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Sample records for disease modifying agents

  1. 77 FR 59930 - Clinical Development Programs for Disease-Modifying Agents for Peripheral Neuropathy; Public...

    2012-10-01

    ...] Clinical Development Programs for Disease-Modifying Agents for Peripheral Neuropathy; Public Workshop... to the clinical development of disease-modifying agents for the treatment of peripheral neuropathy... disease-modifying products for the management of peripheral neuropathy. Date and Time: The public workshop...

  2. Design, Synthesis, and Biological Evaluation of 2-(Benzylamino-2-HydroxyalkylIsoindoline-1,3-Diones Derivatives as Potential Disease-Modifying Multifunctional Anti-Alzheimer Agents

    Dawid Panek

    2018-02-01

    Full Text Available The complex nature of Alzheimer’s disease calls for multidirectional treatment. Consequently, the search for multi-target-directed ligands may lead to potential drug candidates. The aim of the present study is to seek multifunctional compounds with expected activity against disease-modifying and symptomatic targets. A series of 15 drug-like various substituted derivatives of 2-(benzylamino-2-hydroxyalkylisoindoline-1,3-diones was designed by modification of cholinesterase inhibitors toward β-secretase inhibition. All target compounds have been synthesized and tested against eel acetylcholinesterase (eeAChE, equine serum butyrylcholinesterase (eqBuChE, human β-secretase (hBACE-1, and β-amyloid (Aβ-aggregation. The most promising compound, 12 (2-(5-(benzylamino-4-hydroxypentylisoindoline-1,3-dione, displayed inhibitory potency against eeAChE (IC50 = 3.33 μM, hBACE-1 (43.7% at 50 μM, and Aβ-aggregation (24.9% at 10 μM. Molecular modeling studies have revealed possible interaction of compound 12 with the active sites of both enzymes—acetylcholinesterase and β-secretase. In conclusion: modifications of acetylcholinesterase inhibitors led to the discovery of a multipotent anti-Alzheimer’s agent, with moderate and balanced potency, capable of inhibiting acetylcholinesterase, a symptomatic target, and disease-modifying targets: β-secretase and Aβ-aggregation.

  3. Discovery of novel propargylamine-modified 4-aminoalkyl imidazole substituted pyrimidinylthiourea derivatives as multifunctional agents for the treatment of Alzheimer's disease.

    Xu, Yi-Xiang; Wang, Huan; Li, Xiao-Kang; Dong, Sheng-Nan; Liu, Wen-Wen; Gong, Qi; Wang, Tian-Duan-Yi; Tang, Yun; Zhu, Jin; Li, Jian; Zhang, Hai-Yan; Mao, Fei

    2018-01-01

    A series of novel propargylamine-modified pyrimidinylthiourea derivatives (1-3) were designed and synthesized as multifunctional agents for Alzheimer's disease (AD) therapy, and their potential was evaluated through various biological experiments. Among these derivatives, compound 1b displayed good selective inhibitory activity against AChE (vs BuChE, IC 50  = 0.324 μM, SI > 123) and MAO-B (vs MAO-A, IC 50  = 1.427 μM, SI > 35). Molecular docking study showed that the pyrimidinylthiourea moiety of 1b could bind to the catalytic active site (CAS) of AChE, and the propargylamine moiety interacted directly with the flavin adenine dinucleotide (FAD) of MAO-B. Moreover, 1b demonstrated mild antioxidant ability, good copper chelating property, effective inhibitory activity against Cu 2+ -induced Aβ 1-42 aggregation, moderate neuroprotection, low cytotoxicity, and appropriate blood-brain barrier (BBB) permeability in vitro and was capable of ameliorating scopolamine-induced cognitive impairment in mice. These results indicated that 1b has the potential to be a multifunctional candidate for the treatment of Alzheimer's disease. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  4. MS Disease-Modifying Medications

    ... disease-modifying therapies Approval: 2014 US; 2014 CAN Pregnancy Category C (see footnote, page 11) Rash, headache, fever, nasal congestion, nausea, urinary tract infection, fatigue, insomnia, upper respiratory tract infection, herpes viral ...

  5. EFFECTS OF SYNTHETIC DISEASE-MODIFYING ANTIRHEUMATIC DRUGS, BIOLOGICAL AGENTS, AND PSYCHOPHARMACOTHERAPY ON THE MENTAL DISORDERS IN PATIENTS WITH RHEUMATOID ARTHRITIS

    A. A. Abramkin

    2017-01-01

    Full Text Available Mental disorders (MDs of the anxiety-depressive spectrum (ADS and cognitive impairment (CI are characteristic of the majority of patients with rheumatoid arthritis (RA; however, the effects of disease-modifying antirheumatic drugs (DMARDs, biological agents (BAs, and their combinations with psychopharmacological drugs (PPDs on these abnormalities have been insufficiently studied. Objective: to investigate trends in the incidence of MDs in RA patients receiving different treatment regimens.Subjects and methods. The investigation included 128 RA patients (13% men and 87% women who fulfilled the 1987 American College of Rheumatology criteria; their mean age was 47.4±0.9 years; the median duration of RA was 96 [48; 228] months. RA activity was found to be high, moderate, and low in 48, 56, and 24 patients, respectively. DAS28 averaged 5.34±0.17. 80% of the patients received DMARDs. MDs were diagnosed based on ICD-10 coding, by using a semi-structured interview and scales, such as the Hospital Anxiety and Depression Scale, the Hamilton Anxiety Scale, and the Montgomery-Asberg Depression Rating Scale. Clinical and psychological procedures were used to diagnose CI. At the study inclusion stage, ADS disorders were detected in 123 (96.1% patients; CI was found in 88 (68.7%. Forty-one (32.1% patients were diagnosed with major depression (an obvious or moderate depressive episode, 53 (41.4% patients had minor depression (a mild depressive episode and dysthymia, and 29 (22.6% had anxiety disorders (ADs (adjustment disorders with anxiety symptoms, as well as generalized anxiety disorder. The dynamics of MDs was estimated in 112 (87.5% of the 128 patients and in 83 (64.8% at one- and five-year follow-ups, respectively. The following groups were identified according to the performed therapy: 1 synthetic DMARDs (n = 39; 2 synthetic DMARDs + PPDs (n = 43; 3 BAs + DMARDs (n = 32; 4 BAs + DMARDs + PPDs (n = 9.Results and discussion. In Group 1, the

  6. Disease-modifying drugs in Alzheimer's disease

    Ghezzi L

    2013-12-01

    Full Text Available Laura Ghezzi, Elio Scarpini, Daniela Galimberti Neurology Unit, Department of Pathophysiology and Transplantation, University of Milan, Fondazione Cà Granda, IRCCS Ospedale Maggiore Policlinico, Milan, Italy Abstract: Alzheimer's disease (AD is an age-dependent neurodegenerative disorder and the most common cause of dementia. The early stages of AD are characterized by short-term memory loss. Once the disease progresses, patients experience difficulties in sense of direction, oral communication, calculation, ability to learn, and cognitive thinking. The median duration of the disease is 10 years. The pathology is characterized by deposition of amyloid beta peptide (so-called senile plaques and tau protein in the form of neurofibrillary tangles. Currently, two classes of drugs are licensed by the European Medicines Agency for the treatment of AD, ie, acetylcholinesterase inhibitors for mild to moderate AD, and memantine, an N-methyl-D-aspartate receptor antagonist, for moderate and severe AD. Treatment with acetylcholinesterase inhibitors or memantine aims at slowing progression and controlling symptoms, whereas drugs under development are intended to modify the pathologic steps leading to AD. Herein, we review the clinical features, pharmacologic properties, and cost-effectiveness of the available acetylcholinesterase inhibitors and memantine, and focus on disease-modifying drugs aiming to interfere with the amyloid beta peptide, including vaccination, passive immunization, and tau deposition. Keywords: Alzheimer's disease, acetylcholinesterase inhibitors, memantine, disease-modifying drugs, diagnosis, treatment

  7. Environmental impact assessment of genetically modified biocontrol agents

    Migheli, Q.

    2001-01-01

    This review summarises the theoretical basis of risk analysis, and the political and social implications of introducing new biotechnology products in agricultural environments. The main factors to be considered under the present European regulation in the environmental impact assessment of genetically modified biocontrol agents are briefly discussed. Finally, an alternative risk assessment paradigm is proposed for genetically modified microorganisms, which shall consider the intrinsic properties of each antagonist, rather than the method used for generating it [it

  8. The Promise of Neuroprotective Agents in Parkinson’s Disease

    Judith ePotashkin

    2011-11-01

    Full Text Available Parkinson’s Disease is characterized by loss of dopamine neurons in the substantia nigra of the brain. Since there are limited treatment options for PD, neuroprotective agents are currently being tested as a means to slow disease progression. Agents targeting oxidative stress, mitochondrial dysfunction and inflammation are prime candidates for neuroprotection. This review identifies Rasagiline, Minocycline and creatine, as the most promising neuroprotective agents for PD, and they are all currently in phase III trials. Other agents possessing protective characteristics in delaying PD include stimulants, vitamins, supplements, and other drugs. Additionally, combination therapies also show benefits in slowing PD progression. The identification of neuroprotective agents for PD provides us with therapeutic opportunities for modifying the course of disease progression and, perhaps, reducing the risk of onset when preclinical biomarkers become available.

  9. Viruses: agents of coral disease?

    Davy, S K; Burchett, S G; Dale, A L; Davies, P; Davy, J E; Muncke, C; Hoegh-Guldberg, O; Wilson, W H

    2006-03-23

    The potential role of viruses in coral disease has only recently begun to receive attention. Here we describe our attempts to determine whether viruses are present in thermally stressed corals Pavona danai, Acropora formosa and Stylophora pistillata and zoanthids Zoanthus sp., and their zooxanthellae. Heat-shocked P. danai, A. formosa and Zoanthus sp. all produced numerous virus-like particles (VLPs) that were evident in the animal tissue, zooxanthellae and the surrounding seawater; VLPs were also seen around heat-shocked freshly isolated zooxanthellae (FIZ) from P. danai and S. pistillata. The most commonly seen VLPs were tail-less, hexagonal and about 40 to 50 nm in diameter, though a diverse range of other VLP morphotypes (e.g. rounded, rod-shaped, droplet-shaped, filamentous) were also present around corals. When VLPs around heat-shocked FIZ from S. pistillata were added to non-stressed FIZ from this coral, they resulted in cell lysis, suggesting that an infectious agent was present; however, analysis with transmission electron microscopy provided no clear evidence of viral infection. The release of diverse VLPs was again apparent when flow cytometry was used to enumerate release by heat-stressed A. formosa nubbins. Our data support the infection of reef corals by viruses, though we cannot yet determine the precise origin (i.e. coral, zooxanthellae and/or surface microbes) of the VLPs seen. Furthermore, genome sequence data are required to establish the presence of viruses unequivocally.

  10. Arthropods: Vectors of Disease Agents

    1994-07-01

    Trypanosoma cruzi Kissing bugs (reduviidsl Enteric diseases Salmonella, Shigella , others Roaches, filth flies, ants, others? *Question marks indicate... monkeys Biological NA Humans Biological 9,957 imported, 4 species 20 congenital, 21 induced, 75 introduced or cryptic Canines Biological NA Coin

  11. Classifying PML risk with disease modifying therapies.

    Berger, Joseph R

    2017-02-01

    To catalogue the risk of PML with the currently available disease modifying therapies (DMTs) for multiple sclerosis (MS). All DMTs perturb the immune system in some fashion. Natalizumab, a highly effective DMT, has been associated with a significant risk of PML. Fingolimod and dimethyl fumarate have also been unquestionably associated with a risk of PML in the MS population. Concerns about PML risk with other DMTs have arisen due to their mechanism of action and pharmacological parallel to other agents with known PML risk. A method of contextualizing PML risk for DMTs is warranted. Classification of PML risk was predicated on three criteria:: 1) whether the underlying condition being treated predisposes to PML in the absence of the drug; 2) the latency from initiation of the drug to the development of PML; and 3) the frequency with which PML is observed. Among the DMTs, natalizumab occupies a place of its own with respect to PML risk. Significantly lesser degrees of risk exist for fingolimod and dimethyl fumarate. Whether PML will be observed with other DMTs in use for MS, such as, rituximab, teriflunomide, and alemtuzumab, remains uncertain. A logical classification for stratifying DMT PML risk is important for both the physician and patient in contextualizing risk/benefit ratios. As additional experience accumulates regarding PML and the DMTs, this early effort will undoubtedly require revisiting. Copyright © 2016 Elsevier B.V. All rights reserved.

  12. Rheological characterization of modified foodstuffs with food grade thickening agents

    Reyes-Ocampo, I.; Aguayo-Vallejo, JP; Ascanio, G.; Córdova-Aguilar, MS

    2017-01-01

    This work describes a rheological characterization in terms of shear and extensional properties of whole milk, modified with food grade thickening agents (xanthan and carboxymethyl cellulose) with the purpose of being utilized in dysphagia treatment. Shear viscosity of the thickened fluids (2% wt. of xanthan and CMC) were measured in a stress-controlled rheometer and for extensional viscosity, a custom-built orifice flowmeter was used, with elongation rates from 20 to 3000 s-1. Such elongation-rate values represent the entire swallowing process, including the pharyngeal and esophageal phases. The steady-state shear and extensional flow curves were compared with the flow curve of a pudding consistency BaSO4 suspension (α=05), typically used as a reference fluid for the specialized commercial dysphagia products. The modified fluids presented non-Newtonian behavior in both, shear and extensional flows, and the comparison with the reference fluid show that the thickened milk prepared here, can be safely used for consumption by patients with severe dysphagia.

  13. Genetic Modifiers of Sickle Cell Disease

    Steinberg, Martin H.; Sebastiani, Paola

    2015-01-01

    Sickle cell anemia is associated with unusual clinical heterogeneity for a Mendelian disorder. Fetal hemoglobin concentration and coincident ∝ thalassemia, both which directly affect the sickle erythrocyte, are the major modulators of the phenotype of disease. Understanding the genetics underlying the heritable subphenotypes of sickle cell anemia would be prognostically useful, could inform personalized therapeutics, and might help the discovery of new “druggable” pathophysiologic targets. Genotype-phenotype association studies have been used to identify novel genetic modifiers. In the future, whole genome sequencing with its promise of discovering hitherto unsuspected variants could add to our understanding of the genetic modifiers of this disease. PMID:22641398

  14. Infectious agents are associated with psychiatric diseases

    Daniela Lydia Krause

    2012-01-01

    Full Text Available There are several infectious agents in the environment that can cause persistent infections in the host. They usually cause their symptoms shortly after first infection and later persist as silent viruses and bacteria within the body. However, these chronic infections may play an important role in the pathogenesis of schizophrenia and Tourette’s syndrome (TS. We investigated the distribution of different neurotrophic infectious agents in TS, schizophrenia and controls. A total of 93 individuals were included (schizophrenic patients, Tourette patients and controls. We evaluated antibodies against cytomegalovirus (CMV, herpes-simplex virus (HSV, Epstein-Barr virus, Toxoplasma, Mycoplasma and Chlamydia trachomatis/pneumoniae. By comparing schizophrenia and TS, we found a higher prevalence of HSV (P=0.017 and CMV (P=0.017 antibodies in schizophrenic patients. Considering the relationship between schizophrenia, TS and healthy controls, we showed that there are associations for Chlamydia trachomatis (P=0.007, HSV (P=0.027 and CMV (P=0.029. When all measured viruses, bacteria and protozoa were combined, schizophrenic patients had a higher rate of antibodies to infectious agents than TS patients (P=0.049. Tourette and schizophrenic patients show a different vulnerability to infectious agents. Schizophrenic patients were found to have a higher susceptibility to viral infections than individuals with TS. This finding might point to a modification in special immune parameters in these diseases.

  15. Fungal endophytes: modifiers of plant disease.

    Busby, Posy E; Ridout, Mary; Newcombe, George

    2016-04-01

    Many recent studies have demonstrated that non-pathogenic fungi within plant microbiomes, i.e., endophytes ("endo" = within, "phyte" = plant), can significantly modify the expression of host plant disease. The rapid pace of advancement in endophyte ecology warrants a pause to synthesize our understanding of endophyte disease modification and to discuss future research directions. We reviewed recent literature on fungal endophyte disease modification, and here report on several emergent themes: (1) Fungal endophyte effects on plant disease span the full spectrum from pathogen antagonism to pathogen facilitation, with pathogen antagonism most commonly reported. (2) Agricultural plant pathosystems are the focus of research on endophyte disease modification. (3) A taxonomically diverse group of fungal endophytes can influence plant disease severity. And (4) Fungal endophyte effects on plant disease severity are context-dependent. Our review highlights the importance of fungal endophytes for plant disease across a broad range of plant pathosystems, yet simultaneously reveals that complexity within plant microbiomes presents a significant challenge to disentangling the biotic environmental factors affecting plant disease severity. Manipulative studies integrating eco-evolutionary approaches with emerging molecular tools will be poised to elucidate the functional importance of endophytes in natural plant pathosystems that are fundamental to biodiversity and conservation.

  16. Handheld Delivery System for Modified Boron-Type Fire Extinguishment Agent

    1993-11-01

    was to develop and test a handheld portable delivery system for use with the modified boron-type fire extinguishing agent for metal fires . B...BACKGROUND A need exists for an extinguishing agent and accompanying delivery system that are effective against complex geometry metal fires . A modified...agent and its delivery system have proven effective against complex geometry metal fires containing up to 200 pounds of magnesium metal. Further

  17. Modified natural nanoparticles as contrast agents for medical imaging

    Cormode, David P.; Jarzyna, Peter A.; Mulder, Willem J. M.; Fayad, Zahi A.

    2010-01-01

    The development of novel and effective contrast agents is one of the drivers of the ongoing improvement in medical imaging. Many of the new agents reported are nanoparticle-based. There are a variety of natural nanoparticles known, e.g. lipoproteins, viruses or ferritin. Natural nanoparticles have

  18. Effect of nano silica based modifying agent for hydrophobic coating application

    Nurul Huda Mudri; Nik Ghazali Nik Salleh; Mek Zah Salleh

    2016-01-01

    Hydrophobic coatings find wide application in industry due to their unique features such as water repellent and self-cleaning properties. In this study, modifying agent was synthesized by way of nano silica particles dispersion in polydimethyl siloxane with addition of surfactant, catalyst and stabilizer using high speed distemper. The modifying agent was added into coating formulation and cured under UV exposure. Scanning Electron Microscopy image of the film found that the nano silica particles were distributed well on substrate. Contact angle measurement gave the highest reading of 116 degree for 20 % wt of the modifying agent. The optical properties of the film were evaluated via transmission and haze test. (author)

  19. Modified Gadonanotubes as a Promising Novel MRI Contrasting Agent

    Rouzbeh Jahanbakhsh; Fatemeh Atyabi; Saeed Shanehsazzadeh; Zahra Sobhani; Mohsen Adeli; Rassoul Dinarvand

    2013-01-01

    Background and purpose of the study Carbon nanotubes (CNTs) are emerging drug and imaging carrier systems which show significant versatility. One of the extraordinary characteristics of CNTs as Magnetic Resonance Imaging (MRI) contrasting agent is the extremely large proton relaxivities when loaded with gadolinium ion (Gdn 3+) clusters. Methods In this study equated Gdn 3+ clusters were loaded in the sidewall defects of oxidized multiwalled (MW) CNTs. The amount of loaded gadolinium ion into ...

  20. Critical appraisal of the guidelines for the management of ankylosing spondylitis: disease-modifying antirheumatic drugs.

    Soriano, Enrique R; Clegg, Daniel O; Lisse, Jeffrey R

    2012-05-01

    Surprisingly, little data are available for the use of disease-modifying antirheumatic drugs in ankylosing spondylitis. Sulfasalazine has been the best studied. Efficacy data for individual agents (including pamidronate) and combinations of agents are detailed in this review. Intriguingly, these agents continue to be used with some frequency, even in the absence of efficacy data. To answer these questions, additional systematic studies of these agents in ankylosing spondylitis are needed and will likely need to be done by interested collaborative groups such as SPARTAN.

  1. Photoluminescence investigation of ZnO quantum dots surface modified with silane coupling agent as a capping agent

    Moghaddam, E., E-mail: e.moghaddam@merc.ac.ir; Youzbashi, A.A; Kazemzadeh, A.; Eshraghi, M.J.

    2015-12-15

    This report presents the luminescence measurement results of surface modified zinc oxide quantum dots (ZnO QDs) performed with different concentrations of 3-aminopropyltriethoxysilane (APTES) as a capping agent. Surface modification was performed by an in situ procedure on the surface of ZnO QDs in a sol gel solution route. The modified samples were characterized by various analytical techniques such as XRD, TEM, FT-IR, and UV–vis spectroscopy. Surface modification efficiency was experimentally investigated by variation of the photoluminescence) PL (emission intensities observed by changing the capping agent concentration. In order to investigate the effectiveness of the capping agent on the stability of the QDs, The PL spectra of the surface modified ZnO QDs were compared with that of unmodified ZnO QDs. Molecular layer of this type and similar silane based molecules with a variety of surface terminations that have the same molecular attachment schemes should enable interface engineering in optimizing the chemical selectivity of ZnO biosensors or electrical and optical properties of ZnO-polymer hybrid films. - Highlights: • Surface modification of ZnO QDs resulted in the small- size QDs (around 2 nm). • Surface modification resulted in the enhancement of the UV emission upon quenching the visible emission. • Surface modification efficiency was decreased with reduction of the QD size • Intensified stability of the surface modified ZnO QDs was obtained from surface modification.

  2. Dependence of radioprotective effect of chemical modifying agents on their intracellular concentrations

    Eidus, L.K.; Korystov, Y.N.; Kublik, L.N.; Vexler, A.M.

    1982-01-01

    Regularities of the radioprotective effect of chemical modifying agents cysteamine, caffeine benzoate, thioglycolic acid, and caffeine, all weak electrolytes, have been studied in cultured Chinese hamster cells. Efficiency of protection is shown to be dependent on pH and concentrations of the drug inside the cells and in the medium. Based on the theory of the dissociation of weak electrolytes and their distribution between the cells and the medium a strong correlation between the efficiency of modification of the radiation response and intracellular concentration of a modifying agent is shown. (author)

  3. Established and novel disease-modifying treatments in multiple sclerosis.

    Cross, A H; Naismith, R T

    2014-04-01

    Multiple sclerosis (MS) is a presumed autoimmune disorder of the central nervous system, resulting in inflammatory demyelination and axonal and neuronal injury. New diagnostic criteria that incorporate magnetic resonance imaging have resulted in earlier and more accurate diagnosis of MS. Several immunomodulatory and immunosuppressive therapeutic agents are available for relapsing forms of MS, which allow individualized treatment based upon the benefits and risks. Disease-modifying therapies introduced in the 1990s, the beta-interferons and glatiramer acetate, have an established track record of efficacy and safety, although they require administration via injection. More recently, monoclonal antibodies have been engineered to act through specific mechanisms such as blocking alpha-4 integrin interactions (natalizumab) or lysing cells bearing specific markers, for example CD52 (alemtuzumab) or CD20 (ocrelizumab and ofatumumab). These agents can be highly efficacious, but sometimes have serious potential complications (natalizumab is associated with progressive multifocal leukoencephalopathy; alemtuzumab is associated with the development of new autoimmune disorders). Three new oral therapies (fingolimod, teriflunomide and dimethyl fumarate, approved for MS treatment from 2010 onwards) provide efficacy, tolerability and convenience; however, as yet, there are no long-term postmarketing efficacy and safety data in a general MS population. Because of this lack of long-term data, in some cases, therapy is currently initiated with the older, safer injectable medications, but patients are monitored closely with the plan to switch therapies if there is any indication of a suboptimal response or intolerance or lack of adherence to the initial therapy. For patients with MS who present with highly inflammatory and potentially aggressive disease, the benefit-to-risk ratio may support initiating therapy using a drug with greater potential efficacy despite greater risks (e

  4. Modern antiplatelet agents in coronary artery disease.

    Power, Rachel F

    2012-10-01

    Dual antiplatelet therapy is well recognized in the prevention of thrombotic complications of acute coronary syndrome and percutaneous coronary interventions. Despite clinical benefits of aspirin and clopidogrel therapy, a number of limitations curtail their efficacy: slow onset of action, variability in platelet inhibitory response and potential drug-drug interactions. Furthermore, the single platelet-activation pathway targeted by these agents allows continued platelet activation via other pathways, ensuring incomplete protection against ischemic events, thus, underscoring the need for alternate antiplatelet treatment strategies. A number of novel antiplatelet agents are currently in advance development and many have established superior effects on platelet inhibition, clinical outcomes and safety profile than clopidogrel in high-risk patients. The aim of this review is to provide an overview of the current status of P2Y12 receptor inhibition and PAR-1 antagonists in determining a future strategy for individualized antiplatelet therapy.

  5. The effect of impact modifier and of nucleating agent on the radiation tolerance of polypropylene

    Liu Dongyuan (Beijing Normal Univ., BJ (China)); Czvikovszky, T.; Dobo, J.; Somogyi, A. (Research Inst. for the Plastics Industry, Budapest (Hungary))

    1990-01-01

    The effect of two types of additives was investigated with respect to the oxidative post-irradiation stability of polypropylene: SBS thermoplastic rubbers as impact modifiers and benzoic acid as nucleating agent. Testing was performed by ultimate deformation on bending. The thermoplastic rubber additive increased the post-irradiation stability of polypropylene substantially. (author).

  6. The effect of impact modifier and of nucleating agent on the radiation tolerance of polypropylene

    Liu Dongyuan; Czvikovszky, T.; Dobo, J.; Somogyi, A.

    1990-01-01

    The effect of two types of additives was investigated with respect to the oxidative post-irradiation stability of polypropylene: SBS thermoplastic rubbers as impact modifiers and benzoic acid as nucleating agent. Testing was performed by ultimate deformation on bending. The thermoplastic rubber additive increased the post-irradiation stability of polypropylene substantially. (author)

  7. Adsorption of hexavalent chromium on modified corn stalk using different cross-linking agents

    Chen, Suhong; Zhu, Yi; Han, Zhijun; Feng, Gao; Jia, Yuling; Fu, Kaifang; Yue, Qinyan

    2017-12-01

    In this study, four different types of adsorbents modified from corn stalk were synthesized after the reaction with epichlorohydrin, N,N-dimethylformamide, triethylamine and different cross-linking agents. The surface functional groups and thermal stability of modified corn stalk (MCSs) were characterized using FTIR and TG analysis, respectively. The feasibility of using MCSs to remove Cr(VI) were evaluated. Adsorption isotherms were determined and modeled with Langmuir, Freundlich and Temkin equations. The experimental results showed that MCS modified using diethylenetriamine (DETA) had the best modification effect, and the adsorption capacity of Cr(VI) reached as high as 227.27 mg/g at 323 K. Thermodynamic study showed that the Cr(VI) adsorption onto MCSs was endothermic processes. As a result, MCS by using DETA as cross-linking agent has good potential for the removal of Cr(VI) from aqueous solutions.

  8. Biologic agents therapy for Saudi children with rheumatic diseases: indications and safety.

    Al-Mayouf, Sulaiman M; Alenazi, Abdullatif; AlJasser, Hind

    2016-06-01

    To report the indications and safety of biologic agents in childhood rheumatic diseases at a tertiary hospital. Children with rheumatic diseases treated with biologic agents at King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia, from January 2001 to December 2011 were included. All patients were reviewed for: demographic characteristics, diagnosis, concomitant treatment and indications of using biologic agents, age at start of therapy and side effects during the treatment period. In all, 134 children (89 female) with various rheumatic diseases were treated with biologic agents. Mean age at starting biologic treatment was 9.3 (4.25-14) years and mean therapy duration was 14.7 (3-88) months. Juvenile idiopathic arthritis (JIA) was the most frequent diagnosis (70.1%) followed by systemic lupus erythematosus (12.7%) and vasculitis (4.5%). All patients received concomitant therapy (corticosteroids and disease-modifying antirheumatic drugs). In total, 273 treatments with biologic agents were used, (95 etanercept, 52 rituximab, 47 adalimumab, 37 infliximab, 23 anakinra, 10 tocilizumab and nine abatacept). Therapy was switched to another agent in 57 (42.5%) patients, mainly because of inefficacy (89.4%) or adverse event (10.6%). A total of 95 (34.8%) adverse events were notified; of these, the most frequent were infusion-related reactions (33.7%) followed by infections (24.2%) and autoantibody positivity (10.6%). One patient developed macrophage activation syndrome. Biologic agents were used in children with a range of rheumatic diseases. Of these, the most frequent was JIA. Off-label use of biologic agents in our cohort is common. These agents seem safe. However, they may associated with various adverse events. Sequential therapy seems well tolerated. However, this should be carefully balanced and considered on an individual basis. © 2014 Asia Pacific League of Associations for Rheumatology and Wiley Publishing Asia Pty Ltd.

  9. Developing Disease-Modifying Treatments in Alzheimer's Disease - A Perspective from Roche and Genentech.

    Doody, R

    2017-01-01

    Alzheimer's disease (AD) is a chronic neurodegenerative disease for which no preventative or disease-modifying treatments currently exist. Pathological hallmarks include amyloid plaques and neurofibrillary tangles composed of hyper-phosphorylated tau protein. Evidence suggests that both pathologies are self-propagating once established. However, the lag time between neuropathological changes in the brain and the onset of even subtle clinical symptomatology means that patients are often diagnosed late when pathology, and neurodegeneration secondary to these changes, may have been established for several years. Complex pathological pathways associated with susceptibility to AD and changes that occur downstream of the neuropathologic process further contribute to the challenging endeavour of developing novel disease-modifying therapy. Recognising this complexity, effective management of AD must include reliable screening and early diagnosis in combination with effective therapeutic management of the pathological processes. Roche and Genentech are committed to addressing these unmet needs through developing a comprehensive portfolio of diagnostics and novel therapies. Beginning with the most scientifically supported targets, this approach includes two targeted amyloid-β monoclonal antibody therapies, crenezumab and gantenerumab, and an anti-tau monoclonal antibody, RO7105705, as well as a robust biomarker platform to aid in the early identification of people at risk or in the early stages of AD. Identification and implementation of diagnostic tools will support the enrolment of patients into clinical trials; furthermore, these tools should also support evaluation of the clinical efficacy and safety profile of the novel therapeutic agents tested in these trials. This review discusses the therapeutic agents currently under clinical development.

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

    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

  11. Modified clay minerals efficiency against chemical and biological warfare agents for civil human protection.

    Plachá, Daniela; Rosenbergová, Kateřina; Slabotínský, Jiří; Kutláková, Kateřina Mamulová; Studentová, Soňa; Martynková, Gražyna Simha

    2014-04-30

    Sorption efficiencies of modified montmorillonite and vermiculite of their mono ionic Na and organic HDTMA and HDP forms were studied against chemical and biological warfare agents such as yperite and selected bacterial strains. Yperite interactions with modified clay minerals were observed through its capture in low-density polyethylene foil-modified clay composites by measuring yperite gas permeation with using chemical indication and gas chromatography methods. The antibacterial activities of synthetized organoclays were tested against selected Gram-positive and Gram-negative bacterial species in minimum inhibitory concentration tests. The obtained results showed a positive influence of modified clay minerals on the significant yperite breakthrough-time increase. The most effective material was the polyethylene-Na form montmorillonite, while the polyethylene-Na form vermiculite showed the lowest efficiency. With increasing organic cations loading in the interlayer space the montmorillonite efficiency decreased, and in the case of vermiculite an opposite effect was observed. Generally the modified montmorillonites were more effective than modified vermiculites. The HDP cations seem to be more effective compare to the HDTMA. The antibacterial activity tests confirmed efficiency of all organically modified clay minerals against Gram-positive bacteria. The confirmation of antibacterial activity against Y. pestis, plague bacteria, is the most interesting result of this part of the study. Copyright © 2014 Elsevier B.V. All rights reserved.

