however, there was evidence of considerable heterogeneity between trials. Overall randomized controlled trials of established synthetic disease-modifying agents were largely negative (methotrexate, ciclosporin and sulfasalazine though leflunomide showed a small positive effect. A new synthetic agent, apremilast, did show a

  6. Similar effects of disease-modifying antirheumatic drugs, glucocorticoids, and biologic agents on radiographic progression in rheumatoid arthritis: meta-analysis of 70 randomized placebo-controlled or drug-controlled studies, including 112 comparisons

    DEFF Research Database (Denmark)

    Graudal, Niels; Jürgens, Gesche

    2010-01-01

    To define the differences in effects on joint destruction in rheumatoid arthritis (RA) patients between therapy with single and combination disease-modifying antirheumatic drugs (DMARDs), glucocorticoids, and biologic agents.......To define the differences in effects on joint destruction in rheumatoid arthritis (RA) patients between therapy with single and combination disease-modifying antirheumatic drugs (DMARDs), glucocorticoids, and biologic agents....

  7. Methotrexate monotherapy and methotrexate combination therapy with traditional and biologic disease modifying antirheumatic drugs for rheumatoid arthritis: abridged Cochrane systematic review and network meta-analysis

    OpenAIRE

    Hazlewood, Glen S; Barnabe, Cheryl; Tomlinson, George; Marshall, Deborah; Devoe, Dan; Bombardier, Claire

    2016-01-01

    Objective To compare methotrexate based disease modifying antirheumatic drug (DMARD) treatments for rheumatoid arthritis in patients naive to or with an inadequate response to methotrexate. Design Systematic review and Bayesian random effects network meta-analysis of trials assessing methotrexate used alone or in combination with other conventional synthetic DMARDs, biologic drugs, or tofacitinib in adult patients with rheumatoid arthritis. Data sources Trials were identified from Medline, Em...

  8. Safety and Efficacy of Biological Disease-Modifying Antirheumatic Drugs in Older Rheumatoid Arthritis Patients: Staying the Distance.

    Science.gov (United States)

    Ishchenko, Alla; Lories, Rik J

    2016-06-01

    The population of older individuals with rheumatoid arthritis (RA) is rapidly expanding, mainly due to increased life expectancy. While targeted biological therapies are well established for the treatment of this disease, their use may be lower in older patients (age > 65 years) and very old patients (age > 75 years) as a result of perceived higher risks for adverse events in this population, taking into account comorbidity, polypharmacy, and frailty. In this review, we discuss the available evidence for the use of biological therapies in this growing patient group with specific attention towards the eventual reasons for biological treatment failure or withdrawal. The majority of data is found in secondary analyses of clinical trials and in retrospective cohorts. The most information available is on tumor necrosis factor (TNF) blockers. Older patients seem to have a less robust response to anti-TNF agents than a younger population, but drug survival as a proxy for efficacy does not seem to be influenced by age. Despite an overall rate of adverse effects comparable to that in younger patients, older RA patients are at higher risk of serious infections. Other biologics appear to have an efficacy similar to anti-TNF agents, also in older RA patients. Again, the drug survival rates for tocilizumab, rituximab, and abatacept resemble those in young RA patients with good general tolerability and safety profiles. The cardiovascular risk and the risk of cancer, increased in RA patients and in the older RA patients, do not appear to be strongly influenced by biologicals. PMID:27154398

  9. Similar effects of disease-modifying antirheumatic drugs, glucocorticoids, and biologic agents on radiographic progression in rheumatoid arthritis: meta-analysis of 70 randomized placebo-controlled or drug-controlled studies, including 112 comparisons

    DEFF Research Database (Denmark)

    Graudal, Niels; Jürgens, Gesche

    2010-01-01

    To define the differences in effects on joint destruction in rheumatoid arthritis (RA) patients between therapy with single and combination disease-modifying antirheumatic drugs (DMARDs), glucocorticoids, and biologic agents....

  10. Biologics or tofacitinib for rheumatoid arthritis in incomplete responders to methotrexate or other traditional disease-modifying anti-rheumatic drugs

    DEFF Research Database (Denmark)

    Singh, Jasvinder A; Hossain, Alomgir; Tanjong Ghogomu, Elizabeth;

    2016-01-01

    , tocilizumab) and small molecule tofacitinib, versus comparator (MTX, DMARD, placebo (PL), or a combination) in adults with rheumatoid arthritis who have failed to respond to methotrexate (MTX) or other disease-modifying anti-rheumatic drugs (DMARDs), i.e., MTX/DMARD incomplete responders (MTX...... serious adverse events on biologic+MTX/DMARD (Peto OR [can be interpreted as RR due to low event rate] 1.12 (95% CI 0.99 to 1.27); absolute risk 1% (0% to 2%), As well, the NMA estimate for TNF biologic+MTX/DMARD (Peto OR 1.20 (95% Crl 1.01 to 1.43)) showed moderate quality evidence of an increase in the...

  11. Psoriatic arthritis treatment: biological response modifiers.

    Science.gov (United States)

    Mease, P J; Antoni, C E

    2005-03-01

    In recent years there has been a surge of interest in the treatment of chronic inflammatory disorders as a result of the development and application of targeted biological therapies. The elucidation of the overlapping cellular and cytokine immunopathology of such diverse conditions as rheumatoid arthritis (RA), Crohn's disease, and psoriasis points to specific targets for bioengineered proteins or small molecules. Similar to clinical trials in RA, trials in psoriatic arthritis (PsA) have shown excellent clinical results with the tumour necrosis factor (TNF) blockers, etanercept, infliximab, and adalimumab in a variety of domains including the joints, quality of life, function, and slowing of disease progress as evidenced radiologically. In addition, these agents have shown benefit in domains more unique to PsA, such as the skin lesions of psoriasis, enthesitis, and dactylitis, pointing out the similar pathogenesis of the disease in the skin, the tendons, and the synovial membrane. This therapy has been generally safe and well tolerated in clinical trials of PsA. Other logical candidates for targeted therapy in development include other anti-TNF agents, costimulatory blockade agents that affect T cell function, blockers of other cytokines such as interleukin (IL)-1, 6, 12, 15, or 18, and B cell modulatory medicines. Also, it will be useful to learn more about the effects of combining traditional disease modifying drugs and the newer biologicals. PMID:15708944

  12. [Biologics and mycobacterial diseases].

    Science.gov (United States)

    Tsuyuguchi, Kazunari; Matsumoto, Tomoshige

    2013-03-01

    Various biologics such as TNF-alpha inhibitor or IL-6 inhibitor are now widely used for treatment of rheumatoid arthritis. Many reports suggested that one of the major issues is high risk of developing tuberculosis (TB) associated with using these agents, which is especially important in Japan where tuberculosis still remains endemic. Another concern is the risk of development of nontuberculous mycobacterial (NTM) diseases and we have only scanty information about it. The purpose of this symposium is to elucidate the role of biologics in the development of mycobacterial diseases and to establish the strategy to control them. First, Dr. Tohma showed the epidemiologic data of TB risks associated with using biologics calculated from the clinical database on National Database of Rheumatic Diseases by iR-net in Japan. He estimated TB risks in rheumatoid arthritis (RA) patients to be about four times higher compared with general populations and to become even higher by using biologics. He also pointed out a low rate of implementation of QuantiFERON test (QFT) as screening test for TB infection. Next, Dr. Tokuda discussed the issue of NTM disease associated with using biologics. He suggested the airway disease in RA patients might play some role in the development of NTM disease, which may conversely lead to overdiagnosis of NTM disease in RA patients. He suggested that NTM disease should not be uniformly considered a contraindication to treatment with biologics, considering from the results of recent multicenter study showing relatively favorable outcome of NTM patients receiving biologics. Patients with latent tuberculosis infection (LTBI) should receive LTBI treatment before starting biologics. Dr. Kato, a chairperson of the Prevention Committee of the Japanese Society for Tuberculosis, proposed a new LTBI guideline including active implementation of LTBI treatment, introducing interferon gamma release assay, and appropriate selection of persons at high risk for

  13. Vaccinations in adults with chronic inflammatory joint disease: Immunization schedule and recommendations for patients taking synthetic or biological disease-modifying antirheumatic drugs.

    Science.gov (United States)

    Morel, Jacques; Czitrom, Séverine Guillaume; Mallick, Auriane; Sellam, Jérémie; Sibilia, Jean

    2016-03-01

    The risk of infection associated with autoimmune diseases is further increased by the use of biotherapies. Recommendations to minimize this risk include administering the full complement of vaccines on the standard immunization schedule, as well as the pneumococcal and influenza vaccines. Adults with chronic inflammatory joint disease (IJD) may receive a 13-valent pneumococcal conjugate vaccine, as well as a live attenuated vaccine against recurrent herpes zoster, recently licensed by European regulatory authorities. Live attenuated vaccines can be given only after an interval without immunosuppressant and/or glucocorticoid therapy. The effectiveness of vaccines, as assessed based on titers of protective antibodies, varies across vaccine types and disease-modifying antirheumatic drugs (DMARDs). Thus, methotrexate and rituximab are usually associated with decreased vaccine responses. The risks associated with vaccines are often considerably exaggerated by the media, which serve lobbies opposed to immunizations and make some patients reluctant to accept immunizations. Increasing immunization coverage may diminish the risk of treatment-related infections. A physician visit dedicated specifically to detecting comorbidities in patients with chronic IJD may result in improved immunization coverage. In this review, we discuss immunizations for adults with chronic IJD based on the treatments used, as well as immunization coverage. Many questions remain unanswered and warrant investigation by studies coordinated by the French networks IREIVAC (Innovative clinical research network in vaccinology) and IMIDIATE (Immune-Mediated Inflammatory Disease Alliance for Translational and Clinical Research). PMID:26453106

  14. Delayed wound healing and postoperative surgical site infections in patients with rheumatoid arthritis treated with or without biological disease-modifying antirheumatic drugs.

    Science.gov (United States)

    Tada, Masahiro; Inui, Kentaro; Sugioka, Yuko; Mamoto, Kenji; Okano, Tadashi; Kinoshita, Takuya; Hidaka, Noriaki; Koike, Tatsuya

    2016-06-01

    Biological disease-modifying antirheumatic drugs (bDMARDs) have become more popular for treating rheumatoid arthritis (RA). Whether or not bDMARDs increase the postoperative risk of surgical site infection (SSI) has remained controversial. We aimed to clarify the effects of bDMARDs on the outcomes of elective orthopedic surgery. We used multivariate logistic regression analysis to analyze risk factors for SSI and delayed wound healing among 227 patients with RA (mean age, 65.0 years; disease duration, 16.9 years) after 332 elective orthopedic surgeries. We also attempted to evaluate the effects of individual medications on infection. Rates of bDMARD and conventional synthetic DMARD (csDMARD) administration were 30.4 and 91.0 %, respectively. Risk factors for SSI were advanced age (odds ratio [OR], 1.11; P = 0.045), prolonged surgery (OR, 1.02; P = 0.03), and preoperative white blood cell count >10,000/μL (OR, 3.66; P = 0.003). Those for delayed wound healing were advanced age (OR, 1.16; P = 0.001), prolonged surgery (OR, 1.02; P = 0.007), preoperative white blood cell count >10,000/μL (OR, 4.56; P = 0.02), and foot surgery (OR, 6.60; P = 0.001). Risk factors for SSI and medications did not significantly differ. No DMARDs were risk factors for any outcome examined. Biological DMARDs were not risk factors for postoperative SSI. Foot surgery was a risk factor for delayed wound healing. PMID:27129711

  15. Biological treatment of Crohn's disease

    DEFF Research Database (Denmark)

    Nielsen, Ole Haagen; Bjerrum, Jacob Tveiten; Seidelin, Jakob Benedict;

    2012-01-01

    Introduction of biological agents for the treatment of Crohn's disease (CD) has led to a transformation of the treatment paradigm. Several biological compounds have been approved for patients with CD refractory to conventional treatment: infliximab, adalimumab and certolizumab pegol (and...

  16. Biologic response modifiers to decrease inflammation: Focus on infection risks

    OpenAIRE

    Le Saux, Nicole

    2012-01-01

    Biologic response modifiers are a novel class of drugs used by sub-specialists to treat immune-mediated conditions such as juvenile idiopathic arthritis and inflammatory bowel disease. Also known as ‘cytokine inhibitors’, they are proteins whose purpose is to block the action of cytokines involved in inflammation. The desired therapeutic effect is to reduce or control inflammation. Tumour necrosis factor-α (TNF-α) inhibitors are the prototypes, but newer agents in this class target other cyto...

  17. Biologics in Paediatric Crohn's Disease

    OpenAIRE

    Oliver Gouldthorpe; Anthony G Catto-Smith; George Alex

    2011-01-01

    Crohn's disease affects increasing numbers of children worldwide. Generally, childhood-onset disease runs a more severe course than in adults and has a greater impact on quality of life. Therapy in children must take account of a different set of risks for toxicity compared to adults, but also to their longevity. Biologic drugs present remarkable advantages in terms of disease control for children, especially in those whose disease cannot be controlled with conventional therapies, but their l...

  18. "Disease modifying nutricals" for multiple sclerosis.

    Science.gov (United States)

    Schmitz, Katja; Barthelmes, Julia; Stolz, Leonie; Beyer, Susanne; Diehl, Olaf; Tegeder, Irmgard

    2015-04-01

    The association between vitamin D and multiple sclerosis has (re)-opened new interest in nutrition and natural compounds in the prevention and treatment of this neuroinflammatory disease. The dietary amount and type of fat, probiotics and biologicals, salmon proteoglycans, phytoestrogens and protease inhibitor of soy, sodium chloride and trace elements, and fat soluble vitamins including D, A and E were all considered as disease-modifying nutraceuticals. Studies in experimental autoimmune encephalomyelitis mice suggest that poly-unsaturated fatty acids and their 'inflammation-resolving' metabolites and the gut microflora may reduce auto-aggressive immune cells and reduce progression or risk of relapse, and infection with whipworm eggs may positively change the gut-brain communication. Encouraged by the recent interest in multiple sclerosis-nutrition nature's pharmacy has been searched for novel compounds with anti-inflammatory, immune-modifying and antioxidative properties, the most interesting being the scorpion toxins that inhibit specific potassium channels of T cells and antioxidative compounds including the green tea flavonoid epigallocatechin-3-gallate, curcumin and the mustard oil glycoside from e.g. broccoli and sulforaphane. They mostly also inhibit pro-inflammatory signaling through NF-κB or toll-like receptors and stabilize the blood brain barrier. Disease modifying functions may also complement analgesic and anti-spastic effects of cannabis, its constituents, and of 'endocannabinoid enhancing' drugs or nutricals like inhibitors of fatty acid amide hydrolase. Nutricals will not solve multiple sclerosis therapeutic challenges but possibly support pharmacological interventions or unearth novel structures. PMID:25435020

  19. The marked and rapid therapeutic effect of tofacitinib in combination with subcutaneous methotrexate in a rheumatoid arthritis patient with poor prognostic factors who is resistant to standard disease-modifying antirheumatic drugs and biologicals: A clinical case

    Directory of Open Access Journals (Sweden)

    N. V. Demidova

    2016-01-01

    Full Text Available Today, it is generally accepted that it is necessary to achieve clinical remission in rheumatoid arthritis (RA or as minimum a low disease activity. The paper describes a clinical case of a female patient diagnosed with RA who was observed to have inefficiency of standard disease-modifying antirheumatic therapy with methotrexate 25 mg/week, secondary inefficiency of tumor necrosis factor-α inhibitors (adalimumab, and inefficiency/poor tolerance of the interlukin-6 receptor antagonist tocilizumab. This determined the need to use fofacitinib (TOFA, a drug with another mechanism of action. TOFA is the first agent from a new group of immunomodulatory and anti-inflammatory drugs, intracellular kinase inhibitors. Disease remission could be achieved during therapy with TOFA, which enables one to consider this synthetic drug as a therapy option that potentially competes with therapy with biologicals.

  20. Genetically Modified Pig Models for Human Diseases

    Institute of Scientific and Technical Information of China (English)

    Nana Fan; Liangxue Lai

    2013-01-01

    Genetically modified animal models are important for understanding the pathogenesis of human disease and developing therapeutic strategies.Although genetically modified mice have been widely used to model human diseases,some of these mouse models do not replicate important disease symptoms or pathology.Pigs are more similar to humans than mice in anatomy,physiology,and genome.Thus,pigs are considered to be better animal models to mimic some human diseases.This review describes genetically modified pigs that have been used to model various diseases including neurological,cardiovascular,and diabetic disorders.We also discuss the development in gene modification technology that can facilitate the generation of transgenic pig models for human diseases.

  1. No predictive effect of body mass index on clinical response in patients with rheumatoid arthritis after 24 weeks of biological disease-modifying antirheumatic drugs: a single-center study.

    Science.gov (United States)

    Kim, Seong-Kyu; Choe, Jung-Yoon; Park, Sung-Hoon; Lee, Hwajeong

    2016-05-01

    The aim of this study was to determine whether body mass index (BMI) is associated with clinical response to biologics in patients with rheumatoid arthritis (RA). We enrolled 68 patients with RA who were treated with biological disease-modifying antirheumatic drugs (bDMARDs). Biologics included abatacept, tocilizumab, and tumor necrosis factor-α (TNF-α) blockers (etanercept and adalimumab). Baseline BMI (kg/m(2)) was classified as normal (BMI < 23.0), overweight (23.0 ≤ BMI < 25.0), or obese (BMI ≥ 25.0). Improvement of disease activity score 28 (DAS28) and achievement of the European League Against Rheumatism (EULAR) remission and responses between baseline and 24 weeks were our measures of clinical improvement. Mean baseline BMI before treatment with bDMARDs in patients with RA was 22.2 (SD 3.6). DAS28-ESR and DAS28-CRP were significantly reduced from baseline after 24 weeks of treatment with bDMARDs (p < 0.001 of both). ∆DAS28-ESR and ∆DAS28-CRP were not found among patients with normal, overweight, or obese BMI (p = 0.133 and p = 0.255, respectively) nor were EULAR responses or EULAR remission (p = 0.540 and p = 0.957, respectively). Logistic regression analysis showed no relationship of BMI with EULAR clinical responses (p = 0.093 for good response and p = 0.878 for EULAR remission). This study reveals that BMI is not a predictive factor of clinical response to bDMARDs in patients with RA. PMID:26932795

  2. Synthetic Biology in Health and Disease

    NARCIS (Netherlands)

    Passel, van M.W.J.; Lam, C.M.C.; Martins dos Santos, V.A.P.; Suarez Diez, M.

    2014-01-01

    Synthetic biology draws on the understanding from genetics, biology, chemistry, physics, engineering, and computational sciences to (re-)design and (re-)engineer biological functions. Here we address how synthetic biology can be possibly deployed to promote health and tackle disease. We discuss how

  3. Mitochondrial Biology and Neurological Diseases.

    Science.gov (United States)

    Arun, Siddharth; Liu, Lei; Donmez, Gizem

    2016-01-01

    Mitochondria are extremely active organelles that perform a variety of roles in the cell including energy production, regulation of calcium homeostasis, apoptosis, and population maintenance through fission and fusion. Mitochondrial dysfunction in the form of oxidative stress and mutations can contribute to the pathogenesis of various neurodegenerative diseases such as Parkinson's (PD), Alzheimer's (AD), and Huntington's diseases (HD). Abnormalities of Complex I function in the electron transport chain have been implicated in some neurodegenerative diseases, inhibiting ATP production and generating reactive oxygen species that can cause major damage to mitochondria. Mutations in both nuclear and mitochondrial DNA can contribute to neurodegenerative disease, although the pathogenesis of these conditions tends to focus on nuclear mutations. In PD, nuclear genome mutations in the PINK1 and parkin genes have been implicated in neurodegeneration [1], while mutations in APP, PSEN1 and PSEN2 have been implicated in a variety of clinical symptoms of AD [5]. Mutant htt protein is known to cause HD [2]. Much progress has been made to determine some causes of these neurodegenerative diseases, though permanent treatments have yet to be developed. In this review, we discuss the roles of mitochondrial dysfunction in the pathogenesis of these diseases. PMID:26903445

  4. Phosphocitrate Is Potentially a Disease-Modifying Drug for Noncrystal-Associated Osteoarthritis

    OpenAIRE

    Yubo Sun; Mauerhan, David R.; Franklin, Atiya M.; James Norton; Hanley, Edward N; Gruber, Helen E.

    2013-01-01

    Phosphocitrate (PC), a calcification inhibitor, inhibits the development of crystal-associated osteoarthritis (OA) in Hartley guinea pigs. However, the molecular mechanisms underlying its disease-modifying effect remain elusive. This study sought to test the hypothesis that PC has calcium crystal-independent biological activities which are, at least in part, responsible for its disease-modifying activity. We found that PC inhibited the proliferation of OA fibroblast-like synoviocytes in the a...

  5. Optimizing biological therapy in Crohn's disease.

    Science.gov (United States)

    Gecse, Krisztina Barbara; Végh, Zsuzsanna; Lakatos, Péter László

    2016-01-01

    Anti-TNF therapy has revolutionized the treatment of inflammatory bowel diseases, including both Crohn's disease and ulcerative colitis. However, a significant proportion of patients does not respond to anti-TNF agents or lose response over time. Recently, therapeutic drug monitoring has gained a major role in identifying the mechanism and management of loss of response. The aim of this review article is to summarize the predictors of efficacy and outcomes, the different mechanisms of anti-TNF/biological failure in Crohn's disease and identify strategies to optimize biological treatment. PMID:26471077

  6. [Development of Disease-modifying Therapy for Alzheimer's Disease].

    Science.gov (United States)

    Akiyama, Haruhiko

    2016-04-01

    The development of disease-modifying therapy (DMT) that can arrest the pathological processes of Alzheimer's disease (AD) has emerged as one of the highest priorities of medical research. Two pathological hallmarks, amyloid-beta (Abeta) protein deposition and tau accumulation, are the major targets of DMT. Immunotherapy for Abeta removal and secretase inhibitors/modulators that reduce total or accumulation-prone Abeta are candidate DMTs against Abeta. Compounds that prevent tau aggregation are also under development. Clinical trials that test the efficacy of these DMT candidates are in preparation or ongoing. Recent studies of biomarkers of AD brain lesions have indicated that Abeta and tau accumulation appears 10 to 30 years before the occurrence of dementia and gradually propagate to reach the level that causes symptoms. Therefore, efficacy of DMT has to be evaluated in the preclinical stage of AD. The incidence of preclinical AD in the cognitively normal, aged population are estimated to be around 19%. Thus, currently available biomarkers, amyloid/tau PET imaging and cerebrospinal fluid measurements of Abeta and tau, are, perhaps, too invasive and costly. An international collaborative effort is needed to overcome this issue. PMID:27056864

  7. Multilevel systems biology modeling characterized the atheroprotective efficiencies of modified dairy fats in a hamster model.

    Science.gov (United States)

    Martin, Jean-Charles; Berton, Amélie; Ginies, Christian; Bott, Romain; Scheercousse, Pierre; Saddi, Alessandra; Gripois, Daniel; Landrier, Jean-François; Dalemans, Daniel; Alessi, Marie-Christine; Delplanque, Bernadette

    2015-09-01

    We assessed the atheroprotective efficiency of modified dairy fats in hyperlipidemic hamsters. A systems biology approach was implemented to reveal and quantify the dietary fat-related components of the disease. Three modified dairy fats (40% energy) were prepared from regular butter by mixing with a plant oil mixture, by removing cholesterol alone, or by removing cholesterol in combination with reducing saturated fatty acids. A plant oil mixture and a regular butter were used as control diets. The atherosclerosis severity (aortic cholesteryl-ester level) was higher in the regular butter-fed hamsters than in the other four groups (P < 0.05). Eighty-seven of the 1,666 variables measured from multiplatform analysis were found to be strongly associated with the disease. When aggregated into 10 biological clusters combined into a multivariate predictive equation, these 87 variables explained 81% of the disease variability. The biological cluster "regulation of lipid transport and metabolism" appeared central to atherogenic development relative to diets. The "vitamin E metabolism" cluster was the main driver of atheroprotection with the best performing transformed dairy fat. Under conditions that promote atherosclerosis, the impact of dairy fats on atherogenesis could be greatly ameliorated by technological modifications. Our modeling approach allowed for identifying and quantifying the contribution of complex factors to atherogenic development in each dietary setup. PMID:26071539

  8. Genetic interactions and modifier genes in Hirschsprung's disease

    Institute of Scientific and Technical Information of China (English)

    Adam S Wallace; Richard B Anderson

    2011-01-01

    Hirschsprung's disease is a congenital disorder that occurs in 1:5000 live births. It is characterised by an absence of enteric neurons along a variable region of the gastrointestinal tract. Hirschsprung's disease is classified as a multigenic disorder, because the same phenotype is associated with mutations in multiple distinct genes. Furthermore, the genetics of Hirschsprung's disease are highly complex and not strictly Mendelian. The phenotypic variability and incomplete penetrance observed in Hirschsprung's disease also suggests the involvement of modifier genes. Here, we summarise the current knowledge of the genetics underlying Hirschsprung's disease based on human and animal studies, focusing on the principal causative genes, their interactions, and the role of modifier genes.

  9. Functional Foods as Modifiers of Cardiovascular Disease

    OpenAIRE

    Johnston, Carol

    2009-01-01

    There is growing consensus that systemic inflammation is at the heart of cardiovascular disease (CVD). Inflammation is a key feature of the immune system, functioning to defend tissue integrity and function. However, chronic stimulation of inflammatory mediators leads to lasting vascular reactivity, insulin resistance, hyperlipidemia, and, subsequently, chronic disease. Dietary practices to minimize inflammatory stimuli and CVD risk include regular intakes of fatty fish rich in the eicosapent...

  10. Biologic therapy for inflammatory bowel disease.

    Science.gov (United States)

    Ardizzone, Sandro; Bianchi Porro, Gabriele

    2005-01-01

    Despite all of the advances in our understanding of the pathophysiology of inflammatory bowel disease (IBD), we still do not know its cause. Some of the most recently available data are discussed in this review; however, this field is changing rapidly and it is increasingly becoming accepted that immunogenetics play an important role in the predisposition, modulation and perpetuation of IBD. The role of intestinal milieu, and enteric flora in particular, appears to be of greater significance than previously thought. This complex interplay of genetic, microbial and environmental factors culminates in a sustained activation of the mucosal immune and non-immune response, probably facilitated by defects in the intestinal epithelial barrier and mucosal immune system, resulting in active inflammation and tissue destruction. Under normal situations, the intestinal mucosa is in a state of 'controlled' inflammation regulated by a delicate balance of proinflammatory (tumour necrosis factor [TNF]-alpha, interferon [IFN]-gamma, interleukin [IL]-1, IL-6, IL-12) and anti-inflammatory cytokines (IL-4, IL-10, IL-11). The mucosal immune system is the central effector of intestinal inflammation and injury, with cytokines playing a central role in modulating inflammation. Cytokines may, therefore, be a logical target for IBD therapy using specific cytokine inhibitors. Biotechnology agents targeted against TNF, leukocyte adhesion, T-helper cell (T(h))-1 polarisation, T-cell activation or nuclear factor (NF)-kappaB, and other miscellaneous therapies are being evaluated as potential therapies for IBD. In this context, infliximab is currently the only biologic agent approved for the treatment of inflammatory and fistulising Crohn's disease. Other anti-TNF biologic agents have emerged, including CDP 571, certolizumab pegol (CDP 870), etanercept, onercept and adalimumab. However, ongoing research continues to generate new biologic agents targeted at specific pathogenic mechanisms involved

  11. Cassava virus diseases: biology, epidemiology, and management.

    Science.gov (United States)

    Legg, James P; Lava Kumar, P; Makeshkumar, T; Tripathi, Leena; Ferguson, Morag; Kanju, Edward; Ntawuruhunga, Pheneas; Cuellar, Wilmer

    2015-01-01

    Cassava (Manihot esculenta Crantz.) is the most important vegetatively propagated food staple in Africa and a prominent industrial crop in Latin America and Asia. Its vegetative propagation through stem cuttings has many advantages, but deleteriously it means that pathogens are passed from one generation to the next and can easily accumulate, threatening cassava production. Cassava-growing continents are characterized by specific suites of viruses that affect cassava and pose particular threats. Of major concern, causing large and increasing economic impact in Africa and Asia are the cassava mosaic geminiviruses that cause cassava mosaic disease in Africa and Asia and cassava brown streak viruses causing cassava brown streak disease in Africa. Latin America, the center of origin and domestication of the crop, hosts a diverse set of virus species, of which the most economically important give rise to cassava frog skin disease syndrome. Here, we review current knowledge on the biology, epidemiology, and control of the most economically important groups of viruses in relation to both farming and cultural practices. Components of virus control strategies examined include: diagnostics and surveillance, prevention and control of infection using phytosanitation, and control of disease through the breeding and promotion of varieties that inhibit virus replication and/or movement. We highlight areas that need further research attention and conclude by examining the likely future global outlook for virus disease management in cassava. PMID:25591878

  12. New oral disease-modifying therapies for multiple sclerosis

    OpenAIRE

    Bagert, Bridget A; Bourdette, Dennis

    2009-01-01

    Several promising, oral disease-modifying therapies for multiple sclerosis are currently being evaluated in clinical trials. The arrival of effective oral agents for multiple sclerosis will be a major advance in the global effort to alter the natural history of this chronic disease.

  13. Biological control of postharvest diseases of fruits.

    Science.gov (United States)

    Janisiewicz, Wojciech J; Korsten, Lise

    2002-01-01

    Losses from postharvest fruit diseases range from 1 to 20 percent in the United States, depending on the commodity. The application of fungicides to fruits after harvest to reduce decay has been increasingly curtailed by the development of pathogen resistance to many key fungicides, the lack of replacement fungicides, negative public perception regarding the safety of pesticides and consequent restrictions on fungicide use. Biological control of postharvest diseases (BCPD) has emerged as an effective alternative. Because wound-invading necrotrophic pathogens are vulnerable to biocontrol, antagonists can be applied directly to the targeted area (fruit wounds), and a single application using existing delivery systems (drenches, line sprayers, on-line dips) can significantly reduce fruit decays. The pioneering biocontrol products BioSave and Aspire were registered by EPA in 1995 for control of postharvest rots of pome and citrus fruit, respectively, and are commercially available. The limitations of these biocontrol products can be addressed by enhancing biocontrol through manipulation of the environment, using mixtures of beneficial organisms, physiological and genetic enhancement of the biocontrol mechanisms, manipulation of formulations, and integration of biocontrol with other alternative methods that alone do not provide adequate protection but in combination with biocontrol provide additive or synergistic effects. PMID:12147766

  14. Behavioural biology of Chagas disease vectors

    Directory of Open Access Journals (Sweden)

    Claudio Ricardo Lazzari

    2013-01-01

    Full Text Available Many arthropod species have adopted vertebrate blood as their main food source. Blood is rich in nutrients and, except for the presence of parasites, sterile. However, this food source is not freely available, nor is obtaining it devoid of risk. It circulates inside vessels hidden underneath the skin of mobile hosts that are able to defend themselves and even predate the insects that try to feed on them. Thus, the haematophagous lifestyle is associated with major morphological, physiological and behavioural adaptations that have accumulated throughout the evolutionary history of the various lineages of blood-sucking arthropods. These adaptations have significant consequences for the evolution of parasites as well as for the epidemiology of vector-transmitted diseases. In this review article, we analyse various aspects of the behaviour of triatomine bugs to illustrate how each behavioural trait represents a particular adaptation to their close association with their hosts, which may easily turn into predators. Our aim is to offer to the reader an up-to-date integrative perspective on the behaviour of Chagas disease vectors and to propose new research avenues to encourage both young and experienced colleagues to explore this aspect of triatomine biology.

  15. Established and emerging biological activity markers of inflammatory bowel disease

    DEFF Research Database (Denmark)

    Nielsen, O H; Vainer, B; Madsen, S M; Seidelin, J B; Heegaard, Niels Henrik Helweg

    2000-01-01

    Assessment of disease activity in inflammatory bowel disease (IBD), i.e., ulcerative colitis (UC) and Crohn's disease (CD), is done using clinical parameters and various biological disease markers. Ideally, a disease marker must: be able to identify individuals at risk of a given disorder, be dis...

  16. Biological durability of wood modified by citric acid

    Directory of Open Access Journals (Sweden)

    Bogoslav Šefc

    2008-07-01

    Full Text Available This paper presents the results of measurement of durability of beech wood (Fagus sylvatica modified by Citric Acid (CA against brown rot fungus Poria placenta according to EN 113. Modification was performedby impregnation with 7.0% CA and 6.5% sodium-hypophosphite (SHP water solution and 10-hour curing at 140 °C. The influence of thermal treatment on durability was also researched. Weight percentage gain (WPG caused by modification, moisture content (MC and mass loss of wood (dm after fungal nutrition were measured. WPG of modified beech wood was 6.1% and that of thermally treated wood was -0.3%. The results showed increased durability of modified wood to be 8.3 times greater than nonmodified, while thermal treatment did not give significant durability improvement. These results indicate modification by CA as a promising alternative, but further research on optimisation of modification parameters is needed to achieve improvement of wood properties.

  17. Disease-threat model explains acceptance of genetically modified products

    Directory of Open Access Journals (Sweden)

    Prokop Pavol

    2013-01-01

    Full Text Available Natural selection favoured survival of individuals who were able to avoid disease. The behavioural immune system is activated especially when our sensory system comes into contact with disease-connoting cues and/or when these cues resemble disease threat. We investigated whether or not perception of modern risky technologies, risky behaviour, expected reproductive goals and food neophobia are associated with the behavioural immune system related to specific attitudes toward genetically modified (GM products. We found that respondents who felt themselves more vulnerable to infectious diseases had significantly more negative attitudes toward GM products. Females had less positive attitudes toward GM products, but engaging in risky behaviours, the expected reproductive goals of females and food neophobia did not predict attitudes toward GM products. Our results suggest that evolved psychological mechanisms primarily designed to protect us against pathogen threat are activated by modern technologies possessing potential health risks.

  18. Telomere biology in healthy aging and disease

    NARCIS (Netherlands)

    Oeseburg, Hisko; de Boer, Rudolf A.; van Gilst, Wiek H.; van der Harst, Pim

    2010-01-01

    Aging is a biological process that affects most cells, organisms and species. Telomeres have been postulated as a universal biological clock that shortens in parallel with aging in cells. Telomeres are located at the end of the chromosomes and consist of an evolutionary conserved repetitive nucleoti

  19. Loss of strength in biologically degraded thermally modified wood

    OpenAIRE

    Ulrika Råberg; Geoffrey Daniel; Nasko Terziev

    2012-01-01

    The durability of thermally modified (TM) and untreated (UT) mini-stakes exposed to in-ground contact was compared by modulus of elasticity (MOE) and mass loss with decay type using microscopy. Results showed a strong correlation between MOE and soft rot decay for UT stakes over a 30 month exposure period. For TM stakes, the correlation between MOE and decay rate (soft rot/bacteria) was not as strong. Loss of MOE of the TM stakes is suggested to be accentuated by the extensive micro-checking ...

  20. Disease-modifying therapies in relapsing–remitting multiple sclerosis

    Directory of Open Access Journals (Sweden)

    Fabricio González-Andrade

    2010-07-01

    Full Text Available Fabricio González-Andrade1, José Luis Alcaraz-Alvarez21Department of Medicine, Metropolitan Hospital, Quito, Ecuador; 2School of Medicine, University of Mayab, Merida, MexicoClinical question: What is the best current disease-modifying therapy for relapsing–remitting multiple sclerosis?Results: The evidence shows that the most effective disease-modifying therapy for delaying short- to medium-term disability progression, prevention of relapses, reducing the area and activity of lesions on magnetic resonance imaging, with the least side effects, is high-dose, high-frequency subcutaneous interferon-β1a 44 μg three times per week.Implementation: The pitfalls in treatment of MS can be avoided by remembering the following points: • The most effective therapy to prevent or delay the appearance of permanent neurological disability with the fewest side effects should be chosen, and treatment should not be delayed.• Adherence to treatment should be monitored closely, and needs comprehensive patient information and education to establish long-term adherence, which is a critical determinant of long-term outcome.• The correct approach to the disease includes disease management, symptom management, and patient management. A combination of tools is necessary to ease the various symptoms, which fall into three broad categories, i.e. rehabilitation, pharmacological, and procedural.• It is important to understand that no treatment modality should be used alone, unless it is in itself sufficient to remedy the particular symptom/problem.Keywords: relapsing–remitting multiple sclerosis, interferon, disease-modifying therapy, relapse prevention

  1. Loss of strength in biologically degraded thermally modified wood

    Directory of Open Access Journals (Sweden)

    Ulrika Råberg

    2012-11-01

    Full Text Available The durability of thermally modified (TM and untreated (UT mini-stakes exposed to in-ground contact was compared by modulus of elasticity (MOE and mass loss with decay type using microscopy. Results showed a strong correlation between MOE and soft rot decay for UT stakes over a 30 month exposure period. For TM stakes, the correlation between MOE and decay rate (soft rot/bacteria was not as strong. Loss of MOE of the TM stakes is suggested to be accentuated by the extensive micro-checking produced in the TM wood tracheids during the original heat treatment. The micro-checks are thought to expand during the winter season due to water expansion during freezing, thereby leading to weakening of the wood in addition to the decay caused by soft rot and bacteria. Using molecular methods, Phialophora hoffmannii was identified as the main fungus causing soft rot decay.

  2. Healthy aging and disease : role for telomere biology?

    NARCIS (Netherlands)

    Zhu, Haidong; Belcher, Matthew; van der Harst, Pim

    2011-01-01

    Aging is a biological process that affects most cells, organisms and species. Human aging is associated with increased susceptibility to a variety of chronic diseases, including cardiovascular disease, Type 2 diabetes, neurological diseases and cancer. Despite the remarkable progress made during the

  3. Endothelin receptor antagonists as disease modifiers in systemic sclerosis.

    Science.gov (United States)

    Shetty, Nagalakshmi; Derk, Chris T

    2011-02-01

    Systemic sclerosis (SSc) is a multisystem connective tissue disease of unknown etiology that is characterized by inflammation, vascular dysfunction and fibrosis of the skin and visceral organs. SSc is clinically diverse both in terms of the burden of skin and organ involvement and the rate of progression of the disease. Recent studies indicate that the endothelin system, especially ET-1 and the ETA and ETB receptors may play a key role in the pathogenesis of SSc. A new class of drugs, endothelin receptor antagonists has been introduced for treatment of patients with pulmonary arterial hypertension (PAH). Bosentan, a dual endothelin receptor antagonist as well as Sitaxsentan and Ambrisentan, selective blockers of the ETA receptor have proven effective in SSc-PAH. This effect may be mediated through both a vasodilatory and antifibrotic effect, thus making these agents attractive as potential disease modifying agents for SSc. PMID:21184655

  4. Infectious Complications With the Use of Biologic Response Modifiers in Infants and Children.

    Science.gov (United States)

    Davies, H Dele

    2016-08-01

    Biologic response modifiers (BRMs) are substances that interact with and modify the host immune system. BRMs that dampen the immune system are used to treat conditions such as juvenile idiopathic arthritis, psoriatic arthritis, or inflammatory bowel disease and often in combination with other immunosuppressive agents, such as methotrexate and corticosteroids. Cytokines that are targeted include tumor necrosis factor α; interleukins (ILs) 6, 12, and 23; and the receptors for IL-1α (IL-1A) and IL-1β (IL-1B) as well as other molecules. Although the risk varies with the class of BRM, patients receiving immune-dampening BRMs generally are at increased risk of infection or reactivation with mycobacterial infections (Mycobacterium tuberculosis and nontuberculous mycobacteria), some viral (herpes simplex virus, varicella-zoster virus, Epstein-Barr virus, hepatitis B) and fungal (histoplasmosis, coccidioidomycosis) infections, as well as other opportunistic infections. The use of BRMs warrants careful determination of infectious risk on the basis of history (including exposure, residence, and travel and immunization history) and selected baseline screening test results. Routine immunizations should be given at least 2 weeks (inactivated or subunit vaccines) or 4 weeks (live vaccines) before initiation of BRMs whenever feasible, and inactivated influenza vaccine should be given annually. Inactivated and subunit vaccines should be given when needed while taking BRMs, but live vaccines should be avoided unless under special circumstances in consultation with an infectious diseases specialist. If the patient develops a febrile or serious respiratory illness during BRM therapy, consideration should be given to stopping the BRM while actively searching for and treating possible infectious causes. PMID:27432853

  5. Biological safety evaluation of the modified urinary catheter

    Energy Technology Data Exchange (ETDEWEB)

    Kowalczuk, Dorota, E-mail: dorota.kowalczuk@umlub.pl [Department of Medicinal Chemistry, Medical University of Lublin, Jaczewskiego 4, 20-090 Lublin (Poland); Przekora, Agata; Ginalska, Grazyna [Department of Biochemistry and Biotechnology, Medical University of Lublin, Chodzki 1, 20-093 Lublin (Poland)

    2015-04-01

    The purpose of this study was to evaluate in vitro safety of the novel tosufloxacin (TOS)-treated catheters with the prolonged antimicrobial activity. The test samples of silicone latex catheter were prepared by the immobilization of TOS on chitosan (CHIT)-coated catheter by means of covalent bonds and non-covalent interactions. Each step of the modification process of catheter surface was observed using ATR–Fourier transform infrared spectroscopy. In vitro cytotoxicity of the modified and unmodified catheters was assessed by direct and indirect tests in accordance with ISO standards using green monkey kidney (GMK) cell line. The MTT, lactate dehydrogenase activity (LDH), WST-8, Sulforhodamine B (SRB) test results and microscopic observation clearly indicated that unmodified silicone latex catheters decrease cell metabolic activity, act as a cytotoxic agent causing cell lysis and induce cell death through necrotic or apoptotic process. We suggest that chitosan coat with TOS immobilized limits leaching of harmful agents from silicone latex material, which significantly enhances survivability of GMK cells and therefore is quite a good protection against the cytotoxic effect of this material. - Highlights: • Characterization of the novel antimicrobial urinary catheters • Monitoring of the catheter modification by FTIR analysis • Confirmation of high cytotoxicity of latex-based catheter used in urological practice • Chitosan-coated and tosufloxacin-treated catheter is less toxic than the untreated one. • The proposed surface modification protects cells against latex-induced death.

  6. Biological safety evaluation of the modified urinary catheter

    International Nuclear Information System (INIS)

    The purpose of this study was to evaluate in vitro safety of the novel tosufloxacin (TOS)-treated catheters with the prolonged antimicrobial activity. The test samples of silicone latex catheter were prepared by the immobilization of TOS on chitosan (CHIT)-coated catheter by means of covalent bonds and non-covalent interactions. Each step of the modification process of catheter surface was observed using ATR–Fourier transform infrared spectroscopy. In vitro cytotoxicity of the modified and unmodified catheters was assessed by direct and indirect tests in accordance with ISO standards using green monkey kidney (GMK) cell line. The MTT, lactate dehydrogenase activity (LDH), WST-8, Sulforhodamine B (SRB) test results and microscopic observation clearly indicated that unmodified silicone latex catheters decrease cell metabolic activity, act as a cytotoxic agent causing cell lysis and induce cell death through necrotic or apoptotic process. We suggest that chitosan coat with TOS immobilized limits leaching of harmful agents from silicone latex material, which significantly enhances survivability of GMK cells and therefore is quite a good protection against the cytotoxic effect of this material. - Highlights: • Characterization of the novel antimicrobial urinary catheters • Monitoring of the catheter modification by FTIR analysis • Confirmation of high cytotoxicity of latex-based catheter used in urological practice • Chitosan-coated and tosufloxacin-treated catheter is less toxic than the untreated one. • The proposed surface modification protects cells against latex-induced death

  7. The biological substrates of Alzheimer's disease

    International Nuclear Information System (INIS)

    This book contains 21 selections. Some of the titles are: Dementia of the Alzheimer Type: Genetic Aspects; Determination of Cerebral Metabolic Patterns in Dementia Using Positron Emission Tomography; Pathology of the Basal Forebrain in Alzheimer's Disease and Other Dementias; Characterization of Neurofibrillary Tangles with Monoclonal Antibodies Raised Against Alzheimer Neurofibrillary Tangles; and HLA Associations in Alzheimer's Disease

  8. Histamine modifies malignant biological behaviour in irradiated breast cancer cells

    International Nuclear Information System (INIS)

    MDA MB 231, a metastatic breast cancer cell line, expresses the four known types of histamine receptors (HAR), which differentially regulate cell proliferation. HA also exerts a radiosensitizing effect when is added to MDA MB 231 cells before irradiation in a way related to the elevation of H2O2 levels. However, ionizing radiation (IR) has also been demonstrated to affect malignant biological behaviour depending upon cell type and irradiation characteristics. The present study was conducted to investigate the action of HA and IR on two events involved in metastatic capacity such as the expression and activity of matrix metalloproteinases (MMPs) and cell motility. HA decreased MMP2 and MMP9 expression assessed by RT-PCR and cytochemistry as well enzymatic activity determined by zimography. This effect was mimicked by H2 agonists, while an opposite action was mainly observed when H4 agonists were employed. Cell motility, evaluated by wound healing assay, was also distinctly modulated through HAR. It was significantly augmented via H4R and to a lesser extent via H1R and H3R, though diminished through H2R. 2 Gy irradiated cells showed an enhanced MMP2 and MMP9 activity and cell motility compared to control cells. However, this effect was counteracted by HA. Results suggest that HA treatment could improve radiotherapy efficacy regarding the potential development of metastases. (authors)

  9. Improved ability of biological and previous caries multimarkers to predict caries disease as revealed by multivariate PLS modelling

    OpenAIRE

    Ericson Thorild; Källestål Carina; Johansson Ingegerd; Nordlund Åke; Sjöström Michael; Strömberg Nicklas

    2009-01-01

    Abstract Background Dental caries is a chronic disease with plaque bacteria, diet and saliva modifying disease activity. Here we have used the PLS method to evaluate a multiplicity of such biological variables (n = 88) for ability to predict caries in a cross-sectional (baseline caries) and prospective (2-year caries development) setting. Methods Multivariate PLS modelling was used to associate the many biological variables with caries recorded in thirty 14-year-old children by measuring the ...

  10. [Biological treatment of rare inflammatory rheumatic diseases

    DEFF Research Database (Denmark)

    Baslund, B.

    2008-01-01

    The current status of the use of biological medicine in the treatment of adult onset morbus still, Wegeners granulomatosis and systemic lupus erythematosus (SLE) is reviewed. The need for controlled trials is emphasized. Anti-CD20 treatment for SLE patients with kidney involvement and patients wi...

  11. Biologic characteristics of premalignant breast disease

    OpenAIRE

    Cole, Kimberly; Tabemero, Maria; Anderson, Karen S.

    2010-01-01

    Breast cancer is the second leading cause of cancer death in women in the United States. While mammography and breast magnetic resonance imaging (MRI) improve detection of early disease, there remains an Ullmet need for biomarkers for risk stratification, early detection, prediction, and disease prognosis. A number of early breast lesions, from atypical hyperplasias to carcinomas in situ, are associated with an increased risk of developing subsequent invasive breast carcinoma. The recent deve...

  12. Modifiable Cardiovascular Disease Risk Factors among Indigenous Populations

    Directory of Open Access Journals (Sweden)

    Adam A. Lucero

    2014-01-01

    Full Text Available Objective. To identify modifiable cardio-metabolic and lifestyle risk factors among indigenous populations from Australia (Aboriginal Australians/Torres Strait Islanders, New Zealand (Māori, and the United States (American Indians and Alaska Natives that contribute to cardiovascular disease (CVD. Methods. National health surveys were identified where available. Electronic databases identified sources for filling missing data. The most relevant data were identified, organized, and synthesized. Results. Compared to their non-indigenous counterparts, indigenous populations exhibit lower life expectancies and a greater prevalence of CVD. All indigenous populations have higher rates of obesity and diabetes, hypertension is greater for Māori and Aboriginal Australians, and high cholesterol is greater only among American Indians/Alaska Natives. In turn, all indigenous groups exhibit higher rates of smoking and dangerous alcohol behaviour as well as consuming less fruits and vegetables. Aboriginal Australians and American Indians/Alaska Natives also exhibit greater rates of sedentary behaviour. Conclusion. Indigenous groups from Australia, New Zealand, and the United States have a lower life expectancy then their respective non-indigenous counterparts. A higher prevalence of CVD is a major driving force behind this discrepancy. A cluster of modifiable cardio-metabolic risk factors precede CVD, which, in turn, is linked to modifiable lifestyle risk factors.

  13. Molecular biology applications to infectious diseases diagnostic

    International Nuclear Information System (INIS)

    This project goes directed to the applications of the techniques of molecular biology in hepatitis virus.A great advance of these techniques it allows its application to the diagnose molecular and it becomes indispensable to have these fundamental tools in the field of the Health Public for the detection precocious, pursuit of the treatment, the one predicts and the evolution of the patient hepatitis bearing virus technical.Use of molecular biology to increase the handling and the control of the patients with hepatitis B and C and to detect an adult numbers of positive cases by means of the training and integration of all the countries participating.Implement the technique of PCR to identify the virus of the hepatitis B and C,implement quantification methods and genotipification for these virus

  14. Phosphocitrate Is Potentially a Disease-Modifying Drug for Noncrystal-Associated Osteoarthritis

    Directory of Open Access Journals (Sweden)

    Yubo Sun

    2013-01-01

    Full Text Available Phosphocitrate (PC, a calcification inhibitor, inhibits the development of crystal-associated osteoarthritis (OA in Hartley guinea pigs. However, the molecular mechanisms underlying its disease-modifying effect remain elusive. This study sought to test the hypothesis that PC has calcium crystal-independent biological activities which are, at least in part, responsible for its disease-modifying activity. We found that PC inhibited the proliferation of OA fibroblast-like synoviocytes in the absence of calcium crystals. Consistent with its effect on cell proliferation, PC downregulated the expression of numerous genes classified in cell proliferation. PC also downregulated the expression of many genes classified in angiogenesis and inflammatory response including prostaglandin-endoperoxide synthase 2, interleukin-1 receptor, type I, and chemokine (C-C motif ligand 2. In contrast, PC upregulated the expression of many genes classified in musculoskeletal tissue development, including aggrecan, type I collagen, and insulin-like growth factor binding protein 5. These findings suggest that PC is not only a promising disease-modifying drug for crystal-associated OA but also for noncrystal-associated OA.

  15. Development of modified release gliclazide biological macromolecules using natural biodegradable polymers.

    Science.gov (United States)

    Prajapati, Vipulkumar D; Mashru, Krupa H; Solanki, Himanshu K; Jani, Girish K

    2013-04-01

    Modified release biological macromolecules (beads) of gliclazide using sodium alginate combined with either gellan gum or pectin in different ratios were prepared by Ionotropic gelation method. Biological macromolecules were evaluated for different physico-chemical parameters. Increase in polymers proportion showed difficulty in production of biological macromolecules due to high viscosity of dispersion. As the polymer concentration increases, the swelling and entrapment efficiency of drug increased. Compared to all other batches and commercial modified release gliclazide tablet, formulated biological macromolecules of sodium alginate with pectin (2:1 ratio) and with gellan gum (6:0.75 ratio) exhibited spherical shape, biphasic in vitro release profile and initial high drug release followed by moderate release up to 12 h as matrix diffusion kinetics and Higuchi model as well as Korsmeyer model. PMID:23305705

  16. The DNA-damage response in human biology and disease

    DEFF Research Database (Denmark)

    Jackson, Stephen P; Bartek, Jiri

    2009-01-01

    , signal its presence and mediate its repair. Such responses, which have an impact on a wide range of cellular events, are biologically significant because they prevent diverse human diseases. Our improving understanding of DNA-damage responses is providing new avenues for disease management....

  17. ChemProt: a disease chemical biology database

    DEFF Research Database (Denmark)

    Taboureau, Olivier; Nielsen, Sonny Kim; Audouze, Karine Marie Laure;

    2011-01-01

    Systems pharmacology is an emergent area that studies drug action across multiple scales of complexity, from molecular and cellular to tissue and organism levels. There is a critical need to develop network-based approaches to integrate the growing body of chemical biology knowledge with network...... biology. Here, we report ChemProt, a disease chemical biology database, which is based on a compilation of multiple chemical-protein annotation resources, as well as disease-associated protein-protein interactions (PPIs). We assembled more than 700 000 unique chemicals with biological annotation for 30...... 578 proteins. We gathered over 2-million chemical-protein interactions, which were integrated in a quality scored human PPI network of 428 429 interactions. The PPI network layer allows for studying disease and tissue specificity through each protein complex. ChemProt can assist in the in silico...

  18. Molecular biology of human muscle disease

    Energy Technology Data Exchange (ETDEWEB)

    Dunne, P.W.; Epstein, H.F. (Baylor Coll. of Medicine, Houston, TX (United States))

    1991-01-01

    The molecular revolution that is transforming the entire biomedical field has had far-reaching impact in its application to inherited human muscle disease. The gene for Duchenne muscular dystrophy was one of the first cloned without knowledge of the defective protein product. This success was based upon the availability of key chromosomal aberrations that provided molecular landmarks for the disease locus. Subsequent discoveries regarding the mode of expression for this gene, the structure and localization of its protein product dystrophin, and molecular diagnosis of affected and carrier individuals constitute a paradigm for investigation of human genetics. Finding the gene for myotonic muscular dystrophy is requiring the brute force approach of cloning several million bases of DNA, identifying expressed sequences, and characterizing candidate genes. The gene that causes hypertrophic cardiomyopathy has been found serendipitously to be one of the genetic markers on chromosome 14, the {beta} myosin heavy chain.

  19. Biologic therapy in inflammatory bowel disease

    DEFF Research Database (Denmark)

    Theede, Klaus; Dahlerup, Jens Frederik; Fallingborg, Jan;

    2013-01-01

    depends on the primary response to induction therapy. Effect of maintenance therapy should be evaluated clinically and paraclinically at least every 26-52 weeks, and maybe supplemented by endoscopy or MRI scan. Decision of treatment discontinuation is based on disease manifestation, treatment response and...... paraclinical parameters. In fistulising Crohn's disease, treatment with infliximab or adalimumab can be initiated in simple fistula with rectal inflammation or complex fistula when the initial treatment has insufficient effect. Further treatment strategy depends on the primary response to induction therapy...... not preferred. Further treatment strategy depends on the response to induction therapy. Treatment efficacy is assessed by symptoms, clinical markers, paraclinical parameters and possibly by endoscopy. Effect of maintenance therapy should be evaluated at least every 26-52 weeks. During treatment with...

  20. Molecular biological aspects of acquired bullous diseases

    DEFF Research Database (Denmark)

    Dabelsteen, Erik

    1998-01-01

    genes have been cloned. The antigens which react with autoantibodies from patients with bullous pemphigoid, cicatricial pemphigoid, acquired epidermolysis bullosa, and linear IgA disease are all proteins of the hemidesmosome basement membrane complex. Interestingly, most of the antigens also appear to...... be the target for mutations seen in patients with the inherited type of epidermolysis bullosa in which bullous lesions are a prominent clinical feature....

  1. Biologic Concentration Testing in Inflammatory Bowel Disease

    OpenAIRE

    Vaughn, Byron P; Sandborn, William J; Cheifetz, Adam S.

    2015-01-01

    Abstract: Anti-TNF medications have revolutionized the care of patients with inflammatory bowel disease. However, despite an initial robust effect, loss of response is common and long-term results are disappointing. Much of this lack of durability may be due to inadequate dose optimization, and recent studies suggest a correlation between serum drug concentrations and clinical outcomes. Currently, in clinical practice, measurement of drug concentrations and antibodies to drug are typically pe...

  2. Biological markers of Alzheimer?s disease

    Directory of Open Access Journals (Sweden)

    Leonardo Cruz de Souza

    2014-03-01

    Full Text Available The challenges for establishing an early diagnosis of Alzheimer’s disease (AD have created a need for biomarkers that reflect the core pathology of the disease. The cerebrospinal fluid (CSF levels of total Tau (T-tau, phosphorylated Tau (P-Tau and beta-amyloid peptide (Aβ42 reflect, respectively, neurofibrillary tangle and amyloid pathologies and are considered as surrogate markers of AD pathophysiology. The combination of low Aβ42 and high levels of T-tau and P-Tau can accurately identify patients with AD at early stages, even before the development of dementia. The combined analysis of the CSF biomarkers is also helpful for the differential diagnosis between AD and other degenerative dementias. The development of these CSF biomarkers has evolved to a novel diagnostic definition of the disease. The identification of a specific clinical phenotype combined with the in vivo evidence of pathophysiological markers offers the possibility to make a diagnosis of AD before the dementia stage with high specificity.

  3. PREFACE: Physics and biology of neurodegenerative diseases Physics and biology of neurodegenerative diseases

    Science.gov (United States)

    Pastore, Annalisa

    2012-06-01

    , about 15 years after the original reports, it is clear that amyloids are special structures that occur in nature under several different guises, some good, some evil [3]. The number of diseases associated with misfolding and fibrillogenesis has steadily increased. Examples of fairly common pathologies associated with fibre formation include Alzheimer's disease (currently one of the major threats for human health in our increasingly aging world), Parkinson's disease and several rare, but not less severe, pathologies. On the other hand, it is also clear that amyloid formation is a convenient mechanism for storing peptides and/or proteins in a compact and resistant way. The number of organisms/tissues in which amyloid deposits are found is thus increasing. It is also not too far-fetched to expect that the mechanical properties of amyloids could be used in biotechnology to design new materials. Because of the importance of this topic in so many scientific fields, we have dedicated this special issue of Journal of Physics: Condensed Matter to the topic of protein aggregation and disease. In the following pages we have collected two reviews and five articles that explore new and interesting developments in the field. References [1] Olby R 1994 The Path of the Double Helix: The Discovery of DNA (New York: Dover) [2] Dobson C M 2004 Principles of protein folding, misfolding and aggregation Semin. Cell Dev. Biol. 15 3-16 [3] Hammer N D, Wang X, McGuffie B A, Chapman M R 2008 Amyloids: friend or foe? J. Alzheimers Dis. 13 407-19 Physics and biology of neurodegenerative diseases contents Protein aggregation and misfolding: good or evil?Annalisa Pastore and Pierandrea Temussi Alzheimer's disease: biological aspects, therapeutic perspectives and diagnostic toolsM Di Carlo, D Giacomazza and P L San Biagio Entrapment of Aβ1-40 peptide in unstructured aggregatesC Corsale, R Carrotta, M R Mangione, S Vilasi, A Provenzano, G Cavallaro, D Bulone and P L San Biagio Elemental micro

  4. Biological and behavioral modifiers of urinary arsenic metabolic profiles in a U.S. population

    Science.gov (United States)

    Biological and behavioral modifiers of urinary arsenic metabolic profiles in a U.S. population David J. Thomas – ISTD, NHEERL Edward F. Hudgens – EHPD, NHEERL John Rogers - Westat Relations between intensity of arsenic exposure from home tap water and levels of inorganic As ...

  5. Biologic concentration testing in inflammatory bowel disease.

    Science.gov (United States)

    Vaughn, Byron P; Sandborn, William J; Cheifetz, Adam S

    2015-06-01

    Anti-TNF medications have revolutionized the care of patients with inflammatory bowel disease. However, despite an initial robust effect, loss of response is common and long-term results are disappointing. Much of this lack of durability may be due to inadequate dose optimization, and recent studies suggest a correlation between serum drug concentrations and clinical outcomes. Currently, in clinical practice, measurement of drug concentrations and antibodies to drug are typically performed only when a patient presents with active inflammatory bowel disease symptoms or during a potential immune-mediated reaction to anti-TNF ("reactive" setting). However, proactive monitoring of anti-TNF concentrations with titration to a therapeutic window (i.e., therapeutic concentration monitoring) represents a new strategy with many potential clinical benefits including prevention of immunogenicity, less need for IFX rescue therapy, and greater durability of IFX treatment. This review will cover the salient features of anti-TNF pharmacokinetics and pharmacodynamics and provide a rational approach for the use of anti-TNF concentration testing in both the reactive and proactive settings. PMID:25590953

  6. Pulmonary complications of biological therapies in children and adults with rheumatic diseases.

    Science.gov (United States)

    Nisar, Muhammad K; Ostör, Andrew J K

    2013-12-01

    The management of rheumatic conditions, including those occurring in children, has improved dramatically over the last decade following the introduction of biologic disease-modifying anti-rheumatic drugs (bDMARDS) into the therapeutic arsenal. The benefits have been realised in multiple aspects of disease including signs and symptoms, bone and cartilage destruction, disability and quality of life. Overall, bDMARDS have an acceptable safety profile in the short to medium term in adults and children, however, that following longer term use remains unclear. As these drugs target key signalling molecules and cells of the immune system, adverse events are not unanticipated. In this review we will discuss pulmonary complications of biologic therapies used in the management of rheumatic diseases in both children and adults. PMID:23462434

  7. Whirling disease revisited: pathogenesis, parasite biology and disease intervention.

    Science.gov (United States)

    Sarker, Subhodeep; Kallert, Dennis Marc; Hedrick, Ronald P; El-Matbouli, Mansour

    2015-05-21

    Whirling disease (WD) is an ecologically and economically debilitating disease of rainbow trout Oncorhynchus mykiss caused by the actinosporean spores of the parasite Myxobolus cerebralis. M. cerebralis has a complex, 2-host life cycle alternating between salmonid fish and the oligochaete host Tubifex tubifex. The parasite alternates between 2 spore forms as transmission stages: an actinosporean triactinomyxon spore that is produced in the oligochaete host and a myxosporean spore that develops in the salmonid host. Waterborne triactinomyxon spores released from infected T. tubifex oligochaetes attach to the salmonid host by polar filament extrusion elicited by chemical (nucleoside) and mechanical (thigmotropy) stimuli-a process which is rapidly followed by active penetration of the sporoplasms into the fish epidermis. Upon penetration, sporoplasms multiply and migrate via peripheral nerves and the central nervous system to reach the cartilage where they form trophozoites which undergo further multiplication and subsequent sporogenesis. M. cerebralis myxospores are released into the aquatic environment when infected fish die and autolyse, or when they are consumed and excreted by predators. Myxospores released into the water are ingested by susceptible T. tubifex where they develop intercellularly in the intestine over a period of 3 mo through 4 developmental stages to give rise to mature actinospores. In this article, we review our current understanding of WD-the parasite and its alternate hosts, life cycle and development of the parasite in either host, disease distribution, susceptibility and resistance mechanisms in salmonid host and strategies involved in diagnosis, prevention and control of WD. PMID:25993890

  8. Diagnosis of Whipple's disease using molecular biology techniques.

    Science.gov (United States)

    Cosme, Ángel; Ojeda, Evelia; Muñagorri, Ana I; Gaminde, Eduardo; Bujanda, Luis; Larzabal, Mikel; Gil, Inés

    2011-04-01

    The diagnosis of Whipple's disease (WD) is based on the existence of clinical signs and symptoms compatible with the disease and in the presence of PAS-positive diastase-resistant granules in the macrophages of the small intestine. If there is suspicion of the disease but no histological findings or only isolated extraintestinal manifestations, species-specific PCR using different sequences of the T. whippleii genome from different tissue types and biological fluids is recommended.This study reports two cases: the first patient had diarrhea and the disease was suspected after an endoscopic examination of the ileum, while the second patient had multi-systemic manifestations,particularly abdominal, thoracic, and peripheral lymphadenopathies. In both cases, the diagnosis was confirmed using molecular biology techniques to samples from the small intestine or from a retroperineal lymph node, respectively. PMID:21526877

  9. Benefits and Costs of Biologically Contained Genetically Modified Tomatoes and Eggplants in Italy and Spain

    Directory of Open Access Journals (Sweden)

    Rolf A. Groeneveld

    2011-08-01

    Full Text Available In this paper we assess the benefits and costs of introducing biologically contained genetically modified (GM crops, with an application to the potential introduction of GM tomatoes and eggplants in Italy and Spain. Such crops possess both the standard beneficial GM traits, and they prevent introgression of transgenes from GM crops to their conventional or wild relatives, thereby adding to the safety of their cultivation. As a result, coexistence regulations for these crops are less stringent than for crops without biological containment. The potential adoption of biologically contained GM tomatoes and eggplants is assessed in a cost-benefit framework for Italy and Spain. We conclude that biological containment has considerable potential benefits if policy makers are willing to loosen the restrictions on the introduction of these varieties.

  10. Moisture sorption, biological durability, and mechanical performance of WPC containing modified wood and polylactates

    Directory of Open Access Journals (Sweden)

    B. Kristoffer Segerholm

    2012-11-01

    Full Text Available Biological durability is an important feature for wood-plastic composites (WPC intended for outdoor applications. One route to achieving WPC products with increased biological durability is to use wood preservative agents in the formulation of the WPC. Another option could be to use a chemically modified wood component that already exhibits increased resistance to biological degradation. There is also a need to use biobased thermoplastics made from renewable resources, which would decrease the dependency on petrochemically-produced thermoplastics in the future. The objective of this study was to examine moisture sorption properties, biological durability, and mechanical performance of injection-molded WPC samples based on acetylated or thermally modified wood components and a polylactate matrix. The biological durability was evaluated in a terrestrial microcosm (TMC test according to ENV 807, followed by mechanical evaluation in a center point bending test. The moisture sorption properties were investigated via both water soaking and exposure in a high-humidity climate. Low or negligible mass losses were observed in the TMC test for all WPC samples. However, the mechanical evaluation after exposure in the TMC test showed 35-40% losses in both strength and stiffness for the WPC containing an unmodified wood component.

  11. The DNA-damage response in human biology and disease

    Czech Academy of Sciences Publication Activity Database

    Jackson, S.P.; Bartek, Jiří

    2009-01-01

    Roč. 461, č. 7267 (2009), s. 1071-1078. ISSN 0028-0836 Institutional research plan: CEZ:AV0Z50520514 Keywords : DNA damage response * human disease * cancer Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 34.480, year: 2009

  12. Using biological networks to improve our understanding of infectious diseases

    Directory of Open Access Journals (Sweden)

    Nicola J. Mulder

    2014-08-01

    Full Text Available Infectious diseases are the leading cause of death, particularly in developing countries. Although many drugs are available for treating the most common infectious diseases, in many cases the mechanism of action of these drugs or even their targets in the pathogen remain unknown. In addition, the key factors or processes in pathogens that facilitate infection and disease progression are often not well understood. Since proteins do not work in isolation, understanding biological systems requires a better understanding of the interconnectivity between proteins in different pathways and processes, which includes both physical and other functional interactions. Such biological networks can be generated within organisms or between organisms sharing a common environment using experimental data and computational predictions. Though different data sources provide different levels of accuracy, confidence in interactions can be measured using interaction scores. Connections between interacting proteins in biological networks can be represented as graphs and edges, and thus studied using existing algorithms and tools from graph theory. There are many different applications of biological networks, and here we discuss three such applications, specifically applied to the infectious disease tuberculosis, with its causative agent Mycobacterium tuberculosis and host, Homo sapiens. The applications include the use of the networks for function prediction, comparison of networks for evolutionary studies, and the generation and use of host–pathogen interaction networks.

  13. The UV-irradiated mouse as a model for testing biological response modifiers

    International Nuclear Information System (INIS)

    In addition to inducing primary cancers of the skin, ultraviolet (UV) radiation produces specific impairments in the immune system that contribute to the growth and pathogenesis of these skin cancers. The cellular basis for the immunological alterations induced in mice by UV radiation has been studied and characterized over the past ten years. It is now possible to make use of this system to study the activity and mode of action of biological response modifiers. The advantages of this system are that it employs primary hosts, which may respond quite differently from normal animals bearing a transplanted tumor, it closely parallels several specific situations relevant to human cancer, and it may be useful in establishing the mechanism of action of certain agents. Studies in which biological response modifiers have been used in conjunction with the UV carcinogenesis model are reviewed. (Auth.)

  14. Benefits and costs of biologically contained genetically modified tomatoes and eggplants in Italy and Spain

    OpenAIRE

    Groeneveld, Rolf A.; Erik Ansink; Clemens C.M. Van de Wiel; Justus Wesseler

    2011-01-01

    In this paper we assess the benefits and costs of introducing biologically contained genetically modified (GM) crops, with an application to the potential introduction of GM tomatoes and eggplants in Italy and Spain. Such crops possess both the standard beneficial GM traits, and they prevent introgression of transgenes from GM crops to their conventional or wild relatives, thereby adding to the safety of their cultivation. As a result, coexistence regulations for these crops are less stringen...

  15. Engineering and control of biological systems: A new way to tackle complex diseases.

    Science.gov (United States)

    Menolascina, Filippo; Siciliano, Velia; di Bernardo, Diego

    2012-07-16

    The ongoing merge between engineering and biology has contributed to the emerging field of synthetic biology. The defining features of this new discipline are abstraction and standardisation of biological parts, decoupling between parts to prevent undesired cross-talking, and the application of quantitative modelling of synthetic genetic circuits in order to guide their design. Most of the efforts in the field of synthetic biology in the last decade have been devoted to the design and development of functional gene circuits in prokaryotes and unicellular eukaryotes. Researchers have used synthetic biology not only to engineer new functions in the cell, but also to build simpler models of endogenous gene regulatory networks to gain knowledge of the "rules" governing their wiring diagram. However, the need for innovative approaches to study and modify complex signalling and regulatory networks in mammalian cells and multicellular organisms has prompted advances of synthetic biology also in these species, thus contributing to develop innovative ways to tackle human diseases. In this work, we will review the latest progress in synthetic biology and the most significant developments achieved so far, both in unicellular and multicellular organisms, with emphasis on human health. PMID:22580058

  16. Biologic targeting in the treatment of inflammatory bowel diseases.

    Science.gov (United States)

    Bosani, Matteo; Ardizzone, Sandro; Porro, Gabriele Bianchi

    2009-01-01

    The etiology of inflammatory bowel disease (IBD) has not yet been clarified and immunosuppressive agents which nonspecifically reduce inflammation and immunity have been used in the conventional therapies for IBD. Evidence indicates that a dysregulation of mucosal immunity in the gut of IBD causes an overproduction of inflammatory cytokines and trafficking of effector leukocytes into the bowel, thus leading to an uncontrolled intestinal inflammation. Under normal situations, the intestinal mucosa is in a state of "controlled" inflammation regulated by a delicate balance of proinflammatory (tumor necrosis factor [TNF-alpha], interferon-gamma [IFN-gamma], interleukin-1 [IL-1], IL-6, IL-12 and anti-inflammatory cytokines IL-4, IL-10, IL-11). The mucosal immune system is the central effector of intestinal inflammation and injury, with cytokines playing a central role in modulating inflammation. Cytokines may therefore be a logical target for inflammatory bowel disease therapy using specific cytokine inhibitors. Biotechnology agents targeted against TNF, leukocyte adhesion, Th1 polarization, T cell activation, nuclear factor-kappaB (NF-kappaB), and other miscellaneous therapies are being evaluated as potential therapies for the treatment of inflammatory bowel disease. In this context, infliximab and adalimumab are currently the only biologic agents approved in Europe for the treatment of inflammatory Crohn's disease. Other anti-TNF biologic agents have emerged, including CDP571, certolizumab pegol, etanercept, onercept. However, ongoing research continues to generate new biologic agents targeted at specific pathogenic mechanism involved in the inflammatory process. Lymphocyte-endothelial interactions mediated by adhesion molecules are important in leukocyte migration and recruitment to sites of inflammation, and selective blockade of these adhesion molecules is a novel and promising strategy to treat Crohn's disease. Therapeutics agents to inhibit leukocyte trafficking

  17. The untapped cell biology of neglected tropical diseases.

    Science.gov (United States)

    Sullivan, William

    2016-03-01

    The World Health Organization lists a constellation of 17 tropical diseases that afflict approximately one in six individuals on the planet and, until recently, few resources have been devoted to the treatment and eradication of those diseases. They are often referred to as the diseases of the "bottom billion," because they are most prevalent among the poorest individuals in impoverished tropical nations. However, the few studies that have been performed reveal an extraordinary world of molecular and cellular adaptations that facilitate the pathogens' survival in hosts ranging from insects to humans. A compelling case can be made that even a modest investment toward understanding the basic molecular and cell biology of these neglected pathogens has a high probability of yielding exciting new cellular mechanisms and insights into novel ways of combating these diseases. PMID:26915691

  18. Morpho-chemistry and functionality of diseased biological tissues

    Science.gov (United States)

    Lange, Marta; Cicchi, Riccardo; Pavone, Francesco

    2014-09-01

    Heart and cardiovascular diseases are one of the most common in the world, in particular - arthrosclerosis. The aim of the research is to distinguish pathological and healthy tissue regions in biological samples, in this case - to distinguish collagen and lipid rich regions within the arterial wall. In the work a specific combination of such methods are used: FLIM and SHG in order to evaluate the biological tissue morphology and functionality, so that this research could give a contribution for creating a new biological tissue imaging standard in the closest future. During the study the most appropriate parameter for fluorescence lifetime decay was chosen in order to evaluate lifetime decay parameters and the isotropy of the arterial wall and deposition, using statistical methods FFT and GLCM. The research gives a contribution or the future investigations for evaluating lipid properties when it can de-attach from the arterial wall and cause clotting in the blood vessel or even a stroke.