  12. Facile Fabrication of a Hierarchical Superhydrophobic Coating with Aluminate Coupling Agent Modified Kaolin

    Hui Li; Mengnan Qu; Zhe Sun; Jinmei He; Anning Zhou

    2013-01-01

    A superhydrophobic coating was fabricated from the dispersion of unmodified kaolin particles and aluminate coupling agent in anhydrous ethanol. Through surface modification, water contact angle of the coating prepared by modified kaolin particles increased dramatically from 0° to 152°, and the sliding angle decreased from 90° to 3°. Scanning electron microscopy was used to examine the surface morphology. A structure composed of micro-nano hierarchical component, combined with the surface modi...

  13. Physical properties of the Creutzfeldt-Jakob disease agent

    Sklaviadis, T.K.; Manuelidis, L.; Manuelidis, E.E.

    1989-03-01

    In this report, the authors present the first physical characterization of the Creutzfeld-Jakob disease agent. Preparations with high yields of infectivity (assayed infectious units) were obtained by a novel, gentle procedure in which initially sedimenting Gp34 (prion protein) was disaggregated by a variety of criteria with no subsequent loss of infectivity. Studies with this preparation indicate that most of the Creutzfeldt-Jakob disease agent has both a viruslike size and density. In velocity sedimentation and isopycnic sucrose gradients, infectivity comigrated with nucleic acid-protein complexes of appreciable size.

  14. Physical properties of the Creutzfeldt-Jakob disease agent

    Sklaviadis, T.K.; Manuelidis, L.; Manuelidis, E.E.

    1989-01-01

    In this report, the authors present the first physical characterization of the Creutzfeld-Jakob disease agent. Preparations with high yields of infectivity (assayed infectious units) were obtained by a novel, gentle procedure in which initially sedimenting Gp34 (prion protein) was disaggregated by a variety of criteria with no subsequent loss of infectivity. Studies with this preparation indicate that most of the Creutzfeldt-Jakob disease agent has both a viruslike size and density. In velocity sedimentation and isopycnic sucrose gradients, infectivity comigrated with nucleic acid-protein complexes of appreciable size

  15. Leukotrienes and leukotriene modifiers in pediatric allergic diseases

    Ehab

    ... 12(1):3-12. 3. Leukotrienes and leukotriene modifiers in pediatric allergic diseases ... childhood allergic diseases. This review ... produce cysteinyl-LTs and LTB4 spontaneously in vitro.8. Although nonleukocyte cells generally do not have sufficient 5-LO and FLAP to synthesize .... uninterrupted sleep in these patients.55.

  16. Characterization of polymer-modified cement as a solidification agent for the radwaste

    Ji, Young-Yong; Kwak, Kyung-Kil; Hong, Dae-Seok; Ryu, Woo-Seog

    2012-01-01

    Highlights: ► Polymer-modified cement (PMC) by modification with water-based resins. ► Determination of the optimized polymer content. ► Evaluation of the improved chemical resistance of the PMC. ► Decrease of the amount of ions released into the demineralized water. ► Highly improved property for the nuclide diffusivity at the Co-60. - Abstract: Polymer-modified cement can be produced by partially replacing cement hydrate binders in ordinary Portland cement with polymeric compounds. It is known that the addition of the polymer to the cement paste leads to improved quality, which would be expected to have a high chemical resistance. In order to investigate the application as a solidification agent for the radwaste, polymer-modified cement specimens, by modification with water-based resins, were prepared according to the polymer content from 0% to 30%. The optimized polymer content in the cement pastes was then determined through the compressive strength and the porosity test. Finally, the improved chemical resistance of the polymer-modified cement with the optimized polymer content was evaluated by the thermal cycling, the immersion, and the leaching tests. From the test results, the amount of ions released into the water showed lower values of about 20% at the polymer-modified cement. Especially, a highly improved nuclide diffusivity of Co-60 was observed in the polymer-modified cement.

  17. [Unconventional disease agents--a danger for humans and animals?].

    Kaaden, O R

    1994-02-01

    The occurrence of bovine spongiform encephalopathy (BSE) in Great Britain in 1985/86, has focused again the public concern as well as scientific interest to the Scrapie disease of sheep and goat known more than 150 years. The agents of scrapie and BSE are characterized by unusual biological and physical-chemical properties, especially their high tenacity. Therefore, they are also designated "unconventional agents of viruses". Different theories have been proposed about their infectious characteristics--especially because of the apparent or real missing of an agent-specific nucleic acid--which are named Virinos, Prions or Nemavirus. The broad host range of Scrapie respective BSE, which includes domestic and wild ruminants, Suidae, Felidae, Mustelidae, small rodents, birds and non-primates, has created some concern since there might be an aetiological correlation between the transmissible spongiform encephalopathies of man (Creutzfeld-Jakob- and Gerstmann-Sträussler-Scheinker-Disease) and that of animals. Although at present neither epidemiological nor molecular biological evidence whatsoever was proved, the hypothesis cannot be completely disproved. The probability of infection through digestive tract seems to be rather unlikely but special precautions should be taken as far as production, investigation and application of human medicine drugs of animal origin. Furthermore, research about the aetiology of "unconventional agents" and pathogenesis of resulting diseases is necessary and should be intensified in Germany. Finally, only an early intra vitam-Diagnose and in vitro detection can avoid an further spread of this new category of diseases.

  18. A new proposal for randomized start design to investigate disease-modifying therapies for Alzheimer disease.

    Zhang, Richard Y; Leon, Andrew C; Chuang-Stein, Christy; Romano, Steven J

    2011-02-01

    The increasing prevalence of Alzheimer disease (AD) and lack of effective agents to attenuate progression have accelerated research and development of disease modifying (DM) therapies. The traditional parallel group design and single time point analysis used in the support of past AD drug approvals address symptomatic benefit over relatively short treatment durations. More recent trials investigating disease modification are by necessity longer in duration and require larger sample sizes. Nevertheless, trial design and analysis remain mostly unchanged and may not be adequate to meet the objective of demonstrating disease modification. Randomized start design (RSD) has been proposed as an option to study DM effects, but its application in AD trials may have been hampered by certain methodological challenges. To address the methodological issues that have impeded more extensive use of RSD in AD trial and to encourage other researchers to develop novel design and analysis methodologies to better ascertain DM effects for the next generation of AD therapies, we propose a stepwise testing procedure to evaluate potential DM effects of novel AD therapies. Alzheimer Disease Assessment Scale-Cognitive Subscale (ADAS-cog) is used for illustration. We propose to test three hypotheses in a stepwise sequence. The three tests pertain to treatment difference at two separate time points and a difference in the rate of change. Estimation is facilitated by the Mixed-effects Model for Repeated Measures approach. The required sample size is estimated using Monte Carlo simulations and by modeling ADAS-cog data from prior longitudinal AD studies. The greatest advantage of the RSD proposed in this article is its ability to critically address the question on a DM effect. The AD trial using the new approach would be longer (12-month placebo period plus 12-month delay-start period; total 24-month duration) and require more subjects (about 1000 subjects per arm for the non-inferiority margin

  19. Facile Fabrication of a Hierarchical Superhydrophobic Coating with Aluminate Coupling Agent Modified Kaolin

    Hui Li

    2013-01-01

    Full Text Available A superhydrophobic coating was fabricated from the dispersion of unmodified kaolin particles and aluminate coupling agent in anhydrous ethanol. Through surface modification, water contact angle of the coating prepared by modified kaolin particles increased dramatically from 0° to 152°, and the sliding angle decreased from 90° to 3°. Scanning electron microscopy was used to examine the surface morphology. A structure composed of micro-nano hierarchical component, combined with the surface modification by aluminate coupling agent which reduced the surface energy greatly, was found to be responsible for the superhydrophobicity. The method adopted is relatively simple, facile, and cost-effective and can potentially be applied to large water-repellent surface coatings.

  20. Modified lysozymes as novel broad spectrum natural antimicrobial agents in foods.

    Aminlari, Ladan; Hashemi, Marjan Mohammadi; Aminlari, Mahmoud

    2014-06-01

    In recent years much attention and interest have been directed toward application of natural antimicrobial agents in foods. Some naturally occurring proteins such as lactoperoxidase, lactoferrin, and lysozyme have received considerable attention and are being considered as potential antimicrobial agents in foods. Lysozyme kills bacteria by hydrolyzing the peptidoglycan layer of the cell wall of certain bacterial species, hence its application as a natural antimicrobial agent has been suggested. However, limitations in the action of lysozyme against only Gram-positive bacteria have prompted scientists to extend the antimicrobial effects of lysozyme by several types of chemical modifications. During the last 2 decades extensive research has been directed toward modification of lysozyme in order to improve its antimicrobial properties. This review will report on the latest information available on lysozyme modifications and examine the applicability of the modified lysozymes in controlling growth of Gram-positive and Gram-negative bacteria in foods. The results of modifications of lysozyme using its conjugation with different small molecule, polysaccharides, as well as modifications using proteolytic enzymes will be reviewed. These types of modifications have not only increased the functional properties of lysozyme (such as solubility and heat stability) but also extended the antimicrobial activity of lysozyme. Many examples will be given to show that modification can decrease the count of Gram-negative bacteria in bacterial culture and in foods by as much as 5 log CFU/mL and in some cases essentially eliminated Escherichia coli. In conclusion this review demonstrates that modified lysozymes are excellent natural food preservatives, which can be used in food industry. The subject described in this review article can lead to the development of methods to produce new broad-spectrum natural antimicrobial agents, based on modification of chicken egg white lysozyme, which

  1. Synthesis of modified pyridine and bipyridine substituted coumarins as potent antimicrobial agents

    Lad Hemali B.

    2015-01-01

    Full Text Available In search for new antimicrobial agents a series of new modified pyridine and bipyridine substituted coumarins 5a-y was designed and synthesized by adopting molecular hybridization strategy. All the synthesized compounds were evaluated for their in vitro antimicrobial activity using broth dilution method against selected bacterial (Gram-positive and Gram-negative and fungal strains. Compounds 5a, 5f, 5g, 5n, 5r, 5t, 5w, 5x and 5y demonstrated promising antibacterial activity while other derivatives showed comparable activity to standard drugs used as reference.

  2. Chromatin Modifying Agents in the In Vitro Production of Bovine Embryos

    Fabio Morato Monteiro

    2011-01-01

    Full Text Available The low efficiency observed in cloning by nuclear transfer is related to an aberrant gene expression following errors in epigenetic reprogramming. Recent studies have focused on further understanding of the modifications that take place in the chromatin of embryos during the preimplantation period, through the use of chromatin modifying agents. The goal of these studies is to identify the factors involved in nuclear reprogramming and to adjust in vitro manipulations in order to better mimic in vivo conditions. Therefore, proper knowledge of epigenetic reprogramming is necessary to prevent possible epigenetic errors and to improve efficiency and the use of in vitro fertilization and cloning technologies in cattle and other species.

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

    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.

  4. Huperzine A: Is it an Effective Disease-Modifying Drug for Alzheimer's Disease?

    Qian, Zhong Ming; Ke, Ya

    2014-01-01

    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.

  5. Huperzine A: Is it an Effective Disease-Modifying Drug for Alzheimer’s Disease?

    Qian, Zhong Ming; Ke, Ya

    2014-01-01

    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. PMID:25191267

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

    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.

  7. Demographic, genetic, and environmental factors that modify disease course.

    Marrie, Ruth Ann

    2011-05-01

    As with susceptibility to disease, it is likely that multiple factors interact to influence the phenotype of multiple sclerosis and long-term disease outcomes. Such factors may include genetic factors, socioeconomic status, comorbid diseases, and health behaviors, as well as environmental exposures. An improved understanding of the influence of these factors on disease course may reap several benefits, such as improved prognostication, allowing us to tailor disease management with respect to intensity of disease-modifying therapies and changes in specific health behaviors, in the broad context of coexisting health issues. Such information can facilitate appropriately adjusted comparisons within and between populations. Elucidation of these factors will require careful study of well-characterized populations in which the roles of multiple factors are considered simultaneously. Copyright © 2011 Elsevier Inc. All rights reserved.

  8. Research on the Preparation and Performance of Binary Modified Maltodextrin Water-Reducing Agent

    Jingzhi Wu

    2016-01-01

    Full Text Available Using maltodextrin (MD of different dextrose equivalent (DE values, 1,3-propanesultone, and maleic anhydride as raw materials, a novel binary modified maltodextrin (BMMD was synthesized and further applied as a water-reducing agent. Its structure was characterized by Fourier transform infrared (FT-IR and UV. The rheological behavior of the sample solution and strengths for concrete were also determined and the adsorption was tested by TOC. The influence of the process parameters to degree of substitution (DS and the dosage on the fluidity of cement paste were investigated. The results show that the optimal conditions of sulfonation were the MD of DE 15, m (sulfonated agent/m (MD of 1.4, the catalyst amount of 1% by mass MD, and the reaction time of 12 h; the optimal conditions of esterification were m (esterified agent/m (SMD of 0.6, the reaction temperature of 90°C, and the reaction time of 4 h. The optimal dosages of sulfonated maltodextrin (SMD and BMMD were 0.475% and 0.45%, respectively. In this dosage, the main dispersion capacity of BMMD attributes to two kinds of anchoring groups (SO3-  &  COO- and the appropriate molecular weight of MD.

  9. Partial Reduction of Esters to Aldehydes Using a Novel Modified Red-Al Reducing Agent

    Shin, Won Kyu; Kang, Daehoon; An, Duk Keun [Kangwon National Univ., Chunchon (Korea, Republic of)

    2014-07-15

    We have developed a convenient alternative method for the synthesis of aldehydes from both aromatic and aliphatic esters in very good to excellent yields in the absence of any additives using a modified Red-Al that was easily prepared by reacting commercially available Red-Al with cis-2,6-dimethyl morpholine. The advantages of the present methodology are as follows: simple preparation procedure of the reducing agent, improved product yields, convenient reaction temperature, and short reaction times. Therefore, the new reagent has great potential to be a useful alternative partial reducing agent for the synthesis of aldehydes from esters in organic synthesis. Aldehydes are valuable building blocks and reactive intermediates in organic synthesis. The general and classical syntheses of aldehydes from esters involve reduction-oxidation and partial reduction using efficient partial reducing agents. Obviously, one-step partial reduction methods are more useful than two-step reduction-oxidation methods owing to their simplicity, and generality in organic synthesis.

  10. Wildlife disease prevalence in human-modified landscapes.

    Brearley, Grant; Rhodes, Jonathan; Bradley, Adrian; Baxter, Greg; Seabrook, Leonie; Lunney, Daniel; Liu, Yan; McAlpine, Clive

    2013-05-01

    Human-induced landscape change associated with habitat loss and fragmentation places wildlife populations at risk. One issue in these landscapes is a change in the prevalence of disease which may result in increased mortality and reduced fecundity. Our understanding of the influence of habitat loss and fragmentation on the prevalence of wildlife diseases is still in its infancy. What is evident is that changes in disease prevalence as a result of human-induced landscape modification are highly variable. The importance of infectious diseases for the conservation of wildlife will increase as the amount and quality of suitable habitat decreases due to human land-use pressures. We review the experimental and observational literature of the influence of human-induced landscape change on wildlife disease prevalence, and discuss disease transmission types and host responses as mechanisms that are likely to determine the extent of change in disease prevalence. It is likely that transmission dynamics will be the key process in determining a pathogen's impact on a host population, while the host response may ultimately determine the extent of disease prevalence. Finally, we conceptualize mechanisms and identify future research directions to increase our understanding of the relationship between human-modified landscapes and wildlife disease prevalence. This review highlights that there are rarely consistent relationships between wildlife diseases and human-modified landscapes. In addition, variation is evident between transmission types and landscape types, with the greatest positive influence on disease prevalence being in urban landscapes and directly transmitted disease systems. While we have a limited understanding of the potential influence of habitat loss and fragmentation on wildlife disease, there are a number of important areas to address in future research, particularly to account for the variability in increased and decreased disease prevalence. Previous studies

  11. The influence of modified zeolites as nucleating agents on crystallization behavior and mechanical properties of polypropylene

    Lv, Zhiping; Wang, Kunjun; Qiao, Zhihua; Wang, Wenjie

    2010-01-01

    Polypropylene (PP) composites with unmodified and modified zeolites were prepared by melt blending in single-screw extruder. The modified zeolites, diethoxy (distearoyl) silane (DDS)-zeolite 13X (DDS-13X) and diethoxy (distearoyl) silane-zeolite 5A (DDS-5A), were obtained by grafting diethoxy (distearoyl) silane onto zeolite 13X and 5A, respectively. The influence of the unmodified and modified zeolites as nucleating agents on properties of polypropylene was investigated with X-ray diffraction (XRD), differential scanning calorimetry (DSC), polarized light microscopy (PLM), Vicat softening temperature (VST) and mechanical properties test. The XRD results revealed that zeolite 13X and DDS-13X had a great influence on nucleation of PP compared to zeolite 5A and DDS-5A. The DSC results showed that the addition of small amount of modified zeolites lead to increase in crystallization temperature (T c ), initial crystallization temperature (T onset ) and crystallinity (X c ) of PP composites compared to unmodified zeolites, especially, DDS-13X was more effective than DDS-5A, and the highest crystallinity X c (50.48%) was observed in PP/0.3 wt.% DDS-13X, which was responsible to the higher tensile strength and flexural strength of PP/DDS-13X. The PP/DDS-5A, however, exhibited evident increase in flexural strength and a little change in tensile strength compared to pure PP. Moreover, as the addition amount of DDS-5A or DDS-13X up to 1 wt.%, the impact strength of both PP/DDS-5A and PP/DDS-13X reached 43 kJ/m 2 , which was about 2.8 times greater than that of the pure PP (11.3 kJ/m 2 ). These results were in good agreement with the spherulite morphology observed from PLM micrographs.

  12. Agent-based modeling of noncommunicable diseases: a systematic review.

    Nianogo, Roch A; Arah, Onyebuchi A

    2015-03-01

    We reviewed the use of agent-based modeling (ABM), a systems science method, in understanding noncommunicable diseases (NCDs) and their public health risk factors. We systematically reviewed studies in PubMed, ScienceDirect, and Web of Sciences published from January 2003 to July 2014. We retrieved 22 relevant articles; each had an observational or interventional design. Physical activity and diet were the most-studied outcomes. Often, single agent types were modeled, and the environment was usually irrelevant to the studied outcome. Predictive validation and sensitivity analyses were most used to validate models. Although increasingly used to study NCDs, ABM remains underutilized and, where used, is suboptimally reported in public health studies. Its use in studying NCDs will benefit from clarified best practices and improved rigor to establish its usefulness and facilitate replication, interpretation, and application.

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

    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.

  14. Biologic and oral disease-modifying antirheumatic drug monotherapy in rheumatoid arthritis

    Emery, Paul; Sebba, Anthony; Huizinga, Tom W J

    2013-01-01

    Clinical evidence demonstrates coadministration of tumour necrosis factor inhibitor (TNFi) agents and methotrexate (MTX) is more efficacious than administration of TNFi agents alone in patients with rheumatoid arthritis, leading to the perception that coadministration of MTX with all biologic agents or oral disease-modifying antirheumatic drugs is necessary for maximum efficacy. Real-life registry data reveal approximately one-third of patients taking biologic agents use them as monotherapy. Additionally, an analysis of healthcare claims data showed that when MTX was prescribed in conjunction with a biologic agent, as many as 58% of patients did not collect the MTX prescription. Given this discrepancy between perception and real life, we conducted a review of the peer-reviewed literature and rheumatology medical congress abstracts to determine whether data support biologic monotherapy as a treatment option for patients with rheumatoid arthritis. Our analysis suggests only for tocilizumab is there evidence that the efficacy of biologic monotherapy is comparable with combination therapy with MTX. PMID:23918035

  15. Microstructure and electrochemical behavior of cerium conversion coating modified with silane agent on magnesium substrates

    Lei, Li; Shi, Jing; Wang, Xin; Liu, Dan; Xu, Haigang

    2016-07-01

    The cerium conversion coating with and without different concentrations of silane agent bis-(γ-triethoxysilylpropyl)-tetrasulfide (BTESPT) modification is obtained on magnesium alloys. Detailed properties of the coatings and the role of BTESPT as an additive are studied and followed with careful discussion. The coating morphology, wettability, chemical composition and corrosion resistance are characterized by scanning electronic microscope (SEM), water contact-angle, X-ray photoelectron spectroscopy (XPS), potentiodynamic measurements and electrochemical impedance spectroscopy (EIS). The electrochemical behavior of the coatings is investigated using EIS. The results indicate that the coating morphology and composition can be controlled by changing silane concentration. The combination of cerium ions and silane molecules could promote the formation of more homogenous and higher hydrophobic coating. The coating turns to be more compact and the adhesive strength between the coating and the magnesium substrate are strongly improved with the formation of Sisbnd Osbnd Si and Sisbnd Osbnd M chemical bonds. The optimum corrosion resistance of the coating in the corrosive media is obtained by 25 ml L-1 BTESPT modification. This whole study implies that the cerium conversion coating modified with certain silane agent deserves cautiousness before its application for corrosion resistance.

  16. Management of coccidioidomycosis in patients receiving biologic response modifiers or disease-modifying antirheumatic drugs.

    Taroumian, Sara; Knowles, Susan L; Lisse, Jeffrey R; Yanes, James; Ampel, Neil M; Vaz, Austin; Galgiani, John N; Hoover, Susan E

    2012-12-01

    Coccidioidomycosis (valley fever) is an endemic fungal infection of the American Southwest, an area with a large population of patients with rheumatic diseases. There are currently no guidelines for management of patients who develop coccidioidomycosis while under treatment with biologic response modifiers (BRMs) or disease-modifying antirheumatic drugs (DMARDs). We conducted a retrospective study of how both concurrent diseases were managed and the patient outcomes at 2 centers in Tucson, Arizona. A retrospective chart review identified patients who developed coccidioidomycosis during treatment with DMARDs or BRMs. Patients were seen at least once in a university-affiliated or Veterans Affairs outpatient rheumatology clinic in Tucson, Arizona, between 2007 and 2009. Forty-four patients were identified. Rheumatologic treatment included a BRM alone (n = 11), a DMARD alone (n = 8), or combination therapy (n = 25). Manifestations of coccidioidomycosis included pulmonary infection (n = 29), disseminated disease (n = 9), and asymptomatic positive coccidioidal serologies (n = 6). After the diagnosis of coccidioidomycosis, 26 patients had BRMs and DMARDs stopped, 8 patients had BRMs stopped but DMARD therapy continued, and 10 patients had no change in their immunosuppressive therapy. Forty-one patients had antifungal therapy initiated for 1 month or longer. Followup data were available for 38 patients. BRM and/or DMARD therapy was continued or resumed in 33 patients, only 16 of whom continued concurrent antifungal therapy. None of the patients have had subsequent dissemination or complications of coccidioidomycosis. Re-treating rheumatic disease patients with a BRM and/or a DMARD after coccidioidomycosis appears to be safe in some patients. We propose a management strategy based on coccidioidomycosis disease activity. Copyright © 2012 by the American College of Rheumatology.

  17. Skin diseases associated with Agent Orange and other organochlorine exposures.

    Patterson, Andrew T; Kaffenberger, Benjamin H; Keller, Richard A; Elston, Dirk M

    2016-01-01

    Organochlorine exposure is an important cause of cutaneous and systemic toxicity. Exposure has been associated with industrial accidents, intentional poisoning, and the use of defoliants, such as Agent Orange in the Vietnam War. Although long-term health effects are systematically reviewed by the Institute of Medicine, skin diseases are not comprehensively assessed. This represents an important practice gap as patients can present with cutaneous findings. This article provides a systematic review of the cutaneous manifestations of known mass organochlorine exposures in military and industrial settings with the goal of providing clinically useful recommendations for dermatologists seeing patients inquiring about organochlorine effects. Patients with a new diagnosis of chloracne, porphyria cutanea tarda, cutaneous lymphomas (non-Hodgkin lymphoma), and soft-tissue sarcomas including dermatofibrosarcoma protuberans and leiomyosarcomas should be screened for a history of Vietnam service or industrial exposure. Inconclusive evidence exists for an increased risk of other skin diseases in Vietnam veterans exposed to Agent Orange including benign fatty tumors, melanomas, nonmelanoma skin cancers, milia, eczema, dyschromias, disturbance of skin sensation, and rashes not otherwise specified. Affected veterans should be informed of the uncertain data in those cases. Referral to Department of Veterans Affairs for disability assessment is indicated for conditions with established associations. Copyright © 2015 American Academy of Dermatology, Inc. All rights reserved.

  18. New FDA-Approved Disease-Modifying Therapies for Multiple Sclerosis.

    English, Clayton; Aloi, Joseph J

    2015-04-01

    Interferon injectables and glatiramer acetate have served as the primary disease-modifying treatments for multiple sclerosis (MS) since their introduction in the 1990s and are first-line treatments for relapsing-remitting forms of MS (RRMS). Many new drug therapies were launched since early 2010, expanding the drug treatment options considerably in a disease state that once had a limited treatment portfolio. The purpose of this review is to critically evaluate the safety profile and efficacy data of disease-modifying agents for MS approved by the US Food and Drug Administration (FDA) from 2010 to the present and provide cost and available pharmacoeconomic data about each new treatment. Peer-reviewed clinical trials, pharmacoeconomic studies, and relevant pharmacokinetic/pharmacologic studies were identified from MEDLINE (January 2000-December 2014) by using the search terms multiple sclerosis, fingolimod, teriflunomide, alemtuzumab, dimethyl fumarate, pegylated interferon, peginterferon beta-1a, glatiramer 3 times weekly, and pharmacoeconomics. Citations from available articles were also reviewed for additional references. The databases publically available at www.clinicaltrials.gov and www.fda.gov were searched for unpublished studies or studies currently in progress. A total of 5 new agents and 1 new dosage formulation were approved by the FDA for the treatment of RRMS since 2010. Peginterferon beta-1a and high-dose glatiramer acetate represent 2 new effective injectable options for MS that reduce burden of administration seen with traditional interferon and low-dose glatiramer acetate. Fingolimod, teriflunomide, and dimethyl fumarate represent new oral agents available for MS, and their efficacy in reducing annualized relapse rates is 48% to 55%, 22% to 36.3%, and 44% to 53%, respectively, compared with placebo. Alemtuzumab is a biologic given over a 2-year span that reduced annualized relapse rates by 55% in treatment-naive patients and by 49% in patients

  19. Guidance for Modifying the Definition of Diseases: A Checklist.

    Doust, Jenny; Vandvik, Per O; Qaseem, Amir; Mustafa, Reem A; Horvath, Andrea R; Frances, Allen; Al-Ansary, Lubna; Bossuyt, Patrick; Ward, Robyn L; Kopp, Ina; Gollogly, Laragh; Schunemann, Holger; Glasziou, Paul

    2017-07-01

    No guidelines exist currently for guideline panels and others considering changes to disease definitions. Panels frequently widen disease definitions, increasing the proportion of the population labeled as unwell and potentially causing harm to patients. We set out to develop a checklist of issues, with guidance, for panels to consider prior to modifying a disease definition. We assembled a multidisciplinary, multicontinent working group of 13 members, including members from the Guidelines International Network, Grading of Recommendations Assessment, Development and Evaluation working group, and the World Health Organisation. We used a 5-step process to develop the checklist: (1) a literature review of issues, (2) a draft outline document, (3) a Delphi process of feedback on the list of issues, (4) a 1-day face-to-face meeting, and (5) further refinement of the checklist. The literature review identified 12 potential issues. From these, the group developed an 8-item checklist that consisted of definition changes, number of people affected, trigger, prognostic ability, disease definition precision and accuracy, potential benefits, potential harms, and the balance between potential harms and benefits. The checklist is accompanied by an explanation of each item and the types of evidence to assess each one. We used a panel's recent consideration of a proposed change in the definition of gestational diabetes mellitus (GDM) to illustrate use of the checklist. We propose that the checklist be piloted and validated by groups developing new guidelines. We anticipate that the use of the checklist will be a first step to guidance and better documentation of definition changes prior to introducing modified disease definitions.

  20. Vancomycin-modified Fe3O4@SiO2@Ag microflowers as effective antimicrobial agents

    Wang C

    2017-04-01

    Full Text Available Chongwen Wang,1,2,* Kehan Zhang,2,* Zhe Zhou,2,* Qingjun Li,2 Liting Shao,2 Rong Zhang Hao,3 Rui Xiao,2 Shengqi Wang1,2 1College of Life Sciences & Bio-Engineering, Beijing University of Technology, 2Beijing Key Laboratory of New Molecular Diagnosis Technologies for Infectious Diseases, Beijing Institute of Radiation Medicine, Beijing, 3Institute for Disease Control and Prevention, Academy of Military Medical Sciences, Beijing, People’s Republic of China *These authors contributed equally to this work Abstract: Nanomaterials combined with antibiotics exhibit synergistic effects and have gained increasing interest as promising antimicrobial agents. In this study, vancomycin-modified magnetic-based silver microflowers (Van/Fe3O4@SiO2@Ag microflowers were rationally designed and prepared to achieve strong bactericidal ability, a wide antimicrobial spectrum, and good recyclability. High-performance Fe3O4@SiO2@Ag microflowers served as a multifunction-supporting matrix and exhibited sufficient magnetic response property due to their 200 nm Fe3O4 core. The microflowers also possessed a highly branched flower-like Ag shell that provided a large surface area for effective Ag ion release and bacterial contact. The modified-vancomycin layer was effectively bound to the cell wall of bacteria to increase the permeability of the cell membrane and facilitate the entry of the Ag ions into the bacterium, resulting in cell death. As such, the fabricated Van/Fe3O4@SiO2@Ag microflowers were predicted to be an effective and environment-friendly antibacterial agent. This hypothesis was verified through sterilization of Gram-negative Escherichia coli and Gram-positive methicillin-resistant Staphylococcus aureus, with minimum inhibitory concentrations of 10 and 20 µg mL-1, respectively. The microflowers also showed enhanced effect compared with bare Fe3O4@SiO2@Ag microflowers and free-form vancomycin, confirming the synergistic effects of the combination of the

  1. Immunological detection and quantification of DNA components structurally modified by alkylating carcinogens, mutagens and chemotherapeutic agents

    Rajewsky, M.F.