  19. Discontinuing disease-modifying therapy in progressive multiple sclerosis: can we stop what we have started?

    LENUS (Irish Health Repository)

    Lonergan, Roisin

    2012-02-01

    Disease-modifying therapy is ineffective in disabled patients (Expanded Disability Status Scale [EDSS] > 6.5) with secondary progressive multiple sclerosis (MS) without relapses, or in primary progressive MS. Many patients with secondary progressive MS who initially had relapsing MS continue to use disease-modifying therapies. The enormous associated costs are a burden to health services. Regular assessment is recommended to guide discontinuation of disease-modifying therapies when no longer beneficial, but this is unavailable to many patients, particularly in rural areas. The objectives of this study are as follows: 1. To observe use of disease-modifying therapies in patients with progressive multiple sclerosis and EDSS > 6.5. 2. To examine approaches used by a group of international MS experts to stopping-disease modifying therapies in patients with secondary progressive MS without relapses. During an epidemiological study in three regions of Ireland (southeast Dublin city, and Wexford and Donegal Counties), we recorded details of disease-modifying therapies in patients with progressive MS and EDSS > 6.5. An e-questionnaire was sent to 26 neurologists with expert knowledge of MS, asking them to share their approach to stopping disease-modifying therapies in patients with secondary progressive MS. Three hundred and thirty-six patients were studied: 88 from southeast Dublin, 99 from Wexford and 149 from Donegal. Forty-four had EDSS > 6.5: 12 were still using disease-modifying therapies. Of the surveyed neurologists, 15 made efforts to stop disease-modifying therapies in progressive multiple sclerosis, but most did not insist. A significant proportion (12 of 44 patients with progressive MS and EDSS > 6.5) was considered to be receiving therapy without benefit. Eleven of the 12 were from rural counties, reflecting poorer access to neurology services. The costs of disease-modifying therapies in this group (>170,000 euro yearly) could be re-directed towards development

  20. Synergy of understanding dermatologic disease and epidermal biology

    OpenAIRE

    Stanley, John R.

    2012-01-01

    Dermatologic disease, although seldom life threatening, can be extremely disfiguring and interfere with the quality of life. In addition, as opposed to other organs, just the aging of skin and its adnexal structure the hair follicle can result in cosmetic concerns that affect most of us. The articles in this dermatology Review Series demonstrate recent progress in understanding the cell biology and molecular pathophysiology of the epidermis and hair follicles, which harbor keratinocyte and me...

  1. Systems Biology Approaches to Epidemiological Studies of Complex Diseases

    OpenAIRE

    Li, Hongzhe

    2013-01-01

    Systems biology approaches to epidemiological studies of complex diseases include collection of genetic, genomic, epigenomic and metagenomic data in large-scale epidemiological studies of complex phenotypes. Designs and analyses of such studies raise many statistical challenges. This paper reviews some issues related to integrative analysis of such high dimensional and inter-related data sets and outline some possible solutions. I focus my review on integrative approaches for genome-wide gene...

  2. Evaluation of the usefulness of modified biological fingerprints in chest radiographs for patient recognition and identification.

    Science.gov (United States)

    Shimizu, Yoichiro; Matsunobu, Yusuke; Morishita, Junji

    2016-07-01

    We have been developing an image-searching method to identify misfiled images in a PACS server. Developing new biological fingerprints (BFs) that would reduce the influence of differences in positioning and breathing phases to improve the performance of recognition is desirable. In our previous studies, the whole lung field (WLF) that included the shadows of the body and lungs was affected by differences in positioning and/or breathing phases. In this study, we showed the usefulness of a circumscribed lung with a rectangular region of interest and the upper half of a chest radiograph as modified BFs. We used 200 images as hypothetically misfiled images. The cross-correlation identifies the resemblance between the BFs in the misfiled images and the corresponding BFs in the database images. The modified BFs indicated better results than did WLF in a receiver operating characteristic analysis; therefore, they could be used as identifiers for patient recognition and identification. PMID:27132238

  3. Biologic targeting in the treatment of inflammatory bowel diseases

    Directory of Open Access Journals (Sweden)

    Matteo Bosani

    2009-02-01

    Full Text Available Matteo Bosani, Sandro Ardizzone, Gabriele Bianchi PorroChair of Gastroenterology, “L. Sacco” University Hospital, Milan, ItalyAbstract: The etiology of inflammatory bowel disease (IBD has not yet been clarified and immunosuppressive agents which nonspecifically reduce inflammation and immunity have been used in the conventional therapies for IBD. Evidence indicates that a dysregulation of mucosal immunity in the gut of IBD causes an overproduction of inflammatory cytokines and trafficking of effector leukocytes into the bowel, thus leading to an uncontrolled intestinal inflammation. Under normal situations, the intestinal mucosa is in a state of “controlled” inflammation regulated by a delicate balance of proinflammatory (tumor necrosis factor [TNF-α], interferon-gamma [IFN-γ], interleukin-1 [IL-1], IL-6, IL-12 and anti-inflammatory cytokines IL-4, IL-10, IL-11. The mucosal immune system is the central effector of intestinal inflammation and injury, with cytokines playing a central role in modulating inflammation. Cytokines may therefore be a logical target for inflammatory bowel disease therapy using specific cytokine inhibitors. Biotechnology agents targeted against TNF, leukocyte adhesion, Th1 polarization, T cell activation, nuclear factor-kappaB (NF-κB, and other miscellaneous therapies are being evaluated as potential therapies for the treatment of inflammatory bowel disease. In this context, infliximab and adalimumab are currently the only biologic agents approved in Europe for the treatment of inflammatory Crohn’s disease. Other anti-TNF biologic agents have emerged, including CDP571, certolizumab pegol, etanercept, onercept. However, ongoing research continues to generate new biologic agents targeted at specific pathogenic mechanism involved in the inflammatory process. Lymphocyte-endothelial interactions mediated by adhesion molecules are important in leukocyte migration and recruitment to sites of inflammation, and

  4. Biologic targeting in the treatment of inflammatory bowel diseases [Retraction

    Directory of Open Access Journals (Sweden)

    Bosani M

    2014-01-01

    Full Text Available Bosani M, Ardizzone S, Porro GB. Biologics: Targets and Therapy. 2009;3:77–97.This paper has been retracted after we were made aware that it contains a large amount of reused, and uncited material that was not placed within quotation marks.The following statement has been supplied by Dr Sandro Ardizzone:The review entitled "Biologic targeting in the treatment of inflammatory bowel disease" has been commissioned by this journal and published in 2009 (Matteo Bosani, Sandro Ardizzone, Gabriele Bianchi Porro. Biologics: Targets & Therapy 2009;3:77–97. The paper was written by our young coworker (Dr M Bosani. He has consulted many papers, including our previous reviews published years before. The not perfect knowledge of English language has greatly influenced the writing of the paper itself. So he saved in word file several parts of our previous papers (Ardizzone S, Bianchi Porro G. Inflammatory bowel disease: new insights into pathogenesis and treatment. J Intern Med 2002;252:475–496 – Ardizzone S, Bianchi Porro G. Biologic therapy for inflammatory bowel disease. Drugs 2005:2253–2286, and then transferred to the final paper. He was unaware as we are, of the fact that he could not reuse previously published material in other journals. The reuse of this material was made in good faith.Taking our responsibility for what happened, we intend to apologize for this inconvenience to the Editor (Dr Doris Benbrook and Publisher (Dr Tim Hill. Moreover, for the reasons mentioned above, I consider appropriate to retract the paper itself.This retraction relates to this paper.

  5. Disease-threat model explains acceptance of genetically modified products

    OpenAIRE

    Prokop Pavol; Ozel Murat; Usak Muhammet; Senay Ibrahim

    2013-01-01

    Natural selection favoured survival of individuals who were able to avoid disease. The behavioural immune system is activated especially when our sensory system comes into contact with disease-connoting cues and/or when these cues resemble disease threat. We investigated whether or not perception of modern risky technologies, risky behaviour, expected reproductive goals and food neophobia are associated with the behavioural immune system related to specific attitudes toward genetically ...

  6. Role of Histone-Modifying Enzymes and Their Complexes in Regulation of Chromatin Biology.

    Science.gov (United States)

    DesJarlais, Renee; Tummino, Peter J

    2016-03-22

    In 1964, Alfrey and colleagues proposed that acetylation and methylation of histones may regulate RNA synthesis and described "the possibility that relatively minor modifications of histone structure, taking place on the intact protein molecule, offer a means of switching-on or off RNA synthesis at different loci along the chromosome" [Allfrey, V., Faulkner, R., and Mirsky, A. (1964) Proc. Natl. Acad. Sci. U.S.A. 51, 786]. Fifty years later, this prescient description provides a simple but conceptually accurate model for the biological role of histone post-translational modifications (PTMs). The basic unit of chromosomes is the nucleosome, with double-stranded DNA wrapped around a histone protein oligomer. The "tails" of histone proteins are post-translationally modified, which alters the physical properties of nucleosomes in a manner that impacts gene accessibility for transcription and replication. Enzymes that catalyze the addition and removal of histone PTMs, histone-modifying enzymes (HMEs), are present in large protein complexes, with DNA-binding proteins, ATP-dependent chromatin remodeling enzymes, and epigenetic reader proteins that bind to post-translationally modified histone residues [Arrowsmith, C. H., Bountra, C., Fish, P. V., Lee, K., and Schapira, M. (2012) Nat. Rev. Drug Discovery 11, 384-400]. The activity of HME complexes is coordinated with that of other chromatin-associated complexes that, together, regulate gene transcription, DNA repair, and DNA replication. In this context, the enzymes that catalyze addition and removal of histone PTMs are an essential component of the highly regulated mechanism for accessing compacted DNA. To fully understand the function of HMEs, the structure of nucleosomes, their natural substrate, will be described. Each major class of HMEs subsequently will be discussed with regard to its biochemistry, enzymatic mechanism, and biological function in the context of a prototypical HME complex. PMID:26745824

  7. T Regulatory Cell Biology in Health and Disease.

    Science.gov (United States)

    Alroqi, Fayhan J; Chatila, Talal A

    2016-04-01

    Regulatory T (Treg) cells that express the transcription factor forkhead box protein P3 (FOXP3) play an essential role in enforcing immune tolerance to self tissues, regulating host-commensal flora interaction, and facilitating tissue repair. Their deficiency and/or dysfunction trigger unbridled autoimmunity and inflammation. A growing number of monogenic defects have been recognized that adversely impact Treg cell development, differentiation, and/or function, leading to heritable diseases of immune dysregulation and autoimmunity. In this article, we review recent insights into Treg cell biology and function, with particular attention to lessons learned from newly recognized clinical disorders of Treg cell deficiency. PMID:26922942

  8. Development and validation of modified disease activity scores in rheumatoid arthritis

    DEFF Research Database (Denmark)

    Baker, Joshua F; Conaghan, Philip G; Smolen, Josef S;

    2014-01-01

    (from all time points) with concurrent MRI measures of synovitis and bone edema in the development cohort. Based on regression coefficients, modified versions of the Disease Activity Score in 28 joints (M-DAS28), Simplified Disease Activity Index (M-SDAI), and Clinical Disease Activity Index (M......-CDAI) were generated for each subject in the validation cohort. The M-DAS28, M-SDAI, and M-CDAI scores were compared to conventional scores of disease activity with regard to associations with MRI measures of synovitis and radiographic progression, assessed using Pearson's and Spearman's correlations, linear......'s global assessment of disease activity using a visual analog scale (EvGA score). Modified disease activity scores were generated using the regression coefficients obtained in the synovitis models for all subjects in the validation cohort; modified scores were calculated as M-DAS28 = 0.49 × ln(CRP) + 0...

  9. The prediction and long-term maintenance of low disease activity during therapy with disease modifying anti-inflammatory drugs for rheumatoid arthritis

    Directory of Open Access Journals (Sweden)

    E.L. Luchikhina

    2014-05-01

    Full Text Available Therapy with biological agents (biologics over the past few years has become an important part of the strategy of medical treatment of patients with rheumatoid arthritis who respond insufficiently to the disease modifying anti-inflammatory drugs. The possibility to predict response to biologics is of special importance. Factors associated with good response to TNF-inhibitors are very different: age, liver and kidney function, body mass index, concomitant therapy, immunogenicity, the presence of ACPA and the rheumatoid factor, the cytokine profile, genetics, smoking, previous therapy by biologics etc. Another factor that significantly affects the long-term prognosis of biologic therapy is the primary response to treatment. Inhibitors of TNF-α as a whole is characterized by the development of the most marked clinical response within the first 12–24 weeks of treatment that can sustain for 12 months or more. Certolizumab pegol is characterized by rapid development of marked clinical response to treatment against disease activity and function with maintaining consistent improvement over the years, and the prognosis can be determined in most patients by the response to therapy in the first 12 weeks. We present a clinical case. 

  10. A systems biology approach identifies molecular networks defining skeletal muscle abnormalities in chronic obstructive pulmonary disease.

    Directory of Open Access Journals (Sweden)

    Nil Turan

    2011-09-01

    Full Text Available Chronic Obstructive Pulmonary Disease (COPD is an inflammatory process of the lung inducing persistent airflow limitation. Extensive systemic effects, such as skeletal muscle dysfunction, often characterize these patients and severely limit life expectancy. Despite considerable research efforts, the molecular basis of muscle degeneration in COPD is still a matter of intense debate. In this study, we have applied a network biology approach to model the relationship between muscle molecular and physiological response to training and systemic inflammatory mediators. Our model shows that failure to co-ordinately activate expression of several tissue remodelling and bioenergetics pathways is a specific landmark of COPD diseased muscles. Our findings also suggest that this phenomenon may be linked to an abnormal expression of a number of histone modifiers, which we discovered correlate with oxygen utilization. These observations raised the interesting possibility that cell hypoxia may be a key factor driving skeletal muscle degeneration in COPD patients.

  11. A Modified Oxidation Ditch with Additional Internal Anoxic Zones for Enhanced Biological Nutrient Removal

    Institute of Scientific and Technical Information of China (English)

    LIU Wei; YANG Dianhai; XU Li; SHEN Changming

    2013-01-01

    A novel modified pilot scale anaerobic oxidation ditch with additional internal anoxic zones was operated experimentally,aiming to study the improvement of biological nitrogen and phosphorus removal and the effect of enhanced denitrifying phosphorus removal in the process.Under all experimental conditions,the anaerobic-oxidation ditch with additional internal anoxic zones and an internal recycle ratio of 200% had the highest nutrient removal efficiency.The effluent NH+4-N,total nitrogen(TN),PO34--P and total phosphorus(TP)contents were 1.2 mg·L-1,13 mg·L-1,0.3 mg·L-1 and 0.4 mg·L-1,respectively,all met the discharge standards in China.The TN and TP removal efficiencies were remarkably improved from 37% and 50% to 65% and 88% with the presence of additional internal anoxic zones and internal recycle ratio of 200%.The results indicated that additional internal anoxic zones can optimize the utilization of available carbon source from the anaerobic outflow for denitrification.It was also found that phosphorus removal via the denitrification process was stimulated in the additional internal anoxic zones,which was beneficial for biological nitrogen and phosphorus removal when treating wastewater with a limited carbon source.However,an excess internal recycle would cause nitrite to accumulate in the system.This seems to be harmful to biological phosphorus removal.

  12. Withanolides: Biologically Active Constituents in the Treatment of Alzheimer's Disease.

    Science.gov (United States)

    Khan, Shahid A; Khan, Sher B; Shah, Zarbad; Asiri, Abdullah M

    2016-01-01

    The use of natural products in drug discovery and development have an important history. Several therapeutic agents have been investigated during the biological screenings of natural compounds. It is well documented that plants are possibly the core of novel substances that led to the discovery of new, novel, and effective therapeutic agents. Therefore, in the last few decades, scientists were thoroughly attempting for the search of benevolent drugs to protect mankind from various diseases and discomforts. The diverse chemical structures of natural products are the key element of their success in modern drug discovery. Cholinesterase enzyme inhibitors (ChEI) are chemicals which inhibit the splitting of cholinesterase enzymes (acetylcholinesterase and butyrylcholinesterase). Acetyl cholinesterase (AChE) and butyrylcholinesterase (BChE) are two types of cholinesterase enzymes that have been identified in vertebrates that are responsible for Alzheimer's disease and related dementia. Withanolides are affective plant secondary metabolites which inhibit acetylcholinesterase and butyrylcholinesterase enzyme and thus possibly will be the future drug for Alzheimer's disease. By viewing the importance of natural products in drug discovery and development, we present here, the importance of withanolides in the treatment of Alzheimer's disease. In this article, we also describe the classification and structural characterization of withanolides. This review comprises of 114 compounds. PMID:26527154

  13. Systems approaches to biology and disease enable translational systems medicine.

    Science.gov (United States)

    Hood, Leroy; Tian, Qiang

    2012-08-01

    The development and application of systems strategies to biology and disease are transforming medical research and clinical practice in an unprecedented rate. In the foreseeable future, clinicians, medical researchers, and ultimately the consumers and patients will be increasingly equipped with a deluge of personal health information, e.g., whole genome sequences, molecular profiling of diseased tissues, and periodic multi-analyte blood testing of biomarker panels for disease and wellness. The convergence of these practices will enable accurate prediction of disease susceptibility and early diagnosis for actionable preventive schema and personalized treatment regimes tailored to each individual. It will also entail proactive participation from all major stakeholders in the health care system. We are at the dawn of predictive, preventive, personalized, and participatory (P4) medicine, the fully implementation of which requires marrying basic and clinical researches through advanced systems thinking and the employment of high-throughput technologies in genomics, proteomics, nanofluidics, single-cell analysis, and computation strategies in a highly-orchestrated discipline we termed translational systems medicine. PMID:23084773

  14. Huperzine A: is it an effective disease-modifying drug for Alzheimer’s disease?

    Directory of Open Access Journals (Sweden)

    Zhong Ming eQian

    2014-08-01

    Full Text Available Alzheimer's disease (AD is a progressive neurodegenerative disorder for which there is no cure. Huperzine A (HupA is a natural inhibitor of acetylcholinesterase (AChE derived from the Chinese folk medicine Huperzia serrata (Qian Ceng Ta. It is a licensed anti-AD drug in China and is available as a nutraceutical in the US. A growing body of evidence has demonstrated that HupA has multifaceted pharmacological effects. In addition to the symptomatic, cognitive-enhancing effect via inhibition of AChE, a number of recent studies have reported that this drug has non-cholinergic effects on AD. Most important among these is the protective effect of HupA on neurons against amyloid beta-induced oxidative injury and mitochondrial dysfunction as well as via the up-regulation of nerve growth factor and antagonizing N-methyl-D-aspartate receptors. The most recent discovery that HupA may reduce brain iron accumulation lends further support to the argument that HupA could serve as a potential disease-modifying agent for AD and also other neurodegenerative disorders by significantly slowing down the course of neuronal death.

  15. The Neuroprotective Disease-Modifying Potential of Psychotropics in Parkinson's Disease

    Directory of Open Access Journals (Sweden)

    Edward C. Lauterbach

    2012-01-01

    Full Text Available Neuroprotective treatments in Parkinson's disease (PD have remained elusive. Psychotropics are commonly prescribed in PD without regard to their pathobiological effects. The authors investigated the effects of psychotropics on pathobiological proteins, proteasomal activity, mitochondrial functions, apoptosis, neuroinflammation, trophic factors, stem cells, and neurogenesis. Only findings replicated in at least 2 studies were considered for these actions. Additionally, PD-related gene transcription, animal model, and human neuroprotective clinical trial data were reviewed. Results indicate that, from a PD pathobiology perspective, the safest drugs (i.e., drugs least likely to promote cellular neurodegenerative mechanisms balanced against their likelihood of promoting neuroprotective mechanisms include pramipexole, valproate, lithium, desipramine, escitalopram, and dextromethorphan. Fluoxetine favorably affects transcription of multiple genes (e.g., MAPT, GBA, CCDC62, HIP1R, although it and desipramine reduced MPTP mouse survival. Haloperidol is best avoided. The most promising neuroprotective investigative priorities will involve disease-modifying trials of the safest agents alone or in combination to capture salutary effects on H3 histone deacetylase, gene transcription, glycogen synthase kinase-3, α-synuclein, reactive oxygen species (ROS, reactive nitrogen species (RNS, apoptosis, inflammation, and trophic factors including GDNF and BDNF.

  16. Effect of three biological response modifiers on chemical carcinogenesis in mice.

    Science.gov (United States)

    Bogdanović, Z; Culo, F; Marusić, M

    1993-01-01

    The modulation of chemical carcinogenesis by three biological response modifiers was assessed in a mouse model. CBA mice given 20-methylcholanthrene s.c. were treated with peptidoglycan monomer, azure B and indomethacin for one month, either from day 0 or 75 after methylcholanthrene injection to assess their effects on tumor incidence (on days 150 and 300), time of tumor appearance, time of death, and duration and dynamics of tumor growth. All three agents significantly influenced some of the parameters of tumor growth, except tumor incidence on day 300. Highly significant sex differences in tumor appearance and growth were observed. Tumors with late appearance grew faster in comparison to tumors with early appearance. The data presented indicate that the effectiveness of anti-cancer body defense mechanisms can be best defined by the time of tumor appearance. PMID:8272149

  17. Epidemiology, classification, and modifiable risk factors of peripheral arterial disease

    Directory of Open Access Journals (Sweden)

    Nicolas W Shammas

    2007-05-01

    Full Text Available Nicolas W ShammasMidwest Cardiovascular Research Foundation, Cardiovascular Medicine, PC, Davenport, IA, USAAbstract: Peripheral arterial disease (PAD is part of a global vascular problem of diffuse atherosclerosis. PAD patients die mostly of cardiac and cerebrovascular-related events and much less frequently due to obstructive disease of the lower extremities. Aggressive risk factors modification is needed to reduce cardiac mortality in PAD patients. These include smoking cessation, reduction of blood pressure to current guidelines, aggressive low density lipoprotein lowering, losing weight, controlling diabetes and the use of oral antiplatelet drugs such as aspirin or clopidogrel. In addition to quitting smoking and exercise, cilostazol and statins have been shown to reduce claudication in patients with PAD. Patients with critical rest limb ischemia or severe progressive claudication need to be treated with revascularization to minimize the chance of limb loss, reduce symptoms, and improve quality of life.Keywords: peripheral arterial disease, epidemiology, risk factors, classification

  18. ANALISIS ARGUMENTASI MAHASISWA PENDIDIKAN BIOLOGI PADA ISU SOSIOSAINFIK KONSUMSI GENETICALLY MODIFIED ORGANISM (GMO

    Directory of Open Access Journals (Sweden)

    Y. Herlanti

    2014-04-01

    Full Text Available Penelitian ini bertujuan untuk menganalisis argumentasi yang dikemukakan oleh mahasiswa pendidikan biologi terkait isu sosiosaintifik yaitu konsumsi pangan Genetically Modified Organism (GMO.  Penelitian menggunakan metode survei secara online.  Partisipan yang berasal dari semester III-VII Universitas Islam Negeri Jakarta yang secara sukarela mengisi kuisioner online yang diunggah pada weblog. Hasil penelitian menunjukkan isu sosiosaintifik GMO lebih banyak ditanggapi secara saintifik oleh partisipan.  Argumentasi sebagian besar berada pada level II, yaitu telah mampu mengungkapkan sebuah klaim disertai dengan alasan. Hanya sedikit yang sudah mampu memberikan argumen secara holistik (level IV, yaitu mampu mengungkapkan argumen dengan alasan yang kuat yang tidak mudah dibantah.  Umumnya argumentasi yang dikemukan partisipan berjenis argumentasi sederhana dan argumentasi tipe rantai.  Berdasarkan temuan ini, perlu dikembangkan sebuah model perkuliahan yang dapat meningkatkan keterampilan berargumentasi. This research aimed to analyze the argument for socioscientifik issue “Genetically Modified Organism (GMO Food Consumtion”.  This reseach used online survey.  Participant filled online questionaire that uploaded in weblog.  Participants are student of biology education in Jakarta Islamic State University. The result showed most participants gave scientific view in their argument.  Most of argumentations were in level II; participants gave a klaim within a warrant.  Only a few argument were in level IV, it’s a holistic argument that contained a klaim, a warrant, a backing, and a rebuttal.  Most of argument had simple type or chain type.  From this result, university must develop strategies of lecturing to improve argumentation skill.

  19. International Biological Engagement Programs Facilitate Newcastle Disease Epidemiological Studies.

    Science.gov (United States)

    Miller, Patti J; Dimitrov, Kiril M; Williams-Coplin, Dawn; Peterson, Melanie P; Pantin-Jackwood, Mary J; Swayne, David E; Suarez, David L; Afonso, Claudio L

    2015-01-01

    Infections of poultry species with virulent strains of Newcastle disease virus (NDV) cause Newcastle disease (ND), one of the most economically significant and devastating diseases for poultry producers worldwide. Biological engagement programs between the Southeast Poultry Research Laboratory (SEPRL) of the United States Department of Agriculture and laboratories from Russia, Pakistan, Ukraine, Kazakhstan, and Indonesia collectively have produced a better understanding of the genetic diversity and evolution of the viruses responsible for ND, which is crucial for the control of the disease. The data from Kazakhstan, Russia, and Ukraine identified possible migratory routes for birds that may carry both virulent NDV (vNDV) and NDV of low virulence into Europe. In addition, related NDV strains were isolated from wild birds in Ukraine and Nigeria, and from birds in continental USA, Alaska, Russia, and Japan, identifying wild birds as a possible mechanism of intercontinental spread of NDV of low virulence. More recently, the detection of new sub-genotypes of vNDV suggests that a new, fifth, panzootic of ND has already originated in Southeast Asia, extended to the Middle East, and is now entering into Eastern Europe. Despite expected challenges when multiple independent laboratories interact, many scientists from the collaborating countries have successfully been trained by SEPRL on molecular diagnostics, best laboratory practices, and critical biosecurity protocols, providing our partners the capacity to further train other employes and to identify locally the viruses that cause this OIE listed disease. These and other collaborations with partners in Mexico, Bulgaria, Israel, and Tanzania have allowed SEPRL scientists to engage in field studies, to elucidate more aspects of ND epidemiology in endemic countries, and to understand the challenges that the scientists and field veterinarians in these countries face on a daily basis. Finally, new viral characterization tools

  20. Modulation at Age of Onset in Tunisian Huntington Disease Patients: Implication of New Modifier Genes

    Directory of Open Access Journals (Sweden)

    Dorra Hmida-Ben Brahim

    2014-01-01

    Full Text Available Huntington’s disease (HD is an autosomal dominant neurodegenerative disorder. The causative mutation is an expansion of more than 36 CAG repeats in the first exon of IT15 gene. Many studies have shown that the IT15 interacts with several modifier genes to regulate the age at onset (AO of HD. Our study aims to investigate the implication of CAG expansion and 9 modifiers in the age at onset variance of 15 HD Tunisian patients and to establish the correlation between these modifiers genes and the AO of this disease. Despite the small number of studied patients, this report consists of the first North African study in Huntington disease patients. Our results approve a specific effect of modifiers genes in each population.

  1. Surface chemical and biological characterization of flax fabrics modified with silver nanoparticles for biomedical applications

    Energy Technology Data Exchange (ETDEWEB)

    Paladini, F., E-mail: federica.paladini@unisalento.it [Department of Engineering for Innovation, University of Salento, Via per Monteroni, 73100 Lecce (Italy); Picca, R.A.; Sportelli, M.C.; Cioffi, N. [Department of Chemistry, University of Bari “Aldo Moro”, Via Orabona 4, 70126 Bari (Italy); Sannino, A.; Pollini, M. [Department of Engineering for Innovation, University of Salento, Via per Monteroni, 73100 Lecce (Italy)

    2015-07-01

    Silver nanophases are increasingly used as effective antibacterial agent for biomedical applications and wound healing. This work aims to investigate the surface chemical composition and biological properties of silver nanoparticle-modified flax substrates. Silver coatings were deposited on textiles through the in situ photo-reduction of a silver solution, by means of a large-scale apparatus. The silver-coated materials were characterized through X-ray Photoelectron Spectroscopy (XPS), to assess the surface elemental composition of the coatings, and the chemical speciation of both the substrate and the antibacterial nanophases. A detailed investigation of XPS high resolution regions outlined that silver is mainly present on nanophases' surface as Ag{sub 2}O. Scanning electron microscopy and energy dispersive X-ray spectroscopy were also carried out, in order to visualize the distribution of silver particles on the fibers. The materials were also characterized from a biological point of view in terms of antibacterial capability and cytotoxicity. Agar diffusion tests and bacterial enumeration tests were performed on Gram positive and Gram negative bacteria, namely Staphylococcus aureus and Escherichia coli. In vitro cytotoxicity tests were performed through the extract method on murine fibroblasts in order to verify if the presence of the silver coating affected the cellular viability and proliferation. Durability of the coating was also assessed, thus confirming the successful scaling up of the process, which will be therefore available for large-scale production. - Highlights: • Silver nanophases are increasingly used as effective antibacterial agent for biomedical applications. • Silver coatings were deposited on textiles through the in situ photo-reduction of a silver solution. • Flax fabrics were characterized from a biological and surface chemical point of view. • Scaling up of the process was confirmed.

  2. Surface chemical and biological characterization of flax fabrics modified with silver nanoparticles for biomedical applications

    International Nuclear Information System (INIS)

    Silver nanophases are increasingly used as effective antibacterial agent for biomedical applications and wound healing. This work aims to investigate the surface chemical composition and biological properties of silver nanoparticle-modified flax substrates. Silver coatings were deposited on textiles through the in situ photo-reduction of a silver solution, by means of a large-scale apparatus. The silver-coated materials were characterized through X-ray Photoelectron Spectroscopy (XPS), to assess the surface elemental composition of the coatings, and the chemical speciation of both the substrate and the antibacterial nanophases. A detailed investigation of XPS high resolution regions outlined that silver is mainly present on nanophases' surface as Ag2O. Scanning electron microscopy and energy dispersive X-ray spectroscopy were also carried out, in order to visualize the distribution of silver particles on the fibers. The materials were also characterized from a biological point of view in terms of antibacterial capability and cytotoxicity. Agar diffusion tests and bacterial enumeration tests were performed on Gram positive and Gram negative bacteria, namely Staphylococcus aureus and Escherichia coli. In vitro cytotoxicity tests were performed through the extract method on murine fibroblasts in order to verify if the presence of the silver coating affected the cellular viability and proliferation. Durability of the coating was also assessed, thus confirming the successful scaling up of the process, which will be therefore available for large-scale production. - Highlights: • Silver nanophases are increasingly used as effective antibacterial agent for biomedical applications. • Silver coatings were deposited on textiles through the in situ photo-reduction of a silver solution. • Flax fabrics were characterized from a biological and surface chemical point of view. • Scaling up of the process was confirmed

  3. Glycogen storage disease type III: modified Atkins diet improves myopathy

    OpenAIRE

    Mayorandan, Sebene; Meyer, Uta; Hartmann, Hans; Das, Anibh Martin

    2014-01-01

    Background Frequent feeds with carbohydrate-rich meals or continuous enteral feeding has been the therapy of choice in glycogen storage disease (Glycogenosis) type III. Recent guidelines on diagnosis and management recommend frequent feedings with high complex carbohydrates or cornstarch avoiding fasting in children, while in adults a low-carb-high-protein-diet is recommended. While this regimen can prevent hypoglycaemia in children it does not improve skeletal and heart muscle function, whic...

  4. Genetically Modified T Cells for the Treatment of Malignant Disease

    OpenAIRE

    Wieczorek, Agnieszka; Uharek, Lutz

    2013-01-01

    The broaden application of adoptive T-cell transfer has been constrained by the technical abilities to isolate and expand antigen-specific T cells potent to selectively kill tumor cells. With the recent progress in the design and manufacturing of cellular products, T cells used in the treatment of malignant diseases may be regarded as anticancer biopharmaceuticals. Genetical manipulation of T cells has given T cells desired specificity but also enable to tailor their activation and proliferat...

  5. Biological Functional Relevance of Asymmetric Dimethylarginine (ADMA in Cardiovascular Disease

    Directory of Open Access Journals (Sweden)

    Sara Franceschelli

    2013-12-01

    Full Text Available There is growing evidence that increased levels of the endogenous NO synthase inhibitor asymmetric dimethylarginine (ADMA may contribute to endothelial dysfunction. Studies in animal models as well as in humans have suggested that the increase in ADMA occurs at a time when vascular disease has not yet become clinically evident. ADMA competitively inhibits NO elaboration by displacing L-arginine from NO synthase. In a concentration-dependent manner, it thereby interferes not only with endothelium-dependent, NO-mediated vasodilation, but also with other biological functions exerted by NO. The upshot may be a pro-atherogenic state. Recently, several studies have investigated the effect of various therapeutical interventions on ADMA plasma concentrations.

  6. [Combination biological therapy for fistular Crohn's disease: clinical demonstration].

    Science.gov (United States)

    Knyazev, O V; Parfenov, A I; Shcherbakov, P L; Konoplyannikov, A G; Ruchkina, I N; Lischchinskaya, A A

    2014-01-01

    Perianal fistulas are the most common and frequently encountered types of fistulas in Crohn's disease (CD). They are incurable, may worsen quality of life in a patient and increase the risk of total bowel resection. Despite the significant impact of biological (anticytokine) therapy for fistular CD, treatment in this category of patients remains a difficult task with the high risk of recurrent CD. Mesenchymal stromal cells (MSCs) having immunomodulatory properties and a great regenerative potential are currently also used to treat fistulas in CD and perianal fistulas of another etiology. The given clinical case demonstrates that complete fistula healing could be achieved only after a few local administrations of MSCs in combination with infliximab and azathioprine. World and our experiences indicate that there is a need for randomized controlled trials with a sufficient number of patients to prove the efficacy of MSCs in the combination therapy of fistulas in CD. PMID:24772517

  7. Recent advances in biological therapy for inflammatory bowel disease.

    Science.gov (United States)

    Kurtovic, Jelica; Segal, Isidor

    2004-01-01

    Immune system is a major determinant of pathophysiology of inflammatory bowel disease (IBD), and cytokines are well known mediators of immune system. Recently, informations on pro-inflammatory cytokines and their role in IBD have led to development of potential therapeutic approach to manipulate these cytokines and there by inhibiting inflammation in IBD. These therapeutic approaches include inhibitors of the tumour necrosis factor (TNF)-alpha lymphocyte trafficking, type 1 T helper (Th1) cell polarization and nuclear factor type beta; immunoregulatory cytokines and various growth factors. Studies on these therapies have documented variable results and the outcomes of many clinical trials are awaited. However, these potential therapies, if become real may revolutionise approach in patients with IBD. Analysis of the inflammed mucosa from patients with Crohn disease (CD) and ulcerative colitis (UC) have shown increased expression of certain proinflammatory cytokines such as interleukin-1 (IL-1), interleukin 6 (IL-6) and TNF-alpha. The latter is important in the recruitment of neutrophils into inflammed tissue, a process which results from three physiological steps: (i) rolling, (ii) adhesion, and (iii) transendothelial migration. Understanding of the biology of chronic inflammation has expanded the therapies available for IBD and particularly CD. At present, the biological therapies that are being used in clinical practice or investigated for the treatment of IBD are predominantly proteins, usually delivered intravenously or subcutaneously. The therapies used include: 1. TNF-alpha inhibitors: infliximab, CDP 571, etanercept, onercept, CNI- 1493 and thalidomide. 2. Inhibitors of lymphocyte trafficking: natalizumab, LPD-02 and ICAM-1. 3. Inhibitors of Th1 polarization: monoclonal antibodies for IL-12, interferon (IFN)-gamma and anti IFN-gamma. 4. Immunoregulatory cytokines: IL-10 and IL-11. 5. Inhibitors of nuclear factor kappa (beta NF-kbeta.) 6. Growth factors

  8. Tubulin acetylation: responsible enzymes, biological functions and human diseases.

    Science.gov (United States)

    Li, Lin; Yang, Xiang-Jiao

    2015-11-01

    Microtubules have important functions ranging from maintenance of cell morphology to subcellular transport, cellular signaling, cell migration, and formation of cell polarity. At the organismal level, microtubules are crucial for various biological processes, such as viral entry, inflammation, immunity, learning and memory in mammals. Microtubules are subject to various covalent modifications. One such modification is tubulin acetylation, which is associated with stable microtubules and conserved from protists to humans. In the past three decades, this reversible modification has been studied extensively. In mammals, its level is mainly governed by opposing actions of α-tubulin acetyltransferase 1 (ATAT1) and histone deacetylase 6 (HDAC6). Knockout studies of the mouse enzymes have yielded new insights into biological functions of tubulin acetylation. Abnormal levels of this modification are linked to neurological disorders, cancer, heart diseases and other pathological conditions, thereby yielding important therapeutic implications. This review summarizes related studies and concludes that tubulin acetylation is important for regulating microtubule architecture and maintaining microtubule integrity. Together with detyrosination, glutamylation and other modifications, tubulin acetylation may form a unique 'language' to regulate microtubule structure and function. PMID:26227334

  9. Disease-modifying antirheumatic drugs in pregnancy - Current status and implications for the future

    OpenAIRE

    Vroom, Fokaline; de Walle, Hermien E.K.; van de Laar, Mart A. J. F.; Brouwers, Jacobus R B J; De Jong-van den Berg, Lolkje T W

    2006-01-01

    Drug use during pregnancy is sometimes unavoidable, especially in chronic inflammatory diseases such as rheumatoid arthritis (RA). The use of disease-modifying antirheumatic drugs (DMARDs) often starts in the early stage of RA; therefore, women of reproductive age are at risk for exposure to a DMARD at time of conception as well as during pregnancy. The aim of this paper was to review recent literature about DMARDs used for rheumatic diseases in pregnancy and to describe the type of study des...

  10. Ischemia-modified albumin in type 2 diabetic patients with and without peripheral arterial disease

    OpenAIRE

    Shao-Gang Ma; Chun-Ling Wei; Bing Hong; Wei-Nan Yu

    2011-01-01

    OBJECTIVE: To determine whether there is an association between serum ischemia-modified albumin and the risk factor profile in type 2 diabetic patients with peripheral arterial disease and to identify the risk markers for peripheral arterial disease. METHODS: Participants included 290 patients (35.2% women) with type 2 diabetes. The ankle-brachial pressure index was measured using a standard protocol, and peripheral arterial disease was defined as an ankle-brachial index 1.3. The basal ischem...

  11. Cognitive training modifies disease symptoms in a mouse model of Huntington's disease.

    Science.gov (United States)

    Yhnell, Emma; Lelos, Mariah J; Dunnett, Stephen B; Brooks, Simon P

    2016-08-01

    Huntington's disease (HD) is an incurable neurodegenerative disorder which causes a triad of motor, cognitive and psychiatric disturbances. Cognitive disruptions are a core feature of the disease, which significantly affect daily activities and quality of life, therefore cognitive training interventions present an exciting therapeutic intervention possibility for HD. We aimed to determine if specific cognitive training, in an operant task of attention, modifies the subsequent behavioural and neuropathological phenotype of the Hdh(Q111) mouse model of HD. Three testing groups comprising both Hdh(Q111) mice and wildtype controls were used. The first group received cognitive training in an operant task of attention at 4months of age. The second group received cognitive training in a comparable non-attentional operant task at 4months of age, and the third group were control animals that did not receive cognitive training. All groups were then tested in an operant task of attention at 12months of age. Relative to naïve untrained mice, both wildtype and Hdh(Q111) mice that received cognitive training in the operant task of attention demonstrated an increased number of trials initiated, greater accuracy, and fewer 'time out' errors. A specific improvement in response time performance was observed in Hdh(Q111) mice, relative to naïve untrained Hdh(Q111) mice. Relative to the group that received comparable training in a non-attentional task, both wildtype and Hdh(Q111) mice that received attentional training demonstrated superior accuracy in the task and made fewer 'time out' errors. Despite significant behavioural change, in both wildtype and Hdh(Q111) mice that had received cognitive training, no significant changes in neuropathology were observed between any of the testing groups. These results demonstrate that attentional cognitive training implemented at a young age significantly improves attentional performance, at an older age, in both wildtype and Hdh(Q111) mice

  12. Gold Finger: Metal Jewellery as a Disease Modifying Antirheumatic Therapy!

    Directory of Open Access Journals (Sweden)

    T. Hlaing

    2009-01-01

    Full Text Available Polyarticular psoriatic arthritis is a chronic, progressive and disabling auto-immune disease often affecting the small joints of the hands in a symmetrical fashion. The disease can progress rapidly causing joint swelling and damaging cartilage and bone around the joints resulting in severe deformities. We report a very unusual case of a 49-year-old woman who presented with polyarticular psoriatic arthritis affecting all proximal interphalangeal (PIP joints of both hands except the left ring finger PIP joint. On clinical examination there was no evidence of arthritis in the left ring finger PIP joint. We confirmed the paucity of joint damage in the PIP joint of the left ring finger using more modern imaging modalities such as musculoskeletal ultrasound and MRI scan of the small joints of the hands. All other PIP joints in both hands demonstrated advanced degrees of joint damage secondary to chronic psoriatic inflammatory arthritis. We postulated that wearing a gold wedding ring has helped protecting the PIP joint of the left ring finger from the damaging effect of inflammatory arthritis. The possible mechanisms by which metal jewellery (gold ring confer protection to adjacent joints was discussed.

  13. A GABBR2 gene variant modifies pathophysiology in Huntington's disease.

    Science.gov (United States)

    Philpott, April L; Fitzgerald, Paul B; Bailey, Neil W; Churchyard, Andrew; Georgiou-Karistianis, Nellie; Cummins, Tarrant D R

    2016-05-01

    Striatal degeneration in Huntington's disease (HD) causes changes in cortico-subcortical pathways. Transcranial magnetic stimulation (TMS) is a valuable tool for assessing pathophysiology within these pathways, yet has had limited application in HD. As cortico-subcortical pathways are largely mediated by GABA and dopamine receptor genes, understanding how these genes modulate neurophysiology in HD may provide new insights into how underlying pathology maps onto clinical phenotype. Twenty-nine participants with HD underwent motor cortex stimulation, while corticospinal excitability, cortical inhibition and intracortical facilitation were indexed via peripheral electromyography. Single-nucleotide polymorphism mapping was performed across six genes that are known to modulate cortico-subcortical pathways (GABRA2, GABBR1, GABBR2, DRD1, DRD2, DRD4). Genetic associations with six TMS measures and age at onset were investigated. Our hierarchical multiple regression analysis, controlling for CAG and age, revealed that a GABBR2 variant, predicted to be disease-causative, was significantly associated with corticospinal excitability at corrected levels. A subsequent uncorrected exploratory analysis revealed associations between GABBR2, GABRA2 and DRD2 variants with TMS measures of corticospinal excitability and cortical inhibition in HD, as well as with age at onset. Our findings support the notion that uncovering genetic associations with pathophysiological measures and age at onset is an important way forward in terms of generating meaningful biomarkers with diagnostic and prognostic sensitivity, and identifying novel human-validated targets for future clinical trials. PMID:27033668

  14. Newcastle disease: Molecular-biological diagnosis in the Russian Federation

    International Nuclear Information System (INIS)

    Newcastle disease is registered in the Russian Federation and for last time it is seen an upward tendency of ND outbreaks in backyards poultry due to lack of specific prophylaxis. Reports on ND outbreaks from 2004 to 2007 submitted to OIE are shown. The use of molecular-biological methods can reveal ND virus in the lab. ARRIAH has acquired practical experience in the diagnosis of ND virus and holds data on ND viruses identified or isolated in the course of the current diagnostic and monitoring investigations of samples from wild and domestic birds. The developed set of molecular-biological methods allows ND virus to be reliably and rapidly detected in field samples. They are also able to characterize ND viruses with F-gene sequencing that can be used for the assessment of potential virulence, their phylogenetic belonging which will aid in making decisions of how to fight the disease, to trace a possible source of infection and further spread. The developed set of molecular-biological methods of ND diagnosis includes: - ND virus detection with RT-PCR and F-gene sequencing, determination of potential virulence based on F0-amino acid restriction site; - ND virus detection with RT-PCR and ND-gene sequencing; - ND virus detection with RT-PCR and vaccine strain La-Sota differentiation based on the Fgene; - Genotyping of ND viruses revealed in Russia Genetic characterization of ND viruses allows rapid and reliable determination of their group belonging and also helps make conclusions about presence or absence of any epizootic links among outbreaks, their possible source, spread routes, current and potential threat to poultry farms. A total of 657 field samples from wild and domestic birds were PCR tested in 2007. The samples covered 20 regions of Russia and the Ukraine. ND virus was found in 8 regions of Russia. 516 samples were from wild birds with 9 positive results and 141 samples were from domestic birds with 16 positive results. PCR and sequencing identified 17

  15. Total and phosphorylated tau protein as biological markers of Alzheimer's disease.

    LENUS (Irish Health Repository)

    Hampel, Harald

    2012-02-01

    Advances in our understanding of tau-mediated neurodegeneration in Alzheimer\\'s disease (AD) are moving this disease pathway to center stage for the development of biomarkers and disease modifying drug discovery efforts. Immunoassays were developed detecting total (t-tau) and tau phosphorylated at specific epitopes (p-tauX) in cerebrospinal fluid (CSF), methods to analyse tau in blood are at the experimental beginning. Clinical research consistently demonstrated CSF t- and p-tau increased in AD compared to controls. Measuring these tau species proved informative for classifying AD from relevant differential diagnoses. Tau phosphorylated at threonine 231 (p-tau231) differentiated between AD and frontotemporal dementia, tau phosphorylated at serine 181 (p-tau181) enhanced classification between AD and dementia with Lewy bodies. T- and p-tau are considered "core" AD biomarkers that have been successfully validated by controlled large-scale multi-center studies. Tau biomarkers are implemented in clinical trials to reflect biological activity, mechanisms of action of compounds, support enrichment of target populations, provide endpoints for proof-of-concept and confirmatory trials on disease modification. World-wide quality control initiatives are underway to set required methodological and protocol standards. Discussions with regulatory authorities gain momentum defining the role of tau biomarkers for trial designs and how they may be further qualified for surrogate marker status.

  16. Alzheimer disease: modeling an Aβ-centered biological network.

    Science.gov (United States)

    Campion, D; Pottier, C; Nicolas, G; Le Guennec, K; Rovelet-Lecrux, A

    2016-07-01

    In genetically complex diseases, the search for missing heritability is focusing on rare variants with large effect. Thanks to next generation sequencing technologies, genome-wide characterization of these variants is now feasible in every individual. However, a lesson from current studies is that collapsing rare variants at the gene level is often insufficient to obtain a statistically significant signal in case-control studies, and that network-based analyses are an attractive complement to classical approaches. In Alzheimer disease (AD), according to the prevalent amyloid cascade hypothesis, the pathology is driven by the amyloid beta (Aβ) peptide. In past years, based on experimental studies, several hundreds of proteins have been shown to interfere with Aβ production, clearance, aggregation or toxicity. Thanks to a manual curation of the literature, we identified 335 genes/proteins involved in this biological network and classified them according to their cellular function. The complete list of genes, or its subcomponents, will be of interest in ongoing AD genetic studies. PMID:27021818

  17. Muscle dysfunction in chronic obstructive pulmonary disease: update on causes and biological findings.

    Science.gov (United States)

    Gea, Joaquim; Pascual, Sergi; Casadevall, Carme; Orozco-Levi, Mauricio; Barreiro, Esther

    2015-10-01

    Respiratory and/or limb muscle dysfunction, which are frequently observed in chronic obstructive pulmonary disease (COPD) patients, contribute to their disease prognosis irrespective of the lung function. Muscle dysfunction is caused by the interaction of local and systemic factors. The key deleterious etiologic factors are pulmonary hyperinflation for the respiratory muscles and deconditioning secondary to reduced physical activity for limb muscles. Nonetheless, cigarette smoke, systemic inflammation, nutritional abnormalities, exercise, exacerbations, anabolic insufficiency, drugs and comorbidities also seem to play a relevant role. All these factors modify the phenotype of the muscles, through the induction of several biological phenomena in patients with COPD. While respiratory muscles improve their aerobic phenotype (percentage of oxidative fibers, capillarization, mitochondrial density, enzyme activity in the aerobic pathways, etc.), limb muscles exhibit the opposite phenotype. In addition, both muscle groups show oxidative stress, signs of damage and epigenetic changes. However, fiber atrophy, increased number of inflammatory cells, altered regenerative capacity; signs of apoptosis and autophagy, and an imbalance between protein synthesis and breakdown are rather characteristic features of the limb muscles, mostly in patients with reduced body weight. Despite that significant progress has been achieved in the last decades, full elucidation of the specific roles of the target biological mechanisms involved in COPD muscle dysfunction is still required. Such an achievement will be crucial to adequately tackle with this relevant clinical problem of COPD patients in the near-future. PMID:26623119

  18. Dissecting Complex and Multifactorial Nature of Alzheimer's Disease Pathogenesis: a Clinical, Genomic, and Systems Biology Perspective.

    Science.gov (United States)

    Talwar, Puneet; Sinha, Juhi; Grover, Sandeep; Rawat, Chitra; Kushwaha, Suman; Agarwal, Rachna; Taneja, Vibha; Kukreti, Ritushree

    2016-09-01

    Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by loss of memory and other cognitive functions. AD can be classified into familial AD (FAD) and sporadic AD (SAD) based on heritability and into early onset AD (EOAD) and late onset AD (LOAD) based on age of onset. LOAD cases are more prevalent with genetically complex architecture. In spite of significant research focused on understanding the etiological mechanisms, search for diagnostic biomarker(s) and disease-modifying therapy is still on. In this article, we aim to comprehensively review AD literature on established etiological mechanisms including role of beta-amyloid and apolipoprotein E (APOE) along with promising newer etiological factors such as epigenetic modifications that have been associated with AD suggesting its multifactorial nature. As genomic studies have recently played a significant role in elucidating AD pathophysiology, a systematic review of findings from genome-wide linkage (GWL), genome-wide association (GWA), genome-wide expression (GWE), and epigenome-wide association studies (EWAS) was conducted. The availability of multi-dimensional genomic data has further coincided with the advent of computational and network biology approaches in recent years. Our review highlights the importance of integrative approaches involving genomics and systems biology perspective in elucidating AD pathophysiology. The promising newer approaches may provide reliable means of early and more specific diagnosis and help identify therapeutic interventions for LOAD. PMID:26351077

  19. ECOLOGY OF PANTOEA AGGLOMERANS 2066-7 STRAIN: A BIOLOGICAL CONTROL OF BACTERIA ONION DISEASES

    Directory of Open Access Journals (Sweden)

    Soumia Sadik

    2016-06-01

    Full Text Available The growth response of the biocontrol agent Pantoea agglomerans 2066-7 to change in water activity (aw, temperature, and pH was determined in vitro in basic medium. The minimum temperature at which 2066-7 was able to grow was 7°C, and the growth of 2066-7 did not change at varying pH levels (4–10.34. The best growth was obtained at a water activity of 0.98 in all media modified with the four solutes (glucose, glycerol, NaCl and polyethylene glycol. The solute used to reduce water activity had a great influence on bacterial growth, especially at unfavorable conditions (low temperature. This study has defined the range of environmental conditions (aw, pH, and temperature over which the bacteria may be developed for biological control of plant diseases.

  20. ChemProt: A disease chemical biology database

    DEFF Research Database (Denmark)

    Taboureau, Olivier; Oprea, Tudor I.

    2013-01-01

    The integration of chemistry, biology, and informatics to study drug actions across multiple biological targets, pathways, and biological systems is an emerging paradigm in drug discovery. Rather than reducing a complex system to simplistic models, fields such as chemogenomics and translational...... chemical biology, drug repurposing, and off-target effects prediction....

  1. Obesity as an effect modifier of the association between leptin and diabetic kidney disease

    OpenAIRE

    Hanai, Ko; Babazono, Tetsuya; Takagi, Michino; Yoshida, Naoshi; Nyumura, Izumi; Toya, Kiwako; Tanaka, Nobue; Uchigata, Yasuko

    2013-01-01

    Abstract Aims/Introduction Obesity has been shown to be a modifier of the association between leptin levels and cardiovascular events. We examined whether obesity modifies the association between serum leptin levels and the progression of diabetic kidney disease. Materials and Methods This was an observational longitudinal study on patients with type 2 diabetes. We enrolled 410 and 348 patients in the eGFR and ACR cohorts, respectively. Patients were classified into three groups by sex‐specif...

  2. Parkinson's disease and segmental coordination during modified figure of eight walking turning task

    OpenAIRE

    Cheung, Rachel

    2016-01-01

    Turning while walking is problematic for individuals with Parkinson’s disease (PD). We hypothesized there would be instability and turning difficulty for the PD subjects while performing a complex motor skill task of the modified figure of eight (MFE) walking task. There were 26 subjects (10 males and 16 females) with clinical diagnosis of “idiopathic” PD and undergoing L-dopa treatment participating in this study. The PD subjects performed the clinical balance modified figure of eight (MFE) ...

  3. Risk factors that may modify the innate and adaptive immune responses in periodontal diseases.

    Science.gov (United States)

    Knight, Ellie T; Liu, Jenny; Seymour, Gregory J; Faggion, Clovis M; Cullinan, Mary P

    2016-06-01

    Plaque-induced periodontal diseases occur in response to the accumulation of dental plaque. Disease manifestation and progression is determined by the nature of the immune response to the bacterial complexes in plaque. In general, predisposing factors for these periodontal diseases can be defined as those factors which retain or hinder the removal of plaque and, depending upon the nature of the immune response to this plaque, the disease will either remain stable and not progress or it may progress and result in chronic periodontitis. In contrast, modifying factors can be defined as those factors that alter the nature or course of the inflammatory lesion. These factors do not cause the disease but rather modify the chronic inflammatory response, which, in turn, is determined by the nature of the innate and adaptive immune responses and the local cytokine and inflammatory mediator networks. Chronic inflammation is characterized by vascular, cellular and repair responses within the tissues. This paper will focus on how common modifying factors, such as smoking, stress, hormonal changes, diabetes, metabolic syndrome and HIV/AIDS, influence each of these responses, together with treatment implications. As treatment planning in periodontics requires an understanding of the etiology and pathogenesis of the disease, it is important for all modifying factors to be taken into account. For some of these, such as smoking, stress and diabetic control, supportive health behavior advice within the dental setting should be an integral component for overall patient management. PMID:27045429

  4. Biological Behavior of Osteoblast Cell and Apatite Forming Ability of the Surface Modified Ti Alloys.

    Science.gov (United States)

    Zhao, Jingming; Hwang, K H; Choi, W S; Shin, S J; Lee, J K

    2016-02-01

    Titanium as one kind of biomaterials comes in direct contact with the body, making evaluation of biocompatibility an important aspect to biomaterials development. Surface chemistry of titanium plays an important role in osseointegration. Different surface modification alters the surface chemistry and result in different biological response. In this study, three kinds of mixed acid solutions were used to treat Ti specimens to induce Ca-P formation. Following a strong mixed acid activation process, Ca-P coating successfully formed on the Ti surfaces in simulated body fluid. Strong mixed acid increased the roughness of the metal surface, because the porous and rough surface allows better adhesion between Ca-P coatings and substrates. After modification of titanium surface by mixed acidic solution and subsequently H2O2/HCL treatment evaluation of biocompatibility was conducted from hydroxyapatite formation by biomimetic process and cell viability on modified titanium surface. Nano-scale modification of titanium surfaces can alter cellular and tissue responses, which may benefit osseointegration and dental implant therapy. Results from this study indicated that surface treatment methods affect the surface morphology, type of TiO2 layer formed and subsequent apatite deposition and biological responses. The thermo scientific alamarblue cell viability assay reagent is used to quantitatively measure the viability of mammalian cell lines, bacteria and fungi by incorporating a rapid, sensitive and reliable fluorometric/colorimetric growth indicator, without any toxic and side effect to cell line. In addition, mixed acid treatment uses a lower temperature and shorter time period than widely used alkali treatment. PMID:27433617

  5. Modulation at Age of Onset in Tunisian Huntington Disease Patients: Implication of New Modifier Genes

    OpenAIRE

    Dorra Hmida-Ben Brahim; Marwa Chourabi; Sana Ben Amor; Imed Harrabi; Saoussen Trabelsi; Marwa Haddaji-Mastouri; Moez Gribaa; Sihem Sassi; Fatma Ezzahra Gahbiche; Turkia Lamouchi; Soumaya Mougou-Zereli; Sofiane Ben Ammou; Ali Saad

    2014-01-01

    Huntington’s disease (HD) is an autosomal dominant neurodegenerative disorder. The causative mutation is an expansion of more than 36 CAG repeats in the first exon of IT15 gene. Many studies have shown that the IT15 interacts with several modifier genes to regulate the age at onset (AO) of HD. Our study aims to investigate the implication of CAG expansion and 9 modifiers in the age at onset variance of 15 HD Tunisian patients and to establish the correlation between these modifiers genes and ...

  6. Activation of a distinct subpopulation of pulmonary macrophages following exposure to biological response modifiers.

    Science.gov (United States)

    Drath, D B; Do, C; Burd, T; Hong, L L

    1994-03-01

    A distinct subpopulation of tissue-associated pulmonary macrophages (TAPM) displayed tumoricidal activity towards syngeneic and xenogeneic targets following in vitro incubation with N-acetylmuramyl-L-alanyl-D-isoglutamine (MDP). This subpopulation, as well as, the predominant population of freely lavagable alveolar macrophages destroyed allogeneic targets following a similar incubation with either 6-0-stearoyl MDP (S-MDP) or recombinant interferon-gamma (IFN-gamma). IFN-gamma-induced in vivo tumoricidal activation of both populations of pulmonary macrophage was most effective when delivered either intravenously or via osmotic minipump infusion and least effective when administered by direct intratracheal instillation. The separate populations also displayed in vivo activation in response to liposome-encapsulated i.v. administered S-MDP. Under comparable conditions, IFN-alpha was not nearly as effective. Metabolic activation of TAPM, assessed by the release of increased levels of superoxide free radicals during phagocytosis, occurred following 24 hr exposure to S-MDP or lipopolysaccharide. Incorporation of these agents into multilamellar vesicle liposomes further augmented the release of superoxide observed at 24 hrs. Our results collectively demonstrated that a subpopulation of lung macrophage, a tissue-associated pulmonary macrophage, may be activated to a tumoricidal state and to release pronounced levels of oxygen free radicals following either in vitro or in situ treatment with several biological response modifiers. PMID:8194852

  7. Physiochemical and Biological Properties of Modified Collagen Sponge from Porcine Skin

    Institute of Scientific and Technical Information of China (English)

    XU Yuanyuan; HUANG Shujie; WU Jimin; GUAN Jing; ZHANG Xizheng; LI Zhihong; WANG Pengfei; LI Ruixin; GUO Yong; NING Bo

    2009-01-01

    The aim of the present study was to compare one-step method to EDC/NHS crosslinking(EDC/NHS group)and one-step simultaneous method to EDC/NHS crosslinking and heparin immobilization(EDC/NHS-Heparin group)in improving physiochemical and biological properties of native collagen sponge(Control group).Modified collagen sponge overcome the disad-vantages of native collagen sponge.IR spectra suggest the change of the functional groups.DSC data indicate that the stability of caloric transformation in EDC/NHS group is slightly higher than that of EDC/NHS-Heparin group.The crosslinking degree,stability against enzymes,stability in morpho-logically and biomechanical properties of EDC/NHS-Heparin group are higher than those of EDC/NHS group,whereas,the water-binding capacity in EDC/NHS-Heparin group is lower than that of EDC/NHS group.HUVECs in EDC/NHS-Heparin group scaffold proliferate fast,migrate well and distribute uniformly.One-step simultaneous method gains the better effects in above aspects, heparinized collagen matrices increase in angiogenic potential and suit for defect repairing and tissue engineering.

  8. Biological activity of a genetically modified BMP-2 variant with inhibitory activity

    Directory of Open Access Journals (Sweden)

    Kübler Alexander C

    2009-02-01

    Full Text Available Abstract Background Alterations of the binding epitopes of bone morphogenetic protein-2 (BMP-2 lead to a modified interaction with the ectodomains of BMP receptors. In the present study the biological effect of a BMP-2 double mutant with antagonistic activity was evaluated in vivo. Methods Equine-derived collagenous carriers were loaded with recombinant human BMP-2 (rhBMP-2 in a well-known dose to provide an osteoinductive stimulus. The study was performed in a split animal design: carriers only coupled with rhBMP-2 (control were implanted into prepared cavities of lower limb muscle of rats, specimens coupled with rhBMP-2 as well as BMP-2 double mutant were placed into the opposite limb in the same way. After 28 days the carriers were explanted, measured radiographically and characterized histologically. Results As expected, the BMP-2 loaded implants showed a typical heterotopic bone formation. The specimens coupled with both proteins showed a significant decreased bone formation in a dose dependent manner. Conclusion The antagonistic effect of a specific BMP-2 double mutant could be demonstrated in vivo. The dose dependent influence on heterotopic bone formation by preventing rhBMP-2 induced osteoinduction suggests a competitive receptor antagonism.

  9. Chromosome substitution strain assessment of a Huntington’s disease modifier locus

    OpenAIRE

    Ramos, Eliana Marisa; Kovalenko, Marina; Guide, Jolene R.; St. Claire, Jason; Gillis, Tammy; Mysore, Jayalakshmi S.; Sequeiros, Jorge; Wheeler, Vanessa C; Alonso, Isabel; MacDonald, Marcy E.

    2015-01-01

    Huntington’s disease (HD) is a dominant neurodegenerative disorder that is due to expansion of an unstable HTT CAG repeat for which genome-wide genetic scans are now revealing chromosome regions that contain disease-modifying genes. We have explored a novel human–mouse cross-species functional prioritisation approach, by evaluating the HD modifier 6q23–24 linkage interval. This unbiased strategy employs C57BL/6J (B6J) HdhQ111 knock-in mice, replicates of the HD mutation, and the C57BL/6J-chr1...

  10. Drogas Modificadoras de la Artritis Reumatoide (DMAR Disease Modifying Antirheumatic Drugs (DMARD

    Directory of Open Access Journals (Sweden)

    José Francisco Díaz-Coto

    2011-02-01

    Full Text Available El nuevo paradigma terapéutico de la artritis reumatoide establece que todo paciente con actividad de la enfermedad debe recibir alguna droga modificadora de la artritis reumatoide. Estas drogas reciben este nombre ya que han demostrado en estudios clínicos controlados modificar el curso natural de la enfermedad.The new paradigm for the treatments of rheumatoid arthritis stablish that all patients suffering disease this should receive some drugs which modifys rheumatoid arthritis. These drugs are so named because according to the controlled clinical studies they have shown the ability of modifying the natural course of the diseases.

  11. Systems Toxicology Assessment of the Biological Impact of a Candidate Modified Risk Tobacco Product on Human Organotypic Oral Epithelial Cultures.

    Science.gov (United States)

    Zanetti, Filippo; Sewer, Alain; Mathis, Carole; Iskandar, Anita R; Kostadinova, Radina; Schlage, Walter K; Leroy, Patrice; Majeed, Shoaib; Guedj, Emmanuel; Trivedi, Keyur; Martin, Florian; Elamin, Ashraf; Merg, Céline; Ivanov, Nikolai V; Frentzel, Stefan; Peitsch, Manuel C; Hoeng, Julia

    2016-08-15

    Cigarette smoke (CS) has been reported to increase predisposition to oral cancer and is also recognized as a risk factor for many conditions including periodontal diseases, gingivitis, and other benign mucosal disorders. Smoking cessation remains the most effective approach for minimizing the risk of smoking-related diseases. However, reduction of harmful constituents by heating rather than combusting tobacco, without modifying the amount of nicotine, is a promising new paradigm in harm reduction. In this study, we compared effects of exposure to aerosol derived from a candidate modified risk tobacco product, the tobacco heating system (THS) 2.2, with those of CS generated from the 3R4F reference cigarette. Human organotypic oral epithelial tissue cultures (EpiOral, MatTek Corporation) were exposed for 28 min to 3R4F CS or THS2.2 aerosol, both diluted with air to comparable nicotine concentrations (0.32 or 0.51 mg nicotine/L aerosol/CS for 3R4F and 0.31 or 0.46 mg/L for THS2.2). We also tested one higher concentration (1.09 mg/L) of THS2.2. A systems toxicology approach was employed combining cellular assays (i.e., cytotoxicity and cytochrome P450 activity assays), comprehensive molecular investigations of the buccal epithelial transcriptome (mRNA and miRNA) by means of computational network biology, measurements of secreted proinflammatory markers, and histopathological analysis. We observed that the impact of 3R4F CS was greater than THS2.2 aerosol in terms of cytotoxicity, morphological tissue alterations, and secretion of inflammatory mediators. Analysis of the transcriptomic changes in the exposed oral cultures revealed significant perturbations in various network models such as apoptosis, necroptosis, senescence, xenobiotic metabolism, oxidative stress, and nuclear factor (erythroid-derived 2)-like 2 (NFE2L2) signaling. The stress responses following THS2.2 aerosol exposure were markedly decreased, and the exposed cultures recovered more completely compared

  12. Modified primers for the identification of nonpathogenic Fusarium oxysporum isolates that have biological control potential against Fusarium wilt of cucumber in Taiwan.

    Directory of Open Access Journals (Sweden)

    Chaojen Wang

    Full Text Available Previous investigations demonstrated that Fusarium oxysporum (Fo, which is not pathogenic to cucumbers, could serve as a biological control agent for managing Fusarium wilt of cucumber caused by Fo f. sp. cucumerinum (Foc in Taiwan. However, thus far it has not been possible to separate the populations of pathogenic Fo from the nonpathogenic isolates that have biological control potential through their morphological characteristics. Although these two populations can be distinguished from one another using a bioassay, the work is laborious and time-consuming. In this study, a fragment of the intergenic spacer (IGS region of ribosomal DNA from an Fo biological control agent, Fo366, was PCR-amplified with published general primers, FIGS11/FIGS12 and sequenced. A new primer, NPIGS-R, which was designed based on the IGS sequence, was paired with the FIGS11 primer. These primers were then evaluated for their specificity to amplify DNA from nonpathogenic Fo isolates that have biological control potential. The results showed that the modified primer pair, FIGS11/NPIGS-R, amplified a 500-bp DNA fragment from five of seven nonpathogenic Fo isolates. These five Fo isolates delayed symptom development of cucumber Fusarium wilt in greenhouse bioassay tests. Seventy-seven Fo isolates were obtained from the soil and plant tissues and then subjected to amplification using the modified primer pair; six samples showed positive amplification. These six isolates did not cause symptoms on cucumber seedlings when grown in peat moss infested with the isolates and delayed disease development when the same plants were subsequently inoculated with a virulent isolate of Foc. Therefore, the modified primer pair may prove useful for the identification of Fo isolates that are nonpathogenic to cucumber which can potentially act as biocontrol agents for Fusarium wilt of cucumber.

  13. [The biological activity of macrophages in health and disease].

    Science.gov (United States)

    Nazimek, Katarzyna; Bryniarski, Krzysztof

    2012-01-01

    Macrophages are involved in immune response as phagocytes, antigen presenting cells and as effector cells of delayed-type hypersensitivity. Moreover, the activity of macrophages is associated with modulation of many biological processes during the whole life and depends on the actual macrophage phenotype induced under the influence of various microenvironmental stimuli. In pregnancy, placental macrophages induce the development of maternal tolerance to fetal antigens, while fetal macrophages are responsible for proper formation of tissues and organs. Residual macrophages play a very important role in tissue homeostasis, apoptotic cell clearance to prevent autoimmunization and first defense in infections. The inflammatory response of macrophages may be modulated by pathogens. Their suppressive activity is observed in immunologically privileged organs such as testes. In pathologies, macrophages are responsible for tissue damage in a case of nonspecific activation followed by overproduction of proinflammatory factors. Suppression of a specific immune response against tumors is mainly the effect of tumor associated macrophage (TAM) action. On the other hand, presentation of allergens or self-antigens by macrophages and their nonspecific activation by necrotic adipocytes leads to the induction of a chronic inflammatory response and impairment of immunity. Therefore, modulation of macrophage functions may be the key for improvement of therapy of cancer and allergic, autoimmune, metabolic, cardiovascular and Alzheimer's diseases. PMID:22922151

  14. ChemProt: A disease chemical biology database

    DEFF Research Database (Denmark)

    Taboureau, Olivier; Oprea, Tudor I.

    2013-01-01

    The integration of chemistry, biology, and informatics to study drug actions across multiple biological targets, pathways, and biological systems is an emerging paradigm in drug discovery. Rather than reducing a complex system to simplistic models, fields such as chemogenomics and translational...

  15. Lithium, as a neuroprotective therapy for Alzheimer’s disease pathology, modifies abeta plaque toxicity

    OpenAIRE

    Trujillo-Estrada, Laura; Castro, Vanesa; Jimenez, S; Sanchez-Varo, Raquel; Sanchez-Mejias, Elisabet; Vizuete, Marisa; Vitorica, Javier; Gutierrez, Antonia

    2014-01-01

    BACKGROUND: Despite the relatively large information about the Alzheimer’s disease (AD) pathology, no effective disease-modifying treatment has been yet developed. Lithium, a primary drug to treat bipolar disorder, has been suggested as a potential treatment against AD. In this work we have evaluated whether lithium treatment could ameliorate the neuropathology progression of the transgenic PS1M146L/APPSwe-London mice. Unlike most transgenic animal models, which do not exhibit the neurodegene...

  16. Genetically modified mouse models for the study of nonalcoholic fatty liver disease

    Institute of Scientific and Technical Information of China (English)

    Perumal Nagarajan; M Jerald Mahesh Kumar; Ramasamy Venkatesan; Subeer S Majundar; Ramesh C Juyal

    2012-01-01

    Nonalcoholic fatty liver disease (NAFLD) is associated with obesity,insulin resistance,and type 2 diabetes.NAFLD represents a large spectrum of diseases ranging from (1) fatty liver (hepatic steatosis); (2) steatosis with inflammation and necrosis; to (3) cirrhosis.The animal models to study NAFLD/nonalcoholic steatohepatitis (NASH) are extremely useful,as there are still many events to be elucidated in the pathology of NASH.The study of the established animal models has provided many clues in the pathogenesis of steatosis and steatohepatitis,but these remain incompletely understood.The different mouse models can be classified in two large groups.The first one includes genetically modified (transgenic or knockout) mice that spontaneously develop liver disease,and the second one includes mice that acquire the disease after dietary or pharmacological manipulation.Although the molecular mechanism leading to the development of hepatic steatosis in the pathogenesis of NAFLD is complex,genetically modified animal models may be a key for the treatment of NAFLD.Ideal animal models for NASH should closely resemble the pathological characteristics observed in humans.To date,no single animal model has encompassed the full spectrum of human disease progression,but they can imitate particular characteristics of human disease.Therefore,it is important that the researchers choose the appropriate animal model.This review discusses various genetically modified animal models developed and used in research on NAFLD.

  17. Mining tissue specificity, gene connectivity and disease association to reveal a set of genes that modify the action of disease causing genes

    Directory of Open Access Journals (Sweden)

    Reverter Antonio

    2008-09-01

    genes. Our guilt-by-association algorithm should be useful for the discovery of additional modifiers of genetic diseases, and more generally, for the ability to associate genes of unknown function to clusters of genes with defined functions allowing for novel biological inference that can be subsequently validated.