    1983-01-01

    The detection and quantification of defined reaction products of chemical mutagens and carcinogens (and of many cancer chemotherapeutic agents) with DNA require highly sensitive analytical techniques. The exceptional capability of immunoglobulins to recognize subtle alterations of molecular structure (especially when monoclonal antibodies are used to maximize specificity), outstanding sensitivity of immunoanalysis by high-affinity antibodies, and the fact that radioactively-labelled agents are not required suggest the utility of a radioimmunoassay to recognize and quantitate alkylated DNA products. We have recently developed a set of high-affinity monoclonal antibodies (secreted by mouse x mouse as well as by rat x rat hybridomas; antibody affinity constants, 10 9 to > 10 10 lmol) specifically directed against several DNA alkylation products with possible relevance in relation to both mutagenesis and malignant transformation of mammalian cells. These alkylation products include 0 6 -N-butyldeoxyguanosine, and 0 4 -ethyldeoxythymidine. When used in a radioimmunassay, an antibody specific for 0 6 -ethyldeoxyguanosine, for example, will detect this product at an 0 6 -ethyldeoxyguanosine/deoxyguanosine molar ratio of approx. 3 x 10 -7 in a hydrolysate of 100 ug of DNA. The limit of detection can be lowered further if the respective alkyldeoxynucleosides are separated by HPLC from the DNA hydrolysate prior to the RIA. The anti-alkyldeoxynucleoside monoclonal antibodies can also be used to visualize, by immunostaining and fluorescence microscopy combined with electronic image intensification, specific alkylation products in the nuclear DNA of individual cells, and to localize structurally modified bases in double-stranded DNA molecules by transmission electron microscopy

  2. Microstructure and electrochemical behavior of cerium conversion coating modified with silane agent on magnesium substrates

    Lei, Li; Shi, Jing, E-mail: shijing@ouc.edu.cn; Wang, Xin, E-mail: wangxin.hd@163.com; Liu, Dan; Xu, Haigang

    2016-07-15

    Graphical abstract: The unmodified coating shows averaged static water contact angles of a little more than 50º, which is clearly hydrophilic for water solutions. With the silane concentration increases, the water contact angles show an increase tendency. Especially, when the silane addition is increased to 25 ml L-1, the coating surface presents a hydrophobic feature, with static water contact angle of more than 110º. - Highlights: • BTESPT modification can effectively improve the uniformity, hydrophobic performance, chemical stability and corrosion inhibition capability of traditional cerium conversion coating. • Si-O-Si linkage builds a robust structure to increase of the coating density. Si−O−Mg bonds strengthen the adhesion between the coating/substrate. • The system modified with 25 ml L{sup −1} BTESPT displays the optimum corrosion protection performance. - Abstract: The cerium conversion coating with and without different concentrations of silane agent bis-(γ-triethoxysilylpropyl)-tetrasulfide (BTESPT) modification is obtained on magnesium alloys. Detailed properties of the coatings and the role of BTESPT as an additive are studied and followed with careful discussion. The coating morphology, wettability, chemical composition and corrosion resistance are characterized by scanning electronic microscope (SEM), water contact-angle, X-ray photoelectron spectroscopy (XPS), potentiodynamic measurements and electrochemical impedance spectroscopy (EIS). The electrochemical behavior of the coatings is investigated using EIS. The results indicate that the coating morphology and composition can be controlled by changing silane concentration. The combination of cerium ions and silane molecules could promote the formation of more homogenous and higher hydrophobic coating. The coating turns to be more compact and the adhesive strength between the coating and the magnesium substrate are strongly improved with the formation of Si−O−Si and Si

  3. Microstructure and electrochemical behavior of cerium conversion coating modified with silane agent on magnesium substrates

    Lei, Li; Shi, Jing; Wang, Xin; Liu, Dan; Xu, Haigang

    2016-01-01

    Graphical abstract: The unmodified coating shows averaged static water contact angles of a little more than 50º, which is clearly hydrophilic for water solutions. With the silane concentration increases, the water contact angles show an increase tendency. Especially, when the silane addition is increased to 25 ml L-1, the coating surface presents a hydrophobic feature, with static water contact angle of more than 110º. - Highlights: • BTESPT modification can effectively improve the uniformity, hydrophobic performance, chemical stability and corrosion inhibition capability of traditional cerium conversion coating. • Si-O-Si linkage builds a robust structure to increase of the coating density. Si−O−Mg bonds strengthen the adhesion between the coating/substrate. • The system modified with 25 ml L"−"1 BTESPT displays the optimum corrosion protection performance. - Abstract: The cerium conversion coating with and without different concentrations of silane agent bis-(γ-triethoxysilylpropyl)-tetrasulfide (BTESPT) modification is obtained on magnesium alloys. Detailed properties of the coatings and the role of BTESPT as an additive are studied and followed with careful discussion. The coating morphology, wettability, chemical composition and corrosion resistance are characterized by scanning electronic microscope (SEM), water contact-angle, X-ray photoelectron spectroscopy (XPS), potentiodynamic measurements and electrochemical impedance spectroscopy (EIS). The electrochemical behavior of the coatings is investigated using EIS. The results indicate that the coating morphology and composition can be controlled by changing silane concentration. The combination of cerium ions and silane molecules could promote the formation of more homogenous and higher hydrophobic coating. The coating turns to be more compact and the adhesive strength between the coating and the magnesium substrate are strongly improved with the formation of Si−O−Si and Si−O−M chemical

  4. Optimizing agent-based transmission models for infectious diseases.

    Willem, Lander; Stijven, Sean; Tijskens, Engelbert; Beutels, Philippe; Hens, Niel; Broeckhove, Jan

    2015-06-02

    Infectious disease modeling and computational power have evolved such that large-scale agent-based models (ABMs) have become feasible. However, the increasing hardware complexity requires adapted software designs to achieve the full potential of current high-performance workstations. We have found large performance differences with a discrete-time ABM for close-contact disease transmission due to data locality. Sorting the population according to the social contact clusters reduced simulation time by a factor of two. Data locality and model performance can also be improved by storing person attributes separately instead of using person objects. Next, decreasing the number of operations by sorting people by health status before processing disease transmission has also a large impact on model performance. Depending of the clinical attack rate, target population and computer hardware, the introduction of the sort phase decreased the run time from 26% up to more than 70%. We have investigated the application of parallel programming techniques and found that the speedup is significant but it drops quickly with the number of cores. We observed that the effect of scheduling and workload chunk size is model specific and can make a large difference. Investment in performance optimization of ABM simulator code can lead to significant run time reductions. The key steps are straightforward: the data structure for the population and sorting people on health status before effecting disease propagation. We believe these conclusions to be valid for a wide range of infectious disease ABMs. We recommend that future studies evaluate the impact of data management, algorithmic procedures and parallelization on model performance.

  5. Modifiable Cardiovascular Disease Risk Factors among Indigenous Populations

    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.

  6. QSAR studies of some side chain modified 7-chloro-4-aminoquinolines as antimalarial agents

    Nitendra K. Sahu

    2014-11-01

    Full Text Available The quantitative structure–activity relationship (QSAR analyses were carried out for a series of new side chain modified 4-amino-7-chloroquinolines to find out the structural requirements of their antimalarial activities against both chloroquine sensitive (HB3 and resistant (Dd2 Plasmodium falciparum strain. The statistically significant best 2D QSAR models for Dd2, having correlation coefficient (r2 = 0.9188 and cross validated squared correlation coefficient (q2 = 0.8349 with external predictive ability (pred_r2 = 0.7258 and for HB3, having r2 = 0.9024, q2 = 0.8089 and pred_r2 = 0.7463 were developed by multiple linear regression coupled with genetic algorithm (GA–MLR and stepwise (SW–MLR forward algorithm, respectively. The results of the present study may be useful on the designing of more potent analogues as antimalarial agents.

  7. Clinical Trials for Disease-Modifying Therapies in Alzheimer's Disease: A Primer, Lessons Learned, and a Blueprint for the Future.

    Cummings, Jeffrey; Ritter, Aaron; Zhong, Kate

    2018-03-16

    Alzheimer's disease (AD) has no currently approved disease-modifying therapies (DMTs), and treatments to prevent, delay the onset, or slow the progression are urgently needed. A delay of 5 years if available by 2025 would decrease the total number of patients with AD by 50% in 2050. To meet the definition of DMT, an agent must produce an enduring change in the course of AD; clinical trials of DMTs have the goal of demonstrating this effect. AD drug discovery entails target identification followed by high throughput screening and lead optimization of drug-like compounds. Once an optimized agent is available and has been assessed for efficacy and toxicity in animals, it progresses through Phase I testing with healthy volunteers, Phase II learning trials to establish proof-of-mechanism and dose, and Phase III confirmatory trials to demonstrate efficacy and safety in larger populations. Phase III is followed by Food and Drug Administration review and, if appropriate, market access. Trial populations include cognitively normal at-risk participants in prevention trials, mildly impaired participants with biomarker evidence of AD in prodromal AD trials, and subjects with cognitive and functional impairment in AD dementia trials. Biomarkers are critical in trials of DMTs, assisting in participant characterization and diagnosis, target engagement and proof-of-pharmacology, demonstration of disease-modification, and monitoring side effects. Clinical trial designs include randomized, parallel group; delayed start; staggered withdrawal; and adaptive. Lessons learned from completed trials inform future trials and increase the likelihood of success.

  8. Divalent Copper as a Major Triggering Agent in Alzheimer's Disease.

    Brewer, George J

    2015-01-01

    Alzheimer's disease (AD) is at epidemic proportions in developed countries, with a steady increase in the early 1900 s, and then exploding over the last 50 years. This epidemiology points to something causative in the environment of developed countries. This paper will review the considerable evidence that that something could be inorganic copper ingestion. The epidemic parallels closely the spread of copper plumbing, with copper leached from the plumbing into drinking water being a main causal feature, aided by the increasingly common use of supplement pills containing copper. Inorganic copper is divalent copper, or copper-2, while we now know that organic copper, or copper in foods, is primarily monovalent copper, or copper-1. The intestinal transport system, Ctr1, absorbs copper-1 and the copper moves to the liver, where it is put into safe channels. Copper-2 is not absorbed by Ctr1, and some of it bypasses the liver and goes directly into the blood, where it appears to be exquisitely toxic to brain cognition. Thus, while aggregation of amyloid-β has been postulated to be the cause of AD under current dogma, the great increase in prevalence over the last century appears to be due to ingestion of copper-2, which may be causing the aggregation, and/or increasing the oxidant toxicity of the aggregates. An alternative hypothesis proposes that oxidant stress is the primary injuring agent, and under this hypothesis, copper-2 accumulation in the brain may be a causal factor of the oxidant injury. Thus, irrespective of which hypothesis is correct, AD can be classified, at least in part, as a copper-2 toxicity disease. It is relatively easy to avoid copper-2 ingestion, as discussed in this review. If most people begin avoiding copper-2 ingestion, perhaps the epidemic of this serious disease can be aborted.

  9. Piezosurgery in Modified Pterional Orbital Decompression Surgery in Graves Disease.

    Grauvogel, Juergen; Scheiwe, Christian; Masalha, Waseem; Jarc, Nadja; Grauvogel, Tanja; Beringer, Andreas

    2017-10-01

    Piezosurgery uses microvibrations to selectively cut bone, preserving the adjacent soft tissue. The present study evaluated the use of piezosurgery for bone removal in orbital decompression surgery in Graves disease via a modified pterional approach. A piezosurgical device (Piezosurgery medical) was used in 14 patients (20 orbits) with Graves disease who underwent orbital decompression surgery in additional to drills and rongeurs for bone removal of the lateral orbital wall and orbital roof. The practicability, benefits, and drawbacks of this technique in orbital decompression surgery were recorded. Piezosurgery was evaluated with respect to safety, preciseness of bone cutting, and preservation of the adjacent dura and periorbita. Preoperative and postoperative clinical outcome data were assessed. The orbital decompression surgery was successful in all 20 orbits, with good clinical outcomes and no postoperative complications. Piezosurgery proved to be a safe tool, allowing selective bone cutting with no damage to the surrounding soft tissue structures. However, there were disadvantages concerning the intraoperative handling in the narrow space and the efficiency of bone removal was limited in the orbital decompression surgery compared with drills. Piezosurgery proved to be a useful tool in bone removal for orbital decompression in Graves disease. It is safe and easy to perform, without any danger of damage to adjacent tissue because of its selective bone-cutting properties. Nonetheless, further development of the device is necessary to overcome the disadvantages in intraoperative handling and the reduced bone removal rate. Copyright © 2017 Elsevier Inc. All rights reserved.

  10. Monamine oxidase inhibitors: current and emerging agents for Parkinson disease.

    Fernandez, Hubert H; Chen, Jack J

    2007-01-01

    Monoamine oxidase type B (MAO-B) is the predominant isoform responsible for the metabolic breakdown of dopamine in the brain. Selective inhibition of brain MAO-B results in elevation of synaptosomal dopamine concentrations. Data have been reported regarding the selective MAO-B inhibitors, rasagiline and selegiline, for the symptomatic treatment of Parkinson disease (PD). Selegiline has demonstrated efficacy as monotherapy in patients with early PD (Deprenyl and Tocopherol Antioxidative Therapy of Parkinsonism study), but evidence of selegiline efficacy as adjunctive treatment in levodopa-treated PD patients with motor fluctuations is equivocal. A new formulation of selegiline (Zydis selegiline) has been evaluated in 2 small, placebo-controlled studies as adjunctive therapy to levodopa. The Zydis formulation allows pregastric absorption of selegiline, minimizing first-pass metabolism, and thereby increasing selegiline bioavailability and reducing the concentration of amphetamine metabolites. Rasagiline is a selective, second-generation, irreversible MAO-B inhibitor, with at least 5 times the potency of selegiline in vitro and in animal models. Rasagiline has demonstrated efficacy in 1 large, randomized, double-blind, placebo-controlled trial (TVP-1012 in Early Monotherapy for Parkinson's Disease Outpatients) as initial monotherapy in patients with early PD, and in 2 large, controlled trials (Parkinson's Rasagiline: Efficacy and Safety in the Treatment of "Off," Lasting Effect in Adjunct Therapy With Rasagiline Given Once Daily) as adjunctive treatment in levodopa-treated PD patients with motor fluctuations. Unlike selegiline, rasagiline is an aminoindan derivative with no amphetamine metabolites. A randomized clinical trial is underway to confirm preclinical and preliminary clinical data suggesting rasagiline has disease-modifying effects.

  11. Nonpeptide neurotrophic agents useful in the treatment of neurodegenerative diseases such as Alzheimer's disease

    Masaaki Akagi

    2015-02-01

    Full Text Available Developed regions, including Japan, have become “aged societies,” and the number of adults with senile dementias, such as Alzheimer's disease (AD, Parkinson's disease, and Huntington's disease, has also increased in such regions. Neurotrophins (NTs may play a role in the treatment of AD because endogenous neurotrophic factors (NFs prevent neuronal death. However, peptidyl compounds have been unable to cross the blood–brain barrier in clinical studies. Thus, small molecules, which can mimic the functions of NFs, might be promising alternatives for the treatment of neurodegenerative diseases. Natural products, such as or nutraceuticals or those used in traditional medicine, can potentially be used to develop new therapeutic agents against neurodegenerative diseases. In this review, we introduced the neurotrophic activities of polyphenols honokiol and magnolol, which are the main constituents of Magnolia obovata Thunb, and methanol extracts from Zingiber purpureum (BANGLE, which may have potential therapeutic applications in various neurodegenerative disorders.

  12. End-functional silicone coupling agent modified PEO/P(VDF-HFP)/SiO2 nanocomposite polymer electrolyte DSSC

    Zhang Jing; Yang Ying; Wu Sujuan; Xu Sheng; Zhou Conghua; Hu Hao; Chen Bolei; Xiong Xiaodong; Sebo, Bobby; Han Hongwei; Zhao Xingzhong

    2008-01-01

    The end-functional silicone coupling agent (dodecyl-trimethoxysilane, DTMS for short) was used to modify the PEO/P(VDF-HFP)/SiO 2 nanocomposite polymer electrolyte (CPE) and the different amounts of DTMS modification effects were studied. The experiments showed the silicone coupling agent with hydrophobic alkyl chains (-C 12 H 25 ) chemically engineered on the SiO 2 nanoparticles, and formed a Si-O-Si cross-linked network in the new nanocomposite polymer electrolyte. Proper content of DTMS modified CPE exhibited improved ionic conductivity and the connection with the photoanode and counter electrode. However, much higher content of the DTMS modification changed the conformation of the polymer network and reduced the ionic movement. Compared with the performance (3.84%) of the original DSSC, the DSSC with functional silicone coupling agent modified CPE (DTMS:SiO 2 = 2:1, mol ratio) exhibited improved J sc (7.94 mA cm -2 ), V oc (0.624 V) and optimal efficiency (5.2%) (measured at AM1.5, light intensity of 58.4 mW cm -2 ). The V oc of the silicone coupling agent modified polymer electrolyte DSSC is obviously improved, which is mainly due to that the hydrophobic alkyl chain end groups formed an insulating layer that retarded the electron recombination at the TiO 2 nanoporous photoanode/polymer electrolyte interface. The DTMS:SiO 2 = 2:1 modified CPE type DSSC exhibited a performance of 6.42% at a light intensity of 32.1 mW cm -2 and 4.94% at 99.2 mW cm -2

  13. Reduced or modified dietary fat for preventing cardiovascular disease

    Lee Hooper

    Full Text Available ABSTRACT: BACKGROUND: Reduction and modification of dietary fats have differing effects on cardiovascular risk factors (such as serum cholesterol, but their effects on important health outcomes are less clear. OBJECTIVE: To assess the effect of reduction and/or modification of dietary fats on mortality, cardiovascular mortality, cardiovascular morbidity and individual outcomes including myocardial infarction, stroke and cancer diagnoses in randomised clinical trials of at least 6 months duration. METHODS: Search methods: For this review update, the Cochrane Central Register of Controlled Trials (CENTRAL, Medline and Embase, were searched through to June 2010. References of Included studies and reviews were also checked. Selection criteria: Trials fulfilled the following criteria: 1 randomized with appropriate control group, 2 intention to reduce or modify fat or cholesterol intake (excluding exclusively omega-3 fat interventions, 3 not multi factorial, 4 adult humans with or without cardiovascular disease, 5 intervention at least six months, 6 mortality or cardiovascular morbidity data available. Data collection and analysis: Participant numbers experiencing health outcomes in each arm were extracted independently in duplicate and random effects meta-analyses, meta-regression, sub-grouping, sensitivity analyses and funnel plots were performed. MAIN RESULTS: This updated review suggested that reducing saturated fat by reducing and/or modifying dietary fat reduced the risk of cardiovascular events by 14% (RR 0.86, 95% CI 0.77 to 0.96, 24 comparisons, 65,508 participants of whom 7% had a cardiovascular event, I2 50%. Subgrouping suggested that this reduction in cardiovascular events was seen in studies of fat modification (not reduction - which related directly to the degree of effect on serum total and LDL cholesterol and triglycerides, of at least two years duration and in studies of men (not of women. There were no clear effects of dietary fat

  14. Reduced or modified dietary fat for preventing cardiovascular disease

    Hooper, Lee; Summerbell, Carolyn D; Thompson, Rachel; Sills, Deirdre; Roberts, Felicia G; Moore, Helen; Smith, George Davey

    2014-01-01

    Background Reduction and modification of dietary fats have differing effects on cardiovascular risk factors (such as serum cholesterol), but their effects on important health outcomes are less clear. Objectives To assess the effect of reduction and/or modification of dietary fats on mortality, cardiovascular mortality, cardiovascular morbidity and individual outcomes including myocardial infarction, stroke and cancer diagnoses in randomised clinical trials of at least 6 months duration. Search methods For this review update, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE and EMBASE, were searched through to June 2010. References of Included studies and reviews were also checked. Selection criteria Trials fulfilled the following criteria: 1) randomised with appropriate control group, 2) intention to reduce or modify fat or cholesterol intake (excluding exclusively omega-3 fat interventions), 3) not multi factorial, 4) adult humans with or without cardiovascular disease, 5) intervention at least six months, 6) mortality or cardiovascular morbidity data available. Data collection and analysis Participant numbers experiencing health outcomes in each arm were extracted independently in duplicate and random effects meta-analyses, meta-regression, sub-grouping, sensitivity analyses and funnel plots were performed. Main results This updated review suggested that reducing saturated fat by reducing and/or modifying dietary fat reduced the risk of cardiovascular events by 14% (RR 0.86, 95% CI 0.77 to 0.96, 24 comparisons, 65,508 participants of whom 7% had a cardiovascular event, I2 50%). Subgrouping suggested that this reduction in cardiovascular events was seen in studies of fat modification (not reduction - which related directly to the degree of effect on serum total and LDL cholesterol and triglycerides), of at least two years duration and in studies of men (not of women). There were no clear effects of dietary fat changes on total mortality (RR 0

  15. Infiltrative Lung Diseases: Complications of Novel Antineoplastic Agents in Patients with Hematological Malignancies

    Bobbak Vahid

    2008-01-01

    Full Text Available Infiltrative lung disease is a well-known complication of antineoplastic agents in patients with hematological malignancies. Novel agents are constantly being added to available treatments. The present review discusses different pulmonary syndromes, pathogenesis and management of these novel agents.

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

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

    2014-11-28

    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, which are compromised in patients with glycogenosis IIIa. Administration of carbohydrates may elicit reactive hyperinsulinism, resulting in suppression of lipolysis, ketogenesis, gluconeogenesis, and activation of glycogen synthesis. Thus, heart and skeletal muscle are depleted of energy substrates. Modified Atkins diet leads to increased blood levels of ketone bodies and fatty acids. We hypothesize that this health care intervention improves the energetic balance of muscles. We treated 2 boys with glycogenosis IIIa aged 9 and 11 years with a modified Atkins diet (10 g carbohydrate per day, protein and fatty acids ad libitum) over a period of 32 and 26 months, respectively. In both patients, creatine kinase levels in blood dropped in response to Atkins diet. When diet was withdrawn in one of the patients he complained of chest pain, reduced physical strength and creatine kinase levels rapidly increased. This was reversed when Atkins diet was reintroduced. One patient suffered from severe cardiomyopathy which significantly improved under diet. Patients with glycogenosis IIIa benefit from an improved energetic state of heart and skeletal muscle by introduction of Atkins diet both on a biochemical and clinical level. Apart from transient hypoglycaemia no serious adverse effects were observed.

  17. Phenolic aminocarboxylic acids - new chelating agents for modifying gallium-67 biodistribution

    Hunt, F.C.; Maddalena, D.J.

    1982-01-01

    The chelating agents EDDHA and HBED were synthesised with carboxyl or sulphonyl groups in the phenolic ring to favour urinary excretion on complexing with gallium. Carboxyl EDDMA was administered to tumor-bearing rats, and its concentration in the tumours and other tissues determined by scintigraphic imaging. The chelating agents increase tumour to blood ratios by chelating gallium in vivo. (U.K.)

  18. Phenolic aminocarboxylic acids - new chelating agents for modifying gallium-67 biodistribution

    Hunt, F.C.; Maddalena, D.J. (Australian Atomic Energy Commission Research Establishment, Lucas Heights)

    The chelating agents EDDHA and HBED were synthesised with carboxyl or sulphonyl groups in the phenolic ring to favour urinary excretion on complexing with gallium. Carboxyl EDDMA was administered to tumor-bearing rats, and its concentration in the tumours and other tissues determined by scintigraphic imaging. The chelating agents increase tumour to blood ratios by chelating gallium in vivo.

  19. Ultrasound contrast-agent improves imaging of lower limb occlusive disease

    Eiberg, J P; Hansen, M A; Jensen, F

    2003-01-01

    to evaluate if ultrasound contrast-agent infusion could improve duplex-ultrasound imaging of peripheral arterial disease (PAD) and increase the agreement with digital subtraction arteriography (DSA).......to evaluate if ultrasound contrast-agent infusion could improve duplex-ultrasound imaging of peripheral arterial disease (PAD) and increase the agreement with digital subtraction arteriography (DSA)....

  20. Incidence of insects, diseases, and other damaging agents in Oregon forests.

    Paul A. Dunham

    2008-01-01

    This report uses data from a network of forest inventory plots sampled at two points in time, annual aerial insect and disease surveys, and specialized pest damage surveys to quantify the incidence and impact of insects, diseases, and other damaging agents on Oregon's forests. The number and volume of trees damaged or killed by various agents is summarized....

  1. The application of modified hydrotalcites as chloride scavengers and inhibitor release agents in cement mortars

    Yang, Z.; Fischer, H.; Polder, R.B.

    2014-01-01

    Owing to the unique molecular structure and high ion exchange capacity, hydrotalcites are believed to have a potential to be modified and tailor-made as an active component of concrete. In this paper, two types of modified hydrotalcites (MHT-pAB and MHT-NO2) were incorporated into cement mortars

  2. Study of chelating agent as a surface modifier for retarding corrosion attack on ferrous metal

    Nur Ubaidah Saidin; Muhamad Daud; Siti Radiah Mohd Kamarudin; Zaifol Samsu; Azali Muhamad; Rusni Rejab; Mohd Saari Ripin; Mohd Shariff Sattar

    2010-01-01

    A different concentration of chelating agents in electrolyte of 3.5 % NaCl was applied to bare ferrous metal and tested for their effectiveness as a corrosion retardant. The performance of the samples was measured using corrosion measurement system. The results indicated that the contribution of chelating agent was expediting the reduction of the passive film. The anodic behavior was clearly found to be influenced by the concentration of the chelating agent. It was also found that some of the corrosion was apparently converted to protective layer over a period of time. Excessive moisture caused breakdown of film by removing the unreacted chelating agent and causing regrowth of the existing rust. (author)

  3. Liposomes for Targeted Delivery of Active Agents against Neurodegenerative Diseases (Alzheimer's Disease and Parkinson's Disease

    Carlos Spuch

    2011-01-01

    Full Text Available Neurodegenerative diseases, such as Alzheimer's disease and Parkinson's disease represent a huge unmet medical need. The prevalence of both diseases is increasing, but the efficacy of treatment is still very limited due to various factors including the blood brain barrier (BBB. Drug delivery to the brain remains the major challenge for the treatment of all neurodegenerative diseases because of the numerous protective barriers surrounding the central nervous system. New therapeutic drugs that cross the BBB are critically needed for treatment of many brain diseases. One of the significant factors on neurotherapeutics is the constraint of the blood brain barrier and the drug release kinetics that cause peripheral serious side effects. Contrary to common belief, neurodegenerative and neurological diseases may be multisystemic in nature, and this presents numerous difficulties for their potential treatment. Overall, the aim of this paper is to summarize the last findings and news related to liposome technology in the treatment of neurodegenerative diseases and demonstrate the potential of this technology for the development of novel therapeutics and the possible applications of liposomes in the two most widespread neurodegenerative diseases, Alzheimer's disease and Parkinson's disease.

  4. Textural and sensory properties of low fat pork sausages with added hydrated oatmeal and tofu as texture-modifying agents.

    Yang, Han-Sul; Choi, Sung-Gil; Jeon, Jin-Tae; Park, Gu-Boo; Joo, Seon-Tea

    2007-02-01

    Low fat sausages were prepared with added hydrated oatmeal or tofu as texture-modifying agents at levels of 10%, 15%, and 25% (w/w), respectively. The effects of the type and level of texture-modifying agents on the physical and sensory properties of low fat sausages were investigated. The water-holding capacity in sausage products increased by increasing the hydrated oatmeal level, but no significant differences was observed by the addition of tofu. The higher level of the agents produced a sausage product with less cooking loss and with a softer texture. The moisture absorption measurements suggest that the decrease in hardness of oatmeal-added sausage products may be due to the higher water-retention properties of oatmeal in response to heat treatment, while that of tofu-added sausage products may be associated with a weaker internal structure of tofu than the pork loin. The sensory evaluations indicated that the greatest overall acceptability in a low fat sausage was attained when the hydrated oatmeal or tofu were at their 15% addition level, respectively.

  5. Chemical functionalization of ceramic tile surfaces by silane coupling agents: polymer modified mortar adhesion mechanism implications

    Alexandra Ancelmo Piscitelli Mansur

    2008-09-01

    Full Text Available Adhesion between tiles and mortars are crucial to the stability of ceramic tile systems. From the chemical point of view, weak forces such as van der Waals forces and hydrophilic interactions are expected to be developed preferably at the tiles and polymer modified Portland cement mortar interface. The main goal of this paper was to use organosilanes as primers to modify ceramic tile hydrophilic properties to improve adhesion between ceramic tiles and polymer modified mortars. Glass tile surfaces were treated with several silane derivatives bearing specific functionalities. Contact angle measurements and Fourier Transform Infrared Spectroscopy (FTIR were used for evaluating the chemical changes on the tile surface. In addition, pull-off tests were conducted to assess the effect on adhesion properties between tile and poly(ethylene-co-vinyl acetate, EVA, modified mortar. The bond strength results have clearly shown the improvement of adherence at the tile-polymer modified mortar interface, reflecting the overall balance of silane, cement and polymer interactions.

  6. Disease-associated prion protein detected in lymphoid tissues from pigs challenged with the agent of chronic wasting disease

    Aims: Chronic wasting disease (CWD) is a naturally-occurring, fatal neurodegenerative disease of cervids. We previously demonstrated that disease-associated prion protein (PrPSc) can be detected in the brain and retina from pigs challenged intracranially or orally with the CWD agent. In that study,...

  7. Screening of biocontrol agents for control of foliar diseases

    Köhl, J.

    2009-01-01

    Candidate antagonists for the development of biocontrol agents have to fulfill many criteria. The criterion often investigated first in detail is the antagonistic potential of candidates against the target pathogen. However, candidates must also have high ecological competence, must be suitable for

  8. A Functional Iron Oxide Nanoparticles Modified with PLA-PEG-DG as Tumor-Targeted MRI Contrast Agent.

    Xiong, Fei; Hu, Ke; Yu, Haoli; Zhou, Lijun; Song, Lina; Zhang, Yu; Shan, Xiuhong; Liu, Jianping; Gu, Ning

    2017-08-01

    Tumor targeting could greatly promote the performance of magnetic nanomaterials as MRI (Magnetic Resonance Imaging) agent for tumor diagnosis. Herein, we reported a novel magnetic nanoparticle modified with PLA (poly lactic acid)-PEG (polyethylene glycol)-DG (D-glucosamine) as Tumor-targeted MRI Contrast Agent. In this work, we took use of the D-glucose passive targeting on tumor cells, combining it on PLA-PEG through amide reaction, and then wrapped the PLA-PEG-DG up to the Fe 3 O 4 @OA NPs. The stability and anti phagocytosis of Fe 3 O 4 @OA@PLA-PEG-DG was tested in vitro; the MRI efficiency and toxicity was also detected in vivo. These functional magnetic nanoparticles demonstrated good biocompatibility and stability both in vitro and in vivo. Cell experiments showed that Fe 3 O 4 @OA@PLA-PEG-DG nanoparticles exist good anti phagocytosis and high targetability. In vivo MRI images showed that the contrast effect of Fe 3 O 4 @OA@PLA-PEG-DG nanoparticles prevailed over the commercial non tumor-targeting magnetic nanomaterials MRI agent at a relatively low dose. The DG can validly enhance the tumor-targetting effect of Fe 3 O 4 @OA@PLA-PEG nanoparticle. Maybe MRI agents with DG can hold promise as tumor-targetting development in the future.