  18. A Practical Guide for Exploring Opportunities of Repurposing Drugs for CNS Diseases in Systems Biology.

    Science.gov (United States)

    Mei, Hongkang; Feng, Gang; Zhu, Jason; Lin, Simon; Qiu, Yang; Wang, Yue; Xia, Tian

    2016-01-01

    Systems biology has shown its potential in facilitating pathway-focused therapy development for central nervous system (CNS) diseases. An integrated network can be utilized to explore the multiple disease mechanisms and to discover repositioning opportunities. This review covers current therapeutic gaps for CNS diseases and the role of systems biology in pharmaceutical industry. We conclude with a Multiple Level Network Modeling (MLNM) example to illustrate the great potential of systems biology for CNS diseases. The system focuses on the benefit and practical applications in pathway centric therapy and drug repositioning. PMID:26235090

  19. A Genome Scan for Modifiers of Age at Onset in Huntington Disease: The HD MAPS Study

    OpenAIRE

    Li, Jian-Liang; Hayden, Michael R.; Almqvist, Elisabeth W.; Brinkman, Ryan R; Durr, Alexandra; Dodé, Catherine; Morrison, Patrick J.; Suchowersky, Oksana; Ross, Christopher A.; Margolis, Russell L.; Rosenblatt, Adam; Gómez-Tortosa, Estrella; Cabrero, David Mayo; Novelletto, Andrea; Frontali, Marina

    2003-01-01

    Huntington disease (HD) is caused by the expansion of a CAG repeat within the coding region of a novel gene on 4p16.3. Although the variation in age at onset is partly explained by the size of the expanded repeat, the unexplained variation in age at onset is strongly heritable (h2=0.56), which suggests that other genes modify the age at onset of HD. To identify these modifier loci, we performed a 10-cM density genomewide scan in 629 affected sibling pairs (295 pedigrees and 695 individuals), ...

  20. Uncovering disease mechanisms through network biology in the era of next generation sequencing.

    OpenAIRE

    Janet Piñero; Ariel Berenstein; Abel Gonzalez-Perez; Ariel Chernomoretz; Furlong, Laura I.

    2016-01-01

    Characterizing the behavior of disease genes in the context of biological networks has the potential to shed light on disease mechanisms, and to reveal both new candidate disease genes and therapeutic targets. Previous studies addressing the network properties of disease genes have produced contradictory results. Here we have explored the causes of these discrepancies and assessed the relationship between the network roles of disease genes and their tolerance to deleterious germline variants ...

  1. Overexpression of a Modified Plant Thionin Enhances Disease Resistance to Citrus Canker and Huanglongbing (HLB).

    Science.gov (United States)

    Hao, Guixia; Stover, Ed; Gupta, Goutam

    2016-01-01

    Huanglongbing (HLB or citrus greening disease) caused by Candidatus Liberibacter asiaticus (Las) is a great threat to the US citrus industry. There are no proven strategies to eliminate HLB disease and no cultivar has been identified with strong HLB resistance. Citrus canker is also an economically important disease associated with a bacterial pathogen (Xanthomonas citri). In this study, we characterized endogenous citrus thionins and investigated their expression in different citrus tissues. Since no HLB-resistant citrus cultivars have been identified, we attempted to develop citrus resistant to both HLB and citrus canker through overexpression of a modified plant thionin. To improve effectiveness for disease resistance, we modified and synthesized the sequence encoding a plant thionin and cloned into the binary vector pBinPlus/ARS. The construct was then introduced into Agrobacterium strain EHA105 for citrus transformation. Transgenic Carrizo plants expressing the modified plant thionin were generated by Agrobacterium-mediated transformation. Successful transformation and transgene gene expression was confirmed by molecular analysis. Transgenic Carrizo plants expressing the modified thionin gene were challenged with X. citri 3213 at a range of concentrations, and a significant reduction in canker symptoms and a decrease in bacterial growth were demonstrated compared to nontransgenic plants. Furthermore, the transgenic citrus plants were challenged with HLB via graft inoculation. Our results showed significant Las titer reduction in roots of transgenic Carrizo compared with control plants and reduced scion Las titer 12 months after graft inoculation. These data provide promise for engineering citrus disease resistance against HLB and canker. PMID:27499757

  2. Adult renal cystic disease: a genetic, biological, and developmental primer.

    Science.gov (United States)

    Katabathina, Venkata S; Kota, Gopi; Dasyam, Anil K; Shanbhogue, Alampady K P; Prasad, Srinivasa R

    2010-10-01

    Renal cystic diseases in adults are a heterogeneous group of disorders characterized by the presence of multiple cysts in the kidneys. These diseases may be categorized as hereditary, acquired, or developmental on the basis of their pathogenesis. Hereditary conditions include autosomal dominant polycystic kidney disease, medullary cystic kidney disease, von Hippel-Lindau disease, and tuberous sclerosis. Acquired conditions include cystic kidney disease, which develops in patients with end-stage renal disease. Developmental cystic diseases of the adult kidney include localized renal cystic disease, multicystic dysplastic kidney, and medullary sponge kidney. In recent years, many molecular and cellular mechanisms involved in the pathogenesis of renal cystic diseases have been identified. Hereditary renal cystic diseases are characterized by genetic mutations that lead to defects in the structure and function of the primary cilia of renal tubular epithelial cells, abnormal proliferation of tubular epithelium, and increased fluid secretion, all of which ultimately result in the development of renal cysts. A better understanding of these pathophysiologic mechanisms is now providing the basis for the development of more targeted therapeutic drugs for some of these disorders. Cross-sectional imaging provides useful information for diagnosis, surveillance, prognostication, and evaluation of treatment response in renal cystic diseases. PMID:21071372

  3. Update on Disease-Modifying/Preventive Therapies in Alzheimer’s Disease

    OpenAIRE

    Apter, Jeffrey T.; Shastri, Kuntal; Pizano, Katherine

    2015-01-01

    Alzheimer’s disease (AD) is increasingly becoming a major health problem throughout the US and Western Europe. As the remnants of the Baby Boom generation begin to reach their seniority at the turn of the twenty-first century, the disease has been unwillingly brought to the attention of the public eye. A disease that has traditionally been associated with an aging population has thus become a heated topic of discussion as modern research attempts to prevent and treat this major health burden ...

  4. Risk Mitigation Strategies for Adverse Reactions Associated with the Disease-Modifying Drugs in Multiple Sclerosis.

    Science.gov (United States)

    Subei, Adnan M; Ontaneda, Daniel

    2015-09-01

    Over the past several years, the number of disease-modifying therapies (DMTs) for the treatment of multiple sclerosis (MS) has doubled in number. The 13 approved agents have shown a wide range of efficacy and safety in their clinical trials and post-marketing experience. While the availability of the newer agents allows for a wider selection of therapy for clinicians and patients, there is a need for careful understanding of the benefits and risks of each agent. Several factors such as the medication efficacy, side-effect profile, patient's preference, and co-morbidities need to be considered. An individualized treatment approach is thus imperative. In this review, risk stratification and mitigation strategies of the various disease-modifying agents are discussed. PMID:26407624

  5. Development of molecular biology techniques for the detection of genetically modified organisms in maize food products

    OpenAIRE

    Sousa, S.C.; Mafra, I; Silva, C.S. Ferreira da; Amaral, J S; Oliveira, M.B.P.P.

    2008-01-01

    In the last years, the increase in the cultivated area of genetically modified (GM) maize has become a reality. GA21, MON810 and MON 863 maize crops are some of the authorized maize events for food and feed under the European Union (EU) regulations. These crops of transgenic maize bring profit towards the conventional ones, as they confer resistence to some plagues and/or herbices. Concerning the raise of production and consumption of foodstuffs derived from genetically modified organisms (GM...

  6. Enhancing biological control of basal stem rot disease (Ganoderma boninense) in oil palm plantations.

    Science.gov (United States)

    Susanto, A; Sudharto, P S; Purba, R Y

    2005-01-01

    Basal Stem Rot (BSR) disease caused by Ganoderma boninense is the most destructive disease in oil palm, especially in Indonesia and Malaysia. The available control measures for BSR disease such as cultural practices and mechanical and chemical treatment have not proved satisfactory due to the fact that Ganoderma has various resting stages such as melanised mycelium, basidiospores and pseudosclerotia. Alternative control measures to overcome the Ganoderma problem are focused on the use of biological control agents and planting resistant material. Present studies conducted at Indonesian Oil Palm Research Institute (IOPRI) are focused on enhancing the use of biological control agents for Ganoderma. These activities include screening biological agents from the oil palm rhizosphere in order to evaluate their effectiveness as biological agents in glasshouse and field trials, testing their antagonistic activities in large scale experiments and eradicating potential disease inoculum with biological agents. Several promising biological agents have been isolated, mainly Trichoderma harzianum, T. viride, Gliocladium viride, Pseudomonas fluorescens, and Bacillus sp. A glasshouse and field trial for Ganoderma control indicated that treatment with T. harzianum and G. viride was superior to Bacillus sp. A large scale trial showed that the disease incidence was lower in a field treated with biological agents than in untreated fields. In a short term programme, research activities at IOPRI are currently focusing on selecting fungi that can completely degrade plant material in order to eradicate inoculum. Digging holes around the palm bole and adding empty fruit bunches have been investigated as ways to stimulate biological agents. PMID:15750748

  7. Lighting the fires within: the cell biology of autoinflammatory diseases

    OpenAIRE

    Park, Heiyoung; Bourla, Ariel Bulua; Kastner, Daniel L.; Colbert, Robert A.; Siegel, Richard M.

    2012-01-01

    Autoinflammatory diseases are characterized by seemingly unprovoked, pathological activation of the innate immune system in the absence of autoantibodies or autoreactive T cells. Discovery of the causative mutations underlying several monogenic autoinflammatory diseases has identified key regulators of innate immune responses. Recent studies have highlighted the role of misfolding, oligomerization and abnormal trafficking of pathogenic mutant proteins in triggering autoinflammation, and sugge...

  8. Biological and clinical aspects of autoimmune inner ear disease.

    OpenAIRE

    Griffith, A J

    1992-01-01

    The clinical presentation, diagnosis, and management of autoimmune inner ear disease are reviewed. Recent studies indicating an autoimmune etiology and pathogenesis are discussed, along with a comparative analysis of several promising new animal models. Further studies to define the natural history, pathogenesis, and diagnosis of the disease are suggested.

  9. Optical Properties and In Vitro Biological Studies of Oligonucleotide-Modified Quantum Dots

    Directory of Open Access Journals (Sweden)

    Valérie A. Gérard

    2013-01-01

    Full Text Available Water-soluble semiconducting nanocrystals or quantum dots (QDs have attracted much interest in recent years due to their tuneable emission and potential applications in photonics and biological imaging. Fluorescence resonance energy transfer (FRET processes are very important for elucidating biochemical mechanisms in vitro, and QDs constitute an excellent substrate for this purpose. In this work, new oligonucleotide-functionalised CdTe-based QDs were prepared, characterised and biologically tested. These QDs demonstrated interesting optical properties as well as remarkable in vitro behaviour and potential for a range of biological applications.

  10. TaBoo SeArch Algorithm with a Modified Inverse Histogram for Reproducing Biologically Relevant Rare Events of Proteins.

    Science.gov (United States)

    Harada, Ryuhei; Takano, Yu; Shigeta, Yasuteru

    2016-05-10

    The TaBoo SeArch (TBSA) algorithm [ Harada et al. J. Comput. Chem. 2015 , 36 , 763 - 772 and Harada et al. Chem. Phys. Lett. 2015 , 630 , 68 - 75 ] was recently proposed as an enhanced conformational sampling method for reproducing biologically relevant rare events of a given protein. In TBSA, an inverse histogram of the original distribution, mapped onto a set of reaction coordinates, is constructed from trajectories obtained by multiple short-time molecular dynamics (MD) simulations. Rarely occurring states of a given protein are statistically selected as new initial states based on the inverse histogram, and resampling is performed by restarting the MD simulations from the new initial states to promote the conformational transition. In this process, the definition of the inverse histogram, which characterizes the rarely occurring states, is crucial for the efficiency of TBSA. In this study, we propose a simple modification of the inverse histogram to further accelerate the convergence of TBSA. As demonstrations of the modified TBSA, we applied it to (a) hydrogen bonding rearrangements of Met-enkephalin, (b) large-amplitude domain motions of Glutamine-Binding Protein, and (c) folding processes of the B domain of Staphylococcus aureus Protein A. All demonstrations numerically proved that the modified TBSA reproduced these biologically relevant rare events with nanosecond-order simulation times, although a set of microsecond-order, canonical MD simulations failed to reproduce the rare events, indicating the high efficiency of the modified TBSA. PMID:27070761

  11. Role of Biological Sex in Normal Cardiac Function and in its Disease Outcome – A Review

    OpenAIRE

    Prabhavathi, K.; Selvi, K.Tamarai; Poornima, K.N.; Sarvanan, A.

    2014-01-01

    Biological sex plays an important role in normal cardiac physiology as well as in the heart‘s response to cardiac disease. Women generally have better cardiac function and survival than do men in the face of cardiac disease; however, this is progressively lost when comparing postmenopausal women with age matched men. Animal model of cardiac disease mirror what is seen in humans. Sex hormones contribute significantly to sex based difference in cardiac functioning and in its disease outcome. Es...

  12. Biological and phylogenetic characterization of a genotype VII Newcastle disease virus from Venezuela: Efficacy of vaccination

    Science.gov (United States)

    Here we describe the characterization a virulent genotype VII Newcastle disease virus (NDV) from Venezuela and evaluate the efficacy of heterologous genotype commercial vaccination under field and controlled rearing conditions. Biological pathotyping and molecular analysis were applied. Results sh...

  13. How Implementation of Systems Biology into Clinical Trials Accelerates Understanding of Diseases

    OpenAIRE

    Bielekova, Bibiana; Vodovotz, Yoram; An, Gary; Hallenbeck, John

    2014-01-01

    Systems biology comprises a series of concepts and approaches that have been used successfully both to delineate novel biological mechanisms and to drive translational advances. The goal of systems biology is to re-integrate putatively critical elements extracted from multi-modality datasets in order to understand how interactions among multiple components form functional networks at the organism/patient-level, and how dysfunction of these networks underlies a particular disease. Due to the g...

  14. How implementation of systems biology into clinical trials accelerates understanding of diseases

    OpenAIRE

    Bibiana eBielekova; Yoram eVodovotz; Gary eAn; John eHallenbeck

    2014-01-01

    Systems biology comprises a series of concepts and approaches that have been used successfully both to delineate novel biological mechanisms and to drive translational advances. The goal of systems biology is to re-integrate putatively critical elements extracted from multi-modality datasets in order to understand how interactions among multiple components form functional networks at the organism/patient-level, and how dysfunction of these networks underlies a particular disease. Due to the...

  15. Optimal use of biologics in the management of Crohn’s disease

    OpenAIRE

    Panaccione, Remo; Ghosh, Subrata

    2010-01-01

    Crohn’s disease (CD) is a chronic relapsing and remitting disorder of the gastrointestinal tract with no known cure. The inflammation that drives the disease can lead to debilitating symptoms and a number of complications that may lead to surgery. The introduction of biologic therapy a decade ago has offered a new option for patients failing conventional therapy. Over time, biologic therapy has also led to the desire to achieve treatment goals beyond the control of symptoms. In order to achie...

  16. Biologic and Genetics Aspects of Chagas Disease at Endemic Areas

    OpenAIRE

    Marilanda Ferreira Bellini; Rosana Silistino-Souza; Marileila Varella-Garcia; Maria Tercília Vilela Azeredo-Oliveira; Ana Elizabete Silva

    2012-01-01

    The etiologic agent of Chagas Disease is the Trypanosoma cruzi, transmitted through blood-sucking insect vectors of the Triatominae subfamily, representing one of the most serious public health concerns in Latin America. There are geographic variations in the prevalence of clinical forms and morbidity of Chagas disease, likely due to genetic variation of the T. cruzi and the host genetic and environmental features. Increasing evidence has supported that inflammatory cytokines and chemokines a...

  17. Diabetes and modifiable risk factors for cardiovascular disease: the prospective Million Women Study

    International Nuclear Information System (INIS)

    To compare the effect of potentially modifiable lifestyle factors on the incidence of vascular disease in women with and without diabetes. In 1996-2001 over one million middle-aged women in the UK joined a prospective study, providing medical history, lifestyle and socio-demographic information. All participants were followed for hospital admissions and deaths using electronic record-linkage. Adjusted relative risks (RRs) and incidence rates were calculated to compare the incidence of coronary heart disease and stroke in women with and without diabetes and by lifestyle factors. At recruitment 25,915 women (2.1% of 1,242,338) reported current treatment for diabetes. During a mean follow-up of 6.1 years per woman, 21,928 had a first hospital admission or death from coronary heart disease (RR for women with versus without diabetes = 3.30, 95% CI 3.14-3.47) and 7,087 had a first stroke (RR = 2.47, 95% CI 2.24-2.74). Adjusted incidence rates of these conditions in women with diabetes increased with duration of diabetes, obesity, inactivity and smoking. The 5-year adjusted incidence rates for cardiovascular disease were 4.6 (95% CI 4.4-4.9) per 100 women aged 50-69 in non-smokers with diabetes, 5.9 (95% CI 4.6-7.6) in smokers with diabetes not using insulin and 11.0 (95% CI 8.3-14.7) in smokers with diabetes using insulin. Non-smoking women with diabetes who were not overweight or inactive still had threefold increased rate for coronary disease or stroke compared with women without diabetes. Of the modifiable factors examined in middle aged women with diabetes, smoking causes the greatest increase in cardiovascular disease, especially in those with insulin treated diabetes

  18. Base-modified nucleotides and DNA for applications in diagnostics and chemical biology

    Czech Academy of Sciences Publication Activity Database

    Hocek, Michal

    Praha: Czech Chemical Society, 2015. s. 31. [Liblice 2015. Advances in Organic , Bioorganic and Pharmaceutical Chemistry /50./. 06.11.2015-08.11.2015, Olomouc] R&D Projects: GA ČR GBP206/12/G151; GA ČR GA14-04289S Institutional support: RVO:61388963 Keywords : base-modified nucleotides * DNA Subject RIV: CC - Organic Chemistry

  19. Synthesis and biological evaluation of asymmetric gramicidin S analogues containing modified D-phenylalanine residues

    NARCIS (Netherlands)

    van der Knaap, Matthijs; Engels, Eefje; Busscher, Henk J.; Otero, Jose M.; Llamas-Saiz, Antonio L.; van Raaij, Mark J.; Mars-Groenendijk, Roos H.; Noort, Daan; van der Marel, Gijsbert A.; Overkleeft, Herman S.; Overhand, Mark

    2009-01-01

    The synthesis of new analogues of the cationic antimicrobial peptide gramicidin S, having a modified D-phenylalanine residue, their antibacterial properties against several Gram positive and negative strains, as well as their hemolytic activity is reported. (C) 2009 Elsevier Ltd. All rights reserved

  20. Synthesis and biological evaluation of asymmetric gramicidin S analogues containing modified d-phenylalanine residues

    NARCIS (Netherlands)

    Knaap, M. van der; Engels, E.; Busscher, H.J.; Otero, J.M.; Llamas-Saiz, A.L.; Raaij, M.J. van; Mars-Groenendijk, R.H.; Noort, D.; Marel, G.A. van der; Overkleeft, H.S.; Overhand, M.

    2009-01-01

    The synthesis of new analogues of the cationic antimicrobial peptide gramicidin S, having a modified d-phenylalanine residue, their antibacterial properties against several Gram positive and negative strains, as well as their hemolytic activity is reported. © 2009 Elsevier Ltd. All rights reserved.

  1. Sensitive determination of domperidone in biological fluids using a conductive polymer modified glassy carbon electrode

    International Nuclear Information System (INIS)

    A simple and sensitive method for domperidone (DP) determination has been developed by electropolymerizing a polymer film on the surface of glassy carbon electrode (GCE) in acidic solution using cyclic voltammetry. The modified sensor was characterized by Field Emission Scanning Electron Microscopy (FE-SEM) and Electrochemical Impedance Spectroscopy (EIS). The electrochemical measurements were carried out using square wave voltammetry and cyclic voltammetry. The modified sensor exhibited an excellent catalytic response towards the oxidation of DP with a well-defined oxidation peak at 840 mV. The modified sensor exhibited linear calibration curve for DP over a concentration range of 0.1 μM to 100 μM in phosphate buffer solution of pH 7.2 with detection limit of 12.0 nM. The sensor was capable to determine DP effectively without any interference from the common metabolites like ascorbic acid, uric acid, xanthine and hypoxanthine. The analytical utilities of the sensor have been demonstrated by determining the DP in human fluids and pharmaceutical samples. Further, the modified sensor displayed voltammetric responses with high sensitivity, good selectivity and reproducibility which make it suitable for clinical diagnosis

  2. Systems Biology of Asthma and Allergic Diseases: A Multiscale Approach

    OpenAIRE

    Bunyavanich, Supinda; Schadt, Eric E.

    2014-01-01

    Systems biology is an approach to understanding living systems that focuses on modeling diverse types of high-dimensional interactions to develop a more comprehensive understanding of complex phenotypes manifested by the system. High throughput molecular, cellular, and physiologic profiling of populations is coupled with bioinformatic and computational techniques to identify new functional roles for genes, regulatory elements, and metabolites in the context of the molecular networks that defi...

  3. Modifying the course of chronic obstructive pulmonary disease: looking beyond the FEV1.

    Science.gov (United States)

    Zuwallack, Richard L; Nici, Linda

    2012-12-01

    COPD is defined by airflow limitation that is not fully reversible and is usually progressive. Thus, airflow obstruction (measured as FEV(1)) has traditionally been used as the benchmark defining disease modification with therapy. However, COPD exacerbations and extrapulmonary effects are common and burdensome and generally become more prominent as the disease progresses. Therefore, disease progression should be broader than FEV(1) alone. Interventions that reduce the frequency or severity of exacerbations or ameliorate extrapulmonary effects should also be considered disease modifiers. A narrow focus on FEV(1) will fail to capture all the beneficial effects of therapy on disease modification. Although smoking cessation has been unequivocally demonstrated to slow the rate of FEV(1) decline, inhaled corticosteroid-long-acting bronchodilator therapy may also have modest effects according to post hoc analysis. Maintenance pharmacotherapy with inhaled long-acting anti-muscarinic or β-adrenergic agents or combined β-adrenergic--inhaled corticosteroid reduces symptoms, improves lung function, reduces the frequency of exacerbations, and improves exercise capacity and HRQL. Pulmonary rehabilitation reduces symptom burden, increases exercise capacity, improves HRQL, and reduces health care utilization, probably through reducing the severity of exacerbations. Smoking cessation, lung volume reduction surgery, inhaled maintenance pharmacotherapy, and pulmonary rehabilitation administered in the post-exacerbation period may reduce mortality in COPD. These improvements over multiple outcome areas and over relatively long durations suggest that disease modification is indeed possible with existing therapies for COPD. Therefore, therapeutic nihilism in COPD is no longer warranted. PMID:22958136

  4. Use of Rats Mesenchymal Stem Cells Modified with mHCN2 Gene to Create Biologic Pacemakers

    Institute of Scientific and Technical Information of China (English)

    马金; 张存泰; 黄深; 王国强; 全小庆

    2010-01-01

    The possibility of rats mesenchymal stem cells (MSCs) modified with murine hyperpolarization-activated cyclic nucleotide-gated 2 (mHCN2) gene as biological pacemakers in vitro was studied. The cultured MSCs were transfected with pIRES2-EGFP plasmid carrying enhanced green fluorescent protein (EGFP) gene and mHCN2 gene. The identification using restriction enzyme and sequencing indicated that the mHCN2 gene was inserted to the pIRES2-EGFP. Green fluorescence could be seen in MSCs after transfection for 24-48...

  5. A Novel Approach to Delayed-Start Analyses for Demonstrating Disease-Modifying Effects in Alzheimer’s Disease

    Science.gov (United States)

    Liu-Seifert, Hong; Andersen, Scott W.; Lipkovich, Ilya; Holdridge, Karen C.; Siemers, Eric

    2015-01-01

    One method for demonstrating disease modification is a delayed-start design, consisting of a placebo-controlled period followed by a delayed-start period wherein all patients receive active treatment. To address methodological issues in previous delayed-start approaches, we propose a new method that is robust across conditions of drug effect, discontinuation rates, and missing data mechanisms. We propose a modeling approach and test procedure to test the hypothesis of noninferiority, comparing the treatment difference at the end of the delayed-start period with that at the end of the placebo-controlled period. We conducted simulations to identify the optimal noninferiority testing procedure to ensure the method was robust across scenarios and assumptions, and to evaluate the appropriate modeling approach for analyzing the delayed-start period. We then applied this methodology to Phase 3 solanezumab clinical trial data for mild Alzheimer’s disease patients. Simulation results showed a testing procedure using a proportional noninferiority margin was robust for detecting disease-modifying effects; conditions of high and moderate discontinuations; and with various missing data mechanisms. Using all data from all randomized patients in a single model over both the placebo-controlled and delayed-start study periods demonstrated good statistical performance. In analysis of solanezumab data using this methodology, the noninferiority criterion was met, indicating the treatment difference at the end of the placebo-controlled studies was preserved at the end of the delayed-start period within a pre-defined margin. The proposed noninferiority method for delayed-start analysis controls Type I error rate well and addresses many challenges posed by previous approaches. Delayed-start studies employing the proposed analysis approach could be used to provide evidence of a disease-modifying effect. This method has been communicated with FDA and has been successfully applied to

  6. A novel approach to delayed-start analyses for demonstrating disease-modifying effects in Alzheimer's disease.

    Science.gov (United States)

    Liu-Seifert, Hong; Andersen, Scott W; Lipkovich, Ilya; Holdridge, Karen C; Siemers, Eric

    2015-01-01

    One method for demonstrating disease modification is a delayed-start design, consisting of a placebo-controlled period followed by a delayed-start period wherein all patients receive active treatment. To address methodological issues in previous delayed-start approaches, we propose a new method that is robust across conditions of drug effect, discontinuation rates, and missing data mechanisms. We propose a modeling approach and test procedure to test the hypothesis of noninferiority, comparing the treatment difference at the end of the delayed-start period with that at the end of the placebo-controlled period. We conducted simulations to identify the optimal noninferiority testing procedure to ensure the method was robust across scenarios and assumptions, and to evaluate the appropriate modeling approach for analyzing the delayed-start period. We then applied this methodology to Phase 3 solanezumab clinical trial data for mild Alzheimer's disease patients. Simulation results showed a testing procedure using a proportional noninferiority margin was robust for detecting disease-modifying effects; conditions of high and moderate discontinuations; and with various missing data mechanisms. Using all data from all randomized patients in a single model over both the placebo-controlled and delayed-start study periods demonstrated good statistical performance. In analysis of solanezumab data using this methodology, the noninferiority criterion was met, indicating the treatment difference at the end of the placebo-controlled studies was preserved at the end of the delayed-start period within a pre-defined margin. The proposed noninferiority method for delayed-start analysis controls Type I error rate well and addresses many challenges posed by previous approaches. Delayed-start studies employing the proposed analysis approach could be used to provide evidence of a disease-modifying effect. This method has been communicated with FDA and has been successfully applied to actual

  7. Modifiable Coronary Heart Disease Risk Factors in the Population Aged 20-49 Years

    Directory of Open Access Journals (Sweden)

    Francisco Carlos Valladares Mas

    2014-04-01

    Full Text Available Background: evidence provided by the Framingham Heart Study established the critical role of risk factors in the development of coronary heart disease. Over half a century later, current detection and control are still inadequate. Objective: to identify modifiable risk factors of coronary heart disease in individuals aged 20 to 49 years. Methods: a descriptive, cross-sectional study was conducted in 276 individuals from the doctor’s office No. 1 of the Fabio di Celmo Community Teaching Polyclinic in Cienfuegos. Patients were examined in the clinic visit and/or whole family visit. The studied variables included age, sex, skin color, risk factors (excess weight/obesity, physical inactivity, smoking, hypertension, diabetes, dyslipidemia and psychosocial factors, which were obtained from the medical interview, physical examination, laboratory tests (total cholesterol and triglycerides and review of individual medical records and family history. Results: risk factors most frequently identified were excess weight/obesity (42.4 %, physical inactivity (34.4 % and smoking (20.3 %. Presence of these risk factors increased with age, showing differences in the distribution by sex and was associated with psychosocial factors. Their coexistence and progress with age was significant. Conclusion: prevalence of modifiable risk factors for coronary heart disease in a young population was high, with frequent association, predominating factors related to unhealthy lifestyles.

  8. Cholangiocarcinoma: new insights into disease pathogenesis and biology.

    Science.gov (United States)

    Braconi, Chiara; Patel, Tushar

    2010-12-01

    Cholangiocarcinomas are rare malignant tumors whose incidence is increasing worldwide. Risk factors for this malignancy include both infectious and non-infectious diseases characterized by chronic inflammation of the bile duct epithelia. Diagnosis of these cancers remains difficult because of the lack of sensitive diagnostic tests. The prognosis is poor probably because of the lack of effective treatments for unresectable cancer. PMID:20937455

  9. PRELIMINARY STUDY ON ENHANCED PROPERTIES AND BIOLOGICAL RESISTANCE OF CHEMICALLY MODIFIED ACACIA SPP.

    OpenAIRE

    H. P. S. Abdul Khalil; Irshad ul Haq Bhat,; Khairul B. Awang

    2010-01-01

    A preliminary experimental study was carried out to examine the ability of a chemically modified Acacia spp. to resist biodegradation. The modifications of Acacia mangium and Acacia hybrid were carried out by propionic anhydride and succinic anhydride in the presence of sodium formate as a catalyst. The treated samples were found resistant to microbial attack, while the untreated ones were damaged on 12 months exposure to a soil burial. The appearance grading, mass loss, mechanical properties...

  10. Improved ability of biological and previous caries multimarkers to predict caries disease as revealed by multivariate PLS modelling

    Directory of Open Access Journals (Sweden)

    Ericson Thorild

    2009-11-01

    Full Text Available Abstract Background Dental caries is a chronic disease with plaque bacteria, diet and saliva modifying disease activity. Here we have used the PLS method to evaluate a multiplicity of such biological variables (n = 88 for ability to predict caries in a cross-sectional (baseline caries and prospective (2-year caries development setting. Methods Multivariate PLS modelling was used to associate the many biological variables with caries recorded in thirty 14-year-old children by measuring the numbers of incipient and manifest caries lesions at all surfaces. Results A wide but shallow gliding scale of one fifth caries promoting or protecting, and four fifths non-influential, variables occurred. The influential markers behaved in the order of plaque bacteria > diet > saliva, with previously known plaque bacteria/diet markers and a set of new protective diet markers. A differential variable patterning appeared for new versus progressing lesions. The influential biological multimarkers (n = 18 predicted baseline caries better (ROC area 0.96 than five markers (0.92 and a single lactobacilli marker (0.7 with sensitivity/specificity of 1.87, 1.78 and 1.13 at 1/3 of the subjects diagnosed sick, respectively. Moreover, biological multimarkers (n = 18 explained 2-year caries increment slightly better than reported before but predicted it poorly (ROC area 0.76. By contrast, multimarkers based on previous caries predicted alone (ROC area 0.88, or together with biological multimarkers (0.94, increment well with a sensitivity/specificity of 1.74 at 1/3 of the subjects diagnosed sick. Conclusion Multimarkers behave better than single-to-five markers but future multimarker strategies will require systematic searches for improved saliva and plaque bacteria markers.

  11. Aortic distensibility measured by pulse-wave velocity is not modified in patients with Chagas' disease

    Directory of Open Access Journals (Sweden)

    Arteaga Edmundo

    2006-06-01

    Full Text Available Abstract Background Experimental studies demonstrate that infection with trypanosoma cruzi causes vasculitis. The inflammatory lesion process could hypothetically lead to decreased distensibility of large and small arteries in advanced Chagas' disease. We tested this hypothesis. Methods and results We evaluated carotid-femoral pulse-wave velocity (PWV in 53 Chagas' disease patients compared with 31 healthy volunteers (control group. The 53 patients were classified into 3 groups: 1 16 with indeterminate form of Chagas' disease; 2 18 with Chagas' disease, electrocardiographic abnormalities, and normal systolic function; 3 19 with Chagas' disease, systolic dysfunction, and mild-to-moderate congestive heart failure. No difference was noted between the 4 groups regarding carotid-femoral PWV (8.4 ± 1.1 vs 8.2 ± 1.5 vs 8.2 ± 1.4 vs 8.7 ± 1.6 m/s, P = 0.6 or pulse pressure (39.5 ± 7.6 vs 39.3 ± 8.1 vs 39.5 ± 7.4 vs 39.7 ± 6.9 mm Hg, P = 0.9. A positive, significant, similar correlation occurred between PWV and age in patients with Chagas' disease (r = 0.42, P = 0.002, in controls (r = 0.48, P = 0.006, and also between PWV and systolic blood pressure in both groups (patients with Chagas' disease, r = 0.38, P = 0.005; healthy subjects, r = 0.36, P = 0.043. Conclusion Carotid femoral pulse-wave velocity is not modified in patients with Chagas' disease, suggesting that elastic properties of large arteries are not affected in this disorder.

  12. How implementation of systems biology into clinical trials accelerates understanding of diseases

    Directory of Open Access Journals (Sweden)

    BibianaBielekova

    2014-06-01

    Full Text Available Systems biology comprises a series of concepts and approaches that have been used successfully both to delineate novel biological mechanisms and to drive translational advances. The goal of systems biology is to re-integrate putatively critical elements extracted from multi-modality datasets in order to understand how interactions among multiple components form functional networks at the organism/patient-level, and how dysfunction of these networks underlies a particular disease. Due to the genetic and environmental diversity of human subjects, identification of critical elements related to a particular disease process from cross-sectional studies requires prohibitively large cohorts. Alternatively, implementation of systems biology principles to interventional clinical trials represents a unique opportunity to gain predictive understanding of complex diseases in comparatively small cohorts of patients. This paper reviews systems biology principles applicable to translational research, focusing on lessons from systems approaches to inflammation applied to multiple sclerosis (MS. We suggest that employing systems biology methods in the design and execution of biomarker-supported, proof-of-principle clinical trials provides a singular opportunity to merge therapeutic development with a basic understanding of disease processes. The ultimate goal is to develop predictive computational models of the disease, which will revolutionize diagnostic process and provide mechanistic understanding necessary for personalized therapeutic approaches. Added, biologically-meaningful information can be derived from diagnostic tests, if they are interpreted in functional relationships, rather than as independent measurements. Such systems-biology based diagnostics will transform disease taxonomies from phenotypical to molecular and will allow physicians to select optimal therapeutic regimens for individual patients.

  13. 4p16.3 haplotype modifying age at onset of Huntington disease

    DEFF Research Database (Denmark)

    Nørremølle, A; Budtz-Jørgensen, E; Fenger, K;

    2009-01-01

    Huntington disease (HD) is caused by an expanded CAG repeat sequence in the HD gene. Although the age at onset is correlated to the CAG repeat length, this correlation only explains approximately half of the variation in onset age. Less variation between siblings indicates that the variation is, in...... part, explained by genetic modifiers. We analyzed polymorphic loci within or close to the HD gene on the HD chromosome in Danish HD patients. We found one specific haplotype segregating with later age at onset, compared with patients with similar CAG repeat length and another haplotype. The nine Danish...

  14. Vaccination with genetically modified Shiga-like toxin IIe prevents edema disease in swine.

    OpenAIRE

    Bosworth, B T; Samuel, J E; Moon, H W; O'Brien, A D; Gordon, V M; Whipp, S C

    1996-01-01

    Escherichia coli strains producing Shiga-like toxin II variant (SLT-IIe, formerly called SLT-IIv) cause edema disease in weaned pigs. Vaccination of pigs with a genetically modified form of Shiga-like toxin IIe, SLT-IIe(E167Q), has been previously shown to be nontoxic and to induce antibodies to SLT-IIe (V.M. Gordon. S.C. Whipp, H.W. Moon, A.D. O'Brien, and J.E. Samuel, Infect, Immun. 60:485-502, 1992). Fifty micrograms of SLT-IIe(E167Q) toxin was used to vaccinate suckling pigs at 1 and 2 we...

  15. Low-Radiation-Dose Modified Small Bowel CT for Evaluation of Recurrent Crohn's Disease

    Directory of Open Access Journals (Sweden)

    A. Z. Kielar

    2012-01-01

    Full Text Available Crohn's disease affects any part of the GI tract, commonly the terminal ileum. To decrease radiation exposure we developed a low-radiation-dose unenhanced CT (modified small Bowel CT, MBCT to evaluate the small bowel using hyperdense oral contrast. Technique. MBCT was investigated in patients with pathologically proven Crohn's disease presenting with new symptoms from recurrent inflammation or stricture. After ethics board approval, 98 consecutive patients were retrospectively evaluated. Kappa values from two independent reviewers were calculated for presence of obstruction, active inflammation versus chronic stricture, and ancillary findings. Forty-two patients underwent surgery or colonoscopy within 3 months. Results. Kappa was 0.84 for presence of abnormality versus a normal exam and 0.89 for differentiating active inflammation from chronic stricture. Level of agreement for presence of skip areas, abscess formation, and fistula was 0.62, 0.75, and 0.78, respectively. In the subset with “gold standard” follow-up, there was 83% agreement. Conclusions. MBCT is a low-radiation technique with good to very good interobserver agreement for determining presence of obstruction and degree of disease activity in patients with Crohn's disease. Further investigation is required to refine parameters of disease activity compared to CT enterography and small bowel follow through.

  16. Therapeutic Potential to Modify the Mucus Barrier in Inflammatory Bowel Disease

    Directory of Open Access Journals (Sweden)

    Jing Sun

    2016-01-01

    Full Text Available Recently, numerous studies have shown that disruption of the mucus barrier plays an important role in the exacerbation of inflammatory bowel disease, particularly in ulcerative colitis. Alterations in the mucus barrier are well supported by published data and are widely accepted. The use of fluorescence in situ hybridization and Carnoy’s fixation has revealed the importance of the mucus barrier in maintaining a mutualistic relationship between host and bacteria. Studies have raised the possibility that modulation of the mucus barrier may provide therapies for the disease, using agents such as short-chain fatty acids, prebiotics and probiotics. This review describes changes in the mucus barrier of patients with inflammatory bowel disease and in animal models of the disease. We also review the involvement of the mucus barrier in the exacerbation of the disease and explore the therapeutic potential of modifying the mucus barrier with short-chain fatty acids, prebiotics, probiotics, fatty acid synthase, H2S, neutrophil elastase inhibitor and phophatidyl choline.

  17. Therapeutic Potential to Modify the Mucus Barrier in Inflammatory Bowel Disease.

    Science.gov (United States)

    Sun, Jing; Shen, Xiao; Li, Yi; Guo, Zhen; Zhu, Weiming; Zuo, Lugen; Zhao, Jie; Gu, Lili; Gong, Jianfeng; Li, Jieshou

    2016-01-01

    Recently, numerous studies have shown that disruption of the mucus barrier plays an important role in the exacerbation of inflammatory bowel disease, particularly in ulcerative colitis. Alterations in the mucus barrier are well supported by published data and are widely accepted. The use of fluorescence in situ hybridization and Carnoy's fixation has revealed the importance of the mucus barrier in maintaining a mutualistic relationship between host and bacteria. Studies have raised the possibility that modulation of the mucus barrier may provide therapies for the disease, using agents such as short-chain fatty acids, prebiotics and probiotics. This review describes changes in the mucus barrier of patients with inflammatory bowel disease and in animal models of the disease. We also review the involvement of the mucus barrier in the exacerbation of the disease and explore the therapeutic potential of modifying the mucus barrier with short-chain fatty acids, prebiotics, probiotics, fatty acid synthase, H₂S, neutrophil elastase inhibitor and phophatidyl choline. PMID:26784223

  18. Can we change the disease biology of multiple myeloma?

    OpenAIRE

    Borrello, Ivan

    2012-01-01

    Despite improvements in disease management, multiple myeloma (MM) remains incurable. Conventional treatment methods are unsatisfactory, leading to a pattern of regression and remission, and ultimately failure. This pattern suggests that one of the possible strategies for improving outcomes is continuous therapy to maintain suppression of the surviving tumor cells. Optimal management of MM requires potent agents and modalities with direct tumoricidal activity, which can also provide continuous...

  19. Using Genomics to Study Human Biology and Disease

    Energy Technology Data Exchange (ETDEWEB)

    Myers, Ricard M. (Stanford University School of Medicine)

    2005-04-06

    The Human Genome Project culminated in April 2003 with the finished DNA sequence of all of the human chromosomes. This book of information, particularly in conjunction with the genome sequences of many other organisms, has already begun to revolutionize the way that biomedical scientists study our species. The identification of essentially all of our genes has provided a template upon which researchers can discover basic processes that govern cells, organs, and the whole organism, and to understand the fundamental causes of the diseases that occur when something goes wrong with a gene or a set of genes. The Genome Project has already made it possible to identify the genes that are defective in more than 1,000 rare inherited diseases, and these discoveries have helped to understand the mechanisms of the more common forms of these disorders. This understanding of primary defects in diseases - which is translated as mutations in genes that encode proteins that serve specific functions - is transforming the way that biotechnology and pharmaceutical companies identify drug targets, and a few notable cases have already had a striking impact on specific diseases. In addition, it has become clear that the differential response to drugs in human populations is heavily influenced by genes, and a whole field called pharmacogenetics has begun to identify these genetic factors. Such knowledge will allow physicians to prescribe drugs targeted to each individual, with the potential to increase efficacy and decrease side-effects. Determining the DNA sequence of the human genome and identifying the genes has been an exciting endeavor, but we are only just beginning to understand the treasures present in all of our DNA. My presentation will briefly describe the road we took to get the sequence, as well as the tools that we are developing to unlock its secrets.

  20. Biologic targeting in the treatment of inflammatory bowel diseases

    OpenAIRE

    Matteo Bosani; Sandro Ardizzone; Gabriele Bianchi Porro

    2009-01-01

    Matteo Bosani, Sandro Ardizzone, Gabriele Bianchi PorroChair of Gastroenterology, “L. Sacco” University Hospital, Milan, ItalyAbstract: The etiology of inflammatory bowel disease (IBD) has not yet been clarified and immunosuppressive agents which nonspecifically reduce inflammation and immunity have been used in the conventional therapies for IBD. Evidence indicates that a dysregulation of mucosal immunity in the gut of IBD causes an overproduction of inflammatory cytokine...

  1. Biologic targeting in the treatment of inflammatory bowel diseases

    OpenAIRE

    Ardizzone, Sandro

    2009-01-01

    This paper has been retracted. Matteo Bosani, Sandro Ardizzone, Gabriele Bianchi PorroChair of Gastroenterology, “L. Sacco” University Hospital, Milan, ItalyAbstract: The etiology of inflammatory bowel disease (IBD) has not yet been clarified and immunosuppressive agents which nonspecifically reduce inflammation and immunity have been used in the conventional therapies for IBD. Evidence indicates that a dysregulation of mucosal immunity in the gut of IBD ...

  2. Angioedema associated with Crohn's disease: Response to biologics

    Institute of Scientific and Technical Information of China (English)

    Flavio Habal; Vivian Huang

    2012-01-01

    A 46-year-old female patient with terminal ileum Crohn's disease and ankylosing spondylitis presented with recurrent angioedema and urticaria.Investigations ruled out hereditary angioedema,and environmental or food allergen triggers.She was diagnosed with chronic idiopathic urticaria with angioedema,and was treated with a trial of intravenous immunoglobulin immunotherapy,danazol,prednisone and hydroxyzine.Due to ongoing bowel and arthritic complaints,she was started on infliximab infusions and within 2 treatments,she had complete resolution of the angioedema and urticaria,as well as of the bowel and arthritic symptoms.Unfortunately she developed allergic reactions to the infliximab and was switched to another anti-tumor necrosis factor (TNF)-α agent,adalimumab.Since then,she has had no further angioedema or urticaria,and her Crohn's disease has been quiescent.This is the first known case report of chronic idiopathic urticaria with angioedema coexistent with Crohn's disease that was successfully treated with anti-TNF-α agents.

  3. Relevance of Crop Biology for Environmental Risk Assessment of Genetically Modified Crops in Africa

    OpenAIRE

    Akinbo, Olalekan; Hancock, James F.; Makinde, Diran

    2015-01-01

    Knowledge about the crop biology of economic crops in Africa is needed for regulators to accurately review dossiers and conduct comprehensive environmental risk assessments (ERAs). This information allows regulators to decide whether biotech crops present a risk to biodiversity, since crossing between domesticated crops and their wild relatives could affect the adaptations of the wild species. The criteria that should be used in the evaluation of African crops for ERA include growth habit, ce...

  4. Functions of microRNAs in cardiovascular biology and disease.

    Science.gov (United States)

    Hata, Akiko

    2013-01-01

    In 1993, lin-4 was discovered as a critical modulator of temporal development in Caenorhabditis elegans and, most notably, as the first in the class of small, single-stranded noncoding RNAs now defined as microRNAs (miRNAs). Another eight years elapsed before miRNA expression was detected in mammalian cells. Since then, explosive advancements in the field of miRNA biology have elucidated the basic mechanism of miRNA biogenesis, regulation, and gene-regulatory function. The discovery of this new class of small RNAs has augmented the complexity of gene-regulatory programs as well as the understanding of developmental and pathological processes in the cardiovascular system. Indeed, the contributions of miRNAs in cardiovascular development and function have been widely explored, revealing the extensive role of these small regulatory RNAs in cardiovascular physiology. PMID:23157557

  5. Development of criteria for evaluating clinical response in thyroid eye disease using a modified Delphi technique

    DEFF Research Database (Denmark)

    Douglas, Raymond S; Tsirbas, Angelo; Gordon, Mark;

    2009-01-01

    OBJECTIVE: To identify components of a provisional clinical response index for thyroid eye disease using a modified Delphi technique. METHODS: The International Thyroid Eye Disease Society conducted a structured, 3-round Delphi exercise establishing consensus for a core set of measures for clinical...... parsed into 11 domains for the Delphi surveys. Eighty-four respondents participated in the Delphi 1 survey, providing 220 unique items. Ninety-two members (100% of the respondents from Delphi 1 plus 8 new participants) responded in Delphi 2 and rated the same 220 items. Sixty-four members (76% of...... participants) rated 153 criteria in Delphi 3 (67 criteria were excluded because of redundancy). Criteria with a mean greater than 6 (1 = least appropriate to 9 = most appropriate) were further evaluated by the nominal group technique and provisional core measures were chosen. CONCLUSIONS: Using a Delphi...

  6. Chronic Disease at Midlife: Do Parent-child Bonds Modify the Effect of Childhood SES?

    Science.gov (United States)

    Andersson, Matthew A

    2016-09-01

    Childhood socioeconomic status (SES) often is associated with physical health even decades later. However, parent-child emotional bonds during childhood may modify the importance of childhood SES to emergent health inequalities across the life course. Drawing on national data on middle-aged adults (1995 and 2005 National Survey of Midlife Development in the United States; MIDUS; Ns = 2,746 and 1,632), I find that compromised parent-child bonds eliminate the association between childhood SES and midlife disease. Longitudinal models of incident disease across one decade show that childhood abuse in particular continues to undermine the health protection associated with childhood SES. When childhood SES is moderate to high, compromised parent-child bonds lead to no predicted health benefits from childhood SES. In total, these findings direct attention to parent-child bonds as social-psychological levers for the transmission of class-based health advantages. PMID:27601411

  7. Electrochemical Cathodic Polarization, a Simplified Method That Can Modified and Increase the Biological Activity of Titanium Surfaces: A Systematic Review.

    Directory of Open Access Journals (Sweden)

    Jose Carlos Bernedo Alcazar

    Full Text Available The cathodic polarization seems to be an electrochemical method capable of modifying and coat biomolecules on titanium surfaces, improving the surface activity and promoting better biological responses.The aim of the systematic review is to assess the scientific literature to evaluate the cellular response produced by treatment of titanium surfaces by applying the cathodic polarization technique.The literature search was performed in several databases including PubMed, Web of Science, Scopus, Science Direct, Scielo and EBSCO Host, until June 2016, with no limits used. Eligibility criteria were used and quality assessment was performed following slightly modified ARRIVE and SYRCLE guidelines for cellular studies and animal research.Thirteen studies accomplished the inclusion criteria and were considered in the review. The quality of reporting studies in animal models was low and for the in vitro studies it was high. The in vitro and in vivo results reported that the use of cathodic polarization promoted hydride surfaces, effective deposition, and adhesion of the coated biomolecules. In the experimental groups that used the electrochemical method, cellular viability, proliferation, adhesion, differentiation, or bone growth were better or comparable with the control groups.The use of the cathodic polarization method to modify titanium surfaces seems to be an interesting method that could produce active layers and consequently enhance cellular response, in vitro and in vivo animal model studies.

  8. PRELIMINARY STUDY ON ENHANCED PROPERTIES AND BIOLOGICAL RESISTANCE OF CHEMICALLY MODIFIED ACACIA SPP.

    Directory of Open Access Journals (Sweden)

    H. P. S. Abdul Khalil

    2010-11-01

    Full Text Available A preliminary experimental study was carried out to examine the ability of a chemically modified Acacia spp. to resist biodegradation. The modifications of Acacia mangium and Acacia hybrid were carried out by propionic anhydride and succinic anhydride in the presence of sodium formate as a catalyst. The treated samples were found resistant to microbial attack, while the untreated ones were damaged on 12 months exposure to a soil burial. The appearance grading, mass loss, mechanical properties, and scanning electron microscopy results revealed that chemical modification enhances the resistance of Acacia mangium and Acacia hybrid wood species to biodegradation.

  9. Psychiatric and cognitive symptoms in Huntington's disease are modified by polymorphisms in catecholamine regulating enzyme genes.

    Science.gov (United States)

    Vinther-Jensen, T; Nielsen, T T; Budtz-Jørgensen, E; Larsen, I U; Hansen, M M; Hasholt, L; Hjermind, L E; Nielsen, J E; Nørremølle, A

    2016-03-01

    Huntington's disease (HD) is an autosomal dominantly inherited neurodegenerative disorder characterized by motor, psychiatric, and cognitive manifestations. HD is caused by a CAG repeat expansion in the Huntingtin (HTT) gene but the exact pathogenesis remains unknown. Dopamine imbalance has previously been shown in HD, and furthermore dopamine is thought to be implicated in cognition, behavioral and motor disturbances. A substantiated inverse correlation between motor onset and the elongated CAG repeat in the HTT has been established. This relation does not account for the full variability of the motor onset, and efforts have been put into finding genetic modifiers of motor onset, however, mostly with unsuccessful outcome. In this study, we took an alternative approach focusing on symptom complexes and searched for modifiers of cognitive impairment and psychiatric symptoms in a well-described cohort of Danish HD gene-expansion carriers. We show that cognitive impairment and psychiatric symptoms in HD are modified by polymorphisms in the monoamine oxidase A (MAOA) and catechol-O-methyltransferase (COMT) genes and by the 4p16.3 B haplotype. These results support the theory of dopamine imbalance in HD, and point toward more personalized treatment modalities of HD in the future. PMID:26081309

  10. Rheological and Biological Characteristics of Hyaluronic Acid Derivative Modified by Polyethylene Glycol

    Institute of Scientific and Technical Information of China (English)

    CHEN Jinghua; CHEN Jingtao; XU Zheng

    2008-01-01

    Hyaluronic acid (HA) was chemically modified by polyethylene glycol. Meanwhile,the dynamic mechanics properties of HA derivative and its viscoelastic changes were measured on 3ARES3 Rheometer (Japan) at 25 ℃. Dried cross-linked films of 10×10 mm2 were immersed in phosphate buffered saline(PBS: pH 7.4) at 37 ℃ with different time periods to measure its water content and in vitro degradation. Moreover, cell cultured solutions, which were in the different cultivation vesse with 1 mg/mL Solution of HA derivative as doing experimental sample for 2 d, 4 d and 7 d, were observed, respectively, by an inverted discrepancy microscope. The cell relative growth rate was analyzed with the SPSS10.0 mathematic statistic software. Based on the above experiments,structure-modified HA derivative can meet the requirements of biomaterials in view of rheological and degradation in vitro and cytotoxicity charactereistics from clinical medical aspect under this experiment conditions.

  11. Chemically and biologically synthesized CPP-modified gelonin for enhanced anti-tumor activity.

    Science.gov (United States)

    Shin, Meong Cheol; Zhang, Jian; David, Allan E; Trommer, Wolfgang E; Kwon, Young Min; Min, Kyoung Ah; Kim, Jin H; Yang, Victor C

    2013-11-28

    The ineffectiveness of small molecule drugs against cancer has generated significant interest in more potent macromolecular agents. Gelonin, a plant-derived toxin that inhibits protein translation, has attracted much attention in this regard. Due to its inability to internalize into cells, however, gelonin exerts only limited tumoricidal effect. To overcome this cell membrane barrier, we modified gelonin, via both chemical conjugation and genetic recombination methods, with low molecular weight protamine (LMWP), a cell-penetrating peptide (CPP) which was shown to efficiently ferry various cargoes into cells. Results confirmed that gelonin-LMWP chemical conjugate (cG-L) and recombinant gelonin-LMWP chimera (rG-L) possessed N-glycosidase activity equivalent to that of unmodified recombinant gelonin (rGel); however, unlike rGel, both gelonin-LMWPs were able to internalize into cells. Cytotoxicity studies further demonstrated that cG-L and rG-L exhibited significantly improved tumoricidal effects, with IC50 values being 120-fold lower than that of rGel. Moreover, when tested against a CT26 s.c. xenograft tumor mouse model, significant inhibition of tumor growth was observed with rG-L doses as low as 2 μg/tumor, while no detectable therapeutic effects were seen with rGel at 10-fold higher doses. Overall, this study demonstrated the potential of utilizing CPP-modified gelonin as a highly potent anticancer drug to overcome limitations of current chemotherapeutic agents. PMID:23973813

  12. Serotype 1 viruses modified by backpassage or insertional mutagenesis: approaching the threshold of vaccine efficacy in Marek's disease.

    Science.gov (United States)

    Witter, R L; Kreager, K S

    2004-12-01

    Improved vaccines to control Marek's disease (MD) in chickens are desired by the poultry industry but have been difficult to develop. Studies were conducted to evaluate strategies for deriving MD vaccines of high protective efficacy, irrespective of virulence. Candidate viruses from parent strains representing v and vv+ pathotypes were modified by cell culture passage, backpassage in chickens, or insertional mutagenesis following cocultivation with retroviruses. Ten strains considered most likely to exhibit high protective efficacy were selected for further study. The ability of these modified viruses to protect commercial or maternal antibody-positive (ab+) chickens against virulent MD virus (MDV) challenge was compared with that of strain CVI988, the standard commercial MD vaccine. Modified strains were also evaluated for the ability to induce lymphomas or other pathologic changes in ab+ and antibody-negative (ab-) chickens. Two of the 10 modified viruses, strains RM1 and CVI988/BP5, provided high levels of protection against highly virulent MDV challenge. The magnitude of protection was greater than that of one laboratory and two commercial preparations of CV1988, but was approximately equal to that of two other commercial preparations of CVI988 in laboratory and field tests. Three of the strains, including RMI and CVI988/BP5, induced lymphoid organ atrophy in ab-chicks but not in ab+ commercial chicks, a property designated here as L phenotype. Seven strains, including two L+ strains, were mildly oncogenic for ab- chicks, a property designated here as O phenotype. Five of these strains caused no tumors in ab+ chickens. The two fully attenuated strains induced neither lymphomas nor lymphoid organ atrophy. The L and O phenotypes appeared not to be linked, and both (especially the L phenotype) appeared associated with high levels of protection. These studies also illustrated differences in the protective efficacy of different preparations of CVI988 vaccine

  13. Biological therapy in inflammatory bowel diseases: access in Central and Eastern Europe.

    Science.gov (United States)

    Rencz, Fanni; Péntek, Márta; Bortlik, Martin; Zagorowicz, Edyta; Hlavaty, Tibor; Śliwczyński, Andrzej; Diculescu, Mihai M; Kupcinskas, Limas; Gecse, Krisztina B; Gulácsi, László; Lakatos, Peter L

    2015-02-14

    Biological drugs opened up new horizons in the management of inflammatory bowel diseases (IBD). This study focuses on access to biological therapy in IBD patients across 9 selected Central and Eastern European (CEE) countries, namely Bulgaria, the Czech Republic, Estonia, Hungary, Latvia, Lithuania, Poland, Romania and Slovakia. Literature data on the epidemiology and disease burden of IBD in CEE countries was systematically reviewed. Moreover, we provide an estimation on prevalence of IBD as well as biological treatment rates. In all countries with the exception of Romania, lower biological treatment rates were observed in ulcerative colitis (UC) compared to Crohn's disease despite the higher prevalence of UC. Great heterogeneity (up to 96-fold) was found in access to biologicals across the CEE countries. Poland, Bulgaria, Romania and the Baltic States are lagging behind Hungary, Slovakia and the Czech Republic in their access to biologicals. Variations of reimbursement policy may be one of the factors explaining the differences to a certain extent in Bulgaria, Latvia, Lithuania, and Poland, but association with other possible determinants (differences in prevalence and incidence, price of biologicals, total expenditure on health, geographical access, and cost-effectiveness results) was not proven. We assume, nevertheless, that health deterioration linked to IBD might be valued differently against other systemic inflammatory conditions in distinct countries and which may contribute to the immense diversity in the utilization of biological drugs for IBD. In conclusion, access to biologicals varies widely among CEE countries and this difference cannot be explained by epidemiological factors, drug prices or total health expenditure. Changes in reimbursement policy could contribute to better access to biologicals in some countries. PMID:25684937

  14. Multitarget Strategy to Address Alzheimer's Disease: Design, Synthesis, Biological Evaluation, and Computational Studies of Coumarin-Based Derivatives.

    Science.gov (United States)

    Montanari, Serena; Bartolini, Manuela; Neviani, Paolo; Belluti, Federica; Gobbi, Silvia; Pruccoli, Letizia; Tarozzi, Andrea; Falchi, Federico; Andrisano, Vincenza; Miszta, Przemysław; Cavalli, Andrea; Filipek, Sławomir; Bisi, Alessandra; Rampa, Angela

    2016-06-20

    Alzheimer's disease (AD) is a major public health challenge that faces an aging global population. Current drug treatment has demonstrated only symptomatic efficacy, leaving an unmet medical need for a new generation of disease-modifying therapies. Following the multitarget-directed ligand approach, a small library of coumarin-based derivatives was designed and synthesized as a follow-up to our studies on AP2238, aimed at expanding its biological profile. The coumarin substitution pattern at the 6- or 7-position was modified by introducing alkyl chains of variable lengths and with different terminal amino functional groups. 3-(4-{[Benzyl(ethyl)amino]methyl}phenyl)-6-({5-[(7-methoxy-6H-indeno[2,1-b]quinolin-11-yl)amino]pentyl}oxy)-2H-chromen-2-one, bearing the bulkiest amine, emerged as a non-neurotoxic dual acetylcholinesterase (AChE)/butyrylcholinesterase (BuChE) inhibitor, potentially suitable for the treatment of the middle stage of AD. Furthermore, the introduction of a diethylamino spacer, as in 3-(4-{[benzyl(ethyl)amino]methyl}phenyl)-6-{[5-(diethylamino)pentyl]oxy}-2H-chromen-2-one and 3-(4-{[benzyl(ethyl)amino]methyl}phenyl)-7-[4-(diethylamino)butoxy]-2H-chromen-2-one, led to nanomolar human AChE inhibitors endowed with significant inhibitory activity toward Aβ42 self-aggregation, whereas the reference compound was completely ineffective. Furthermore, 3-(4-{[benzyl(ethyl)amino]methyl}phenyl)-7-[4-(diethylamino)butoxy]-2H-chromen-2-one also showed promising neuroprotective behavior, which makes it a potential candidate for development into a disease-modifying agent. PMID:26507467

  15. PGC-1alpha downstream transcription factors NRF-1 and TFAM are genetic modifiers of Huntington disease

    Directory of Open Access Journals (Sweden)

    Haghikia Aiden

    2011-05-01

    Full Text Available Abstract Background Huntington disease (HD is an inherited neurodegenerative disease caused by an abnormal expansion of a CAG repeat in the huntingtin HTT (HD gene. The primary genetic determinant of the age at onset (AO is the length of the HTT CAG repeat; however, the remaining genetic contribution to the AO of HD has largely not been elucidated. Recent studies showed that impaired functioning of the peroxisome proliferator-activated receptor gamma coactivator 1a (PGC-1alpha contributes to mitochondrial dysfunction and appears to play an important role in HD pathogenesis. Further genetic evidence for involvement of PGC-1alpha in HD pathogenesis was generated by the findings that sequence variations in the PPARGC1A gene encoding PGC-1alpha exert modifying effects on the AO in HD. In this study, we hypothesised that polymorphisms in PGC-1alpha downstream targets might also contribute to the variation in the AO. Results In over 400 German HD patients, polymorphisms in the nuclear respiratory factor 1 gene, NRF-1, and the mitochondrial transcription factor A, encoded by TFAM showed nominally significant association with AO of HD. When combining these results with the previously described modifiers rs7665116 in PPARGC1A and C7028T in the cytochrome c oxidase subunit I (CO1, mt haplogroup H in a multivariable model, a substantial proportion of the variation in AO can be explained by the joint effect of significant modifiers and their interactions, respectively. Conclusions These results underscore that impairment of mitochondrial function plays a critical role in the pathogenesis of HD and that upstream transcriptional activators of PGC-1alpha may be useful targets in the treatment of HD.

  16. Model systems of protein-misfolding diseases reveal chaperone modifiers of proteotoxicity

    Science.gov (United States)

    2016-01-01

    ABSTRACT Chaperones and co-chaperones enable protein folding and degradation, safeguarding the proteome against proteotoxic stress. Chaperones display dynamic responses to exogenous and endogenous stressors and thus constitute a key component of the proteostasis network (PN), an intricately regulated network of quality control and repair pathways that cooperate to maintain cellular proteostasis. It has been hypothesized that aging leads to chronic stress on the proteome and that this could underlie many age-associated diseases such as neurodegeneration. Understanding the dynamics of chaperone function during aging and disease-related proteotoxic stress could reveal specific chaperone systems that fail to respond to protein misfolding. Through the use of suppressor and enhancer screens, key chaperones crucial for proteostasis maintenance have been identified in model organisms that express misfolded disease-related proteins. This review provides a literature-based analysis of these genetic studies and highlights prominent chaperone modifiers of proteotoxicity, which include the HSP70-HSP40 machine and small HSPs. Taken together, these studies in model systems can inform strategies for therapeutic regulation of chaperone functionality, to manage aging-related proteotoxic stress and to delay the onset of neurodegenerative diseases. PMID:27491084

  17. Modified biological training model for percutaneous renal surgery with ultrasound and fluoroscopy guidance

    Institute of Scientific and Technical Information of China (English)

    QIU Zhi; YANG Yong; ZHANG Yi; SUN Yu-cheng

    2011-01-01

    Background The 12th rib is an important anatomic marker in the process of percutaneous renal surgery; while the previous models without ribs can not provide close simulation conditions to human upper abdomen. To facilitate the learning and training of percutaneous renal access and intrarenal procedures under ultrasound and fluoroscopy guidance, we reported a biological bench model for percutaneous renal surgery. Methods The model was developed using an ex vivo porcine kidney with a longer than 3 cm ureter, a flap of full thickness of thoracic wall with skin, subcutaneous fascia, muscle and two ribs, as well as the standard equipment for percutaneous nephrolithotomy. The porcine kidney with a catheterized ureter was placed within the porcine flap and fixed to a wooden board with two long steel nails. Afterward, contrast medium or physiological saline (0.9% sodium chloride solution) was injected through the ureter, and the urinary system was examined with a fluoroscopy unit or an ultrasound. Artificial stone material was implanted in the renal pelvis. After practicing, the model could be dissected for kidney examination and a technical analysis. Results The advantage of this model was simple to set up and inexpensive, by using widely available material. The biological bench model can be employed for percutanous renal access, tract dilation, nephroscopy, and stone disintegration in the training and learning of clinical practice. Imaging is feasible under fluoroscopic and ultrasound guidance. The kidney models were utilized in hands on courses with over 100 people, and 90.5% attendants rated the porcine kidney model for simulation of percutaneous renal surgery as 'very helpful" or "helpful". Conclusion This biological training model simulates realistically the clinical procedure of percutaneous nephrolithotomy under fluoroscopic and ultrasound guidance.

  18. Electrochemical treatment of COD in biologically pretreated coking wastewater using Ti/RuO2-IrO2 electrodes combined with modified coke

    Institute of Scientific and Technical Information of China (English)

    HE Xu-wen; LIU Li-yuan; GONG Jing-wen; WANG Jian-bing; QIN Qiang; WANG Hao

    2011-01-01

    The electrochemical treatment of COD contained in biologically pretreated coking wastewater treated by a three-dimensional electrode system with modified coke as the particle electrode was investigated.And the electrochemical perfomance of the coke modified with various active components was studied.The results show that the coke modified with Fe(NO3)2 has the lowest energy consumption and higher COD removal rate under the same condition,and the modified coke has better surface characteristics for the purpose of this study.In addition,the kinetic constant was also calculated.The study shows that the three-dimensional electrode system with Fe(NO3)2-modified coke can give a satisfactory solution in biologically pretreated coking wastewater.

  19. Galectin-9: From cell biology to complex disease dynamics.

    Science.gov (United States)

    John, Sebastian; Mishra, Rashmi

    2016-09-01

    Galectins is a family of non-classically secreted, beta-galactoside-binding proteins that has recently received considerable attention in the spatio-temporal regulation of surface 'signal lattice' organization, membrane dynamics, cell-adhesion and disease therapeutics. Galectin-9 is a unique member of this family, with two non-homologous carbohydrate recognition domains joined by a linker peptide sequence of variable lengths, generating isoforms with distinct properties and functions in both physiological and pathological settings, such as during development, immune reaction, neoplastic transformations and metastasis. In this review, we summarize the latest knowledge on the structure, receptors, cellular targets, trafficking pathways and functional properties of galectin-9 and discuss how galectin-9-mediated signalling cascades can be exploited in cancers and immunotherapies. PMID:27581941

  20. Galectin-9: From cell biology to complex disease dynamics

    Indian Academy of Sciences (India)

    SEBASTIAN JOHN; RASHMI MISHRA

    2016-09-01

    Galectins is a family of non-classically secreted, β-galactoside-binding proteins that has recently received considerableattention in the spatio-temporal regulation of surface ‘signal lattice’ organization, membrane dynamics, cell-adhesionand disease therapeutics. Galectin-9 is a unique member of this family, with two non-homologous carbohydraterecognition domains joined by a linker peptide sequence of variable lengths, generating isoforms with distinctproperties and functions in both physiological and pathological settings, such as during development, immunereaction, neoplastic transformations and metastasis. In this review, we summarize the latest knowledge on thestructure, receptors, cellular targets, trafficking pathways and functional properties of galectin-9 and discuss howgalectin-9-mediated signalling cascades can be exploited in cancers and immunotherapies.

  1. Biological tissue magnetism in the frame of iron overload diseases

    International Nuclear Information System (INIS)

    The conspicuous magnetic properties of iron, paradoxically, rarely participate in the methods routinely employed in the clinical environment to detect iron containing species in tissues. In the organism iron is just a trace metal and it mostly occurs as part of haemoproteins or ferritin, which show paramagnetic, diamagnetic or antiferromagnetic behaviour, hence resulting in a very low contribution to the tissue susceptibility. Detailed magnetic measurements make it nowadays possible to identify such species in tissues that correspond to individuals with iron overload pathologies. Since, as alternatives to the conventional biopsy, magnetism-based noninvasive techniques to diagnose and manage such diseases are recently under development, the deep knowledge of the magnetic properties of the different forms of iron in tissues is of high applied interest

  2. IVIG in autoimmune disease - Potential next generation biologics.

    Science.gov (United States)

    Zuercher, Adrian W; Spirig, Rolf; Baz Morelli, Adriana; Käsermann, Fabian

    2016-08-01

    Polyclonal plasma-derived IgG is a mainstay therapeutic of immunodeficiency disorders as well as of various inflammatory autoimmune diseases. In immunodeficiency the primary function of IVIG/SCIG is to replace missing antibody specificities, consequently a diverse Fab-based repertoire is critical for efficacy. Attempts to capture the Ig repertoire and express it as a recombinant IVIG product are currently ongoing. Likewise correction of the defective genes by gene therapy has also been tried. However, both approaches are far from becoming mainstream treatments. In contrast, some of the most important effector mechanisms relevant in therapy of autoimmunity are based on the Fc-portion of IgG; they include scavenging of complement and blockade/modulation of IgG receptors (Fc gamma receptor [FcγR] or the neonatal Fc receptor [FcRn]). These effects might be achieved with appropriately formulated Fc-fragments instead of full-length IgG, as suggested by a pilot study with monomeric plasma-derived Fc in children with ITP and in Kawasaki disease in the 1990s. Since then it has been proposed that structured multimerization of Fc fragments might confer efficacy at much lower doses than with IVIG. Accordingly, various molecular strategies are currently being explored to achieve controlled Fc multimerization, e.g. by fusion of IgG1 Fc to the IgG2 hinge-region or to the IgM tail-piece. Safety considerations will be crucial in the evaluation of these new entities. In a different approach, mutant Fc fragments and monoclonal antibodies have been designed for blockade of the FcRn. PMID:27019051

  3. Update and future perspectives of a thymic biological response modifier (Thymomodulin).

    Science.gov (United States)

    Cazzola, P; Mazzanti, P; Kouttab, N M

    1987-01-01

    Thymomodulin (Ellem Industria Farmaceutica spa, Milan, Italy) is a calf thymus acid lysate with immunomodulating activities. It is composed of several peptides with a molecular weight range of 1-10kD. Extensive studies in animal systems showed that Thymomodulin exhibited no, or very little toxicity even when used at high doses. Studies done in vitro and in vivo demonstrated that Thymomodulin is a biologically active compound which regulates the maturation of human and murine pre T lymphocytes, as well as modulate the functions of apparently mature human and animal B and T lymphocytes. It was observed that Thymomodulin can promote myelopoiesis as demonstrated by an increase of granulocyte-macrophage colonies in agar. Although additional studies to examine its target cell lineage are required, it appears that Thymomodulin exhibits specificity toward T cells. Therefore, enhancement of other cell lineage functions by Thymomodulin may be indirect, and mainly due to its effect on T cells. Of major importance is to note that Thymomodulin is prepared in a manner which allows it to maintain its biological activity when administered orally. PMID:3325544

  4. Biological control of botrytis cinerea growth on apples stored in modified atmospheres

    DEFF Research Database (Denmark)

    Dock, Lise Lotte; Nielsen, Per Væggemose; Floros, John D.

    1998-01-01

    The combined effect of modified-atmosphere packaging and theapplication of a bacterial antagonist (Erwinia sp.) on Botrytiscinerea growth on apples (cv. 'Golden Delicious') was investigated.Inoculated apples were stored in polyethylene bags at 5 degrees C. Theinitial gas composition in each bag was...... set according to a centralcomposite experimental design involving five levels of O2 (1 to 15%)and CO2 (0 to 15%). Control samples under ambient conditions were alsoincluded. Without the antagonist, measurements of mold colony diameterover time showed that O2 had no effect on the growth of B. cinerea......,while increased CO2 levels delayed its growth by about 4 days.Application of the antagonist resulted in a significant interactionbetween O2 and CO2. At low O2 levels, CO2 had no effect on moldgrowth, but at high O2, CO2 enhanced mold growth. O2 and theantagonist worked synergistically to reduce mold growth by...

  5. A Systems Biology Approach to Infectious Disease Research: Innovating the Pathogen-Host Research Paradigm

    Energy Technology Data Exchange (ETDEWEB)

    Aderem, Alan; Adkins, Joshua N.; Ansong, Charles; Galagan, James; Kaiser, Shari; Korth, Marcus J.; Law, G. L.; McDermott, Jason E.; Proll, Sean; Rosenberger, Carrie; Schoolnik, Gary; Katze, Michael G.

    2011-02-01

    The 20th century was marked by extraordinary advances in our understanding of microbes and infectious disease, but pandemics remain, food and water borne illnesses are frequent, multi-drug resistant microbes are on the rise, and the needed drugs and vaccines have not been developed. The scientific approaches of the past—including the intense focus on individual genes and proteins typical of molecular biology—have not been sufficient to address these challenges. The first decade of the 21st century has seen remarkable innovations in technology and computational methods. These new tools provide nearly comprehensive views of complex biological systems and can provide a correspondingly deeper understanding of pathogen-host interactions. To take full advantage of these innovations, the National Institute of Allergy and Infectious Diseases recently initiated the Systems Biology Program for Infectious Disease Research. As participants of the Systems Biology Program we think that the time is at hand to redefine the pathogen-host research paradigm.

  6. The KUPNetViz: a biological network viewer for multiple -omics datasets in kidney diseases

    OpenAIRE

    Moulos, Panagiotis; Klein, Julie; Jupp, Simon; Stevens, Robert; Bascands, Jean-Loup; Schanstra, Joost

    2013-01-01

    BACKGROUND: Constant technological advances have allowed scientists in biology to migrate from conventional single-omics to multi-omics experimental approaches, challenging bioinformatics to bridge this multi-tiered information. Ongoing research in renal biology is no exception. The results of large-scale and/or high throughput experiments, presenting a wealth of information on kidney disease are scattered across the web. To tackle this problem, we recently presented the KUPKB, a multi-omics ...

  7. Transfusion-related acute lung injury: transfusion, platelets and biological response modifiers.

    Science.gov (United States)

    Tariket, Sofiane; Sut, Caroline; Hamzeh-Cognasse, Hind; Laradi, Sandrine; Pozzetto, Bruno; Garraud, Olivier; Cognasse, Fabrice

    2016-05-01

    Transfusion-related acute lung injury (TRALI) may be induced by plasma, platelet concentrates and red blood cell concentrates. The mechanism leading to TRALI is thought to involve two steps. The priming step consists of previous inflammatory pathological conditions or external factors attracting leukocytes to lung vessels and creating conditions favorable for the second step, in which anti-HLA or anti-HNA antibodies or biologically active lipids, usually in transfused blood products, stress leukocytes and inflame lung epithelia. Platelets may be involved in the pathogenesis of TRALI because of their secretory potential and capacity to interact with other immune cells. There is no drug based-prophylaxis, but transfusion strategies are used to mitigate the risk of TRALI. PMID:26855042

  8. Inflammatory Bowel Disease: An Overview of Immune Mechanisms and Biological Treatments

    Directory of Open Access Journals (Sweden)

    Bruno Rafael Ramos de Mattos

    2015-01-01

    Full Text Available Inflammatory bowel diseases (IBD are characterized by chronic inflammation of the intestinal tract associated with an imbalance of the intestinal microbiota. Crohn’s disease (CD and ulcerative colitis (UC are the most widely known types of IBD and have been the focus of attention due to their increasing incidence. Recent studies have pointed out genes associated with IBD susceptibility that, together with environment factors, may contribute to the outcome of the disease. In ulcerative colitis, there are several therapies available, depending on the stage of the disease. Aminosalicylates, corticosteroids, and cyclosporine are used to treat mild, moderate, and severe disease, respectively. In Crohn’s disease, drug choices are dependent on both location and behavior of the disease. Nowadays, advances in treatments for IBD have included biological therapies, based mainly on monoclonal antibodies or fusion proteins, such as anti-TNF drugs. Notwithstanding the high cost involved, these biological therapies show a high index of remission, enabling a significant reduction in cases of surgery and hospitalization. Furthermore, migration inhibitors and new cytokine blockers are also a promising alternative for treating patients with IBD. In this review, an analysis of literature data on biological treatments for IBD is approached, with the main focus on therapies based on emerging recombinant biomolecules.

  9. Inflammatory Bowel Disease: An Overview of Immune Mechanisms and Biological Treatments

    Science.gov (United States)

    de Mattos, Bruno Rafael Ramos; Garcia, Maellin Pereira Gracindo; Nogueira, Julia Bier; Paiatto, Lisiery Negrini; Albuquerque, Cassia Galdino; Souza, Caique Lopes; Fernandes, Luís Gustavo Romani; Tamashiro, Wirla Maria da Silva Cunha; Simioni, Patricia Ucelli

    2015-01-01

    Inflammatory bowel diseases (IBD) are characterized by chronic inflammation of the intestinal tract associated with an imbalance of the intestinal microbiota. Crohn's disease (CD) and ulcerative colitis (UC) are the most widely known types of IBD and have been the focus of attention due to their increasing incidence. Recent studies have pointed out genes associated with IBD susceptibility that, together with environment factors, may contribute to the outcome of the disease. In ulcerative colitis, there are several therapies available, depending on the stage of the disease. Aminosalicylates, corticosteroids, and cyclosporine are used to treat mild, moderate, and severe disease, respectively. In Crohn's disease, drug choices are dependent on both location and behavior of the disease. Nowadays, advances in treatments for IBD have included biological therapies, based mainly on monoclonal antibodies or fusion proteins, such as anti-TNF drugs. Notwithstanding the high cost involved, these biological therapies show a high index of remission, enabling a significant reduction in cases of surgery and hospitalization. Furthermore, migration inhibitors and new cytokine blockers are also a promising alternative for treating patients with IBD. In this review, an analysis of literature data on biological treatments for IBD is approached, with the main focus on therapies based on emerging recombinant biomolecules. PMID:26339135

  10. The role of the Biological Weapons Convention in disease surveillance and response.

    Science.gov (United States)

    Enemark, Christian

    2010-11-01

    This article assesses the role and significance of the Biological Weapons Convention (BWC) with respect to infectious disease surveillance and response to outbreaks. Increasingly, the BWC is being used as a platform for addressing infectious disease threats arising naturally as well as traditional concerns about malicious dissemination of pathogenic microorganisms. The latter have long had a place on the security agenda, but natural disease outbreaks too are now being partially 'securitized' through the use of the BWC as a forum for exchanging information and ideas on disease surveillance and response. The article focuses on two prominent issues discussed at recent meetings of BWC member states: enhancing capacity for disease surveillance and response; and responding to allegations of biological weapons use and investigating outbreaks deemed suspicious. It concludes, firstly, that the BWC supports the efforts of international health organizations to enhance disease surveillance and response capacity worldwide. And secondly, that the BWC, rather than the World Health Organization (WHO), is the appropriate institution to deal with biological weapons allegations and investigations of suspicious outbreaks. The overall message is that securitization in the health sphere cuts both ways. Adding a security dimension (BW) alongside the task of detecting and responding to naturally occurring disease outbreaks is beneficial, but requiring a non-security organization (the WHO) to assume a security role would be counterproductive. PMID:20961949

  11. The gene coding for PGC-1α modifies age at onset in Huntington's Disease

    Directory of Open Access Journals (Sweden)

    Oberkofler Hannes

    2009-01-01

    Full Text Available Abstract Huntington's disease (HD is one of the most common autosomal dominant inherited, neurodegenerative disorders. It is characterized by progressive motor, emotional and cognitive dysfunction. In addition metabolic abnormalities such as wasting and altered energy expenditure are increasingly recognized as clinical hallmarks of the disease. HD is caused by an unstable CAG repeat expansion in the HD gene (HTT, localized on chromosome 4p16.3. The number of CAG repeats in the HD gene is the main predictor of disease-onset, but the remaining variation is strongly heritable. Transcriptional dysregulation, mitochondrial dysfunction and enhanced oxidative stress have been implicated in the pathogenesis. Recent studies suggest that PGC-1α, a transcriptional master regulator of mitochondrial biogenesis and metabolism, is defective in HD. A genome wide search for modifier genes of HD age-of-onset had suggested linkage at chromosomal region 4p16-4p15, near the locus of PPARGC1A, the gene coding for PGC-1α. We now present data of 2-loci PPARGC1A block 2 haplotypes, showing an effect upon age-at-onset in 447 unrelated HD patients after statistical consideration of CAG repeat lengths in both HTT alleles. Block 1 haplotypes were not associated with the age-at-onset. Homozygosity for the 'protective' block 2 haplotype was associated with a significant delay in disease onset. To our knowledge this is the first study to show clinically relevant effects of the PGC-1α system on the course of Huntington's disease in humans.

  12. Metformin: A Novel Biological Modifier of Tumor Response to Radiation Therapy

    Energy Technology Data Exchange (ETDEWEB)

    Koritzinsky, Marianne, E-mail: mkoritzi@uhnresearch.ca

    2015-10-01

    Over the last decade, evidence has emerged to support a role for the antidiabetic drug metformin in the prevention and treatment of cancer. In particular, recent studies demonstrate that metformin enhances tumor response to radiation in experimental models, and retrospective analyses have shown that diabetic cancer patients treated with radiation therapy have improved outcomes if they take metformin to control their diabetes. Metformin may therefore be of utility for nondiabetic cancer patients treated with radiation therapy. The purpose of this review is to examine the data pertaining to an interaction between metformin and radiation, highlighting the essential steps needed to advance our current knowledge. There is also a focus on key biomarkers that should accompany prospective clinical trials in which metformin is being examined as a modifying agent with radiation therapy. Existing evidence supports that the mechanism underlying the ability of metformin to enhance radiation response is multifaceted, and includes direct radiosensitization as well as a reduction in tumor stem cell fraction, proliferation, and tumor hypoxia. Interestingly, metformin may enhance radiation response specifically in certain genetic backgrounds, such as in cells with loss of the tumor suppressors p53 and LKB1, giving rise to a therapeutic ratio and potential predictive biomarkers.

  13. Effect of substrate concentration on biodegradation of 2,4-dichlorophenol using modified rotating biological contactors

    Energy Technology Data Exchange (ETDEWEB)

    Swaminathan, G. [Regional Engineering College, Tiruchirapalli 620 015 (India); Ramanujam, T.K. [Indian Inst. of Tech., Madras (India). Dept. of Chemical Engineering

    1999-08-01

    2,4-Dichlorophenol used in the manufacture of pesticides, germicides, resins, seed disinfectants and antiseptics, if disposed untreated causes greater havoc for land and aquatic environment. In all the earlier works, 2,4-dichlorophenol has been fed along with easily biodegradable substrate, glucose as one of the constituents. A modified 4-stage RBC was used for the biodegradation studies of 2,4-dichlorophenol. The micro organisms attached to the disks were specially acclimatised to the extent that the 2,4-dichlorophenol alone serves as the sole carbon source supporting their metabolic activities. The RBC was operated at 12 rpm. The toxic substrate removal studies were carried out in the hydraulic loading rates ranging from 0.005 m{sup 3}/m{sup 2}/d to 0.035 m{sup 3}/m{sup 2}/d and organic loading rates from 0.35 g/m{sup 2}/d to 6.15 g/m{sup 2}/d. A correlation plot between 2,4-dichlorophenol removal and organic loading rate is presented. A mathematical model is proposed using regression analysis. (orig.) With 10 figs., 1 tab., 4 refs.

  14. Metformin: A Novel Biological Modifier of Tumor Response to Radiation Therapy

    International Nuclear Information System (INIS)

    Over the last decade, evidence has emerged to support a role for the antidiabetic drug metformin in the prevention and treatment of cancer. In particular, recent studies demonstrate that metformin enhances tumor response to radiation in experimental models, and retrospective analyses have shown that diabetic cancer patients treated with radiation therapy have improved outcomes if they take metformin to control their diabetes. Metformin may therefore be of utility for nondiabetic cancer patients treated with radiation therapy. The purpose of this review is to examine the data pertaining to an interaction between metformin and radiation, highlighting the essential steps needed to advance our current knowledge. There is also a focus on key biomarkers that should accompany prospective clinical trials in which metformin is being examined as a modifying agent with radiation therapy. Existing evidence supports that the mechanism underlying the ability of metformin to enhance radiation response is multifaceted, and includes direct radiosensitization as well as a reduction in tumor stem cell fraction, proliferation, and tumor hypoxia. Interestingly, metformin may enhance radiation response specifically in certain genetic backgrounds, such as in cells with loss of the tumor suppressors p53 and LKB1, giving rise to a therapeutic ratio and potential predictive biomarkers

  15. Disease-modifying antirheumatic drugs in pregnancy: current status and implications for the future.

    Science.gov (United States)

    Vroom, Fokaline; de Walle, Hermien E K; van de Laar, Mart A J F; Brouwers, Jacobus R B J; de Jong-van den Berg, Lolkje T W

    2006-01-01

    Drug use during pregnancy is sometimes unavoidable, especially in chronic inflammatory diseases such as rheumatoid arthritis (RA). The use of disease-modifying antirheumatic drugs (DMARDs) often starts in the early stage of RA; therefore, women of reproductive age are at risk for exposure to a DMARD at time of conception as well as during pregnancy. The aim of this paper was to review recent literature about DMARDs used for rheumatic diseases in pregnancy and to describe the type of study designs and results reported.Twenty-nine studies; eight on hydroxychloroquine/chloroquine, thirteen on methotrexate, three on sulfasalazine and six on azathioprine were identified. With respect to hydroxychloroquine, most studies concluded that it could be safely used in systemic lupus erythematosus or RA. The same conclusions were drawn from the azathioprine studies, but the available evidence is scarce. Although the evidence regarding the safety of methotrexate during pregnancy is conflicting, a high rate of pregnancy losses indicates a risk to the fetus. For each individual case it must be decided whether the benefits outweigh the potential risks. No major teratogenic effects of sulfasalazine were seen although teratogenic effects still can not be excluded. For all other DMARDs, the information on their use in pregnancy was limited. This review underscores the gross absence of data on safety and risks of DMARD use during conception and pregnancy. While young women use these drugs in pregnancy, this review stresses the importance of good monitoring and further research. PMID:16970509

  16. The Genetic Modifiers of Motor Onset Age (GeM MOA) website: genome-wide association analysis for genetic modifiers of Huntington's disease

    Science.gov (United States)

    Correia, Kevin; Harold, Denise; Kim, Kyung-Hee; Holmans, Peter; Jones, Lesley; Orth, Michael; Myers, Richard H.; Kwak, Seung; Wheeler, Vanessa C.; MacDonald, Marcy E.; Gusella, James F.; Lee, Jong-Min

    2016-01-01

    BACKGROUND Huntington's disease (HD) is a dominantly inherited disease caused by a CAG expansion mutation in HTT. The age at onset of clinical symptoms is determined primarily by the length of this CAG expansion but is also influenced by other genetic and/or environmental factors. OBJECTIVE Recently, through genome-wide association studies (GWAS) aimed at discovering genetic modifiers, we identified loci associated with age at onset of motor signs that are significant at the genome-wide level. However, many additional HD modifiers may exist but may not have achieved statistical significance due to limited power. METHODS In order to disseminate broadly the entire GWAS results and make them available to complement alternative approaches, we have developed the internet website "GeM MOA" where genetic association results can be searched by gene name, SNP ID, or genomic coordinates of a region of interest. RESULTS Users of the Genetic Modifiers of Motor Onset Age (GeM MOA) site can therefore examine support for association between any gene region and age at onset of HD motor signs. GeM MOA's interactive interface also allows users to navigate the surrounding region and to obtain association p-values for individual SNPs. CONCLUSIONS Our website conveys a comprehensive view of the genetic landscape of modifiers of HD from the existing GWAS, and will provide the means to evaluate the potential influence of genes of interest on the onset of HD. GeM MOA is freely available at https://www.hdinhd.org/. PMID:26444025

  17. Optimization of the treatment with immunosuppressants and biologics in inflammatory bowel disease

    OpenAIRE

    Renna, S; Cottone, M; Orlando, A

    2014-01-01

    Many placebo controlled trials and meta-analyses evaluated the efficacy of different drugs for the treatment of inflammatory bowel disease (IBD), including immunosuppressants and biologics. Their use is indicated in moderate to severe disease in non responders to corticosteroids and in steroid-dependent patients, as induction and maintainance treatment. Infliximab, as well as cyclosporine, is considered a second line therapy in the case of severe ulcerative colitis, or non-responders to intra...

  18. Biology, diversity and strategies for the monitoring and control of triatomines - Chagas disease vectors

    OpenAIRE

    Jane Costa; Marcelo Lorenzo

    2009-01-01

    Despite the relevant achievements in the control of the main Chagas disease vectors Triatoma infestans and Rhodnius prolixus, several factors still promote the risk of infection. The disease is a real threat to the poor rural regions of several countries in Latin America. The current situation in Brazil requires renewed attention due to its high diversity of triatomine species and to the rapid and drastic environmental changes that are occurring. Using the biology, behaviour and diversity of ...

  19. A medicoeconomic review of early intervention with biologic agents in the treatment of inflammatory bowel diseases

    OpenAIRE

    Odes S; Greenberg D

    2014-01-01

    Shmuel Odes,1 Dan Greenberg21Department of Gastroenterology and Hepatology, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer Sheva, Israel; 2Department of Health Systems Management, Faculty of Health Sciences and Guilford Glazer Faculty of Business and Management, Ben-Gurion University of the Negev, Beer Sheva, IsraelAbstract: The treatment of inflammatory bowel disease with standard therapy fails to control the disease in many patients. Biologic therapy has an increasing ...

  20. Single-stage Modified Duhamel procedure for Hirschsprung′s disease : Our experience

    Directory of Open Access Journals (Sweden)

    Paras R Kothari

    2012-01-01

    Full Text Available Introduction: Primary single-stage pull-through for Hirschsprung′s disease (HD has been reported to give comparable surgical outcomes to staged operations with less morbidity. Herein, we present our experience with single-stage Modified Duhamel procedure for management of HD. Patients and Methods: This was a review of 48 cases of HD who underwent single-stage Modified Duhamel procedure without a protective colostomy. Results: The age at surgery ranged from 6 months to 10 years (median - 9 months, mean - 2.3 years. The average weight of the child was 7.2 kg (range, 4.9-22 kg. 38 (79.2% patients had classical rectosigmoid HD, the rest being long segment HD (the proximal most level being the splenic flexure. The average duration of surgery was 175 minutes (range, 130-245 minutes. The average blood loss was 45 ml. The average hospital stay was 7.2 days (range: 6-10 days. The major postoperative complications (n=3 included postoperative adhesive intestinal obstruction, anastomotic leak and persistent constipation due to residual aganglionosis. Each required a re-exploration. Minor complications included surgical site infection (n=3 and post-operative enterocolitis (n=3, which were managed conservatively. Six patients had constipation for a limited period post-operatively. All patients have a satisfactory functional outcome and normal development and growth. Conclusions: For HD, we recommend that single-stage Modified Duhamel procedure should be the preferred approach in view of its low morbidity, satisfactory functional outcome and avoidance of stoma, multiple surgeries and economic benefit in view of decreased hospital stay.

  1. The Use of Oral Disease-Modifying Therapies in Multiple Sclerosis.

    Science.gov (United States)

    Kretzschmar, Benedikt; Pellkofer, Hannah; Weber, Martin S

    2016-04-01

    Three oral disease-modifying drugs-fingolimod, teriflunomide, and dimethyl fumarate (DMF)-are available for treatment of relapsing forms of multiple sclerosis (MS). All three agents were approved in the last decade, primarily on the basis of a moderate to substantial reduction in the occurrence of MS relapses and central nervous system lesion formation detected by MRI. In the trials leading to approval, the first oral disease-modifying drug, fingolimod, reduced the annualized relapse rate (ARR) from 0.40 in placebo-treated patients to 0.18 (FREEDOMS) and from 0.33 in patients treated with interferon β1a intramuscularly to 0.16 (TRANSFORMS). Teriflunomide, approved on the basis of the two placebo-controlled trials TEMSO and TOWER, demonstrated a reduction in the ARR from 0.54 to 0.37 and from 0.50 to 0.32 respectively. The latest oral MS medication, approved in 2014, is DMF, which had been used in a different formulation for treatment of psoriasis for decades. In the 2-year DEFINE study, the proportion of patients with a relapse was reduced to 27 %, compared with 46 % in placebo arm, whereas in the CONFIRM trial, the ARR was reduced from 0.40 (placebo) to 0.22 in the DMF-treated group of patients. In this review, we will elucidate the mechanisms of action of these three medications and compare their efficacy, safety, and tolerability as a practical guideline for their use. We will further discuss effects other than relapse reduction these small molecules may exert, including potential activities within the central nervous system, and briefly summarize emerging data on new oral MS drugs in clinical development. PMID:26944956

  2. Gaseous VOCs rapidly modify particulate matter and its biological effects – Part 1: Simple VOCs and model PM

    Directory of Open Access Journals (Sweden)

    H. E. Jeffries

    2012-02-01

    Full Text Available This is the first of a three-part study designed to demonstrate dynamic entanglements among gaseous organic compounds (VOC, particulate matter (PM, and their subsequent potential biological effects. We study these entanglements in increasingly complex VOC and PM mixtures in urban-like conditions in a large outdoor chamber. To the traditional chemical and physical characterizations of gas and PM, we added new measurements of gas-only- and PM-only-biological effects, using cultured human lung cells as model indicators. These biological effects are assessed here as increases in cellular damage or expressed irritation (i.e., cellular toxic effects from cells exposed to chamber air relative to cells exposed to clean air. The exposure systems permit gas-only- or PM-only-exposures from the same air stream containing both gases and PM in equilibria, i.e., there are no extractive operations prior to cell exposure. Our simple experiments in this part of the study were designed to eliminate many competing atmospheric processes to reduce ambiguity in our results. Simple volatile and semi-volatile organic gases that have inherent cellular toxic properties were tested individually for biological effect in the dark (at constant humidity. Airborne mixtures were then created with each compound and PM that has no inherent cellular toxic properties for another cellular exposure. Acrolein and p-tolualdehyde were used as model VOCs and mineral oil aerosol (MOA was selected as a surrogate for organic-containing PM. MOA is appropriately complex in composition to represent ambient PM, and it exhibits no inherent cellular toxic effects and thus did not contribute any biological detrimental effects on its own. Chemical measurements, combined with the responses of our biological exposures, clearly demonstrate that gas-phase pollutants can modify the composition of PM (and its resulting detrimental effects on lung cells – even if the gas-phase pollutants are not

  3. Gaseous VOCs rapidly modify particulate matter and its biological effects – Part 1: Simple VOCs and model PM

    Directory of Open Access Journals (Sweden)

    H. E. Jeffries

    2012-12-01

    Full Text Available This is the first of a three-part study designed to demonstrate dynamic entanglements among gaseous organic compounds (VOC, particulate matter (PM, and their subsequent potential biological effects. We study these entanglements in increasingly complex VOC and PM mixtures in urban-like conditions in a large outdoor chamber. To the traditional chemical and physical characterizations of gas and PM, we added new measurements of biological effects, using cultured human lung cells as model indicators. These biological effects are assessed here as increases in cellular damage or expressed irritation (i.e., cellular toxic effects from cells exposed to chamber air relative to cells exposed to clean air. The exposure systems permit virtually gas-only- or PM-only-exposures from the same air stream containing both gases and PM in equilibria, i.e., there are no extractive operations prior to cell exposure. Our simple experiments in this part of the study were designed to eliminate many competing atmospheric processes to reduce ambiguity in our results. Simple volatile and semi-volatile organic gases that have inherent cellular toxic properties were tested individually for biological effect in the dark (at constant humidity. Airborne mixtures were then created with each compound to which we added PM that has no inherent cellular toxic properties for another cellular exposure. Acrolein and p-tolualdehyde were used as model VOCs and mineral oil aerosol (MOA was selected as a surrogate for organic-containing PM. MOA is appropriately complex in composition to represent ambient PM, and exhibits no inherent cellular toxic effects and thus did not contribute any biological detrimental effects on its own. Chemical measurements, combined with the responses of our biological exposures, clearly demonstrate that gas-phase pollutants can modify the composition of PM (and its resulting detrimental effects on lung cells. We observed that, even if the gas-phase pollutants

  4. Gaseous VOCs rapidly modify particulate matter and its biological effects - Part 1: Simple VOCs and model PM

    Science.gov (United States)

    Ebersviller, S.; Lichtveld, K.; Sexton, K. G.; Zavala, J.; Lin, Y.-H.; Jaspers, I.; Jeffries, H. E.

    2012-12-01

    This is the first of a three-part study designed to demonstrate dynamic entanglements among gaseous organic compounds (VOC), particulate matter (PM), and their subsequent potential biological effects. We study these entanglements in increasingly complex VOC and PM mixtures in urban-like conditions in a large outdoor chamber. To the traditional chemical and physical characterizations of gas and PM, we added new measurements of biological effects, using cultured human lung cells as model indicators. These biological effects are assessed here as increases in cellular damage or expressed irritation (i.e., cellular toxic effects) from cells exposed to chamber air relative to cells exposed to clean air. The exposure systems permit virtually gas-only- or PM-only-exposures from the same air stream containing both gases and PM in equilibria, i.e., there are no extractive operations prior to cell exposure. Our simple experiments in this part of the study were designed to eliminate many competing atmospheric processes to reduce ambiguity in our results. Simple volatile and semi-volatile organic gases that have inherent cellular toxic properties were tested individually for biological effect in the dark (at constant humidity). Airborne mixtures were then created with each compound to which we added PM that has no inherent cellular toxic properties for another cellular exposure. Acrolein and p-tolualdehyde were used as model VOCs and mineral oil aerosol (MOA) was selected as a surrogate for organic-containing PM. MOA is appropriately complex in composition to represent ambient PM, and exhibits no inherent cellular toxic effects and thus did not contribute any biological detrimental effects on its own. Chemical measurements, combined with the responses of our biological exposures, clearly demonstrate that gas-phase pollutants can modify the composition of PM (and its resulting detrimental effects on lung cells). We observed that, even if the gas-phase pollutants are not

  5. Modifying influence of occupational inflammatory diseases on the level of chromosome aberrations in coal miners.

    Science.gov (United States)

    Volobaev, Valentin P; Sinitsky, Maxim Yu; Larionov, Aleksey V; Druzhinin, Vladimir G; Gafarov, Nikolay I; Minina, Varvara I; Kulemin, Jury E

    2016-03-01

    Coal miners are exposed to a wide range of genotoxic agents that can induce genome damage. In addition, miners are characterised by a high risk of the initiation of different occupational inflammatory as well as non-inflammatory diseases. The aim of this investigation is to analyse the modifying influence of occupational pulmonary inflammatory diseases on the level of chromosome aberrations (CAs) in miners working in underground coal mines in Kemerovo Region (Russian Federation). The study group included 90 coal miners with the following pulmonary diseases: chronic dust-induced bronchitis (CDB) and coal-workers' pneumoconiosis (CWP) (mean age = 53.52±2.95 years; mean work experience in coal-mining conditions = 27.70±3.61 years). As a population control (control 1), we have used venous blood extracted from 124 healthy unexposed men. The mean age in this group was 50.92±4.56 years. Control 2 was the venous blood extracted from 42 healthy coal miners (mean age = 51.56±6.38 years; mean work experience in coal-mining conditions = 25.43±8.14 years). We have discovered that coal miners are characterised by an increased general level of CAs as well as an increased frequency of several types of CAs. The significant increase in the frequency of aberration per 100 cells and aberration of chromosome type was discovered in the group of pulmonary disease patients (study group). No correlations of the level of chromosome damage with age, smoking status and work experience in coal-mining conditions were discovered. PMID:26609129

  6. Regulatory and biosafety issues in relation to transgenic animals in food and agriculture, feeds containing genetically modified organisms (GMO) and veterinary biologics

    International Nuclear Information System (INIS)

    biotechnology must be shown to be pure, potent, safe and effective when used according to label recommendations. The Canadian regulatory system relies on the 'precautionary principle' in its approach to regulate the 'product' instead of the 'process'. The regulatory framework captures transgenic animals under the Canadian Environmental Protection Act (CEPA). Food from transgenic animals is assessed for safety by Health Canada under its Novel Foods Regulations of the Food and Drugs Act. Feed containing any genetically modified organism is considered Novel Feed under the Feeds Act and Regulations. The regulation of veterinary biologics, in an effort to prevent and diagnose infectious diseases of animals, relies on effective science-based regulatory controls under the Health of Animals Act and Regulations. The Canadian system of regulation for feeds, veterinary biologics and transgenic animals could be useful to developing countries in the process of establishing an effective framework for new regulations. (author)

  7. Concise review: current status of stem cells and regenerative medicine in lung biology and diseases.

    Science.gov (United States)

    Weiss, Daniel J

    2014-01-01

    Lung diseases remain a significant and devastating cause of morbidity and mortality worldwide. In contrast to many other major diseases, lung diseases notably chronic obstructive pulmonary diseases (COPDs), including both asthma and emphysema, are increasing in prevalence and COPD is expected to become the third leading cause of disease mortality worldwide by 2020. New therapeutic options are desperately needed. A rapidly growing number of investigations of stem cells and cell therapies in lung biology and diseases as well as in ex vivo lung bioengineering have offered exciting new avenues for advancing knowledge of lung biology as well as providing novel potential therapeutic approaches for lung diseases. These initial observations have led to a growing exploration of endothelial progenitor cells and mesenchymal stem (stromal) cells in clinical trials of pulmonary hypertension and COPD with other clinical investigations planned. Ex vivo bioengineering of the trachea, larynx, diaphragm, and the lung itself with both biosynthetic constructs as well as decellularized tissues have been used to explore engineering both airway and vascular systems of the lung. Lung is thus a ripe organ for a variety of cell therapy and regenerative medicine approaches. Current state-of-the-art progress for each of the above areas will be presented as will discussion of current considerations for cell therapy-based clinical trials in lung diseases. PMID:23959715

  8. Adherence to Disease Modifying Drugs among Patients with Multiple Sclerosis in Germany: A Retrospective Cohort Study.

    Directory of Open Access Journals (Sweden)

    Kerstin Hansen

    Full Text Available Long-term therapies such as disease modifying therapy for Multiple Sclerosis (MS demand high levels of medication adherence in order to reach acceptable outcomes. The objective of this study was to describe adherence to four disease modifying drugs (DMDs among statutorily insured patients within two years following treatment initiation. These drugs were interferon beta-1a i.m. (Avonex, interferon beta-1a s.c. (Rebif, interferon beta-1b s.c. (Betaferon and glatiramer acetate s.c. (Copaxone.This retrospective cohort study used pharmacy claims data from the data warehouse of the German Institute for Drug Use Evaluation (DAPI from 2001 through 2009. New or renewed DMD prescriptions in the years 2002 to 2006 were identified and adherence was estimated during 730 days of follow-up by analyzing the medication possession ratio (MPR as proxy for compliance and persistence defined as number of days from initiation of DMD therapy until discontinuation or interruption.A total of 52,516 medication profiles or therapy cycles (11,891 Avonex, 14,060 Betaferon, 12,353 Copaxone and 14,212 Rebif from 50,057 patients were included into the analysis. Among the 4 cohorts, no clinically relevant differences were found in available covariates. The Medication Possession Ratio (MPR measured overall compliance, which was 39.9% with a threshold MPR≥0.8. There were small differences in the proportion of therapy cycles during which a patient was compliant for the following medications: Avonex (42.8%, Betaferon (40.6%, Rebif (39.2%, and Copaxone (37%. Overall persistence was 32.3% at the end of the 24 months observation period, i.e. during only one third of all included therapy cycles patients did not discontinue or interrupt DMD therapy. There were also small differences in the proportion of therapy cycles during which a patient was persistent as follows: Avonex (34.2%, Betaferon (33.4%, Rebif (31.7% and Copaxone (29.8%.Two years after initiating MS-modifying therapy, only

  9. Validation of Modified Estimated Glomerular Filtration Rate in Chronic Kidney Disease Patients

    International Nuclear Information System (INIS)

    Objective: To derive the ethnic factor and validate the modified estimated Glomerular Filtration Rate (eGFR) by Modification of Diet in Renal Disease (MDRD) equation for Chronic Kidney Disease (CKD) patients of Rawalpindi. Study Design: Cross- sectional study. Place and Duration of Study: Armed Forces Institute of Pathology (AFIP), Rawalpindi, from July 2011 to July 2012. Methodology: A total of 140 patients with CKD reporting to AFIP for GFR measurement by 99mTechnetium diethylenethiaminepenta-acetic acid (99mTc-DTPA) renal scan were consecutively inducted. Serum creatinine was measured by the Jaffe's assay on Beckman DxC 600 Analyzer prior to the renal scan. Ethnic factor for population of Rawalpindi with CKD was derived for the MDRD eGFR equation using 99mTc-DTPA renal scan by Gates method as the reference method. MDRD equation was modified by inclusion of the ethnic factor in it. Agreement between the reference GFR (rGFR) and the modified MDRD eGFR (mGFR) was assessed by applying paired samples t-test. Results: Out of 140 patients of CKD, 99 (71%) were males and 41 (29%) females, with mean age of 55 A+- 13.42 years. The mean values were 32.91 A+- 14.96, 34.89 A+- 16.45, 0.971 A+- 0.20 and 33.87 A+- 15.97 for rGFR, original eGFR, ethnic factor and mGFR respectively. The mGFR with new ethnic factor of 0.971 showed improved performance as compared to original eGFR and showed a significant level of correlation with rGFR (r2 = 0.817), at a p-value of 0.000. Conclusion: This study validates the mGFR equation by inclusion of newly derived ethnic factor of 0.971 in the population of Rawalpindi with CKD and it was found to be not significantly different from the rGFR. (author)

  10. The chemical synthesis of α-conotoxins and structurally modified analogs with enhanced biological stability.

    Science.gov (United States)

    Banerjee, Jayati; Gyanda, Reena; Chang, Yi-Pin; Armishaw, Christopher J

    2013-01-01

    α-Conotoxins are peptide neurotoxins isolated from the venom ducts of carnivorous marine cone snails that exhibit exquisite pharmacological potency and selectivity for various nicotinic acetylcholine receptor subtypes. As such, they are important research tools and drug leads for treating various diseases of the central nervous system, including pain and tobacco addiction. Despite their therapeutic potential, the chemical synthesis of α-conotoxins for use in structure-activity relationship studies is complicated by the possibility of three disulfide bond isomers, where inefficient folding methods can lead to a poor recovery of the pharmacologically active isomer. In order to achieve higher yields of the native isomer, especially in high-throughput syntheses it is necessary to select appropriate oxidative folding conditions. Moreover, the poor biochemical stability exhibited by α-conotoxins limits their general therapeutic applicability in vivo. Numerous strategies to enhance their stability including the substitution of disulfide bond with diselenide bond and N-to-C cyclization via an oligopeptide spacer have successfully overcome these limitations. This chapter describes methods for performing both selective and nonselective disulfide bond oxidation strategies for controlling the yields and formation of α-conotoxin disulfide bond isomers, as well as methods for the production of highly stable diselenide-containing and N-to-C cyclized conotoxin analogs. PMID:24014431

  11. Constraints on Biological Mechanism from Disease Comorbidity Using Electronic Medical Records and Database of Genetic Variants

    Science.gov (United States)

    Bagley, Steven C.; Sirota, Marina; Chen, Richard; Butte, Atul J.; Altman, Russ B.

    2016-01-01

    Patterns of disease co-occurrence that deviate from statistical independence may represent important constraints on biological mechanism, which sometimes can be explained by shared genetics. In this work we study the relationship between disease co-occurrence and commonly shared genetic architecture of disease. Records of pairs of diseases were combined from two different electronic medical systems (Columbia, Stanford), and compared to a large database of published disease-associated genetic variants (VARIMED); data on 35 disorders were available across all three sources, which include medical records for over 1.2 million patients and variants from over 17,000 publications. Based on the sources in which they appeared, disease pairs were categorized as having predominant clinical, genetic, or both kinds of manifestations. Confounding effects of age on disease incidence were controlled for by only comparing diseases when they fall in the same cluster of similarly shaped incidence patterns. We find that disease pairs that are overrepresented in both electronic medical record systems and in VARIMED come from two main disease classes, autoimmune and neuropsychiatric. We furthermore identify specific genes that are shared within these disease groups. PMID:27115429

  12. Constraints on Biological Mechanism from Disease Comorbidity Using Electronic Medical Records and Database of Genetic Variants.

    Directory of Open Access Journals (Sweden)

    Steven C Bagley

    2016-04-01

    Full Text Available Patterns of disease co-occurrence that deviate from statistical independence may represent important constraints on biological mechanism, which sometimes can be explained by shared genetics. In this work we study the relationship between disease co-occurrence and commonly shared genetic architecture of disease. Records of pairs of diseases were combined from two different electronic medical systems (Columbia, Stanford, and compared to a large database of published disease-associated genetic variants (VARIMED; data on 35 disorders were available across all three sources, which include medical records for over 1.2 million patients and variants from over 17,000 publications. Based on the sources in which they appeared, disease pairs were categorized as having predominant clinical, genetic, or both kinds of manifestations. Confounding effects of age on disease incidence were controlled for by only comparing diseases when they fall in the same cluster of similarly shaped incidence patterns. We find that disease pairs that are overrepresented in both electronic medical record systems and in VARIMED come from two main disease classes, autoimmune and neuropsychiatric. We furthermore identify specific genes that are shared within these disease groups.

  13. Historical perspective on biological control of postharvest diseases – past, present, and future

    Science.gov (United States)

    The birth of the field of biological control of postharvest diseases can be traced back to 1984 when a researcher testing an antagonist (Bacillus subtilis) in the field to control brown rot of peaches (caused by Monilinia fructicola ) decided to apply the antagonist directly to the peach to control ...

  14. Compost and Biological Amendment Effects on Soilborne Disease and Soil Microbial Communities

    Science.gov (United States)

    Effects of compost and biological amendments on soilborne diseases and microorganisms were assessed in field trials in northern Maine under both conventional and organic potato production practices. Three different biocontrol amendments, hypovirulent Rhizoctonia solani Rhs 1A1 (HvRs), Bacillus subti...

  15. Biologics for rheumatoid arthritis: an overview of Cochrane reviews

    DEFF Research Database (Denmark)

    Singh, Jasvinder A; Christensen, Robin; Wells, George A;

    2010-01-01

    the biologic disease-modifying anti-rheumatic drugs (DMARDs) are very effective in treating rheumatoid arthritis (RA), however there is a lack of head-to-head comparison studies.......the biologic disease-modifying anti-rheumatic drugs (DMARDs) are very effective in treating rheumatoid arthritis (RA), however there is a lack of head-to-head comparison studies....

  16. Systems biology elucidates common pathogenic mechanisms between nonalcoholic and alcoholic-fatty liver disease.

    Directory of Open Access Journals (Sweden)

    Silvia Sookoian

    Full Text Available The abnormal accumulation of fat in the liver is often related either to metabolic risk factors associated with metabolic syndrome in the absence of alcohol consumption (nonalcoholic fatty liver disease, NAFLD or to chronic alcohol consumption (alcoholic fatty liver disease, AFLD. Clinical and histological studies suggest that NAFLD and AFLD share pathogenic mechanisms. Nevertheless, current data are still inconclusive as to whether the underlying biological process and disease pathways of NAFLD and AFLD are alike. Our primary aim was to integrate omics and physiological data to answer the question of whether NAFLD and AFLD share molecular processes that lead to disease development. We also explored the extent to which insulin resistance (IR is a distinctive feature of NAFLD. To answer these questions, we used systems biology approaches, such as gene enrichment analysis, protein-protein interaction networks, and gene prioritization, based on multi-level data extracted by computational data mining. We observed that the leading disease pathways associated with NAFLD did not significantly differ from those of AFLD. However, systems biology revealed the importance of each molecular process behind each of the two diseases, and dissected distinctive molecular NAFLD and AFLD-signatures. Comparative co-analysis of NAFLD and AFLD clarified the participation of NAFLD, but not AFLD, in cardiovascular disease, and showed that insulin signaling is impaired in fatty liver regardless of the noxa, but the putative regulatory mechanisms associated with NAFLD seem to encompass a complex network of genes and proteins, plausible of epigenetic modifications. Gene prioritization showed a cancer-related functional map that suggests that the fatty transformation of the liver tissue is regardless of the cause, an emerging mechanism of ubiquitous oncogenic activation. In conclusion, similar underlying disease mechanisms lead to NAFLD and AFLD, but specific ones depict a

  17. Plague in Egypt: Disease biology, history and contemporary analysis: A minireview

    OpenAIRE

    Lotfy, Wael M.

    2013-01-01

    Plague is a zoonotic disease with a high mortality rate in humans. Unfortunately, it is still endemic in some parts of the world. Also, natural foci of the disease are still found in some countries. Thus, there may be a risk of global plague re-emergence. This work reviews plague biology, history of major outbreaks, and threats of disease re-emergence in Egypt. Based on the suspected presence of potential natural foci in the country, the global climate change, and the threat posed by some nei...

  18. Biological agents: investigation into leprosy and other infectious diseases before indication.

    Science.gov (United States)

    Antônio, João Roberto; Soubhia, Rosa Maria Cordeiro; Paschoal, Vania Del Arco; Amarante, Carolina Forte; Travolo, Ana Regina Franchi

    2013-01-01

    Biological agents are widely used for various immune-mediated diseases, with remarkable effectiveness in the treatment of rheumatoid arthritis (RA), psoriasis, psoriatic arthritis, ankylosing spondylitis and Crohn's disease. However, attention needs to be drawn to the adverse effects of these therapies and the risk of reactivating underlying granulomatous infectious diseases such as tuberculosis, leprosy, syphilis, leishmaniasis, among others. The objective of this paper is to describe a case of leprosy in a patient with RA using anti-TNF alfa, demonstrating the need for systematic investigation of skin lesions suggestive of leprosy in patients who require rheumatoid arthritis therapeutic treatment, especially in endemic regions like Brazil. PMID:24346871

  19. Cigarette use and cardiovascular risk in chronic kidney disease: an unappreciated modifiable lifestyle risk factor.

    LENUS (Irish Health Repository)

    Stack, Austin G

    2012-01-31

    Tobacco use is a major modifiable cardiovascular risk factor in the general population and contributes to excess cardiovascular risk. Emerging evidence from large-scale observational studies suggests that continued tobacco use is also an independent cardiovascular risk factor among patients with chronic kidney disease (CKD). The benefits of smoking cessation programs on improving the heath status of patients and reducing mortality are unequivocal in the general population. Despite this, there has been little effort in pursuing tobacco cessation programs in dialysis cohorts or those with lesser degrees of kidney impairment. Most of our attention to date has focused on the development of "kidney-specific" interventions that reduce rates of renal disease progression and improve dialysis outcomes. The purpose of this current review is to describe the epidemiology of tobacco use among patients with CKD, draw attention to its negative impact on cardiovascular morbidity and mortality, and finally highlight potential strategies for successful intervention. We hope that this study heightens the importance of tobacco use in CKD, stimulates renewed interest in the barriers and challenges that exist in achieving smoking cessation, and endorses the efficacy of intervention strategies and the immeasurable benefits of quitting on cardiovascular and noncardiovascular outcomes.

  20. Curcumin: A multi-target disease-modifying agent for late-stage transthyretin amyloidosis.

    Science.gov (United States)

    Ferreira, Nelson; Gonçalves, Nádia P; Saraiva, Maria J; Almeida, Maria R

    2016-01-01

    Transthyretin amyloidoses encompass a variety of acquired and hereditary diseases triggered by systemic extracellular accumulation of toxic transthyretin aggregates and fibrils, particularly in the peripheral nervous system. Since transthyretin amyloidoses are typically complex progressive disorders, therapeutic approaches aiming multiple molecular targets simultaneously, might improve therapy efficacy and treatment outcome. In this study, we evaluate the protective effect of physiologically achievable doses of curcumin on the cytotoxicity induced by transthyretin oligomers in vitro by showing reduction of caspase-3 activity and the levels of endoplasmic reticulum-resident chaperone binding immunoglobulin protein. When given to an aged Familial Amyloidotic Polyneuropathy mouse model, curcumin not only reduced transthyretin aggregates deposition and toxicity in both gastrointestinal tract and dorsal root ganglia but also remodeled congophilic amyloid material in tissues. In addition, curcumin enhanced internalization, intracellular transport and degradation of transthyretin oligomers by primary macrophages from aged Familial Amyloidotic Polyneuropathy transgenic mice, suggesting an impaired activation of naïve phagocytic cells exposed to transthyretin toxic intermediate species. Overall, our results clearly support curcumin or optimized derivatives as promising multi-target disease-modifying agent for late-stage transthyretin amyloidosis. PMID:27197872

  1. Synergizing Engineering and Biology to Treat and Model Skeletal Muscle Injury and Disease

    Science.gov (United States)

    Bursac, Nenad; Juhas, Mark; Rando, Thomas A.

    2016-01-01

    Although skeletal muscle is one of the most regenerative organs in our body, various genetic defects, alterations in extrinsic signaling, or substantial tissue damage can impair muscle function and the capacity for self-repair. The diversity and complexity of muscle disorders have attracted much interest from both cell biologists and, more recently, bioengineers, leading to concentrated efforts to better understand muscle pathology and develop more efficient therapies. This review describes the biological underpinnings of muscle development, repair, and disease, and discusses recent bioengineering efforts to design and control myomimetic environments, both to study muscle biology and function and to aid in the development of new drug, cell, and gene therapies for muscle disorders. The synergy between engineering-aided biological discovery and biology-inspired engineering solutions will be the path forward for translating laboratory results into clinical practice. PMID:26643021

  2. Treatment adherence to disease-modifying antirheumatic drugs in Chinese patients with rheumatoid arthritis

    Directory of Open Access Journals (Sweden)

    Xia Y

    2016-05-01

    Full Text Available Yunfei Xia,1,* Rulan Yin,1,2,* Ting Fu,1,2 Lijuan Zhang,1,2 Qiuxiang Zhang,1,2 Genkai Guo,1 Liren Li,2 Zhifeng Gu11Department of Rheumatology, Affiliated Hospital of Nantong University, 2School of Nursing, Nantong University, Nantong, People’s Republic of China *These authors contributed equally to this work Objective: Nonadherence in rheumatoid arthritis (RA patients using disease-modifying antirheumatic drugs (DMARDs may lead to joint damage and function loss. The aim of this cross-sectional study was to explore Chinese RA patients’ adherence rates and investigate potential risk factors for nonadherence.Methods: A total of 122 RA patients were recruited from the Affiliated Hospital of Nantong University from January 2014 to April 2015. Patients were asked to complete a set of standardized self-report questionnaires (Compliance Questionnaire on Rheumatology, Health Assessment Questionnaire, Short Form-36 questionnaire, 28-joint Disease Activity Score, Hospital Anxiety and Depression Scale, and Visual Analog Scale. Independent samples t-tests, chi-square analyses, and logistic regression modeling were used to analyze these data.Results: Based on Compliance Questionnaire on Rheumatology, 38% of the patients adhered to DMARDs. Adherence was associated with education, income, depression, and the total number of DMARDs. Other demographic and clinical characteristics were not associated with adherence. Logistic regression models identified income, depression, and the total number of DMARDs as predictors of medication nonadherence.Conclusion: In this study, 62% of patients with RA were not adherent to their DMARD prescription. Education, income, depression, and the total number of DMARDs were associated with medication adherence, and income, depression, and the total number of DMARDs were independent predictors of medication adherence in patients with RA. These findings could help medical personnel develop helpful interventions to improve

  3. Possibility of biological control of primocane fruiting raspberry disease caused by Fusarium sambucinum.

    Science.gov (United States)

    Shternshis, Margarita V; Belyaev, Anatoly A; Matchenko, Nina S; Shpatova, Tatyana V; Lelyak, Anastasya A

    2015-10-01

    Biological control agents are a promising alternative to chemical pesticides for plant disease suppression. The main advantage of the natural biocontrol agents, such as antagonistic bacteria compared with chemicals, includes environmental pollution prevention and a decrease of chemical residues in fruits. This study is aimed to evaluate the impact of three Bacillus strains on disease of primocane fruiting raspberry canes caused by Fusarium sambucinum under controlled infection load and uncontrolled environmental factors. Bacillus subtilis, Bacillus licheniformis, and Bacillus amyloliquefaciens were used for biocontrol of plant disease in 2013 and 2014 which differed by environmental conditions. The test suspensions were 10(5) CFU/ml for each bacterial strain. To estimate the effect of biological agents on Fusarium disease, canes were cut at the end of vegetation, and the area of outer and internal lesions was measured. In addition to antagonistic effect, the strains revealed the ability to induce plant resistance comparable with chitosan-based formulation. Under variable ways of cane treatment by bacterial strains, the more effective were B. subtilis and B. licheniformis demonstrating dual biocontrol effect. However, environmental factors were shown to impact the strain biocontrol ability; changes in air temperature and humidity led to the enhanced activity of B. amyloliquefaciens. For the first time, the possibility of replacing chemicals with environmentally benign biological agents for ecologically safe control of the raspberry primocane fruiting disease was shown. PMID:26018288

  4. Advances in systems biology are enhancing our understanding of disease and moving us closer to novel disease treatments.

    Science.gov (United States)

    Schadt, Eric E; Zhang, Bin; Zhu, Jun

    2009-06-01

    With tens of billions of dollars spent each year on the development of drugs to treat human diseases, and with fewer and fewer applications for investigational new drugs filed each year despite this massive spending, questions now abound on what changes to the drug discovery paradigm can be made to achieve greater success. The high rate of failure of drug candidates in clinical development, where the great majority of these drugs fail due to lack of efficacy, speak directly to the need for more innovative approaches to study the mechanisms of disease and drug discovery. Here we review systems biology approaches that have been devised over the last several years to understand the biology of disease at a more holistic level. By integrating a diversity of data like DNA variation, gene expression, protein-protein interaction, DNA-protein binding, and other types of molecular phenotype data, more comprehensive networks of genes both within and between tissues can be constructed to paint a more complete picture of the molecular processes underlying physiological states associated with disease. These more integrative, systems-level methods lead to networks that are demonstrably predictive, which in turn provides a deeper context within which single genes operate such as those identified from genome-wide association studies or those targeted for therapeutic intervention. The more comprehensive views of disease that result from these methods have the potential to dramatically enhance the way in which novel drug targets are identified and developed, ultimately increasing the probability of success for taking new drugs through clinical development. We highlight a number of the integrative approaches via examples that have resulted not only in the identification of novel genes for diabetes and cardiovascular disease, but in more comprehensive networks as well that describe the context in which the disease genes operate. PMID:19363597

  5. The Role of Ischemia Modified Albumin as a Biomarker in Patients with Chronic Liver Disease

    Science.gov (United States)

    Subramanian, Kavitha

    2016-01-01

    Introduction Chronic Liver Disease (CLD) is characterised by gradual destruction of liver tissue over time. Ischemia Modified Albumin (IMA) is an upcoming biomarker shown to be elevated in conditions associated with ischemia and oxidative stress. Albumin levels are greatly reduced in patients with CLD and studying its alterations will provide essential information regarding the molecular changes occurring to it. Aim The study aims to estimate IMA and IMA/Albumin ratio in patients with CLD and to correlate it with parameters assessing liver function and the Model for End Stage Liver Disease (MELD) score. Materials and Methods The study consisted of 43 CLD patients as test subjects and 28 apparently healthy individuals as controls. Multiple parameters assessing liver function like albumin, bilirubin, aspartate transaminase (AST), alanine transaminase (ALT), Gamma Glutamyl Transpeptidase (GGT), alkaline phosphatase (ALP), Prothrombin Time (PT) INR and creatinine were estimated and the MELD score calculated. Serum IMA expressed as Absorbance Units (ABSU) was estimated using the Albumin Cobalt Binding test (ABT). Student’s t-test and correlation coefficient was used for statistical analysis. Results Serum IMA was significantly higher in CLD patients (0.5320 ± 0.1677) as compared to the control group (0.3203 ± 0.1257) with a p-value of <0.0001. The IMA/Albumin ratio was also significantly higher (0.2035 ± 0.0970) in patients with CLD compared to control group (0.0714 ± 0.0283) with a p-value of <0.0001. IMA has a negative correlation with albumin. The IMA/Albumin ratio shows positive correlation with MELD score, bilirubin and ALP. There was no correlation with ALT, AST, GGT and PT INR. Conclusion Decreased serum albumin correlates with increase in IMA in CLD could indicate a qualitative change and not merely a quantitative reduction of albumin. IMA can serve as a biomarker to assess the disease severity and prognosis of CLD patients.

  6. Design, synthesis and biological activity of new polyenolic inhibitors of matrix metalloproteinases: a focus on chemically-modified curcumins.

    Science.gov (United States)

    Zhang, Yu; Gu, Ying; Lee, Hsi-Ming; Hambardjieva, Elena; Vranková, Kveta; Golub, Lorne M; Johnson, Francis

    2012-01-01

    Matrix metalloproteinases (MMPs) are essential for the degradation and turnover of components of the extracellular matrix (ECM) and, when pathologically elevated, mediate connective tissue loss (including bone destruction) in various inflammatory and other diseases. Tetracyclines (TCs) are known inhibitors of mammalian-derived MMPs, and non-antibiotic formulations of Doxycycline are FDA-approved to treat periodontitis and the chronic inflammatory skin disease, rosacea. Because the C-11/ C-12 diketonic moiety of the tetracyclines is primarily responsible, through zinc-binding, for MMP inhibition, we have uniquely modified curcumin as a "core" molecule, since it contains a similar enolic system and is known to have beneficial effects in diseases where connective-tissue loss occurs. Specifically we have developed new congeners which exhibit improved zinc-binding and solubility, and potent reduction of excessive MMP levels and activity. We now describe a series of curcuminoid bi- and tri-carbonylmethanes in which all of these properties are substantially improved. An N-phenylaminocarbonyl derivative of bis-demethoxycurcumin (CMC2.24) was selected as the "lead" substance because it showed superior potency in vitro (i.e., the lowest IC(50)) against a series of neutral proteases (MMPs) associated with tissue erosion. Moreover, CMC2.24 administered to diabetic rats orally (30mg/kg), reduced the secretion of pathologically-excessive levels of MMP-9 to normal in cultured peritoneal macrophages with no evidence of toxicity. Thus, this (and other similar novel) compound(s) may be useful in various diseases of connective-tissue loss. PMID:22830350

  7. Relationship between Periodontal Diseases and Preterm Birth: Recent Epidemiological and Biological Data

    Directory of Open Access Journals (Sweden)

    O. Huck

    2011-01-01

    Full Text Available For ten years, the incidence of preterm birth does not decrease in developed countries despite the promotion of public health programs. Many risk factors have been identified including ethnicity, age, tobacco, and infection. However, almost 50% of preterm birth causes remain unknown. The periodontal diseases are highly prevalent inflammatory and infectious diseases of tooth supporting tissues leading to an oral disability. They influence negatively general health worsening cardiovascular diseases and diabetes. Periodontal diseases have been also suspected to increase the rate of preterm birth, but data remain contradictory. The objective of this review is to present the principal results of epidemiological, biological, and interventional studies on the link between periodontal diseases and preterm birth. The conclusions of this work underline the importance for the physician/obstetrician to identify women at risk for preterm birth and to address these patients to dentist for periodontal examination and treatment in order to limit adverse pregnancy outcomes.

  8. Use of a modified alpha-N-acetylgalactosaminidase in the development of enzyme replacement therapy for Fabry disease.

    Science.gov (United States)

    Tajima, Youichi; Kawashima, Ikuo; Tsukimura, Takahiro; Sugawara, Kanako; Kuroda, Mayuko; Suzuki, Toshihiro; Togawa, Tadayasu; Chiba, Yasunori; Jigami, Yoshifumi; Ohno, Kazuki; Fukushige, Tomoko; Kanekura, Takuro; Itoh, Kohji; Ohashi, Toya; Sakuraba, Hitoshi

    2009-11-01

    A modified alpha-N-acetylgalactosaminidase (NAGA) with alpha-galactosidase A (GLA)-like substrate specificity was designed on the basis of structural studies and was produced in Chinese hamster ovary cells. The enzyme acquired the ability to catalyze the degradation of 4-methylumbelliferyl-alpha-D-galactopyranoside. It retained the original NAGA's stability in plasma and N-glycans containing many mannose 6-phosphate (M6P) residues, which are advantageous for uptake by cells via M6P receptors. There was no immunological cross-reactivity between the modified NAGA and GLA, and the modified NAGA did not react to serum from a patient with Fabry disease recurrently treated with a recombinant GLA. The enzyme cleaved globotriaosylceramide (Gb3) accumulated in cultured fibroblasts from a patient with Fabry disease. Furthermore, like recombinant GLA proteins presently used for enzyme replacement therapy (ERT) for Fabry disease, the enzyme intravenously injected into Fabry model mice prevented Gb3 storage in the liver, kidneys, and heart and improved the pathological changes in these organs. Because this modified NAGA is hardly expected to cause an allergic reaction in Fabry disease patients, it is highly promising as a new and safe enzyme for ERT for Fabry disease. PMID:19853240

  9. Genetically modifying the insect gut microbiota to control Chagas disease vectors through systemic RNAi.

    Directory of Open Access Journals (Sweden)

    Mabel L Taracena

    2015-02-01

    Full Text Available Technologies based on RNA interference may be used for insect control. Sustainable strategies are needed to control vectors of Chagas disease such as Rhodnius prolixus. The insect microbiota can be modified to deliver molecules to the gut. Here, Escherichia coli HT115(DE3 expressing dsRNA for the Rhodnius heme-binding protein (RHBP and for catalase (CAT were fed to nymphs and adult triatomine stages. RHBP is an egg protein and CAT is an antioxidant enzyme expressed in all tissues by all developmental stages. The RNA interference effect was systemic and temporal. Concentrations of E. coli HT115(DE3 above 3.35 × 10(7 CFU/mL produced a significant RHBP and CAT gene knockdown in nymphs and adults. RHBP expression in the fat body was reduced by 99% three days after feeding, returning to normal levels 10 days after feeding. CAT expression was reduced by 99% and 96% in the ovary and the posterior midgut, respectively, five days after ingestion. Mortality rates increased by 24-30% in first instars fed RHBP and CAT bacteria. Molting rates were reduced by 100% in first instars and 80% in third instars fed bacteria producing RHBP or CAT dsRNA. Oviposition was reduced by 43% (RHBP and 84% (CAT. Embryogenesis was arrested in 16% (RHBP and 20% (CAT of laid eggs. Feeding females 105 CFU/mL of the natural symbiont, Rhodococcus rhodnii, transformed to express RHBP-specific hairpin RNA reduced RHBP expression by 89% and reduced oviposition. Modifying the insect microbiota to induce systemic RNAi in R. prolixus may result in a paratransgenic strategy for sustainable vector control.

  10. Mechanical and biological complication rates of the modified lateral-screw-retained implant prosthesis in the posterior region: an alternative to the conventional Implant prosthetic system

    Science.gov (United States)

    2016-01-01

    PURPOSE The modified lateral-screw-retained implant prosthesis (LSP) is designed to combine the advantages of screw- and cement-retained implant prostheses. This retrospective study evaluated the mechanical and biological complication rates of implant-supported single crowns (ISSCs) inserted with the modified LSP in the posterior region, and determined how these complication rates are affected by clinical factors. MATERIALS AND METHODS Mechanical complications (i.e., lateral screw loosening [LSL], abutment screw loosening, lateral screw fracture, and ceramic fracture) and biological complications (i.e., peri-implant mucositis [PM] and peri-implantitis) were identified from the patients' treatment records, clinical photographs, periapical radiographs, panoramic radiographs, and clinical indices. The correlations between complication rates and the following clinical factors were determined: gender, age, position in the jaw, placement location, functional duration, clinical crown-to-implant length ratio, crown height space, and the use of a submerged or nonsubmerged placement procedure. RESULTS Mechanical and biological complications were present in 25 of 73 ISSCs with the modified LSP. LSL (n=11) and PM (n=11) were the most common complications. The incidence of mechanical complications was significantly related to gender (P=.018). The other clinical factors were not significantly associated with mechanical and biological complication rates. CONCLUSION Within the limitations of this study, the incidence of mechanical and biological complications in the posterior region was similar for both modified LSP and conventional implant prosthetic systems. In addition, the modified LSP is amenable to maintenance care, which facilitates the prevention and treatment of mechanical and biological complications. PMID:27141260

  11. Polymorphism of the dopamine transporter type 1 gene modifies the treatment response in Parkinson's disease.

    Science.gov (United States)

    Moreau, Caroline; Meguig, Sayah; Corvol, Jean-Christophe; Labreuche, Julien; Vasseur, Francis; Duhamel, Alain; Delval, Arnaud; Bardyn, Thomas; Devedjian, Jean-Christophe; Rouaix, Nathalie; Petyt, Gregory; Brefel-Courbon, Christine; Ory-Magne, Fabienne; Guehl, Dominique; Eusebio, Alexandre; Fraix, Valérie; Saulnier, Pierre-Jean; Lagha-Boukbiza, Ouhaid; Durif, Frank; Faighel, Mirela; Giordana, Caroline; Drapier, Sophie; Maltête, David; Tranchant, Christine; Houeto, Jean-Luc; Debû, Bettina; Azulay, Jean-Philippe; Tison, François; Destée, Alain; Vidailhet, Marie; Rascol, Olivier; Dujardin, Kathy; Defebvre, Luc; Bordet, Régis; Sablonnière, Bernard; Devos, David

    2015-05-01

    variants were significantly associated with greater efficacy of l-DOPA for motor symptoms. The SLC6A3 variants were also associated with greater efficacy of methylphenidate for motor symptoms and gait disorders in the ON l-DOPA condition. The difference between motor Unified Parkinson's Disease Rating Scale scores for patients with different SLC6A3 genotypes was statistically significant in a multivariate analysis that took account of other disease-related, treatment-related and pharmacogenetic parameters. Our preliminary results suggest that variants of SLC6A3 are genetic modifiers of the treatment response to l-DOPA and methylphenidate in Parkinson's disease. Further studies are required to assess the possible value of these genotypes for (i) guiding l-DOPA dose adaptations over the long term; and (ii) establishing the risk/benefit balance associated with methylphenidate treatment for gait disorders. PMID:25805645

  12. Age-at-Onset in Late Onset Alzheimer Disease is Modified by Multiple Genetic Loci

    Science.gov (United States)

    Naj, Adam C.; Jun, Gyungah; Reitz, Christiane; Kunkle, Brian W.; Perry, William; Park, YoSon; Beecham, Gary W.; Rajbhandary, Ruchita A.; Hamilton-Nelson, Kara L.; Wang, Li-San; Kauwe, John S.K.; Huentelman, Matthew J.; Myers, Amanda J.; Bird, Thomas D.; Boeve, Bradley F.; Baldwin, Clinton T.; Jarvik, Gail P.; Crane, Paul K.; Rogaeva, Ekaterina; Barmada, Michael M.; Demirci, F. Yesim; Cruchaga, Carlos; Kramer, Patricia; Ertekin-Taner, Nilufer; Hardy, John; Graff-Radford, Neill R.; Green, Robert C.; Larson, Eric B.; St George-Hyslop, Peter; Buxbaum, Joseph D.; Evans, Denis; Schneider, Julie A.; Lunetta, Kathryn L.; Kamboh, M. Ilyas; Saykin, Andrew J.; Reiman, Eric M.; De Jager, Philip L.; Bennett, David A.; Morris, John C.; Montine, Thomas J.; Goate, Alison M.; Blacker, Deborah; Tsuang, Debby W.; Hakonarson, Hakon; Kukull, Walter A.; Foroud, Tatiana M.; Martin, Eden R.; Haines, Jonathan L.; Mayeux, Richard; Farrer, Lindsay A.; Schellenberg, Gerard D.; Pericak-Vance, Margaret A.

    2015-01-01

    Importance As APOE locus variants contribute to both risk of late-onset Alzheimer disease and differences in age-at-onset, it is important to know if other established late-onset Alzheimer disease risk loci also affect age-at-onset in cases. Objectives To investigate the effects of known Alzheimer disease risk loci in modifying age-at-onset, and to estimate their cumulative effect on age-at-onset variation, using data from genome-wide association studies in the Alzheimer’s Disease Genetics Consortium (ADGC). Design, Setting and Participants The ADGC comprises 14 case-control, prospective, and family-based datasets with data on 9,162 Caucasian participants with Alzheimer’s occurring after age 60 who also had complete age-at-onset information, gathered between 1989 and 2011 at multiple sites by participating studies. Data on genotyped or imputed single nucleotide polymorphisms (SNPs) most significantly associated with risk at ten confirmed LOAD loci were examined in linear modeling of AAO, and individual dataset results were combined using a random effects, inverse variance-weighted meta-analysis approach to determine if they contribute to variation in age-at-onset. Aggregate effects of all risk loci on AAO were examined in a burden analysis using genotype scores weighted by risk effect sizes. Main Outcomes and Measures Age at disease onset abstracted from medical records among participants with late-onset Alzheimer disease diagnosed per standard criteria. Results Analysis confirmed association of APOE with age-at-onset (rs6857, P=3.30×10−96), with associations in CR1 (rs6701713, P=7.17×10−4), BIN1 (rs7561528, P=4.78×10−4), and PICALM (rs561655, P=2.23×10−3) reaching statistical significance (P<0.005). Risk alleles individually reduced age-at-onset by 3-6 months. Burden analyses demonstrated that APOE contributes to 3.9% of variation in age-at-onset (R2=0.220) over baseline (R2=0.189) whereas the other nine loci together contribute to 1.1% of

  13. Is mental disease just brain disease? The limits to biological psychiatry.

    Science.gov (United States)

    McLaren, N

    1992-06-01

    As a process of rational enquiry into an empirical field, psychiatry must submit itself to the same discipline as other areas of science. Effectively, it must show that its fundamental premises are both internally and externally consistent, and that its methods of investigation satisfy prevailing criteria of scientific methodology. When psychoanalytic psychology (and hence all psychodynamic models) and behaviourism were analysed from these points of view, they were found wanting. To date, there has been little or no meta-analysis of the third great school of psychiatric theorizing, biological psychiatry. A preliminary analysis establishes sharp limits to the notion that biological psychiatry is the "wave of the future". Like psychoanalysis and behaviourism, it cannot form the basis of a general theory of psychiatry. Since it lacks an adequate theoretical framework, the inescapable conclusion is that psychiatry is nothing more than protoscience. PMID:1642619

  14. Carryover effect of postpartum inflammatory diseases on developmental biology and fertility in lactating dairy cows.

    Science.gov (United States)

    Ribeiro, E S; Gomes, G; Greco, L F; Cerri, R L A; Vieira-Neto, A; Monteiro, P L J; Lima, F S; Bisinotto, R S; Thatcher, W W; Santos, J E P

    2016-03-01

    The objective of this series of studies was to investigate the effects of inflammatory diseases occurring before breeding on the developmental biology and reproductive responses in dairy cows. Data from 5 studies were used to investigate different questions associating health status before breeding and reproductive responses. Health information for all studies was composed of the incidence of retained fetal membranes, metritis, mastitis, lameness, and respiratory and digestive problems from parturition until the day of breeding. Retained placenta and metritis were grouped as uterine disease (UTD). Mastitis, lameness, digestive and respiratory problems were grouped as nonuterine diseases (NUTD). Study 1 evaluated the effect of disease before artificial insemination (AI), anovulation before synchronization of the estrous cycle, and low body condition score at AI on pregnancy per AI, as well as their potential interactions or additive effects. Study 2 investigated the effect of site of inflammation (UTD vs. NUTD) and time of occurrence relative to preantral or antral stages of ovulatory follicle development, and the effect of UTD and NUTD on fertility responses of cows bred by AI or by embryo transfer. Study 3 evaluated the effect of disease on fertilization and embryonic development to the morula stage. Study 4 evaluated the effect of disease on preimplantation conceptus development as well as secretion of IFN-τ and transcriptome. Study 5 investigated the effect of diseases before AI on the transcript expression of interferon-stimulated genes in peripheral blood leukocytes during peri-implantation stages of conceptus development after first AI postpartum. Altogether, these studies demonstrated that inflammatory disease before breeding reduced fertilization of oocytes and development to morula, and impaired early conceptus development to elongation stages and secretion of IFN-τ in the uterine lumen. Diseases caused inflammation-like changes in transcriptome of

  15. Deciphering Diseases and Biological Targets for Environmental Chemicals using Toxicogenomics Networks

    DEFF Research Database (Denmark)

    Audouze, Karine Marie Laure; Juncker, Agnieszka; Roque, Francisco José Sousa Simões Almeida;

    2010-01-01

    Exposure to environmental chemicals and drugs may have a negative effect on human health. A better understanding of the molecular mechanism of such compounds is needed to determine the risk. We present a high confidence human protein-protein association network built upon the integration of...... chemical toxicology and systems biology. This computational systems chemical biology model reveals uncharacterized connections between compounds and diseases, thus predicting which compounds may be risk factors for human health. Additionally, the network can be used to identify unexpected potential...

  16. [What have biological drugs changed in inflammatory rheumatic, skin and bowel diseases?].

    Science.gov (United States)

    Hannonen, Pekka; Rantanen, Tapio; Jussila, Airi

    2016-01-01

    Biological drugs are the most rapidly growing group of medicinal agents. In addition to hormone and vaccine products, the significance of drugs produced using genetic engineering has increased in numerous indications, especially in oncology. Furthermore, they have significantly contributed to the treatment of inflammatory musculoskeletal as well as cutaneous and intestinal diseases. Their use is limited by parenteral administration, immunogenicity, uncertainty about possible severe adverse effects and especially the high price of the drugs. The cessation of patent protection of the original brand pharmaceuticals, and marketing of biosimilar drugs are expected to lower the prices of the original biological, as well. PMID:27017788

  17. SHOULD DISEASE-MODIFYING THERAPY BE STOPPED IN PATIENTS WITH RHEUMATOID ARTHRITIS BEFORE ENDOPROSTHETIC JOINT REPLACEMENT?

    Directory of Open Access Journals (Sweden)

    N. A. Savenkova

    2011-06-01

    Full Text Available Objective: to analyze disease activity, functional state, quality of life (QL, and the frequency of infectious complications in methotrexate (MT – or leflunomide (LF-treated patients with rheumatoid arthritis (RA who had undergone endoprosthetic replacement of the large joints of the lower limbs. Subjects and methods. One hundred and fourteen patients with RA who had undergone endoprosthetic replacement of the knee and hip joints were divided into 3 groups: 1 36 patients who continuously received MT or LF in the perioperative period; 2 42 patients who dis- continued MT or LF 2 and 4 weeks, respectively, prior to surgery; 3 36 patients who took no disease-modifying anti-rheumatic drugs (DMARDs within 12 months before surgery. Disease activity was estimated by the DAS28 index. QL was determined using the EQ-5D questionnaire and functional capacity was estimated by the HAQ index. Results and discussion. In all the groups, there was a preponderance of patients with moderate RA activity (more than 60%. In Groups 1 and 2, the mean dose of MT was about 10 mg weekly and that of LF was 20 mg daily. The use duration of glucocorticoids (GC and their doses were comparable in all the groups. Twelve months after surgery, DAS28 significantly reduced from 4.22±1.08 to 3.58±1.07 months in Group 1 (p = 0.01; in Group 2, the decrease was insignificant: from 4.17±1.17 to 3.80±1.15 (p > 005; in Group 3, RA activity remained as before. All the groups achieved 50% functional improvement; better results were obtained in the group of patients who continued to use DMARDs in the perioperative period (∆HAQ=-0.67. The difference in the Eq-5D index corresponded to a moderate QL improvement: ∆EQ-5D = 0.28, 0.29, and 0.31 in Groups 1, 2, and 3, respectively (p < 0.05. There were no significant group differences. Deep infection in the endoprosthetic replacement area was detected in 2.8, 2.4, and 8.3% of cases, respectively (p > 005. Conclusion. Continuous use of MT

  18. Patient perspectives on switching disease-modifying therapies in the NARCOMS registry

    Directory of Open Access Journals (Sweden)

    Salter AR

    2014-07-01

    Full Text Available Amber R Salter,1 Ruth Ann Marrie,2,3 Neetu Agashivala,4 Daniel A Belletti,4 Edward Kim,4 Gary R Cutter,1 Stacey S Cofield,1 Tuula Tyry51Department of Biostatistics, University of Alabama at Birmingham, Birmingham, AL, USA; 2Department of Internal Medicine, 3Department of Community Health Sciences, University of Manitoba, Winnipeg, MB, Canada; 4Novartis Pharmaceutical Corporation, East Hanover, NJ, USA; 5Division of Neurology, St. Joseph’s Hospital and Medical Center, Phoenix, AZ, USAIntroduction: The evolving landscape of disease-modifying therapies (DMTs for multiple sclerosis raises important questions about why patients change DMTs. Physicians and patients could benefit from a better understanding of the reasons for switching therapy. Purpose: To investigate the reasons patients switch DMTs and identify characteristics associated with the decision to switch.Method: The North American Research Committee on Multiple Sclerosis (NARCOMS Registry conducted a supplemental survey among registry participants responding to the 2011 update survey. The supplemental survey investigated reasons for switching DMT, origin of the discussion of DMT change, and which factors influenced the decision. Chi-square tests, Fisher’s exact tests, and logistic regression were used for the analyses. Results: Of the 691 eligible candidates, 308 responded and met the inclusion criteria (relapsing disease course, switched DMT after September 2010. The responders were 83.4% female, on average 52 years old, with a median (interquartile range Patient-Determined Disease Steps score of 4 (2–5. The most recent prior therapy included first-line injectables (74.5%, infusions (18.1%, an oral DMT (3.4%, and other DMTs (4.0%. The discussion to switch DMT was initiated almost equally by physicians and participants. The primary reason for choosing the new DMT was based most frequently on physician’s recommendation (24.5% and patient perception of efficacy (13.7%. Conclusion

  19. Diltiazem Treatment for Preclinical Hypertrophic Cardiomyopathy Mutation Carriers: A Pilot Randomized Trial to Modify Disease Expression

    Science.gov (United States)

    Ho, Carolyn Y.; Lakdawala, Neal K.; Cirino, Allison L.; Lipshultz, Steven E.; Sparks, Elizabeth; Abbasi, Siddique A.; Kwong, Raymond Y.; Antman, Elliott M.; Semsarian, Christopher; González, Arantxa; López, Begoña; Diez, Javier; Orav, E. John; Colan, Steven D.; Seidman, Christine E.