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

    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

  10. Waste Material of Propolis as a Film Forming Agent Intended to Modify the Metronidazole Release: Preparation and Characterization.

    de Toledo, Lucas de Alcântara Sica; Rosseto, Hélen Cássia; Ravani, Laura; Cortesi, Rita; Bruschi, Marcos Luciano

    2016-01-01

    Metronidazole is an antimicrobial agent utilized for the treatment of protozoa and anaerobic bacteria infections. Many times, it is necessary to modify the metronidazole release, and the development of modified release systems may be suggested. In this study, we are able to investigate the use of the residue normally thrown out from the preparation of propolis extracts (BP) as strategy to modify the metronidazole release. We prepared films containing polymeric adjuvant (gelatin or ethylcellulose) and metronidazole, by solvent casting method. Density, mechanical properties, water vapor permeability (WVP), moisture uptake capacity (MUC), thermogravimetry, differential scanning calorimetry, Fourier transform infrared spectroscopy (FT-IR), and in vitro metronidazole release were investigated. Thickness and density of the preparations indicated that the compounds were homogeneously dispersed throughout. Mechanical properties were influenced by film composition. Films containing gelatin showed higher resistance to stress while those containing ethylcellulose presented greater flexibility. The greater the adjuvant concentrations lower the resistance to rupture and the elasticity, but higher MUC and WVP of formulations. FT-IR tests suggested interactions between BP and the adjuvants. Films were capable to protect the metronidazole and changed its release profile. BP films are of great practical importance constituting a novel strategy to modify the metronidazole release.

  11. A few bad apples: a model of disease influenced agent behaviour in a heterogeneous contact environment.

    Jessica Enright

    Full Text Available For diseases that infect humans or livestock, transmission dynamics are at least partially dependent on human activity and therefore human behaviour. However, the impact of human behaviour on disease transmission is relatively understudied, especially in the context of heterogeneous contact structures such as described by a social network. Here, we use a strategic game, coupled with a simple disease model, to investigate how strategic agent choices impact the spread of disease over a contact network. Using beliefs that are based on disease status and that build up over time, agents choose actions that stochastically determine disease spread on the network. An agent's disease status is therefore a function of both his own and his neighbours actions. The effect of disease on agents is modelled by a heterogeneous payoff structure. We find that the combination of network shape and distribution of payoffs has a non-trivial impact on disease prevalence, even if the mean payoff remains the same. An important scenario occurs when a small percentage (called noncooperators have little incentive to avoid disease. For diseases that are easily acquired when taking a risk, then even when good behavior can lead to disease eradication, a small increase in the percentage of noncooperators (less than 5% can yield a large (up to 25% increase in prevalence.

  12. 10. An Overview Of The Aetiologic Agents Of Diarrhoea Diseases In ...

    user

    primarily supportive with oral or intravenous fluid ... celiac disease, tuberculosis, and cancer of the colon has also be ... agents of diarrhoea include Candida albicans, C krusei, C .... Vitamin A replacement therapy has been advocated. 55.

  13. Self-interested agents create, maintain, and modify group-functional culture.

    Singh, Manvir; Glowacki, Luke; Wrangham, Richard W

    2016-01-01

    We agree that institutions and rules are crucial for explaining human sociality, but we question the claim of there not being "alternatives to CGS [that] can easily account for the institutionalized cooperation that characterizes human societies" (target article, sect. 7). Hypothesizing that self-interested individuals coercively and collaboratively create rules, we propose that agent-based hypotheses offer viable alternatives to cultural group selection (CGS).

  14. Comparison of crystal and solution hemoglobin binding of selected antigelling agents and allosteric modifiers

    Mehanna, A.S.; Abraham, D.J.

    1990-01-01

    This paper details comprehensive binding studies (solution and X-ray) of human hemoglobin A with a group of halogenated carboxylic acids that were investigated as potential antisickling agents. It is, to our knowledge, the first study to compare solution and crystal binding for a series of compounds under similar high-salt conditions used for cocrystallization. The compounds include [(3,4-dichlorobenzyl)oxy]acetic acid, [(p-bromobenzyl)oxy]acetic acid, clofibric acid, and bezafibrate. The location and stereochemistry of binding sites have been established by X-ray crystallography, while the number of binding sites and affinity constants were measured by using equilibrium dialysis. The observed crystal structures are consistent with the binding observed in solution and that the number of binding sites is independent of salt concentration, while the binding constant increases with increasing salt concentration. The studies also reveal that relatively small changes in the chemical structure of a drug molecule can result in entirely different binding sites on the protein. Moreover, the X-ray studies provide a possible explanation for the multiplicity in function exhibited by these compounds as allosteric modulators and/or antisickling agents. Finally, the studies indicate that these compounds bind differently to the R and T states of hemoglobin, and observation of special significance to the original design of these agents

  15. [The trend of developing new disease-modifying drugs in Alzheimer's disease].

    Arai, Hiroyuki; Furukawa, Katsutoshi; Tomita, Naoki; Ishiki, Aiko; Okamura, Nobuyuki; Kudo, Yukitsuka

    2016-03-01

    Development of symptomatic treatment of Alzheimer s disease by cholinesterase inhibitors like donepezil was successful. However, it is a disappointment that development of disease-modifying drugs such as anti-amyloid drug based on amyloid-cascade theory has been interrupted or unsuccessful. Therefore, we have to be more cautious regarding inclusion criteria for clinical trials of new drugs. We agree that potentially curative drugs should be started before symptoms begin as a preemptive therapy or prevention trial. The concept of personalized medicine also is important when ApoE4-related amyloid reducing therapy is considered. Unfortunately, Japanese-ADNI has suffered a setback since 2014. However, Ministry of Health, Labour and Welfare gave a final remark that there was nothing wrong in the data managing process in the J-ADNI data center. We should pay more attention to worldwide challenges of speeding up new drug development.

  16. CT study of pancreatic diseases with modified dynamic scanning

    Qian Minghui; Zhu Guangying

    1990-01-01

    Experience of 20 cases modified dynamic CT scanning is presented. With a slight increased X-ray tube burden, it is possible to investigate tumor blood supply and find small pancreatic insulinoma with this method. The capsular sign typical for chronic traumatic pancreatic hematoma on CT is presented

  17. Astaxanthin as a Potential Neuroprotective Agent for Neurological Diseases

    Haijian Wu

    2015-09-01

    Full Text Available Neurological diseases, which consist of acute injuries and chronic neurodegeneration, are the leading causes of human death and disability. However, the pathophysiology of these diseases have not been fully elucidated, and effective treatments are still lacking. Astaxanthin, a member of the xanthophyll group, is a red-orange carotenoid with unique cell membrane actions and diverse biological activities. More importantly, there is evidence demonstrating that astaxanthin confers neuroprotective effects in experimental models of acute injuries, chronic neurodegenerative disorders, and neurological diseases. The beneficial effects of astaxanthin are linked to its oxidative, anti-inflammatory, and anti-apoptotic characteristics. In this review, we will focus on the neuroprotective properties of astaxanthin and explore the underlying mechanisms in the setting of neurological diseases.

  18. ROMP-based thermosetting polymers from modified castor oil with various cross-linking agents

    Ding, Rui

    Polymers derived from bio-renewable resources are finding an increase in global demand. In addition, polymers with distinctive functionalities are required in certain advanced fields, such as aerospace and civil engineering. In an attempt to meet both these needs, the goal of this work aims to develop a range of bio-based thermosetting matrix polymers for potential applications in multifunctional composites. Ring-opening metathesis polymerization (ROMP), which recently has been explored as a powerful method in polymer chemistry, was employed as a unique pathway to polymerize agricultural oil-based reactants. Specifically, a novel norbornyl-functionalized castor oil alcohol (NCA) was investigated to polymerize different cross-linking agents using ROMP. The effects of incorporating dicyclopentadiene (DCPD) and a norbornene-based crosslinker (CL) were systematically evaluated with respect to curing behavior and thermal mechanical properties of the polymers. Isothermal differential scanning calorimetry (DSC) was used to investigate the conversion during cure. Dynamic DSC scans at multiple heating rates revealed conversion-dependent activation energy by Ozawa-Flynn-Wall analysis. The glass transition temperature, storage modulus, and loss modulus for NCA/DCPD and NCA/CL copolymers with different cross-linking agent loading were compared using dynamic mechanical analysis. Cross-link density was examined to explain the very different dynamic mechanical behavior. Mechanical stress-strain curves were developed through tensile test, and thermal stability of the cross-linked polymers was evaluated by thermogravimetric analysis to further investigate the structure-property relationships in these systems.

  19. Applications of Genetically Modified Immunobiotics with High Immunoregulatory Capacity for Treatment of Inflammatory Bowel Diseases.

    Shigemori, Suguru; Shimosato, Takeshi

    2017-01-01

    Inflammatory bowel diseases (IBDs), including ulcerative colitis and Crohn's disease, are chronic inflammatory diseases characterized by dysregulated immune responses of the gastrointestinal tract. In recent years, the incidence of IBDs has increased in developed nations, but their prophylaxis/treatment is not yet established. Site-directed delivery of molecules showing anti-inflammatory properties using genetically modified (gm)-probiotics shows promise as a new strategy for the prevention and treatment of IBD. Advantages of gm-probiotics include (1) the ability to use bacteria as a delivery vehicle, enabling safe and long-term use by humans, (2) decreased risks of side effects, and (3) reduced costs. The intestinal delivery of anti-inflammatory proteins such as cytokines and enzymes using Lactococcus lactis has been shown to regulate host intestinal homeostasis depending on the delivered protein-specific machinery. Additionally, clinical experience using interleukin 10-secreting Lc. lactis has been shown to be safe and to facilitate biological containment in IBD therapy. On the other hand, some preclinical studies have demonstrated that gm-strains of immunobiotics (probiotic strains able to beneficially regulate the mucosal immunity) provide beneficial effects on intestinal inflammation as a result of the synergy between the immunoregulatory effects of the bacterium itself and the anti-inflammatory effects of the delivered recombinant proteins. In this review, we discuss the rapid progression in the development of strategies for the prophylaxis and treatment of IBD using gm-probiotics that exhibit immune regulation effects (gm-immunobiotics). In particular, we discuss the type of strains used as delivery agents.

  20. An agent-based model on disease management in potato cultivation in the Netherlands

    Pacilly, F.C.A.; Hofstede, G.J.; Groot, J.C.J.; Lammerts Van Bueren, E.

    2015-01-01

    In this project the host-pathogen system of potato (Solanum tuberosum) - late blight (Phytophthora infestans) was analysed as a model system to study management of crop-disease interactions. Resistant cultivars play an important role in sustainable management of the disease. We used an agent-based

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

    Ostergaard, Soren D.; Mukherjee, Shubhabrata; Sharp, Stephen J.; Proitsi, Petroula; Lotta, Luca A.; Day, Felix; Perry, John R. B.; Boehme, Kevin L.; Walter, Stefan; Kauwe, John S.; Gibbons, Laura E.; Larson, Eric B.; Powell, John F.; Langenberg, Claudia; Crane, Paul K.; Wareham, Nicholas J.; Scott, Robert A.; van der Schouw, YT

    Background 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

  2. Polyphenols as potential therapeutical agents against cardiovascular diseases.

    Curin, Yann; Andriantsitohaina, Ramaroson

    2005-01-01

    Increasing evidence suggests that polyphenols from fruits, vegetables and beverages such as wine and tea may exert protective effects on the cardiovascular system. Indeed, research in the field of polyphenols points out their antioxidant and free radical scavenging properties, leading to lower low-density lipoprotein (LDL) oxidation and platelet aggregation. These compounds are also able to modulate the generation of nitric oxide (NO) from vascular endothelium and to interfere with the mechanisms leading to inflammation and endothelial apoptosis, contributing to the prevention of the endothelial dysfunction, known to play a central role in the pathogenesis of cardiovascular diseases. This article reviews the potential targets of polyphenols involved in the complex pathophysiological events occurring in cardiovascular diseases, such as hypertension, atherosclerosis and stroke.

  3. Acute effects of vascular modifying agents in solid tumors assessed by noninvasive laser Doppler flowmetry and near infrared spectroscopy

    Kragh, Michael; Quistorff, Bjørn; Horsman, Michael R

    2002-01-01

    LDF, using a 41 degrees C heated custom-built LDF probe with four integrated laser/receiver units, and tumor blood volume was estimated by NIRS, using light guide coupled reflectance measurements at 800+/-10 nm. FAA, DMXAA, CA4DP, and HDZ significantly decreased tumor perfusion by 50%, 47%, 73......The potential of noninvasive laser Doppler flowmetry (LDF) and near infrared spectroscopy (NIRS) to detect acute effects of different vascular-modifying agents on perfusion and blood volume in tumors was evaluated. C3H mouse mammary carcinomas (approximately 200 mm(3)) in the rear foot of CDF1 mice......%, and 78%, respectively. In addition, FAA, DMXAA, and HDZ significantly reduced the blood volume within the tumor, indicating that these compounds to some degree shunted blood from the tumor to adjacent tissue, HDZ being most potent. CA4DP caused no change in the tumor blood volume, indicating...

  4. Acute Effects of Vascular Modifying Agents in Solid Tumors Assessed by Noninvasive Laser Doppler Flowmetry and Near Infrared Spectroscopy

    Michael Kragh

    2002-01-01

    Full Text Available The potential of noninvasive laser Doppler flowmetry (LDF and near infrared spectroscopy (NIRS to detect acute effects of different vascular-modifying agents on perfusion and blood volume in tumors was evaluated. C3H mouse mammary carcinomas (∼200 mm3 in the rear foot of CDF1 mice were treated with flavone acetic acid (FAA, 150 mg/kg, 5,6-dimethylxanthenone-4acetic acid (DMXAA, 20 mg/kg, combretastatin A-4 disodium phosphate (CAMP, 250 mg/kg, hydralazine (HDZ, 5 mg/kg, or nicotinamide (NTA, 500 mg/kg. Tumor perfusion before and after treatment was evaluated by noninvasive LDF, using a 41°C heated custombuilt LDF probe with four integrated laser/receiver units, and tumor blood volume was estimated by MRS, using light guide coupled reflectance measurements at 800±10 nm. FAA, DMXAA, CAMP, and HDZ significantly decreased tumor perfusion by 50%, 47%, 73%, and 78%, respectively. In addition, FAA, DMXAA, and HDZ significantly reduced the blood volume within the tumor, indicating that these compounds to some degree shunted blood from the tumor to adjacent tissue, HDZ being most potent. CAMP caused no change in the tumor blood volume, indicating that the mechanism of action of CAMP was vascular shut down with the blood pool trapped in the tumor. NTA caused no change in either tumor perfusion or tumor blood volume. We conclude that noninvasive LDF and MRS can determine acute effects of vascular modifying agents on tumor perfusion and blood volume.

  5. Mesquite Gum as a Novel Reducing and Stabilizing Agent for Modified Tollens Synthesis of Highly Concentrated Ag Nanoparticles

    Maira Berenice Moreno‐Trejo

    2016-10-01

    Full Text Available The synthesis that is described in this study is for the preparation of silver nanoparticles of sizes ranging from 10 nm to 30 nm with a defined shape (globular, confirmed by UV-vis, SEM, STEM and DLS analysis. This simple and favorable one-step modified Tollens reaction does not require any special equipment or other stabilizing or reducing agent except for a solution of purified mesquite gum, and it produces aqueous colloidal dispersions of silver nanoparticles with a stability thatexceeds three months, a relatively narrow size distribution, a low tendency to aggregate and a yield of at least 95% for all cases. Reaction times are between 15 min and 60 min to obtain silver nanoparticles in concentrations ranging from 0.1 g to 3 g of Ag per 100 g of reaction mixture. The proposed synthetic method presents a high potential for scale-up, since its production capacity is rather high and the methodology is simple.The synthesis that is described in this study is for the preparation of silver nanoparticles of sizes ranging from 10 nm to 30 nm with a defined shape (globular, confirmed by UV-vis, SEM, STEM and DLS analysis. This simple and favorable one-step modified Tollens reaction does not require any special equipment or other stabilizing or reducing agent except for a solution of purified mesquite gum, and it produces aqueous colloidal dispersions of silver nanoparticles with a stability thatexceeds three months, a relatively narrow size distribution, a low tendency to aggregate and a yield of at least 95% for all cases. Reaction times are between 15 min and 60 min to obtain silver nanoparticles in concentrations ranging from 0.1 g to 3 g of Ag per 100 g of reaction mixture. The proposed synthetic method presents a high potential for scale-up, since its production capacity is rather high and the methodology is simple.

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

    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

  7. Synthesis and evaluation of modified chalcone based p53 stabilizing agents

    Iftikhar, Sunniya

    2017-07-15

    Tumor suppressor protein p53 induces cell cycle arrest and apoptotic cell death in response to various cellular stresses thereby preventing cancer development. Activation and stabilization of p53 through small organic molecules is, therefore, an attractive approach for the treatment of cancers retaining wild-type p53. In this context, a series of nineteen chalcones with various substitution patterns of functional groups including chloro, fluoro, methoxy, nitro, benzyloxy, 4-methyl benzyloxy was prepared using Claisen-Schmidt condensation. The compounds were characterized using NMR, HRMS, IR and melting points. Evaluation of synthesized compounds against human colorectal (HCT116) and breast (Cal-51) cancer cell lines revealed potent antiproliferative activities. Nine compounds displayed GI50 values in the low micromolar to submicromolar range; for example (E)-1-phenyl-3-(3,4,5-trimethoxyphenyl)prop-2-en-1-one (SSE14108) showed GI50 of 0.473 ± 0.043 µM against HCT116 cells. Further analysis of these compounds revealed that (E)-3-(4-chlorophenyl)-1-phenylprop-2-en-1-one (SSE14105) and (E)-3-(4-methoxyphenyl)-1-phenylprop-2-en-1-one (SSE14106) caused rapid (4 and 8-hour post-treatment) accumulation of p53 in HCT116 cells similar to its induction by positive control, Nutlin-3. Such activities were absent in 3-(4-methoxyphenyl)propiophenone (SSE14106H2) demonstrating the importance of conjugated ketone for antiproliferative and p53 stabilizing activity of the chalcones. We further evaluated p53 levels in the presence of cycloheximide (CHX) and the results showed that the p53 stabilization was regulated at post-translational level through blockage of its degradation. These chalcones can, therefore, act as fragment leads for further structure optimization to obtain more potent p53 stabilizing agents with enhanced anti-proliferative activities.

  8. Synthesis and evaluation of modified chalcone based p53 stabilizing agents

    Iftikhar, Sunniya; Khan, Sardraz; Bilal, Aishah; Manzoor, Safia; Abdullah, Muhammad; Emwas, Abdul-Hamid M.; Sioud, Salim; Gao, Xin; Chotana, Ghayoor Abbas; Faisal, Amir; Saleem, Rahman Shah Zaib

    2017-01-01

    Tumor suppressor protein p53 induces cell cycle arrest and apoptotic cell death in response to various cellular stresses thereby preventing cancer development. Activation and stabilization of p53 through small organic molecules is, therefore, an attractive approach for the treatment of cancers retaining wild-type p53. In this context, a series of nineteen chalcones with various substitution patterns of functional groups including chloro, fluoro, methoxy, nitro, benzyloxy, 4-methyl benzyloxy was prepared using Claisen-Schmidt condensation. The compounds were characterized using NMR, HRMS, IR and melting points. Evaluation of synthesized compounds against human colorectal (HCT116) and breast (Cal-51) cancer cell lines revealed potent antiproliferative activities. Nine compounds displayed GI50 values in the low micromolar to submicromolar range; for example (E)-1-phenyl-3-(3,4,5-trimethoxyphenyl)prop-2-en-1-one (SSE14108) showed GI50 of 0.473 ± 0.043 µM against HCT116 cells. Further analysis of these compounds revealed that (E)-3-(4-chlorophenyl)-1-phenylprop-2-en-1-one (SSE14105) and (E)-3-(4-methoxyphenyl)-1-phenylprop-2-en-1-one (SSE14106) caused rapid (4 and 8-hour post-treatment) accumulation of p53 in HCT116 cells similar to its induction by positive control, Nutlin-3. Such activities were absent in 3-(4-methoxyphenyl)propiophenone (SSE14106H2) demonstrating the importance of conjugated ketone for antiproliferative and p53 stabilizing activity of the chalcones. We further evaluated p53 levels in the presence of cycloheximide (CHX) and the results showed that the p53 stabilization was regulated at post-translational level through blockage of its degradation. These chalcones can, therefore, act as fragment leads for further structure optimization to obtain more potent p53 stabilizing agents with enhanced anti-proliferative activities.

  9. Identification and Control of Cladobotryum spp., Causal Agents of Cobeweb Disease of Cultivated Mushroom

    Ivana Potočnik

    2009-01-01

    Cladobotryum spp. are causal agents of cobweb disease, one of the most serious diseases of cultivated mushroom (Agaricus bisporus (Lange) Imbach) in Serbia and worldwide, which affects product quality and yield. The disease symptoms are: cottony fluffy white or yellowish to pink colonies on mushroom casing, rapid colonization of casing surface, covering of host basidiomata by mycelia, and their decay. Prochloraz-Mn has been officially recommended for mushroom cultivation in EU countries. Howe...

  10. Curcumin: a potential neuroprotective agent in Parkinson's disease.

    Mythri, R B; Bharath, M M Srinivas

    2012-01-01

    Parkinson's disease (PD) is an age-associated neurodegenerative disease clinically characterized as a movement disorder. The motor symptoms in PD arise due to selective degeneration of dopaminergic neurons in the substantia nigra of the ventral midbrain thereby depleting the dopamine levels in the striatum. Most of the current pharmacotherapeutic approaches in PD are aimed at replenishing the striatal dopamine. Although these drugs provide symptomatic relief during early PD, many patients develop motor complications with long-term treatment. Further, PD medications do not effectively tackle tremor, postural instability and cognitive deficits. Most importantly, most of these drugs do not exhibit neuroprotective effects in patients. Consequently, novel therapies involving natural antioxidants and plant products/molecules with neuroprotective properties are being exploited for adjunctive therapy. Curcumin is a polyphenol and an active component of turmeric (Curcuma longa), a dietary spice used in Indian cuisine and medicine. Curcumin exhibits antioxidant, anti-inflammatory and anti-cancer properties, crosses the blood-brain barrier and is neuroprotective in neurological disorders. Several studies in different experimental models of PD strongly support the clinical application of curcumin in PD. The current review explores the therapeutic potential of curcumin in PD.

  11. Cannabinoids: New Promising Agents in the Treatment of Neurological Diseases

    Sabrina Giacoppo

    2014-11-01

    Full Text Available Nowadays, Cannabis sativa is considered the most extensively used narcotic. Nevertheless, this fame obscures its traditional employ in native medicine of South Africa, South America, Turkey, Egypt and in many regions of Asia as a therapeutic drug. In fact, the use of compounds containing Cannabis and their introduction in clinical practice is still controversial and strongly limited by unavoidable psychotropic effects. So, overcoming these adverse effects represents the main open question on the utilization of cannabinoids as new drugs for treatment of several pathologies. To date, therapeutic use of cannabinoid extracts is prescribed in patients with glaucoma, in the control of chemotherapy-related vomiting and nausea, for appetite stimulation in patients with anorexia-cachexia syndrome by HIV, and for the treatment of multiple sclerosis symptoms. Recently, researcher efforts are aimed to employ the therapeutic potentials of Cannabis sativa in the modulation of cannabinoid receptor activity within the central nervous system, particularly for the treatment of neurodegenerative diseases, as well as psychiatric and non-psychiatric disorders. This review evaluates the most recent available data on cannabinoids utilization in experimental and clinical studies, and highlights their beneficial effects in the prevention of the main neurological diseases and for the clinical treatment of symptoms with them correlated.

  12. Effects of irradiation, antimicrobial agents and modified packaging on histamine production by Morganella morganii in mackerel fillets

    Aytac, S.A.; Ozbas, Z.Y.; Vural, H.

    2000-01-01

    The effects of gamma irradiation (0.5 and 2.0 kGy), antimicrobial agents (5% sodium chloride and 1% potassium sorbate) and modified atmosphere (100% CO2) packaging (MAP) on histamine production by Morganella morganii were examined in mackerel fillets during 8 days of cold storage. MAP combined with antimicrobial agents was also applied to the fillets. The changes in histamine levels, M. morganii and total aerobic bacterial counts were determined during the storage. All methods used in this study showed beneficial effect in controlling bacterial growth and histamine production on mackerel fillets during 2-3 days of storage. MAP combined with 5% sodium chloride has more retarding effect on production of histamine than the other methods. For M. morganii, maximum inhibition effect was found at the dose of 2.0 kGy. Irradiation with a dose of 2.0 kGy, MAP combined with sodium chloride and MAP were also found to have the most inhibiting effects on total aerobic bacterial count during the storage

  13. Evaluation of performance of modified sodium lignosulfonate additives as reinforcing agent in porcelain stoneware tiles

    Rastelli, E.

    2010-10-01

    Full Text Available A sodium salt of a modified lignosulfonate at different percentages was added to a porcelain stoneware suspension and the effects on the rheological properties of slips and on the mechanical properties of prepared samples were investigated. As the presence of sulfonates groups can change the stability of dispersion, a rheological characterisation was necessary to find the critical concentration to obtain well dispersed suspensions and high MOR values. The suspensions stability was tested by oscillatory measurements and the increase of elastic modulus in the suspension corresponded to a MOR and to Young’s modulus increase as well. Finally, to explain the results obtained by the mechanical characterisation of the prepared samples, a model drawing on the composite materials experience, is suggested.

    Usando distintos porcentajes, se añadió sal de sodio de un lignosulfonato modificado, a una suspensión de gres porcelánico, y se investigaron los efectos sobre las propiedades reológicas de las suspensiones y sobre las propiedades mecánicas de las muestras preparadas. Debido a que la presencia de grupos de sulfonatos puede modificar la estabilidad de la dispersión, fue necesario realizar una caracterización reológica para averiguar la concentración crítica necesaria para la obtención de suspensiones bien dispersas y altos valores de MOR. Se analizó la estabilidad de las suspensiones por medio de mediciones oscilatorias y el incremento del módulo elástico en la suspensión que corresponde al incremento de un módulo MOR y de un módulo de Young también. Finalmente, para explicar los resultados obtenidos por medio de la caracterización mecánica de las muestras preparadas, se sugiere un modelo que parte de la experiencia con los materiales compuestos.

  14. Electrochemical Sensor Based on Rh(III) Ion-Imprinted Polymer as a New Modifying Agent for Rhodium Determination.

    Bai, Huiping; Xiong, Caiyun; Wang, Chunqiong; Liu, Peng; Dong, Su; Cao, Qiue

    2018-05-01

    A rhodium (III) ion carbon paste electrode (CPE) based on an ion imprinted polymer (IIP) as a new modifying agent has been prepared and studied. Rh(III) ion imprinted polymer was synthesized by copolymerization of acrylamide-Rh(III) complex and ethylene glycol dimethacrylate according to the precipitation polymerization. Acrylamide acted as both functional monomer and complexing agent to create selective coordination sites in a cross-linked polymer. The ion imprinted carbon paste electrode (IIP-CPE) was prepared by mixing rhodium IIP-nanoparticles and graphite powder in n-eicosane as an adhesive and then embedding them in a Teflon tube. Amperometric i-t curve method was applied as the determination technique. Several parameters, including the functional monomer, molar ratio of template, monomer and cross-linking agent, the amounts of IIP, the applied potential, the buffer solution and pH have been studied. According to the results, IIP-CPE showed a considerably higher response in comparison with the electrode embedded with non-imprinted polymer (NIP), indicating the formation of suitable recognition sites in the IIP structure during the polymerization stage. The introduced electrode showed a linear range of 1.00×10-8~3.0×10-5 mol·L-1 and detection limit of 6.0 nmol L-1 (S/N = 3). The IIP-CPE was successfully applied for the trace rhodium determination in catalyst and plant samples with RSD of less than 3.3% (n = 5) and recoveries in the range of 95.5~102.5%.

  15. Shear Resistance Properties of Modified Nano-SiO2/AA/AM Copolymer Oil Displacement Agent

    Nanjun Lai

    2016-12-01

    Full Text Available To address the problem regarding poor shear resistance of commonly employed polymers for oil displacement, modified nano-SiO2/AA/AM copolymer (HPMNS oil displacement agents were synthesized using acrylic acid (AA, acrylamide (AM, and modified nano-SiO2 of different modification degrees as raw materials. HPMNS was characterized by means of infrared spectroscopy (IR, nuclear magnetic resonance (1H-NMR, 13C-NMR, dynamic/static light scattering, and scanning electron microscope. A comparative study of the shear resistance properties for partially hydrolyzed polyacrylamide (HPAM and HPMNS was conducted. Compared to HPAM, the introduced hyperbranched structure endowed HPMNS with good shear resistance, which was quantified from the viscosity retention ratio of the polymer solutions. From the perspective of rheological property, HPMNS also showed great shear stability after shearing by a Mixing Speed Governor and porous media shear model. Furthermore, with a higher degree of modification, HPMNS-2 had better shear stability in terms of viscosity and rheological property than HPMNS-1. The phenomena were due to its lower hydrodynamic radius, weight-average molecular weight, and better flexibility of its molecular chains. In addition, upon the indoor displacement test, the resistance factor and residual resistance factor values of HPMNS-2 were higher than those of HPAM. This behavior is beneficial for increasing oil recovery.

  16. Resveratrol as a Therapeutic Agent for Alzheimer's Disease

    Ma, Teng; Tan, Meng-Shan; Yu, Jin-Tai; Tan, Lan

    2014-01-01

    Alzheimer's disease (AD) is the most common cause of dementia, but there is no effective therapy till now. The pathogenic mechanisms of AD are considerably complex, including Aβ accumulation, tau protein phosphorylation, oxidative stress, and inflammation. Exactly, resveratrol, a polyphenol in red wine and many plants, is indicated to show the neuroprotective effect on mechanisms mostly above. Recent years, there are numerous researches about resveratrol acting on AD in many models, both in vitro and in vivo. However, the effects of resveratrol are limited by its pool bioavailability; therefore researchers have been trying a variety of methods to improve the efficiency. This review summarizes the recent studies in cell cultures and animal models, mainly discusses the molecular mechanisms of the neuroprotective effects of resveratrol, and thus investigates the therapeutic potential in AD. PMID:25525597

  17. Dental Acrylics - Potential Agent for a Myriad of Diseases

    Shivangi Gajwani

    2007-01-01

    Full Text Available An allergic reaction also known as a hypersensitivity reaction is caused by the immune system in response to a foreign substance (or allergen. Allergenic chemicals can be found in many products used in the dental operatory. With repeated exposure, these chemicals can cause allergic reactions in dental professionals, resulting in local as well as systemic manifestations. According to various studies done, it became evident that the prevalence of acrylic allergy most commonly in the form of allergic contact dermatitis is affecting the dental personnel to a much greater degree than is believed. Awareness of this disease complex in the form of any new symptoms and potential exposure is paramount for dental personals.

  18. Resveratrol as a Therapeutic Agent for Alzheimer’s Disease

    Teng Ma

    2014-01-01

    Full Text Available Alzheimer’s disease (AD is the most common cause of dementia, but there is no effective therapy till now. The pathogenic mechanisms of AD are considerably complex, including Aβ accumulation, tau protein phosphorylation, oxidative stress, and inflammation. Exactly, resveratrol, a polyphenol in red wine and many plants, is indicated to show the neuroprotective effect on mechanisms mostly above. Recent years, there are numerous researches about resveratrol acting on AD in many models, both in vitro and in vivo. However, the effects of resveratrol are limited by its pool bioavailability; therefore researchers have been trying a variety of methods to improve the efficiency. This review summarizes the recent studies in cell cultures and animal models, mainly discusses the molecular mechanisms of the neuroprotective effects of resveratrol, and thus investigates the therapeutic potential in AD.