    2014-01-01

    Background Hypertrophic cardiomyopathy (HCM) is caused by sarcomere mutations and characterized by left ventricular hypertrophy (LVH) with increased risk of heart failure and sudden death. HCM typically cannot be diagnosed early in life, although subtle phenotypes are present. Animal studies indicate alterations in intracellular calcium handling before LVH develops. Furthermore, early treatment with diltiazem appeared to attenuate disease emergence. Objectives To assess the safety, feasibility, and effect of diltiazem as disease-modifying therapy for at-risk HCM mutation carriers. Methods In a pilot, double-blind trial, we randomly assigned 38 sarcomere mutation carriers without LVH (mean age 15.8 years) to therapy with diltiazem 360 mg/day (or 5 mg/kg/day) or placebo. Treatment duration ranged from 12 to 42 months (median 25 months). Study procedures included electrocardiography, echocardiography, cardiac magnetic resonance imaging, and serum biomarker measurement. Results Diltiazem was not associated with serious adverse events. Heart rate and blood pressure did not differ significantly between groups. However, mean left ventricular end diastolic diameter improved towards normal in the diltiazem group but decreased further in controls (change in z-scores, +0.6 vs. −0.5; P<0.001). Mean LV thickness-to-dimension ratio was stable in the diltiazem group, but increased in controls (−0.02 vs. +0.15; P=0.04). Among MYBPC3 mutation carriers, LV wall thickness and mass, diastolic filling, and cardiac troponin I levels improved in those taking diltiazem compared with controls. Four participants developed overt HCM, two in each treatment group. Conclusions Preclinical administration of diltiazem is safe and may improve early LV remodeling in HCM. This novel strategy merits further exploration. PMID:25543971

  20. Wear and biological effects of a semi-constrained total disc replacement subject to modified ISO standard test conditions.

    Science.gov (United States)

    Hyde, P J; Tipper, J; Fisher, J; Hall, R M

    2015-04-01

    Development of pre-clinical testing methodologies is an important goal for improving prediction of artificial replacement joint performance and for guiding future device design. Total disc replacement wear and the potential for osteolysis is a growing concern, therefore a parametric study on the effects on wear of altered kinematics and loading was undertaken. A standard ISO testing protocol was modified in order to study the wear behaviour of lumbar total disc replacements when subject to low cross shear input kinematics, reduced axial loading and smaller flexion-extension magnitude. Volumetric wear, bearing surface topography, and wear debris biological reactivity were assessed. The ISO standard results were expected, however, the very low cross shear test produced a level of wear approximately two orders of magnitude higher than that reported for zero cross shear motions on UHMWPE bearings. When the osteolytic potential of the wear particles was calculated, all total disc replacement simulations had lower predicted osteolytic potential compared to total hip replacements, as a consequence of the generally lower wear rates found. PMID:25598071

  1. Update on the role of modified release mesalamine in the management of ulcerative colitis and Crohn’s disease

    Directory of Open Access Journals (Sweden)

    Glen A Doherty

    2009-12-01

    Full Text Available Glen A Doherty, Mark A PeppercornCenter for Inflammatory Bowel Disease, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston MA, USAAbstract: 5-aminosalicyclates (5-ASA remain a key first-line therapy for patients with ulcerative colitis (UC. A range of 5-ASA preparations is available and Eudragit-S® coated modified release formulations of mesalamine, such as Asacol®, remain among the most popular choices. We here review the current understanding of the mechanism of action of 5-ASA in inflammatory bowel disease. We evaluate evidence supporting the efficacy and safety of modified release mesalamine for both induction and remission maintenance in UC, including a review of the data from the recent ASCEND studies. We also examine the controversial issue of the role of mesalamine in treatment of Crohn’s disease (CD and highlight data supporting its use following surgically induced remission of CD. Evidence supporting the use of mesalamine as prophylaxis for colorectal cancer and dysplasia will be considered. Finally, recent developments in our understanding of how to use modified release mesalamine in a safe and cost-effective manner are evaluated, including discussion of the importance of studying patient non-adherence as a key component of future studies in this area.Keywords: mesalamine (mesalazine, 5-aminosalicyclate, ulcerative colitis, Crohn’s disease, modified release

  2. Selective biologics for ulcerative colitis and Crohn's disease – clinical utility of vedolizumab

    Directory of Open Access Journals (Sweden)

    Petkau JM

    2016-03-01

    Full Text Available Jill MV Petkau, Bertus Eksteen Snyder Institute for Chronic Diseases, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada Abstract: Inflammatory bowel disease (IBD encompasses a cluster of different disease phenotypes which are broadly classified into ulcerative colitis and Crohn's disease. Disease pathogenesis is driven by abnormal host immune responses to their resident gut microbiome in genetically susceptible individuals. Clinical disease features and outcomes are heterogenous and not unexpected as over 163 genetic loci are associated with disease susceptibility, and there are great variability in environmental exposures. Despite this variability, there has been relatively few efficacious therapies for particularly moderate-to-severe IBD. Treatment has been dominated by antitumor necrosis alpha agents with significant success but equally potentially serious adverse events. Therapeutic targeting of leucocyte trafficking has emerged as a viable alternative therapy, with vedolizumab being the lead compound. This review focuses primarily on its biological function as a selective gut immunotherapy, its safety and efficacy, and its emerging role as a mainstream therapy in managing IBD. Keywords: adhesion molecule antagonist, anti-α4β7 integrin, inflammatory bowel disease, leukocyte trafficking, monoclonal antibody, selective gut immunotherapy, tumor necrosis factor alpha

  3. Hospital Admissions, Biological Therapy, and Surgery in Familial and Sporadic Cases of Inflammatory Bowel Disease

    DEFF Research Database (Denmark)

    Trier Moller, Frederik; Andersen, Vibeke; Andersson, Mikael;

    2015-01-01

    -related hospitalization, biological treatment, and surgery in familial versus sporadic cases of IBD. RESULTS: A total of 27,886 IBD cases, including 1006 IBD-relative pairs, were followed-up for up to 16 years, totaling 164,979 person-years. We observed no difference in risk of hospital admissions between familial and......BACKGROUND: Easily accessible predictors of disease course in inflammatory bowel disease (IBD) are scarce, and it remains largely unknown whether a family history of IBD predicts the course of Crohn's disease (CD) and ulcerative colitis (UC). We aimed to compare the course of disease in familial...... and sporadic cases of IBD in a nationwide cohort study. METHODS: From national registries, covering a population of 8,295,773 individuals, we obtained information on date and year of diagnosis of IBD cases, gender, age, and family ties. Using Cox regression, we estimated hazard ratios for IBD...

  4. Optical force on diseased blood cells: Towards the optical sorting of biological matter

    KAUST Repository

    Gongora, Juan Sebastian Totero

    2015-05-01

    By employing a series of massively parallel ab-initio simulations, we study how optical forces act on biological matter subject to morphological disease. As a representative case study, we here consider the case of Plasmodium falciparum on red blood cells (RBC) illuminated by a monochromatic plane wave. Realistic parameters for the geometry and the refractive index are then taken from published experiments. In our theoretical campaign, we study the dependence of the optical force on the disease stage for different incident wavelengths. We show that optical forces change significantly with the disease, with amplitude variation in the hundreds of pN range. Our results open up new avenues for the design of new optical systems for the treatment of human disease. © 2015 Elsevier Ltd.

  5. Optical force on diseased blood cells: Towards the optical sorting of biological matter

    Science.gov (United States)

    Gongora, Juan Sebastian Totero; Fratalocchi, Andrea

    2016-01-01

    By employing a series of massively parallel ab-initio simulations, we study how optical forces act on biological matter subject to morphological disease. As a representative case study, we here consider the case of Plasmodium falciparum on red blood cells (RBC) illuminated by a monochromatic plane wave. Realistic parameters for the geometry and the refractive index are then taken from published experiments. In our theoretical campaign, we study the dependence of the optical force on the disease stage for different incident wavelengths. We show that optical forces change significantly with the disease, with amplitude variation in the hundreds of pN range. Our results open up new avenues for the design of new optical systems for the treatment of human disease.

  6. Diabetes and cardiovascular disease: Epidemiology, biological mechanisms, treatment recommendations and future research

    Institute of Scientific and Technical Information of China (English)

    Benjamin; M; Leon; Thomas; M; Maddox

    2015-01-01

    The incidence of diabetes mellitus(DM) continues to rise and has quickly become one of the most prevalent and costly chronic diseases worldwide. A close link exists between DM and cardiovascular disease(CVD), which is the most prevalent cause of morbidity and mortality in diabetic patients. Cardiovascular(CV) risk factors such as obesity, hypertension and dyslipidemia are common in patients with DM, placing them at increased risk for cardiac events. In addition, many studies have found biological mechanisms associated with DM that independently increase the risk of CVD in diabetic patients. Therefore, targeting CV risk factors in patients with DM is critical to minimize the long-term CV complications of the disease. This paper summarizes the relationship between diabetes and CVD, examines possible mechanisms of disease progression, discusses current treatment recommendations, and outlines future research directions.

  7. Diabetes and cardiovascular disease: Epidemiology, biological mechanisms, treatment recommendations and future research.

    Science.gov (United States)

    Leon, Benjamin M; Maddox, Thomas M

    2015-10-10

    The incidence of diabetes mellitus (DM) continues to rise and has quickly become one of the most prevalent and costly chronic diseases worldwide. A close link exists between DM and cardiovascular disease (CVD), which is the most prevalent cause of morbidity and mortality in diabetic patients. Cardiovascular (CV) risk factors such as obesity, hypertension and dyslipidemia are common in patients with DM, placing them at increased risk for cardiac events. In addition, many studies have found biological mechanisms associated with DM that independently increase the risk of CVD in diabetic patients. Therefore, targeting CV risk factors in patients with DM is critical to minimize the long-term CV complications of the disease. This paper summarizes the relationship between diabetes and CVD, examines possible mechanisms of disease progression, discusses current treatment recommendations, and outlines future research directions. PMID:26468341

  8. Optical force on diseased blood cells: towards the optical sorting of biological matter

    CERN Document Server

    Gongora, Juan Sebastian Totero

    2016-01-01

    By employing a series of massively parallel ab-initio simulations, we study how optical forces act on biological matter subject to morphological disease. As a representative case study, we here consider the case of Plasmodium Falciparum on red blood cells (RBC) illuminated by a monochromatic plane wave. Realistic parameters for the geometry and the refractive index are then taken from published experiments. In our theoretical campaign, we study the dependence of the optical force on the disease stage for different incident wavelengths. We show that optical forces change significantly with the disease, with amplitude variation in the hundreds of pN range. Our results open up new avenues for the design of new optical systems for the treatment of human disease.

  9. A novel chemically modified curcumin reduces severity of experimental periodontal disease in rats: initial observations.

    Science.gov (United States)

    Elburki, Muna S; Rossa, Carlos; Guimaraes, Morgana R; Goodenough, Mark; Lee, Hsi-Ming; Curylofo, Fabiana A; Zhang, Yu; Johnson, Francis; Golub, Lorne M

    2014-01-01

    Tetracycline-based matrix metalloproteinase- (MMP-) inhibitors are currently approved for two inflammatory diseases, periodontitis and rosacea. The current study addresses the therapeutic potential of a novel pleiotropic MMP-inhibitor not based on an antibiotic. To induce experimental periodontitis, endotoxin (LPS) was repeatedly injected into the gingiva of rats on one side of the maxilla; the contralateral (control) side received saline injections. Two groups of rats were treated by daily oral intubation with a chemically modified curcumin, CMC 2.24, for two weeks; the control groups received vehicle alone. After sacrifice, gingiva, blood, and maxilla were collected, the jaws were defleshed, and periodontal (alveolar) bone loss was quantified morphometrically and by μ-CT scan. The gingivae were pooled per experimental group, extracted, and analyzed for MMPs (gelatin zymography; western blot) and for cytokines (e.g., IL-1β; ELISA); serum and plasma samples were analyzed for cytokines and MMP-8. The LPS-induced pathologically excessive bone loss was reduced to normal levels based on either morphometric (P = 0.003) or μ-CT (P = 0.008) analysis. A similar response was seen for MMPs and cytokines in the gingiva and blood. This initial study, on a novel triketonic zinc-binding CMC, indicates potential efficacy on inflammatory mediators and alveolar bone loss in experimental periodontitis and warrants future therapeutic and pharmacokinetic investigations. PMID:25104884

  10. Modifying health behavior to prevent cardiovascular diseases: a nationwide survey among German primary care physicians.

    Science.gov (United States)

    Schneider, Sven; Diehl, Katharina; Bock, Christina; Herr, Raphael M; Mayer, Manfred; Görig, Tatiana

    2014-04-01

    Cardiovascular diseases (CVD) are a major public health concern as they are the leading cause of death in developed countries. Primary care is considered to be the ideal setting for CVD prevention. Therefore, more than 4,000 German primary care physicians (PCPs) were asked about their attitudes towards and their activities regarding the prevention of CVD in the nationwide ÄSP-kardio Study. The focus of the study was on health behavior modification. Two thirds of the participating PCPs stated that they routinely provided brief inventions to assist patients in reducing both their tobacco (72%) and alcohol (61%) consumption, to encourage them to increase their levels of physical activity (72%), and to assist them in adjusting to a more healthy diet (66%), and in achieving a healthy body weight (69%). However, only between 23% (quitting smoking) and 49% (diet modification) of PCPs felt that they had been successful in helping patients modify their lifestyles. Insufficient reimbursement, cultural diversity and a lack of time were reported to be the most problematic barriers to successful intervention in the primary care setting. Despite these obstacles, the majority of German PCPs was engaged in prevention and health behavior intervention to reduce the incidence and progression of CVD. PMID:24739770

  11. Modifying Health Behavior to Prevent Cardiovascular Diseases: A Nationwide Survey among German Primary Care Physicians

    Directory of Open Access Journals (Sweden)

    Sven Schneider

    2014-04-01

    Full Text Available Cardiovascular diseases (CVD are a major public health concern as they are the leading cause of death in developed countries. Primary care is considered to be the ideal setting for CVD prevention. Therefore, more than 4,000 German primary care physicians (PCPs were asked about their attitudes towards and their activities regarding the prevention of CVD in the nationwide ÄSP-kardio Study. The focus of the study was on health behavior modification. Two thirds of the participating PCPs stated that they routinely provided brief inventions to assist patients in reducing both their tobacco (72% and alcohol (61% consumption, to encourage them to increase their levels of physical activity (72%, and to assist them in adjusting to a more healthy diet (66%, and in achieving a healthy body weight (69%. However, only between 23% (quitting smoking and 49% (diet modification of PCPs felt that they had been successful in helping patients modify their lifestyles. Insufficient reimbursement, cultural diversity and a lack of time were reported to be the most problematic barriers to successful intervention in the primary care setting. Despite these obstacles, the majority of German PCPs was engaged in prevention and health behavior intervention to reduce the incidence and progression of CVD.

  12. A Novel Chemically Modified Curcumin Reduces Severity of Experimental Periodontal Disease in Rats: Initial Observations

    Directory of Open Access Journals (Sweden)

    Muna S. Elburki

    2014-01-01

    Full Text Available Tetracycline-based matrix metalloproteinase- (MMP- inhibitors are currently approved for two inflammatory diseases, periodontitis and rosacea. The current study addresses the therapeutic potential of a novel pleiotropic MMP-inhibitor not based on an antibiotic. To induce experimental periodontitis, endotoxin (LPS was repeatedly injected into the gingiva of rats on one side of the maxilla; the contralateral (control side received saline injections. Two groups of rats were treated by daily oral intubation with a chemically modified curcumin, CMC 2.24, for two weeks; the control groups received vehicle alone. After sacrifice, gingiva, blood, and maxilla were collected, the jaws were defleshed, and periodontal (alveolar bone loss was quantified morphometrically and by μ-CT scan. The gingivae were pooled per experimental group, extracted, and analyzed for MMPs (gelatin zymography; western blot and for cytokines (e.g., IL-1β; ELISA; serum and plasma samples were analyzed for cytokines and MMP-8. The LPS-induced pathologically excessive bone loss was reduced to normal levels based on either morphometric (P=0.003 or μ-CT (P=0.008 analysis. A similar response was seen for MMPs and cytokines in the gingiva and blood. This initial study, on a novel triketonic zinc-binding CMC, indicates potential efficacy on inflammatory mediators and alveolar bone loss in experimental periodontitis and warrants future therapeutic and pharmacokinetic investigations.

  13. Designing biologic selectivity for inflammatory bowel disease – role of vedolizumab

    Science.gov (United States)

    Krupka, Niklas; Baumgart, Daniel C

    2015-01-01

    Crohn’s disease and ulcerative colitis are two chronic inflammatory bowel conditions. Current approved biologic therapies are limited to blocking tumor necrosis factor alpha. Unfortunately, some patients are primary nonresponders, experiencing a loss of response, intolerance, or side effects. This defines an unmet need for novel therapeutic strategies. The rapid recruitment and inappropriate retention of leukocytes is a hallmark of chronic inflammation and a potentially promising therapeutic target. Here we discuss the clinical trial results of vedolizumab (anti-α4β7, LDP-02, MLN-02, and MLN0002) and its impact on future management of inflammatory bowel disease. PMID:25552903

  14. Designing biologic selectivity for inflammatory bowel disease--role of vedolizumab.

    Science.gov (United States)

    Krupka, Niklas; Baumgart, Daniel C

    2015-01-01

    Crohn's disease and ulcerative colitis are two chronic inflammatory bowel conditions. Current approved biologic therapies are limited to blocking tumor necrosis factor alpha. Unfortunately, some patients are primary nonresponders, experiencing a loss of response, intolerance, or side effects. This defines an unmet need for novel therapeutic strategies. The rapid recruitment and inappropriate retention of leukocytes is a hallmark of chronic inflammation and a potentially promising therapeutic target. Here we discuss the clinical trial results of vedolizumab (anti-α4β7, LDP-02, MLN-02, and MLN0002) and its impact on future management of inflammatory bowel disease. PMID:25552903

  15. Chronic Graft-versus-Host Disease: Disease Biology and Novel Therapeutic Strategies

    Directory of Open Access Journals (Sweden)

    Nishimori,Hisakazu

    2013-02-01

    Full Text Available Graft-versus-host disease (GVHD is a major complication after allogeneic hematopoietic stem cell transplantation. Chronic GVHD often presents with clinical manifestations that resemble those observed in autoimmune diseases. Standard treatment is 1-2mg/kg/day of prednisone or an equivalent dose of methylprednisolone, with continued administration of a calcineurin inhibitor for steroid sparing. However, the prognosis of steroid-refractory chronic GVHD remains poor. Classically, chronic GVHD was said to involve predominantly Th2 responses. We are now faced with a more complex picture, involving possible roles for thymic dysfunction, transforming growth factor-β (TGF-β and platelet-derived growth factor (PDGF, B cells and autoantibodies, and Th1/Th2/Th17 cytokines, as well as regulatory T cells (Tregs, in chronic GVHD. More detailed research on the pathophysiology of chronic GVHD may facilitate the establishment of novel strategies for its prevention and treatment.

  16. A systems biology approach identifies Molecular networks defining skeletal muscle abnormalities in chronic obstructive pulmonary disease.

    OpenAIRE

    Nil Turan; Susana Kalko; Anna Stincone; Kim Clarke; Ayesha Sabah; Katherine Howlett; S John Curnow; Rodriguez, Diego A.; Marta Cascante; Laura O'Neill; Stuart Egginton; Josep Roca; Francesco Falciani

    2011-01-01

    Chronic Obstructive Pulmonary Disease (COPD) is an inflammatory process of the lung inducing persistent airflow limitation. Extensive systemic effects, such as skeletal muscle dysfunction, often characterize these patients and severely limit life expectancy. Despite considerable research efforts, the molecular basis of muscle degeneration in COPD is still a matter of intense debate. In this study, we have applied a network biology approach to model the relationship between muscle molecular an...

  17. Designing biologic selectivity for inflammatory bowel disease – role of vedolizumab

    OpenAIRE

    Krupka N; Baumgart DC

    2014-01-01

    Niklas Krupka, Daniel C Baumgart Division of Gastroenterology and Hepatology, Department of Medicine, Charité Medical School, Humboldt-University of Berlin, Berlin, Germany Abstract: Crohn’s disease and ulcerative colitis are two chronic inflammatory bowel conditions. Current approved biologic therapies are limited to blocking tumor necrosis factor alpha. Unfortunately, some patients are primary nonresponders, experiencing a loss of response, intolerance, or side effects. This ...

  18. Designing biologic selectivity for inflammatory bowel disease – role of vedolizumab

    OpenAIRE

    Baumgart, Daniel

    2014-01-01

    Niklas Krupka, Daniel C Baumgart Division of Gastroenterology and Hepatology, Department of Medicine, Charité Medical School, Humboldt-University of Berlin, Berlin, Germany Abstract: Crohn’s disease and ulcerative colitis are two chronic inflammatory bowel conditions. Current approved biologic therapies are limited to blocking tumor necrosis factor alpha. Unfortunately, some patients are primary nonresponders, experiencing a loss of response, intolerance, or side effect...

  19. Biological Threats

    Science.gov (United States)

    ... Workplace Plans School Emergency Plans Main Content Biological Threats Biological agents are organisms or toxins that can ... for Disease Control and Prevention . Before a Biological Threat Unlike an explosion, a biological attack may or ...

  20. Biologic

    CERN Document Server

    Kauffman, L H

    2002-01-01

    In this paper we explore the boundary between biology and the study of formal systems (logic). In the end, we arrive at a summary formalism, a chapter in "boundary mathematics" where there are not only containers but also extainers ><, entities open to interaction and distinguishing the space that they are not. The boundary algebra of containers and extainers is to biologic what boolean algebra is to classical logic. We show how this formalism encompasses significant parts of the logic of DNA replication, the Dirac formalism for quantum mechanics, formalisms for protein folding and the basic structure of the Temperley Lieb algebra at the foundations of topological invariants of knots and links.

  1. Evidence for a modifier of onset age in Huntington disease linked to the HD gene in 4p16

    OpenAIRE

    Djoussé, Luc; Knowlton, Beth; Hayden, Michael R.; Almqvist, Elisabeth W.; Brinkman, Ryan R; Ross, Christopher A.; Margolis, Russel L.; Rosenblatt, Adam; Durr, Alexandra; Dode, Catherine; Morrison, Patrick J.; Novelletto, Andrea; Frontali, Marina; Trent, Ronald J. A.; McCusker, Elizabeth

    2004-01-01

    Huntington disease (HD) is a neurodegenerative disorder caused by the abnormal expansion of CAG repeats in the HD gene on chromosome 4p16.3. A recent genome scan for genetic modifiers of age at onset of motor symptoms (AO) in HD suggests that one modifier may reside in the region close to the HD gene itself. We used data from 535 HD participants of the New England Huntington cohort and the HD MAPS cohort to assess whether AO was influenced by any of the three markers in the 4p16 region: MSX1 ...

  2. A Mutation in DAOA Modifies the Age of Onset in PSEN1 E280A Alzheimer’s Disease

    OpenAIRE

    Vélez, Jorge I.; Dora Rivera; Claudio A. Mastronardi; Patel, Hardip R.; Carlos Tobón; Andrés Villegas; Yeping Cai; Simon Easteal; Francisco Lopera; Mauricio Arcos-Burgos

    2016-01-01

    We previously reported age of onset (AOO) modifier genes in the world’s largest pedigree segregating early-onset Alzheimer’s disease (AD), caused by the p.Glu280Ala (E280A) mutation in the PSEN1 gene. Here we report the results of a targeted analysis of functional exonic variants in those AOO modifier genes in sixty individuals with PSEN1 E280A AD who were whole-exome genotyped for ~250,000 variants. Standard quality control, filtering, and annotation for functional variants were applied, and...

  3. Biological behaviour and role of endothelial progenitor cells in vascular diseases

    Institute of Scientific and Technical Information of China (English)

    ZHANG Qiu-hua; SHE Ming-peng

    2007-01-01

    Obiective To review the biological behaviour of endothelial progenitor cells and their role in vascular diseases.Data sources The data used in this review were mainly from Medline and PubMed for relevant English language articles published from 1985 to March 2007.The search term was "endothelial progenitor cells".Study selection Articles about the biological behaviour of endothelial progenitor cells and their roles in the pathogenesis of vascular diseases such as atherogenesis were used.Results Progenitor cells in bone marrow,peripheral blood and adventitia can differentiate into mature endothelial cells (ECs).The progenitor cells,which express certain surface markers including AC133,CD34 and KDR,enable restoration of the microcirculation and ECs when injury or ischaemia occurs.Endothelial progenitor cells used in experimental models and clinical trials for ischaemic syndromes could restore endothelial integrity and inhibit neointima development.Moreover,their number and functional properties are influenced by certain cytokines and atherosclerotic risk factors.Impairment of the progenitor cells might limit the regenerative capacity,even lead to the development of atherosclerosis or other vascular diseases.Conclusions Endothelial progenitor cells have a particular role in prevention and treatment of certain cardiovascular diseases.However,many challenges remain in understanding differentiation of endothelial progenitor cells,their mobilization and revascularization.

  4. Biological effects of several extreme space flight factors (acceleration, magnetically activated water) on mouse natural or modified radiosensitivity

    International Nuclear Information System (INIS)

    Irradiated and Adeturon-protected mice were used to assess biological effects of several static (magnetically-activated water - MW) and dynamic (acceleration) factors of space flight. The study shows that increased gravitation, 20 G, 5 min, generated by a small radius centrifuge, increases static ability to work, while the number of peripheral blood cells decreases. Continuous exposure of mice to MW induces a decrease in dynamic ability to work, in comparison with the physiological controls, without substantial changes in other indices. Extreme factors in space flight (acceleration MW, radiation, radiation protector), alone or in combination, decrease the animal's growth rate. After administration of 200 mg/kg Adeturone, mouse dynamic ability to work increases, while its capabilities for adaptation and training are lowered, and pronounced leucocytosis is observed. MW, acceleration, or Adeturone pre-treatment of mice increases their survival and dynamic ability to work, following exposure to 600 R, when compared to irradiated animals, but decreases their capabilities for adaptation and training. Acceleration and Adeturone protect peripheral blood from radiation injury, while MW alone intensifies radiation cytopenia. Irradiation does not significantly modify the static ability to work, upon preceding exposure to MW or acceleration. In this case, Adeturone exerts protective effect. ME and Adeturone combined action results in increased survival rate and mean duration of life of irradiated animals, as compared to their single administration. Acceleration reduces MW, Adeturone and MW + Adeturone effect on survival. Peripheral blood parameters do not correlate with survival rates. Combined pre-treatment with two or three of the factors studied increases dynamic ability to work following irradiation, and in many cases the static ability as well. The combination of Adeturone and MW was the only one with negative effect on the static ability to work. (A.B.)

  5. Enhanced biological nutrient removal in modified carbon source division anaerobic anoxic oxic process with return activated sludge pre-concentration☆

    Institute of Scientific and Technical Information of China (English)

    Qin Lu; Haiyan Wu; Haoyan Li; Dianhai Yang

    2015-01-01

    A pilot-scale modified carbon source division anaerobic anoxic oxic (AAO) process with pre-concentration of returned activated sludge (RAS) was proposed in this study for the enhanced biological nutrient removal (BNR) of municipal wastewater with limited carbon source. The influent carbon source was fed in step while a novel RAS pre-concentration tank was adopted to improve BNR efficiency, and the effects of an influent carbon source distribution ratio and a RAS pre-concentration ratio were investigated. The results show that the removal efficiency of TN is mainly influenced by the carbon source distribution ratio while the TP removal relies on the RAS pre-concentration ratio. The optimum carbon source distribution ratio and RAS pre-concentration ratio are 60%and 50%, respectively, with an inner recycling ratio of 100%under the optimum steady operation of pilot test, reaching an average effluent TN concentration of 9.8 mg·L−1 with a removal efficiency of 63%and an average TP removal efficiency of 94%. The mechanism of nutrient removal is discussed and the kinetics is analyzed. The results reveal that the optimal carbon source distribution ratio provides sufficient denitrifying carbon source to each anoxic phase, reducing nitrate accumulation while the RAS pre-concentration ratio improves the condition of anaerobic zone to ensure the phosphorus release due to less nitrate in the returned sludge. Therefore, nitrifying bacteria, denitrifying bacteria and phosphorus accumulation organisms play an important role under the optimum condition, enhancing the performance of nutrient removal in this test.

  6. Genetically modified plants and food hypersensitivity diseases: usage and implications of experimental models for risk assessment.

    Science.gov (United States)

    Prescott, Vanessa E; Hogan, Simon P

    2006-08-01

    The recent advances in biotechnology in the plant industry have led to increasing crop production and yield that in turn has increased the usage of genetically modified (GM) food in the human food chain. The usage of GM foods for human consumption has raised a number of fundamental questions including the ability of GM foods to elicit potentially harmful immunological responses, including allergic hypersensitivity. To assess the safety of foods derived from GM plants including allergenic potential, the US FDA, Food and Agriculture Organization of the United Nations (FAO)/World Health Organization (WHO), and the EU have developed approaches for evaluation assessment. One assessment approach that has been a very active area of research and debate is the development and usage of animal models to assess the potential allergenicity of GM foods. A number of specific animal models employing rodents, pigs, and dogs have been developed for allergenicity assessment. However, validation of these models is needed and consideration of the criteria for an appropriate animal model for the assessment of allergenicity in GM plants is required. We have recently employed a BALB/c mouse model to assess the potential allergenicity of GM plants. We have been able to demonstrate that this model is able to detect differences in antigenicity and identify aspects of protein post-translational modifications that can alter antigenicity. Furthermore, this model has also enabled us to examine the usage of GM plants as a therapeutic approach for the treatment of allergic diseases. This review discusses the current approaches to assess the allergenic potential of GM food and particularly focusing on the usage of animal models to determine the potential allergenicity of GM foods and gives an overview of our recent findings and implications of these studies. PMID:16364445

  7. Racism, society, and disease: an exploration of the social and biological mechanisms of differential mortality.

    Science.gov (United States)

    Cooper, R; Steinhauer, M; Miller, W; David, R; Schatzkin, A

    1981-01-01

    Racial differentials in mortality provide important insight into the nature of mass disease in capitalist society. Not only are the differentials sizable in magnitude, they are consistent for multiple causes of death and appear to evolve in response to social development. The relationships among social factors and the biological and physical agents of disease can be identified through racial contrasts and a pattern of causation which applies to both the minority and majority populations described. Furthermore, the impact of exploitation as the primary disease-mediating factor under capitalist social relations can be estimated. This paper attempts to combine an analysis of bio-medical mechanisms with Marxist social theory in a comprehensive framework for the study of the social origins of racial differentials. PMID:7298254

  8. Designing biologic selectivity for inflammatory bowel disease – role of vedolizumab

    Directory of Open Access Journals (Sweden)

    Krupka N

    2014-12-01

    Full Text Available Niklas Krupka, Daniel C Baumgart Division of Gastroenterology and Hepatology, Department of Medicine, Charité Medical School, Humboldt-University of Berlin, Berlin, Germany Abstract: Crohn’s disease and ulcerative colitis are two chronic inflammatory bowel conditions. Current approved biologic therapies are limited to blocking tumor necrosis factor alpha. Unfortunately, some patients are primary nonresponders, experiencing a loss of response, intolerance, or side effects. This defines an unmet need for novel therapeutic strategies. The rapid recruitment and inappropriate retention of leukocytes is a hallmark of chronic inflammation and a potentially promising therapeutic target. Here we discuss the clinical trial results of vedolizumab (anti-α4β7, LDP-02, MLN-02, and MLN0002 and its impact on future management of inflammatory bowel disease. Keywords: ulcerative colitis, Crohn’s disease, vedolizumab, MLN0002, MLN-02, LDP-02, anti-α4β7

  9. Synthesis of Base-Modified 2 '-Deoxyribonucleoside Triphosphates and Their Use in Enzymatic Synthesis of Modified DNA for Applications in Bioanalysis and Chemical Biology

    Czech Academy of Sciences Publication Activity Database

    Hocek, Michal

    2014-01-01

    Roč. 79, č. 21 (2014), s. 9914-9921. ISSN 0022-3263 R&D Projects: GA ČR GBP206/12/G151; GA ČR GA14-04289S Institutional support: RVO:61388963 Keywords : cross-coupling reactions * modified nucleoside triphosphates * nucleic acids Subject RIV: CC - Organic Chemistry Impact factor: 4.721, year: 2014

  10. Whole-genome sequencing suggests a chemokine gene cluster that modifies age at onset in familial Alzheimer's disease.

    Science.gov (United States)

    Lalli, M A; Bettcher, B M; Arcila, M L; Garcia, G; Guzman, C; Madrigal, L; Ramirez, L; Acosta-Uribe, J; Baena, A; Wojta, K J; Coppola, G; Fitch, R; de Both, M D; Huentelman, M J; Reiman, E M; Brunkow, M E; Glusman, G; Roach, J C; Kao, A W; Lopera, F; Kosik, K S

    2015-11-01

    We have sequenced the complete genomes of 72 individuals affected with early-onset familial Alzheimer's disease caused by an autosomal dominant, highly penetrant mutation in the presenilin-1 (PSEN1) gene, and performed genome-wide association testing to identify variants that modify age at onset (AAO) of Alzheimer's disease. Our analysis identified a haplotype of single-nucleotide polymorphisms (SNPs) on chromosome 17 within a chemokine gene cluster associated with delayed onset of mild-cognitive impairment and dementia. Individuals carrying this haplotype had a mean AAO of mild-cognitive impairment at 51.0 ± 5.2 years compared with 41.1 ± 7.4 years for those without these SNPs. This haplotype thus appears to modify Alzheimer's AAO, conferring a large (~10 years) protective effect. The associated locus harbors several chemokines including eotaxin-1 encoded by CCL11, and the haplotype includes a missense polymorphism in this gene. Validating this association, we found plasma eotaxin-1 levels were correlated with disease AAO in an independent cohort from the University of California San Francisco Memory and Aging Center. In this second cohort, the associated haplotype disrupted the typical age-associated increase of eotaxin-1 levels, suggesting a complex regulatory role for this haplotype in the general population. Altogether, these results suggest eotaxin-1 as a novel modifier of Alzheimer's disease AAO and open potential avenues for therapy. PMID:26324103

  11. Screening prior to biological therapy in Crohn's disease : Adherence to guidelines and prevalence of infections. Results from a multicentre retrospective study

    NARCIS (Netherlands)

    van der Have, Mike; Belderbos, Tim D. G.; Fidder, Herma H.; Leenders, Max; Dijkstra, Gerard; Peters, Charlotte P.; Eshuis, Emma J.; Ponsioen, Cyriel Y.; Siersema, Peter D.; van Oijen, Martijn G. H.; Oldenburg, Bas

    2014-01-01

    Background: Screening for opportunistic infections prior to starting biological therapy in patients with inflammatory bowel disease is recommended. Aims: To assess adherence to screening for opportunistic infections prior to starting biological therapy in Crohn's disease patients and its yield. Meth

  12. Use of a modified Delphi panel to identify and weight criteria for prioritization of zoonotic diseases in Switzerland.

    Science.gov (United States)

    Stebler, N; Schuepbach-Regula, G; Braam, P; Falzon, L C

    2015-09-01

    Zoonotic diseases have a significant impact on public health globally. To prevent or reduce future zoonotic outbreaks, there is a constant need to invest in research and surveillance programs while updating risk management strategies. However, given the limited resources available, disease prioritization based on the need for their control and surveillance is important. This study was performed to identify and weight disease criteria for the prioritization of zoonotic diseases in Switzerland using a semi-quantitative research method based on expert opinion. Twenty-eight criteria relevant for disease control and surveillance, classified under five domains, were selected following a thorough literature review, and these were evaluated and weighted by seven experts from the Swiss Federal Veterinary Office using a modified Delphi panel. The median scores assigned to each criterion were then used to rank 16 notifiable and/or emerging zoonoses in Switzerland. The experts weighted the majority of the criteria similarly, and the top three criteria were Severity of disease in humans, incidence and prevalence of the disease in humans and treatment in humans. Based on these weightings, the three highest ranked diseases were Avian Influenza, Bovine Spongiform Encephalitis, and Bovine Tuberculosis. Overall, this study provided a preliminary list of criteria relevant for disease prioritization in Switzerland. These were further evaluated in a companion study which involved a quantitative prioritization method and multiple stakeholders. PMID:26036342

  13. Application of systems biology to the study of chronic kidney disease

    Institute of Scientific and Technical Information of China (English)

    CAO Yu-han; L(U) Lin-li; ZHANG Jian-dong; LIU Bi-cheng

    2012-01-01

    Chronic kidney disease (CKD) is a major public health problem that affects about 10% of the general population.Current approaches to characterize the category and progression of CKD are normally based on renal histopathological results and clinical parameters.However,this information is not sufficient to predict CKD progression risk reliably or to guide preventive interventions.Nowadays,the appearance of systems biology has brought forward the concepts of "-omics"technologies,including genomics,transcriptomics,proteomics,and metabolomics.Systems biology,together with molecular analysis approaches such as microarray analysis,genome-wide association studies (GWAS),and serial analysis of gene expression (SAGE),has provided the framework for a comprehensive analysis of renal disease and serves as a starting point for generating novel molecular diagnostic tools for use in nephrology.In particular,analysis of urinary mRNA and protein levels is rapidly evolving as a non-invasive approach for CKD monitoring.All these systems biological molecular approaches are required for application of the concept of "personalized medicine" to progressive CKD,which will result in tailoring therapy for each patient,in contrast to the "one-size-fits-all" therapies currently in use.

  14. THE EFFECT OF AYURVEDIC DRUGS WHEN USED AS DISEASE MODIFYING ANTIREUMATIC DRUGS (DMARD’S IN AMAVATA (RHEUMATOID ARTHRITIS

    Directory of Open Access Journals (Sweden)

    Panthulu Raghupathi Goud

    2012-02-01

    Full Text Available The Disease Modifying Anti-Rheumatic Drugs (DMARD’S are therapeutic agents which rapidly reduce the intensity of inflammation and facilitate induction of remission. The sages of Ayurveda invented many remedies to combat this disease. Here an effort is made to evaluate once again the efficacy of some of the remedies. Ama and Vata are the two chief pathognomonic factors in causing Amavata. Ama has the qualities of heaviness (guru, unctuousness (Snigdha, immobility (Sthira, bulkiness (Sthula, and sliminess or stickiness (Pichhila. Vata has the properties of lightness (Laghu, dryness (Ruksha, movement (Chala, subtleness (Sukshma, and clearness (Vishada. Ama is the undigested food which results due to Mandagni (sluggish digestive fire which is caused due to various reasons. All types of metabolic fires (Agnis become sluggish in this disease. The stagnant Ama is called Ama visha. Ama is the substance which is the resultant of improper digestion of the food due to hypo-functioning of the gastric juices (Jatharagni. The drugs having the qualities of Tiktam (astringent, Deepana (appetizer and Katu (pungent modify the disease due to their qualities. The purgation property (Virechana guna modifies the process of disease. Castor oil (Eranda Tailam cures Vata diseases. It has been observed that after administration of Castor oil, the fluid from the inflamed joints and tissues has been drained away. Castor oil relieves pain, reduces inflammation and swelling, increases lymphatic circulation, reduces flatulence, stimulates the liver and the gall bladder, and reduces toxins. A scientific study on the effect of castor oil on humans found castor oil to be an antitoxin, and as having an impact on the lymphatic system enhancing the immune functioning of the body. Panchakola churnam is anti-inflammatory; it is an anti-oxidant, an immunomodulator, and a rejuvenator too. Hingu Triguna Tailam is digestive, carminative, analgesic and anti-rheumatic.

  15. Gaseous VOCs rapidly modify particulate matter and its biological effects – Part 2: Complex urban VOCs and model PM

    Directory of Open Access Journals (Sweden)

    H. E. Jeffries

    2012-12-01

    for "effect modification". Fortunately, in the absence of "seed particles", the complex highly-reactive VOC system used does not create any secondary aerosol in situ. All PM present in these tests were, therefore, introduced by injection of MOA to serve as PM-to-be-modified by the gaseous environment. PM addition was only done during dark periods, either before or after the daylight period. The purpose of this design is to test if a non-toxic PM becomes toxic in initially unreacted ("Fresh", or in reacted ("Aged" complex VOC conditions. To have a complete design, we also tested the effects of clean air and the same VOC conditions, but without introducing any PM. Thus, there were six exposure treatment conditions that were evaluated with the side-by-side, gas-only- and PM-only-effects exposure systems; five separate chamber experiments were performed: two with clean air and three with the complex VOC/NOx mixture. For all of these experiments and exposures, chemical composition data and matching biological effects results for two end-points were compared. Chemical measurements demonstrate the temporal evolution of oxidized species, with a corresponding increase in toxicity observed from exposed cells. The largest increase in gas-phase toxicity was observed in the two "Aged" VOC exposures. The largest increase in particle-phase toxicity was observed in the "Aged" VOC exposure with the addition of PM after sunset. These results are a clear demonstration that the findings from Part 1 can be extended to the complex urban oxidized environment. This further demonstrates that the atmosphere itself cannot be ignored as a source of toxic species when establishing the risks associated with exposure to PM. Because gases and PM are transported and deposited differently within the atmosphere and lungs, these results have significant consequences. In the next (and final part of the study, testing is further applied to systems with real diesel exhaust, including primary PM from a

  16. Gaseous VOCs rapidly modify particulate matter and its biological effects – Part 2: Complex urban VOCs and model PM

    Directory of Open Access Journals (Sweden)

    S. Ebersviller

    2012-03-01

    target PM for "effect modification". Fortunately, in the absence of "seed particles", the complex highly-reactive VOC system used does not create any secondary aerosol in situ. All PM present in these tests were, therefore, introduced by injection of MOA to serve as PM-to-be-modified by the gaseous environment. PM addition was only done during dark periods, either before or after the daylight period. The purpose of this design is to test if a non-toxic PM becomes toxic in initially unreacted ("Fresh", or in reacted ("Aged" complex VOC conditions. To have a complete design, we also tested the effects of clean air and the same VOC conditions, but without introducing any PM. Thus, there were six exposure treatment conditions that were evaluated with the side-by-side, gas-only- and PM-only-effects exposure systems; five separate chamber experiments were performed: two with clean air and three with the complex VOC/NOx mixture.

    For all of these experiments and exposures, chemical composition data and matching biological effects results for two end-points were compared. Chemical measurements demonstrate the temporal evolution of oxidized species, with a corresponding increase in toxicity observed from exposed cells. The largest increase in gas-phase toxicity was observed in the two "Aged" VOC exposures. The largest increase in particle-phase toxicity was observed in the "Aged" VOC exposure with the addition of PM after sunset. These results are a clear demonstration that the findings from Part 1 can be extended to the complex urban oxidized environment. This further demonstrates that the atmosphere itself cannot be ignored as a source of toxic species when establishing the risks associated with exposure to PM. Because gases and PM are transported and deposited differently within the atmosphere and lungs, these results have significant consequences. In the next (and final part of the study, testing is further applied to systems with real diesel exhaust

  17. Gaseous VOCs rapidly modify particulate matter and its biological effects - Part 2: Complex urban VOCs and model PM

    Science.gov (United States)

    Ebersviller, S.; Lichtveld, K.; Sexton, K. G.; Zavala, J.; Lin, Y.-H.; Jaspers, I.; Jeffries, H. E.

    2012-12-01

    modification". Fortunately, in the absence of "seed particles", the complex highly-reactive VOC system used does not create any secondary aerosol in situ. All PM present in these tests were, therefore, introduced by injection of MOA to serve as PM-to-be-modified by the gaseous environment. PM addition was only done during dark periods, either before or after the daylight period. The purpose of this design is to test if a non-toxic PM becomes toxic in initially unreacted ("Fresh"), or in reacted ("Aged") complex VOC conditions. To have a complete design, we also tested the effects of clean air and the same VOC conditions, but without introducing any PM. Thus, there were six exposure treatment conditions that were evaluated with the side-by-side, gas-only- and PM-only-effects exposure systems; five separate chamber experiments were performed: two with clean air and three with the complex VOC/NOx mixture. For all of these experiments and exposures, chemical composition data and matching biological effects results for two end-points were compared. Chemical measurements demonstrate the temporal evolution of oxidized species, with a corresponding increase in toxicity observed from exposed cells. The largest increase in gas-phase toxicity was observed in the two "Aged" VOC exposures. The largest increase in particle-phase toxicity was observed in the "Aged" VOC exposure with the addition of PM after sunset. These results are a clear demonstration that the findings from Part 1 can be extended to the complex urban oxidized environment. This further demonstrates that the atmosphere itself cannot be ignored as a source of toxic species when establishing the risks associated with exposure to PM. Because gases and PM are transported and deposited differently within the atmosphere and lungs, these results have significant consequences. In the next (and final) part of the study, testing is further applied to systems with real diesel exhaust, including primary PM from a vehicle operated with

  18. Comparison of renal dynamic imaging and modified MDRD equation in determining the stage of chronic kidney disease patients

    International Nuclear Information System (INIS)

    Objective: To compare the accuracy of 99Tcm-diethylene triamine pentaacetic acid (99Tcm-DTPA) renal dynamic imaging and modified modification of diet in renal disease trail (MDRD) equation in determining the stage of the chronic kidney disease (CKD) patients in clinical practice. Methods: A total of 169 patients were enrolled whose glomerular filtration rate (GFR) were determined simultaneously by 3 methods: dual plasma sample clearance method, renal dynamic imaging and modified MDRD equation. The dual plasma sample clearance method was employed as the reference method. The accuracy of the other methods in determining the stage of CKD patients was compared and the comparison was repeated based on the different stages. Results: The accuracy of renal dynamic imaging and modified MDRD equation was 56.80% and 68.64%, respectively (P=0.019<0.05). And only in the stage of uremia, the difference of the above-mentioned two method reached statistical significance (P=0.012<0.05), while in other stages they showed similar performance (P=0.180, 0.424, 0.629 and 0.754, all P>0.05). Conclusion: Modified MDRD equation showed better performance than renal dynamic imaging or as good as the second one in determining the stage of CKD patients and the former one should be the first choice in clinical practice because of its simplicity and economy. (authors)

  19. Phenotypic charactheristics of fluorescent pseudomonss, biological control agent of lincat disease of temanggung tobacco

    Directory of Open Access Journals (Sweden)

    NINING NURUL AZIZAH

    2007-04-01

    Full Text Available Fluorescent pseudomonass isolated from local plants-rishosphere in temanggung controlled lincat disease of tobacco. This report describe phenotypic charactheristics of the bacteria in order to be used as a base for the development of the bacteria as a biological control agent of lincat disease. Phenotypic charactheristics of six isolates of fluorescent Pseudomonass which controlled lincat disease in the field were determined in the laboratory of Plant Bacteriology, Faculty of Agriculture, Gadjah Mada University. Plant pathogenicity tests were conducted by hypersensitive reaction into tobacco leaf and inoculation to tobacco plants. Antagonism test between fluorescent Pseudomonass and other candidate of biological control agents were also conducted. The results indicated that the bacteria were rod shape, Gram negative, positive reaction in catalase and oxidase tests. Nitrate reduce to nitrite, arginine was hydrolysed, fluorescent pigment were produced on King’s B medium, levan formation positive and all bacteria denitrifiy. The bacteria used urea, tween 80 and amylum were not hydrolised, poly--hydroxybutyrate was not accumulated in the cells. Negative reactions were observed for lysine decarboxylation, indol production, VP/MR reaction, and gelatn liquefation. Some compounds could be used as solely carbon sources. All isolates grew on the medium containing 2% NaCl. The best pH for growth was 6-7 and all isolates grew at 20-41C. Negative result were obtained for hypersensitive reaction and pathogenicity tests.

  20. Validation and reliability of a modified sphygmomanometer for the assessment of handgrip strength in Parkinson´s disease

    OpenAIRE

    Soraia M. Silva; Corrêa, Fernanda I.; Paula F. C. Silva; Daniela F. T. Silva; Lucareli, Paulo R. G.; Corrêa, João C F

    2015-01-01

    BACKGROUND: Handgrip strength is currently considered a predictor of overall muscle strength and functional capacity. Therefore, it is important to find reliable and affordable instruments for this analysis, such as the modified sphygmomanometer test (MST). OBJECTIVES: To assess the concurrent criterion validity of the MST, to compare the MST with the Jamar dynamometer, and to analyze the reproducibility (i.e. reliability and agreement) of the MST in individuals with Parkinson's disease (PD)....

  1. A Mutation in DAOA Modifies the Age of Onset in PSEN1 E280A Alzheimer's Disease

    Science.gov (United States)

    Vélez, Jorge I.; Rivera, Dora; Mastronardi, Claudio A.; Patel, Hardip R.; Tobón, Carlos; Villegas, Andrés; Cai, Yeping; Easteal, Simon; Arcos-Burgos, Mauricio

    2016-01-01

    We previously reported age of onset (AOO) modifier genes in the world's largest pedigree segregating early-onset Alzheimer's disease (AD), caused by the p.Glu280Ala (E280A) mutation in the PSEN1 gene. Here we report the results of a targeted analysis of functional exonic variants in those AOO modifier genes in sixty individuals with PSEN1 E280A AD who were whole-exome genotyped for ~250,000 variants. Standard quality control, filtering, and annotation for functional variants were applied, and common functional variants located in those previously reported as AOO modifier loci were selected. Multiloci linear mixed-effects models were used to test the association between these variants and AOO. An exonic missense mutation in the G72 (DAOA) gene (rs2391191, P = 1.94 × 10−4, PFDR = 9.34 × 10−3) was found to modify AOO in PSEN1 E280A AD. Nominal associations of missense mutations in the CLUAP1 (rs9790, P = 7.63 × 10−3, PFDR = 0.1832) and EXOC2 (rs17136239, P = 0.0325, PFDR = 0.391) genes were also found. Previous studies have linked polymorphisms in the DAOA gene with the occurrence of neuropsychiatric symptoms such as depression, apathy, aggression, delusions, hallucinations, and psychosis in AD. Our findings strongly suggest that this new conspicuous functional AOO modifier within the G72 (DAOA) gene could be pivotal for understanding the genetic basis of AD. PMID:26949549

  2. Estimating long-term effects of disease-modifying drug therapy in multiple sclerosis patients.

    Science.gov (United States)

    Rudick, R A; Cutter, G R; Baier, M; Weinstock-Guttman, B; Mass, M K; Fisher, E; Miller, D M; Sandrock, A W

    2005-12-01

    Two methods were used to estimate the long-term impact of disease-modifying drug therapy (DMDT) in patients with relapsing multiple sclerosis (MS) who completed a placebo-controlled, randomized clinical trial of interferon beta-1a (IFNbeta-1a). The study cohort consisted of patients with ambulatory relapsing MS who had previously participated in a placebo-controlled clinical trial for two years. At its end, patients were managed in an unstructured fashion by their neurologists and re-evaluated at an average of 6.1 years after the end of the trial. Follow-up evaluation was obtained for 93% of the 172 eligible patients. Because study inclusion criteria required that all patients have an Expanded Disability Status Scale (EDSS) score of or = 6.0. Two methods were used to estimate the expected proportions that reached EDSS > or = 6.0 at follow-up. Estimates were compared with observed proportions. Method 1 used progression rates observed during the two-year phase III clinical trial and the percentage of time that patients were on DMDT during the follow-up period. Method 2 used progression rates from a natural history comparison group of relapsing-remitting MS patients. At the eight-year follow-up, 42.0% of the original placebo patients and 29.1% of the original IFNbeta-1a patients reached an EDSS > or = 6.0, an observed treatment effect of approximately 30%. Using method 1, it was estimated that 36.3% of the original placebo patients and 27.6% of the original IFNbeta-1a patients should have reached an EDSS > or = 6.0. Use of the natural history control group (method 2) predicted less plausible outcomes. Estimated proportions of patients reaching the endpoint were 63.3% for the original placebo group and 55.8% for the original IFNbeta-1a group. Treatment effect sizes of 75-90% would be required to match estimates from method 2 with the observed outcome. The paucity of data on the long-term treatment of patients with MS may be aided by applying these or similar methods to

  3. Associations between Potentially Modifiable Risk Factors and Alzheimer Disease: A Mendelian Randomization Study.

    Directory of Open Access Journals (Sweden)

    Søren D Østergaard

    2015-06-01

    Full Text Available Potentially modifiable risk factors including obesity, diabetes, hypertension, and smoking are associated with Alzheimer disease (AD and represent promising targets for intervention. However, the causality of these associations is unclear. We sought to assess the causal nature of these associations using Mendelian randomization (MR.We used SNPs associated with each risk factor as instrumental variables in MR analyses. We considered type 2 diabetes (T2D, NSNPs = 49, fasting glucose (NSNPs = 36, insulin resistance (NSNPs = 10, body mass index (BMI, NSNPs = 32, total cholesterol (NSNPs = 73, HDL-cholesterol (NSNPs = 71, LDL-cholesterol (NSNPs = 57, triglycerides (NSNPs = 39, systolic blood pressure (SBP, NSNPs = 24, smoking initiation (NSNPs = 1, smoking quantity (NSNPs = 3, university completion (NSNPs = 2, and years of education (NSNPs = 1. We calculated MR estimates of associations between each exposure and AD risk using an inverse-variance weighted approach, with summary statistics of SNP-AD associations from the International Genomics of Alzheimer's Project, comprising a total of 17,008 individuals with AD and 37,154 cognitively normal elderly controls. We found that genetically predicted higher SBP was associated with lower AD risk (odds ratio [OR] per standard deviation [15.4 mm Hg] of SBP [95% CI]: 0.75 [0.62-0.91]; p = 3.4 × 10(-3. Genetically predicted higher SBP was also associated with a higher probability of taking antihypertensive medication (p = 6.7 × 10(-8. Genetically predicted smoking quantity was associated with lower AD risk (OR per ten cigarettes per day [95% CI]: 0.67 [0.51-0.89]; p = 6.5 × 10(-3, although we were unable to stratify by smoking history; genetically predicted smoking initiation was not associated with AD risk (OR = 0.70 [0.37, 1.33]; p = 0.28. We saw no evidence of causal associations between glycemic traits, T2D, BMI, or educational attainment and risk of AD (all p > 0.1. Potential limitations of this study

  4. Do parental coronary heart disease risk factors(non-modifiable) effect their young ones?

    Institute of Scientific and Technical Information of China (English)

    Arun; Kumar

    2015-01-01

    Objective:To study the differences between the lipid profiles of the subjects whose parents are having known non-modifiable risk factors such as obesity,hypertension(HTN),myocardial infarction and diabetes,and compare them with the lipid profiles of the subjects whose parents are not having those risk factors.Methods:A total of 402 subjects were recruited to this study.A detailed questionnaire which included information on the past medical history,height,weight,blood pressure,physical activity,smoke,alcohol,family history of coronary heart disease,HTN.diabetics and obesity.Basic demographic data and dietary habits were completed by all participants.Blood samples were obtained from all subjects after 14 h.Lipid profiles were analyzed using automated analyzer.The results were analyzed using SPSS software packages.Results:The mean body mass index of the population was well below the cut-off value of obesity(>24.5 kg/m") and high risk of future cardiovascular disorder(CVD) events in this age group.The mean levels of total cholesterol(TC),triglycerides(TG) and TC/high density lipoprotein(HDL) were less than the risk levels indicative of future CVD events according to the ATP Ⅲ cut-off values.However the mean HDL level in our population was slightly greater than the cut-off value while the mean low density lipoprotein level was almost similar to the risk level.Differences were observed when the subjects without history of maternal obesity were compared with subjects with history of maternal obesity.The greater percentage of subjects who are having risk levels of body mass index.TC.low density lipoprotein.TG.and TC/HDI.indicated that maternal obesity contributed to the greater susceptibility of developing CVD risk in their offspring.Conclusions:Advancing age may result in changes that could be atherogenic in the future.Such atherogenic changes have already initialed when the subjects are about 21 years old.The incidence of atherogenic changes is far greater when mothers

  5. Biological and functional diversity of bird communities in natural and human modified habitats in Northern Flank of Knuckles Mountain Forest Range, Sri Lanka

    Directory of Open Access Journals (Sweden)

    KALYA SUBASINGHE

    2014-10-01

    Full Text Available Subasinghe K, Sumanapala AP. 2014. Biological and functional diversity of bird communities in natural and human modified habitats in Northern Flank of Knuckles Mountain Forest Range, Sri Lanka. Biodiversitas 15: 200-205. The Knuckles Mountain Forest Range (KMFR has a complex mosaic of natural and human modified habitats and the contribution of these habitats to the biological and functional diversities has not been deeply studied. Present study investigated both of these diversities in five habitat types (two natural habitats: Sub-montane forest and Pitawala Patana grassland; three modified habitats: cardamom, pinus and abandoned tea plantations in Northern Flank of KMFR using birds as the indicator group. Bird communities were surveyed using point count method. A total of 1,150 individuals belonging to 56 species were observed. The highest species richness was reported from the cardamom plantation where as sub-montane forest had the highest feeding guild diversity in terms of Shannon Weiner index. The abandoned tea plantation and the Pitawala Patana grasslands with fairly open habitats, showed relatively lower levels of feeding guild diversities. It is clear that the structurally complex habitats contribute more to the area’s biological and functional diversities and need to be taken into consideration when developing conservation plans.

  6. Biological control agents for suppression of post-harvest diseases of potatoes: strategies on discovery and development

    Science.gov (United States)

    As used in plant pathology, the term "biological control" or its short form “biocontrol” commonly refers to the decrease in the inoculum or the disease-producing activity of a pathogen accomplished through one or more organisms, including the host plant but excluding man. Biological control of plant...

  7. Unraveling human complexity and disease with systems biology and personalized medicine

    OpenAIRE

    Naylor, Stephen; Jake Y Chen

    2010-01-01

    We are all perplexed that current medical practice often appears maladroit in curing our individual illnesses or disease. However, as is often the case, a lack of understanding, tools and technologies are the root cause of such situations. Human individuality is an often-quoted term but, in the context of human biology, it is poorly understood. This is compounded when there is a need to consider the variability of human populations. In the case of the former, it is possible to quantify human ...

  8. Presence of other allergic disease modifies the effect of early childhood traffic-related air pollution exposure on asthma prevalence.

    Science.gov (United States)

    Dell, Sharon D; Jerrett, Michael; Beckerman, Bernard; Brook, Jeffrey R; Foty, Richard G; Gilbert, Nicolas L; Marshall, Laura; Miller, J David; To, Teresa; Walter, Stephen D; Stieb, David M

    2014-04-01

    Nitrogen dioxide (NO2), a surrogate measure of traffic-related air pollution (TRAP), has been associated with incident childhood asthma. Timing of exposure and atopic status may be important effect modifiers. We collected cross-sectional data on asthma outcomes from Toronto school children aged 5-9years in 2006. Lifetime home, school and daycare addresses were obtained to derive birth and cumulative NO2 exposures for a nested case-control subset of 1497 children. Presence of other allergic disease (a proxy for atopy) was defined as self-report of one or more of doctor-diagnosed rhinitis, eczema, or food allergy. Generalized estimating equations were used to adjust for potential confounders, and examine hypothesized effect modifiers while accounting for clustering by school. In children with other allergic disease, birth, cumulative and 2006 NO2 were associated with lifetime asthma (OR 1.46, 95% CI 1.08-1.98; 1.37, 95% CI 1.00-1.86; and 1.60, 95% CI 1.09-2.36 respectively per interquartile range increase) and wheeze (OR 1.44, 95% CI 1.10-1.89; 1.31, 95% CI 1.02-1.67; and 1.60, 95% CI 1.16-2.21). No or weaker effects were seen in those without allergic disease, and effect modification was amplified when a more restrictive algorithm was used to define other allergic disease (at least 2 of doctor diagnosed allergic rhinitis, eczema or food allergy). The effects of modest NO2 levels on childhood asthma were modified by the presence of other allergic disease, suggesting a probable role for allergic sensitization in the pathogenesis of TRAP initiated asthma. PMID:24472824

  9. From molecule to man: integrating molecular biology with whole organ physiology in studying respiratory disease.

    Science.gov (United States)

    Königshoff, Melanie; Uhl, Franziska; Gosens, Reinoud

    2011-10-01

    Chronic lung diseases such as asthma, chronic obstructive pulmonary disease (COPD), and idiopathic pulmonary fibrosis (IPF) are all characterized by structural changes of the airways and/or lungs that limit airflow and/or gas exchange. Currently, there is no therapy available that adequately targets the structural remodeling of the airways and lungs in these diseases. This underscores the great need for insight into the mechanisms that underpin the development of airway remodeling, fibrosis and emphysema in these diseases, in order to identify suitable drug targets. It is increasingly evident that structural cell-cell communication within the lung is central to the development of remodeling, indicating that a more integrative approach should be considered when studying molecular and cellular mechanisms of remodeling. Therefore, there is a great need to study molecular and cellular physiological and pathophysiological mechanisms in as much detail as possible, but with as little as possible loss of the physiological context. Here, we will review the use of models such as cellular co-culture, tissue culture, and lung slice culture, in which cell-cell communication and tissue architecture are better preserved or mimicked than in cell culture, and zoom in on the usefulness of molecular and cellular biological tools in these complex model systems to read out or control signaling and gene/protein regulation. PMID:21356323

  10. Screening of chitinolytic actinomycetes for biological control of Sclerotium rolfsii stem rot disease of chilli

    Directory of Open Access Journals (Sweden)

    Pranee Pattanapipitpaisal

    2012-09-01

    Full Text Available Two hundred and eighty three strains were isolated from rhizoshere-associated soils, from Ubon Ratchathani andSrisaket province, using Enrichment Media for isolation of Chitinase-producing Actinomycetes agar (EMCA agar. All strainswere screened for chitinolytic activity and sixty eight strains gave significant clear zone on EMCA agar plates. The selectedchitinolytic strains were assayed for in vitro antagonism against Sclerotium rolfsii using cornmeal agar (CMA agar assayprocedure and the result showed that thirteen isolates have remarkable inhibiting the growth of the fungus and the top fiveantagonistic actinomycetes were PACCH 277, PACCH129, PACCH225, PACCH24 and PACCH246, respectively. The resultindicated that these actinomycetes produce chitinase which catalyze the degradation of chitin, resulting in inhibition of S.rolfsii growth. Their abilities to control the disease development were tested for in vivo biocontrol assay on chilli seedlings.Two out of thirteen candidate, PACCH24 and PACCH225, antagonists reduced the disease development at 90%. It wassuggested that the ability to inhibit the growth of pathogen in vitro was not related to the disease reduction in vivo. Thestrain PACCH24 was further identified as Streptomyces hygroscopicus according to morphological characteristic, cell walland cellular sugar analysis and 16S rDNA sequencing. The study implies a novel chitinolytic actinomycete which could bedeveloped to be a biological agent which would be included as a complement with organic fertilizers in order to control stemrot disease and promote growth of chilli.

  11. EVALUATION OF BIOLOGICAL EFFICACY OF TRICHODERMA SPECIES ISOLATES AGAINST ALTERNARIA LEAF SPOT DISEASE OF SESAME

    Directory of Open Access Journals (Sweden)

    A. S. Lubaina

    2015-03-01

    Full Text Available Alternaria leaf spot disease is a major threat to sesame (Sesamum orientale L. caused by Alternari asesami. Induced resistance is an alternative to systemic disease resistance response of plants. The present study aims to evaluate Trichoderma species efficacy as biocontrol via induction of resistance against A. sesami in sesame species. During in vitro bio control test, T. harzianum colonize and parallely inhibit the growth of the fungal pathogen. Expression of various defence related enzymes observed in sesame induce resistance against the pathogen infection in the host. T. harzianum coupled with inoculation of A. sesami enhance the remarkable induction of defence enzyme such as peroxidase (POX, polyphenol oxidase (PPO, phenylalanine ammonia lyase (PAL and also the phenolic content compared with the control. The enzyme activity increased from 48 h of sampling and peaked at 72 h and then decreased after 72 h. In greenhouse and field experiments, soil treatment with a powder formulation of T. harzianum two weeks before planting or at the time of planting reduced significantly the incidence of diseases on both the wild and cultivar Thilarani.The results demonstrate that T. harzianumcan be successfully applied as a biological control against Alternaria leaf spot disease in sesame.

  12. Disease control by chemical and biological fungicides in cultivated mushrooms: button mushroom, oyster mushroom and shiitake

    Directory of Open Access Journals (Sweden)

    Ivana Potočnik

    2015-12-01

    Full Text Available The most commonly cultivated basidiomycetes worldwide and in Serbia are button mushroom (Agaricus bisporus, oyster mushroom (Pleurotus sp. and shiitake (Lentinus edodes. Production of their fruiting bodies is severely afflicted by fungal, bacterial, and viral pathogens that are able to cause diseases which affect yield and quality. Major A. bisporus fungal pathogens include Mycogone perniciosa, Lecanicillium fungicola, and Cladobotryum spp., the causal agents of dry bubble, wet bubble, and cobweb disease, respectively. Various Trichoderma species, the causal agents of green mould, also affect all three kinds of edible mushrooms. Over the past two decades, green mould caused by T. aggressivum has been the most serious disease of button mushroom. Oyster mushroom is susceptible to T. pleurotum and shiitake to T. harzianum. The bacterial brawn blotch disease, caused by Pseudomonas tolaasii, is distributed globally. Disease control on mushroom farms worldwide is commonly based on the use of fungicides. However, evolution of pathogen resistance to fungicides after frequent application, and host sensitivity to fungicides are serious problems. Only a few fungicides are officially recommended in mushroom production: chlorothalonil and thiabendazol in North America and prochloraz in the EU and some other countries. Even though decreased sensitivity levels of L. fungicola and Cladobotryum mycophilum to prochloraz have been detected, disease control is still mainly provided by that chemical fungicide. Considering such resistance evolution, harmful impact to the environment and human health, special attention should be focused on biofungicides, both microbiological products based on Bacillus species and various natural substances of biological origin, together with good programs of hygiene. Introduction of biofungicides has created new possibilities for crop protection with reduced application of chemicals.

  13. Enhancement of biological control agents for use against forest insect pests and diseases through biotechnology

    Science.gov (United States)

    Slavicek, James M.

    1991-01-01

    Research and development efforts in our research group are focused on the generation of more efficacious biological control agents through the techniques of biotechnology for use against forest insect pests and diseases. Effective biological controls for the gypsy moth and for tree fungal wilt pathogens are under development. The successful use of Gypchek, a formulation of the Lymantria dispar nuclear polyhedrosis virus (LdNPV), in gypsy moth control programs has generated considerable interest in that agent. As a consequence of its specificity, LdPNV has negligible adverse ecological impacts compared to most gypsy moth control agents. However, LdNPV is not competitive with other control agents in terms of cost and efficacy. We are investigating several parameters of LdNPV replication and polyhedra production in order to enhance viral potency and efficacy thus mitigating the current disadvantages of LdNPV for gypsy moth control, and have identified LdNPV variants that will facilitate these efforts. Tree endophytic bacteria that synthesize antifungal compounds were identified and an antibiotic compound from one of these bacteria was characterized. The feasibility of developing tree endophytes as biological control agents for tree vascular fungal pathogens is being investigated.

  14. GeneWeaver: data driven alignment of cross-species genomics in biology and disease.

    Science.gov (United States)

    Baker, Erich; Bubier, Jason A; Reynolds, Timothy; Langston, Michael A; Chesler, Elissa J

    2016-01-01

    The GeneWeaver data and analytics website (www.geneweaver.org) is a publically available resource for storing, curating and analyzing sets of genes from heterogeneous data sources. The system enables discovery of relationships among genes, variants, traits, drugs, environments, anatomical structures and diseases implicitly found through gene set intersections. Since the previous review in the 2012 Nucleic Acids Research Database issue, GeneWeaver's underlying analytics platform has been enhanced, its number and variety of publically available gene set data sources has been increased, and its advanced search mechanisms have been expanded. In addition, its interface has been redesigned to take advantage of flexible web services, programmatic data access, and a refined data model for handling gene network data in addition to its original emphasis on gene set data. By enumerating the common and distinct biological molecules associated with all subsets of curated or user submitted groups of gene sets and gene networks, GeneWeaver empowers users with the ability to construct data driven descriptions of shared and unique biological processes, diseases and traits within and across species. PMID:26656951

  15. Protocatechuic acid and human disease prevention: biological activities and molecular mechanisms.

    Science.gov (United States)

    Masella, R; Santangelo, C; D'Archivio, M; Li Volti, G; Giovannini, C; Galvano, F

    2012-01-01

    Epidemiological evidence has shown that a high dietary intake of vegetables and fruit rich in polyphenols is associated with a reduction of cancer incidence and mortality from coronary heart disease. The healthy effects associated with polyphenol consumption have made the study of the mechanisms of action a matter of great importance. In particular, the hydroxybenzoic acid protocatechuic acid (PCA) has been eliciting a growing interest for several reasons. Firstly, PCA is one of the main metabolites of complex polyphenols such as anthocyanins and procyanidins that are normally found at high concentrations in vegetables and fruit, and are absorbed by animals and humans. Since the daily intake of anthocyanins has been estimated to be much higher than that of other polyphenols, the nutritional value of PCA is increasingly recognized. Secondly, a growing body of evidence supports the concept that PCA can exert a variety of biological effects by acting on different molecular targets. It has been shown that PCA possesses antioxidant, anti-inflammatory as well as antihyperglycemic and neuroprotective activities. Furthermore, PCA seems to have chemopreventive potential because it inhibits the in vitro chemical carcinogenesis and exerts pro-apoptotic and anti-proliferative effects in different tissues. This review is aimed at providing an up-dated and comprehensive report on PCA giving a special emphasis on its biological activities and the molecular mechanisms of action most likely responsible for a beneficial role in human disease prevention. PMID:22519395

  16. Modifiable factors associated with tuberculosis disease in children: a case-control study.

    Science.gov (United States)

    Franke, Molly F; del Castillo, Hernán; Pereda, Ynés; Lecca, Leonid; Cárdenas, Luz; Fuertes, Jhoelma; Murray, Megan B; Bayona, Jaime; Becerra, Mercedes C

    2014-01-01

    We conducted a case-control study among children in Lima, Peru to identify factors associated with tuberculosis disease. Known close contact with someone with tuberculosis disease, prior hospitalization, and history of anemia were associated with a higher tuberculosis disease rate. Consumption of fruits/vegetables ≥5 days/week was associated with a lower rate. Isoniazid uptake was low among children with a known contact. PMID:24064556

  17. Psychiatric and cognitive symptoms in Huntington's disease are modified by polymorphisms in catecholamine regulating enzyme genes

    DEFF Research Database (Denmark)

    Vinther-Jensen, T; Nielsen, T T; Budtz-Jørgensen, E;

    2016-01-01

    -described cohort of Danish HD gene-expansion carriers. We show that cognitive impairment and psychiatric symptoms in HD are modified by polymorphisms in the monoamine oxidase A (MAOA) and catechol-O-methyltransferase (COMT) genes and by the 4p16.3 B haplotype. These results support the theory of dopamine imbalance...

  18. Proposed draft permit guidance for genetically modified animal disease organisms and their vectors

    International Nuclear Information System (INIS)

    This paper consists of proposed draft guidance and represents the author's opinions only. They are presented below solely for the purpose of open discussion and comments on the subject of genetically modified arthropod regulations and should not be construed as representing actual or current regulations or opinions of the USDA, Animal and Plant Health Inspection Service (APHIS). (author)

  19. [QUALITY OF LIFE IN CARERS OF PATIENTS WITH MULTIPLE SCLEROSIS TAKING A DISEASE-MODIFYING MEDICATION: A PILOT STUDY].

    Science.gov (United States)

    Gigineishvili, D; Kiziria, M; Tsiskaridze, A; Shakarishvili, R

    2016-04-01

    A chronic physical disease not only has direct consequences for the chronically ill person but can also distort the life of the healthy family member. The aim of our study was to measure the health-related quality of life (QOL) in people caring for patients with relapsing-remitting form of multiple sclerosis (MS) and currently treated with disease-modifying drugs. Eligible patients were selected via Sarajishvili Institute of Neurology database for MS. 25 carers (mean age 40.7; 56% women, 56% partners) and 25 sex and age-matched controls completed 36-item Short Form Health Survey (SF-36), version 2. Carers also completed the Beck depression Inventory (BDI-II). Compared to carers, patients were found to have a lower QOL (P<0.05 for five dimensions). However, no significant difference was observed in SF-36 domains scores between carers and controls except general health score which was lower in carers (63.3 vs 75.6, p=0.016). A strong negative correlation was found between BDI and all SF-36 dimension scores of carers. The association remains unchanged even adjusted to carers other independent variables. Last year relapse rate was the only clinical variable correlated with carers QOL dimensions. Our pilot study demonstrated that QOL in carers of patients with relapsing-remitting MS receiving disease-modifying treatment is minimally affected. Further study with large sample size is warranted. PMID:27249435

  20. SCLC extensive disease – treatment guidance by extent or/and biology of response?

    International Nuclear Information System (INIS)

    In extensive disease of small cell lung cancer a doubling of the one-year-survival rate was reported in August 2007 by prophylactic cranial irradiation applied to patients who experienced any response to initial chemotherapy. We discuss the treatment concept of extensive disease in the face of the latest results and older studies with additional thoracic irradiation in this subgroup. A randomized trial with prophylactic cranial irradiation published in 1999 demonstrated an improvement of 5-year-overall-survival for complete responders (at least at distant levels) receiving additional thoracic radiochemotherapy compared to chemotherapy alone (9.1% vs. 3.7%). But, these results were almost neglected and thoracic radiotherapy was not further investigated for good responders of extensive disease. However, in the light of current advances by prophylactic cranial irradiation these findings are noteworthy on all accounts. Considering both, a possible interpretation of these data could be a survival benefit of local control by simultaneous thoracic radiochemotherapy in the case of improved distant control due to chemotherapy and prophylactic cranial irradiation. Furthermore the question arises whether the tumor biology indicated by the response to chemotherapy should be integrated in the present classification

  1. Interstitial Lung Disease in Rheumatoid Arthritis in the Era of Biologics

    Directory of Open Access Journals (Sweden)

    A. Picchianti Diamanti

    2011-01-01

    Full Text Available Interstitial lung disease (ILD represents a severe manifestation in connective tissue diseases (CTD, with an overall incidence of 15%, and it is still a challenge for clinicians evaluation and management. ILD is the most common manifestation of lung involvement in Rheumatoid Arthritis (RA, observed in up to 80% of biopsies, 50% of chest Computed Tomography (CT and only 5% of chest radiographs. Histopatological patterns of ILD in RA may present with different patterns, such as: usual interstitial pneumonia, non specific interstitial pneumonia, desquamative interstitial pneumonia, organizing pneumonia, and eosinophilic infiltration. The incidence of ILD in RA patients is not only related to the disease itself, many drugs may be in fact associated with the development of pulmonary damage. Some reports suggest a causative role for TNFα inhibitors in RA-ILD development/worsening, anyway, no definitive statement can be drawn thus data are incomplete and affected by several variables. A tight control (pulmonary function tests and/or HRCT is mandatory in patients with preexisting ILD, but it should be also performed in those presenting risk factors for ILD and mild respiratory symptoms. Biologic therapy should be interrupted, and, after excluding triggering infections, corticosteroids should be administered.

  2. Hdac6 knock-out increases tubulin acetylation but does not modify disease progression in the R6/2 mouse model of Huntington's disease.

    Directory of Open Access Journals (Sweden)

    Anna Bobrowska

    Full Text Available Huntington's disease (HD is a progressive neurodegenerative disorder for which there is no effective disease modifying treatment. Following-on from studies in HD animal models, histone deacetylase (HDAC inhibition has emerged as an attractive therapeutic option. In parallel, several reports have demonstrated a role for histone deacetylase 6 (HDAC6 in the modulation of the toxicity caused by the accumulation of misfolded proteins, including that of expanded polyglutamine in an N-terminal huntingtin fragment. An important role for HDAC6 in kinesin-1 dependent transport of brain-derived neurotrophic factor (BDNF from the cortex to the striatum has also been demonstrated. To elucidate the role that HDAC6 plays in HD progression, we evaluated the effects of the genetic depletion of HDAC6 in the R6/2 mouse model of HD. Loss of HDAC6 resulted in a marked increase in tubulin acetylation throughout the brain. Despite this, there was no effect on the onset and progression of a wide range of behavioural, physiological, molecular and pathological HD-related phenotypes. We observed no change in the aggregate load or in the levels of soluble mutant exon 1 transprotein. HDAC6 genetic depletion did not affect the efficiency of BDNF transport from the cortex to the striatum. Therefore, we conclude that HDAC6 inhibition does not modify disease progression in R6/2 mice and HDAC6 should not be prioritized as a therapeutic target for HD.

  3. A Mutation in DAOA Modifies the Age of Onset in PSEN1 E280A Alzheimer's Disease.

    Science.gov (United States)

    Vélez, Jorge I; Rivera, Dora; Mastronardi, Claudio A; Patel, Hardip R; Tobón, Carlos; Villegas, Andrés; Cai, Yeping; Easteal, Simon; Lopera, Francisco; Arcos-Burgos, Mauricio

    2016-01-01

    We previously reported age of onset (AOO) modifier genes in the world's largest pedigree segregating early-onset Alzheimer's disease (AD), caused by the p.Glu280Ala (E280A) mutation in the PSEN1 gene. Here we report the results of a targeted analysis of functional exonic variants in those AOO modifier genes in sixty individuals with PSEN1 E280A AD who were whole-exome genotyped for ~250,000 variants. Standard quality control, filtering, and annotation for functional variants were applied, and common functional variants located in those previously reported as AOO modifier loci were selected. Multiloci linear mixed-effects models were used to test the association between these variants and AOO. An exonic missense mutation in the G72 (DAOA) gene (rs2391191, P = 1.94 × 10(-4), P FDR = 9.34 × 10(-3)) was found to modify AOO in PSEN1 E280A AD. Nominal associations of missense mutations in the CLUAP1 (rs9790, P = 7.63 × 10(-3), P FDR = 0.1832) and EXOC2 (rs17136239, P = 0.0325, P FDR = 0.391) genes were also found. Previous studies have linked polymorphisms in the DAOA gene with the occurrence of neuropsychiatric symptoms such as depression, apathy, aggression, delusions, hallucinations, and psychosis in AD. Our findings strongly suggest that this new conspicuous functional AOO modifier within the G72 (DAOA) gene could be pivotal for understanding the genetic basis of AD. PMID:26949549

  4. A Mutation in DAOA Modifies the Age of Onset in PSEN1 E280A Alzheimer’s Disease

    Directory of Open Access Journals (Sweden)

    Jorge I. Vélez

    2016-01-01

    Full Text Available We previously reported age of onset (AOO modifier genes in the world’s largest pedigree segregating early-onset Alzheimer’s disease (AD, caused by the p.Glu280Ala (E280A mutation in the PSEN1 gene. Here we report the results of a targeted analysis of functional exonic variants in those AOO modifier genes in sixty individuals with PSEN1 E280A AD who were whole-exome genotyped for ~250,000 variants. Standard quality control, filtering, and annotation for functional variants were applied, and common functional variants located in those previously reported as AOO modifier loci were selected. Multiloci linear mixed-effects models were used to test the association between these variants and AOO. An exonic missense mutation in the G72 (DAOA gene (rs2391191, P = 1.94 × 10−4, PFDR = 9.34 × 10−3 was found to modify AOO in PSEN1 E280A AD. Nominal associations of missense mutations in the CLUAP1 (rs9790, P = 7.63 × 10−3, PFDR = 0.1832 and EXOC2 (rs17136239, P = 0.0325, PFDR = 0.391 genes were also found. Previous studies have linked polymorphisms in the DAOA gene with the occurrence of neuropsychiatric symptoms such as depression, apathy, aggression, delusions, hallucinations, and psychosis in AD. Our findings strongly suggest that this new conspicuous functional AOO modifier within the G72 (DAOA gene could be pivotal for understanding the genetic basis of AD.

  5. Mast cells are important modifiers of autoimmune disease: With so much evidence, why is there controversy?

    Directory of Open Access Journals (Sweden)

    Melissa Ann Brown

    2012-06-01

    Full Text Available There is abundant evidence that mast cells are active participants in events that mediate tissue damage in autoimmune disease. Disease-associated increases in mast cell numbers accompanied by mast cell degranulation and elaboration of numerous mast cell mediators at sites of inflammation are commonly observed in many human autoimmune diseases including multiple sclerosis, rheumatoid arthritis and bullous pemphigoid. In animal models, treatment with mast cell stabilizing drugs or mast cell ablation can result in diminished disease. A variety of receptors including those engaged by antibody, complement, pathogens and intrinsic danger signals are implicated in mast cell activation in disease. Similar to their role as first responders in infection settings, mast cells likely orchestrate early recruitment of immune cells, including neutrophils, to the sites of autoimmune destruction. This co-localization promotes cellular crosstalk and activation and results in the amplification of the local inflammatory response thereby promoting and sustaining tissue damage. Despite the evidence, there is still a debate regarding the relative role of mast cells in these processes. However, by definition, mast cells can only act as accessory cells to the self-reactive T and/or antibody driven autoimmune responses. Thus, when evaluating mast cell involvement using existing and somewhat imperfect animal models of disease, their importance is sometimes obscured. However, these potent immune cells are undoubtedly major contributors to autoimmunity and should be considered as important targets for therapeutic disease intervention.

  6. [Gender and kidney diseases: the clinical importance and mechanisms of modifying effects].

    Science.gov (United States)

    Grzegorczyk, Katarzyna; Krajewska, Magdalena; Weyde, Wacław; Jakuszko, Katarzyna; Gniewek, Andrzej; Klinger, Marian

    2011-01-01

    This review focuses on the underlying pathways of gender-dependent renal diseases and presents specific examples of diseases influenced by gender. In the literature it has been shown, in many clinical and experimental observations, that the incidence and the rate of progression of renal disease are influenced by many gender-dependent factors, such as kidney and glomerular size, differences in glomerular hemodynamics, and direct effects of sex hormones on renal tissue and signal pathways such as the renin-angiotensin-aldosterone system and signal molecules (e.g. nitric oxide, reactive oxygen species, cytokines and growth factors). It has been shown that the main female hormone, 17 β estradiol, is capable of inhibiting inflammatory and pro apoptotic processes and protects the renal tissue. In contrast, the male hormones, testosterone and dehydroepiandrosterone, have the opposite effect. Hormonal manipulation by male or female castration changes the course of renal disease progression and confirms the influence of the sex hormones. Female gender is therefore considered a protective factor in many kidney diseases, such as primary glomerulonephritis, autosomal dominant polycystic kidney disease (ADPKD) and hypertensive nephropathy. Similarly, women are more predisposed to autoimmune diseases with secondary glomerulonephritis, e.g. systemic lupus erythematosus, as the female sex hormones have the ability of autoimmune process activation. After menopause the protective effect of female gender is not observed, which confirms the role of the female sex hormones. PMID:22204762

  7. Gender and kidney diseases: the clinical importance and mechanisms of modifying effects

    Directory of Open Access Journals (Sweden)

    Katarzyna Grzegorczyk

    2011-12-01

    Full Text Available This review focuses on the underlying pathways of gender-dependent renal diseases and presents specific examples of diseases influenced by gender. In the literature it has been shown, in many clinical and experimental observations, that the incidence and the rate of progression of renal disease are influenced by many gender-dependent factors, such as kidney and glomerular size, differences in glomerular hemodynamics, and direct effects of sex hormones on renal tissue and signal pathways such as the renin-angiotensin-aldosterone system and signal molecules (e.g. nitric oxide, reactive oxygen species, cytokines and growth factors. It has been shown that the main female hormone, 17 β estradiol, is capable of inhibiting inflammatory and pro apoptotic processes and protects the renal tissue. In contrast, the male hormones, testosterone and dehydroepiandrosterone, have the opposite effect. Hormonal manipulation by male or female castration changes the course of renal disease progression and confirms the influence of the sex hormones. Female gender is therefore considered a protective factor in many kidney diseases, such as primary glomerulonephritis, autosomal dominant polycystic kidney disease (ADPKD and hypertensive nephropathy. Similarly, women are more predisposed to autoimmune diseases with secondary glomerulonephritis, e.g. systemic lupus erythematosus, as the female sex hormones have the ability of autoimmune process activation. After menopause the protective effect of female gender is not observed, which confirms the role of the female sex hormones.

  8. Ecological interactions between herbivores and silver birch and aspen trees genetically modified for fungal disease resistance

    OpenAIRE

    Vihervuori , Liisa

    2015-01-01

    Many risks and environmental concerns have been linked with the cultivation of genetically modified (GM) trees. Among the most frequently mentioned risks are the unintentional/pleiotropic effects of transgenes on organisms or plant properties that are not the targets of genetic modification. Risks in forest ecosystems are difficult to predict, due to the long life cycles of trees and their complex ecological interactions. This thesis is focused on the interactions between insect and mammal he...

  9. Frontiers in the bioarchaeology of stress and disease: cross-disciplinary perspectives from pathophysiology, human biology, and epidemiology.

    Science.gov (United States)

    Klaus, Haagen D

    2014-10-01

    Over the last four decades, bioarchaeology has experienced significant technical growth and theoretical maturation. Early 21st century bioarchaeology may also be enhanced from a renewed engagement with the concept of biological stress. New insights on biological stress and disease can be gained from cross-disciplinary perspectives regarding human skeletal variation and disease. First, pathophysiologic and molecular signaling mechanisms can provide more precise understandings regarding formation of pathological phenotypes in bone. Using periosteal new bone formation as an example, various mechanisms and pathways are explored in which new bone can be formed under conditions of biological stress, particularly in bone microenvironments that involve inflammatory changes. Second, insights from human biology are examined regarding some epigenetic factors and disease etiology. While epigenetic effects on stress and disease outcomes appear profoundly influential, they are mostly invisible in skeletal tissue. However, some indirect and downstream effects, such as the developmental origins of adult health outcomes, may be partially observable in bioarchaeological data. Emerging perspectives from the human microbiome are also considered. Microbiomics involves a remarkable potential to understand ancient biology, disease, and stress. Third, tools from epidemiology are examined that may aid bioarchaeologists to better cope with some of the inherent limitations of skeletal samples to better measure and quantify the expressions of skeletal stress markers. Such cross-disciplinary synergisms hopefully will promote more complete understandings of health and stress in bioarchaeological science. PMID:25082158

  10. Efficacy of fingolimod is superior to injectable disease modifying therapies in second-line therapy of relapsing remitting multiple sclerosis

    OpenAIRE

    Braune, Stefan; Lang, M.; Bergmann, A; ,

    2015-01-01

    Although fingolimod is registered in Europe for treatment of relapsing-remitting multiple sclerosis (RRMS) if earlier disease modifying therapy (DMT) has failed, no data regarding its efficacy in this patient group are available. This observational cohort study of the NeuroTransData network includes German RRMS outpatients with failure of earlier therapy with injectable DMT (iDMT), therefore switching to either another iDMT (n = 133) or to fingolimod (n = 300). Statistical comparison of clini...

  11. Endothelin 1 gene is not a major modifier of chronic kidney disease advancement among the autosomal dominant polycystic kidney disease patients

    Directory of Open Access Journals (Sweden)

    Annapareddy Shiva Nagendra Reddy

    2016-01-01

    Full Text Available Introduction: Autosomal dominant polycystic kidney disease (ADPKD is characterized by the presence of numerous cysts in the kidney and manifest with various renal and extra-renal complications leading to ESRD. Endothelin may contribute to various renal and extra-renal manifestations pointing to genetic and environmental modifying factors that alter the risk of developing chronic kidney disease (CKD in ADPKD. In the present study we investigated six genes coding for endothelin 1 (EDN1 tagging-single nucleotide polymorphisms (tag-SNPs to unravel the EDN1 gene modifier effect for renal disease progression in ADPKD. Materials and Methods: The tag-SNPs were genotyped using FRET-based KASPar method in 108 ADPKD patients and 119 healthy subjects. Cochran-Armitage trend test was used to determine the association between ADPKD and EDN1 tag-SNPs. Multivariate logistic regression analysis was performed to assess the effect of tag-SNPs on CKD progression. The relationship between different CKD stages and hypertension and their interaction Mantel-Haenszel stratified analysis was performed. Results: All loci are polymorphic and followed Hardy-Weinberg equilibrium. Distribution of EDN1 genotypes and haplotypes in control and ADPKD is not statistically significant. Five SNPs covering 3.4 kb forming single LD block, but the LD was not strong between SNPs. The EDN1 genotypes are not contributing to the CKD advancement among the ADPKD patients. Conclusion: These results suggest that the EDN1 gene is not a major modifier of CKD advancement among ADPKD patients.

  12. Cell biology and genetics of minimal change disease [version 1; referees: 2 approved

    Directory of Open Access Journals (Sweden)

    Moin A. Saleem

    2016-03-01

    Full Text Available Minimal change disease (MCD is an important cause of nephrotic syndrome and is characterized by massive proteinuria and hypoalbuminemia, resulting in edema and hypercholesterolemia. The podocyte plays a key role in filtration and its disruption results in a dramatic loss of function leading to proteinuria. Immunologic disturbance has been suggested in the pathogenesis of MCD. Because of its clinical features, such as recurrent relapse/remission course, steroid response in most patients, and rare familial cases, a genetic defect has been thought to be less likely in MCD. Recent progress in whole-exome sequencing reveals pathogenic mutations in familial cases in steroid-sensitive nephrotic syndrome (SSNS and sheds light on possible mechanisms and key molecules in podocytes in MCD. On the other hand, in the majority of cases, the existence of circulating permeability factors has been implicated along with T lymphocyte dysfunction. Observations of benefit with rituximab added B cell involvement to the disease. Animal models are unsatisfactory, and the humanized mouse may be a good model that well reflects MCD pathophysiology to investigate suggested “T cell dysfunction” directly related to podocytes in vivo. Several candidate circulating factors and their effects on podocytes have been proposed but are still not sufficient to explain whole mechanisms and clinical features in MCD. Another circulating factor disease is focal segmental glomerulosclerosis (FSGS, and it is not clear if this is a distinct entity, or on the same spectrum, implicating the same circulating factor(s. These patients are mostly steroid resistant and often have a rapid relapse after transplantation. In clinical practice, predicting relapse or disease activity and response to steroids is important and is an area where novel biomarkers can be developed based on our growing knowledge of podocyte signaling pathways. In this review, we discuss recent findings in genetics and

  13. Biological markers of amyloid beta-related mechanisms in Alzheimer's disease.

    LENUS (Irish Health Repository)

    Hampel, Harald

    2010-06-01

    Recent research progress has given detailed knowledge on the molecular pathogenesis of Alzheimer\\'s disease (AD), which has been translated into an intense, ongoing development of disease-modifying treatments. Most new drug candidates are targeted on inhibiting amyloid beta (Abeta) production and aggregation. In drug development, it is important to co-develop biomarkers for Abeta-related mechanisms to enable early diagnosis and patient stratification in clinical trials, and to serve as tools to identify and monitor the biochemical effect of the drug directly in patients. Biomarkers are also requested by regulatory authorities to serve as safety measurements. Molecular aberrations in the AD brain are reflected in the cerebrospinal fluid (CSF). Core CSF biomarkers include Abeta isoforms (Abeta40\\/Abeta42), soluble APP isoforms, Abeta oligomers and beta-site APP-cleaving enzyme 1 (BACE1). This article reviews recent research advances on core candidate CSF and plasma Abeta-related biomarkers, and gives a conceptual review on how to implement biomarkers in clinical trials in AD.

  14. Biological markers of amyloid beta-related mechanisms in Alzheimer's disease.

    LENUS (Irish Health Repository)

    Hampel, Harald

    2012-02-01

    Recent research progress has given detailed knowledge on the molecular pathogenesis of Alzheimer\\'s disease (AD), which has been translated into an intense, ongoing development of disease-modifying treatments. Most new drug candidates are targeted on inhibiting amyloid beta (Abeta) production and aggregation. In drug development, it is important to co-develop biomarkers for Abeta-related mechanisms to enable early diagnosis and patient stratification in clinical trials, and to serve as tools to identify and monitor the biochemical effect of the drug directly in patients. Biomarkers are also requested by regulatory authorities to serve as safety measurements. Molecular aberrations in the AD brain are reflected in the cerebrospinal fluid (CSF). Core CSF biomarkers include Abeta isoforms (Abeta40\\/Abeta42), soluble APP isoforms, Abeta oligomers and beta-site APP-cleaving enzyme 1 (BACE1). This article reviews recent research advances on core candidate CSF and plasma Abeta-related biomarkers, and gives a conceptual review on how to implement biomarkers in clinical trials in AD.

  15. A Journey with Elie Metchnikoff: From Innate Cell Mechanisms in Infectious Diseases to Quantum Biology

    Science.gov (United States)

    Merien, Fabrice

    2016-01-01

    Many reviews of Elie Metchnikoff’s work have been published, all unanimously acknowledging the significant contributions of his cellular theory to the fields of immunology and infectious diseases. In 1883, he published a key paper describing phagocytic cells in frogs. His descriptions were not just about phagocytes involved in host defense, he also described how these specialized cells eliminated degenerating or dying cells of the host. This perspective focuses on key concepts developed by Metchnikoff by presenting relevant excerpts of his 1883 paper and matching these concepts with challenges of modern immunology. A new approach to macrophage polarization is included to introduce some creative thinking about the exciting emerging area of quantum biology. PMID:27379227

  16. Use of biological molecules in the treatment of inflammatory bowel disease

    DEFF Research Database (Denmark)

    Nielsen, O H; Seidelin, J B; Munck, Lena;

    2011-01-01

    CD. However, many questions still remain about the true efficacy and the best treatment regimens. Thus, a need for further treatment options still exists as up to 40% of IBD patients treated with the presently available biologicals do not have positive clinical responses. Better patient selection...... might maximize the clinical benefit for those in most need of an effective therapy to avoid disabling disease whilst also minimizing the complications associated with therapy. Further, the 'trough-level strategy' may help clinicians to optimize therapy and to avoid loss of response and/or immunogenicity....... The idea behind this dosage regimen is that correct dosing must ensure that the patient's lowest level of drug concentration (i.e. the trough level) occurring just before the next drug administration is high enough for the full effect to be seen. Controversy continues regarding the appropriate use of...

  17. Biological characterization of a serotype 1 Marek’s disease virus-vectored Bi-valent 4 vaccine for infectious laryngotracheitis and Marek’s disease

    Science.gov (United States)

    Laryngotracheitis (LT) is a highly contagious respiratory disease of chickens that produces significant economic losses to the poultry industry. Traditionally LT has been controlled by administration of modified live vaccines. In recent years, the use of recombinant DNA-derived vaccines using turkey...

  18. Mycobacterium avium subsp. Paratuberculosis (MAP) as a modifying factor in Crohn's disease.

    LENUS (Irish Health Repository)

    Sibartie, Shomik

    2010-02-01

    Crohn\\'s disease (CD) is a multifactorial syndrome with genetic and environmental contributions. Mycobacterium avium subspecies paratuberculosis (MAP) has been frequently isolated from mucosal tissues of patients with CD but the cellular immune response to this bacterium has been poorly described. Our aim was to examine the influence of MAP on T-cell proliferation and cytokine responses in patients with inflammatory bowel disease (IBD).

  19. Grunting in genetically modified minipig animal model for Huntington ´s disease - a pilot experiment

    Czech Academy of Sciences Publication Activity Database

    Tykalová, T.; Hlavnička, J.; Mačáková, Monika; Baxa, Monika; Cmejla, R.; Motlík, Jan; Klempíř, J.; Rusz, J.

    2015-01-01

    Roč. 78, Suppl 2 (2015), s. 12-13. ISSN 1210-7859. [Conference on Animal Models for neurodegenerative Diseases /3./. 08.11.2015-10.11.2015, Liblice] R&D Projects: GA MŠk ED2.1.00/03.0124; GA MŠk(CZ) 7F14308 Institutional support: RVO:67985904 Keywords : Huntington´s disease * mitochondria * DNA damage Subject RIV: FH - Neurology

  20. A Novel Approach to Delayed-Start Analyses for Demonstrating Disease-Modifying Effects in Alzheimer’s Disease

    OpenAIRE

    Liu-Seifert, Hong; Andersen, Scott W.; Lipkovich, Ilya; Holdridge, Karen C.; Siemers, Eric

    2015-01-01

    One method for demonstrating disease modification is a delayed-start design, consisting of a placebo-controlled period followed by a delayed-start period wherein all patients receive active treatment. To address methodological issues in previous delayed-start approaches, we propose a new method that is robust across conditions of drug effect, discontinuation rates, and missing data mechanisms. We propose a modeling approach and test procedure to test the hypothesis of noninferiority, comparin...

  1. Genetic analysis for a shared biological basis between migraine and coronary artery disease

    Science.gov (United States)

    Winsvold, Bendik S.; Nelson, Christopher P.; Malik, Rainer; Gormley, Padhraig; Anttila, Verneri; Vander Heiden, Jason; Elliott, Katherine S.; Jacobsen, Line M.; Palta, Priit; Amin, Najaf; de Vries, Boukje; Hämäläinen, Eija; Freilinger, Tobias; Ikram, M. Arfan; Kessler, Thorsten; Koiranen, Markku; Ligthart, Lannie; McMahon, George; Pedersen, Linda M.; Willenborg, Christina; Won, Hong-Hee; Olesen, Jes; Artto, Ville; Assimes, Themistocles L.; Blankenberg, Stefan; Boomsma, Dorret I.; Cherkas, Lynn; Davey Smith, George; Epstein, Stephen E.; Erdmann, Jeanette; Ferrari, Michel D.; Göbel, Hartmut; Hall, Alistair S.; Jarvelin, Marjo-Riitta; Kallela, Mikko; Kaprio, Jaakko; Kathiresan, Sekar; Lehtimäki, Terho; McPherson, Ruth; März, Winfried; Nyholt, Dale R.; O'Donnell, Christopher J.; Quaye, Lydia; Rader, Daniel J.; Raitakari, Olli; Roberts, Robert; Schunkert, Heribert; Schürks, Markus; Stewart, Alexandre F.R.; Terwindt, Gisela M.; Thorsteinsdottir, Unnur; van den Maagdenberg, Arn M.J.M.; van Duijn, Cornelia; Wessman, Maija; Kurth, Tobias; Kubisch, Christian; Dichgans, Martin; Chasman, Daniel I.; Cotsapas, Chris; Zwart, John-Anker; Samani, Nilesh J.

    2015-01-01

    Objective: To apply genetic analysis of genome-wide association data to study the extent and nature of a shared biological basis between migraine and coronary artery disease (CAD). Methods: Four separate methods for cross-phenotype genetic analysis were applied on data from 2 large-scale genome-wide association studies of migraine (19,981 cases, 56,667 controls) and CAD (21,076 cases, 63,014 controls). The first 2 methods quantified the extent of overlapping risk variants and assessed the load of CAD risk loci in migraineurs. Genomic regions of shared risk were then identified by analysis of covariance patterns between the 2 phenotypes and by querying known genome-wide significant loci. Results: We found a significant overlap of genetic risk loci for migraine and CAD. When stratified by migraine subtype, this was limited to migraine without aura, and the overlap was protective in that patients with migraine had a lower load of CAD risk alleles than controls. Genes indicated by 16 shared risk loci point to mechanisms with potential roles in migraine pathogenesis and CAD, including endothelial dysfunction (PHACTR1) and insulin homeostasis (GIP). Conclusions: The results suggest that shared biological processes contribute to risk of migraine and CAD, but surprisingly this commonality is restricted to migraine without aura and the impact is in opposite directions. Understanding the mechanisms underlying these processes and their opposite relationship to migraine and CAD may improve our understanding of both disorders. PMID:27066539

  2. Laccase on Black Pearl 2000 modified glassy carbon electrode: Characterization of direct electron transfer and biological sensing properties for pyrocatechol

    International Nuclear Information System (INIS)

    Highlights: ► Laccase can complete direct electron transfer process on BP2000 matrices. ► Laccase immobilized on BP2000 matrices has catalytic oxidation effect to pyrocatechol. ► A pyrocatechol biosensor has constructed been using Nafion/Lac-BP2000/GC electrode. ► Detection limit and linear range of the biosensor are 0.003 mM and 0.003–5.555 mM. - Abstract: In this paper, it was found that Laccase (Lac) could be stably immobilized on the glassy carbon electrode modified with Black Pearl 2000 (BP2000) and Nafion by a simple technique. The adsorption behavior of Lac immobilized on BP2000 matrix was characterized by environment scanning electron microscope (ESEM), ultraviolet–visible (UV–vis) and Fourier transform infrared (FTIR), which demonstrated that BP2000 could facilitate the electron exchange between the active center of Lac and modified electrode. The direct electrochemistry and electrocatalysis behavior of Lac on the modified electrode were characterized by cyclic voltammogram (CV) which indicated that Lac immobilized on the modified electrode displayed a direct, nearly reversible and surface-controlled redox reaction with an enhanced electron-transfer rate constant of 1.940 s−1 at the scan rate of 100 mV s−1 in 0.1 M phosphate buffer solution (PBS) (pH 7.0). Furthermore, it was also discovered that, in the presence of O2, Lac immobilized on the modified electrode exhibited the electrocatalytic response to pyrocatechol, and the kinetic apparent Michaelis-constant (KMapp) obtained from the Lineweaver–Burk equation was 1.79 mM. The detection limit, linear range and sensitivity of the Lac biosensor were 0.003 mM, 0.003–5.555 mM and 99.84 μA mM−1 cm−2, respectively.

  3. A simple epidemiological model for populations in the wild with Allee effects and disease-modified fitness.

    Science.gov (United States)

    Kang, Yun; Castillo-Chavez, Carlos

    2014-01-01

    further conclude that increases in (a) the Allee effect threshold, or (b) in disease transmission rates, or in (c) the competitive ability of infected individuals at high density levels, can destabilize the system, possibly leading to the eventual collapse of the population. The results obtained from the analyses of this toy model highlight the significant role that factors like an Allee effect may play on the survival and persistence of animal populations. Scientists involved in biological conservation and pest management or interested in finding sustainability solutions, may find these results of this study compelling enough to suggest additional focused research on the role of disease in the regulation and persistence of animal populations. The risk faced by endangered species may turn out to be a lot higher than initially thought. PMID:24817831

  4. Nimesulide improves the symptomatic and disease modifying effects of leflunomide in collagen induced arthritis.

    Directory of Open Access Journals (Sweden)

    Ahmed M Al-Abd

    Full Text Available Nimesulide is a COX-2 inhibitor used for symptomatic relief of rheumatoid arthritis. Leflunomide is an anti-pyrimidine used to manage the progression of rheumatoid arthritis. Herein we studied the influence of nimesulide and leflunomide combination in terms of disease symptoms and progression using collagen-induced arthritis model in mice, as a model for rheumatoid arthritis. Collagen induced arthritis was induced by immunization with type II collagen. Assessment of joint stiffness and articular hyperalgesia were evaluated using a locomotor activity cage and the Hargreaves method, respectively. Disease progression was assessed via arthritic index scoring, X-ray imaging, myeloperoxidase enzyme activity and histopathologic examination. Nimesulide induced only transient symptomatic alleviation on the top of decreased leucocytic infiltration compared to arthritis group. However, nimesulide alone failed to induce any significant improvement in the radiological or pathological disease progression. Leflunomide alone moderately alleviates the symptoms of arthritis and moderately retarded the radiological and pathological disease progression. Combination of nimesulide and leflunomide significantly improved symptomatic (analgesia and joint stiffness and arthritic disease progression (radiological, pathological and Myeloperoxidase enzyme activity in collagen induced arthritis animal model.

  5. Obesity, Exercise, Obstructive Sleep Apnea, and Modifiable Atherosclerotic Cardiovascular Disease Risk Factors in Atrial Fibrillation.

    Science.gov (United States)

    Miller, Jared D; Aronis, Konstantinos N; Chrispin, Jonathan; Patil, Kaustubha D; Marine, Joseph E; Martin, Seth S; Blaha, Michael J; Blumenthal, Roger S; Calkins, Hugh

    2015-12-29

    Classically, the 3 pillars of atrial fibrillation (AF) management have included anticoagulation for prevention of thromboembolism, rhythm control, and rate control. In both prevention and management of AF, a growing body of evidence supports an increased role for comprehensive cardiac risk factor modification (RFM), herein defined as management of traditional modifiable cardiac risk factors, weight loss, and exercise. In this narrative review, we summarize the evidence demonstrating the importance of each facet of RFM in AF prevention and therapy. Additionally, we review emerging data on the importance of weight loss and cardiovascular exercise in prevention and management of AF. PMID:26718677

  6. Leveraging existing data sets to generate new insights into Alzheimer's disease biology in specific patient subsets.

    Science.gov (United States)

    Fowler, Kevin D; Funt, Jason M; Artyomov, Maxim N; Zeskind, Benjamin; Kolitz, Sarah E; Towfic, Fadi

    2015-01-01

    To generate new insights into the biology of Alzheimer's Disease (AD), we developed methods to combine and reuse a wide variety of existing data sets in new ways. We first identified genes consistently associated with AD in each of four separate expression studies, and confirmed this result using a fifth study. We next developed algorithms to search hundreds of thousands of Gene Expression Omnibus (GEO) data sets, identifying a link between an AD-associated gene (NEUROD6) and gender. We therefore stratified patients by gender along with APOE4 status, and analyzed multiple SNP data sets to identify variants associated with AD. SNPs in either the region of NEUROD6 or SNAP25 were significantly associated with AD, in APOE4+ females and APOE4+ males, respectively. We developed algorithms to search Connectivity Map (CMAP) data for medicines that modulate AD-associated genes, identifying hypotheses that warrant further investigation for treating specific AD patient subsets. In contrast to other methods, this approach focused on integrating multiple gene expression datasets across platforms in order to achieve a robust intersection of disease-affected genes, and then leveraging these results in combination with genetic studies in order to prioritize potential genes for targeted therapy. PMID:26395074

  7. Non-random distribution of homo-repeats: links with biological functions and human diseases.

    Science.gov (United States)

    Lobanov, Michail Yu; Klus, Petr; Sokolovsky, Igor V; Tartaglia, Gian Gaetano; Galzitskaya, Oxana V

    2016-01-01

    The biological function of multiple repetitions of single amino acids, or homo-repeats, is largely unknown, but their occurrence in proteins has been associated with more than 20 hereditary diseases. Analysing 122 bacterial and eukaryotic genomes, we observed that the number of proteins containing homo-repeats is significantly larger than expected from theoretical estimates. Analysis of statistical significance indicates that the minimal size of homo-repeats varies with amino acid type and proteome. In an attempt to characterize proteins harbouring long homo-repeats, we found that those containing polar or small amino acids S, P, H, E, D, K, Q and N are enriched in structural disorder as well as protein- and RNA-interactions. We observed that E, S, Q, G, L, P, D, A and H homo-repeats are strongly linked with occurrence in human diseases. Moreover, S, E, P, A, Q, D and T homo-repeats are significantly enriched in neuronal proteins associated with autism and other disorders. We release a webserver for further exploration of homo-repeats occurrence in human pathology at http://bioinfo.protres.ru/hradis/. PMID:27256590

  8. The Association of Smoking and Surgery in Inflammatory Bowel Disease is Modified by Age at Diagnosis

    Science.gov (United States)

    Frolkis, Alexandra D; de Bruyn, Jennifer; Jette, Nathalie; Lowerison, Mark; Engbers, Jordan; Ghali, William; Lewis, James D; Vallerand, Isabelle; Patten, Scott; Eksteen, Bertus; Barnabe, Cheryl; Panaccione, Remo; Ghosh, Subrata; Wiebe, Samuel; Kaplan, Gilaad G

    2016-01-01

    Objectives: We assessed the association of smoking at diagnosis of inflammatory bowel disease (IBD) on the need for an intestinal resection. Methods: The Health Improvement Network was used to identify an inception cohort of Crohn's disease (n=1519) and ulcerative colitis (n=3600) patients from 1999–2009. Poisson regression explored temporal trends for the proportion of newly diagnosed IBD patients who never smoked before their diagnosis and the risk of surgery within 3 years of diagnosis. Cox proportional hazard models assessed the association between smoking and surgery, and effect modification was explored for age at diagnosis. Results: The rate of never smokers increased by 3% per year for newly diagnosed Crohn's disease patients (incidence rate ratio (IRR) 1.03; 95% confidence interval (CI): 1.02–1.05), but not for ulcerative colitis. The rate of surgery decreased among Crohn's disease patients aged 17–40 years (IRR 0.96; 95% CI: 0.93–0.98), but not for ulcerative colitis. Smoking at diagnosis increased the risk of surgery for Crohn's disease patients diagnosed after the age of 40 (hazard ratio (HR) 2.99; 95% CI: 1.52–5.92), but not for those diagnosed before age 40. Ulcerative colitis patients diagnosed between the ages of 17 and 40 years and who quit smoking before their diagnosis were more likely to undergo a colectomy (ex-smoker vs. never smoker: HR 1.66; 95% CI: 1.04–2.66). The age-specific findings were consistent across sensitivity analyses for Crohn's disease, but not ulcerative colitis. Conclusions: In this study, the association of smoking and surgical resection was dependent on the age at diagnosis of IBD. PMID:27101004

  9. Evidence for three loci modifying age-at-onset of Alzheimer's disease in early-onset PSEN2 families.

    Science.gov (United States)

    Marchani, Elizabeth E; Bird, Thomas D; Steinbart, Ellen J; Rosenthal, Elisabeth; Yu, Chang-En; Schellenberg, Gerard D; Wijsman, Ellen M

    2010-07-01

    Families with early-onset Alzheimer's disease (AD) sharing a single PSEN2 mutation exhibit a wide range of age-at-onset, suggesting that modifier loci segregate within these families. While APOE is known to be an age-at-onset modifier, it does not explain all of this variation. We performed a genome scan within nine such families for loci influencing age-at-onset, while simultaneously controlling for variation in the primary PSEN2 mutation (N141I) and APOE. We found significant evidence of linkage between age-at-onset and chromosome 1q23.3 (P 17p13.2 (P = 0.0002), 7q33 (P = 0.017), and 11p14.2 (P = 0.017) in a single large pedigree. Simultaneous analysis of these four chromosomes maintained strong evidence of linkage to chromosomes 1q23.3 and 17p13.2 when all families were analyzed, and to chromosomes 1q23.3, 7q33, and 17p13.2 within the same single pedigree. Inclusion of major gene covariates proved essential to detect these linkage signals, as all linkage signals dissipated when PSEN2 and APOE were excluded from the model. The four chromosomal regions with evidence of linkage all coincide with previous linkage signals, associated SNPs, and/or candidate genes identified in independent AD study populations. This study establishes several candidate regions for further analysis and is consistent with an oligogenic model of AD risk and age-at-onset. More generally, this study also demonstrates the value of searching for modifier loci in existing datasets previously used to identify primary causal variants for complex disease traits. PMID:20333730

  10. Simultaneous determination of cysteamine and folic acid in pharmaceutical and biological samples using modified multiwall carbon nanotube paste electrode

    Institute of Scientific and Technical Information of China (English)

    Ali Taherkhani; Hassan Karimi-Maleh; Ali A.Ensafi; Hadi Beitollahi; Ahmad Hosseini; Mohammad A.Khalilzadeh; Hassan Bagheri

    2012-01-01

    A carbon paste electrode (CPE) chemically modified with multiwall carbon nanotubes and ferrocene (FC) was used as a selective electrochemical sensor for the simultaneous determination of trace amounts of cysteamine (CA) and folic acid (FA).This modified electrode showed very efficient electrocatalytic activity for the anodic oxidation of CA.The peak current of differential pulse voltammograms of CA and FA increased linearly with their concentration in the ranges of 0.7-200 μmol/L CA and 5.0-700 μmol/L FA.The detection limits for CA and FA were 0.3 μmol/L and 2.0 μ mol/L,respectively.The diffusion coefficient (D) and transfer coefficient (α) of CA were also determined.These conditions are sufficient to allow determination of CA and FA both individually and simultaneously.

  11. Nutritional Systems Biology

    DEFF Research Database (Denmark)

    Jensen, Kasper

    and network biology has the potential to increase our understanding of how small molecules affect metabolic pathways and homeostasis, how this perturbation changes at the disease state, and to what extent individual genotypes contribute to this. A fruitful strategy in approaching and exploring the field...... biology research. The paper also shows as a proof-of-concept that a systems biology approach to diet is meaningful and demonstrates some basic principles on how to work with diet systematic. The second chapter of this thesis we developed the resource NutriChem v1.0. A foodchemical database linking...... sites of diet on the disease pathway. We propose a framework for interrogating the critical targets in colon cancer process and identifying plant-based dietary interventions as important modifiers using a systems chemical biology approach. The fifth chapter of the thesis is on discovering of novel anti...

  12. Assessment of Disease Activity in Small Bowel Crohn’s Disease: Comparison between Endoscopy and Magnetic Resonance Enterography Using MRIA and Modified MRIA Score

    Directory of Open Access Journals (Sweden)

    Arnaldo Scardapane

    2015-01-01

    Full Text Available Objectives. To retrospectively compare the results of the MRIA (magnetic resonance index of activity with a modified MRIA (mMRIA, which was calculated excluding from MRIA formula the data of relative contrast enhancement (RCE. Materials and Methods. MR-E and corresponding endoscopic records of 100 patients were reviewed. MRIA, mMRIA, and SES endoscopic index were calculated for all the patients. Namely, MRIA was calculated as follows: (1.5 × wall thickening + 0.02 × RCE + 5 × intramural edema + 10 × ulcers, while mMRIA was calculated with the modified formula (1.5 × wall thickening + 5 × intramural edema + 10 × ulcers. Results. Mean MRIA and mMRIA values were 19.3 and 17.68, respectively p<0.0001. A significant correlation p<0.0001 was observed between MRIA and mMRIA scores and between both MR indexes and SES p<0.0001. Conclusions. mMRIA was comparable to MRIA in the evaluation of disease activity in Crohn’s disease.

  13. Assessment of Disease Activity in Small Bowel Crohn's Disease: Comparison between Endoscopy and Magnetic Resonance Enterography Using MRIA and Modified MRIA Score

    Science.gov (United States)

    Scardapane, Arnaldo; Ambrosi, Annalisa; Salinaro, Emanuela; Mancini, Maria Elisabetta; Principi, Mariabeatrice; Di Leo, Alfredo; Lorusso, Filomenamila; Stabile Ianora, Amato Antonio; Angelelli, Giuseppe

    2015-01-01

    Objectives. To retrospectively compare the results of the MRIA (magnetic resonance index of activity) with a modified MRIA (mMRIA), which was calculated excluding from MRIA formula the data of relative contrast enhancement (RCE). Materials and Methods. MR-E and corresponding endoscopic records of 100 patients were reviewed. MRIA, mMRIA, and SES endoscopic index were calculated for all the patients. Namely, MRIA was calculated as follows: (1.5 × wall thickening + 0.02 × RCE + 5 × intramural edema + 10 × ulcers), while mMRIA was calculated with the modified formula (1.5 × wall thickening + 5 × intramural edema + 10 × ulcers). Results. Mean MRIA and mMRIA values were 19.3 and 17.68, respectively (p < 0.0001). A significant correlation (p < 0.0001) was observed between MRIA and mMRIA scores and between both MR indexes and SES (p < 0.0001). Conclusions. mMRIA was comparable to MRIA in the evaluation of disease activity in Crohn's disease. PMID:26759554

  14. Global Foot-and-Mouth Disease Research Update and Gap Analysis: 7 - Pathogenesis and Molecular Biology.

    Science.gov (United States)

    Robinson, L; Knight-Jones, T J D; Charleston, B; Rodriguez, L L; Gay, C G; Sumption, K J; Vosloo, W

    2016-06-01

    We assessed research knowledge gaps in the fields of FMDV (foot-and-mouth disease virus) pathogenesis and molecular biology by performing a literature review (2011-15) and collecting research updates (2014) from 33 institutes from across the world. Findings were used to identify priority areas for future research. There have been important advances in FMDV pathogenesis; FMDV remains in lymph nodes of many recovered animals that otherwise do not appear persistently infected, even in species previously not associated with the carrier state. Whether virus retention helps maintain host immunity and/or virus survival is not known. Studies of FMDV pathogenesis in wildlife have provided insights into disease epidemiology, in endemic and epidemic settings. Many aspects of FMDV infection and virus entry remain unknown; however, at the cellular level, we know that expression level and availability of integrins (that permit viral entry), rate of clearance of infected cells and strength of anti-viral type I IFN (interferon) response are key determinants of tissue tropism. Extending findings to improved understanding of transmission requires a standardized approach and adoption of natural routes of infection during experimental study. There has been recognition of the importance of autophagosomes for FMDV entry into the cytoplasm following cell surface receptor binding, and that distinct internal cellular membranes are exploited for viral replication and immune evasion. New roles for viral proteins in blocking type I IFN production and downstream signalling have been identified facilitating research in anti-viral therapeutics. We know more about how infection affects cell protein expression, and research into molecular determinants of capsid stability has aided the development of stable vaccines. We have an expanding knowledge of viral and host molecular determinates of virulence and infectiousness, and of how phylogenetics may be used to estimate vaccine match and strain

  15. Biology, etiology, and control of virus diseases of banana and plantain.

    Science.gov (United States)

    Kumar, P Lava; Selvarajan, Ramasamy; Iskra-Caruana, Marie-Line; Chabannes, Matthieu; Hanna, Rachid

    2015-01-01

    Banana and plantain (Musa spp.), produced in 10.3 million ha in the tropics, are among the world's top 10 food crops. They are vegetatively propagated using suckers or tissue culture plants and grown almost as perennial plantations. These are prone to the accumulation of pests and pathogens, especially viruses which contribute to yield reduction and are also barriers to the international exchange of germplasm. The most economically important viruses of banana and plantain are Banana bunchy top virus (BBTV), a complex of banana streak viruses (BSVs) and Banana bract mosaic virus (BBrMV). BBTV is known to cause the most serious economic losses in the "Old World," contributing to a yield reduction of up to 100% and responsible for a dramatic reduction in cropping area. The BSVs exist as episomal and endogenous forms are known to be worldwide in distribution. In India and the Philippines, BBrMV is known to be economically important but recently the virus was discovered in Colombia and Costa Rica, thus signaling its spread into the "New World." Banana and plantain are also known to be susceptible to five other viruses of minor significance, such as Abaca mosaic virus, Abaca bunchy top virus, Banana mild mosaic virus, Banana virus X, and Cucumber mosaic virus. Studies over the past 100 years have contributed to important knowledge on disease biology, distribution, and spread. Research during the last 25 years have led to a better understanding of the virus-vector-host interactions, virus diversity, disease etiology, and epidemiology. In addition, new diagnostic tools were developed which were used for surveillance and the certification of planting material. Due to a lack of durable host resistance in the Musa spp., phytosanitary measures and the use of virus-free planting material are the major methods of virus control. The state of knowledge on BBTV, BBrMV, and BSVs, and other minor viruses, disease spread, and control are summarized in this review. PMID:25591881

  16. Interferon and biologic signatures in dermatomyositis skin: specificity and heterogeneity across diseases.

    Directory of Open Access Journals (Sweden)

    David Wong

    Full Text Available BACKGROUND: Dermatomyositis (DM is an autoimmune disease that mainly affects the skin, muscle, and lung. The pathogenesis of skin inflammation in DM is not well understood. METHODOLOGY AND FINDINGS: We analyzed genome-wide expression data in DM skin and compared them to those from healthy controls. We observed a robust upregulation of interferon (IFN-inducible genes in DM skin, as well as several other gene modules pertaining to inflammation, complement activation, and epidermal activation and differentiation. The interferon (IFN-inducible genes within the DM signature were present not only in DM and lupus, but also cutaneous herpes simplex-2 infection and to a lesser degree, psoriasis. This IFN signature was absent or weakly present in atopic dermatitis, allergic contact dermatitis, acne vulgaris, systemic sclerosis, and localized scleroderma/morphea. We observed that the IFN signature in DM skin appears to be more closely related to type I than type II IFN based on in vitro IFN stimulation expression signatures. However, quantitation of IFN mRNAs in DM skin shows that the majority of known type I IFNs, as well as IFN g, are overexpressed in DM skin. In addition, both IFN-beta and IFN-gamma (but not other type I IFN transcript levels were highly correlated with the degree of the in vivo IFN transcriptional response in DM skin. CONCLUSIONS AND SIGNIFICANCE: As in the blood and muscle, DM skin is characterized by an overwhelming presence of an IFN signature, although it is difficult to conclusively define this response as type I or type II. Understanding the significance of the IFN signature in this wide array of inflammatory diseases will be furthered by identification of the nature of the cells that both produce and respond to IFN, as well as which IFN subtype is biologically active in each diseased tissue.

  17. Disease-modifying anti-rheumatic drugs til behandling af ankyloserende spondylitis

    DEFF Research Database (Denmark)

    Madsen, Ole Rintek; Egsmose, Charlotte

    2009-01-01

    Ankylosing spondylitis (AS) is an inflammatory disorder affecting the axial skeleton, peripheral joints, entheses and extra-articular sites. Patients with early disease, a higher level of erythrocyte sedimentation rate and/or peripheral arthritis might benefit from sulfasalazine. Otherwise, there...

  18. Unacknowledged Health Benefits Of Genetically Modified Food - Salmon And Heart Disease Deaths

    OpenAIRE

    Lutter, Randall; Tucker, Katherine

    2003-01-01

    Randall Lutter and Katherine Tuckerargue that the marketing of GM salmon will lower salmon prices and increase consumption of salmon, an exceptionally good source of omega-3 fatty acids linked to lower risk of heart disease.The authors estimateestimate that the resulting increase in omega-3 intake will prevent between 600 and 2600 deaths per year in the U.S.

  19. Epigenetic histone acetylation modifiers in vascular remodelling : New targets for therapy in cardiovascular disease

    NARCIS (Netherlands)

    Pons, D.; Vries, F.R. de; Elsen, P.J. van den; Heijmans, B.T.; Quax, P.H.A.; Jukema, J.W.

    2009-01-01

    Significant progress has been made in the clinical management of a variety of cardiovascular diseases. Nevertheless, the therapeutic efficacy of the current treatment modalities for atherosclerosis and restenosis is not fully sufficient in a large proportion of patients. One of the major contributin

  20. Alemtuzumab for patients with relapsing multiple sclerosis after disease-modifying therapy

    DEFF Research Database (Denmark)

    Coles, Alasdair J; Twyman, Cary L; Arnold, Douglas L;

    2012-01-01

    The anti-CD52 monoclonal antibody alemtuzumab reduces disease activity in previously untreated patients with relapsing-remitting multiple sclerosis. We aimed to assess efficacy and safety of alemtuzumab compared with interferon beta 1a in patients who have relapsed despite first-line treatment....

  1. Evaluation of a genetically modified foot-and-mouth disease virus vaccine candidate generated by reverse genetics

    Directory of Open Access Journals (Sweden)

    Li Pinghua

    2012-05-01

    Full Text Available Abstract Background Foot-and-mouth disease (FMD is the most economically important and highly contagious disease of cloven-hoofed animals worldwide. Control of the disease has been mainly based on large-scale vaccinations with whole-virus inactivated vaccines. In recent years, a series of outbreaks of type O FMD occurred in China (including Chinese Taipei, Chinese Hong Kong posed a tremendous threat to Chinese animal husbandry. Its causative agent, type O FMDV, has evolved into three topotypes (East–South Asia (ME-SA, Southeast Asia (SEA, Cathay (CHY in these regions, which represents an important obstacle to disease control. The available FMD vaccine in China shows generally good protection against ME-SA and SEA topotype viruses infection, but affords insufficient protection against some variants of the CHY topotype. Therefore, the choice of a new vaccine strain is of fundamental importance. Results The present study describes the generation of a full-length infectious cDNA clone of FMDV vaccine strain and a genetically modified virus with some amino acid substitutions in antigenic sites 1, 3, and 4, based on the established infectious clone. The recombinant viruses had similar growth properties to the wild O/HN/CHA/93 virus. All swine immunized with inactivated vaccine prepared from the O/HN/CHA/93 were fully protected from challenge with the viruses of ME-SA and SEA topotypes and partially protected against challenge with the virus of CHY topotype at 28 days post-immunization. In contrast, the swine inoculated with the genetically modified vaccine were completely protected from the infection of viruses of the three topotypes. Conclusions Some amino acid substitutions in the FMDV vaccine strain genome did not have an effect on the ability of viral replication in vitro. The vaccine prepared from genetically modified FMDV by reverse genetics significantly improved the protective efficacy to the variant of the CHY topotype, compared with the

  2. The quest for the Holy Grail: a disease-modifying osteoarthritis drug

    Science.gov (United States)

    Berenbaum, Francis

    2007-01-01

    The unfortunate story of the matrix metalloproteinase inhibitor PG116800, which had no effect on the osteoarthritic process but had unexpected side effects, highlights the following. First, reality does not always match the theory. Second, cell biology data must be interpreted within the context of a specific environment. Third, the specificity of an enzyme inhibitor is always relative. Finally, a critical evaluation of the benefit/risk ratio of a drug must be carefully conducted and checked before and after launch. Well designed post-marketing surveillance is mandatory. PMID:18096086

  3. The quest for the Holy Grail: a disease-modifying osteoarthritis drug.

    Science.gov (United States)

    Berenbaum, Francis

    2007-01-01

    The unfortunate story of the matrix metalloproteinase inhibitor PG116800, which had no effect on the osteoarthritic process but had unexpected side effects, highlights the following. First, reality does not always match the theory. Second, cell biology data must be interpreted within the context of a specific environment. Third, the specificity of an enzyme inhibitor is always relative. Finally, a critical evaluation of the benefit/risk ratio of a drug must be carefully conducted and checked before and after launch. Well designed post-marketing surveillance is mandatory. PMID:18096086

  4. Construction of biological control strain of Trichoderma viride and study of their ability to induce plant disease resistance

    Institute of Scientific and Technical Information of China (English)

    LIU Shi-wang; GUO Ze-jian

    2004-01-01

    @@ Plant diseases heavily affct plant growth and crop yield even in modern agriculture. Control its difficult because pathogens mutate frequently, and this leads in frequent breaking of disease resistance in commercial cultivars. The excessive application of chemical pesticides is not only producing pesticideresistant pathogens, but it is harming the environment threatening the health of human beings.Therefore, the use of biological control agents (BCA) may provide an environmental friendly alternative to chemicals for plant disease control. Hypersensitive response (HR) and systemic acquired resistance (SAR) are the typical expressions of plant defense reactions. Once SAR is established,, the plants exhibits a broad-spectrum of disease resistance against pathogen attack. Researchers have identified elicitor proteins, such as elicitins and harpins, which activate plant defense reactions. It would be useful to explore the possibility of using biological control agents to induce a status of SAR in crop plants.

  5. Relation between disease modifying anti-rheumatic drugs and herpes zoster in rheumatoid arthritis.

    Science.gov (United States)

    Yamaoka, Kunihiro

    2016-01-01

      Biologics have revolutionized the treatment of rheumatoid arthritis (RA). However certain amount of the patients cannot achieve goal of therapy. Recently, compounds targeting the intracellular kinase, Janus kinase (JAK) have demonstrated therapeutic effects resembling biologics. Tofacitinib is the only JAK inhibitor approved for RA and during the clinical trial, increased events of herpes zoster (HZ) was observed. Incidence rate was twice as much as patients treated with conventional anti-rheumatic drug and was especially increased in Japan that was four times as much. The risk factors were age and glucocorticoid that is identical to that of common RA patients and there was nothing specific for tofacitinib. Mechanism of increased incidence of HZ and the difference in ethnicity remains unknown. Analysis of clinical trials have identified that HZ do not correlate with further adverse events. Therefore, it is extremely important to accumulate clinical data with considerable amount of patients with long term follow up including the post marketing surveillance in Japan to reveal the significance of increased HZ in RA patients. PMID:27320933

  6. Systems biology of interstitial lung diseases: integration of mRNA and microRNA expression changes

    OpenAIRE

    Price Jennifer; Dakhallah Duaa; Batte Kara; Piper Melissa G; Wang Kai; Etheridge Alton; Gelinas Richard; Cho Ji-Hoon; Bornman Dan; Zhang Shile; Marsh Clay; Galas David

    2011-01-01

    Abstract Background The molecular pathways involved in the interstitial lung diseases (ILDs) are poorly understood. Systems biology approaches, with global expression data sets, were used to identify perturbed gene networks, to gain some understanding of the underlying mechanisms, and to develop specific hypotheses relevant to these chronic lung diseases. Methods Lung tissue samples from patients with different types of ILD were obtained from the Lung Tissue Research Consortium and total cell...

  7. Implementation of a Tool to Modify Behavior in a Chronic Disease Management Program

    Directory of Open Access Journals (Sweden)

    Nicole D. Gillespie

    2011-01-01

    Full Text Available Chronic diseases like diabetes, hypertension, and dyslipidemia continue to be a significant burden on the US health care system. As a result, many healthcare providers are implementing strategies to prevent the incidence of heart disease and other chronic conditions. Among these strategies are proper drug therapy and lifestyle modifications. Behavior change is often the rate-limiting step in the prevention and maintenance of lifestyle modifications. The purpose of this paper is to describe a tool used to guide the progression and assess the effectiveness of a cardiovascular risk reduction program. The tool uses the Transtheoretical Model of Behavior Change to determine the readiness and confidence to change specific lifestyle behaviors pertinent to cardiovascular health. The tool aids the practitioner in developing a patient-centered plan to implement and maintain lifestyle changes and can be tailored to use in any situation requiring a behavior change on the part of the patient.

  8. Lifestyle modifies obesity-associated risk of cardiovascular disease in a genetically homogeneous population

    DEFF Research Database (Denmark)

    Jørgensen, Marit E; Borch-Johnsen, Knut; Bjerregaard, Peter

    2006-01-01

    BACKGROUND: The association between obesity and cardiovascular disease risk differs across populations. Whether such differences in obesity-related risk factors exist within population groups of the same genetic origin but with differences in lifestyle remains to be determined. OBJECTIVE: The aim...... was to analyze whether obesity was associated with the same degree of metabolic disturbances in 2 groups of genetically homogeneous Inuit who were exposed to considerable differences in lifestyle. DESIGN: We studied obesity and cardiovascular disease risk factors in a cross-sectional population survey...... insulin than did the Inuit migrants in Denmark. The trend in the association with obesity categories was different only for HDL cholesterol, with higher concentrations observed in women Inuit migrants in Denmark than in women Inuit residents in Greenland. CONCLUSIONS: The health risk associated with...

  9. Grafting fibroblasts genetically modified to produce L-dopa in a rat model of Parkinson disease

    International Nuclear Information System (INIS)

    Rat fibroblasts were infected with a retroviral vector containing the cDNA for rat tyrosine hydroxylase. A TH-positive clone was identified by biochemical assay and immunohistochemical staining. When supplemented in vitro with pterin cofactors required for TH activity, these cells produced L-dopa and released it into the cell cultured medium. Uninfected control cells and fibroblasts infected with the TH vector were grafted separately to the caudate of rats with unilateral 6-hydroxydopamine lesions of the nigrostriatal pathway. Only grafts containing TH-expressing fibroblasts were found to reduce rotational asymmetry. These results have general implications for the application of gene therapy to human neurological disease and specific implications for Parkinson disease

  10. A Novel Chemically Modified Curcumin Reduces Severity of Experimental Periodontal Disease in Rats: Initial Observations

    OpenAIRE

    2014-01-01

    Tetracycline-based matrix metalloproteinase- (MMP-) inhibitors are currently approved for two inflammatory diseases, periodontitis and rosacea. The current study addresses the therapeutic potential of a novel pleiotropic MMP-inhibitor not based on an antibiotic. To induce experimental periodontitis, endotoxin (LPS) was repeatedly injected into the gingiva of rats on one side of the maxilla; the contralateral (control) side received saline injections. Two groups of rats were treated by daily o...

  11. Nimesulide Improves the Symptomatic and Disease Modifying Effects of Leflunomide in Collagen Induced Arthritis

    OpenAIRE

    Al-Abd, Ahmed M.; Al-Abbasi, Fahad A.; Nofal, Salwa M.; Khalifa, Amani E.; Williams, Richard O.; El-Eraky, Wafaa I.; Nagy, Ayman A.; Abdel-Naim, Ashraf B.

    2014-01-01

    Nimesulide is a COX-2 inhibitor used for symptomatic relief of rheumatoid arthritis. Leflunomide is an anti-pyrimidine used to manage the progression of rheumatoid arthritis. Herein we studied the influence of nimesulide and leflunomide combination in terms of disease symptoms and progression using collagen-induced arthritis model in mice, as a model for rheumatoid arthritis. Collagen induced arthritis was induced by immunization with type II collagen. Assessment of joint stiffness and articu...

  12. Matrix Metalloproteinases are Modifiers of Huntingtin Proteolysis and Toxicity in Huntington’s Disease

    OpenAIRE

    Miller, John P.; Holcomb, Jennifer; Al-Ramahi, Ismael; de Haro, Maria; Gafni, Juliette; Zhang, Ningzhe; Kim, Eugene; Sanhueza, Mario; Torcassi, Cameron; Kwak, Seung; Botas, Juan; Hughes, Robert E.; Ellerby, Lisa M.

    2010-01-01

    Proteolytic cleavage of huntingtin (Htt) is known to be a key event in the pathogenesis of Huntington’s disease (HD). Our understanding of proteolytic processing of Htt has thus far focused on the cysteine protease families of caspases and calpains. Identifying critical protease families involved in Htt proteolysis and toxicity using an unbiased approach has not been reported. To accomplish this, we designed a high-throughput western blot-based screen to examine the generation of the smallest...

  13. Bipolar disorder and diabetes mellitus: evidence for disease-modifying effects and treatment implications

    OpenAIRE

    Charles, Ellen F.; Lambert, Christophe G; Kerner, Berit

    2016-01-01

    Background Bipolar disorder refers to a group of chronic psychiatric disorders of mood and energy levels. While dramatic psychiatric symptoms dominate the acute phase of the diseases, the chronic course is often determined by an increasing burden of co-occurring medical conditions. High rates of diabetes mellitus in patients with bipolar disorder are particularly striking, yet unexplained. Treatment and lifestyle factors could play a significant role, and some studies also suggest shared path...

  14. Inefficient DNA Repair Is an Aging-Related Modifier of Parkinson’s Disease

    OpenAIRE

    Sara Sepe; Chiara Milanese; Sylvia Gabriels; Derks, Kasper W.J.; Cesar Payan-Gomez; Wilfred F.J. van IJcken; Yvonne M.A. Rijksen; Alex L. Nigg; Sandra Moreno; Silvia Cerri; Fabio Blandini; Hoeijmakers, Jan H.J.; Pier G. Mastroberardino

    2016-01-01

    The underlying relation between Parkinson’s disease (PD) etiopathology and its major risk factor, aging, is largely unknown. In light of the causative link between genome stability and aging, we investigate a possible nexus between DNA damage accumulation, aging, and PD by assessing aging-related DNA repair pathways in laboratory animal models and humans. We demonstrate that dermal fibroblasts from PD patients display flawed nucleotide excision repair (NER) capacity and that Ercc1 mutant mice...

  15. Inefficient DNA Repair Is an Aging-Related Modifier of Parkinson’s Disease

    OpenAIRE

    Sepe, Sara; Milanese, Chiara; Gabriels, Sylvia; Derks, Kasper W.J.; Payan-Gomez, Cesar; Wilfred F.J. van IJcken; Yvonne M.A. Rijksen; Nigg, Alex L.; Moreno, Sandra; Cerri, Silvia; Blandini, Fabio; Hoeijmakers, Jan H.J.; Mastroberardino, Pier G.

    2016-01-01

    Summary The underlying relation between Parkinson’s disease (PD) etiopathology and its major risk factor, aging, is largely unknown. In light of the causative link between genome stability and aging, we investigate a possible nexus between DNA damage accumulation, aging, and PD by assessing aging-related DNA repair pathways in laboratory animal models and humans. We demonstrate that dermal fibroblasts from PD patients display flawed nucleotide excision repair (NER) capacity and that Ercc1 mut...

  16. Modified impact of emotion on temporal discrimination in a transgenic rat model of Huntington disease

    OpenAIRE

    Alexis Faure; Brown, Bruce L.; Nguyen, Hoa P.; Stephan Von Horsten

    2013-01-01

    Huntington's disease (HD) is characterized by triad of motor, cognitive, and emotional symptoms along with neuropathology in fronto-striatal circuit and limbic system including amygdala. Emotional alterations, which have a negative impact on patient well-being, represent some of the earliest symptoms of HD and might be related to the onset of the neurodegenerative process. In the transgenic rat model (tgHD rats), evidence suggest emotional alterations at the symptomatic stage along with neuro...

  17. Scintimetric assessment of synovitis activity during treatment with disease modifying antirheumatic drugs

    DEFF Research Database (Denmark)

    Olsen, N; Halberg, P; Halskov, O; Bentzon, M W

    1988-01-01

    In a double blind trial of 36 patients with rheumatoid arthritis a new scintimetric method was applied to three comparable patient groups before and after eight months' treatment with levamisole, penicillamine, or azathioprine. Technetium-99m pyrophosphate scintigraphy of both hands was performed...... joints decreased in the penicillamine and azathioprine groups. The scintimetric method reliably reflected local synovitis activity and its changes but, like grip strength and PIP circumference, was not a representative measure of the overall activity of the disease....

  18. Effect of cold spells and their modifiers on cardiovascular disease events: evidence from two prospective studies

    OpenAIRE

    Sartini, Claudio; Barry, Sarah J. E.; Wannamethee, S Goya; Whincup, Peter H.; Lennon, Lucy; Ford, Ian; Morris, Richard W.

    2016-01-01

    Objective: To investigate effects of cold weather spells on incidence of cardiovascular disease (CVD), and potential effect modification of socio-demographic, clinical, behavioural and environmental exposures. Methods: Data from two prospective studies were analysed: the British Regional Heart Study (BRHS), a population-based study of British men aged 60–79 years, followed for CVD incidence from 1998–2000 to 2012; and the PROSPER study of men and women aged 70–82 recruited to a tr...

  19. Effect of cold spells and their modifiers on cardiovascular disease events: evidence from two prospective studies

    OpenAIRE

    Sartini, C.; Barry, S.J.E.; Wannamethee, S. G.; Whincup, P H; Lennon, L; Ford, I; Morris, R W

    2016-01-01

    Objective: To investigate effects of cold weather spells on incidence of cardiovascular disease (CVD), and potential effect modification of socio-demographic, clinical, behavioural and environmental exposures. / Methods: Data from two prospective studies were analysed: the British Regional Heart Study (BRHS), a population-based study of British men aged 60–79 years, followed for CVD incidence from 1998–2000 to 2012; and the PROSPER study of men and women aged 70–82 recruited to a trial of pra...

  20. Purification and biochemical characterization of the complete structure of a proteolytically modified beta-2-microglobulin with biological activity

    DEFF Research Database (Denmark)

    Nissen, Mogens Holst; Thim, L; Christensen, M

    1987-01-01

    . (1985) Clin. Chem. 31, 1411-1412; Nissen et al. (1984) Clin. Chim. Acta 141, 41-50]. In the present study we describe the purification and characterization of this modified human serum beta-2-m from patients with small-cell lung cancer. Purified urinary beta-2-m was added to the serum samples incubated...... analyzed by sodium dodecyl sulphate/polyacrylamide gel electrophoresis and analytical isoelectric focusing respectively. Amino acid analysis of m-beta-2-m revealed that the protein is missing one lysine residue compared to the composition deduced from the cDNA sequence of beta-2-m. Amino acid sequence...

  1. Microglial TNF and IL-1 as early disease-modifiers in Alzheimer's-like disease in mice

    DEFF Research Database (Denmark)

    Ilkjær, Laura; Babcock, Alicia; Finsen, Bente

    2015-01-01

    and IL-1, and to phagocytose and clear amyloid beta (As), however, the influence of TNF and IL-1, and inflammation in general, on these processes is still poorly understood. We have studied the development of As pathology, and basal and lipopolysaccharide (LPS) stimulated microglial cytokine...... production in the APPswe/PS1DE9 mouse model of AD. In these mice, cortical As plaque load shows a sigmoidal trajectory with age, as it does in AD. At 12 months of age, when As pathology is welldeveloped, TNF and IL-1s are produced in significantly higher proportions of microglia in the APPswe/PS1DE9 mice......, than in wildtype mice. Microglial expression of TNF and IL-1s can be significantly increased by i.p. injection of LPS, which we find reduces cortical As pathology at 12 months. Results will also be reported on the influence of IL-1 in modulating As pathology during early disease stages in APPswe/PS1DE9...

  2. Tofacitinib for acute rheumatoid arthritis patients who have had an inadequate response to disease-modifying antirheumatic drug (DMARD): a systematic review and meta-analysis.

    Science.gov (United States)

    Zhang, Xingming; Liang, Fuxiang; Yin, Xiaoxue; Xiao, Xiaojuan; Shi, Peiyu; Wei, Dang; Yao, Liang; Wang, Qi; Chen, Yaolong

    2014-02-01

    The aim of this systematic review and meta-analysis is to assess the efficacy and safety of tofacitinib for the treatment of patients with acute rheumatoid arthritis (RA) who have had an inadequate response to disease-modifying antirheumatic drug (DMARD). Randomized controlled trials were searched in MEDLINE (1966-2013), Embase (1947-2013), the Cochrane Central Register of Controlled Trials (1948-2013), WHO International Clinical Trial Registration Platform (2004-2013), Clinical Trial.gov (1999-2013), and China Biology Medicine disc (1978-2013). The review included 10 studies involving 4,929 patients. A pooled analysis of six studies showed that tofacitinib had a superior effect over placebo (both with background therapy) at weeks 12 and 24. Also, the pooled results of three studies showed that tofacitinib monotherapy had a significantly greater effect over placebo. Compared to adalimumab, tofacitinib was found to be more efficacious as well. For safety, tofacitinib monotherapy had less serious adverse events (sAE) than placebo but not other adverse effects (oAE). In the comparison of tofacitinib and placebo both with background therapy, no difference in sAE and oAE were found. However, the quality of the evidence was quite low when evaluated using GRADE. Tofacitinib alone, or together with non-biologic DMARDs, was associated with more favorable remission in the signs and symptoms of RA than adalimumab or placebo. Also, tofacitinib monotherapy was safer than placebo with regards to reported sAE, but not oAE. However, the quality of evidence is exceedingly low; long-term, large-scale, and high-quality post-marketing research is suggested to further verify the conclusion. PMID:24389749

  3. Biologic therapies for juvenile arthritis

    OpenAIRE

    Wilkinson, N; Jackson, G.; Gardner-Medwin, J.

    2003-01-01

    A group of therapies with exciting potential has emerged for children and young people with severe juvenile idiopathic arthritis (JIA) uncontrolled by conventional disease modifying drugs. Theoretical understanding from molecular biologic research has identified specific targets within pathophysiological pathways that control rheumatoid arthritis (RA) and JIA. This review identifies the pathways of autoimmunity to begin to show how biologic agents have been produced to replicate, mimic, or bl...

  4. De novo mutations in histone modifying genes in congenital heart disease

    OpenAIRE

    Zaidi, Samir; Choi, Murim; Wakimoto, Hiroko; Ma, Lijiang; Jiang, Jianming; Overton, John D; Romano-Adesman, Angela; Bjornson, Robert D.; Breitbart, Roger E.; Brown, Kerry K.; Carriero, Nicholas J.; Cheung, Yee Him; Deanfield, John; Depalma, Steve; Fakhro, Khalid A.

    2013-01-01

    Congenital heart disease (CHD) is the most frequent birth defect, affecting 0.8% of live births1. Many cases occur sporadically and impair reproductive fitness, suggesting a role for de novo mutations. By analysis of exome sequencing of parent-offspring trios, we compared the incidence of de novo mutations in 362 severe CHD cases and 264 controls. CHD cases showed a significant excess of protein-altering de novo mutations in genes expressed in the developing heart, with an odds ratio of 7.5 f...

  5. De novo mutations in histone modifying genes in congenital heart disease

    OpenAIRE

    Zaidi, Samir; Choi, Murim; Wakimoto, Hiroko; Ma, Lijiang; Jiang, Jianming; Overton, John D; Romano-Adesman, Angela; Bjornson, Robert D.; Breitbart, Roger E.; Brown, Kerry K.; Carriero, Nicholas J.; Cheung, Yee Him; Deanfield, John; Depalma, Steve; Fakhro, Khalid A.

    2013-01-01

    Congenital heart disease (CHD) is the most frequent birth defect, affecting 0.8% of live births 1 . Many cases occur sporadically and impair reproductive fitness, suggesting a role for de novo mutations. By analysis of exome sequencing of parent-offspring trios, we compared the incidence of de novo mutations in 362 severe CHD cases and 264 controls. CHD cases showed a significant excess of protein-altering de novo mutations in genes expressed in the developing heart, with an odds ratio of 7.5...