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

    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.

  20. Agent Orange exposure and prevalence of self-reported diseases in Korean Vietnam veterans.

    Yi, Sang-Wook; Ohrr, Heechoul; Hong, Jae-Seok; Yi, Jee-Jeon

    2013-09-01

    The aim of this study was to evaluate the association between Agent Orange exposure and self-reported diseases in Korean Vietnam veterans. A postal survey of 114 562 Vietnam veterans was conducted. The perceived exposure to Agent Orange was assessed by a 6-item questionnaire. Two proximity-based Agent Orange exposure indices were constructed using division/brigade-level and battalion/company-level unit information. Adjusted odds ratios (ORs) for age and other confounders were calculated using a logistic regression model. The prevalence of all self-reported diseases showed monotonically increasing trends as the levels of perceived self-reported exposure increased. The ORs for colon cancer (OR, 1.13), leukemia (OR, 1.56), hypertension (OR, 1.03), peripheral vasculopathy (OR, 1.07), enterocolitis (OR, 1.07), peripheral neuropathy (OR, 1.07), multiple nerve palsy (OR, 1.14), multiple sclerosis (OR, 1.24), skin diseases (OR, 1.05), psychotic diseases (OR, 1.07) and lipidemia (OR, 1.05) were significantly elevated for the high exposure group in the division/brigade-level proximity-based exposure analysis, compared to the low exposure group. The ORs for cerebral infarction (OR, 1.08), chronic bronchitis (OR, 1.05), multiple nerve palsy (OR, 1.07), multiple sclerosis (OR, 1.16), skin diseases (OR, 1.05), and lipidemia (OR, 1.05) were significantly elevated for the high exposure group in the battalion/company-level analysis. Korean Vietnam veterans with high exposure to Agent Orange experienced a higher prevalence of several self-reported chronic diseases compared to those with low exposure by proximity-based exposure assessment. The strong positive associations between perceived self-reported exposure and all self-reported diseases should be evaluated with discretion because the likelihood of reporting diseases was directly related to the perceived intensity of Agent Orange exposure.

  1. RHIZOBACTERIA AS BIOCONTROL AGENTS OF ROOT ROT DISEASE ON SHALLOT

    Nunik Iriyanti Ramadhan

    2015-01-01

    Full Text Available Shallot is a high-economic value commodity, but so far the supply is still lower than the demand. One of the production problem is “moler” disease of shallot (MDS caused by Fusarium oxysporum f.sp. cepae (FOCe. The aim of this research was to study the potentiality of shallot rhizobacteria (SRB from various soil ordo to inhibit (MDS. This research was held in the Laboratory of Biology and Soil Health and Greenhouse at UNS. This research was carried out by exploring rhizobacteria of shallot planted on Entisols, Andisols, and Vertisols. Rhizobacteria exploration results were tested for their ability to control Fusarium oxysporum f.sp.cepae (FOCe. Inhibitory ability test of SRB to FOCe was carried out in vitro and on shallot in the greenhouse. The green house research used a Completely Randomized Design (CDR with two factors. The first factor was rhizobacteria combination and the second factor was various soil ordo (Andisols, Entisols, and Vertisols. Each treatment was replicated three times. It was obtained three rhizobacteria isolates from Vertisols (B15: 70%, Andisols (B12:45,55%, and Entisols (B10:46,67% being the highest inhibition results to FOCe. The combination of rhizobacteria B12 and B10 provided the lowest intensity.

  2. Modifiable risk factors in periodontitis: at the intersection of aging and disease.

    Reynolds, Mark A

    2014-02-01

    Chronic inflammation is a prominent feature of aging and of common age-related diseases, including atherosclerosis, cancer and periodontitis. This volume examines modifiable risk factors for periodontitis and other chronic inflammatory diseases. Oral bacterial communities and viral infections, particularly with cytomegalovirus and other herpesviruses, elicit distinct immune responses and are central in the initiation of periodontal diseases. Risk of disease is dynamic and changes in response to complex interactions of genetic, environmental and stochastic factors over the lifespan. Many modifiable risk factors, such as smoking and excess caloric intake, contribute to increases in systemic markers of inflammation and can modify gene regulation through a variety of biologic mechanisms (e.g. epigenetic modifications). Periodontitis and other common chronic inflammatory diseases share multiple modifiable risk factors, such as tobacco smoking, psychological stress and depression, alcohol consumption, obesity, diabetes, metabolic syndrome and osteoporosis. Interventions that target modifiable risk factors have the potential to improve risk profiles for periodontitis as well as for other common chronic diseases. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

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

    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

  4. Morphological and Molecular Identification of the Causal Agent of Anthracnose Disease of Avocado in Kenya.

    Kimaru, S K; Monda, E; Cheruiyot, R C; Mbaka, J; Alakonya, A

    2018-01-01

    Anthracnose disease of avocado contributes to a huge loss of avocado fruits due to postharvest rot in Kenya. The causal agent of this disease has not been clear but presumed to be Colletotrichum gloeosporioides as reported in other regions where avocado is grown. The fungus mainly infects fruits causing symptoms such as small blackish spots, "pepper spots," and black spots with raised margin which coalesce as infection progresses. Due to economic losses associated with the disease and emerging information of other species of fungi as causal agents of the disease, this study was aimed at identifying causal agent(s) of the disease. A total of 80 fungal isolates were collected from diseased avocado fruits in Murang'a County, the main avocado growing region in Kenya. Forty-six isolates were morphologically identified as Colletotrichum spp. based on their cultural characteristics, mainly whitish, greyish, and creamish colour and cottony/velvety mycelia on the top side of the culture and greyish cream with concentric zonation on the reverse side. Their spores were straight with rounded end and nonseptate. Thirty-four isolates were identified as Pestalotiopsis spp. based on their cultural characteristics: whitish grey mycelium with black fruiting structure on the upper side and greyish black one on the lower side and septate spores with 3-4 septa and 2 or 3 appendages at one end. Further molecular studies using ITS indicated Colletotrichum gloeosporioides , Colletotrichum boninense , and Pestalotiopsis microspora as the causal agents of anthracnose disease in avocado. However, with this being the first report, there is a need to conduct further studies to establish whether there is coinfection or any interaction thereof.

  5. Morphological and Molecular Identification of the Causal Agent of Anthracnose Disease of Avocado in Kenya

    S. K. Kimaru

    2018-01-01

    Full Text Available Anthracnose disease of avocado contributes to a huge loss of avocado fruits due to postharvest rot in Kenya. The causal agent of this disease has not been clear but presumed to be Colletotrichum gloeosporioides as reported in other regions where avocado is grown. The fungus mainly infects fruits causing symptoms such as small blackish spots, “pepper spots,” and black spots with raised margin which coalesce as infection progresses. Due to economic losses associated with the disease and emerging information of other species of fungi as causal agents of the disease, this study was aimed at identifying causal agent(s of the disease. A total of 80 fungal isolates were collected from diseased avocado fruits in Murang’a County, the main avocado growing region in Kenya. Forty-six isolates were morphologically identified as Colletotrichum spp. based on their cultural characteristics, mainly whitish, greyish, and creamish colour and cottony/velvety mycelia on the top side of the culture and greyish cream with concentric zonation on the reverse side. Their spores were straight with rounded end and nonseptate. Thirty-four isolates were identified as Pestalotiopsis spp. based on their cultural characteristics: whitish grey mycelium with black fruiting structure on the upper side and greyish black one on the lower side and septate spores with 3-4 septa and 2 or 3 appendages at one end. Further molecular studies using ITS indicated Colletotrichum gloeosporioides, Colletotrichum boninense, and Pestalotiopsis microspora as the causal agents of anthracnose disease in avocado. However, with this being the first report, there is a need to conduct further studies to establish whether there is coinfection or any interaction thereof.

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

    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.

  7. Predicting the characteristics of the aetiological agent for Kawasaki disease from other paediatric infectious diseases in Japan.

    Nagao, Y; Urabe, C; Nakamura, H; Hatano, N

    2016-02-01

    Although Kawasaki disease (KD), which was first reported in the 1960s, is assumed to be infectious, its aetiological agent(s) remains unknown. We compared the geographical distribution of the force of infection and the super-annual periodicity of KD and seven other paediatric infectious diseases in Japan. The geographical distribution of the force of infection, which was estimated as the inverse of the mean patient age, was similar in KD and other paediatric viral infections. This similarity was due to the fact that the force of infection was determined largely by the total fertility rate. This finding suggests that KD shares a transmission route, i.e. sibling-to-sibling infection, with other paediatric infections. The super-annual periodicity, which is positively associated with the sum of an infectious disease's incubation period and infectious period, was much longer for KD and exanthema subitum than other paediatric infectious diseases. The virus for exanthema subitum is known to persist across the host's lifespan, which suggests that the aetiological agent for KD may also be capable of persistent infection. Taken together, these findings suggest that the aetiological agent for KD is transmitted through close contact and persists asymptomatically in most hosts.

  8. Immunotherapeutics in Pediatric Autoimmune Central Nervous System Disease: Agents and Mechanisms.

    Nosadini, Margherita; Sartori, Stefano; Sharma, Suvasini; Dale, Russell C

    2017-08-01

    Beyond the major advances produced by careful clinical-radiological phenotyping and biomarker development in autoimmune central nervous system disorders, a comprehensive knowledge of the range of available immune therapies and a deeper understanding of their action should benefit therapeutic decision-making. This review discusses the agents used in neuroimmunology and their mechanisms of action. First-line treatments typically include corticosteroids, intravenous immunoglobulin, and plasmapheresis, while for severe disease second-line "induction" agents such as rituximab or cyclophosphamide are used. Steroid-sparing agents such as mycophenolate, azathioprine, or methotrexate are often used in potentially relapsing or corticosteroid-dependent diseases. Lessons from adult neuroimmunology and rheumatology could be translated into pediatric autoimmune central nervous system disease in the future, including the potential utility of monoclonal antibodies targeting lymphocytes, adhesion molecules for lymphocytic migration, cytokines or their receptors, or complement. Finally, many agents used in other fields have multiple mechanisms of action, including immunomodulation, with potential usefulness in neuroimmunology, such as antibiotics, psychotropic drugs, probiotics, gut health, and ketogenic diet. All currently accepted and future potential agents have adverse effects, which can be severe; therefore, a "risk-versus-benefit" determination should guide therapeutic decision-making. Copyright © 2017 Elsevier Inc. All rights reserved.

  9. Older Americans' risk-benefit preferences for modifying the course of Alzheimer disease.

    Hauber, A Brett; Johnson, F Reed; Fillit, Howard; Mohamed, Ateesha F; Leibman, Christopher; Arrighi, H Michael; Grundman, Michael; Townsend, Raymond J

    2009-01-01

    Alzheimer disease (AD) is a progressive, ultimately fatal neurodegenerative illness affecting millions of patients, families, and caregivers. Effective disease-modifying therapies for AD are desperately needed, but none currently exist on the market. Thus, accelerating the discovery, development, and approval of new disease-modifying drugs for AD is a high priority for individuals, physicians, and medical decision makers. Potentially disease-modifying drugs likely will have significant therapeutic benefits but also may have treatment-related risks. We quantified older Americans' treatment-related risk tolerance by eliciting their willingness to accept the risk of treatment-related death or permanent severe disability in exchange for modifying the course of AD. A stated-choice survey instrument was administered to 2146 American residents 60 years of age and older. On average, subjects were willing to accept a 1-year risk of treatment-related death or permanent severe disability from stroke of over 30% for a treatment that prevents AD from progressing beyond the mild stage. Thus, most people in this age cohort are willing to accept considerable risks in return for disease-modifying benefits of new AD drugs. These results are consistent with other studies indicating that individuals view AD as a serious, life threatening illness that imposes heavy burdens on both patients and caregivers.

  10. Experiences of community health agents in the care of the elderly affected by chronic diseases

    Marinês Tambara Leite

    2016-01-01

    Full Text Available Objective: to understand which are the experiences of community health agents in the care of patients with chronic diseases. Methods: qualitative research carried out through the interview of 20 community health agents. Data were analyzed following the steps of content analysis. Results: the care for the elderly has limitations due to their low educational level, resistance to adhere to drug therapy and low frequency of visits to health facilities. Another reason is the aging process in itself that may compromise the ability of self-care and the development of daily activities. Conclusion: difficulties of community health agents were identified in the care of elderly people with chronic diseases due to low adherence to treatment and to the health service.

  11. Intestinal microbiology in Crohn's disease: a study of Escherichia coli as a potential etiologic agent

    Martínez Medina, Margarita

    2009-01-01

    Crohn's disease is a chronic inflammatory bowel disorder of unknown aetiology. Genetic and immunologic features that confer susceptibility on the host, together with external or environmental factors such as microorganisms and lifestyle, are thought to be involved. The main purpose of this work was to describe the bacterial populations particularly related with Crohn's disease patients in order to identify putative etiologic agents. The results are in agreement with previous research on the ...

  12. CONTEMPORARY PERSPECTIVES ON INFECTIOUS DISEASE AGENTS IN SEWAGE SLUDGE AND MANURE

    The USEPA and the USDA convened a three-day Workshop on Emerging Infectious Disease Agents and Issues Associated with Sewage Sludge, Animal Manures, and Other Organic By-Products on June 4-6, 2001 in Cincinnati, Ohio. The purpose of the workshop was to review and discuss the effe...

  13. In silico search for modifier genes associated with pancreatic and liver disease in Cystic Fibrosis.

    Pascal Trouvé

    Full Text Available Cystic Fibrosis is the most common lethal autosomal recessive disorder in the white population, affecting among other organs, the lung, the pancreas and the liver. Whereas Cystic Fibrosis is a monogenic disease, many studies reveal a very complex relationship between genotype and clinical phenotype. Indeed, the broad phenotypic spectrum observed in Cystic Fibrosis is far from being explained by obvious genotype-phenotype correlations and it is admitted that Cystic Fibrosis disease is the result of multiple factors, including effects of the environment as well as modifier genes. Our objective was to highlight new modifier genes with potential implications in the lung, pancreatic and liver outcomes of the disease. For this purpose we performed a system biology approach which combined, database mining, literature mining, gene expression study and network analysis as well as pathway enrichment analysis and protein-protein interactions. We found that IFI16, CCNE2 and IGFBP2 are potential modifiers in the altered lung function in Cystic Fibrosis. We also found that EPHX1, HLA-DQA1, HLA-DQB1, DSP and SLC33A1, GPNMB, NCF2, RASGRP1, LGALS3 and PTPN13, are potential modifiers in pancreas and liver, respectively. Associated pathways indicate that immune system is likely involved and that Ubiquitin C is probably a central node, linking Cystic Fibrosis to liver and pancreatic disease. We highlight here new modifier genes with potential implications in Cystic Fibrosis. Nevertheless, our in silico analysis requires functional analysis to give our results a physiological relevance.

  14. Comblike poly(ethylene oxide)/hydrophobic C6 branched chitosan surfactant polymers as anti-infection surface modifying agents.

    Mai-ngam, Katanchalee

    2006-05-01

    A series of structurally well-defined poly(ethylene oxide)/hydrophobic C6 branched chitosan surfactant polymers that undergo surface induced self assembly on hydrophobic biomaterial surfaces were synthesized and characterized. The surfactant polymers consist of low molecular weight (Mw) chitosan backbone with hydrophilic poly(ethylene oxide) (PEO) and hydrophobic hexyl pendant groups. Chitosan was depolymerized by nitrous acid deaminative cleavage. Hexanal and aldehyde-terminated PEO chains were simultaneously attached to low Mw chitosan hydrochloride via reductive amination. The surfactant polymers were prepared with various ratios of the two side chains. The molecular composition of the surfactant polymers was determined by FT-IR and 1H NMR. Surface active properties at the air-water interface were determined by Langmuir film balance measurements. The surfactant polymers with PEO/hexyl ratios of 1:3.0 and 1:14.4 were used as surface modifying agents to investigate their anti-infection properties. E. coli adhesion on Silastic surface was decreased significantly by the surfactant polymer with PEO/hexyl 1:3.0. Surface growth of adherent E. coli was effectively suppressed by both tested surfactant polymers.

  15. A modifier of Huntington's disease onset at the MLH1 locus.

    Lee, Jong-Min; Chao, Michael J; Harold, Denise; Abu Elneel, Kawther; Gillis, Tammy; Holmans, Peter; Jones, Lesley; Orth, Michael; Myers, Richard H; Kwak, Seung; Wheeler, Vanessa C; MacDonald, Marcy E; Gusella, James F

    2017-10-01

    Huntington's disease (HD) is a dominantly inherited neurodegenerative disease caused by an expanded CAG repeat in HTT. Many clinical characteristics of HD such as age at motor onset are determined largely by the size of HTT CAG repeat. However, emerging evidence strongly supports a role for other genetic factors in modifying the disease pathogenesis driven by mutant huntingtin. A recent genome-wide association analysis to discover genetic modifiers of HD onset age provided initial evidence for modifier loci on chromosomes 8 and 15 and suggestive evidence for a locus on chromosome 3. Here, genotyping of candidate single nucleotide polymorphisms in a cohort of 3,314 additional HD subjects yields independent confirmation of the former two loci and moves the third to genome-wide significance at MLH1, a locus whose mouse orthologue modifies CAG length-dependent phenotypes in a Htt-knock-in mouse model of HD. Both quantitative and dichotomous association analyses implicate a functional variant on ∼32% of chromosomes with the beneficial modifier effect that delays HD motor onset by 0.7 years/allele. Genomic DNA capture and sequencing of a modifier haplotype localize the functional variation to a 78 kb region spanning the 3'end of MLH1 and the 5'end of the neighboring LRRFIP2, and marked by an isoleucine-valine missense variant in MLH1. Analysis of expression Quantitative Trait Loci (eQTLs) provides modest support for altered regulation of MLH1 and LRRFIP2, raising the possibility that the modifier affects regulation of both genes. Finally, polygenic modification score and heritability analyses suggest the existence of additional genetic modifiers, supporting expanded, comprehensive genetic analysis of larger HD datasets. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  16. Gaucher disease in the liver on hepatocyte specific contrast agent enhanced MR imaging

    Ayyala, Rama S.; Teot, Lisa A.; Perez Rossello, Jeanette M.

    2017-01-01

    Gaucher disease is a hereditary lipid storage disorder that affects the enzyme beta glucocerebrosidase, causing accumulation of glucocerebroside in macrophages of the reticuloendothelial system. Accumulation can occur in the liver and spleen, manifesting as hepatosplenomegaly, as well as within the bone marrow. Hepatic involvement is usually diffuse but can occasionally manifest as focal liver lesions. We present a case of a 2-year-old boy with Gaucher disease and an infiltrating liver lesion detected on imaging, which was pathologically shown to be focal changes related to the disease. Imaging characteristics of this lesion using hepatocyte specific contrast agent enhanced MRI, which have not been previously discussed in the literature, are described. (orig.)

  17. Gaucher disease in the liver on hepatocyte specific contrast agent enhanced MR imaging

    Ayyala, Rama S. [Morgan Stanley Children' s Hospital, Department of Radiology, Columbia University Medical Center, New York, NY (United States); Teot, Lisa A. [Boston Children' s Hospital, Department of Pathology, Harvard Medical School, Boston, MA (United States); Perez Rossello, Jeanette M. [Boston Children' s Hospital, Department of Radiology, Harvard Medical School, Boston, MA (United States)

    2017-04-15

    Gaucher disease is a hereditary lipid storage disorder that affects the enzyme beta glucocerebrosidase, causing accumulation of glucocerebroside in macrophages of the reticuloendothelial system. Accumulation can occur in the liver and spleen, manifesting as hepatosplenomegaly, as well as within the bone marrow. Hepatic involvement is usually diffuse but can occasionally manifest as focal liver lesions. We present a case of a 2-year-old boy with Gaucher disease and an infiltrating liver lesion detected on imaging, which was pathologically shown to be focal changes related to the disease. Imaging characteristics of this lesion using hepatocyte specific contrast agent enhanced MRI, which have not been previously discussed in the literature, are described. (orig.)

  18. Agent Orange exposure and disease prevalence in Korean Vietnam veterans: the Korean veterans health study.

    Yi, Sang-Wook; Hong, Jae-Seok; Ohrr, Heechoul; Yi, Jee-Jeon

    2014-08-01

    Between 1961 and 1971, military herbicides were used by the United States and allied forces for military purposes. Agent Orange, the most-used herbicide, was a mixture of 2,4-dichlorophenoxyacetic acid (2,4-D) and 2,4,5-trichlorophenoxyacetic acid, and contained an impurity of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Many Korean Vietnam veterans were exposed to Agent Orange during the Vietnam War. The aim of this study was to evaluate the association between Agent Orange exposure and the prevalence of diseases of the endocrine, nervous, circulatory, respiratory, and digestive systems. The Agent Orange exposure was assessed by a geographic information system-based model. A total of 111,726 Korean Vietnam veterans were analyzed for prevalence using the Korea National Health Insurance claims data from January 2000 to September 2005. After adjusting for covariates, the high exposure group had modestly elevated odds ratios (ORs) for endocrine diseases combined and neurologic diseases combined. The adjusted ORs were significantly higher in the high exposure group than in the low exposure group for hypothyroidism (OR=1.13), autoimmune thyroiditis (OR=1.93), diabetes mellitus (OR=1.04), other endocrine gland disorders including pituitary gland disorders (OR=1.43), amyloidosis (OR=3.02), systemic atrophies affecting the nervous system including spinal muscular atrophy (OR=1.27), Alzheimer disease (OR=1.64), peripheral polyneuropathies (OR=1.09), angina pectoris (OR=1.04), stroke (OR=1.09), chronic obstructive pulmonary diseases (COPD) including chronic bronchitis (OR=1.05) and bronchiectasis (OR=1.16), asthma (OR=1.04), peptic ulcer (OR=1.03), and liver cirrhosis (OR=1.08). In conclusion, Agent Orange exposure increased the prevalence of endocrine disorders, especially in the thyroid and pituitary gland; various neurologic diseases; COPD; and liver cirrhosis. Overall, this study suggests that Agent Orange/2,4-D/TCDD exposure several decades earlier may increase morbidity

  19. The effect of anti-tumor necrosis factor alpha agents on postoperative anastomotic complications in Crohn's disease

    El-Hussuna, Alaa Abdul-Hussein H; Krag, Aleksander; Olaison, Gunnar

    2013-01-01

    Patients with Crohn's disease treated with anti-tumor necrosis factor alpha agents may have an increased risk of surgical complications.......Patients with Crohn's disease treated with anti-tumor necrosis factor alpha agents may have an increased risk of surgical complications....

  20. The effect of salivary pH on diametral tensile strength of resin modified glass ionomer cement coated with coating agent

    Ismayanti, D.; Triaminingsih, S.; Eriwati, Y. K.

    2017-08-01

    The aim of this study was to evaluate the effect of artificial saliva with different acidities on the diametral tensile strength of Resin Modified Glass Ionomer Cement (RMGIC) coated with varnish and nanofilled coating agent. The specimens coated with coating agents were immersed in artificial saliva with pH of 4.5, 5.5, and 7 for 24 hours in an incubatorat 37°C. The diametral tensile strength of the specimens was tested with Universal Testing Machine. There were no significant differences on the diametral tensile strength of all specimens that were put into groups based on the acidity of the saliva and the type of coating agent (p>0.05). Both varnish and nanofilled coating agent stayed on the RMGIC in the acidic condition that simulated the true condition of oral cavity in people with high caries risk for the 24 hours of maturation.

  1. CLC-2 single nucleotide polymorphisms (SNPs) as potential modifiers of cystic fibrosis disease severity

    Blaisdell, Carol J; Howard, Timothy D; Stern, Augustus; Bamford, Penelope; Bleecker, Eugene R; Stine, O Colin

    2004-01-01

    Background Cystic fibrosis (CF) lung disease manifest by impaired chloride secretion leads to eventual respiratory failure. Candidate genes that may modify CF lung disease severity include alternative chloride channels. The objectives of this study are to identify single nucleotide polymorphisms (SNPs) in the airway epithelial chloride channel, CLC-2, and correlate these polymorphisms with CF lung disease. Methods The CLC-2 promoter, intron 1 and exon 20 were examined for SNPs in adult CF dF508/dF508 homozygotes with mild and severe lung disease (forced expiratory volume at one second (FEV1) > 70% and < 40%). Results PCR amplification of genomic CLC-2 and sequence analysis revealed 1 polymorphism in the hClC -2 promoter, 4 in intron 1, and none in exon 20. Fisher's analysis within this data set, did not demonstrate a significant relationship between the severity of lung disease and SNPs in the CLC-2 gene. Conclusions CLC-2 is not a key modifier gene of CF lung phenotype. Further studies evaluating other phenotypes associated with CF may be useful in the future to assess the ability of CLC-2 to modify CF disease severity. PMID:15507145

  2. CLC-2 single nucleotide polymorphisms (SNPs as potential modifiers of cystic fibrosis disease severity

    Bleecker Eugene R

    2004-10-01

    Full Text Available Abstract Background Cystic fibrosis (CF lung disease manifest by impaired chloride secretion leads to eventual respiratory failure. Candidate genes that may modify CF lung disease severity include alternative chloride channels. The objectives of this study are to identify single nucleotide polymorphisms (SNPs in the airway epithelial chloride channel, CLC-2, and correlate these polymorphisms with CF lung disease. Methods The CLC-2 promoter, intron 1 and exon 20 were examined for SNPs in adult CF dF508/dF508 homozygotes with mild and severe lung disease (forced expiratory volume at one second (FEV1 > 70% and Results PCR amplification of genomic CLC-2 and sequence analysis revealed 1 polymorphism in the hClC -2 promoter, 4 in intron 1, and none in exon 20. Fisher's analysis within this data set, did not demonstrate a significant relationship between the severity of lung disease and SNPs in the CLC-2 gene. Conclusions CLC-2 is not a key modifier gene of CF lung phenotype. Further studies evaluating other phenotypes associated with CF may be useful in the future to assess the ability of CLC-2 to modify CF disease severity.

  3. Identification and Control of Cladobotryum spp., Causal Agents of Cobeweb Disease of Cultivated Mushroom

    Ivana Potočnik

    2009-01-01

    Full Text Available Cladobotryum spp. are causal agents of cobweb disease, one of the most serious diseases of cultivated mushroom (Agaricus bisporus (Lange Imbach in Serbia and worldwide, which affects product quality and yield. The disease symptoms are: cottony fluffy white oryellowish to pink colonies on mushroom casing, rapid colonization of casing surface, covering of host basidiomata by mycelia, and their decay. Prochloraz-Mn has been officially recommended for mushroom cultivation in EU countries. However, inefficiency of prochloraz-Mn has been noted at a level of spotting symptoms of cobweb disease. With regard to cases of resistance evolution and a general threat to the environment and human health, special attention should be focused on good programmes of hygiene, and inventing and developing alternative methods of disease control.

  4. Proposal for a new nomenclature of disease-modifying antirheumatic drugs

    Smolen, Josef S.; van der Heijde, Desiree; Machold, Klaus P.; Aletaha, Daniel; Landewe, Robert

    2014-01-01

    In light of the recent emergence of new therapeutics for rheumatoid arthritis, such as kinase inhibitors and biosimilars, a new nomenclature for disease-modifying antirheumatic drugs (DMARDs), which are currently often classified as synthetic (or chemical) DMARDs (sDMARDS) and biological DMARDs

  5. Use of modified cornstarch therapy to extend fasting in glycogen storage disease types Ia and Ib

    Correia, Catherine E.; Bhattacharya, Kaustuv; Lee, Philip J.; Shuster, Jonathan J.; Theriaque, Douglas W.; Shankar, Meena N.; Smit, G. Peter A.; Weinstein, David A.

    2008-01-01

    Background: Type I glycogen storage disease (GSD) is caused by a deficiency of glucose-6-phosphatase resulting in severe fasting hypoglycemia. Objective: We compared the efficacy of a new modified starch with the currently used cornstarch therapy in patients with type Ia and Ib GSD. Design: This was

  6. Relationship between leukotriene-modifying agent prescriptions dispensed and rate of suicide deaths by county in the US

    Schumock GT

    2011-09-01

    Full Text Available Glen T Schumock1, Robert D Gibbons2, Todd A Lee1,3,4,6, Min J Joo4, Robert J Valuck5, Leslie T Stayner61Center for Pharmacoeconomic Research, and Department of Pharmacy Practice, College of Pharmacy, University of Illinois at Chicago, Chicago, IL, USA; 2Center for Health Statistics, and Departments of Medicine and Health Studies, Pritzker School of Medicine, University of Chicago, Chicago, IL, USA; 3Center for Management of Complex Chronic Care, Hines VA Hospital, Hines, IL, USA; 4Section of Pulmonary, Critical Care, Sleep and Allergy, Department of Medicine, College of Medicine, University of Illinois at Chicago, Chicago, IL, USA; 5Department of Clinical Pharmacy, School of Pharmacy, University of Colorado, Aurora, CO, USA; 6Division of Epidemiology and Biostatistics, School of Public Health, University of Illinois at Chicago, Chicago, IL, USABackground: The US Food and Drug Administration has issued warnings about a potential link between leukotriene receptor-modifying agents (LTMA and suicide. These warnings are based on case reports and there is controversy about the association. While spontaneous reporting of suicide-related events attributed to LTMA has risen dramatically, these data may be biased by the warnings. The objective of this study was to explore the relationship between LTMA and suicide deaths using event data preceding the Food and Drug Administration warnings.Methods: We conducted a mixed-effects Poisson regression analysis of the association between LTMA prescriptions dispensed and suicide deaths at the county level. Counts of suicide deaths in each US county, stratified by race, age group, gender, and year were obtained from the National Center for Health Statistics for the period January 1, 1999 to December 31, 2006. Counts of LTMA prescriptions dispensed in each US county were obtained from IMS Health Incorporated. The model estimated the overall suicide rate conditional on LTMA use, adjusted for age, gender, race, year

  7. Highly efficient amplification of chronic wasting disease agent by protein misfolding cyclical amplification with beads (PMCAb)

    Johnson, Chad J.; Aiken, Judd M.; McKenzie, Debbie; Samuel, Michael D.; Pedersen, Joel A.

    2012-01-01

    Protein misfolding cyclic amplification (PMCA) has emerged as an important technique for detecting low levels of pathogenic prion protein in biological samples. The method exploits the ability of the pathogenic prion protein to convert the normal prion protein to a proteinase K-resistant conformation. Inclusion of Teflon® beads in the PMCA reaction (PMCAb) has been previously shown to increase the sensitivity and robustness of detection for the 263 K and SSLOW strains of hamster-adapted prions. Here, we demonstrate that PMCAb with saponin dramatically increases the sensitivity of detection for chronic wasting disease (CWD) agent without compromising the specificity of the assay (i.e., no false positive results). Addition of Teflon® beads increased the robustness of the PMCA reaction, resulting in a decrease in the variability of PMCA results. Three rounds of serial PMCAb allowed detection of CWD agent from a 6.7×10−13 dilution of 10% brain homogenate (1.3 fg of source brain). Titration of the same brain homogenate in transgenic mice expressing cervid prion protein (Tg(CerPrP)1536+/−mice) allowed detection of CWD agent from the 10−6 dilution of 10% brain homogenate. PMCAb is, thus, more sensitive than bioassay in transgenic mice by a factor exceeding 105. Additionally, we are able to amplify CWD agent from brain tissue and lymph nodes of CWD-positive white-tailed deer having Prnp alleles associated with reduced disease susceptibility.