  6. Addressing Health Literacy Challenges with a Cutting-Edge Infectious Disease Curriculum for the High School Biology Classroom

    Science.gov (United States)

    Jacque, Berri; Koch-Weser, Susan; Faux, Russell; Meiri, Karina

    2016-01-01

    This study reports the secondary analysis of evaluation data from an innovative high school biology curriculum focused on infectious disease (ID) to examine the health literacy implications of teaching claims evaluation, data interpretation, and risk assessment skills in the context of 21st-Century health science. The curriculum was implemented…

  7. Biological and mechanical properties of an experimental glass-ionomer cement modified by partial replacement of CaO with MgO or ZnO

    Directory of Open Access Journals (Sweden)

    Dong-Ae KIM

    2015-08-01

    Full Text Available AbstractSome weaknesses of conventional glass ionomer cement (GIC as dental materials, for instance the lack of bioactive potential and poor mechanical properties, remain unsolved.Objective The purpose of this study was to investigate the effects of the partial replacement of CaO with MgO or ZnO on the mechanical and biological properties of the experimental glass ionomer cements.Material and Methods Calcium fluoro-alumino-silicate glass was prepared for an experimental glass ionomer cement by melt quenching technique. The glass composition was modified by partial replacement (10 mol% of CaO with MgO or ZnO. Net setting time, compressive and flexural properties, and in vitrorat dental pulp stem cells (rDPSCs viability were examined for the prepared GICs and compared to a commercial GIC.Results The experimental GICs set more slowly than the commercial product, but their extended setting times are still within the maximum limit (8 min specified in ISO 9917-1. Compressive strength of the experimental GIC was not increased by the partial substitution of CaO with either MgO or ZnO, but was comparable to the commercial control. For flexural properties, although there was no significance between the base and the modified glass, all prepared GICs marked a statistically higher flexural strength (p<0.05 and comparable modulus to control. The modified cements showed increased cell viability for rDPSCs.Conclusions The experimental GICs modified with MgO or ZnO can be considered bioactive dental materials.

  8. Microparticles as biomarkers of lung disease: enumeration in biological fluids using lipid bilayer microspheres.

    Science.gov (United States)

    McVey, Mark J; Spring, Christopher M; Semple, John W; Maishan, Mazharul; Kuebler, Wolfgang M

    2016-05-01

    Extracellular vesicles, specifically microparticles (MPs), are rapidly gaining attention for their capacity to act as biomarkers for diagnosis, prognosis, or responsiveness to therapy in lung disease, in keeping with the concept of precision medicine. However, MP analysis by high-sensitivity flow cytometry (FCM) is complicated by a lack of accurate means for MP enumeration. To address this gap, we report here an enhanced FCM MP gating and enumeration technique based on the use of novel engineered lipid bilayer microspheres (LBMs). By comparison of LBM-based MP enumeration with conventional bead- or fluorescent-based FCM enumeration techniques and a gravimetric consumption gold standard, we found LBMs to be superior to commercial bead preparations, showing the smallest fixed bias and limits of agreement in Bland Altman analyses. LBMs had simultaneous capacity to aid FCM enumeration of MPs in plasma, BAL, and cell culture supernatants. LBM enumeration detected differences in MP counts in mice exposed to intraperitoneal lipopolysaccharide or saline. LBMs provided for 1) higher sensitivity for gating MPs populations, 2) reduced background within MP gates, 3) more appropriate size, and 4) an inexpensive alternative amenable to different fluorescent tags. LBM-based MP enumeration was useful for a series of different FCM systems assessed, whereas LBM gating benefited high- but not low-sensitivity FCM systems compared with fluorescence gating. By offering exclusive advantages over current means of gating and enumerating MPs, LBMs are uniquely suited to realizing the potential of MPs as biomarkers in biological lung fluids and facilitating precision medicine in lung disease. PMID:26944090

  9. Transthyretin (ATTR) amyloidosis: clinical spectrum, molecular pathogenesis and disease-modifying treatments.

    Science.gov (United States)

    Sekijima, Yoshiki

    2015-09-01

    Transthyretin (ATTR) amyloidosis is a life-threatening, gain-of-toxic-function disease characterised by extracellular deposition of amyloid fibrils composed of transthyretin (TTR). TTR protein destabilised by TTR gene mutation is prone to dissociate from its native tetramer to monomer, and to then misfold and aggregate into amyloid fibrils, resulting in autosomal dominant hereditary amyloidosis, including familial amyloid polyneuropathy, familial amyloid cardiomyopathy and familial leptomeningeal amyloidosis. Analogous misfolding of wild-type TTR results in senile systemic amyloidosis, now termed wild-type ATTR amyloidosis, characterised by acquired amyloid disease in the elderly. With the availability of genetic, biochemical and immunohistochemical diagnostic tests, patients with ATTR amyloidosis have been found in many nations; however, misdiagnosis is still common and considerable time is required before correct diagnosis in many cases. The current standard first-line treatment for hereditary ATTR amyloidosis is liver transplantation, which allows suppression of the main source of variant TTR. However, large numbers of patients are not suitable transplant candidates. Recently, the clinical effects of TTR tetramer stabilisers, diflunisal and tafamidis, were demonstrated in randomised clinical trials, and tafamidis has been approved for treatment of hereditary ATTR amyloidosis in European countries and in Japan. Moreover, antisense oligonucleotides and small interfering RNAs for suppression of variant and wild-type TTR synthesis are promising therapeutic approaches to ameliorate ATTR amyloidosis and are currently in phase III clinical trials. These newly developed therapies are expected to be effective for not only hereditary ATTR amyloidosis but also wild-type ATTR amyloidosis. PMID:25604431

  10. Evaluation of a Fiber-Modified Adenovirus Vector Vaccine against Foot-and-Mouth Disease in Cattle

    Science.gov (United States)

    Medina, Gisselle N.; Montiel, Nestor; Diaz-San Segundo, Fayna; Sturza, Diego; Ramirez-Medina, Elizabeth; Grubman, Marvin J.

    2015-01-01

    Novel vaccination approaches against foot-and-mouth disease (FMD) include the use of replication-defective human adenovirus type 5 (Ad5) vectors that contain the capsid-encoding regions of FMD virus (FMDV). Ad5 containing serotype A24 capsid sequences (Ad5.A24) has proved to be effective as a vaccine against FMD in livestock species. However, Ad5-vectored FMDV serotype O1 Campos vaccine (Ad5.O1C.2B) provides only partial protection of cattle against homologous challenge. It has been reported that a fiber-modified Ad5 vector expressing Arg-Gly-Asp (RGD) enhances transduction of antigen-presenting cells (APC) in mice. In the current study, we assessed the efficacy of a fiber-modified Ad5 (Adt.O1C.2B.RGD) in cattle. Expression of FMDV capsid proteins was superior in cultured cells infected with the RGD-modified vector. Furthermore, transgene expression of Adt.O1C.2B.RGD was enhanced in cell lines that constitutively express integrin αvβ6, a known receptor for FMDV. In contrast, capsid expression in cattle-derived enriched APC populations was not enhanced by infection with this vector. Our data showed that vaccination with the two vectors yielded similar levels of protection against FMD in cattle. Although none of the vaccinated animals had detectable viremia, FMDV RNA was detected in serum samples from animals with clinical signs. Interestingly, CD4+ and CD8+ gamma interferon (IFN-γ)+ cell responses were detected at significantly higher levels in animals vaccinated with Adt.O1C.2B.RGD than in animals vaccinated with Ad5.O1C.2B. Our results suggest that inclusion of an RGD motif in the fiber of Ad5-vectored FMD vaccine improves transgene delivery and cell-mediated immunity but does not significantly enhance vaccine performance in cattle. PMID:26607309

  11. The higher proportion of men with psoriasis treated with biologics may be explained by more severe disease in men.

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    David Hägg

    Full Text Available OBJECTIVES: Moderate to severe psoriasis, once regarded as merely a skin disease, is today seen as an inflammatory systemic disease. The sex ratio of the prevalence of psoriasis is balanced. In recent years several reports have documented that men receive more systemic or UV treatment than women, and different hypotheses were made. In PsoReg, the national registry for systemic treatment of psoriasis in Sweden, we have, like other European registries, observed a predominance of men (59%, especially of men treated with biologics (63%. Biologics are a relatively new group of very effective but high-priced drugs. The objective of this study was to analyse if women are discriminated by not having the same access to the high-priced biologics. DESIGN: Population based cohort study using data from a nationwide quality register of psoriasis patients. POPULATION: 2294 patients with moderate to severe psoriasis receiving systemic treatment from a specialist in dermatology. MAIN OUTCOME MEASURES: Time to initiation of biologic treatment. A multiple Cox proportional hazard's regression was performed, with time to initiating a biologic treatment as the outcome in order to assess the independent role of the patient's sex in initiating such therapy. The psoriasis severity was defined as a time-varying variable. RESULTS: Men had more severe psoriasis than women according to the Psoriasis Area and Severity Index (PASI, regardless of age at enrolment, and throughout the study period. The analysis in the multiple Cox regression show that age, psoriasis severity and psoriasis arthropathy were relevant factors for initiating biologic therapy, whereas sex is not. CONCLUSIONS: Although as many women as men are believed to suffer from psoriasis, men seem to be more severely affected by psoriasis. The asymmetry in allocation of biologic therapy thereby probably reflects the differing disease activity between the sexes, and is not a discrimination against women per se.

  12. A Computational Systems Biology Software Platform for Multiscale Modeling and Simulation: Integrating Whole-Body Physiology, Disease Biology, and Molecular Reaction Networks

    Science.gov (United States)

    Eissing, Thomas; Kuepfer, Lars; Becker, Corina; Block, Michael; Coboeken, Katrin; Gaub, Thomas; Goerlitz, Linus; Jaeger, Juergen; Loosen, Roland; Ludewig, Bernd; Meyer, Michaela; Niederalt, Christoph; Sevestre, Michael; Siegmund, Hans-Ulrich; Solodenko, Juri; Thelen, Kirstin; Telle, Ulrich; Weiss, Wolfgang; Wendl, Thomas; Willmann, Stefan; Lippert, Joerg

    2011-01-01

    Today, in silico studies and trial simulations already complement experimental approaches in pharmaceutical R&D and have become indispensable tools for decision making and communication with regulatory agencies. While biology is multiscale by nature, project work, and software tools usually focus on isolated aspects of drug action, such as pharmacokinetics at the organism scale or pharmacodynamic interaction on the molecular level. We present a modeling and simulation software platform consisting of PK-Sim® and MoBi® capable of building and simulating models that integrate across biological scales. A prototypical multiscale model for the progression of a pancreatic tumor and its response to pharmacotherapy is constructed and virtual patients are treated with a prodrug activated by hepatic metabolization. Tumor growth is driven by signal transduction leading to cell cycle transition and proliferation. Free tumor concentrations of the active metabolite inhibit Raf kinase in the signaling cascade and thereby cell cycle progression. In a virtual clinical study, the individual therapeutic outcome of the chemotherapeutic intervention is simulated for a large population with heterogeneous genomic background. Thereby, the platform allows efficient model building and integration of biological knowledge and prior data from all biological scales. Experimental in vitro model systems can be linked with observations in animal experiments and clinical trials. The interplay between patients, diseases, and drugs and topics with high clinical relevance such as the role of pharmacogenomics, drug–drug, or drug–metabolite interactions can be addressed using this mechanistic, insight driven multiscale modeling approach. PMID:21483730

  13. A computational systems biology software platform for multiscale modeling and simulation: Integrating whole-body physiology, disease biology, and molecular reaction networks

    Directory of Open Access Journals (Sweden)

    Thomas eEissing

    2011-02-01

    Full Text Available Today, in silico studies and trial simulations already complement experimental approaches in pharmaceutical R&D and have become indispensable tools for decision making and communication with regulatory agencies. While biology is multi-scale by nature, project work and software tools usually focus on isolated aspects of drug action, such as pharmacokinetics at the organism scale or pharmacodynamic interaction on the molecular level. We present a modeling and simulation software platform consisting of PK-Sim® and MoBi® capable of building and simulating models that integrate across biological scales. A prototypical multiscale model for the progression of a pancreatic tumor and its response to pharmacotherapy is constructed and virtual patients are treated with a prodrug activated by hepatic metabolization. Tumor growth is driven by signal transduction leading to cell cycle transition and proliferation. Free tumor concentrations of the active metabolite inhibit Raf kinase in the signaling cascade and thereby cell cycle progression. In a virtual clinical study, the individual therapeutic outcome of the chemotherapeutic intervention is simulated for a large population with heterogeneous genomic background. Thereby, the platform allows efficient model building and integration of biological knowledge and prior data from all biological scales. Experimental in vitro model systems can be linked with observations in animal experiments and clinical trials. The interplay between patients, diseases, and drugs and topics with high clinical relevance such as the role of pharmacogenomics, drug-drug or drug-metabolite interactions can be addressed using this mechanistic, insight driven multiscale modeling approach.

  14. Effectiveness of interventions designed to modify and maintain perceptual abilities in people with Alzheimer's disease and related dementias.

    Science.gov (United States)

    Letts, Lori; Minezes, Jacqueline; Edwards, Mary; Berenyi, Julie; Moros, Kathy; O'Neill, Colleen; O'Toole, Colleen

    2011-01-01

    An evidence-based review was undertaken to answer the question, "What is the evidence for the effect of interventions designed to modify and maintain perceptual abilities on the occupational performance of people with Alzheimer's disease and related dementias?" A systematic search of electronic databases and application of inclusion and exclusion criteria guided the selection of 31 articles. Each article was critically appraised, and the evidence was synthesized. Some interventions use remaining perceptual abilities to enable people to find their way in a facility and decrease attempts at exiting. Preliminary evidence has supported use of visual stimulation and barriers. We found some evidence for the use of auditory stimuli and group therapy that aim to change perceptual abilities. Research with high-level evidence is required to validate these findings. Evidence on the benefits of Snoezelen is not conclusive for occupational performance outcomes; further research to justify its use as an occupational therapy intervention may be warranted. PMID:22026318

  15. Biological response of stainless steel surface modified by N2O/O2 glow discharge plasma

    International Nuclear Information System (INIS)

    Stainless steel wafers were treated with the glow discharge plasma of mixed N2O and O2 at different molar ratios at a certain discharge condition to create desirable biological characteristics to the surfaces. It was found that the molar ratio of N2O to O2 in the mixture at 1:1 used for plasma surface modification caused high apoptotic percentage. Contact angle measurement showed that the surface of stainless steel samples became very hydrophilic after the plasma modification with a value of 15o-30o. The control stainless steel chips without plasma treatment had a contact angle of 40 ± 2o. The data of Electron Spectroscopy for Chemical Analysis (ESCA) indicated that there was a certain amount of oxynitrites formed on the plasma treated surfaces, which was considered to play an important role to cell apoptosis and anti-clot formation in cell culture tests. The ESCA depth profile of up to 250 A from the top surface showed the change of elemental compositions within 40-50 A of the surface by the plasma treatment. The decreased platelet attachment, combined with increased apoptosis in fibroblasts is a distinct combination of biological responses arising from the mixed gas plasma treatment. These initial results suggest it may be of particular use relative to stainless steel stents where decreased platelet attachments are advantageous and induction of apoptosis could limit in-stent restenosis.

  16. Hydrothermally modified slow release corn starch: a potential new therapeutic option for treating hypoglycemia in autoimmune hypoglycemia (Hirata's disease).

    Science.gov (United States)

    Lechner, K; Aulinger, B; Brand, S; Waldmann, E; Parhofer, K G

    2015-12-01

    We report the successful treatment of autoimmune hypoglycemia in an 82-year-old non-diabetic Caucasian male with hydrothermally modified slow release corn starch, a product which is used in other conditions associated with hypoglycemia, most typically glycogen storage disease type I. An 82-year-old-Caucasian male presented with recurrent spontaneous hypoglycemia as low as 30 mg/dl following in-patient treatment for community acquired pneumonia. During a fasting-test, symptomatic hypoglycemia occurred. Plasma concentrations of c-peptide and insulin were considerably elevated. Autoimmune hypoglycemia was confirmed by the presence of insulin autoantibodies. While dietary restriction alone did not result in sufficient glucose control in this patient with autoimmune hypoglycemia, treatment with hydrothermally modified slow release corn starch led to stable euglycemia. This easy, well tolerated and non-invasive treatment may constitute a new therapeutic option for hypoglycemia in patients with autoimmune hypoglycemia who do not achieve sufficient control of hypoglycemia by dietary restriction alone. PMID:26373963

  17. Messina: a novel analysis tool to identify biologically relevant molecules in disease.

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    Mark Pinese

    Full Text Available BACKGROUND: Morphologically similar cancers display heterogeneous patterns of molecular aberrations and follow substantially different clinical courses. This diversity has become the basis for the definition of molecular phenotypes, with significant implications for therapy. Microarray or proteomic expression profiling is conventionally employed to identify disease-associated genes, however, traditional approaches for the analysis of profiling experiments may miss molecular aberrations which define biologically relevant subtypes. METHODOLOGY/PRINCIPAL FINDINGS: Here we present Messina, a method that can identify those genes that only sometimes show aberrant expression in cancer. We demonstrate with simulated data that Messina is highly sensitive and specific when used to identify genes which are aberrantly expressed in only a proportion of cancers, and compare Messina to contemporary analysis techniques. We illustrate Messina by using it to detect the aberrant expression of a gene that may play an important role in pancreatic cancer. CONCLUSIONS/SIGNIFICANCE: Messina allows the detection of genes with profiles typical of markers of molecular subtype, and complements existing methods to assist the identification of such markers. Messina is applicable to any global expression profiling data, and to allow its easy application has been packaged into a freely-available stand-alone software package.

  18. Death in the intestinal epithelium-basic biology and implications for inflammatory bowel disease.

    Science.gov (United States)

    Blander, J Magarian

    2016-07-01

    Every 4-5 days, intestinal epithelial cells (IEC) are terminated as they reach the end of their life. This process ensures that the epithelium is comprised of the fittest cells that maintain an impermeable barrier to luminal contents and the gut microbiota, as well as the most metabolically able cells that conduct functions in nutrient absorption, digestion, and secretion of antimicrobial peptides. IEC are terminated by apical extrusion-or shedding-from the intestinal epithelial monolayer into the gut lumen. Whether death by apoptosis signals extrusion or death follows expulsion by younger IEC has been a matter of debate. Seemingly a minor detail, IEC death before or after apical extrusion bears weight on the potential contribution of apoptotic IEC to intestinal homeostasis as a consequence of their recognition by intestinal lamina propria phagocytes. In inflammatory bowel disease (IBD), excessive death is observed in the ileal and colonic epithelium. The precise mode of IEC death in IBD is not defined. A highly inflammatory milieu within the intestinal lamina propria, rich in the proinflammatory cytokine, TNF-α, increases IEC shedding and compromises barrier integrity fueling more inflammation. A milestone in the treatment of IBD, anti-TNF-α therapy, may promote mucosal healing by reversing increased and inflammation-associated IEC death. Understanding the biology and consequences of cell death in the intestinal epithelium is critical to the design of new avenues for IBD therapy. PMID:27250564

  19. Influence of avian leukosis virus long terminal repeat on biological activities of Marek's disease virus.

    Science.gov (United States)

    Sun, Peng; Cui, Ning; Su, Shuai; Chen, Zimeng; Li, Yanpeng; Ding, Jiabo; Cui, Zhizhong

    2015-01-01

    GX0101 was the first reported field strain of recombinant Marek's disease virus (MDV) that contained a long terminal repeat (LTR) from the reticuloendotheliosis virus (REV). It is a very virulent MDV strain, with relatively high horizontal transmission ability. The REV LTR in GX0101 genome was proved to decrease the pathogenicity but increase the potential for horizontal transmission of the virus. Here we constructed a recombinant MDV GX0101-ALV-LTR to study stability of avian leukosis virus (ALV) LTR at the REV LTR insertion site in GX0101 genome and its influence on biological activities of the recombinant virus. The results showed that GX0101-ALV-LTR was able to replicate stably both in vitro and in vivo. ALV LTR remained stable in chickens infected either by inoculation with the recombinant virus GX0101-ALV-LTR or by horizontal transmission, as well as in cell culture. The pathogenic properties of GX0101-ALV-LTR virus were evaluated in infected specific-pathogen-free chickens. The present study demonstrated that the GX0101-ALV-LTR virus had a weaker inhibitory effect on the growth rates of the infected chickens and induced weaker immunosuppressive effects. Horizontal transmission ability of the GX0101-ALV-LTR virus appeared to be similar with its parental virus GX0101. In short, ALV LTR was stable in GX0101 after replacing REV LTR, and the recombinant virus showed similar horizontal transmission ability but decreased pathogenicity. PMID:26274570

  20.  The biological activity of macrophages in health and disease

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    Katarzyna Nazimek

    2012-07-01

    Full Text Available  Macrophages are involved in immune response as phagocytes, antigen presenting cells and as effector cells of delayed-type hypersensitivity. Moreover, the activity of macrophages is associated with modulation of many biological processes during the whole life and depends on the actual macrophage phenotype induced under the influence of various microenvironmental stimuli.In pregnancy, placental macrophages induce the development of maternal tolerance to fetal antigens, while fetal macrophages are responsible for proper formation of tissues and organs.Residual macrophages play a very important role in tissue homeostasis, apoptotic cell clearance to prevent autoimmunization and first defense in infections. The inflammatory response of macrophages may be modulated by pathogens. Their suppressive activity is observed in immunologically privileged organs such as testes.In pathologies, macrophages are responsible for tissue damage in a case of nonspecific activation followed by overproduction of proinflammatory factors. Suppression of a specific immune response against tumors is mainly the effect of tumor associated macrophage (TAM action. On the other hand, presentation of allergens or self-antigens by macrophages and their nonspecific activation by necrotic adipocytes leads to the induction of a chronic inflammatory response and impairment of immunity. Therefore, modulation of macrophage functions may be the key for improvement of therapy of cancer and allergic, autoimmune, metabolic, cardiovascular and Alzheimer’s diseases.

  1. CARDIOVASCULAR RISK IN PATIENTS WITH EARLY RHEUMATOID ARTHRITIS BEFORE DISEASE-MODIFYING ANTIRHEUMATIC THERAPY (PRELIMINARY DATA OF THE REMARCА STUDY

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    Yu. N. Gorbunova

    2014-01-01

    Full Text Available Objective: to estimate the level of cardiovascular risk in patients with early rheumatoid arthritis (RA before therapy with disease-modifying antirheumatic drugs (DMARDs.Subjects and methods: Seventy-three patients with early RA who had not previously taken DMARDs or glucocorticoids were examined. Disease activity was assessed by the DAS28, SDAI, and CDAI. All the patients were examined by a cardiologist. The investigators assessed traditional risk factors (RF, by determining the overall coronary risk according tothe modified SCORE scale, the degree of a risk for cardiovascular events (CVE, carried out 24-hour ECG and blood pressure monitoring, echocardiography (EchoCG, and carotid duplex scanning, identified coronary artery calcification by multislice spiral computed tomography, and, if indicated, performed stress EchoCG and coronary angiography.Results. The diagnosis of coronary heart disease was established in 13 patients. NYHA functional class I or II chronic heart failure (HF was diagnosed in 8 patients, systolic HF in 2, HF with preserved left ventricular ejection fraction in 6 cases. There was left ventricular hypertrophy in 22 (30.1% patients, carotid atherosclerotic plaques in 26 (35.6%, coronary artery calcification in 30 (41.1%, hypertension in 38 (52.1%, abdominal obesity in 34 (46.6%, dyslipidemia in 40 (54.8%, hypercholesterolemia in 37 (50.7%, hypoalphalipoproteinemia in 21 (28.8%, hypertriglyceridemia in 12 (16.4%, low physical activity in 30 (41.1%, and smoking in 13 (17.8%. Thirty-three of 53 women weremenopausal. Fasting hyperglycemia was found in 11 (15.1% patients; type 2 diabetes mellitus in 4 (5.5%. Thirty-one (42.5% patients had at least three RFs. In accordance with the current classification of the degree of cardiovascular risk, very high, high, moderate, and low risks for CVE were observed in 58, 8, 8, and 26% of the RA patients, respectively.Conclusion. Most rheumatoid factor- and anticyclic citrullinated

  2. Disease-modifying therapy in multiple sclerosis and chronic inflammatory demyelinating polyradiculoneuropathy: common and divergent current and future strategies

    Science.gov (United States)

    Melzer, N; Meuth, S G

    2014-01-01

    Multiple sclerosis (MS) and chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) represent chronic, autoimmune demyelinating disorders of the central and peripheral nervous system. Although both disorders share some fundamental pathogenic elements, treatments do not provide uniform effects across both disorders. We aim at providing an overview of current and future disease-modifying strategies in these disorders to demonstrate communalities and distinctions. Intravenous immunoglobulins (IVIG) have demonstrated short-and long-term beneficial effects in CIDP but are not effective in MS. Dimethyl fumarate (BG-12), teriflunomide and laquinimod are orally administered immunomodulatory drugs that are already approved or likely to be approved in the near future for the basic therapy of patients with relapsing–remitting MS (RRMS) due to positive results in Phase III clinical trials. However, clinical trials with these drugs in CIDP have not (yet) been initiated. Natalizumab and fingolimod are approved for the treatment of RRMS, and trials to evaluate their safety and efficacy in CIDP are now planned. Alemtuzumab, ocrelizumab and daclizumab respresent monoclonal antibodies in advanced stages of clinical development for their use in RRMS patients. Attempts to study the safety and efficacy of alemtuzumab and B cell-depleting anti-CD20 antibodies, i.e. rituximab, ocrelizumab or ofatumumab, in CIDP patients are currently under way. We provide an overview of the mechanism of action and clinical data available on disease-modifying immunotherapy options for MS and CIDP. Enhanced understanding of the relative effects of therapies in these two disorders may aid rational treatment selection and the development of innovative treatment approaches in the future. PMID:24032475

  3. Thorough investigation of a canine autoinflammatory disease (AID confirms one main risk locus and suggests a modifier locus for amyloidosis.

    Directory of Open Access Journals (Sweden)

    Mia Olsson

    Full Text Available Autoinflammatory disease (AID manifests from the dysregulation of the innate immune system and is characterised by systemic and persistent inflammation. Clinical heterogeneity leads to patients presenting with one or a spectrum of phenotypic signs, leading to difficult diagnoses in the absence of a clear genetic cause. We used separate genome-wide SNP analyses to investigate five signs of AID (recurrent fever, arthritis, breed specific secondary dermatitis, otitis and systemic reactive amyloidosis in a canine comparative model, the pure bred Chinese Shar-Pei. Analysis of 255 DNA samples revealed a shared locus on chromosome 13 spanning two peaks of association. A three-marker haplotype based on the most significant SNP (p<2.6×10(-8 from each analysis showed that one haplotypic pair (H13-11 was present in the majority of AID individuals, implicating this as a shared risk factor for all phenotypes. We also noted that a genetic signature (F ST distinguishing the phenotypic extremes of the breed specific Chinese Shar-Pei thick and wrinkled skin, flanked the chromosome 13 AID locus; suggesting that breed development and differentiation has played a parallel role in the genetics of breed fitness. Intriguingly, a potential modifier locus for amyloidosis was revealed on chromosome 14, and an investigation of candidate genes from both this and the chromosome 13 regions revealed significant (p<0.05 renal differential expression in four genes previously implicated in kidney or immune health (AOAH, ELMO1, HAS2 and IL6. These results illustrate that phenotypic heterogeneity need not be a reflection of genetic heterogeneity, and that genetic modifiers of disease could be masked if syndromes were not first considered as individual clinical signs and then as a sum of their component parts.

  4. How do patients with inflammatory bowel disease want their biological therapy administered?

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    Lindsay Hannah

    2010-01-01

    Full Text Available Abstract Background Infliximab is usually administered by two monthly intravenous (iv infusions, therefore requiring visits to hospital. Adalimumab is administered by self subcutaneous (sc injections every other week. Both of these anti-TNF drugs appear to be equally efficacious in the treatment of Crohn's Disease and therefore the decision regarding which drug to choose will depend to some extent on patient choice, which may be based on the mode of administration. The aims of this study were to compare preferences in Inflammatory Bowel Disease (IBD patients for two currently available anti-TNF agents and the reasons for their choices. Methods An anonymous questionnaire was distributed to IBD patients who had attended the Gastroenterology service (Ulster Hospital, Dundonald, Belfast, N. Ireland. UK between January 2007 and December 2007. The patients were asked in a hypothetical situation if the following administering methods of anti-TNF drugs (intravenous or subcutaneous were available, which drug route of administration would they choose. Results One hundred and twenty-five patients fulfilled the inclusion criteria and were issued questionnaires, of these 78 questionnaires were returned (62 percent response. The mean age of respondent was 44 years. Of the total number of respondents, 33 patients (42 percent preferred infliximab and 19 patients (24 percent preferred adalimumab (p = 0.07. Twenty-six patients (33 percent did not indicate a preference for either biological therapy and were not included in the final analysis. The commonest reason cited for those who chose infliximab (iv was: "I do not like the idea of self-injecting," (67 percent. For those patients who preferred adalimumab (sc the commonest reason cited was: "I prefer the convenience of injecting at home," (79 percent. Of those patients who had previously been treated with an anti-TNF therapy (n = 10, all infliximab six patients stated that they would prefer infliximab if given

  5. Inefficient DNA Repair Is an Aging-Related Modifier of Parkinson's Disease.

    Science.gov (United States)

    Sepe, Sara; Milanese, Chiara; Gabriels, Sylvia; Derks, Kasper W J; Payan-Gomez, Cesar; van IJcken, Wilfred F J; Rijksen, Yvonne M A; Nigg, Alex L; Moreno, Sandra; Cerri, Silvia; Blandini, Fabio; Hoeijmakers, Jan H J; Mastroberardino, Pier G

    2016-05-31

    The underlying relation between Parkinson's disease (PD) etiopathology and its major risk factor, aging, is largely unknown. In light of the causative link between genome stability and aging, we investigate a possible nexus between DNA damage accumulation, aging, and PD by assessing aging-related DNA repair pathways in laboratory animal models and humans. We demonstrate that dermal fibroblasts from PD patients display flawed nucleotide excision repair (NER) capacity and that Ercc1 mutant mice with mildly compromised NER exhibit typical PD-like pathological alterations, including decreased striatal dopaminergic innervation, increased phospho-synuclein levels, and defects in mitochondrial respiration. Ercc1 mouse mutants are also more sensitive to the prototypical PD toxin MPTP, and their transcriptomic landscape shares important similarities with that of PD patients. Our results demonstrate that specific defects in DNA repair impact the dopaminergic system and are associated with human PD pathology and might therefore constitute an age-related risk factor for PD. PMID:27210754

  6. Identification of DNA polymerase molecules repairing DNA irradiated damage and molecular biological study on modified factors of mutation rate

    Energy Technology Data Exchange (ETDEWEB)

    Yamada, Koichi; Inoue, Shuji [National Inst. of Healthand Nutrition, Tokyo (Japan)

    1999-02-01

    DNA repairing polymerase has not been identified in human culture cells because the specificities of enzyme inhibitors used in previous studies were not so high. In this study, anti-sense oligonucleotides were transfected into human fibroblast cells by electroporation and several clones selected by geneticin treatment were found to express the RNA of the incorporated DNA. However, the expression was not significant and its reproducibility was poor. Then, a study on repairing mechanism was made using XP30 RO and XP 115 LO cells which are variant cells of xeroderma pigmentosum, a human hereditary disease aiming to identify the DNA polymerase related to the disease. There were abnormalities in DNA polymerase subunit {delta} or {epsilon} which consists DNA replication complex. Thus, it was suggested that the DNA replication of these mutant cells might terminate at the site containing such abnormality. (M.N.)

  7. Identification of DNA polymerase molecules repairing DNA irradiated damage and molecular biological study on modified factors of mutation rate

    International Nuclear Information System (INIS)

    DNA repairing polymerase has not been identified in human culture cells because the specificities of enzyme inhibitors used in previous studies were not so high. In this study, anti-sense oligonucleotides were transfected into human fibroblast cells by electroporation and several clones selected by geneticin treatment were found to express the RNA of the incorporated DNA. However, the expression was not significant and its reproducibility was poor. Then, a study on repairing mechanism was made using XP30 RO and XP 115 LO cells which are variant cells of xeroderma pigmentosum, a human hereditary disease aiming to identify the DNA polymerase related to the disease. There were abnormalities in DNA polymerase subunit δ or ε which consists DNA replication complex. Thus, it was suggested that the DNA replication of these mutant cells might terminate at the site containing such abnormality. (M.N.)

  8. Proteins Encoded in Genomic Regions Associated with Immune-Mediated Disease Physically Interact and Suggest Underlying Biology

    DEFF Research Database (Denmark)

    Rossin, Elizabeth J.; Hansen, Kasper Lage; Raychaudhuri, Soumya;

    2011-01-01

    Genome-wide association studies (GWAS) have defined over 150 genomic regions unequivocally containing variation predisposing to immune-mediated disease. Inferring disease biology from these observations, however, hinges on our ability to discover the molecular processes being perturbed by these...... that the RA and CD networks have predictive power by demonstrating that proteins in these networks, not encoded in the confirmed list of disease associated loci, are significantly enriched for association to the phenotypes in question in extended GWAS analysis. Finally, we test our method in 3 non-immune...... risk variants. It has previously been observed that different genes harboring causal mutations for the same Mendelian disease often physically interact. We sought to evaluate the degree to which this is true of genes within strongly associated loci in complex disease. Using sets of loci defined in...

  9. Quality of Life Philosophy III. Towards a New Biology: Understanding the Biological Connection between Quality of Life, Disease, and Healing

    Directory of Open Access Journals (Sweden)

    Soren Ventegodt

    2003-01-01

    Full Text Available This paper addresses (in a philosophical way the complex and enigmatic interface between matter, life, and consciousness in modern medical science. The problem today in understanding living matter is not at the molecular level, but at the macro level where all molecular activities in the individual cell are coordinated, and especially at a higher level, where the activities of all the organism’s cells are coordinated. Although we understand very much of the body’s chemistry, we have only just started to get the gist of the tremendous organization of living matter. We are just beginning to acknowledge the enormous flow of information that is needed to make everything function in a healthy organism, including consciousness, where every cell does exactly what it has to do to make the organs function.A concept that seems to be able to bridge the scientifically very different domains of matter, life, and consciousness seems to be “biological information”. If a cell is seen as a liquid crystal in which the cell’s molecules constantly connect in firm mutual relationships only to dissolve again and become fluid and free, whenever the cell needs it, the backbone of the cell seems to be the information that organizes the cell. For example, in cell motion a cell is able to crawl with the help of a skeleton of fibers that can be created guided by biological information, whenever the cell needs the solidity provided by the fibers. The moment it has finished crawling or intends to crawl in another direction, these fibers will dissolve again. The fibers are made of millions of molecules that connect in an arranged pattern, and they dissolve when these molecules again let go of each other. How the cell precisely regulates such processes is today a complete mystery. How cells cocreate consciousness is also an enigma. All we can do is describe the cell and the organisms arising from its cells as filled with energy and information as well as an

  10. Action Schools! BC: A Socioecological Approach to Modifying Chronic Disease Risk Factors in Elementary School Children

    Directory of Open Access Journals (Sweden)

    Patti-Jean Naylor, PhD

    2006-03-01

    Full Text Available Background Childhood physical inactivity and obesity are serious public health threats. Socioecological approaches to addressing these threats have been proposed. The school is a critical environment for promoting children’s health and provides the opportunity to explore the impact of a socioecological approach. Context Thirty percent of children in British Columbia, Canada, are overweight or obese, and 50% of youths are not physically active enough to yield health benefits. Methods Action Schools! BC, a socioecological model, was developed to create 1 an elementary school environment where students are provided with more opportunities to make healthy choices and 2 a supportive community and provincial environment to facilitate change at the school and individual levels. Consequences The environment in British Columbia for school- and provincial-level action on health behaviors improved. Focus group and project tracking results indicated that the Action Schools! BC model enhanced the conceptual use of knowledge and was an influencing factor. Political will and public interest were also cited as influential factors. Interpretation The Action Schools! BC model required substantial and demanding changes in the approach of the researchers, policy makers, and support team toward health promotion. Despite challenges, Action Schools! BC provides a good example of how to enhance knowledge exchange and multilevel intersectoral action in chronic disease prevention.

  11. Inefficient DNA Repair Is an Aging-Related Modifier of Parkinson’s Disease

    Directory of Open Access Journals (Sweden)

    Sara Sepe

    2016-05-01

    Full Text Available The underlying relation between Parkinson’s disease (PD etiopathology and its major risk factor, aging, is largely unknown. In light of the causative link between genome stability and aging, we investigate a possible nexus between DNA damage accumulation, aging, and PD by assessing aging-related DNA repair pathways in laboratory animal models and humans. We demonstrate that dermal fibroblasts from PD patients display flawed nucleotide excision repair (NER capacity and that Ercc1 mutant mice with mildly compromised NER exhibit typical PD-like pathological alterations, including decreased striatal dopaminergic innervation, increased phospho-synuclein levels, and defects in mitochondrial respiration. Ercc1 mouse mutants are also more sensitive to the prototypical PD toxin MPTP, and their transcriptomic landscape shares important similarities with that of PD patients. Our results demonstrate that specific defects in DNA repair impact the dopaminergic system and are associated with human PD pathology and might therefore constitute an age-related risk factor for PD.

  12. Does Caffeine Consumption Modify Cerebrospinal Fluid Amyloid-β Levels in Patients with Alzheimer's Disease?

    DEFF Research Database (Denmark)

    Travassos, Maria; Santana, Isabel; Baldeiras, Inês;

    2015-01-01

    Caffeine may be protective against Alzheimer's disease (AD) by modulating amyloid-β (Aβ) metabolic pathways. The present work aimed to study a possible association of caffeine consumption with the cerebrospinal fluid (CSF) biomarkers, particularly Aβ. The study included 88 patients with AD or mild...... cognitive impairment. The consumption of caffeine and theobromine was evaluated using a validated food questionnaire. Quantification of caffeine and main active metabolites was performed with liquid chromatography coupled to tandem mass spectrometry. The levels of A(1-42), total tau, and phosphorylated tau...... in the CSF were determined using sandwich ELISA methods and other Aβ species, Aβ(X-38), Aβ(X-40), and Aβ(X-42), with the MSD Aβ Triplex assay. The concentration of caffeine was 0.79±1.15 μg/mL in the CSF and 1.20±1.88 μg/mL in the plasma. No correlation was found between caffeine consumption and Aβ42...

  13. Dithizone chloroform single drop microextraction system combined with electrothermal atomic absorption spectrometry using Ir as permanent modifier for the determination of Cd in water and biological samples

    Science.gov (United States)

    Fan, Zhefeng; Zhou, Wei

    2006-07-01

    A simple and sensitive method using dithizone-chloroform single drop microextraction has been developed for separation and preconcentration of trace Cd prior to its determination by electrothermal atomic absorption spectrometry with Ir as permanent modifier. Parameters, such as pyrolysis and atomization temperature, solvent type, pH, dithizone concentration, extraction time, organic drop volume, stirring rate and sample volume were investigated. Under the optimized conditions, a detection limit (3 σ) of 0.7 ng/l and enrichment factor of 65 were achieved. The relative standard deviation was 7.4% ( c = 0.2 μg/l, n = 5). The developed method has been applied to the determination of trace Cd in water samples and biological reference materials with satisfactory results.

  14. Dithizone-chloroform single drop microextraction system combined with electrothermal atomic absorption spectrometry using Ir as permanent modifier for the determination of Cd in water and biological samples

    Energy Technology Data Exchange (ETDEWEB)

    Fan Zhefeng [Department of Chemistry, Shanxi Normal University, Linfen 041004 (China)]. E-mail: zhefengfan@163.com; Zhou Wei [Department of Chemistry, Shanxi Normal University, Linfen 041004 (China)

    2006-07-15

    A simple and sensitive method using dithizone-chloroform single drop microextraction has been developed for separation and preconcentration of trace Cd prior to its determination by electrothermal atomic absorption spectrometry with Ir as permanent modifier. Parameters, such as pyrolysis and atomization temperature, solvent type, pH, dithizone concentration, extraction time, organic drop volume, stirring rate and sample volume were investigated. Under the optimized conditions, a detection limit (3{sigma}) of 0.7 ng/l and enrichment factor of 65 were achieved. The relative standard deviation was 7.4% (c = 0.2 {mu}g/l, n = 5). The developed method has been applied to the determination of trace Cd in water samples and biological reference materials with satisfactory results.

  15. Performance of a modified multi-stage bubble column reactor for lead(II) and biological oxygen demand removal from wastewater using activated rice husk

    International Nuclear Information System (INIS)

    The excessive release of wastewater into the environment is a major concern worldwide. Adsorption is the one of the most effective technique for treatment of wastewater. In this work activated carbon prepared from rice husk has been used as an adsorbent. In the present investigation a three phase modified multi-stage bubble column reactor (MMBCR) has been designed to remove lead and biochemical oxygen demand (BOD) from wastewater by means of its adsorption onto the surface of activated rice husk. The multi-staging has been achieved by hydrodynamically induced continuous bubble generation, breakup and regeneration. Under optimum conditions, maximum lead and BOD reduction achieved using activated rice husk was 77.15% and 19.05%, respectively. Results showed MMBCR offered appreciated potential benefits for lead removal from wastewater and BOD removal, even this extent of removal is encouraging and the MMBCR can be used a pretreatment unit before subjecting the wastewater to biological treatment

  16. The modification of radiation therapy by RP-170, hypoxic cell sensitizer, and OK-432, biological response modifier (BRM)

    International Nuclear Information System (INIS)

    Combination therapy with radiation, RP-170 and OK-432, was applied aiming a high therapeutic gain. C3H/HeN mice bearing SCC VII tumors in their legs were irradiated locally 40 min after administration of 200 mg/kg RP-170 orally. OK-432 was administered at 2KE one day before irradiation, at 4KE immediately after irradiation, and 4KE 6 days later. After this multimodal treatment, its TCD50 (the radiation dose to control 50% of irradiated tumor) reduced markedly and as a result, dose modifying factor (DMF) increased to more than 2. Moreover, this combination therapy could reduce the dose of RP-170; radiotherapy with 50 mg/kg RP-170 and OK-432 could produce the same DMF as that from irradiation with 150 mg/kg of RP-170. The higher antitumor effect in this study could also be demonstrated by the significantly increased autologous tumor-cell killing (ATK) activity in tumor infiltrating lymphocyte. (author)

  17. Using of ants and earthworm to modify of soil biological quality and its effect on cocoa seedlings growth

    Science.gov (United States)

    Kilowasid, Laode Muhammad Harjoni; Budianto, Wayan; Syaf, Hasbullah; Tufaila, Muhammad; Safuan, La Ode

    2015-09-01

    Ant and earthworm can act as soil ecosystem engineers. Ant and earthworm are very dominant in smallholder cocoa plantation. The first experiment aimed to study the effect of the abundance of ants and earthworms on soil microbial activity and microfauna, and the second experiment to analyse the effect of soil modified by ants and earthworms on the cocoa seedlings growth. Ant (Ponera sp.) and earthworm (Pontoscolex sp.) collected from smallholder cocoa plantation, and kept in a container up to applied. In the first experiment, nine combinations of the abundance of ants and earthworms applied to each pot containing 3 kg of soil from smallholder cocoa plantation, and each combination of the abundance was repeated five times in a completely randomized design. After the soil was incubated for thirty days, ants and earthworms removed from the soil using hand sorting techniques. Soil from each pot was analysed for soil microbial activity, abundance of flagellates and nematodes. In the second experiment, the soil in each pot was planted with cocoa seedlings and maintained up to ninety days. The results showed the FDA hydrolytic activity of microbes, the abundance of flagellates and nematodes between the combination of the abundance of ants and earthworms have been significantly different. Dry weight of root, shoot and seedling cacao have been significantly different between the combination of the abundance of ants and earthworms. It was concluded that the combination of the abundance of ants and earthworms can be used in ecological engineering to improve soil quality.

  18. Thorough investigation of a canine autoinflammatory disease (AID) confirms one main risk locus and suggests a modifier locus for amyloidosis.

    Science.gov (United States)

    Olsson, Mia; Tintle, Linda; Kierczak, Marcin; Perloski, Michele; Tonomura, Noriko; Lundquist, Andrew; Murén, Eva; Fels, Max; Tengvall, Katarina; Pielberg, Gerli; Dufaure de Citres, Caroline; Dorso, Laetitia; Abadie, Jérôme; Hanson, Jeanette; Thomas, Anne; Leegwater, Peter; Hedhammar, Åke; Lindblad-Toh, Kerstin; Meadows, Jennifer R S

    2013-01-01

    Autoinflammatory disease (AID) manifests from the dysregulation of the innate immune system and is characterised by systemic and persistent inflammation. Clinical heterogeneity leads to patients presenting with one or a spectrum of phenotypic signs, leading to difficult diagnoses in the absence of a clear genetic cause. We used separate genome-wide SNP analyses to investigate five signs of AID (recurrent fever, arthritis, breed specific secondary dermatitis, otitis and systemic reactive amyloidosis) in a canine comparative model, the pure bred Chinese Shar-Pei. Analysis of 255 DNA samples revealed a shared locus on chromosome 13 spanning two peaks of association. A three-marker haplotype based on the most significant SNP (pELMO1, HAS2 and IL6). These results illustrate that phenotypic heterogeneity need not be a reflection of genetic heterogeneity, and that genetic modifiers of disease could be masked if syndromes were not first considered as individual clinical signs and then as a sum of their component parts. PMID:24130694

  19. Modified impact of emotion on temporal discrimination in a transgenic rat model of Huntington disease

    Directory of Open Access Journals (Sweden)

    Alexis Faure

    2013-09-01

    Full Text Available Huntington’s disease (HD is characterized by triad of motor, cognitive and emotional symptoms along with neuropathology in fronto-striatal circuit and limbic system including amygdala. Emotional alterations, which have a negative impact on patient well-being, represent some of the earliest symptoms of HD and might be related to the onset of the neurodegenerative process. In the transgenic rat model (tgHD rats, evidence suggest emotional alterations at the symptomatic stage along with neuropathology of the central nucleus of amygdala (CE. Studies in humans and animals demonstrate that emotion can modulate time perception. The impact of emotion on time perception has never been tested in HD, nor is it known if that impact could be part of the presymptomatic emotional phenotype of the pathology. The aim of this paper was to characterize the effect of emotion on temporal discrimination in presymptomatic tgHD animals. In the first experiment, we characterized the acute effect of an emotion (fear conditioned stimulus on temporal discrimination using a bisection procedure, and tested its dependency upon an intact central amygdala. The second experiment was aimed at comparing presymptomatic homozygous transgenic animals at 7-months of age and their wild-type littermates (WT in their performance on the modulation of temporal discrimination by emotion. Our principal findings show that (1 a fear cue produces a short-lived decrease of temporal precision after its termination, and (2 animals with medial CE lesion and presymptomatic tgHD animals demonstrate an alteration of this emotion-evoked temporal distortion. The results contribute to our knowledge about the presymptomatic phenotype of this HD rat model, showing susceptibility to emotion that may be related to dysfunction of the central nucleus of amygdala.

  20. Modified impact of emotion on temporal discrimination in a transgenic rat model of Huntington disease.

    Science.gov (United States)

    Faure, Alexis; Es-Seddiqi, Mouna; Brown, Bruce L; Nguyen, Hoa P; Riess, Olaf; von Hörsten, Stephan; Le Blanc, Pascale; Desvignes, Nathalie; Bozon, Bruno; El Massioui, Nicole; Doyère, Valérie

    2013-01-01

    Huntington's disease (HD) is characterized by triad of motor, cognitive, and emotional symptoms along with neuropathology in fronto-striatal circuit and limbic system including amygdala. Emotional alterations, which have a negative impact on patient well-being, represent some of the earliest symptoms of HD and might be related to the onset of the neurodegenerative process. In the transgenic rat model (tgHD rats), evidence suggest emotional alterations at the symptomatic stage along with neuropathology of the central nucleus of amygdala (CE). Studies in humans and animals demonstrate that emotion can modulate time perception. The impact of emotion on time perception has never been tested in HD, nor is it known if that impact could be part of the presymptomatic emotional phenotype of the pathology. The aim of this paper was to characterize the effect of emotion on temporal discrimination in presymptomatic tgHD animals. In the first experiment, we characterized the acute effect of an emotion (fear) conditioned stimulus on temporal discrimination using a bisection procedure, and tested its dependency upon an intact central amygdala. The second experiment was aimed at comparing presymptomatic homozygous transgenic animals at 7-months of age and their wild-type littermates (WT) in their performance on the modulation of temporal discrimination by emotion. Our principal findings show that (1) a fear cue produces a short-lived decrease of temporal precision after its termination, and (2) animals with medial CE lesion and presymptomatic tgHD animals demonstrate an alteration of this emotion-evoked temporal distortion. The results contribute to our knowledge about the presymptomatic phenotype of this HD rat model, showing susceptibility to emotion that may be related to dysfunction of the central nucleus of amygdala. PMID:24133419

  1. Human procollagen type I surface-modified PHB-based non-woven textile scaffolds for cell growth: preparation and short-term biological tests

    International Nuclear Information System (INIS)

    3D fine porous structures obtained by electrospinning a poly[(R,S)-3-hydroxybutyrate] (aPHB)/ poly[(R)-3-hydroxybutyrate] (PHB) (85/15 w/w) blend were successfully modified with human procollagen type I by simple immersion of the polyester scaffold in an aqueous solution of the protein. Effective modification of the scaffold with human procollagen I was confirmed by an immunodetection test, which revealed the presence of the procollagen type I as an outer layer even on inner structures of the porous matrixes. Biological tests of 3D fabrics made of the PHB blend provide support for the adhesion and proliferation of human fibroblasts, while their modification with procollagen type I increased the biocompatibility of the final scaffolds significantly, as shown by the notable increase in the number of attached cells during the early hours of their incubation. Based on these findings, human procollagen type I surface-modified aPHB/PHB scaffolds should be considered a promising material in regenerative medicine. (paper)

  2. Surgery, Crohn's disease, and the biological era: has there been an impact?

    LENUS (Irish Health Repository)

    Slattery, Eoin

    2012-02-01

    INTRODUCTION: The management of Crohn\\'s disease (CD) has changed considerably over the last 20 years. Immunomodulators and biological therapies now play a role in treating patients with CD, but little is known of their influence on surgical rates. AIM: To review the surgery rates for CD in an Irish university hospital over a 20-year period and to determine whether newer therapies had an impact on surgical rates. METHOD: Seven hundred twenty-two patients attending St Vincent\\'s University Hospital, Dublin, with CD over a 20-year period (January 1986 to December 2005) were identified. The patients were divided into quartiles. Resection rates were determined in all the quartiles, at both 1 and 3 years from diagnosis. RESULTS: A decline in surgery, 3 years from diagnosis, was noted between the first quartile (72 patients, 40%) and the second quartile (58 patients, 32%; P=0.03). No significant change in surgical rates at 3 years occurred between the other 3 quartiles (32%, 30%, and 35%, respectively; P=NS). The patients who required a resection within 3 years were diagnosed at a younger age in later years. There was a similar predominance of 60% of female patients requiring surgery in all groups. The patients requiring surgery were twice as likely to be ex-smokers or current smokers in all groups. Use of infliximab, within 3 years from diagnosis, increased from 0, 0, and 16 patients (8.8%) to 40 patients (22.1%) in the last quartile. The majority of patients were treated with infliximab on an "on demand" basis. Use of infliximab earlier within the course of the disease was seen in later quartiles (ie, within 1 y of diagnosis): 0, 0, 6, and 21 patients. CONCLUSION: Despite the introduction of infliximab over the past 10 years, no demonstrable difference has been seen in the rates of patients requiring resection surgery within 3 years of diagnosis. The reasons for this are unclear, but may relate to episodic treatment, rather than regular maintenance treatment. Female

  3. How do patients with inflammatory bowel disease want their biological therapy administered?

    LENUS (Irish Health Repository)

    Allen, Patrick B

    2010-01-01

    BACKGROUND: Infliximab is usually administered by two monthly intravenous (iv) infusions, therefore requiring visits to hospital. Adalimumab is administered by self subcutaneous (sc) injections every other week. Both of these anti-TNF drugs appear to be equally efficacious in the treatment of Crohn\\'s Disease and therefore the decision regarding which drug to choose will depend to some extent on patient choice, which may be based on the mode of administration.The aims of this study were to compare preferences in Inflammatory Bowel Disease (IBD) patients for two currently available anti-TNF agents and the reasons for their choices. METHODS: An anonymous questionnaire was distributed to IBD patients who had attended the Gastroenterology service (Ulster Hospital, Dundonald, Belfast, N. Ireland. UK) between January 2007 and December 2007. The patients were asked in a hypothetical situation if the following administering methods of anti-TNF drugs (intravenous or subcutaneous) were available, which drug route of administration would they choose. RESULTS: One hundred and twenty-five patients fulfilled the inclusion criteria and were issued questionnaires, of these 78 questionnaires were returned (62 percent response). The mean age of respondent was 44 years. Of the total number of respondents, 33 patients (42 percent) preferred infliximab and 19 patients (24 percent) preferred adalimumab (p = 0.07). Twenty-six patients (33 percent) did not indicate a preference for either biological therapy and were not included in the final analysis. The commonest reason cited for those who chose infliximab (iv) was: "I do not like the idea of self-injecting," (67 percent). For those patients who preferred adalimumab (sc) the commonest reason cited was: "I prefer the convenience of injecting at home," (79 percent). Of those patients who had previously been treated with an anti-TNF therapy (n = 10, all infliximab) six patients stated that they would prefer infliximab if given the choice

  4. Biological Evaluation of Double Point Modified Analogues of 1,25-Dihydroxyvitamin D2 as Potential Anti-Leukemic Agents

    Directory of Open Access Journals (Sweden)

    Aoife Corcoran

    2016-02-01

    Full Text Available Structurally similar double-point modified analogues of 1,25-dihydroxyvitamin D2 (1,25D2 were screened in vitro for their pro-differentiating activity against the promyeloid cell line HL60. Their affinities towards human full length vitamin D receptor (VDR and metabolic stability against human vitamin D 24-hydroxylase (CYP24A1 were also tested. The analogues (PRI-1730, PRI-1731, PRI-1732, PRI-1733 and PRI-1734 contained 5,6-trans modification of the A-ring and of the triene system, additional hydroxyl or unsaturation at C-22 in the side chain and reversed absolute configuration (24-epi at C-24 of 1,25D2. As presented in this paper, introduction of selected structural modifications simultaneously in two distinct parts of the vitamin D molecule resulted in a divergent group of analogues. Analogues showed lower VDR affinity in comparison to that of the parent hormones, 1,25D2 and 1,25D3, and they caused effective HL60 cell differentiation only at high concentrations of 100 nM and above. Unexpectedly, introducing of a 5,6-trans modification combined with C-22 hydroxyl and 24-epi configuration switched off entirely the cell differentiation activity of the analogue (PRI-1734. However, this analogue remained a moderate substrate for CYP24A1, as it was metabolized at 22%, compared to 35% for 1,25D2. Other analogues from this series were either less (12% for PRI-1731 and PRI-1733 or more (52% for PRI-1732 resistant to the enzymatic deactivation. Although the inactive analogue PRI-1734 failed to show VDR antagonism, when tested in HL60 cells, its structure might be a good starting point for our design of a vitamin D antagonist.

  5. Characteristics of leachate in Foot and Mouth Disease Carcass Disposal using Molecular Biology Method

    Science.gov (United States)

    Choi, E. J.; Kim, B. J.; Wi, D. W.; Choi, N. C.; Lee, S. J.; Min, J. E.; Park, C. Y.

    2012-04-01

    The Leachate from Foot and Mouth Disease(FMD) carcass disposal by is one of the types of high-concentration contaminated wastewater with the greatest environmental impact. This is due to its pollutants: nitrate nitrogen (NO3--N) and pathogenic microorganisms. Satisfactory treatment of leachate is not an easy task for its high concentrations of nitrate nitrogen and pathogenic microorganisms. Therefore suitable FMD leachate treatment processes should be adopted to improve treatment performance and to reduce overall running costs. The objective of this study was to determine the leachate characteristics through environmental analysis and molecular biology method (bacteria identification and Polymerase Chain Reaction) using FMD leachate samples for optimal FMD leachate treatment processes. The Sixteen FMD leachate samples was obtained from carcass disposal regions in Korea. Results of environmental analysis showed that pH and Eh was observed from 5.57 to 7.40, -134~358mV. This data was exhibited typical early carcass disposal (Neutral pH and Reducing Environment by abundant organic matter). TOC and nitrate nitrogen high concentrations in FMD leachate showed a large variability from 2.3 to 38,730 mg/L(mean - 6,821.93mg/L) and 0.335 ~231.998mg/L(mean - 37.46mg/L), respectively. The result of bacteria identification was observed Bacillus cereus, Pseudomonas putida, Acinetobacter ursingii, Aeromonas hydrophila, Serratia liquefaciens, Brevundimonas naejangsanensis, Serratia liquefaciens, Pseudomonas fluorescens, Pseudomonas aeruginosa, Acinetobacter ursingii. The results of Polymerase Chain Reaction(PCR) using EzTaxon server data revealed Pseudoclavibacter helvolus, Pseudochrobactrum saccharolyticum, Corynebacterium callunae, Paenibacillus lautus, Paenibacillus sp., Bacillus arvi, Brevundimonas bullata, Acinetobacter ursingii, Lysinibacillus sphaericus, Bacillus pumilus, Bacillus sphaericus, Bacillus psychrodurans, Pseudomonas sp.

  6. Clinical indications and biological mechanisms of splenic irradiation in autoimmune diseases

    International Nuclear Information System (INIS)

    Background: Splenic irradiation (SI) is a fairly unknown treatment modality in autoimmune disorders like autoimmune thrombocytopenia (AIT) or autoimmune hemolytic anemia (AIHA), which may provide an effective, low toxic and cost-effective treatment for selected patients. Patients, Materials and Methods: This article reviews the limited experiences on splenic irradiation in autoimmune thrombocytopenia by analyzing the current studies including 71 patients and some preliminary reports on splenic irradiation in autoimmune hemolytic anemia. Results: In autoimmune thrombocytopenia between 40 and 90% of all patients responded, but most of them relapsed within 4 to 6 months after splenic irradiation. Between 10 and 20% of all patients had a sustained response. The efficacy of splenic irradiation in HIV-associated cases of thrombocytopenia is probably lower than in other forms of autoimmune thrombocytopenia, but especially in this group immunosuppressive drug treatment of autoimmune thrombocytopenia exposes some problems. In autoimmune hemolytic anemia there are some case reports about efficacy of splenic irradiation. Toxicity of splenic irradiation in both diseases was very moderate. Conclusions: For HIV patients, for elderly patients or patients at high risk for complications following splenectomy splenic irradiation might be a treatment option. Splenic irradiation as preoperative treatment in patients not responding to or not suitable for immunosuppressive drugs prior to splenectomy may be a promising new application of splenic irradiation to reduce adverse effects of splenectomy in thrombocytopenic patients. A further analysis of the biological mechanisms underlying splenic irradiation may help to improve patient selection, to optimize dose concepts and treatment schedules and will improve understanding of radiotherapy as an immunomodulatory treatment modality. (orig.)

  7. Gender Modifies the Effects of Education and Income on Sleep Quality of the Patients with Coronary Artery Disease

    Directory of Open Access Journals (Sweden)

    Shervin Assari

    2013-12-01

    Full Text Available Background: This study aimed to investigate the interaction between gender and other socio-economic characteristics on sleep quality of the patients with Coronary Artery Disease (CAD. Methods: This cross sectional study was conducted on 717 patients with CAD. The socio- economic status (education level, income, marital status, and place of residence was considered as the independent variable. Besides, the study outcome was the quality of sleep which was measured using Pittsburgh Sleep Quality Index (PSQI. Gender was considered as a possible effect modifier. Two-way ANOVA was used to evaluate the interaction between gender and socio-economic factors on sleep quality. As defined by Baron and Kenny, moderator was defined as a variable that affected the direction or magnitude of the association of interest. Results: Female gender, low education level, and low income were predictive of poor sleep quality. Among female (10.0 ± 4.3 vs. 7.6 ± 5.0, P 0.05, low education was associated with poor sleep quality. Also, among female (10.0 ± 4.3 vs. 5.7 ± 2.5, P 0.05, low income was predictive of poor sleep quality. Gender did not modify the effect of other socio-economic factors on sleep quality. Conclusions: Among female but not male patients with CAD, low education and income were associated with poor sleep quality. This information helps us better understand the mechanisms behind the poor sleep quality of the female patients with CAD. This is important because poor sleep is a prognostic factor among the CAD patients.

  8. Validation and reliability of a modified sphygmomanometer for the assessment of handgrip strength in Parkinson´s disease

    Directory of Open Access Journals (Sweden)

    Soraia M. Silva

    2015-04-01

    Full Text Available BACKGROUND: Handgrip strength is currently considered a predictor of overall muscle strength and functional capacity. Therefore, it is important to find reliable and affordable instruments for this analysis, such as the modified sphygmomanometer test (MST. OBJECTIVES: To assess the concurrent criterion validity of the MST, to compare the MST with the Jamar dynamometer, and to analyze the reproducibility (i.e. reliability and agreement of the MST in individuals with Parkinson's disease (PD. METHOD: The authors recruited 50 subjects, 24 with PD (65.5±6.2 years of age and 26 healthy elderly subjects (63.4±7.2 years of age. The handgrip strength was measured using the Jamar dynamometer and modified sphygmomanometer. The concurrent criterion validity was analyzed using Pearson's correlation coefficient and a simple linear regression test. The reproducibility of the MST was evaluated with the coefficient of intra-class correlation (ICC2,1, the standard error of measurement (SEM, the minimal detectable change (MDC, and the Bland-Altman plot. For all of the analyses, α≤0.05 was considered a risk. RESULTS: There was a significant correlation of moderate magnitude (r≥0.45 between the MST and the Jamar dynamometer. The MST had excellent reliability (ICC2,1≥0.7. The SEM and the MDC were adequate; however, the Bland-Altman plot indicated an unsatisfactory interrater agreement. CONCLUSIONS: The MST exhibited adequate validity and excellent reliability and is, therefore, suitable for monitoring the handgrip strength in PD. However, if the goal is to compare the measurements between examiners, the authors recommend that the data be interpreted with caution.

  9. The V471A polymorphism in autophagy-related gene ATG7 modifies age at onset specifically in Italian Huntington disease patients

    DEFF Research Database (Denmark)

    Metzger, Silke; Walter, Carolin; Riess, Olaf;

    2013-01-01

    , we identified the V471A polymorphism in the autophagy-related gene ATG7, a key component of the autophagy pathway that plays an important role in HD pathogenesis, to be associated with the age at onset in a large group of European Huntington disease patients. To confirm this association in a second......The cause of Huntington disease (HD) is a polyglutamine repeat expansion of more than 36 units in the huntingtin protein, which is inversely correlated with the age at onset of the disease. However, additional genetic factors are believed to modify the course and the age at onset of HD. Recently...... independent patient cohort, we analysed the ATG7 V471A polymorphism in additional 1,464 European HD patients of the "REGISTRY" cohort from the European Huntington Disease Network (EHDN). In the entire REGISTRY cohort we could not confirm a modifying effect of the ATG7 V471A polymorphism. However, analysing a...

  10. Biological soil disinfestation : a safe and effective approach for controlling soilborne pests and diseases

    NARCIS (Netherlands)

    Lamers, J.G.; Wanten, P.J.; Blok, W.J.

    2004-01-01

    Biological soil disinfestation (bsd) is an environmentally friendly method to disinfest the soil from soilborne fungi and nematodes. With biological soil disinfestation a green manure crop (40 tonnes per ha) or other green biomass is homogeneously incorporated into the soil layer that has to be disi

  11. Effectiveness of a team intervention in reducing modifiable cardiovascular disease risk in HIV-infected subjects on antiretroviral therapy

    Directory of Open Access Journals (Sweden)

    Mark Bloch

    2014-11-01

    Full Text Available Introduction: The increasing age, higher modifiable and inherent cardiovascular disease (CVD risk of HIV-infected patients [1] necessitates improved approaches to reducing co-morbidities. We aimed to assess the effectiveness of a team intervention in reducing modifiable CVD risk. Materials and Methods: HIV-infected patients ≥50 years attending a large HIV caseload primary-care practice, who were virologically suppressed on antiretroviral therapy (ART, with moderate or severe 10-year CVD Framingham risk (≥10% were recruited for this prospective case-control study. Intervention participants were provided a team approach to care, which involved treatment by study doctors for lipid, hypertension and ART management, and monthly review by a team of research nurses and dieticians for smoking cessation, exercise and dietary advice over 12 months. Controls were matched on age and smoking status, and were given standard of care (SOC by non-study doctors. Outcomes included CVD risk factors, body composition and CVD risk assessment, including Framingham 10-yr risk [2] and D:A:D 5-year estimated risk of coronary heart disease (CHD [3]. Repeated measures analysis of variance was used to examine pre- and post-intervention differences, with p-values used to assess time and main effects of approach to care (Intervention, SOC. Results: A total of 33 patients completed the intervention, with 33 controls (58.0±6.8 and 59.1±6.9 years, respectively. Smoking cessation occurred in 25% cases versus nil controls. There was a significant change in CVD risk between intervention and control groups, in both Framingham scores (time and group×time interaction and D:A:D scores (group×time interaction only (Table 1. There was also a significant difference in change in total cholesterol over the study period (time and group×time interaction. Body composition was only measured in intervention patients, with a significant loss in % body fat observed in pre- and post

  12. Biological function of Foot-and-mouth disease virus non-structural proteins and non-coding elements

    OpenAIRE

    Gao, Yuan; Sun, Shi-Qi; Guo, Hui-Chen

    2016-01-01

    Foot-and-mouth disease virus (FMDV) represses host translation machinery, blocks protein secretion, and cleaves cellular proteins associated with signal transduction and the innate immune response to infection. Non-structural proteins (NSPs) and non-coding elements (NCEs) of FMDV play a critical role in these biological processes. The FMDV virion consists of capsid and nucleic acid. The virus genome is a positive single stranded RNA and encodes a single long open reading frame (ORF) flanked b...

  13. Harnessing the Power of Integrated Mitochondrial Biology and Physiology: A Special Report on the NHLBI Mitochondria in Heart Diseases Initiative

    OpenAIRE

    Ping, P.; Gustafsson, ÅB; Bers, DM; Blatter, LA; Cai, H; Jahangir, A; Kelly, D; Muoio, D; O'Rourke, B; Rabinovitch, P; Trayanova, N; van Eyk, J.; Weiss, JN; Wong, R; Longacre, LS

    2015-01-01

    © 2015 American Heart Association, Inc. Mitochondrial biology is the sum of diverse phenomena from molecular profiles to physiological functions. A mechanistic understanding of mitochondria in disease development, and hence the future prospect of clinical translations, relies on a systems-level integration of expertise from multiple fields of investigation. Upon the successful conclusion of a recent National Institutes of Health, National Heart, Lung, and Blood Institute initiative on integra...

  14. Aberrant Free Radical Biology Is a Unifying Theme in the Etiology and Pathogenesis of Major Human Diseases

    Directory of Open Access Journals (Sweden)

    Frederick E. Domann

    2013-04-01

    Full Text Available The seemingly disparate areas of oxygen toxicity, radiation exposure, and aging are now recognized to share a common feature—the aberrant production and/or removal of biologically derived free radicals and other reactive oxygen and nitrogen species (ROS/RNS. Advances in our understanding of the effects of free radicals in biology and medicine have been, and continue to be, actively translated into clinically tractable diagnostic and therapeutic applications. This issue is dedicated to recent advances, both basic discoveries and clinical applications, in the field of free radicals in biology and medicine. As more is understood about the proximal biological targets of aberrantly produced or removed reactive species, their sensors, and effectors of compensatory response, a great deal more will be learned about the commonalities in mechanisms underlying seemingly disparate disease states. Together with this deeper understanding, opportunities will arise to devise rational therapeutic interventions to decrease the incidence and severity of these diseases and positively impact the human healthspan.

  15. Pharmacogenetics of antipsychotic-induced movement disorders as a resource for better understanding Parkinson's disease modifier genes

    Directory of Open Access Journals (Sweden)

    Lior eGreenbaum

    2015-02-01

    Full Text Available Antipsychotic-induced movement disorders are major side effects of antipsychotic drugs among schizophrenia patients, and include antipsychotic-induced parkinsonism (AIP and tardive dyskinesia (TD. Substantial pharmacogenetic work has been done in this field, and several susceptibility variants have been suggested. In this paper, the genetics of antipsychotic-induced movement disorders is considered in a broader context. We hypothesize that genetic variants that are risk factors for AIP and TD may provide insights into the pathophysiology of Parkinson's disease (PD. Since loss of dopaminergic stimulation (albeit pharmacological in AIP and degenerative in PD is shared by the two clinical entities, genes associated with susceptibility to AIP may be modifier genes that influence clinical expression of PD sub-phenotypes, such as age at onset, disease severity or rate of progression. This is due to their possible functional influence on compensatory mechanisms for striatal dopamine loss. Better compensatory potential might be beneficial at the early and later stages of the PD course. AIP vulnerability variants may also be related to latent impairment in the nigrostriatal pathway, affecting its functionality, and leading to subclinical dopaminergic deficits in the striatum. Susceptibility of PD patients to early development of L-dopa induced dyskinesia (LID, is an additional relevant sub-phenotype. LID may share a common genetic background with TD, with which it shares clinical features. Genetic risk variants may predispose to both phenotypes, exerting a pleiotropic effect. According to this hypothesis, elucidating the genetics of antipsychotic-induced movement disorders may advance our understanding of multiple aspects of PD and it clinical course, rendering this a potentially rewarding field of study.

  16. A systematic review and meta-analysis of 130,000 individuals shows smoking does not modify the association of APOE genotype on risk of coronary heart disease

    DEFF Research Database (Denmark)

    Holmes, Michael V; Frikke-Schmidt, Ruth; Melis, Daniela;

    2014-01-01

    BACKGROUND: Conflicting evidence exists on whether smoking acts as an effect modifier of the association between APOE genotype and risk of coronary heart disease (CHD). METHODS AND RESULTS: We searched PubMed and EMBASE to June 11, 2013 for published studies reporting APOE genotype, smoking statu...

  17. Medication possession ratio: implications of using fixed and variable observation periods in assessing adherence with disease-modifying drugs in patients with multiple sclerosis

    Directory of Open Access Journals (Sweden)

    Kozma CM

    2013-06-01

    Full Text Available Chris M Kozma,1 Michael Dickson,2 Amy L Phillips,3 Dennis M Meletiche31CK Consulting Associates, LLC St Helena Island, SC, 2University of South Carolina College of Pharmacy, Columbia, SC, 3EMD Serono Inc, Rockland, MA, USABackground: The purpose of this study was to compare two methods of adherence calculation using administrative data for patients with multiple sclerosis (MS who are prescribed disease-modifying drugs.Methods: Pharmacy-billed disease-modifying drug prescription claims were selected from the 2007–2008 LifeLink™ Health Plan Claims Database. The index date was the first disease-modifying drug prescription claim. Two cohorts were created: all patients with a disease-modifying drug claim in 2007 and a subset with continuous eligibility for 12 months post-index. Adherence was calculated across all disease-modifying drugs for 12 months post-index. Medication possession ratios (MPRs with variable (start to end of therapy and fixed (365 days duration denominators were calculated. Variable MPR was calculated by summing days supply from the first to the last prescription (inclusive divided by time between the last prescription date plus days supply and the first prescription date. Variable MPR was evaluated for all patients and the continuously eligible cohort. Fixed MPR used the same numerator but divided by 365 days of follow-up and evaluated only for the continuously eligible cohort.Results: There were 3405 patients with MS and a disease-modifying drug claim in 2007 and 2145 in the continuously eligible cohort. Means for variable MPR ranged from 87.5% ± 16.6% for the continuously eligible cohort to 90.5% ± 16.0% for the 2007 cohort. The comparable value for fixed MPR was 78.0% ± 28.2% for the continuously eligible cohort. Fixed MPR gave a consistently lower rate of adherence than variable MPR at an 80% adherence threshold.Conclusion: Different adherence measures can yield different outcomes, especially when using different

  18. Modified serpinA1 as risk marker for Parkinson’s disease dementia: Analysis of baseline data

    Science.gov (United States)

    Halbgebauer, Steffen; Nagl, Magdalena; Klafki, Hans; Haußmann, Ute; Steinacker, Petra; Oeckl, Patrick; Kassubek, Jan; Pinkhardt, Elmar; Ludolph, Albert C.; Soininen, Hilkka; Herukka, Sanna-Kaisa; Wiltfang, Jens; Otto, Markus

    2016-01-01

    Early detection of dementia in Parkinson disease is a prerequisite for preventive therapeutic approaches. Modified serpinA1 in cerebrospinal fluid (CSF) was suggested as an early biomarker for differentiation between Parkinson patients with (PDD) or without dementia (PD). Within this study we aimed to further explore the diagnostic value of serpinA1. We applied a newly developed nanoscale method for the detection of serpinA1 based on automated capillary isoelectric focusing (CIEF). A clinical sample of 102 subjects including neurologically healthy controls (CON), PD and PDD patients was investigated. Seven serpinA1 isoforms of different charge were detected in CSF from all three diagnostic groups. The mean CSF signals of the most acidic serpinA1 isoform differed significantly (p < 0.01) between PDD (n = 29) and PD (n = 37) or CON (n = 36). Patients above the cut-off of 6.4 have a more than six times higher risk for an association with dementia compared to patients below the cut off. We propose this serpinA1 CIEF-immunoassay as a novel tool in predicting cognitive impairment in PD patients and therefore for patient stratification in therapeutic trials. PMID:27184740

  19. Efficacy of fingolimod is superior to injectable disease modifying therapies in second-line therapy of relapsing remitting multiple sclerosis.

    Science.gov (United States)

    Braune, Stefan; Lang, M; Bergmann, A

    2016-02-01

    Although fingolimod is registered in Europe for treatment of relapsing-remitting multiple sclerosis (RRMS) if earlier disease modifying therapy (DMT) has failed, no data regarding its efficacy in this patient group are available. This observational cohort study of the NeuroTransData network includes German RRMS outpatients with failure of earlier therapy with injectable DMT (iDMT), therefore switching to either another iDMT (n = 133) or to fingolimod (n = 300). Statistical comparison of clinical baseline characteristics showed more severely affected patients in the fingolimod group. A propensity-score matched group comparison was performed (n = 99 in each group) covering more than 2-year observation time. Fingolimod showed statistically significant superior efficacy in comparison to iDMT regarding annualized relapse rate (0.21 versus 0.33 per year), time-to-relapse and likelihood of relapse (iDMT hazard ratio 1.7), proportion and likelihood of patients with EDSS progression (15.10 versus 31.00%; iDMT hazard ratio 1.7), persistence on medication and likelihood of discontinuation (iDMT hazard ratio 3.0). Significantly more patients were free of relapse and EDSS progression with fingolimod than with their second iDMT (64.4 versus 46.5%, p < 0.03). This real-life evidence in German RRMS outpatients support data from controlled clinical studies and can quantitatively support clinical decision finding processes if iDMT therapy fails in RRMS. PMID:26645389

  20. [PREVALENCE OF MODIFIABLE RISK FACTORS OF CHRONIC NON INFECTION DISEASES AMONG URBAN AND RURAL RESIDENTS OF KARAGANDA REGION].

    Science.gov (United States)

    Turgunova, L; Laryushina, E; Amirkhanova, D; Alina, A; Bayesheva, T

    2016-03-01

    The study aimed to investigate prevalence of modifiable risk factors of chronic non infection diseases among urban and rural residents in Karaganda region. The cross-sectional screening study of 1453 respondents' age 18 to 65 among the urban and rural population of the Karaganda region: 672 urban and 781 rural adult residents were included into the study. The screening stage included conducting survey using international questionnaires, anthropometry, arterial blood pressure, fasting plasma glucose and total cholesterol measurement. According study results the most common risk factors among residents of Saran town and Osakarovsky area included: hypercholesterolemia (46,2 % and 36,9 %, respectively), arterial hypertension (39,3 % and 32,2 %, respectively) and smoking (26,3 % and 19,5 % respectively). Frequency of active and passive smoking, hypertension, hypercholesterolemia, obesity and alcohol abuse 1.2-2.0 times higher compared in urban population in comparison rural population. These differences gave possibility to identify special groups need to management preventive targeted measures. PMID:27119832

  1. Termination of disease-modifying antirheumatic drugs in rheumatoid arthritis and in psoriatic arthritis. A comparative study of 270 cases.

    Science.gov (United States)

    Ujfalussy, I; Koó, E; Seszták, M; Gergely, P

    2003-04-01

    102 rheumatoid arthritis (RA) and 104 psoriatic arthritis (PsA) patients' records were analysed according to a standardised protocol. Using Cox regression, life-table analysis and log rank test, the effectiveness and toxicity of, and duration of disease modifying antirheumatic drug (DMARD) treatment were compared in RA and PsA. RA patients were treated with gold sodium thiomalate (GST), methotrexate (MTX) and sulphasalazine (SSZ) for a median duration of 35, 72 and 12 months respectively, whereas PsA patients were treated for 12, 12 and 17 months. The differences for GST and MTX were statistically significant (p=0.0043 and 0.0447). Drug toxicity was more frequently seen among patients with PsA (p=0.0023). No difference in efficacy could be proved. Results suggest that there is a significant difference between RA and PsA patients in terms of toxicity of these agents. Therefore, separate treatment strategies are needed, and earlier results with RA may not be directly applicable to PsA. PMID:12721703

  2. DISEASES

    DEFF Research Database (Denmark)

    Pletscher-Frankild, Sune; Pallejà, Albert; Tsafou, Kalliopi;

    2015-01-01

    Text mining is a flexible technology that can be applied to numerous different tasks in biology and medicine. We present a system for extracting disease-gene associations from biomedical abstracts. The system consists of a highly efficient dictionary-based tagger for named entity recognition of...... human genes and diseases, which we combine with a scoring scheme that takes into account co-occurrences both within and between sentences. We show that this approach is able to extract half of all manually curated associations with a false positive rate of only 0.16%. Nonetheless, text mining should not...... stand alone, but be combined with other types of evidence. For this reason, we have developed the DISEASES resource, which integrates the results from text mining with manually curated disease-gene associations, cancer mutation data, and genome-wide association studies from existing databases. The...

  3. BIOLOGICAL AMENDMENTS AND CROP ROTATIONS FOR MANAGING SOIL MICROBIAL COMMUNITIES AND SOILBORNE DISEASES OF POTATO

    Science.gov (United States)

    Various biological amendments, including commercial biocontrol agents, microbial inoculants, mycorrhizae, and an aerobic compost tea (CT), were evaluated, alone and in conjunction with different crop rotations, for their efficacy in introducing beneficial microorganisms, affecting soil microbial com...

  4. The impact of biologics on health-related quality of life in patients with inflammatory bowel disease

    Directory of Open Access Journals (Sweden)

    Lauran Vogelaar

    2009-09-01

    Full Text Available Lauran Vogelaar1, Adriaan van’t Spijker2, C Janneke van der Woude11Department of Gastroenterology and Hepatology, 2Department of Psychology and Psychotherapy, Erasmus Medical Centre, RotterdamBackground: Inflammatory bowel disease (IBD is characterized by a chronic relapsing inflammation of the gastrointestinal tract. Adult IBD patients suffer from a disabling disease which greatly affects health-related quality of life (HRQoL. A worse HRQoL in these patients may result in a defensive and ineffective use of medical attention and thus higher medical costs. Because of its chronic nature, IBD may also cause psychological problems in many patients which may also influence HRQoL and care-seeking behavior. An important factor reducing HRQoL is disease activity. Induction of remission and long-term remission are important goals for improving HRQoL. Furthermore, remission is associated with a decreased need for hospitalization and surgery and increased employment, which in turn improve HRQoL. Treatment strategies available for many years are corticosteroids, 5-aminosalicylates and immunnosuppressants, but these treatments did not show significant long-term improvement on HRQoL. The biologics, which induce rapid and sustained remission, may improve HRQoL.Objective: To review and evaluate the current literature on the effect of biologics on HRQoL of IBD patients.Methods: We performed a MEDLINE search and reviewed the effect of different biologics on HRQoL. The following subjects and synonyms of these terms were used: inflammatory bowel disease, Crohn’s disease, ulcerative colitis, quality of life, health-related quality of life, fatigue, different anti-TNF medication, and biologicals/biologics (MESH. Studies included were limited to English-language, adult population, full-text, randomized, double-blind, placebo-controlled in which HRQoL was measured.Results: Out of 202 identified articles, 8 randomized controlled trials (RCT met the inclusion

  5. Causality, Information and Biological Computation: An algorithmic software approach to life, disease and the immune system

    OpenAIRE

    Zenil, Hector; Schmidt, Angelika; Tegnér, Jesper

    2015-01-01

    Biology has taken strong steps towards becoming a computer science aiming at reprogramming nature after the realisation that nature herself has reprogrammed organisms by harnessing the power of natural selection and the digital prescriptive nature of replicating DNA. Here we further unpack ideas related to computability, algorithmic information theory and software engineering, in the context of the extent to which biology can be (re)programmed, and with how we may go about doing so in a more ...

  6. Genetic and Biological Changes of Newcastle Disease Virus Due to The Development of Chicken Production System

    Directory of Open Access Journals (Sweden)

    Sudarisman

    2009-09-01

    Full Text Available In many countries, Newcastle Disease (ND is one of the most important diseases of poultry. It causes serious economic losses in poultry industry. Newcastle Disease or pseudo-fowl pest is a highly infectious viral disease that causes very high mortality (up to 100% in severe epidemics in poultry and wild birds around the world. Newcastle Disease remains endemic in many regions and continues to severely limit poultry production in some developing countries. The disease is currently being controlled by routine vaccinations in many countries. However, it was reported that outbreaks of ND in vaccinated flocks often occur on the field may not only be due to differences in the antigenicity of the NDV wild field strains and vaccine strains, but could also be as a result of differences in pathogenicity and virulence between different strains used as vaccine seed in NDV vaccine production.

  7. Comparison of the cerebral SPECT and biological markers in the Alzheimer disease

    International Nuclear Information System (INIS)

    This study aim was to compare the contribution of SPECT of cerebral perfusion and bio markers of the cerebrospinal liquid in the diagnosis of Alzheimer disease. Our preliminary conclusions show that the concordance of the SPECT and cerebrospinal liquid is good in the possible Alzheimer disease. the interest of the cerebral SPECT and bio markers of the cerebrospinal liquid, used alone or conjointly, for a more reliable diagnosis of Alzheimer disease must be evaluated of prospective way. (N.C.)

  8. The common biological basis for common complex diseases: evidence from lipoprotein lipase gene

    OpenAIRE

    Xie, Cui; Wang, Zeng Chan; Liu, Xiao Feng; Yang, Mao Sheng

    2009-01-01

    The lipoprotein lipase (LPL) gene encodes a rate-limiting enzyme protein that has a key role in the hydrolysis of triglycerides. Hypertriglyceridemia, one widely prevalent syndrome of LPL deficiency and dysfunction, may be a risk factor in the development of dyslipidemia, type II diabetes (T2D), essential hypertension (EH), coronary heart disease (CHD) and Alzheimer's disease (AD). Findings from earlier studies indicate that LPL may have a role in the pathology of these diseases and therefore...

  9. Genetic Susceptibility to Peripheral Arterial Disease: A Dark Corner in Vascular Biology

    OpenAIRE

    Knowles, Joshua W.; Assimes, Themistocles L.; Li, Jun; Quertermous, Thomas; Cooke, John P.

    2007-01-01

    Peripheral arterial disease (PAD) is characterized by reduced blood flow to the limbs, usually as a consequence of atherosclerosis, and affects ≈12 million Americans. It is a common cause of cardiovascular morbidity and an independent predictor of cardiovascular mortality. Similar to other atherosclerotic diseases, such as coronary artery disease, PAD is the result of the complex interplay between injurious environmental stimuli and genetic predisposing factors of the host. Genetic susceptibi...

  10. A two decade contribution of molecular cell biology to the centennial of Alzheimer's disease: are we progressing toward therapy?

    Science.gov (United States)

    Dillen, Katleen; Annaert, Wim

    2006-01-01

    Alzheimer's disease (AD), described for the first time 100 years ago, is a neurodegenerative disease characterized by two neuropathological hallmarks: neurofibrillary tangles containing hyperphosphorylated tau and senile plaques. These lesions are likely initiated by an imbalance between production and clearance of amyloid beta, leading to increased oligomerization of these peptides, formation of amyloid plaques in the brain of the patient, and final dementia. Amyloid beta is generated from amyloid precursor protein (APP) by subsequent beta- and gamma-secretase cleavage, the latter being a multiprotein complex consisting of presenilin-1 or -2, nicastrin, APH-1, and PEN-2. Alternatively, APP can be cleaved by alpha- and gamma-secretase, precluding the production of Abeta. In this review, we discuss the major breakthroughs during the past two decades of molecular cell biology and the current genetic and cell biological state of the art on APP proteolysis, including structure-function relationships and subcellular localization. Finally, potential directions for cell biological research toward the development of AD therapies are briefly discussed. PMID:17148000

  11. Clinical indications and biological mechanisms of splenic irradiation in autoimmune diseases

    Energy Technology Data Exchange (ETDEWEB)

    Weinmann, M.; Becker, G. [Tuebingen Univ. (Germany). Abt. fuer Strahlenonkologie; Einsele, H.; Bamberg, M. [Tuebingen Univ. (Germany). Abt. fuer Innere Medizin 2

    2001-02-01

    Background: Splenic irradiation (SI) is a fairly unknown treatment modality in autoimmune disorders like autoimmune thrombocytopenia (AIT) or autoimmune hemolytic anemia (AIHA), which may provide an effective, low toxic and cost-effective treatment for selected patients. Patients, Materials and Methods: This article reviews the limited experiences on splenic irradiation in autoimmune thrombocytopenia by analyzing the current studies including 71 patients and some preliminary reports on splenic irradiation in autoimmune hemolytic anemia. Results: In autoimmune thrombocytopenia between 40 and 90% of all patients responded, but most of them relapsed within 4 to 6 months after splenic irradiation. Between 10 and 20% of all patients had a sustained response. The efficacy of splenic irradiation in HIV-associated cases of thrombocytopenia is probably lower than in other forms of autoimmune thrombocytopenia, but especially in this group immunosuppressive drug treatment of autoimmune thrombocytopenia exposes some problems. In autoimmune hemolytic anemia there are some case reports about efficacy of splenic irradiation. Toxicity of splenic irradiation in both diseases was very moderate. Conclusions: For HIV patients, for elderly patients or patients at high risk for complications following splenectomy splenic irradiation might be a treatment option. Splenic irradiation as preoperative treatment in patients not responding to or not suitable for immunosuppressive drugs prior to splenectomy may be a promising new application of splenic irradiation to reduce adverse effects of splenectomy in thrombocytopenic patients. A further analysis of the biological mechanisms underlying splenic irradiation may help to improve patient selection, to optimize dose concepts and treatment schedules and will improve understanding of radiotherapy as an immunomodulatory treatment modality. (orig.) [German] Hintergrund: Die Bestrahlung der Milz zur Behandlung von haematologischen

  12. Gold nanoparticles decorated poly-melamine modified glassy carbon sensor for the voltammetric estimation of domperidone in pharmaceuticals and biological fluids.

    Science.gov (United States)

    Rosy; Goyal, Rajendra N

    2015-08-15

    The electrochemical response of an unmodified glassy carbon (GCE), poly-melamine/GCE and gold nanoparticle (AuNP)/poly-melamine/GCE is compared in the present protocol for the sensitive and selective determination of domperidone (DOM). The AuNPs were synthesized in the laboratory and characterized using UV-visible spectroscopy and Transmission Electron Microscopy (TEM). Melamine was electropolymerized onto the glassy carbon surface using cyclic voltammetry and was investigated using Field Emission Scanning Electron Microscopy (FE-SEM) and Electrochemical Impedance Spectroscopy (EIS). The AuNP/poly-melamine/GCE exhibited the best electrochemical response among the three electrodes for the electro-oxidation of DOM, that was inferred from the EIS, cyclic and square wave voltammetry. The modified sensor showed a sensitive, stable and linear response in the concentration range of 0.05-100µM with a detection limit of 6nM. The selectivity of the proposed sensor was assessed in the presence of high concentration of major interfering molecules as xanthine, hypoxanthine, and uric acid. The analytical application of the sensor for the quantification of DOM in pharmaceutical formulations and biological fluids as urine and serum was also investigated and the results demonstrated a recovery of >95% with R.S.D of <5%. PMID:25966380

  13. Evidence for Three Loci Modifying Age-at-Onset of Alzheimer’s Disease in Early-Onset PSEN2 Families

    OpenAIRE

    Marchani, Elizabeth E; Bird, Thomas D.; Steinbart, Ellen J; Rosenthal, Elisabeth; Yu, Chang-En; Schellenberg, Gerard D; Wijsman, Ellen M.

    2010-01-01

    Families with early-onset Alzheimer’s disease (AD) sharing a single PSEN2 mutation exhibit a wide range of age-at-onset, suggesting that modifier loci segregate within these families. While APOE is known to be an age-at-onset modifier, it does not explain all of this variation. We performed a genome scan within nine such families for loci influencing age-at-onset, while simultaneously controlling for variation in the primary PSEN2 mutation (N141I) and APOE. We found significant evidence of li...

  14. Pharmacovigilance Analysis of Serious Adverse Events Reported for Biologic Response Modifiers Used as Prophylaxis against Transplant Rejection: a Real-World Postmarketing Experience from the US FDA Adverse Event Reporting System (FAERS)

    Science.gov (United States)

    Ali, A. K.

    2013-01-01

    Background: Immunosuppression by biologic response modifiers (BRM) is a crucial component for successful organ transplantation. In addition to their variable effectiveness in the prevention of organ rejection, these medications have safety concerns that complicate therapeutic outcomes in organ transplant patients. Objective: This study aims at identifying and characterizing safety signals of serious adverse events associated with exposure to BRM among organ transplant patients in a real-world environment. Methods: The FDA Adverse Event Reporting System was utilized to apply a pharmacovigilance disproportionality analysis to indentify serious adverse events. Associations between drugs and events were measured by empirical Bayes geometric mean (EBGM) and the corresponding 95% confidence intervals (EB05–EB95). Associations with EBGM≥2 were considered significant safety signals. Results: From 1997 to 2012, a total of 12,151 serious adverse event reports for BRM were reported; 15.6% of them (n=1,711) met the safety signal threshold of EB05>1, and 11.6% of these signals (n=199) were significant (EBGM≥2). Sirolimus and mycophenolate accounted for the majority of all signals; antithymocyte immunoglobulin (ATI) and cyclosporine contributed to the majority of significant signals. The following significant signals were identified for ATI (reduced therapeutic response, pulmonary edema, hypotension, serum sickness, infusion-related reaction, and anaphylactic reaction); for azathioprine (alternaria infection, fungal skin infection, and lymphoproliferative disorder); for cyclosporine (neurotoxicity, graft vs. host disease, and thyroid cancer); for cyclophosphamide (disease progression); for daclizumab (cytomegalovirus infection); and for tacrolimus (coma and tremor). 33.6% of these events contributed to patient death (n=67); 6.5% were life-threatening (n=13); 32.1% lead to hospitalization (n=64); and 27.6% resulted in other serious outcomes (n=55). Conclusion: Utilization

  15. Pharmacovigilance Analysis of Serious Adverse Events Reported for Biologic Response Modifiers Used as Prophylaxis against Transplant Rejection: a Real-World Postmarketing Experience from the US FDA Adverse Event Reporting System (FAERS

    Directory of Open Access Journals (Sweden)

    A. K. Ali

    2013-04-01

    Full Text Available Background: Immunosuppression by biologic response modifiers (BRM is a crucial component for successfulorgan transplantation. In addition to their variable effectiveness in the prevention of organ rejection,these medications have safety concerns that complicate therapeutic outcomes in organ transplantpatients.Objective: This study aims at identifying and characterizing safety signals of serious adverse events associatedwith exposure to BRM among organ transplant patients in a real-world environment.Methods: The FDA Adverse Event Reporting System was utilized to apply a pharmacovigilance disproportionalityanalysis to indentify serious adverse events. Associations between drugs and events weremeasured by empirical Bayes geometric mean (EBGM and the corresponding 95% confidence intervals(EB05–EB95. Associations with EBGM≥2 were considered significant safety signals.Results: From 1997 to 2012, a total of 12,151 serious adverse event reports for BRM were reported; 15.6%of them (n=1,711 met the safety signal threshold of EB05>1, and 11.6% of these signals (n=199 weresignificant (EBGM≥2. Sirolimus and mycophenolate accounted for the majority of all signals; antithymocyteimmunoglobulin (ATI and cyclosporine contributed to the majority of significant signals. The followingsignificant signals were identified for ATI (reduced therapeutic response, pulmonary edema, hypotension,serum sickness, infusion-related reaction, and anaphylactic reaction; for azathioprine (alternariainfection, fungal skin infection, and lymphoproliferative disorder; for cyclosporine (neurotoxicity,graft vs. host disease, and thyroid cancer; for cyclophosphamide (disease progression; for daclizumab(cytomegalovirus infection; and for tacrolimus (coma and tremor. 33.6% of these events contributedto patient death (n=67; 6.5% were life-threatening (n=13; 32.1% lead to hospitalization (n=64; and27.6% resulted in other serious outcomes (n=55.Conclusion: Utilization of BRM for the

  16. Biology and Genetics of Lettuce Dieback Disease and Lettuce Necrotic Stunt Virus.

    Science.gov (United States)

    Lettuce dieback, a new soil-borne disease of lettuce, emerged in the 1990s to cause severe losses for lettuce production in the western United States. The disease is caused by Tomato bushy stunt virus (TBSV) and the recently described tombusvirus, Lettuce necrotic stunt virus (LNSV). The complete ge...

  17. Molecular entomology: analyzing tiny molecules to answer big questions about disease vectors and their biology

    Science.gov (United States)

    The entomologists at the Arthropod-Borne Animal Diseases Research Unit at USDA-Agricultural Research Service are tasked with protecting the nation’s livestock from domestic, foreign and emerging vector-borne diseases. To accomplish this task, a vast array of molecular techniques are being used in pr...

  18. The role of neutrophil gelatinase associated lipocalin (NGAL) as biological constituent linking depression and cardiovascular disease

    NARCIS (Netherlands)

    Gouweleeuw, Leonie; Naudé, Petrus; Rots, Marianne; de Jongste, Michel; Eisel, Ulrich; Schoemaker, Regina

    2015-01-01

    Depression is more common in patients with cardiovascular disease than in the general population. Conversely, depression is a risk factor for developing cardiovascular disease. Comorbidity of these two pathologies worsens prognosis. Several mechanisms have been indicated in the link between cardiova

  19. Association Between Changes in Coronary Artery Disease Progression and Treatment With Biologic Agents for Severe Psoriasis

    DEFF Research Database (Denmark)

    Hjuler, Kasper Fjellhaugen; Bøttcher, Morten; Vestergaard, Christian;

    2016-01-01

    , controlled, observer-blinded clinical study at a tertiary dermatology university hospital clinic enrolled patients with severe psoriasis initiating biological therapy and matched controls not receiving systemic therapy from April 11, 2011, through June 30, 2014. Interventions: Biological therapy approved for...... index remained unchanged from baseline to follow-up in the intervention group (mean [SD] baseline, 7.1 [1.5], follow-up, 7.1 [1.7]; P = .91), while controls demonstrated statistically nonsignificant progression (baseline, 8.3 [1.6], follow-up, 8.9 [2.2]; P = .06). Conclusions and Relevance: Clinically...

  20. Perspectives and experiences of Dutch multiple sclerosis patients and multiple sclerosis-specialized neurologists on injectable disease-modifying treatment

    Science.gov (United States)

    Visser, Leo H; Heerings, Marco A; Jongen, Peter J; van der Hiele, Karin

    2016-01-01

    Background The adherence to treatment with injectable disease-modifying drugs (DMDs) in multiple sclerosis (MS) may benefit from adequate information provision and management of expectations. The communication between patients and physicians is very important in this respect. The current study investigated the perspectives and experiences of the MS patients and neurologists concerning the choice and course of treatment with DMDs in the Netherlands. Methods The MS patients (aged 18–60 years; diagnosed with MS at least a year ago, currently treated with injectable DMD treatment) and MS-specialized neurologists (practicing for ≥3 years, treating ≥15 MS patients/month on average, and spending >60% of their time in clinical practice) were asked to complete semistructured Internet-based questionnaires. The neurologists in this study were not necessarily the treating neurologists of the participating MS patients. Results In all, 107 MS patients and 18 MS-specialized neurologists completed the questionnaires. The MS-specialized neurologists in this study reported discussing most of the suggested treatment goals with their patients. The MS patients indicated that certain important treatment goals, ie, reduction in disease progression, reduction or prolongation of time to long-term disability, and reduction in new magnetic resonance imaging lesions, were not discussed with them. More than one-quarter of the patients (27%) would appreciate more information about their treatment. We found evidence for suboptimal patient adherence to MS therapy (23% indicated taking a treatment break) due to diverse side effects, lack of efficacy, or practical issues. As compared to these patient reports, the scale of poor adherence was overestimated by more than half of the neurologists (on average, 30% estimated treatment breaks). Conclusion The MS patients and MS-specialized neurologists in this study differ in their experiences and perspectives on information provision and adherence

  1. Exploring Genetic Factors Involved in Huntington Disease Age of Onset: E2F2 as a New Potential Modifier Gene

    Science.gov (United States)

    Valcárcel-Ocete, Leire; Alkorta-Aranburu, Gorka; Iriondo, Mikel; Fullaondo, Asier; García-Barcina, María; Fernández-García, José Manuel; Lezcano-García, Elena; Losada-Domingo, José María; Ruiz-Ojeda, Javier; Álvarez de Arcaya, Amaia; Pérez-Ramos, José María; Roos, Raymund A. C.; Nielsen, Jørgen E.; Saft, Carsten; Zubiaga, Ana M.; Aguirre, Ana

    2015-01-01

    Age of onset (AO) of Huntington disease (HD) is mainly determined by the length of the CAG repeat expansion (CAGexp) in exon 1 of the HTT gene. Additional genetic variation has been suggested to contribute to AO, although the mechanism by which it could affect AO is presently unknown. The aim of this study is to explore the contribution of candidate genetic factors to HD AO in order to gain insight into the pathogenic mechanisms underlying this disorder. For that purpose, two AO definitions were used: the earliest age with unequivocal signs of HD (earliest AO or eAO), and the first motor symptoms age (motor AO or mAO). Multiple linear regression analyses were performed between genetic variation within 20 candidate genes and eAO or mAO, using DNA and clinical information of 253 HD patients from REGISTRY project. Gene expression analyses were carried out by RT-qPCR with an independent sample of 35 HD patients from Basque Country Hospitals. We found suggestive association signals between HD eAO and/or mAO and genetic variation within the E2F2, ATF7IP, GRIN2A, GRIN2B, LINC01559, HIP1 and GRIK2 genes. Among them, the most significant was the association between eAO and rs2742976, mapping to the promoter region of E2F2 transcription factor. Furthermore, rs2742976 T allele patient carriers exhibited significantly lower lymphocyte E2F2 gene expression, suggesting a possible implication of E2F2-dependent transcriptional activity in HD pathogenesis. Thus, E2F2 emerges as a new potential HD AO modifier factor. PMID:26148071

  2. Coronary heart disease, chronic inflammation, and pathogenic social hierarchy: a biological limit to possible reductions in morbidity and mortality.

    Science.gov (United States)

    Wallace, Rodrick; Wallace, Deborah; Wallace, Robert G

    2004-05-01

    We suggest that a particular form of social hierarchy, which we characterize as "pathogenic", can, from the earliest stages of life, exert a formal analog to evolutionary selection pressure, literally writing a permanent developmental image of itself upon immune function as chronic vascular inflammation and its consequences. The staged nature of resulting disease emerges "naturally" as a rough analog to punctuated equilibrium in evolutionary theory, although selection pressure is a passive filter rather than an active agent, like structured psychosocial stress. Exposure differs according to the social constructs of race, class, and ethnicity, accounting in large measure for observed population-level differences in rates of coronary heart disease across industrialized societies. American Apartheid, which enmeshes both majority and minority communities in a social construct of pathogenic hierarchy, appears to present a severe biological limit to continuing declines in coronary heart disease for powerful as well as subordinate subgroups: "Culture"--to use the words of the evolutionary anthropologist Robert Boyd--"is as much a part of human biology as the enamel on our teeth". PMID:15160975

  3. P-solubilizing Fungi as Biological Control Agents to Increase Growth and Prevent Moler Disease on Red Onion

    Directory of Open Access Journals (Sweden)

    Hadiwiyono

    2014-07-01

    Full Text Available This research aim to obtain phosphate-solubilizing fungi have antagonistic ability to Fusarium oxysporum f. cepae, and increase soil available-P. The experiment was hold in April 2013 to February 2014. Antagonistic capability was observed in two stages i.e. in vitro test which was conducted in the Laboratory of Soil Biology and Biotechnology, while in vivo test in green house, Faculty of Agriculture, Sebelas Maret University Surakarta. The experimental design used was completely randomized design (CRD. The treatment factors of in vitro test were kinds of phosphate solubilizing fungi and incubation time with Pikovkaya liquid medium, while the treatment factor of in vivo test was isolates combination of phosphate solubilizing fungi. Each treatment combination was repilcate three times. The observated variable included soil available phosphate, shallot height, shoot dry weight, moler disease intensity, infection rate, and area under the disease progress curve. The research obtained 3 isolates of fungi with high potential as inoculums of P-solubilizing biofertilizer and biological control agents against moler desease of red onion. The resullt showed that mix of JK12 isolate (isolated from Entisol of Bantul District and isolate of JK14 (from Andisol of Tawangmangu sub district demonstrated the highest ability in solubilizing phosphate and suppressing moler disease of red onion.

  4. Enhancing the role of veterinary vaccines reducing zoonotic diseases of humans: Linking systems biology with vaccine development

    Energy Technology Data Exchange (ETDEWEB)

    Adams, Leslie G.; Khare, Sangeeta; Lawhon, Sara D.; Rossetti, Carlos A.; Lewin, Harris A.; Lipton, Mary S.; Turse, Joshua E.; Wylie, Dennis C.; Bai, Yu; Drake, Kenneth L.

    2011-09-22

    The aim of research on infectious diseases is their prevention, and brucellosis and salmonellosis as such are classic examples of worldwide zoonoses for application of a systems biology approach for enhanced rational vaccine development. When used optimally, vaccines prevent disease manifestations, reduce transmission of disease, decrease the need for pharmaceutical intervention, and improve the health and welfare of animals, as well as indirectly protecting against zoonotic diseases of people. Advances in the last decade or so using comprehensive systems biology approaches linking genomics, proteomics, bioinformatics, and biotechnology with immunology, pathogenesis and vaccine formulation and delivery are expected to enable enhanced approaches to vaccine development. The goal of this paper is to evaluate the role of computational systems biology analysis of host:pathogen interactions (the interactome) as a tool for enhanced rational design of vaccines. Systems biology is bringing a new, more robust approach to veterinary vaccine design based upon a deeper understanding of the host pathogen interactions and its impact on the host's molecular network of the immune system. A computational systems biology method was utilized to create interactome models of the host responses to Brucella melitensis (BMEL), Mycobacterium avium paratuberculosis (MAP), Salmonella enterica Typhimurium (STM), and a Salmonella mutant (isogenic *sipA, sopABDE2) and linked to the basis for rational development of vaccines for brucellosis and salmonellosis as reviewed by Adams et al. and Ficht et al. [1,2]. A bovine ligated ileal loop biological model was established to capture the host gene expression response at multiple time points post infection. New methods based on Dynamic Bayesian Network (DBN) machine learning were employed to conduct a comparative pathogenicity analysis of 219 signaling and metabolic pathways and 1620 gene ontology (GO) categories that defined the host

  5. The Effect of Disease Modifying Therapies on Disease Progression in Patients with Relapsing-Remitting Multiple Sclerosis: A Systematic Review and Meta-Analysis

    Science.gov (United States)

    Tsivgoulis, Georgios; Katsanos, Aristeidis H.; Grigoriadis, Nikolaos; Hadjigeorgiou, Georgios M.; Heliopoulos, Ioannis; Papathanasopoulos, Panagiotis; Kilidireas, Constantinos; Voumvourakis, Konstantinos; Dardiotis, Efthimios

    2015-01-01

    Importance A number of officially approved disease-modifying drugs (DMD) are currently available for the early intervention in patients with relapsing-remitting multiple sclerosis (RRMS). The aim of the present study was to systematically evaluate the effect of DMDs on disability progression in RRMS Methods We performed a systematic review on MEDLINE and SCOPUS databases to include all available placebo-controlled randomized clinical trials (RCTs) of RRMS patients that reported absolute numbers or percentages of disability progression during each study period. Observational studies, case series, case reports, RCTs without placebo subgroups and studies reporting the use of RRMS therapies that are not still officially approved were excluded. Risk ratios (RRs) were calculated in each study protocol to express the comparison of disability progression in RRMS patients treated with a DMD and those RRMS patients receiving placebo. The mixed-effects model was used to calculate both the pooled point estimate in each subgroup and the overall estimates. Results DMDs for RRMS were found to have a significantly lower risk of disability progression compared to placebo (RR = 0.72, 95%CI: 0.66–0.79; p20%) rates of loss to follow-up were reported in many study protocols, while financial and/or other support from pharmaceutical industries with a clear conflict of interest on the study outcomes was documented in all included studies. Conclusions Available DMD are effective in reducing disability progression in patients with RRMS, independently of the route of administration and their classification as “first” or “second” line therapies. Attrition bias needs to be taken into account in the interpretation of these findings. PMID:26642051

  6. Validation of Alzheimer's disease CSF and plasma biological markers: the multicentre reliability study of the pilot European Alzheimer's Disease Neuroimaging Initiative (E-ADNI)

    DEFF Research Database (Denmark)

    Buerger, Katharina; Frisoni, Giovanni; Uspenskaya, Olga;

    2009-01-01

    BACKGROUND: Alzheimer's Disease Neuroimaging Initiatives ("ADNI") aim to validate neuroimaging and biochemical markers of Alzheimer's disease (AD). Data of the pilot European-ADNI (E-ADNI) biological marker programme of cerebrospinal fluid (CSF) and plasma candidate biomarkers are reported. METHODS......: Six academic EADC centres recruited 49 subjects (healthy controls, subjects with mild cognitive impairment (MCI) and AD). We measured CSF beta-amyloid 42 (CSF Abeta42), total tau-protein (t-tau), phosphorylated tau-proteins (P-tau181, P-tau231), plasma beta-amyloid 40 and 42 (Abeta40/Abeta42......). Immediate fresh shipment was compared to freezing and later shipment on dry ice. RESULTS: CSF T-tau (fresh samples) was increased in AD versus controls (p=0.049), CSF Abeta42 (frozen samples) was decreased in MCI and AD (p=0.02), as well as plasma Abeta40 (fresh and frozen samples) in AD (p=0.049 and p=0...

  7. An Official American Thoracic Society Workshop Report 2015. Stem Cells and Cell Therapies in Lung Biology and Diseases.

    Science.gov (United States)

    Wagner, Darcy E; Cardoso, Wellington V; Gilpin, Sarah E; Majka, Susan; Ott, Harald; Randell, Scott H; Thébaud, Bernard; Waddell, Thomas; Weiss, Daniel J

    2016-08-01

    The University of Vermont College of Medicine, in collaboration with the NHLBI, Alpha-1 Foundation, American Thoracic Society, Cystic Fibrosis Foundation, European Respiratory Society, International Society for Cellular Therapy, and the Pulmonary Fibrosis Foundation, convened a workshop, "Stem Cells and Cell Therapies in Lung Biology and Lung Diseases," held July 27 to 30, 2015, at the University of Vermont. The conference objectives were to review the current understanding of the role of stem and progenitor cells in lung repair after injury and to review the current status of cell therapy and ex vivo bioengineering approaches for lung diseases. These are all rapidly expanding areas of study that both provide further insight into and challenge traditional views of mechanisms of lung repair after injury and pathogenesis of several lung diseases. The goals of the conference were to summarize the current state of the field, discuss and debate current controversies, and identify future research directions and opportunities for both basic and translational research in cell-based therapies for lung diseases. This 10th anniversary conference was a follow up to five previous biennial conferences held at the University of Vermont in 2005, 2007, 2009, 2011, and 2013. Each of those conferences, also sponsored by the National Institutes of Health, American Thoracic Society, and respiratory disease foundations, has been important in helping guide research and funding priorities. The major conference recommendations are summarized at the end of the report and highlight both the significant progress and major challenges in these rapidly progressing fields. PMID:27509163

  8. Biological treatment in rheumatic diseases: results from a longitudinal surveillance: adverse events.

    Science.gov (United States)

    Konttinen, L; Honkanen, V; Uotila, T; Pöllänen, J; Waahtera, M; Romu, M; Puolakka, K; Vasala, M; Karjalainen, A; Luukkainen, R; Nordström, D C

    2006-08-01

    The objective of this study was to assess the long-term safety and tolerability of biologicals in a clinical setting. Data on adverse events (AEs) have been collected over a 5-year period by means of detailed reports sent in to the National Register of Biological Treatment in Finland (ROB-FIN) and validated by information collected by the National Agency for Medicines. Three hundred and eight reports on AEs were filed, concerning a total of 248 patients; this corresponds to 17% of all patients in the ROB-FIN register who started biological treatments. Skin reactions and infections comprised 35 and 28% of the AEs, respectively. Some cases of tuberculosis and other infections, heart failure and demyelinating conditions were seen. Our work demonstrates no unexpected AEs in a Finnish patient cohort consisting of rheumatoid arthritis and spondylarthropathy patients, although many of them were treated with combination treatments in common use in Finland. Biological treatment appears safe in the hands of the Finnish rheumatologists. PMID:16402217

  9. Biological control of Polymyxa betae, fungal vector of rhizomania disease of sugar beets in greenhouse conditions

    OpenAIRE

    Naraghi Laleh; Heydari Asghar; Askari Hassan; Pourrahim Reza; Marzban Rasoul

    2014-01-01

    Rhizomania is one of the most important diseases of sugar beet around the world – including in Iran. The disease causes a severe decrease in sugar yield and is a limiting factor in sugar beet cultivation. Control of the disease is very difficult due to the long-term survival of its fungal vector (Polymyxa betae) in the soil. In this study, we investigated the effects of antagonistic fungal isolates on the population of the resting structure (cystosorus) of P. betae, under greenhouse condition...

  10. Radiological features and therapeutic responses of pulmonary nontuberculous mycobacterial disease in rheumatoid arthritis patients receiving biological agents: a retrospective multicenter study in Japan

    OpenAIRE

    Mori, Shunsuke; Tokuda, Hitoshi; Sakai, Fumikazu; Johkoh, Takeshi; Mimori, Akio; Nishimoto, Norihiro; Tasaka, Sadatomo; Hatta, Kazuhiro; Matsushima, Hidekazu; Kaise, Shunji; Kaneko, Atsushi; Makino, Shigeki; Minota, Seiji; Yamada, Takashi; Akagawa, Shinobu

    2011-01-01

    Objective This study was performed to evaluate the radiological features of and therapeutic responses to pulmonary disease caused by nontuberculous mycobacteria (NTM) in the setting of biological therapy for rheumatoid arthritis (RA). Methods We conducted a retrospective chart review of 13 patients from multiple centers who had developed pulmonary NTM disease during biological therapy for RA, including infliximab, etanercept, adalimumab, and tocilizumab. Results Most cases were asymptomatic o...

  11. Thermal conductivity of biological cells at cellular level and correlation with disease state

    Science.gov (United States)

    Park, Byoung Kyoo; Woo, Yunho; Jeong, Dayeong; Park, Jaesung; Choi, Tae-Youl; Simmons, Denise Perry; Ha, Jeonghong; Kim, Dongsik

    2016-06-01

    This paper reports the thermal conductivity k of matched pair cell lines: two pairs of a normal and a cancer cell, one pair of a primary and metastatic cell. The 3ω method with a nanoscale thermal sensor was used to measure k at the single-cell level. To observe the difference in k between normal and cancer cells, the measurements were conducted for Hs 578Bst/Hs 578 T (human breast cells) and TE 353.Sk/TE 354.T (human skin cells). Then k of WM-115/WM-266-4, a primary and metastatic pair of human skin cell, was measured to find the effect of disease progression on k. The measured k data for normal and disease cell samples show statistically meaningful differences. In all cases, k decreased as the disease progressed. This work shows that thermal-analysis schemes, such as the 3ω method, have a potential to detect diseases at the cell level.

  12. [What Hansen's disease research learned from tuberculosis research: from molecular biological aspect].

    Science.gov (United States)

    Suzuki, Yasuhiko; Yamaguchi, Tomoyuki; Kim, Hyun; Yokoyama, Kazumasa; Nakajima, Chie

    2014-12-01

    As for the Mycobacterium leprae which is a causative agent of Hansen's disease, many studies had been done since it was identified in 1873. However, those studies, at the same time, experienced many struggles because of the difficulty of culture of M. leprae on the artificial growth media. Hence, the study of Hansen's disease progressed by taking the knowledge from the study of tuberculosis caused by the bacteria belonging to the same genus, genus Mycobacterium. For instance, the knowledge of mutations in specific genes responsible for rifampicin- and quinolone-resistance in M. tuberculosis led the elucidation of drug-resistant acquisition mechanism of M. leprae. Similarly, it is necessary for the researcher of Hansen's disease to get important information from the latest topic of the tuberculosis study and utilize them to the study of the disease. PMID:25826852

  13. RECENT ADVANCES IN PATHO-BIOLOGY OF MYELOMA BONE DISEASE: CLINICOPATHOLOGY AND LITERATURE OF REVIEW

    OpenAIRE

    Lohit Kumar; Bhubaneswar

    2016-01-01

    Bone disease is a hallmark of multiple myeloma, presenting as lytic lesions associated with bone pain, pathological fractures requiring surgery and/or radiation to bone, spinal cord compression and hypercalcaemia. Increased osteoclastic activity unaccompanied by a compensatory increase in osteoblast function, leading to enhanced bone resorption results in bone disease. The interaction of plasma cells with the bone marrow microenvironment has been shown to play a vital role. Also,...

  14. Endophytic Bacillus Spp. of Theobroma cacao: Ecology and potential for biological control of cacao diseases

    OpenAIRE

    Melnick, Rachel L

    2010-01-01

    In South America, there are three key diseases that affect the yield of Theobroma cacao: black pod, caused by Phytophthora spp.; frosty pod, caused by Moniliophthora roreri; and witches' broom, caused by Moniliophthora perniciosa. Although chemical control options exist, farmers typically only use cultural disease management such as phytosanitary pruning. Agrochemical use can be problematic in the developing countries where cacao is grown due to large risks to human health and the environment...

  15. MicroRNAs: The Missing Link in the Biology of Graft-Versus-Host Disease?

    OpenAIRE

    Atarod, Sadaf; Dickinson, Anne Mary

    2013-01-01

    Graft-versus-host disease (GVHD) is still the major complication of allogeneic hematopoietic stem cell transplantation. Despite extensive studies in understanding the pathophysiology of GVHD, its pathogenesis remains unclear. Recently, important functions of microRNAs have been demonstrated in various autoimmune diseases and cancers such as psoriasis and lymphoma. This review highlights the need to investigate the role of microRNAs in GVHD and hypothesizes that microRNAs may be one of the mis...

  16. Relationship between Periodontal Diseases and Preterm Birth: Recent Epidemiological and Biological Data

    OpenAIRE

    Huck, O.; H. Tenenbaum; J.-L. Davideau

    2011-01-01

    For ten years, the incidence of preterm birth does not decrease in developed countries despite the promotion of public health programs. Many risk factors have been identified including ethnicity, age, tobacco, and infection. However, almost 50% of preterm birth causes remain unknown. The periodontal diseases are highly prevalent inflammatory and infectious diseases of tooth supporting tissues leading to an oral disability. They influence negatively general health worsening cardiovascular dise...

  17. Diabetes and cardiovascular disease: Epidemiology, biological mechanisms, treatment recommendations and future research

    OpenAIRE

    Leon, Benjamin M; Maddox, Thomas M.

    2015-01-01

    The incidence of diabetes mellitus (DM) continues to rise and has quickly become one of the most prevalent and costly chronic diseases worldwide. A close link exists between DM and cardiovascular disease (CVD), which is the most prevalent cause of morbidity and mortality in diabetic patients. Cardiovascular (CV) risk factors such as obesity, hypertension and dyslipidemia are common in patients with DM, placing them at increased risk for cardiac events. In addition, many studies have found bio...

  18. Future impact of molecular biology and biotechnology on bacterial and viral diseases.

    Science.gov (United States)

    Pang, T

    1993-06-01

    The advent of recombinant DNA technology has already made a significant impact on various aspects related to the basic understanding of pathogenic mechanisms in infectious diseases, as well as practical applications related to diagnostics and prevention. The present paper discusses recent technological innovations and increased analytical capabilities which promise to have an even more significant impact on the control of viral and bacterial diseases. PMID:8350782

  19. The Role of microRNAs in the Biology of Rare Diseases

    Directory of Open Access Journals (Sweden)

    Domenica Taruscio

    2011-10-01

    Full Text Available Rare diseases (RD are characterized by low prevalence and affect not more than five individuals per 10,000 in the European population; they are a large and heterogeneous group of disorders including more than 7,000 conditions and often involve all organs and tissues, with several clinical subtypes within the same disease. Very often information concerning either diagnosis and/or prognosis on many RD is insufficient. microRNAs are a class of small non-coding RNAs that regulate gene expression at the posttranscriptional level by either degrading or blocking translation of messenger RNA targets. Recently, microRNA expression patterns of body fluids underscored their potential as noninvasive biomarkers for various diseases. The role of microRNAs as potential biomarkers has become particularly attractive. The identification of disease-related microRNAs is essential for understanding the pathogenesis of diseases at the molecular level, and is critical for designing specific molecular tools for diagnosis, treatment and prevention. Computational analysis of microRNA-disease associations is an important complementary means for prioritizing microRNAs for further experimental examination. In this article, we explored the added value of miRs as biomarkers in a selected panel of RD hitting different tissues/systems at different life stages, but sharing the need of better biomarkers for diagnostic and prognostic purposes.

  20. Banking of biological fluids for studies of disease-associated protein biomarkers

    DEFF Research Database (Denmark)

    Rasmussen, Anne-Sofie Schrohl; Würtz, Sidse Ørnbjerg; Kohn, Elise;

    2008-01-01

    biological fluids, especially serum and plasma, intended for study of protein biomarkers. In biomarker studies the process from the decision to take a sample from an individual to the moment the sample is safely placed in the biobank consists of several phases including collection of samples, transport of...... biobank as well as conclusions and clinical recommendations based on analysis of such material may be severely affected....

  1.  The biological activity of macrophages in health and disease

    OpenAIRE

    Katarzyna Nazimek; Krzysztof Bryniarski

    2012-01-01

     Macrophages are involved in immune response as phagocytes, antigen presenting cells and as effector cells of delayed-type hypersensitivity. Moreover, the activity of macrophages is associated with modulation of many biological processes during the whole life and depends on the actual macrophage phenotype induced under the influence of various microenvironmental stimuli.In pregnancy, placental macrophages induce the development of maternal tolerance to fetal antigens, while fetal macrophages ...

  2. Study of cardiovascular disease biomarkers among tobacco consumers, part 2: biomarkers of biological effect

    OpenAIRE

    Nordskog, Brian K.; Brown, Buddy G.; Marano, Kristin M.; Campell, Leanne R.; Jones, Bobbette A.; Borgerding, Michael F.

    2015-01-01

    Abstract An age-stratified, cross-sectional study was conducted in the US among healthy adult male cigarette smokers, moist snuff consumers, and non-tobacco consumers to evaluate cardiovascular biomarkers of biological effect (BoBE). Physiological assessments included flow-mediated dilation, ankle-brachial index, carotid intima-media thickness and expired carbon monoxide. Approximately one-half of the measured serum BoBE showed statistically significant differences; IL-12(p70), sICAM-1 and IL...

  3. Use of biological based therapy in patients with cardiovascular diseases in a university-hospital in New York City

    Directory of Open Access Journals (Sweden)

    Rozenfeld Vitalina

    2005-03-01

    Full Text Available Abstract Background The use of complementary and alternative products including Biological Based Therapy (BBT has increased among patients with various medical illnesses and conditions. The studies assessing the prevalence of BBT use among patients with cardiovascular diseases are limited. Therefore, an evaluation of BBT in this patient population would be beneficial. This was a survey designed to determine the effects of demographics on the use of Biological Based Therapy (BBT in patients with cardiovascular diseases. The objective of this study was to determine the effect of the education level on the use of BBT in cardiovascular patients. This survey also assessed the perceptions of users regarding the safety/efficacy of BBT, types of BBT used and potential BBT-drug interactions. Method The survey instrument was designed to assess the findings. Patients were interviewed from February 2001 to December 2002. 198 inpatients with cardiovascular diseases (94 BBT users and 104 non-users in a university hospital were included in the study. Results Users had a significantly higher level of education than non-users (college graduate: 28 [30%] versus 12 [12%], p = 0.003. Top 10 BBT products used were vitamin E [41(43.6%], vitamin C [30(31.9%], multivitamins [24(25.5%], calcium [19(20.2%], vitamin B complex [17(18.1%], fish oil [12(12.8%], coenzyme Q10 [11(11.7%], glucosamine [10(10.6%], magnesium [8(8.5%] and vitamin D [6(6.4%]. Sixty percent of users' physicians knew of the BBT use. Compared to non-users, users believed BBT to be safer (p Conclusion Incidence of use of BBT in cardiovascular patients is high (47.5%, as is the risk of potential drug interaction. Health care providers need to monitor BBT use in patients with cardiovascular diseases.

  4. New biologics in the management of Crohn’s disease: focus on certolizumab pegol

    Directory of Open Access Journals (Sweden)

    Elisabetta Colombo

    2009-06-01

    Full Text Available Elisabetta Colombo1, Fabrizio Bossa1, Anna Latiano2, Orazio Palmieri2, Angelo Andriulli1,2, Vito Annese2,31Unit of Gastroenterology, 2Laboratory of Genetic Research, 3Unit of Endoscopy, Department of Medical Sciences, IRCCS-CSS Hospital, San Giovanni Rotondo, ItalyAbstract: Crohn’s disease (CD is a chronic inflammatory condition involving the gastrointestinal tract characterized by recurrent exacerbations and remission. The disease frequently occurs in the lower part of the small bowel, but can affect any part of the digestive tract, from the mouth to the anus. The traditional goals of treatment of Crohn’s disease were to induce and maintain clinical remission. More recently targets such as mucosal healing, reduced hospitalization and surgery, and improved quality of life are becoming increasingly achievable. The general principles for treatment should consider clinical activity, site and behavior of disease; however, the appropriate choice of medication depends on many factors that are the best tailored to the individual patient. This review focuses on certolizumab pegol, the first Fc-free PEGylated Fab' fragment of humanized monoclonal antibody that binds and neutralizes human tumor necrosis factor alpha. Data on indication, pharmacokinetics, efficacy, safety, and influence on quality of life are reviewed.Keywords: Crohn’s disease, certolizumab (CDP870, antiTNF-α agents

  5. Psychiatric comorbidities in patients with celiac disease: Is there any concrete biological association?

    Science.gov (United States)

    Sharma, Taral R; Kline, Daniel B; Shreeve, Daniel F; Hartman, David W

    2011-06-01

    Celiac disease (CD) is a unique autoimmune disorder that occurs in genetically susceptible individuals after the ingestion of gluten, a protein found in wheat and some other cereals. The immunologically based inflammation induces atrophy of the villous structure of the jejunum, leading to malabsorption of variable severity. Subclinical and nonspecific forms of CD have been found to be increasingly common with a classic presentation of malabsorption syndrome (reference A). We present a case of OCD (obsessive compulsive disorder) in combination with depressive symptoms with the further complication of eating disorder not otherwise specified, in an adolescent male, for whom psychiatry was consulted because of treatment-refractory weight loss. We compare the elements of the case to other descriptions in the current, English language professional literature. Our literature review includes multiple search terms for the professional journals including, but not limited to, psychiatric comorbidities in celiac disease, behavioral disturbances of celiac disease, celiac disease in psychiatry, etc., to establish a possible association of psychiatric disorders, especially obsessive compulsive disorder and Celiac disease. PMID:23051084

  6. Modified Ionic Liquid Cold-Induced Aggregation Dispersive Liquid-Liquid Microextraction Combined with Spectrofluorimetry for Trace Determination of Ofloxacin in Pharmaceutical and Biological Samples

    Directory of Open Access Journals (Sweden)

    P. Norouzi

    2011-12-01

    Full Text Available Background and the purpose of the study: Ofloxacin is a quinolone synthetic antibiotic, which acts against resistant mutants of bacteria by inhibiting DNA gyrase. This antibacterial agent is widely used in the treatment of respiratory tract, urinary tract and tissue-based infections, which are caused by Gram-positive and Gram-negative bacteria. In this work, an efficient modified ionic liquid cold-induced aggregation dispersive liquid-liquid microextraction (M-IL-CIA-DLLME was combined with spectrofluorimetry for trace determination of ofloxacin in real samples.Methods: In this microextraction method, hydrophobic 1-hexyl-3-methylimidazolium hexafluorophosphate ([Hmim] [PF6] ionic liquid (IL as a microextraction solvent was dispersed into a heated sample solution containing sodium hexafluorophosphate (NaPF6 (as a common ion and the analyte of interest. Afterwards, the resultant solution was cooled in an ice-water bath and a cloudy condition was formed due to a considerable decrease of IL solubility. After centrifuging, the enriched phase was introduced to the spectrofluorimeter for the determination of ofloxacin.Results and major conclusion: In this technique, the performance of the microextraction method was not influenced by variations in the ionic strength of the sample solution (up to 30% w/v. Furthermore, [Hmim][PF6] IL was chosen as a green microextraction phase and an alternative to traditional toxic organic solvents. Different parameters affecting the analytical performance were studied and optimized. At optimum conditions, a relatively broad linear dynamic range of 0.15-125 μg l-1 and a limit of detection (LOD of 0.029 μg l-1 were obtained. The relative standard deviation (R.S.D. obtained for the determination of five replicates of the 10 ml solution containing 50 μg l-1 ofloxacin was 2.7%. Finally, the combined methodology was successfully applied to ofloxacin determination in actual pharmaceutical formulations and biological samples.

  7. Gene expression of hematoregulatory cytokines is elevated endogenously after sublethal gamma irradiation and is differentially enhanced by therapeutic administration of biologic response modifiers

    International Nuclear Information System (INIS)

    Prompt, cytokine-mediated restoration of hematopoiesis is a prerequisite for survival after irradiation. Therapy with biologic response modifiers (BRMs), such as LPS, 3D monophosphoryl lipid A (MPL), and synthetic trehalose dicrynomycolate (S-TDCM) presumably accelerates hematopoietic recovery after irradiation are poorly defined. One hour after sublethal (7.0 Gy) 60Co gamma irradiation, B6D2F1/J female mice received a single i.p. injection of LPS, MPL, S-TDCM, an extract from Serratia marcescens (Sm-BRM), or Tween 80 in saline (TS). Five hours later, a quantitative reverse transcription-PCR assay demonstrated marked splenic gene expression for IL-1β, IL-3, IL-6, and granulocyte-CSF (G-CSF). Enhanced gene expression for TNF-α, macrophage-CSF (M-CSF), and stem cell factor (SCF) was not detected. Injection of any BRM further enhanced cytokine gene expression and plasma levels of CSF activity within 24 h after irradiation and hastened bone marrow recovery. Mice injected with S-TDCM or Sm-BRM sustained expression of the IL-6 gene for at least 24 h after irradiation. Sm-BRM-treated mice exhibited greater gene expression for IL-1β, IL-3, TNF-α, and G-CSF at day 1 than any other BRM. When challenged with 2 LD50/30 of Klebsiella pneumoniae 4 days after irradiation, 100% of Sm-BRM-treated mice and 70% of S-TDCM-treated mice survived, whereas ≤30% of mice treated with LPS, MPL, or TS survived. Thus, sublethal irradiation induces transient, splenic cytokine gene expression that can be differentially amplified and prolonged by BRMs. BRMs that sustained and/or enhanced irradiation-induced expression of specific cytokine genes improved survival after experimental infection. 67 refs., 7 figs., 1 tab

  8. Efficacy of genetically engineered biological agents in the treatment of uveitis associated with rheumatic diseases in children

    Directory of Open Access Journals (Sweden)

    V V Neroyev

    2012-01-01

    Full Text Available The efficiency of incorporating genetically engineered biological agents (GEBAs into a combination treatment regimen for rheumatic diseases (RD (juvenile idiopathic arthritis, Behcet's disease in relation to associated uveitis of varying severity was studied in 92 children aged 2 to 17 years. The follow-up lasted 1.5 to 49 months. Twenty-three patients took consecutively 2 to 5 GEBAs. When infliximab was used, remission of uveitis occurred in 21% of 38 children and the disease activity and/or recurrence rates reduced in an additional 21%. These were in 45 and 38.6% of 44 patients on adalimumab (ADA and in 27.8 and 27.8% of 18 patients on abatacept, respectively. There was an association of the efficiency of therapy with the severity of uveitis at the start of treatment. The use of ADA induced a steady remission of panuveitis resistant to therapy with glucocorticoids and cyclosporine in both patients with Behcet's disease. One of 4 rituximab-treated patients achieved a steady remission. Tocilizumab therapy caused an exacerbation of uveitis in 1 patient. The postoperative period showed no inflammatory complications in most cases (37 operations, 26 eyes, 20 patients. No local adverse reactions were seen; systemic reactions occurred in 14% of the patients, this caused GEBAs to be discontinued in 7%. There is evidence for a need for further investigations into the efficacy of GEBAs in RD-associated uveitis in children in order to define success criteria, differentiated indications, and therapy regimens.

  9. Systems to assess the progression of finger joint osteoarthritis and the effects of disease modifying osteoarthritis drugs.

    Science.gov (United States)

    Verbruggen, G; Goemaere, S; Veys, E M

    2002-06-01

    Our objective was to assess the progression of osteoarthritis (OA) using scoring systems based on the anatomical changes recorded in the finger joints on standard radiographs and to test how far these scoring systems could be used to evaluate the effects of candidate "disease modifying osteoarthritis drugs" (DMOAD). The appearance and growth of osteophytes, narrowing of the joint space and subchondral bone changes allowed the classic OA-associated anatomical lesions to be used to score the progression of finger joint OA. Progression of OA in the finger joints was also assessed by the their evolution through previously described and predictable anatomical phases on standard X-rays. These phases were characterised by complete loss of the joint space preceding or coinciding with the appearance of subchondral cysts eroding the entire subchondral plate, and have been described in "inflammatory" or "erosive" OA. The erosive episodes were followed by processes of remodelling. In order to interfere with the progression of osteoarthritis, two chondroitin sulphates with possible DMOAD effects were used in two series of patients with OA of the finger joints. The patients were included in two separate randomised, double-blind placebo-controlled trials: 46 of them received chondroitin polysulphate and 34 received chondroitin sulphate. Eighty-five patients were kept on placebo medication and were used as controls. All 165 patients were followed for 3 years. Posteroanterior X-rays of the metacarpophalangeal and interphalangeal (IP) finger joints were obtained at the start of this prospective study and at yearly intervals thereafter. Almost 80% of the distal IP and 50% of the proximal IP were affected at study entry. In approximately 40% of the patients the classic picture of OA of the IP joints was complicated by manifest erosive OA changes. The two systems to score the progression of OA (Anatomical Lesion and Anatomical Phase Progression Score System) showed definite progression

  10. Applying the theory of planned behaviour to multiple sclerosis patients’ decisions on disease modifying therapy – questionnaire concept and validation

    Science.gov (United States)

    2012-01-01

    Background Patients making important medical decisions need to evaluate complex information in the light of their own beliefs, attitudes and priorities. The process can be considered in terms of the theory of planned behaviour. Decision support technologies aim at helping patients making informed treatment choices. Instruments assessing informed choices need to include risk knowledge, attitude (towards therapy) and actual uptake. However, mechanisms by which decision support achieves its goals are poorly understood. Our aim was therefore to develop and validate an instrument modeling the process of multiple sclerosis (MS) patients’ decision making about whether to undergo disease modifying (immuno-)therapies (DMT). Methods We constructed a 30-item patient administered questionnaire to access the elaboration of decisions about DMT in MS according to the theory of planned behaviour. MS-patients’ belief composites regarding immunotherapy were classified according to the domains “attitude”, “subjective social norm” and “control beliefs” and within each domain to either “expectations” or “values” yielding 6 sub-domains. A randomized controlled trial (n = 192) evaluating an evidence based educational intervention tested the instrument’s predictive power regarding intention to use immunotherapy and its sensitivity to the intervention. Results The psychometric properties of the questionnaire were satisfactory (mean item difficulty 62, mean SD 0.9, range 0–3). Responses explain up to 68% of the variability in the intention to use DMT was explained by up to 68% in the total sample. Four weeks after an educational intervention, predictive power was higher in the intervention (IG) compared to the control group (CG) (intention estimate: CG 56% / IG 69%, p = .179; three domains CG 56% / IG 74%, p = .047; six sub-domains CG 64% / IG 78%, p = .073). The IG held more critical beliefs towards immunotherapy (p = .002) and were less

  11. Applying the theory of planned behaviour to multiple sclerosis patients’ decisions on disease modifying therapy – questionnaire concept and validation

    Directory of Open Access Journals (Sweden)

    Kasper Jürgen

    2012-07-01

    Full Text Available Abstract Background Patients making important medical decisions need to evaluate complex information in the light of their own beliefs, attitudes and priorities. The process can be considered in terms of the theory of planned behaviour. Decision support technologies aim at helping patients making informed treatment choices. Instruments assessing informed choices need to include risk knowledge, attitude (towards therapy and actual uptake. However, mechanisms by which decision support achieves its goals are poorly understood. Our aim was therefore to develop and validate an instrument modeling the process of multiple sclerosis (MS patients’ decision making about whether to undergo disease modifying (immuno-therapies (DMT. Methods We constructed a 30-item patient administered questionnaire to access the elaboration of decisions about DMT in MS according to the theory of planned behaviour. MS-patients’ belief composites regarding immunotherapy were classified according to the domains “attitude”, “subjective social norm” and “control beliefs” and within each domain to either “expectations” or “values” yielding 6 sub-domains. A randomized controlled trial (n = 192 evaluating an evidence based educational intervention tested the instrument’s predictive power regarding intention to use immunotherapy and its sensitivity to the intervention. Results The psychometric properties of the questionnaire were satisfactory (mean item difficulty 62, mean SD 0.9, range 0–3. Responses explain up to 68% of the variability in the intention to use DMT was explained by up to 68% in the total sample. Four weeks after an educational intervention, predictive power was higher in the intervention (IG compared to the control group (CG (intention estimate: CG 56% / IG 69%, p = .179; three domains CG 56% / IG 74%, p = .047; six sub-domains CG 64% / IG 78%, p = .073. The IG held more critical beliefs towards immunotherapy (p = .002

  12. The Role of microRNAs in the Biology of Rare Diseases

    OpenAIRE

    Domenica Taruscio; Armando Magrelli; Marco Salvatore

    2011-01-01

    Rare diseases (RD) are characterized by low prevalence and affect not more than five individuals per 10,000 in the European population; they are a large and heterogeneous group of disorders including more than 7,000 conditions and often involve all organs and tissues, with several clinical subtypes within the same disease. Very often information concerning either diagnosis and/or prognosis on many RD is insufficient. microRNAs are a class of small non-coding RNAs that regulate gene expression...

  13. RECENT ADVANCES IN PATHO-BIOLOGY OF MYELOMA BONE DISEASE: CLINICOPATHOLOGY AND LITERATURE OF REVIEW

    Directory of Open Access Journals (Sweden)

    Lohit Kumar

    2016-03-01

    Full Text Available Bone disease is a hallmark of multiple myeloma, presenting as lytic lesions associated with bone pain, pathological fractures requiring surgery and/or radiation to bone, spinal cord compression and hypercalcaemia. Increased osteoclastic activity unaccompanied by a compensatory increase in osteoblast function, leading to enhanced bone resorption results in bone disease. The interaction of plasma cells with the bone marrow microenvironment has been shown to play a vital role. Also, interactions of myeloma cells with osteoclasts enhance myeloma growth and survival, and thereby create a vicious cycle leading to extensive bone destruction and myeloma cell expansion.

  14. WENDI: A tool for finding non-obvious relationships between compounds and biological properties, genes, diseases and scholarly publications

    Directory of Open Access Journals (Sweden)

    Zhu Qian

    2010-08-01

    Full Text Available Abstract Background In recent years, there has been a huge increase in the amount of publicly-available and proprietary information pertinent to drug discovery. However, there is a distinct lack of data mining tools available to harness this information, and in particular for knowledge discovery across multiple information sources. At Indiana University we have an ongoing project with Eli Lilly to develop web-service based tools for integrative mining of chemical and biological information. In this paper, we report on the first of these tools, called WENDI (Web Engine for Non-obvious Drug Information that attempts to find non-obvious relationships between a query compound and scholarly publications, biological properties, genes and diseases using multiple information sources. Results We have created an aggregate web service that takes a query compound as input, calls multiple web services for computation and database search, and returns an XML file that aggregates this information. We have also developed a client application that provides an easy-to-use interface to this web service. Both the service and client are publicly available. Conclusions Initial testing indicates this tool is useful in identifying potential biological applications of compounds that are not obvious, and in identifying corroborating and conflicting information from multiple sources. We encourage feedback on the tool to help us refine it further. We are now developing further tools based on this model.

  15. Social and Behavioral Risk Marker Clustering Associated with Biological Risk Factors for Coronary Heart Disease: NHANES 2001–2004

    Directory of Open Access Journals (Sweden)

    Nicholas J. Everage

    2014-01-01

    Full Text Available Background. Social and behavioral risk markers (e.g., physical activity, diet, smoking, and socioeconomic position cluster; however, little is known whether clustering is associated with coronary heart disease (CHD risk. Objectives were to determine if sociobehavioral clustering is associated with biological CHD risk factors (total cholesterol, HDL cholesterol, systolic blood pressure, body mass index, waist circumference, and diabetes and whether associations are independent of individual clustering components. Methods. Participants included 4,305 males and 4,673 females aged ≥20 years from NHANES 2001–2004. Sociobehavioral Risk Marker Index (SRI included a summary score of physical activity, fruit/vegetable consumption, smoking, and educational attainment. Regression analyses evaluated associations of SRI with aforementioned biological CHD risk factors. Receiver operator curve analyses assessed independent predictive ability of SRI. Results. Healthful clustering (SRI = 0 was associated with improved biological CHD risk factor levels in 5 of 6 risk factors in females and 2 of 6 risk factors in males. Adding SRI to models containing age, race, and individual SRI components did not improve C-statistics. Conclusions. Findings suggest that healthful sociobehavioral risk marker clustering is associated with favorable CHD risk factor levels, particularly in females. These findings should inform social ecological interventions that consider health impacts of addressing social and behavioral risk factors.

  16. Addressing Health Literacy Challenges With a Cutting-Edge Infectious Disease Curriculum for the High School Biology Classroom.

    Science.gov (United States)

    Jacque, Berri; Koch-Weser, Susan; Faux, Russell; Meiri, Karina

    2016-02-01

    This study reports the secondary analysis of evaluation data from an innovative high school biology curriculum focused on infectious disease (ID) to examine the health literacy implications of teaching claims evaluation, data interpretation, and risk assessment skills in the context of 21st-Century health science. The curriculum was implemented between 2010 and 2013 in Biology II classes held in four public high schools (three in Massachusetts and one in Ohio), plus a private school in Virginia. A quasi-experimental design was used in which student participants (n = 273) were compared to an age-matched, nonparticipant, peer group (N = 125). Participants in each school setting demonstrated increases in conceptual content knowledge (Cohen's d > 1.89) as well as in understanding how to apply scientific principles to health claims evaluation and risk assessment (Cohen's d > 1.76) and in self-efficacy toward learning about ID (Cohen's d > 2.27). Participants also displayed enhanced communication about ID within their social networks relative to the comparison group (p < .05). The data show that integrating the claims evaluation, data interpretation, and risk assessment skills critical for 21st-century health literacy health into high school biology classrooms is effective at fostering both the skills and self-efficacy pertinent to health literacy learning in diverse populations. PMID:26194205

  17. Biologic therapy of rheumatoid arthritis

    Directory of Open Access Journals (Sweden)

    Damjanov Nemanja

    2009-01-01

    Full Text Available Rheumatoid arthritis (RA and juvenile idiopathic/rheumatoid arthritis (JIA are chronic, inflammatory, systemic, auto-immune diseases characterized by chronic arthritis leading to progressive joint erosions. The individual functional and social impact of rheumatoid arthritis is of great importance. Disability and joint damage occur rapidly and early in the course of the disease. The remarkably improved outcomes have been achieved initiating biologic therapy with close monitoring of disease progression. Biologic agents are drugs, usually proteins, which can influence chronic immune dysregulation resulting in chronic arthritis. According to the mechanism of action these drugs include: 1 anti-TNF drugs (etanercept, infiximab, adalimumab; 2 IL-1 blocking drugs (anakinra; 3 IL-6 blocking drugs (tocilizumab; 4 agents blocking selective co-stimulation modulation (abatacept; 5 CD 20 blocking drugs (rituximab. Biologics targeting TNF-alpha with methotrexate have revolutionized the treatment of RA, producing significant improvement in clinical, radiographic, and functional outcomes not seen previously. The new concept of rheumatoid arthritis treatment defines early diagnosis, early aggressive therapy with optimal doses of disease modifying antirheumatic drugs (DMARDs and, if no improvement has been achieved during six months, early introduction of biologic drugs. The three-year experience of biologic therapy in Serbia has shown a positive effect on disease outcome.

  18. Immunosuppression for 6-8 weeks after modified donor lymphocyte infusion reduced acute graft-versus-host disease without influencing graft-versus-leukemia effect in haploidentical transplant

    Institute of Scientific and Technical Information of China (English)

    Yan Chenhua; Xu Lanping; Liu Daihong; Chen Huan; Wang Yu; Liu Kaiyan; Huang Xiaojun

    2014-01-01

    Background In haploidentical hematopoietic stem cell transplantation (HSCT),the duration of graft-versus-host disease (GVHD) prophylaxis after modified donor lymphocyte infusion (DLI) was the only risk factor of DLI-associated grades 3-4 acute GVHD.However,the successful application of modified DLI depended not only on the reduction of severe GVHD,but also on the preservation of graft-versus-leukemia (GVL) effect.Therefore,this study was performed to compare the impact of prophylaxis for 6-8 weeks and prophylaxis for <6 weeks on GVL effect after modified DLI in haploidentical HSCT.Methods A total of 103 consecutive patients developing hematological relapse or minimal residual disease (MRD)-positive status after haploidentical HSCT and receiving modified DLI were investigated retrospectively.Fifty-two patients received prophylaxis for 6-8 weeks after modified DLI; the remaining 51 patients received prophylaxis for <6 weeks.Results First,compared with prophylaxis for <6 weeks,prophylaxis for 6-8 weeks reduced incidence of relapse in total patients (26.6% vs.69.0%,P <0.001).Besides,prophylaxis for 6-8 weeks also reduced incidence of relapse in 54 patients developing hematological relapse post-transplant (P=0.018) and in 49 patients developing MRD-positive status post-transplant (P <0.001).Second,prophylaxis for 6-8 weeks reduced incidence of acute GVHD (P <0.05),reduced the therapeutic application of immunosuppressive agents (P=0.019),but increased the incidence of chronic GVHD (P<0.05).Third,prophylaxis for 6-8 weeks improved overall survival and disease-free survival in total patients,as well as in patients developing hematological relapse post-transplant and in patients developing MRD-positive status post-transplant (P <0.05).Conclusions In haploidentical HSCT,prophylaxis for 6-8 weeks after modified DLI does not reduce GVL effect,but reduces the incidence of DLI-associated acute GVHD compared with prophylaxis for <6 weeks.This strategy will

  19. Genetic Variants in the Bone Morphogenic Protein Gene Family Modify the Association between Residential Exposure to Traffic and Peripheral Arterial Disease cardiovascular disease cohort.

    Science.gov (United States)

    There is a growing literature indicating that genetic variants modify many of the associations between environmental exposures and clinical outcomes, potentially by increasing susceptibility to these exposures. However, genome-scale investigations of these interactions have been ...

  20. ChemProt-3.0: a global chemical biology diseases mapping

    DEFF Research Database (Denmark)

    Kringelum, Jens Vindahl; Kjærulff, Sonny Kim; Brunak, Søren;

    2016-01-01

    ChemProt is a publicly available compilation of chemical-protein-disease annotation resources that enables the study of systems pharmacology for a small molecule across multiple layers of complexity from molecular to clinical levels. In this third version, ChemProt has been updated to more than 1...