  8. Highly efficient amplification of chronic wasting disease agent by protein misfolding cyclic amplification with beads (PMCAb.

    Chad J Johnson

    Full Text Available Protein misfolding cyclic amplification (PMCA has emerged as an important technique for detecting low levels of pathogenic prion protein in biological samples. The method exploits the ability of the pathogenic prion protein to convert the normal prion protein to a proteinase K-resistant conformation. Inclusion of Teflon® beads in the PMCA reaction (PMCAb has been previously shown to increase the sensitivity and robustness of detection for the 263 K and SSLOW strains of hamster-adapted prions. Here, we demonstrate that PMCAb with saponin dramatically increases the sensitivity of detection for chronic wasting disease (CWD agent without compromising the specificity of the assay (i.e., no false positive results. Addition of Teflon® beads increased the robustness of the PMCA reaction, resulting in a decrease in the variability of PMCA results. Three rounds of serial PMCAb allowed detection of CWD agent from a 6.7 × 10(-13 dilution of 10% brain homogenate (1.3 fg of source brain. Titration of the same brain homogenate in transgenic mice expressing cervid prion protein (Tg(CerPrP1536(+/- mice allowed detection of CWD agent from the 10(-6 dilution of 10% brain homogenate. PMCAb is, thus, more sensitive than bioassay in transgenic mice by a factor exceeding 10(5. Additionally, we are able to amplify CWD agent from brain tissue and lymph nodes of CWD-positive white-tailed deer having Prnp alleles associated with reduced disease susceptibility.

  9. Possible role of common spices as a preventive and therapeutic agent for Alzheimer′s disease

    Omid Mirmosayyeb

    2017-01-01

    Full Text Available For centuries, spices have been consumed as food additives or medicinal agents. However, there is increasing evidence indicating the plant-based foods in regular diet may lower the risk of neurodegenerative diseases including Alzheimer disease. Spices, as one of the most commonly used plant-based food additives may provide more than just flavors, but as agents that may prevent or even halt neurodegenerative processes associated with aging. In this article, we review the role and application of five commonly used dietary spices including saffron turmeric, pepper family, zingiber, and cinnamon. Besides suppressing inflammatory pathways, these spices may act as antioxidant and inhibit acetyl cholinesterase and amyloid β aggregation. We summarized how spice-derived nutraceuticals mediate such different effects and what their molecular targets might be. Finally, some directions for future research are briefly discussed.

  10. Oral hypoglycaemic agents, insulin resistance and cardiovascular disease in patients with type 2 diabetes

    Hemmingsen, Bianca; Lund, Søren S; Wetterslev, Jørn

    2009-01-01

    This article is a narrative review of the current evidence of the effects on cardiovascular disease (CVD) of oral hypoglycaemic agents that increase insulin sensitivity in patients with type 2 diabetes (T2D). In overweight T2D patients, metformin has been demonstrated to reduce CVD risk, and this......This article is a narrative review of the current evidence of the effects on cardiovascular disease (CVD) of oral hypoglycaemic agents that increase insulin sensitivity in patients with type 2 diabetes (T2D). In overweight T2D patients, metformin has been demonstrated to reduce CVD risk......, and this beneficial effect may be conserved with the combination of metformin and insulin treatment. However, the effect of glitazones on CVD is uncertain. There is conflicting evidence from large randomized trials to support a protective effect against CVD of lowering blood glucose per se but a systematic review...

  11. Antibody-Based Agents in the Management of Antibiotic-Resistant Staphylococcus aureus Diseases

    Speziale, Pietro; Rindi, Simonetta

    2018-01-01

    Staphylococcus aureus is a human pathogen that can cause a wide spectrum of diseases, including sepsis, pneumonia, arthritis, and endocarditis. Ineffective treatment of a number of staphylococcal infections with antibiotics is due to the development and spread of antibiotic-resistant strains following decades of antibiotic usage. This has generated renewed interest within the scientific community in alternative therapeutic agents, such as anti-S. aureus antibodies. Although the role of antibodies in the management of S. aureus diseases is controversial, the success of this pathogen in neutralizing humoral immunity clearly indicates that antibodies offer the host extensive protection. In this review, we report an update on efforts to develop antibody-based agents, particularly monoclonal antibodies, and their therapeutic potential in the passive immunization approach to the treatment and prevention of S. aureus infections. PMID:29533985

  12. Emerging infectious diseases: a guide to diseases, causative agents, and surveillance

    Beltz, Lisa A

    2011-01-01

    "This important resource offers a comprehensive introduction to emerging and reemerging infectious disease, including the underlying mechanisms of microbial emergence, the technology used to detect...

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

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

    2014-01-01

    -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......OBJECTIVE: To develop and validate composite disease activity scores, based on widely available clinical measures, that would demonstrate improved correlation with detection of synovitis on magnetic resonance imaging (MRI) and radiographic progression, in comparison with conventional measures.......15 × SJC28 + 0.22 × EvGA + 1 and M-SDAI = CRP + SJC28 + EvGA. Both modified and conventional disease activity scores correlated significantly with MRI measures of synovitis. Modified scores showed superior correlation with synovitis, as compared to conventional scores, at all time points (P

  14. In Vitro Screening of Antibacterial Agents for Suppression of Fire Blight Disease in Korea

    Min Su Lee

    2018-03-01

    Full Text Available Since fire blight disease on apple and pear was produced in Korea in 2015, there were no registered chemicals to control against this disease. Instead, several antibacterial chemicals that were registered for other bacterial diseases such as soft rot and bacterial spot have been authorized by Rural Development Administration (RDA. However, these chemicals are not tested efficacy for fire blight disease except damage by those treatments on apple and pear in Korea. Thus, we evaluated efficiency using in vitro and in planta assays of antibacterial chemicals such as antibiotics and copper compounds including kasugamycin, oxytetracycline, oxolinic acid and streptomycin, and copper hydroxide, copper sulfate, oxine copper and tribasic copper sulfate, respectively. We also tested two kinds of biological agents. As expected, significant antibacterial effect was observed in vitro test of both antibiotics and copper-based chemicals. In planta test based on disease severity including ooze and water-soaked formation on immature pears, bacterial populations on blooms, and blight lesion formation in artificially inoculated shoots, kasugamycin, oxytetracycline and streptomycin have been shown the most efficiency among tested antibiotics. Four copper-based chemicals tested in this study, control effects are little bit lower than agricultural antibiotics but they seem to be available to use in terms of winter season. Biocontrol agents were also shown possibility to treat in eco-friendly farms. In addition, there are no antibiotic resistance genes in Korean isolates against antibiotics, which were selected for suppression of fire blight in this study.

  15. Heterocyclic N-oxides - A Promising Class of Agents Against Tuberculosis, Malaria and Neglected Tropical Diseases.

    Dos Santos Fernandes, Guilherme Felipe; Pavan, Aline Renata; Dos Santos, Jean Leandro

    2018-04-17

    Heterocyclic N-oxides have emerged as promising agents against a number of diseases and disorders, especially infectious diseases. This review analyzes the emergence and development of this scaffold in the medicinal chemistry, focusing mainly on the discovery of new heterocyclic N-oxide compounds with potent activity against tuberculosis, malaria and neglected tropical diseases (i.e. leishmaniasis and Chagas disease). A number of heterocyclic N-oxide are described herein, nevertheless, the following chemical classes deserve to be highlighted due to the large number of reports in the literature about their promising pharmacological effects: furoxan, benzofuroxan, quinoxaline 1,4-di-N-oxide, indolone N-oxide and benzimidazole N-oxide. In order to describe those most promising compounds, we included in this review only those most biologically active heterocyclic N-oxide published since 2000. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  16. Potential of chromatin modifying compounds for the treatment of Alzheimer's disease.

    Karagiannis, Tom C; Ververis, Katherine

    2012-01-01

    Alzheimer's disease is a very common progressive neurodegenerative disorder affecting the learning and memory centers in the brain. The hallmarks of disease are the accumulation of β-amyloid neuritic plaques and neurofibrillary tangles formed by abnormally phosphorylated tau protein. Alzheimer's disease is currently incurable and there is an intense interest in the development of new potential therapies. Chromatin modifying compounds such as sirtuin modulators and histone deacetylase inhibitors have been evaluated in models of Alzheimer's disease with some promising results. For example, the natural antioxidant and sirtuin 1 activator resveratrol has been shown to have beneficial effects in animal models of disease. Similarly, numerous histone deacetylase inhibitors including Trichostatin A, suberoylanilide hydroxamic acid, valproic acid and phenylbutyrate reduction have shown promising results in models of Alzheimer's disease. These beneficial effects include a reduction of β-amyloid production and stabilization of tau protein. In this review we provide an overview of the histone deacetylase enzymes, with a focus on enzymes that have been identified to have an important role in the pathobiology of Alzheimer's disease. Further, we discuss the potential for pharmacological intervention with chromatin modifying compounds that modulate histone deacetylase enzymes.

  17. Potential of chromatin modifying compounds for the treatment of Alzheimer's disease

    Tom C. Karagiannis

    2012-02-01

    Full Text Available Alzheimer's disease is a very common progressive neurodegenerative disorder affecting the learning and memory centers in the brain. The hallmarks of disease are the accumulation of β-amyloid neuritic plaques and neurofibrillary tangles formed by abnormally phosphorylated tau protein. Alzheimer's disease is currently incurable and there is an intense interest in the development of new potential therapies. Chromatin modifying compounds such as sirtuin modulators and histone deacetylase inhibitors have been evaluated in models of Alzheimer's disease with some promising results. For example, the natural antioxidant and sirtuin 1 activator resveratrol has been shown to have beneficial effects in animal models of disease. Similarly, numerous histone deacetylase inhibitors including Trichostatin A, suberoylanilide hydroxamic acid, valproic acid and phenylbutyrate reduction have shown promising results in models of Alzheimer's disease. These beneficial effects include a reduction of β-amyloid production and stabilization of tau protein. In this review we provide an overview of the histone deacetylase enzymes, with a focus on enzymes that have been identified to have an important role in the pathobiology of Alzheimer's disease. Further, we discuss the potential for pharmacological intervention with chromatin modifying compounds that modulate histone deacetylase enzymes.

  18. Comparison of an Agent-based Model of Disease Propagation with the Generalised SIR Epidemic Model

    2009-08-01

    utilising 10 metre square buildings with the outcome of in-building combat resolved using a modified Lanchester equation. This limited the usefulness of...observations and the Australian Army’s “Future Land Warfighting Concept – Complex Warfare ” [9] document that highlighted three inter-related complex...by military commanders wishing to assess the impact of disease (naturally occurring or through deliberate biological warfare attack) on their

  19. 2016 guidelines for the use of antifungal agents in patients with invasive fungal diseases in Taiwan

    Hsiang-Chi Kung

    2018-02-01

    Full Text Available The Infectious Diseases Society of Taiwan, Medical Foundation in Memory of Dr. Deh-Lin Cheng, Foundation of Professor Wei-Chuan Hsieh for Infectious Diseases Research and Education, and CY Lee's Research Foundation for Pediatric Infectious Diseases and Vaccines have updated the guidelines for the use of antifungal agents in adult patients with invasive fungal diseases in Taiwan. This guideline replaces the 2009 version. Recommendations are provided for Candida, Cryptococcus, Aspergillus and Mucormycetes. The focus is based on up-to-date evidence on indications for treatment or prophylaxis of the most common clinical problems. To support the recommendations in this guideline, the committee considered the rationale, purpose, local epidemiology, and key clinical features of invasive fungal diseases to select the primary and alternative antifungal agents. This is the first guideline that explicitly describes the quality and strength of the evidence to support these recommendations. The strengths of the recommendations are the quality of the evidence, the balance between benefits and harms, resource and cost. The guidelines are not intended nor recommended as a substitute for bedside judgment in the management of individual patients, the advice of qualified health care professionals, and more recent evidence concerning therapeutic efficacy and emergence of resistance. Practical considerations for individualized selection of antifungal agents include patient factors, pathogen, site of infection and drug-related factors, such as drug–drug interaction, drug-food intervention, cost and convenience. The guidelines are published in the Journal of Microbiology, Immunology and Infection and are also available on the Society website.

  20. Oxygen-saving effect of a new cardiotonic agent, MCI-154, in diseased human hearts.

    Mori, M; Takeuchi, M; Takaoka, H; Hata, K; Hayashi, Y; Yamakawa, H; Yokoyama, M

    1997-03-01

    The aim of this study was to examine the left ventricular mechanoenergetic effects of a novel Ca2+ sensitizing agent, MCI-154, on diseased human hearts compared with dobutamine. Unlike conventional cardiotonic agents, a Ca2+ sensitizer that could produce a positive inotropic action by altering the responsiveness of myofilament to Ca2+ could generate force with smaller amounts of Ca2+; thus, it may potentially save energy expenditure. The left ventricular pressure-volume relation and myocardial oxygen consumption per beat (Vo2) were measured by a conductance (volume) catheter and a Webster catheter. Left ventricular contractility (Emax), systolic pressure-volume area (PVA [index of left ventricular total mechanical energy]) and Vo2 were assessed before and after infusion of MCI-154 or dobut-amine. The PVA-independent Vo2 (Vo2 mainly for excitation-contraction coupling) was assessed as the Vo2 at zero PVA. Both agents increased Emax comparably (dobutamine: from 3.55 +/- 1.10 [mean +/- SD] to 5.04 +/- 1.16 mm Hg/ml per m2, p delta PVA-independent Vo2/delta Emax) was less with MCI-154 than with dobutamine (0.14 +/- 0.18 vs. 1.10 +/- 0.80 J/mm Hg per ml per m2, p action mediated by MCI-154 could provide an energetic advantage over the conventional cardiotonic action with currently used inotropic agents.

  1. Using data-driven agent-based models for forecasting emerging infectious diseases

    Srinivasan Venkatramanan

    2018-03-01

    Full Text Available Producing timely, well-informed and reliable forecasts for an ongoing epidemic of an emerging infectious disease is a huge challenge. Epidemiologists and policy makers have to deal with poor data quality, limited understanding of the disease dynamics, rapidly changing social environment and the uncertainty on effects of various interventions in place. Under this setting, detailed computational models provide a comprehensive framework for integrating diverse data sources into a well-defined model of disease dynamics and social behavior, potentially leading to better understanding and actions. In this paper, we describe one such agent-based model framework developed for forecasting the 2014–2015 Ebola epidemic in Liberia, and subsequently used during the Ebola forecasting challenge. We describe the various components of the model, the calibration process and summarize the forecast performance across scenarios of the challenge. We conclude by highlighting how such a data-driven approach can be refined and adapted for future epidemics, and share the lessons learned over the course of the challenge. Keywords: Emerging infectious diseases, Agent-based models, Simulation optimization, Bayesian calibration, Ebola

  2. Evaluation of a genetically modified foot-and-mouth disease virus vaccine candidate generated by reverse genetics

    2012-01-01

    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 wild O/HN/CHA/93 virus

  3. Evaluation of a genetically modified foot-and-mouth disease virus vaccine candidate generated by reverse genetics

    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

  4. Effect of Viscous Agents on Corneal Density in Dry Eye Disease.

    Wegener, Alfred R; Meyer, Linda M; Schönfeld, Carl-Ludwig

    2015-10-01

    To investigate the effect of the viscous agents, hydroxypropyl methylcellulose (HPMC), carbomer, povidone, and a combination of HPMC and povidone on corneal density in patients with dry eye disease. In total, 98 eyes of 49 patients suffering from dry eye and 65 eyes of 33 healthy age-matched individuals were included in this prospective, randomized study. Corneal morphology was documented with Scheimpflug photography and corneal density was analyzed in 5 anatomical layers (epithelium, bowman membrane, stroma, descemet's membrane, and endothelium). Corneal density was evaluated for the active ingredients HPMC, carbomer, povidone, and a combination of HPMC and povidone as the viscous agents contained in the artificial tear formulations used by the dry eye patients. Data were compared to the age-matched healthy control group without medication. Corneal density in dry eye patients was reduced in all 5 anatomical layers compared to controls. Corneal density was highest and very close to control in patients treated with HPMC containing ocular lubricants. Patients treated with lubricants, including carbomer as the viscous agent displayed a significant reduction of corneal density in layers 1 and 2 compared to control. HPMC containing ocular lubricants can help to maintain physiological corneal density and may be beneficial in the treatment of dry eye disease.

  5. Effects of Immunomodulators and Biologic Agents on Sexual Health in Patients With Inflammatory Bowel Disease.

    Kanar, Ozdemir; Berry, Andrew C; Nakshabendi, Rahman; Lee, Ann Joo; Aldridge, Petra; Myers, Travis; Eid, Emely

    2017-01-01

    Although much knowledge has been gained regarding the medical and surgical management of inflammatory bowel disease (IBD), a paucity of information is available on the psychosexual issues related to IBD. The aim of this study was to evaluate the sexual health of patients with IBD who were taking immunomodulators and/or biologic agents vs patients with IBD who were not on that medication regimen. All study participants completed a validated sexual health questionnaire, the Female Sexual Function Index or the International Index of Erectile Function, to assess their subjective perception of the effect of IBD on the different domains of sexual function during the prior 1-month time period. No statistically significant differences in any baseline demographic variables were found for either sex between the group taking immunomodulators/biologic agents and the nontreatment group. Among females and males, individual question responses, domain scores, and total scores showed no statistically significant differences between the 2 treatment groups. Our data suggest that the use of immunomodulators or biologic agents does not affect female or male sexual health. However, treatment of patients with IBD must be individualized based on the aggressive nature of the disease, treatment goals, and the tolerability of various medications.

  6. Recent trends in the transdermal delivery of therapeutic agents used for the management of neurodegenerative diseases.

    Ita, Kevin

    2017-06-01

    With the increasing proportion of the global geriatric population, it becomes obvious that neurodegenerative diseases will become more widespread. From an epidemiological standpoint, it is necessary to develop new therapeutic agents for the management of Alzheimer's disease, Parkinson's disease, multiple sclerosis and other neurodegenerative disorders. An important approach in this regard involves the use of the transdermal route. With transdermal drug delivery systems (TDDS), it is possible to modulate the pharmacokinetic profiles of these medications and improve patient compliance. Transdermal drug delivery has also been shown to be useful for drugs with short half-life and low or unpredictable bioavailability. In this review, several transdermal drug delivery enhancement technologies are being discussed in relation to the delivery of medications used for the management of neurodegenerative disorders.

  7. Etiologic Agents and Diseases Found Associated with Clinical Aspergillosis in Falcons

    Walter Tarello

    2011-01-01

    Full Text Available The aim of this study was to describe parasitological, microbiological, and pathological findings associated with the isolation of Aspergillus species in 94 clinically diseased captive falcons from Dubai. Concomitant agents and/or diseases were identified in 64 cases, causing either single (=36 or multiple coinfections (=28. Diagnoses found more often in association with aspergillosis were chronic fatigue and immune dysfunction syndrome (CFIDS (=29, Caryospora sp. (=16, Serratospiculum seurati infestation (=14, cestodiasis (=6, bumblefoot (=5, trematodosis due to Strigea falconispalumbi (=5, trichomoniasis (=4, Babesia shortti (=4, Mannheimia (Pastorella haemolytica (=4, interstitial hepatitis (=4, Escherichia coli (=3, and Clostridium perfringens enterotoxemia (=2. Compared with a control group of 2000 diseased falcons without evidence of aspergillosis, the prevalence of Babesia shortti, CFIDS, Mannheimia (Pastorella haemolytica, Escherichia coli, and falcon herpes virus infection was conspicuously higher in association with aspergillosis. These entities may be considered suitable candidates as predisposing factors for the mycosis.

  8. Trichoderma spp.: a biocontrol agent for sustainable management of plant diseases

    Naher, L.; Ismail, A.

    2014-01-01

    Trichoderma spp. are mainly asexual fungi that are present in all types of agricultural soils and also in decaying wood. The antagonistic activity of Trichoderma species showed that it is parasitic on many soil-borne and foliage pathogens. The fungus is also a decomposer of cellulosic waste materials. Recent discoveries show that the fungi not only act as biocontrol agents, but also stimulate plant resistance, and plant growth and development resulting in an increase in crop production. The biocontrol activity involving mycoparasitism, antibiotics and competition for nutrients, also induces defence responses or systemic resistance responses in plants. These responses are an important part of Trichoderma in biocontrol program. Currently, Trichoderma spp., is being used to control plant diseases in sustainable diseases management systems. This paper reviews the published information on Trichoderma spp., and its biocontrol activity in sustainable disease management programs. (author)

  9. Clinical Perspectives of Urocortin and Related Agents for the Treatment of Cardiovascular Disease

    Keiichi Ikeda

    2012-01-01

    Full Text Available The effects of corticotropin-releasing hormone, also known as corticotropin-releasing factor (CRF, on the cardiovascular system have been intensively researched since its discovery. Moreover, the actions of urocortin (Ucn I on the cardiovascular system have also been intensively scrutinized following the cloning and identification of its receptor, CRF receptor type 2 (CRFR2, in peripheral tissues including the heart. Given the cardioprotective actions of CRFR2 ligands, the clinical potential of not only Ucn I but also Ucn II and III, which were later identified as more specific ligands for CRFR2, has received considerable attention from researchers. In addition, recent work has indicated that CRF type 1 receptor may be also involved in cardioprotection against ischemic/reperfusion injury. Here we provide a historical overview of research on Ucn I and related agents, their effects on the cardiovascular system, and the clinical potential of the use of such agents to treat cardiovascular diseases.

  10. Modified Harrington Procedure for Acetabular Insuficiency Due to Metastatic Malignant Disease

    WI Faisham

    2009-05-01

    Full Text Available Extensive peri-acetabular osteolysis caused by malignant disease process is a major surgical challenge as conventional hip arthroplasty is not adequate. We describe a modified use of the Harrington procedure for acetabular insufficiency secondary to metastatic disease in twelve patients. The procedures include application of multiple threaded pins to bridge the acetabular columns, anti-protrusio cage and cemented acetabular cup. Eleven patients were able to walk pain free and achieved a mean Musculoskeletal Tumour Society Functional Score of 80 (range, 68 to 86.

  11. Protection of Mobile Agents Execution Using a Modified Self-Validating Branch-Based Software Watermarking with External Sentinel

    Tomàs-Buliart, Joan; Fernández, Marcel; Soriano, Miguel

    Critical infrastructures are usually controlled by software entities. To monitor the well-function of these entities, a solution based in the use of mobile agents is proposed. Some proposals to detect modifications of mobile agents, as digital signature of code, exist but they are oriented to protect software against modification or to verify that an agent have been executed correctly. The aim of our proposal is to guarantee that the software is being executed correctly by a non trusted host. The way proposed to achieve this objective is by the improvement of the Self-Validating Branch-Based Software Watermarking by Myles et al.. The proposed modification is the incorporation of an external element called sentinel which controls branch targets. This technique applied in mobile agents can guarantee the correct operation of an agent or, at least, can detect suspicious behaviours of a malicious host during the execution of the agent instead of detecting when the execution of the agent have finished.

  12. Modified vegetation indices for Ganoderma disease detection in oil palm from field spectroradiometer data

    Shafri, Helmi Z. M.; Anuar, M. Izzuddin; Saripan, M. Iqbal

    2009-10-01

    High resolution field spectroradiometers are important for spectral analysis and mobile inspection of vegetation disease. The biggest challenges in using this technology for automated vegetation disease detection are in spectral signatures pre-processing, band selection and generating reflectance indices to improve the ability of hyperspectral data for early detection of disease. In this paper, new indices for oil palm Ganoderma disease detection were generated using band ratio and different band combination techniques. Unsupervised clustering method was used to cluster the values of each class resultant from each index. The wellness of band combinations was assessed by using Optimum Index Factor (OIF) while cluster validation was executed using Average Silhouette Width (ASW). 11 modified reflectance indices were generated in this study and the indices were ranked according to the values of their ASW. These modified indices were also compared to several existing and new indices. The results showed that the combination of spectral values at 610.5nm and 738nm was the best for clustering the three classes of infection levels in the determination of the best spectral index for early detection of Ganoderma disease.

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

    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.

  14. Ultrasound enhanced delivery of molecular imaging and therapeutic agents in Alzheimer's disease mouse models.

    Scott B Raymond

    Full Text Available Alzheimer's disease is a neurodegenerative disorder typified by the accumulation of a small protein, beta-amyloid, which aggregates and is the primary component of amyloid plaques. Many new therapeutic and diagnostic agents for reducing amyloid plaques have limited efficacy in vivo because of poor transport across the blood-brain barrier. Here we demonstrate that low-intensity focused ultrasound with a microbubble contrast agent may be used to transiently disrupt the blood-brain barrier, allowing non-invasive, localized delivery of imaging fluorophores and immunotherapeutics directly to amyloid plaques. We administered intravenous Trypan blue, an amyloid staining red fluorophore, and anti-amyloid antibodies, concurrently with focused ultrasound therapy in plaque-bearing, transgenic mouse models of Alzheimer's disease with amyloid pathology. MRI guidance permitted selective treatment and monitoring of plaque-heavy anatomical regions, such as the hippocampus. Treated brain regions exhibited 16.5+/-5.4-fold increase in Trypan blue fluorescence and 2.7+/-1.2-fold increase in anti-amyloid antibodies that localized to amyloid plaques. Ultrasound-enhanced delivery was consistently reproduced in two different transgenic strains (APPswe:PSEN1dE9, PDAPP, across a large age range (9-26 months, with and without MR guidance, and with little or no tissue damage. Ultrasound-mediated, transient blood-brain barrier disruption allows the delivery of both therapeutic and molecular imaging agents in Alzheimer's mouse models, which should aid pre-clinical drug screening and imaging probe development. Furthermore, this technique may be used to deliver a wide variety of small and large molecules to the brain for imaging and therapy in other neurodegenerative diseases.

  15. Knowledge of modifiable risk factors of Coronary Atherosclerotic Heart Disease (CASHD among a sample in India

    Ku Melvin

    2009-02-01

    Full Text Available Abstract Background The prevalence of Coronary Atherosclerotic Heart Disease (CASHD is increasing in India. Several modifiable risk factors contribute directly to this disease burden. Public knowledge of such risk factors among the urban Indian population is largely unknown. This investigation attempts to quantify knowledge of modifiable risk factors of CASHD as sampled among an Indian population at a large metropolitan hospital. Methods A hospital-based, cross sectional study was conducted at All India Institute of Medical Sciences (AIIMS, a major tertiary care hospital in New Delhi, India. Participants (n = 217 recruited from patient waiting areas in the emergency room were provided with standardized questionnaires to assess their knowledge of modifiable risk factors of CASHD. The risk factors specifically included smoking, hypertension, elevated cholesterol levels, diabetes mellitus and obesity. Identifying 3 or less risk factors was regarded as a poor knowledge level, whereas identifying 4 or more risk factors was regarded as a good knowledge level. A multiple logistic regression model was used to isolate independent demographic markers predictive of a participant's level of knowledge. Results 41% of the sample surveyed had a good level of knowledge. 68%, 72%, 73% and 57% of the population identified smoking, obesity, hypertension, and high cholesterol correctly, respectively. 30% identified diabetes mellitus as a modifiable risk factor of CASHD. In multiple logistic regression analysis independent demographic predictors of a good knowledge level with a statistically significant (p Conclusion An Indian population in a hospital setting shows a lack of knowledge pertaining to modifiable risk factors of CASHD. By isolating demographic predictors of poor knowledge, such as current smokers and persons who do not exercise regularly, educational interventions can be effectively targeted and implemented as primary and secondary prevention strategies

  16. NUTRITION AS POSSIBLE ETHIOLOGICAL AGENT OF WINTER DISEASE SYNDROME IN SEA BREAM (Sparus aurata L.

    Gordana Šarušić

    2000-12-01

    Full Text Available The circumstance of winter disease phenomenon in intensively reared sea bream (Sparus aurata L. has been described. It’s occurence in Mediterranean has been registered and reported by several authors. The aim of this paper is to contribute to the comprehension on the aethiology of this syndrome which is causing significant losses in one year old cultured fish. Different types of commercial diets were introduced during 1994/95 rearing season to the sea bream reared in floating cages. The feeds were displaying differences in energetic compound level and vitamin A, D3 and E content. Health difficulties and mortality in the observed fish groups at the beginning of the problem, did not indicate any biotic agent as being responsible for such condition. Clinical features and mortality in the groups affected by winter disease syndrome were increasing by low sea temperature and correlating with feeding period by food containing low levels of protein, lipids and vitamins. Pathological findings were in particularly related to the organs involved in digestion. Growth rate was characteristic for the group that were suffering winter disease, where increasing in length was not followed by body weight. Clinical signs, simptomathology related to the organs involved in digestion, liver histology analyses, weight losses and pattern of weight and length relation, correlation between used feeds and occurrence of winter disease, implicated nutrition as one of most possible ethiological agent of this condition. Nutritional interventions applied contributed in comprehension of the winter disease syndrome. The relationship between nutritional requirements, particularly regerding autumn-winter period, has been researched and analyzed. The results approved our basic hypothesis.

  17. Pre-Clinical Testing of Real-Time PCR Assays for Diarrheal Disease Agents of Genera Escherichia and Shigella

    2014-05-16

    FOR DIARRHEAL DISEASE AGENTS OF GENERA ESCHERICHIA AND SHIGELLA May 16, 2014 Reporting Period: October 1, 2010 to September 30, 2013...10-2010 - 30-09-2013 PRE-CLINICAL TESTING OF REAL-TIME PCR ASSAYS FOR DIARRHEAL DISEASE AGENTS OF GENERA ESCHERICHIA AND SHIGELLA ...Texas (MOA 2007 - 2013. Agreement No.: DODI 4000.19; AFI 25-201). Pre-clinical test results qualify ETEC and Shigella real-time PCR assays as lead

  18. Characterisation of the casual agent of mango anthracnose disease in Ghana

    Honger, Joseph Okani

    2014-05-01

    This research work was carried out to update information on the nature, the identity of the causal agent and the importance of mango anthracnose disease in Ghana. It was also to determine the effect of the disease on the juice quality of fruits and come up with appropriate control measures in the country. A field survey was carried out in 12 administrative districts of Ghana in 2010 and 2011 to assess the disease incidence and severity. The effect of the disease on yield/fruit quality was assessed in a commercial farm by determining the percentage of fruits that dropped or could not be marketed due to the disease. The pathogen causing the disease was isolated from the diseased lesions and characterised using cultural, morphological, biochemical and molecular approaches. The total soluble solids and acidity content of infected fruits were measured as means of determining the effect of the disease on juice quality of the fruits. The susceptibility of the different strains of the pathogen to fungicides available in Ghana was assessed using PDA amended with the fungicides after which efficacy of fungicides was evaluated in the field. The results show that two different symptoms, a sunken dark lesion and cracked skins were observable in Ghana. The disease was not found in the field in 5 out of the 12 districts surveyed and the incidence ranged from 0% in the Hohoe, Berekum, Kintampo, Savelungu/Nanton and Tolon/Kumbungu districts to 100% in the Kwaebibrem and Kumasi metro districts in both the 2010 and 2011 major mango growing seasons. The severity index of the disease on a scale of 0-5 ranged from 0 to 3.8 in 2010 and 0 to 3.7 in 2011. The disease was found to cause shriveling of fruit panicles and blemishes on skin of fruits resulting in yield loss of 4.5% in the major season and 29.9% in the minor season in a mango orchard in the Yilo Krobo district. Colletotrichum gloeosporioides. sensu lato was confirmed as the causal agent of the disease. From a total of 45

  19. Ca2+ sensitizers: An emerging class of agents for counterbalancing weakness in skeletal muscle diseases?

    Ochala, Julien

    2010-02-01

    Ca(2+) ions are key regulators of skeletal muscle contraction. By binding to contractile proteins, they initiate a cascade of molecular events leading to cross-bridge formation and ultimately, muscle shortening and force production. The ability of contractile proteins to respond to Ca(2+) attachment, also known as Ca(2+) sensitivity, is often compromised in acquired and congenital skeletal muscle disorders. It constitutes, undoubtedly, a major physiological cause of weakness for patients. In this review, we discuss recent studies giving strong molecular and cellular evidence that pharmacological modulators of some of the contractile proteins, also termed Ca(2+) sensitizers, are efficient agents to improve Ca(2+) sensitivity and function in diseased skeletal muscle cells. In fact, they compensate for the impaired contractile proteins response to Ca(2+) binding. Currently, such Ca(2+) sensitizing compounds are successfully used for reducing problems in cardiac disorders. Therefore, in the future, under certain conditions, these agents may represent an emerging class of agents to enhance the quality of life of patients suffering from skeletal muscle weakness. Copyright 2009 Elsevier B.V. All rights reserved.

  20. The role of bacillus-based biological control agents in integrated pest management systems: plant diseases.

    Jacobsen, B J; Zidack, N K; Larson, B J

    2004-11-01

    ABSTRACT Bacillus-based biological control agents (BCAs) have great potential in integrated pest management (IPM) systems; however, relatively little work has been published on integration with other IPM management tools. Unfortunately, most research has focused on BCAs as alternatives to synthetic chemical fungicides or bactericides and not as part of an integrated management system. IPM has had many definitions and this review will use the national coalition for IPM definition: "A sustainable approach to managing pests by combining biological, cultural, physical and chemical tools in a way that minimizes economic, health and environmental risks." This review will examine the integrated use of Bacillus-based BCAs with disease management tools, including resistant cultivars, fungicides or bactericides, or other BCAs. This integration is important because the consistency and degree of disease control by Bacillus-based BCAs is rarely equal to the control afforded by the best fungicides or bactericides. In theory, integration of several tools brings stability to disease management programs. Integration of BCAs with other disease management tools often provides broader crop adaptation and both more efficacious and consistent levels of disease control. This review will also discuss the use of Bacillus-based BCAs in fungicide resistance management. Work with Bacillus thuringiensis and insect pest management is the exception to the relative paucity of reports but will not be the focus of this review.

  1. Uncommon and Neglected Venezuelan Viral Diseases: Etiologic Agents, Physiopathological, Clinical and Epidemiological Characteristics

    Juan C. Gabaldon-Figueira

    2015-10-01

    Full Text Available Abstract (english Viral infectious diseases are common in Venezuela, influenza, dengue, yellow fever, HIV infection, viral Hepatitis, chikungunya fever and many others represent public health problems in the country and therefore, have been well documented. However, other rarer and even unique or lethal viral illnesses present in Venezuela are usually poorly understood or even unknown. This review described Venezuelan Hemorrhagic Fever, Venezuelan Equine Encephalitis, Hantavirus Infections and Mayaro fever, named as neglected diseases, emphasizing the etiologic agents and their most relevant pathogenic mechanisms, clinical and epidemiological characteristics. Although there is not an official report about the re-emergence of these diseases, falling living standards and unsanitary conditions, together with limited accessibility to hygiene products and medical supplies, put us on alert about the re-emergence of these neglected diseases. Resumen (español Las enfermedades infecciosas virales son comunes en Venezuela, influenza, dengue, fiebre amarilla, infección por VIH, hepatitis viral, fiebre chikungunya y muchas otras representan problemas de salud pública en el país y por lo tanto, han sido bien documentadas. Sin embargo, otras enfermedades virales más raras e incluso únicas y letales presentes en Venezuela son generalmente poco estudiadas y hasta desconocidas. Esta revisión describe alguna de estas enfermedades olvidadas tales como la fiebre hemorrágica venezolana, la encefalitis equina venezolana, las infecciones por hantavirus y la fiebre de Mayaro, haciendo hincapié en los agentes etiológicos y en sus mecanismos patogénicos más relevantes, características clínicas y epidemiológicas. Aunque no hay informes oficiales sobre el resurgimiento de estas enfermedades, la caída de los niveles de vida y las condiciones insalubres, junto con el acceso limitado a los productos de higiene y suministros médicos, debe alertar sobre el

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

    Spencer, Elizabeth A.; Pirie, Kirstin L.; Stevens, Richard J.; Beral, Valerie; Brown, Anna; Liu, Bette; Green, Jane; Reeves, Gillian K.

    2008-01-01

    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

  3. New-onset vitiligo and progression of pre-existing vitiligo during treatment with biological agents in chronic inflammatory diseases.

    Méry-Bossard, L; Bagny, K; Chaby, G; Khemis, A; Maccari, F; Marotte, H; Perrot, J L; Reguiai, Z; Sigal, M L; Avenel-Audran, M; Boyé, T; Grasland, A; Gillard, J; Jullien, D; Toussirot, E

    2017-01-01

    The development of vitiligo during treatment with biological agents is an unusual event and only a few isolated cases have been reported. To describe the clinical characteristics and evolution of patients developing new-onset vitiligo following initiation of a biological agent for chronic inflammatory disease; and also to report the clinical course of pre-existing vitiligo under biological therapy. This nationwide multicentre, retrospective study, carried out between July 2013 and January 2015, describes the characteristics of a large series of 18 patients (psoriasis N = 8, inflammatory rheumatic diseases N = 8, ulcerative colitis N = 1, uveitis N = 1) who developed new-onset vitiligo while receiving a biological agent. TNFα inhibitors were the most common biological agent involved (13/18) while anti-IL-12/23 and anti-IL-17 agents or abatacept were less common (4/18 and 1/18 respectively). Mean duration of biological agent exposure before vitiligo onset was 13.9 ± 16.5 months. Outcome was favourable for most patients (15/17) while maintaining the biological agent. Data were also collected for 18 patients (psoriasis N = 5, inflammatory rheumatic diseases N = 10, inflammatory bowel diseases N = 2, SAPHO N = 1) who had pre-existing vitiligo when treatment with a biological agent started (TNFα inhibitors N = 15, ustekinumab N = 1, rituximab N = 1, tocilizumab N = 1). Vitiligo progressed in seven patients and was stable or improved in eight cases. Vitiligo may thus emerge and/or progress during treatment with various biological agents, mainly TNFα inhibitors and could be a new paradoxical skin reaction. De novo vitiligo displays a favourable outcome when maintaining the biological agent, whereas the prognosis seems worse in cases of pre-existing vitiligo. © 2016 European Academy of Dermatology and Venereology.

  4. Proliferative kidney disease (PKD) agent Tetracapsuloides bryosalmonae in brown trout populations in Estonia.

    Dash, Megha; Vasemägi, Anti

    2014-05-13

    Proliferative kidney disease (PKD) caused by the myxozoan parasite Tetracapsuloides bryosalmonae is a serious parasitic disease threatening both farmed and wild salmonid populations, but very little is currently known about the distribution of the parasite in the Baltic Sea region. In this study we (1) report the development of a novel multiplex PCR method for fast and reliable screening of T. bryosalmonae; (2) use this multiplex PCR method to show that the PKD agent T. bryosalmonae is widespread in natural brown trout Salmo trutta L. populations in Estonia; (3) evaluate monthly and yearly variation of T. bryosalmonae prevalence in juvenile trout; (4) assess T. bryosalmonae prevalence in different age-classes of fish (0+ vs. 1+ and older) and report the presence of the PKD agent in the kidneys of returning sea trout spawners; and (5) suggest the freshwater bryozoan Plumatella fungosa as a putative invertebrate host of T. bryosalmonae in Estonia. Our results demonstrate a highly heterogeneous distribution of T. bryosalmonae at the micro-geographic scale, indicating that PKD could have an important negative effect on recruitment in Estonian brown trout populations.

  5. Metal-Organic Framework Modified Glass Substrate for Analysis of Highly Volatile Chemical Warfare Agents by Paper Spray Mass Spectrometry.

    Dhummakupt, Elizabeth S; Carmany, Daniel O; Mach, Phillip M; Tovar, Trenton M; Ploskonka, Ann M; Demond, Paul S; DeCoste, Jared B; Glaros, Trevor

    2018-03-07

    Paper spray mass spectrometry has been shown to successfully analyze chemical warfare agent (CWA) simulants. However, due to the volatility differences between the simulants and real G-series (i.e., sarin, soman) CWAs, analysis from an untreated paper substrate proved difficult. To extend the analytical lifetime of these G-agents, metal-organic frameworks (MOFs) were successfully integrated onto the paper spray substrates to increase adsorption and desorption. In this study, several MOFs and nanoparticles were tested to extend the analytical lifetimes of sarin, soman, and cyclosarin on paper spray substrates. It was found that the addition of either UiO-66 or HKUST-1 to the paper substrate increased the analytical lifetime of the G-agents from less than 5 min detectability to at least 50 min.

  6. SQ grass sublingual allergy immunotherapy tablet for disease-modifying treatment of grass pollen allergic rhinoconjunctivitis

    Dahl, Ronald; Roberts, Graham; de Blic, Jacques

    2016-01-01

    BACKGROUND: Allergy immunotherapy is a treatment option for allergic rhinoconjunctivitis (ARC). It is unique compared with pharmacotherapy in that it modifies the immunologic pathways that elicit an allergic response. The SQ Timothy grass sublingual immunotherapy (SLIT) tablet is approved in North...... America and throughout Europe for the treatment of adults and children (≥5 years old) with grass pollen-induced ARC. OBJECTIVE: The clinical evidence for the use of SQ grass SLIT-tablet as a disease-modifying treatment for grass pollen ARC is discussed in this review. METHODS: The review included...... the suitability of SQ grass SLIT-tablet for patients with clinically relevant symptoms to multiple Pooideae grass species, single-season efficacy, safety, adherence, coseasonal initiation, and cost-effectiveness. The data from the long-term SQ grass SLIT-tablet clinical trial that evaluated a clinical effect 2...

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

    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. Towards a Hybrid Agent-based Model for Mosquito Borne Disease.

    Mniszewski, S M; Manore, C A; Bryan, C; Del Valle, S Y; Roberts, D

    2014-07-01

    Agent-based models (ABM) are used to simulate the spread of infectious disease through a population. Detailed human movement, demography, realistic business location networks, and in-host disease progression are available in existing ABMs, such as the Epidemic Simulation System (EpiSimS). These capabilities make possible the exploration of pharmaceutical and non-pharmaceutical mitigation strategies used to inform the public health community. There is a similar need for the spread of mosquito borne pathogens due to the re-emergence of diseases such as chikungunya and dengue fever. A network-patch model for mosquito dynamics has been coupled with EpiSimS. Mosquitoes are represented as a "patch" or "cloud" associated with a location. Each patch has an ordinary differential equation (ODE) mosquito dynamics model and mosquito related parameters relevant to the location characteristics. Activities at each location can have different levels of potential exposure to mosquitoes based on whether they are inside, outside, or somewhere in-between. As a proof of concept, the hybrid network-patch model is used to simulate the spread of chikungunya through Washington, DC. Results are shown for a base case, followed by varying the probability of transmission, mosquito count, and activity exposure. We use visualization to understand the pattern of disease spread.

  9. A Choline Oxidase Amperometric Bioassay for the Detection of Mustard Agents Based on Screen-Printed Electrodes Modified with Prussian Blue Nanoparticles

    Fabiana Arduini

    2015-02-01

    Full Text Available In this work a novel bioassay for mustard agent detection was proposed. The bioassay is based on the capability of these compounds to inhibit the enzyme choline oxidase. The enzymatic activity, which is correlated to the mustard agents, was electrochemically monitored measuring the enzymatic product, hydrogen peroxide, by means of a screen-printed electrode modified with Prussian Blue nanoparticles. Prussian Blue nanoparticles are able to electrocatalyse the hydrogen peroxide concentration reduction at low applied potential (−50 mV vs. Ag/AgCl, thus allowing the detection of the mustard agents with no electrochemical interferences. The suitability of this novel bioassay was tested with the nitrogen mustard simulant bis(2-chloroethylamine and the sulfur mustard simulants 2-chloroethyl ethyl sulfide and 2-chloroethyl phenyl sulfide. The bioassay proposed in this work allowed the detection of mustard agent simulants with good sensitivity and fast response, which are excellent premises for the development of a miniaturised sensor well suited for an alarm system in case of terrorist attacks.

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

    Hong Liu-Seifert

    Full Text Available 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

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

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

    2016-01-01

    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......-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...

  12. Reductive Stress in Inflammation-Associated Diseases and the Pro-Oxidant Effect of Antioxidant Agents

    Israel Pérez-Torres

    2017-10-01

    Full Text Available Abstract: Reductive stress (RS is the counterpart oxidative stress (OS, and can occur in response to conditions that shift the redox balance of important biological redox couples, such as the NAD+/NADH, NADP+/NADPH, and GSH/GSSG, to a more reducing state. Overexpression of antioxidant enzymatic systems leads to excess reducing equivalents that can deplete reactive oxidative species, driving the cells to RS. A feedback regulation is established in which chronic RS induces OS, which in turn, stimulates again RS. Excess reducing equivalents may regulate cellular signaling pathways, modify transcriptional activity, induce alterations in the formation of disulfide bonds in proteins, reduce mitochondrial function, decrease cellular metabolism, and thus, contribute to the development of some diseases in which NF-κB, a redox-sensitive transcription factor, participates. Here, we described the diseases in which an inflammatory condition is associated to RS, and where delayed folding, disordered transport, failed oxidation, and aggregation are found. Some of these diseases are aggregation protein cardiomyopathy, hypertrophic cardiomyopathy, muscular dystrophy, pulmonary hypertension, rheumatoid arthritis, Alzheimer’s disease, and metabolic syndrome, among others. Moreover, chronic consumption of antioxidant supplements, such as vitamins and/or flavonoids, may have pro-oxidant effects that may alter the redox cellular equilibrium and contribute to RS, even diminishing life expectancy.

  13. Analysis of genetic diversity of Fusarium tupiense, the main causal agent of mango malformation disease in southern Spain

    Mango malformation disease (MMD) has become an important global disease affecting this crop. The aim of this study was to identify the main causal agents of MMD in the Axarquía region of southern Spain and determine their genetic diversity. Fusarium mangiferae was previously described in the Axarquí...

  14. [Public health pests. Arthropods and rodents as causative disease agents as well as reservoirs and vectors of pathogens].

    Faulde, M; Freise, J

    2014-05-01

    Globally, infectious diseases pose the most important cause of death. Among known human pathogenic diseases, approximately 50 % are zoonoses. When considering emerging infectious diseases separately 73 % currently belong to the group of zoonoses. In Central Europe, hard ticks show by far the biggest potential as vectors of agents of human disease. Lyme borreliosis, showing an estimated annual incidence between 60,000 and 214,000 cases is by far the most frequent tick-borne disease in Germany. Continually, formerly unknown disease agents could be discovered in endemic vector species. Additionally, introduction of new arthropod vectors and/or agents of disease occur constantly. Recently, five mosquito species of the genus Aedes have been newly introduced to Europe where they are currently spreading in different regions. Uncommon autochthonous transmission of dengue and chikungunya fever viruses in Southern Europe could be directly linked to these vector species and of these Ae. albopictus and Ae. japonicus are currently reported to occur in Germany. The German Protection against Infection Act only covers the control of public health pests which are either active hematophagous vectors or mechanical transmitters of agents of diseases. Use of officially recommended biocidal products aiming to interrupt transmission cycles of vector-borne diseases, is confined to infested buildings only, including sewage systems in the case of Norway rat control. Outdoor vectors, such as hard ticks and mosquitoes, are currently not taken into consideration. Additionally, adjustments of national public health regulations, detailed arthropod vector and rodent reservoir mapping, including surveillance of vector-borne disease agents, are necessary in order to mitigate future disease risks.

  15. Amine modified polyethylenes, prepared in near critical propane, as adhesion promoting agents in multilayered HDPE/PET films

    Gooijer, de J.M.; Scheltus, M.; Koning, C.E.

    2001-01-01

    High d. polyethylene (HDPE) grafted with 0.13, 0.40 and 1.04 wt% maleic anhydride (abbreviation PEMA) was modified with an excess of a variety of diamines in near crit. propane. The resulting amic acid groups were quant. imidized to the corresponding imide (PEMI) in the melt. Increasing the

  16. Analysis of recent failures of disease modifying therapies in Alzheimer's disease suggesting a new methodology for future studies.

    Amanatkar, Hamid Reza; Papagiannopoulos, Bill; Grossberg, George Thomas

    2017-01-01

    Pharmaceutical companies and the NIH have invested heavily in a variety of potential disease-modifying therapies for Alzheimer's disease (AD) but unfortunately all double-blind placebo-controlled Phase III studies of these drugs have failed to show statistically significant results supporting their clinical efficacy on cognitive measures. These negative results are surprising as most of these medications have the capability to impact the biomarkers which are associated with progression of Alzheimer's disease. Areas covered: This contradiction prompted us to review all study phases of Intravenous Immunoglobulin (IVIG), Bapineuzumab, Solanezumab, Avagacestat and Dimebolin to shed more light on these recent failures. We critically analyzed these studies, recommending seven lessons from these failures which should not be overlooked. Expert commentary: We suggest a new methodology for future treatment research in Alzheimer's disease considering early intervention with more focus on cognitive decline as a screening tool, more sophisticated exclusion criteria with more reliance on biomarkers, stratification of subjects based on the rate of cognitive decline aiming less heterogeneity, and a longer study duration with periodic assessment of cognition and activities of daily living during the study and also after a washout period.

  17. Ball python nidovirus: a candidate etiologic agent for severe respiratory disease in Python regius.

    Stenglein, Mark D; Jacobson, Elliott R; Wozniak, Edward J; Wellehan, James F X; Kincaid, Anne; Gordon, Marcus; Porter, Brian F; Baumgartner, Wes; Stahl, Scott; Kelley, Karen; Towner, Jonathan S; DeRisi, Joseph L

    2014-09-09

    A severe, sometimes fatal respiratory disease has been observed in captive ball pythons (Python regius) since the late 1990s. In order to better understand this disease and its etiology, we collected case and control samples and performed pathological and diagnostic analyses. Electron micrographs revealed filamentous virus-like particles in lung epithelial cells of sick animals. Diagnostic testing for known pathogens did not identify an etiologic agent, so unbiased metagenomic sequencing was performed. Abundant nidovirus-like sequences were identified in cases and were used to assemble the genome of a previously unknown virus in the order Nidovirales. The nidoviruses, which were not previously known to infect nonavian reptiles, are a diverse order that includes important human and veterinary pathogens. The presence of the viral RNA was confirmed in all diseased animals (n = 8) but was not detected in healthy pythons or other snakes (n = 57). Viral RNA levels were generally highest in the lung and other respiratory tract tissues. The 33.5-kb viral genome is the largest RNA genome yet described and shares canonical characteristics with other nidovirus genomes, although several features distinguish this from related viruses. This virus, which we named ball python nidovirus (BPNV), will likely establish a new genus in Torovirinae subfamily. The identification of a novel nidovirus in reptiles contributes to our understanding of the biology and evolution of related viruses, and its association with lung disease in pythons is a promising step toward elucidating an etiology for this long-standing veterinary disease. Ball pythons are popular pets because of their diverse coloration, generally nonaggressive behavior, and relatively small size. Since the 1990s, veterinarians have been aware of an infectious respiratory disease of unknown cause in ball pythons that can be fatal. We used unbiased shotgun sequencing to discover a novel virus in the order Nidovirales that was

  18. Work-Family Conflict Modifies the Association of Smoking and Periodontal Disease.

    Brennan, David S; Spencer, A John; Roberts-Thomson, Kaye F

    2017-02-01

    The aims of the study were to assess the association of periodontal loss of attachment with smoking and work-family conflict and assess whether work-family conflict modifies the association of smoking and periodontal disease. A random sample of 45-54 year olds from metropolitan Adelaide, South Australia, was surveyed by mailed self-complete questionnaire during 2004-2005. Oral examinations were performed on persons who responded to the questionnaire, providing an assessment of periodontal status. A total of 879 responded (participation rate = 43.8 %), with n = 709 oral examinations (completion rate = 80.7 %). Prevalence of periodontal loss of attachment (LOA) of 6+ mm was higher (p periodontal disease. Higher levels of work interfering with family were associated with higher levels of periodontal LOA for smokers compared with non-smokers.

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

    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...

  20. Preventative and Curative Effects of Several Plant Derived Agents Against Powdery Mildew Disease of Okra

    Moustafa Hemdan Ahmed MOHARAM

    2012-08-01

    Full Text Available The preventative and curative effects of some plant derived agents based on plant extracts or essential oils were studied at different concentrations against Erysiphe cichoracearum DC. ex Merat, the causal pathogen of okra powdery mildew by the detached leaf-disk and potted plants bioassays. Through detached leaf-disk assay, the highest mean preventative effect (97.74% was recorded by neem seed oil followed by jojoba oil (89.82% and extract of Rynoutria sachalinensis (82.77%. Neem seed oil at 1% was the most effective agent followed by jojoba oil and extract of R. sachalinensis at 1.5% and 2%, respectively, where they suppressed E. cichoracearum completely. Potted plants assay revealed that neem seed oil, jojoba oil and extract of R. sachalinensis as well as the fungicide (active ingredient dinocap showed higher preventative efficacy at all leaf olds treated after 7 and 14 days of inoculation as compared with extracts of henna and garlic. Moreover, the preventative efficacy partly remained apparent after 14 days of inoculation at all leaf olds tested. In field trials through 2010 and 2011 growing seasons, when the first symptoms of powdery mildew appeared naturally, 1.5% jojoba oil, 2% extract of R. sachalinensis and 1% neem seed oil were sprayed individually twice on grown plants to evaluate their efficacy on controlling powdery mildew, growth and yield of okra. Resulted showed that neem seed oil was the most effective agent and highly decreased the disease severity to 29.92%, recorded the highly curative effect (68.15% and also improved plant growth and pods yield.

  1. Use of health care services and pharmaceutical agents in coeliac disease: a prospective nationwide study

    Ukkola Anniina

    2012-09-01

    Full Text Available Abstract Background Approximately 1% of the population suffer from coeliac disease. However, the disease is heavily underdiagnosed. Unexplained symptoms may lead to incremented medical consultations and productivity losses. The aim here was to estimate the possible concealed burden of untreated coeliac disease and the effects of a gluten-free diet. Methods A nationwide cohort of 700 newly detected adult coeliac patients were prospectively evaluated. Health care service use and sickness absence from work during the year before diagnosis were compared with those in the general population; the data obtained from an earlier study. Additionally, the effect of one year on dietary treatment on the aforementioned parameters and on consumption of pharmaceutical agents was assessed. Results Untreated coeliac patients used primary health care services more frequently than the general population. On a gluten-free diet, visits to primary care decreased significantly from a mean 3.6 to 2.3. The consumption of medicines for dyspepsia (from 3.7 to 2.4 pills/month and painkillers (6.8-5.5 pills/month and the number of antibiotic courses (0.6-0.5 prescriptions/year was reduced. There were no changes in hospitalizations, outpatient visits to secondary and tertiary care, use of other medical services, or sickness absence, but the consumption of nutritional supplements increased on treatment. Conclusions Coeliac disease was associated with excessive health care service use and consumption of drugs before diagnosis. Dietary treatment resulted in a diminished burden to the health care system and lower use of on-demand medicines and antibiotic treatment. The results support an augmented diagnostic approach to reduce underdiagnosis of coeliac disease. Trial registration ClinicalTrials.gov NCT01145287

  2. Use of health care services and pharmaceutical agents in coeliac disease: a prospective nationwide study.

    Ukkola, Anniina; Kurppa, Kalle; Collin, Pekka; Huhtala, Heini; Forma, Leena; Kekkonen, Leila; Mäki, Markku; Kaukinen, Katri

    2012-09-27

    Approximately 1% of the population suffer from coeliac disease. However, the disease is heavily underdiagnosed. Unexplained symptoms may lead to incremented medical consultations and productivity losses. The aim here was to estimate the possible concealed burden of untreated coeliac disease and the effects of a gluten-free diet. A nationwide cohort of 700 newly detected adult coeliac patients were prospectively evaluated. Health care service use and sickness absence from work during the year before diagnosis were compared with those in the general population; the data obtained from an earlier study. Additionally, the effect of one year on dietary treatment on the aforementioned parameters and on consumption of pharmaceutical agents was assessed. Untreated coeliac patients used primary health care services more frequently than the general population. On a gluten-free diet, visits to primary care decreased significantly from a mean 3.6 to 2.3. The consumption of medicines for dyspepsia (from 3.7 to 2.4 pills/month) and painkillers (6.8-5.5 pills/month) and the number of antibiotic courses (0.6-0.5 prescriptions/year) was reduced. There were no changes in hospitalizations, outpatient visits to secondary and tertiary care, use of other medical services, or sickness absence, but the consumption of nutritional supplements increased on treatment. Coeliac disease was associated with excessive health care service use and consumption of drugs before diagnosis. Dietary treatment resulted in a diminished burden to the health care system and lower use of on-demand medicines and antibiotic treatment. The results support an augmented diagnostic approach to reduce underdiagnosis of coeliac disease. ClinicalTrials.gov NCT01145287.

  3. Comparison of gadolinium Cy2DOTA, a new hepatobiliary agent, and gadolinium HP-DO3A, an extracellular agent, in healthy liver and metastatic disease

    Runge, V.M.; Wells, J.W.; Williams, N.M.

    1995-01-01

    A new gadolinium (Gd) chelate with preferential hepatobiliary uptake, Gd Cy 2 DOTA, was compared in two animal species with Gd HP-DO3A (gadoteridol), a clinically approved contrast agent with extracellular distribution. Liver enhancement was evaluated for these two contrast agents using magnetic resonance imaging, whereas an experimental model of metastatic disease was used to evaluate the agents' efficacy for liver-lesion delineation. The two agents were compared in four healthy Rhesus monkeys (eight studies) and five New Zealand White rabbits with implanted VX-2 liver tumors (ten studies). The contrast dose was 0.1 mmol/kg, with the agents given in random order and at least 72 hours between contrast injections. Breathhold T1-weighted spin echo scans were obtained at 1.5 tesla (T) before and after contrast was administered. Postcontrast scans were obtained 1 to 90 minutes after injection in the monkeys and 1 to 240 minutes after injection in the rabbits. Prolonged hepatic enhancement, superior in degree to that with Gd HP-DO3A, was noted to both monkeys and rabbits after injection of Gd Cy 2 DOTA. Two minutes after contrast, liver SI was 1.94 ± 0.05 with Gd Cy 2 DOTA compared with 1.5 ± 0.05 with Gd HP-DO3A in monkeys. Sixty minutes after contrast, liver SI was 1.60 ± 0.09 compared with 1.20 ± 0.02. The difference between agents was significant at all times from 2 to 60 minutes after contrast injection (P 2 DOTA but not with Gd HP-DO3A. The maximum improvement in lesion conspicuity (rabbit) occurred 45 minutes after injection of Gd Cy 2 DOTA and 5 minutes after injection of Gd HP-DO3A. 22 refs., 12 figs

  4. Disease-modifying treatments for early and advanced multiple sclerosis: a new treatment paradigm.

    Giovannoni, Gavin

    2018-06-01

    The treatment of multiple sclerosis is evolving rapidly with 11 classes of disease-modifying therapies (DMTs). This article provides an overview of a new classification system for DMTs and treatment paradigm for using these DMTs effectively and safely. A summary of research into the use of more active approaches to early and effective treatment of multiple sclerosis with defined treatment targets of no evident disease activity (NEDA). New insights are discussed that is allowing the field to begin to tackle more advanced multiple sclerosis, including people with multiple sclerosis using wheelchairs. However, the need to modify expectations of what can be achieved in more advanced multiple sclerosis are discussed; in particular, the focus on neuronal systems with reserve capacity, for example, upper limb, bulbar and visual function. The review describes a new more active way of managing multiple sclerosis and concludes with a call to action in solving the problem of slow adoption of innovations and the global problem of untreated, or undertreated, multiple sclerosis.

  5. Potential disease agents in domestic goats and relevance to bighorn sheep (Ovis canadensis) management.

    Drew, Mark L; Weiser, Glen C

    2017-01-01

    Domestic goats are raised for meat, milk and hair production, in herds for rangeland weed control, and as pack animals. Domestic sheep, goats and wild bighorn sheep are all susceptible to a multifactorial pneumonia. We sampled 43 herd goats from 7 herds and 48 pack goats from 11 herds for viral and bacterial serology, parasitology, and Pasteurellaceae microbiology. The goats in this study were in generally good health, although most goats did harbor various pathogens and parasites including several bacteria, specifically Pasteurellaceae, which have been associated with pneumonia in free-ranging bighorn sheep. It is not known if domestic goats can transmit the Pasteurellaceae or other pathogens found in this study readily to wild bighorn sheep. However, due the possibility of transmission, domestic goats in areas in or near bighorn sheep habitat should be managed to minimize the risk of spreading disease agents to bighorn sheep.

  6. Potential disease agents in domestic goats and relevance to bighorn sheep (Ovis canadensis management.

    Mark L Drew

    Full Text Available Domestic goats are raised for meat, milk and hair production, in herds for rangeland weed control, and as pack animals. Domestic sheep, goats and wild bighorn sheep are all susceptible to a multifactorial pneumonia. We sampled 43 herd goats from 7 herds and 48 pack goats from 11 herds for viral and bacterial serology, parasitology, and Pasteurellaceae microbiology. The goats in this study were in generally good health, although most goats did harbor various pathogens and parasites including several bacteria, specifically Pasteurellaceae, which have been associated with pneumonia in free-ranging bighorn sheep. It is not known if domestic goats can transmit the Pasteurellaceae or other pathogens found in this study readily to wild bighorn sheep. However, due the possibility of transmission, domestic goats in areas in or near bighorn sheep habitat should be managed to minimize the risk of spreading disease agents to bighorn sheep.

  7. Potential disease agents in domestic goats and relevance to bighorn sheep (Ovis canadensis) management

    Weiser, Glen C.

    2017-01-01

    Domestic goats are raised for meat, milk and hair production, in herds for rangeland weed control, and as pack animals. Domestic sheep, goats and wild bighorn sheep are all susceptible to a multifactorial pneumonia. We sampled 43 herd goats from 7 herds and 48 pack goats from 11 herds for viral and bacterial serology, parasitology, and Pasteurellaceae microbiology. The goats in this study were in generally good health, although most goats did harbor various pathogens and parasites including several bacteria, specifically Pasteurellaceae, which have been associated with pneumonia in free-ranging bighorn sheep. It is not known if domestic goats can transmit the Pasteurellaceae or other pathogens found in this study readily to wild bighorn sheep. However, due the possibility of transmission, domestic goats in areas in or near bighorn sheep habitat should be managed to minimize the risk of spreading disease agents to bighorn sheep. PMID:28282407

  8. Microbiome and metabolome modifying effects of several cardiovascular disease interventions in apo-E-/- mice.

    Ryan, Paul M; London, Lis E E; Bjorndahl, Trent C; Mandal, Rupasri; Murphy, Kiera; Fitzgerald, Gerald F; Shanahan, Fergus; Ross, R Paul; Wishart, David S; Caplice, Noel M; Stanton, Catherine

    2017-03-13

    There is strong evidence indicating that gut microbiota have the potential to modify, or be modified by the drugs and nutritional interventions that we rely upon. This study aims to characterize the compositional and functional effects of several nutritional, neutraceutical, and pharmaceutical cardiovascular disease interventions on the gut microbiome, through metagenomic and metabolomic approaches. Apolipoprotein-E-deficient mice were fed for 24 weeks either high-fat/cholesterol diet alone (control, HFC) or high-fat/cholesterol in conjunction with one of three dietary interventions, as follows: plant sterol ester (PSE), oat β-glucan (OBG) and bile salt hydrolase-active Lactobacillus reuteri APC 2587 (BSH), or the drug atorvastatin (STAT). The gut microbiome composition was then investigated, in addition to the host fecal and serum metabolome. We observed major shifts in the composition of the gut microbiome of PSE mice, while OBG and BSH mice displayed more modest fluctuations, and STAT showed relatively few alterations. Interestingly, these compositional effects imparted by PSE were coupled with an increase in acetate and reduction in isovalerate (p metabolome, including alterations in several acylcarnitines previously associated with a state of metabolic dysfunction (p < 0.05). We observed functional alterations in microbial and host-derived metabolites, which may have important implications for systemic metabolic health, suggesting that cardiovascular disease interventions may have a significant impact on the microbiome composition and functionality. This study indicates that the gut microbiome-modifying effects of novel therapeutics should be considered, in addition to the direct host effects.

  9. A radiobiological approach to cancer treatment. Possible chemical and physical agents modifying radiosensitivity in comparison with high LET radiations

    Sugahara, T.

    1982-01-01

    Biological characteristics of high LET radiations are summarized to be low oxygen enhancement ratio, high RBE, low repair and low cell cycle dependency of radiosensitivity. Various chemical modifiers of radiosensitivity and radiological effect of hyperthermia are classified into these four properties. It is evident that we have now various means to mimic high LET radiations as far as biological response is concerned though some of them are still in experimental stage. Among them, the means to cope with hypoxia and repair which are assumed to be the most important causes of radioresistance of human tumors are discussed in some detail. It is expected that through the present seminar we would have consensus to concentrate our effort of development for new modifying means available and useful in developing countries. (author)

  10. Multifunctional PEG modified DOX loaded mesoporous silica nanoparticle@CuS nanohybrids as photo-thermal agent and thermal-triggered drug release vehicle for hepatocellular carcinoma treatment

    Wu, Lingjie; Wu, Ming; Zeng, Yongyi; Zhang, Da; Zheng, Aixian; Liu, Xiaolong; Liu, Jingfeng

    2015-01-01

    The combination of a multi-therapeutic mode with a controlled fashion is a key improvement in nanomedicine. Here, we synthesized polyethylene glycol (PEG)-modified doxorubicin (DOX)-loaded mesoporous silica nanoparticle (MSN) @CuS nanohybrids as efficient drug delivery carriers, combined with photothermal therapy and chemotherapy to enhance the therapeutic efficacy on hepatocellular carcinoma (HCC). The physical properties of the nanohybrids were characterized by transmission electron microscopy (TEM), N2 adsorption and desorption experiments and by the Vis-NIR absorption spectra. The results showed that the doxorubicin could be stored in the inner pores of mesoporous silica nanoparticles; the CuS nanoparticles, which are coated on the surface of a mesoporous silica nanoparticle, could serve as efficient photothermal therapy (PTT) agents; the loaded drug release could be easily triggered by NIR irradiation. The combination of the PTT treatment with controlled chemotherapy could further enhance the cancer ablation ability compared to any of the single approaches alone. Hence, the reported PEG-modified DOX-loaded mesoporous silica nanoparticle@CuS nanohybrids might be very promising therapeutic agents for HCC treatment.

  11. Seaweeds as Preventive Agents for Cardiovascular Diseases: From Nutrients to Functional Foods

    Susana M. Cardoso

    2015-11-01

    Full Text Available Being naturally enriched in key nutrients and in various health-promoting compounds, seaweeds represent promising candidates for the design of functional foods. Soluble dietary fibers, peptides, phlorotannins, lipids and minerals are macroalgae’s major compounds that can hold potential in high-value food products derived from macroalgae, including those directed to the cardiovascular-health promotion. This manuscript revises available reported data focusing the role of diet supplementation of macroalgae, or extracts enriched in bioactive compounds from macroalgae origin, in targeting modifiable markers of cardiovascular diseases (CVDs, like dyslipidemia, oxidative stress, vascular inflammation, hypertension, hypercoagulability and activation of the sympathetic and renin-angiotensin systems, among others. At last, the review also describes several products that have been formulated with the use of whole macroalgae or extracts, along with their claimed cardiovascular-associated benefits.

  12. Construction of multi-agent mobile robots control system in the problem of persecution with using a modified reinforcement learning method based on neural networks

    Patkin, M. L.; Rogachev, G. N.

    2018-02-01

    A method for constructing a multi-agent control system for mobile robots based on training with reinforcement using deep neural networks is considered. Synthesis of the management system is proposed to be carried out with reinforcement training and the modified Actor-Critic method, in which the Actor module is divided into Action Actor and Communication Actor in order to simultaneously manage mobile robots and communicate with partners. Communication is carried out by sending partners at each step a vector of real numbers that are added to the observation vector and affect the behaviour. Functions of Actors and Critic are approximated by deep neural networks. The Critics value function is trained by using the TD-error method and the Actor’s function by using DDPG. The Communication Actor’s neural network is trained through gradients received from partner agents. An environment in which a cooperative multi-agent interaction is present was developed, computer simulation of the application of this method in the control problem of two robots pursuing two goals was carried out.

  13. Disease modifying therapies in type 1 diabetes: Where have we been, and where are we going?

    Lord, Sandra; Greenbaum, Carla J

    2015-08-01

    With more than four decades of clinical research and 25 years of clinical trials, much is known about the natural history of T1D before and after clinical diagnosis. We know that autoimmunity occurs early in life, that islet autoimmunity inevitably leads to clinically overt disease, and that some immune therapies can alter the disease course. In the future, we will likely conduct trials to more deeply explore mechanisms of disease and response to therapy, employ combinations of agents including those aimed at supporting beta cells, consider the use of chronic, intermittent therapy, focus studies on preventing progression from islet autoimmunity, and consider the potential benefits of studying children independently from adults. Much of this work will depend upon clinical trial networks such as Diabetes TrialNet. Such networks not only have the expertise to conduct studies but their sharing of data and samples also allows for discovery work by multiple investigators, laying the groundwork for the future. Working with patients, families, funders and industry, such collaborative networks can accelerate the translation of science to clinical practice to improve the lives of those living with T1D. Copyright © 2015 Elsevier Ltd. All rights reserved.

  14. Selection and Characterization of Endophytic Bacteria as Biocontrol Agents of Tomato Bacterial Wilt Disease

    ABDJAD ASIH NAWANGSIH

    2011-06-01

    Full Text Available Biological control of bacterial wilt pathogen (Ralstonia solanacearum of tomato using endophytic bacteria is one of the alternative control methods to support sustainable agriculture. This study was conducted to select and characterize endophytic bacteria isolated from healthy tomato stems and to test their ability to promote plant growth and suppress bacterial wilt disease. Among 49 isolates successfully isolated, 41 were non-plant pathogenic. Green house test on six selected isolates based on antagonistic effect on R. solanacearum or ability to suppress R. solanacearum population in dual culture assays obtained BC4 and BL10 isolates as promising biocontrol agents. At six weeks after transplanting, plants treated with BC4 isolate showed significantly lower disease incidence (33% than that of control (83%. Plants height was not significantly affected by endophytic bacterial treatments. Based on 16S rRNA sequence, BC4 isolate had 97% similarity with Staphylococcus epidermidis (accession number EU834240.1, while isolate BL10 had 98% similarity with Bacillus amyloliquefaciens strain JK-SD002 (accession number AB547229.1.

  15. Synthesis of Superparamagnetic Iron Oxide Nanoparticles Modified with MPEG-PEI via Photochemistry as New MRI Contrast Agent

    Yancong Zhang

    2015-01-01

    Full Text Available Novel method for synthesis of superparamagnetic iron oxide nanoparticles (SPIONs coated with polyethylenimine (PEI and modified with poly(ethylene glycol methyl ether (MPEG, MPEG-PEI-SPIONs, was developed. PEI-SPIONs were successfully prepared in aqueous system via photochemistry, and their surface was modified with poly(ethylene glycol methyl ether (MPEG. The so-obtained MPEG-PEI-SPIONs had a uniform hydrodynamic particle size of 34 nm. The successful coating of MPEG-PEI on the SPIONs was ascertained from FT-IR analysis, and the PEI and MPEG fractions in MPEG-PEI-SPIONs were calculated to account for 31% and 12%, respectively. Magnetic measurement revealed that the saturated magnetization of MPEG-PEI-SPIONs reached 46 emu/g and the nanoparticles showed the characteristic of being superparamagnetic. The stability experiment revealed that the MPEG-PEI modification improved the nanoparticles stability greatly. T2 relaxation measurements showed that MPEG-PEI-SPIONs show similar R2 value to the PEI-SPIONs. The T2-weighted magnetic resonance imaging (MRI of MPEG-PEI-SPIONs showed that the magnetic resonance signal was enhanced significantly with increasing nanoparticle concentration in water. These results indicated that the MPEG-PEI-SPIONs had great potential for application in MRI.

  16. Biomarker-driven phenotyping in Parkinson disease: a translational missing link in disease-modifying clinical trials

    Espay, Alberto J.; Schwarzschild, Michael A.; Tanner, Caroline M.; Fernandez, Hubert H; Simon, David K.; Leverenz, James B.; Merola, Aristide; Chen-Plotkin, Alice; Brundin, Patrik; Kauffman, Marcelo A.; Erro, Roberto; Kieburtz, Karl; Woo, Daniel; Macklin, Eric A.; Standaert, David G.; Lang, Anthony E.

    2016-01-01

    Past clinical trials of putative neuroprotective therapies have targeted Parkinson disease (PD) as a single pathogenic disease entity. From an Oslerian clinico-pathologic perspective, the wide complexity of PD converges into Lewy bodies and justifies a reductionist approach to PD: a single-mechanism therapy can affect most of those sharing the classic pathologic hallmark. From a systems-biology perspective, PD is a group of disorders that, while related by sharing the feature of nigral dopamine-neuron degeneration, exhibit unique genetic, biological and molecular abnormalities, which probably respond differentially to a given therapeutic approach, particularly for strategies aimed at neuroprotection. Under this model, only biomarker-defined, homogenous subtypes of PD are likely to respond optimally to therapies proven to affect the biological processes within each subtype. Therefore, we suggest that precision medicine applied to PD requires a reevaluation of the biomarker-discovery effort. This effort is currently centered on correlating biological measures to clinical features of PD and on identifying factors that predict whether various prodromal states will convert into the classical movement disorder. We suggest, instead, that subtyping of PD requires the reverse view, where abnormal biological signals (i.e., biomarkers) rather than clinical definitions are used to define disease phenotypes. Successful development of disease-modifying strategies will depend on how relevant the specific biological processes addressed by an intervention are to the pathogenetic mechanisms in the subgroup of targeted patients. This precision-medicine approach will likely yield smaller but well-defined subsets of PD amenable to successful neuroprotection. PMID:28233927

  17. A conceptual framework for managing modifiable risk factors for cardiovascular diseases in Fiji.

    Witter, Trevor; Poudevigne, Melanie; Lambrick, Danielle M; Faulkner, James; Lucero, Adam A; Page, Rachel; Perry, Lane G; Tarrant, Michael A; Stoner, Lee

    2015-03-01

    The current review will look at modifiable lifestyle (physical inactivity, poor nutrition, risky alcohol behavior and cigarette smoking) and cardio-metabolic (obesity, diabetes mellitus, high cholesterol and high blood pressure) cardiovascular disease (CVD) risk factors among Indigenous-Fijian and Indo-Fijian subgroups. A framework for monitoring and managing these risk factors will be presented. National health surveys were identified where available. Electronic databases identified sources for filling missing data. The most relevant data were identified, organized and synthesized. Compared to Indo-Fijians, Indigenous-Fijians have higher rates of obesity (17% vs 11%) and hypertension (21% vs 16%), but lower rates of diabetes mellitus (12% vs 21%) and high cholesterol (33% vs 39%). Indigenous-Fijians report higher rates of prescribed physical activity (25% vs 21%), but poorer recommended vegetable intake (48% vs 56%), greater risky alcohol behavior (17% vs 15%) and a much greater prevalence of cigarette smoking (45% vs 24%). Both Indigenous-Fijians and Indo-Fijians report a low prevalence of recommended fruit intake (17% vs 15%). Fiji is progressing through demographic and epidemiological transitions, including a decline in infectious diseases and improved life expectancy. However, in concert with other developing nations, 'modernization' is accompanied by increased mortality from non-communicable diseases, with CVD being the most prevalent. This transition has been associated with changes to socio-cultural aspects of Fiji, including poor lifestyle choices that may contribute to a cluster of cardio-metabolic conditions which precede CVD. © Royal Society for Public Health 2013.

  18. Modified Hemocorrection in the Complex Treatment of Patients with Pyoinflammatory Lung Diseases

    V. V. Gavrikov

    2007-01-01

    Full Text Available Objective: To evaluate the efficiency of extracorporeal hemocorrection used in the complex therapy in patients with a pyoinflammatory process in the lung.Materials and methods: 62 patients, including 22 patients with lung abscess who underwent routine plasmapheresis and 40 patients with varying pyoinflammatory lung diseases who received modified hemocorrection — plasma exchange combined with laser extracorporeally washed-off cytomass irradiation, were examined and treated. The severity of their general condition was assessed by the SAPS scale and the severity of intoxication was evaluated by the content of low and medium-molecular weight substances (LMMWSs. The hemostatic system was studied by standardized studies.Results. Routine plasmapheresis was established to produce no impact on platelet functional activity within the first 24 hours and, three days later, promoted the progression of disseminated intravascular coagulation. A combination of plasma exchange and laser extracorporeally washed-off cytomass irradiation in patients with pyoinflam-matory lung diseases was attended by a lower blood coagulative activity and plasmin stabilization with attenuated throm-binemia. The plasma and erythrocytic levels of LMMWSs decreased and their urinary concentrations increased, which is indicative of the body’s detoxification block disorders irrespective of the severity of the disease.Conclusion. It is expedient to apply the plasma-exchanging technique in combination with laser extracorporeally washed-off cytomass irradiation to patients with the uncomplicated and complicated course of pulmonary pyoinflammatory processes without the signs of multiple organ dysfunction on admission to a specialized hospital. 

  19. [Application of Ischemia Modified Albumin for Acute Ischemic Heart Disease in Forensic Science].

    Wang, P; Zhu, Z L; Zhu, N; Yu, H; Yue, Q; Wang, X L; Feng, C M; Wang, C L; Zhang, G H

    2017-10-01

    To explore the application value and forensic significance of ischemia modified albumin (IMA) in pericardial fluid to diagnose sudden cardiac death. IMA level in pericardial fluid was detected in acute ischemic heart disease group ( n =36), acute myocardial infarction group ( n =6), cardiomyopathy group ( n =4) and control group ( n =15) by albumin cobalt binding method. The levels of IMA were compared among these groups. The best cut-off IMA value was estimated and the sensitivity and specificity of acute myocardial ischemia group was distinguished from control group by receiver operating characteristics (ROC) curve. The IMA level in acute ischemic heart disease group was significantly higher than that of control group ( P 0.05). The cut-off value for the identification of acute myocardial ischemia which obtained by ROC analysis was 40.65 U/mL. And the sensitivity and specificity for distinguishing acute ischemia cardiac disease was 60.0% and 80.5%, respectively. The IMA value in pericardial fluid can be a reference marker for the diagnosis of acute myocardial ischemia, which also can provide objective basis for the forensic identification of sudden cardiac death. Copyright© by the Editorial Department of Journal of Forensic Medicine

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

    Kumar, Prashanth Ashok; Subramanian, Kavitha

    2016-03-01

    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. 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. 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. 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 CLD compared to control group (0.0714 ± 0.0283) with a p-value of 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.

  1. Modifiable risk factors for Alzheimer disease and subjective memory impairment across age groups.

    Stephen T Chen

    Full Text Available INTRODUCTION: Previous research has identified modifiable risk factors for Alzheimer's disease (AD in older adults. Research is limited on the potential link between these risk factors and subjective memory impairment (SMI, which may precede AD and other dementias. Examination of these potential relationships may help identify those at risk for AD at a stage when interventions may delay or prevent further memory problems. The objective of this study was to determine whether risk factors for AD are associated with SMI among different age groups. METHOD: Trained interviewers conducted daily telephone surveys (Gallup-Healthways of a representative community sample of 18,614 U.S. respondents, including 4,425 younger (age 18 to 39 years, 6,365 middle-aged (40 to 59 years, and 7,824 older (60 to 99 years adults. The surveyors collected data on demographics, lifestyles, and medical information. Less education, smoking, hypertension, diabetes, less exercise, obesity and depression, and interactions among them, were examined for associations with SMI. Weighted logistic regressions and chi-square tests were used to calculate odds ratios and confidence intervals for SMI with each risk factor and pairwise interactions across age groups. RESULTS: Depression, less education, less exercise, and hypertension were significantly associated with SMI in all three age groups. Several interactions between risk factors were significant in younger and middle-aged adults and influenced their associations with SMI. Frequency of SMI increased with age and number of risk factors. Odds of having SMI increased significantly with just having one risk factor. CONCLUSIONS: These results indicate that modifiable risk factors for AD are also associated with SMI, suggesting that these relationships occur in a broad range of ages and may be targeted to mitigate further memory problems. Whether modifying these risk factors reduces SMI and the eventual incidence of AD and other

  2. Modifiable risk factors for Alzheimer disease and subjective memory impairment across age groups.

    Chen, Stephen T; Siddarth, Prabha; Ercoli, Linda M; Merrill, David A; Torres-Gil, Fernando; Small, Gary W

    2014-01-01

    Previous research has identified modifiable risk factors for Alzheimer's disease (AD) in older adults. Research is limited on the potential link between these risk factors and subjective memory impairment (SMI), which may precede AD and other dementias. Examination of these potential relationships may help identify those at risk for AD at a stage when interventions may delay or prevent further memory problems. The objective of this study was to determine whether risk factors for AD are associated with SMI among different age groups. Trained interviewers conducted daily telephone surveys (Gallup-Healthways) of a representative community sample of 18,614 U.S. respondents, including 4,425 younger (age 18 to 39 years), 6,365 middle-aged (40 to 59 years), and 7,824 older (60 to 99 years) adults. The surveyors collected data on demographics, lifestyles, and medical information. Less education, smoking, hypertension, diabetes, less exercise, obesity and depression, and interactions among them, were examined for associations with SMI. Weighted logistic regressions and chi-square tests were used to calculate odds ratios and confidence intervals for SMI with each risk factor and pairwise interactions across age groups. Depression, less education, less exercise, and hypertension were significantly associated with SMI in all three age groups. Several interactions between risk factors were significant in younger and middle-aged adults and influenced their associations with SMI. Frequency of SMI increased with age and number of risk factors. Odds of having SMI increased significantly with just having one risk factor. These results indicate that modifiable risk factors for AD are also associated with SMI, suggesting that these relationships occur in a broad range of ages and may be targeted to mitigate further memory problems. Whether modifying these risk factors reduces SMI and the eventual incidence of AD and other dementias later in life remains to be determined.

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

    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.

  4. Development of Ocular Delivery System for Glaucoma Therapy Using Natural Hydrogel as Film Forming Agent and Release Modifier.

    Kulkarni, Giriraj T; Sethi, Nitin; Awasthi, Rajendra; Pawar, Vivek Kumar; Pahuja, Vineet

    2016-01-01

    Glaucoma is characterized by increased intraocular pressure, which results in damage to the optic nerve. The existing therapy with conventional eye drops is inefficient due to nasolachrymal drainage, resulting in a reduced corneal residence of the drug. The objective was to develop controlled-release ocular films of timolol maleate using natural hydrogel from Tamarindus indica seeds as a sustaining and film-forming agent, to overcome the problems associated with eye drops. The hydrogel was isolated using hot aqueous extraction followed by precipitation with ethanol. Six batches of ocular films were prepared and evaluated for drug content, weight variation, thickness, diameter and in vitro release profile. The ideal batch of the films was subjected to stability, pharmacodynamic and ocular safety studies. The yield of the hydrogel was 58.29%. The thickness of the ocular films was in the range of 0.17 to 0.25 mm and the weight of the films was found to increase with the increase in polymer content. The drug release from the films was found to be controlled over a period of 8 h. The films were found to be stable and were able to reduce the intraocular pressure for 24 h in a more efficient manner than the eye drops. The films were found to be practically non-irritating to the eye. It can be concluded that the hydrogel from tamarind seeds can be used as a film-forming and release-controlling agent for the development of an ocular drug delivery system for the effective therapy of glaucoma.

  5. Infections in patients with multiple sclerosis: Implications for disease-modifying therapy.

    Celius, E G

    2017-11-01

    Patients with multiple sclerosis have an increased risk of infections compared to the general population. The increased risk has been described for decades and is not alone attributed to the use of disease-modifying drugs, but secondary to the disability. The introduction of more potent immunomodulatory drugs may cause an additional challenge, and depending on the mechanism of action, a treatment-induced increased risk of bacterial, viral, fungal or parasitic infections is observed. The choice of treatment in the individual patient with infections and multiple sclerosis must be guided by the drugs' specific mechanism of action, the drug-specific risk of infection and comorbidities. Increased monitoring and follow-up through treatment registries is warranted to increase our understanding and thereby improve management. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  6. Patients’ satisfaction with and views about treatment with disease-modifying drugs in multiple sclerosis

    Caroline Vieira Spessotto

    2016-08-01

    Full Text Available ABSTRACT Objective The treatment of multiple sclerosis (MS with disease-modifying-drugs (DMDs is evolving and new drugs are reaching the market. Efficacy and safety aspects of the drugs are crucial, but the patients’ satisfaction with the treatment must be taken into consideration. Methods Individual interview with patients with MS regarding their satisfaction and points of view on the treatment with DMDs. Results One hundred and twenty eight patients attending specialized MS Units in five different cities were interviewed. Over 80% of patients were very satisfied with the drugs in use regarding convenience and perceived benefits. The only aspect scoring lesser values was tolerability. Conclusion Parameters for improving treatment in MS must include efficacy, safety, and patient satisfaction with the given DMD.

  7. [Validation of the Russian version of the modified Addenbrooke's cognitive examination for Alzheimer's disease diagnosis].

    Levin, O S; Lavrov, A Yu; Lyashenko, Е А; Vasenina, E E; Trusova, N A; Datieva, V K; Makotrova, T A; Pilipenko, A Yu

    2015-01-01

    To evaluate the validity of the Russian version of the modified Addenbrooke's cognitive examination (ACE-m) for Alzheimer's disease (AD) diagnosis. ACE-m and MMSE, as a comparison scale, were administered to 78 patients including 49 patients with AD and 29 healthy people. ACE-m demonstrated the high validity in the diagnosis of dementia in AD. Cronbach's alpha was 0.89. ACE-m is a brief and simple in use test that measures a wide spectrum of cognitive functions, gives a general impression about cognitive deficit and diagnoses dementia in AD with the greater validity compared to MMSE. This scale is useful not only in diagnosis of AD but also in differentiation with other causes of dementia.

  8. Multi-agent systems in epidemiology: a first step for computational biology in the study of vector-borne disease transmission

    Guégan Jean-François

    2008-10-01

    Full Text Available Abstract Background Computational biology is often associated with genetic or genomic studies only. However, thanks to the increase of computational resources, computational models are appreciated as useful tools in many other scientific fields. Such modeling systems are particularly relevant for the study of complex systems, like the epidemiology of emerging infectious diseases. So far, mathematical models remain the main tool for the epidemiological and ecological analysis of infectious diseases, with SIR models could be seen as an implicit standard in epidemiology. Unfortunately, these models are based on differential equations and, therefore, can become very rapidly unmanageable due to the too many parameters which need to be taken into consideration. For instance, in the case of zoonotic and vector-borne diseases in wildlife many different potential host species could be involved in the life-cycle of disease transmission, and SIR models might not be the most suitable tool to truly capture the overall disease circulation within that environment. This limitation underlines the necessity to develop a standard spatial model that can cope with the transmission of disease in realistic ecosystems. Results Computational biology may prove to be flexible enough to take into account the natural complexity observed in both natural and man-made ecosystems. In this paper, we propose a new computational model to study the transmission of infectious diseases in a spatially explicit context. We developed a multi-agent system model for vector-borne disease transmission in a realistic spatial environment. Conclusion Here we describe in detail the general behavior of this model that we hope will become a standard reference for the study of vector-borne disease transmission in wildlife. To conclude, we show how this simple model could be easily adapted and modified to be used as a common framework for further research developments in this field.

  9. Non-malignant disease mortality in meat workers: a model for studying the role of zoonotic transmissible agents in non-malignant chronic diseases in humans.

    Johnson, E S; Zhou, Y; Sall, M; Faramawi, M El; Shah, N; Christopher, A; Lewis, N

    2007-12-01

    Current research efforts have mainly concentrated on evaluating the role of substances present in animal food in the aetiology of chronic diseases in humans, with relatively little attention given to evaluating the role of transmissible agents that are also present. Meat workers are exposed to a variety of transmissible agents present in food animals and their products. This study investigates mortality from non-malignant diseases in workers with these exposures. A cohort mortality study was conducted between 1949 and 1989, of 8520 meat workers in a union in Baltimore, Maryland, who worked in manufacturing plants where animals were killed or processed, and who had high exposures to transmissible agents. Mortality in meat workers was compared with that in a control group of 6081 workers in the same union, and also with the US general population. Risk was estimated by proportional mortality and standardised mortality ratios (SMRs) and relative SMR. A clear excess of mortality from septicaemia, subarachnoid haemorrhage, chronic nephritis, acute and subacute endocarditis, functional diseases of the heart, and decreased risk of mortality from pre-cerebral, cerebral artery stenosis were observed in meat workers when compared to the control group or to the US general population. The authors hypothesise that zoonotic transmissible agents present in food animals and their products may be responsible for the occurrence of some cases of circulatory, neurological and other diseases in meat workers, and possibly in the general population exposed to these agents.

  10. Impact of gadolinium-based contrast agent in the assessment of Crohn's disease activity: Is contrast agent injection necessary?

    Quaia, Emilio; Sozzi, Michele; Gennari, Antonio Giulio; Pontello, Michele; Angileri, Roberta; Cova, Maria Assunta

    2016-03-01

    To determine whether magnetic resonance enterography (MRE) performed without intravenous contrast injection is diagnostically noninferior to conventional contrast-enhanced MRE (CE-MRE) in patients with Crohn's disease (CD). This was an Institutional Review Board (IRB)-approved retrospective study. Ninety-six patients (52 male and 44 female; 47.18 years ± 13.6) with a diagnosis of CD underwent MRE at 1.5T including T2 -weighted single-shot turbo-spin-echo, T2 -weighted spectral fat presaturation with inversion recovery (SPAIR), T1 -weighted balanced fast-field-echo MR sequences, and CE-MRE consisting in T1 -weighted breath-hold THRIVE 3D MRI sequences after administration of gadobenate dimeglumine (0.2 mL/kg of body weight). Unenhanced MRE, CE-MRE, and unenhanced MRE plus CE-MRE were reviewed in separate sessions with blinding by two readers in consensus, and subsequently by two other readers independently considering a subgroup of 20 patients. Crohn's Disease Endoscopic Index of Severity (CDEIS) and/or histologic analysis of the surgical specimen were considered as reference standards for the assessment of inflammatory activity. Patients revealed prevalently active (n = 55 patients) or quiescent CD (n = 41 patients). The agreement between unenhanced MRE vs. CE-MRE in interpreting active bowel inflammation was 96% (123/128 bowel segments; one-sided 95% confidence interval [CI], >94.4%). Unenhanced MRE vs. CE-MRE vs. unenhanced MRE plus CE-MRE revealed a diagnostic accuracy of 93% [90/96] vs. 92% [88/96] vs. 97% [93/96] (P > 0.05) in the diagnosis of active CD. Interreader agreement was very good for all variables (κ value = 0.8-0.9) except for the measurement of the length of disease (κ value = 0.45). Unenhanced MRE was noninferior to CE-MRE in diagnosing active inflammation in patients with CD. © 2015 Wiley Periodicals, Inc.

  11. Early cost-utility analysis of general and cerebrospinal fluid-specific Alzheimer's disease biomarkers for hypothetical disease-modifying treatment decision in mild cognitive impairment

    Handels, Ron L. H.; Joore, Manuela A.; Tran-Duy, An; Wimo, Anders; Wolfs, Claire A. G.; Verhey, Frans R. J.; Severens, Johan L.

    Introduction: The study aimed to determine the room for improvement of a perfect cerebrospinal fluid (CSF) biomarker and the societal incremental net monetary benefit of CSF in subjects with mild cognitive impairment (MCI) assuming a hypothetical disease-modifying Alzheimer's disease (AD) treatment.

  12. Cognitive enhancers (Nootropics). Part 3: drugs interacting with targets other than receptors or enzymes. Disease-modifying drugs. Update 2014.

    Froestl, Wolfgang; Pfeifer, Andrea; Muhs, Andreas

    2014-01-01

    Scientists working in the field of Alzheimer's disease and, in particular, cognitive enhancers, are very productive. The review "Drugs interacting with Targets other than Receptors or Enzymes. Disease-modifying Drugs" was accepted in October 2012. In the last 20 months, new targets for the potential treatment of Alzheimer's disease were identified. Enormous progress was realized in the pharmacological characterization of natural products with cognitive enhancing properties. This review covers the evolution of research in this field through May 2014.

  13. Zoonotic and vector borne agents causing disease in adult patients hospitalized due to fever of unknown origin in Thailand

    Soawapak Hinjoy

    2017-10-01

    Full Text Available Objective: To determine the etiologic agents of fever of unknown origin among populations in agricultural communities and to assess the possible risk factors for zoonotic infections. Methods: Hospitalized patients with fever of unknown origin under physician care were asked to participate and provide blood samples for laboratory tests and screening for endemic diseases at the hospitals. Samples were stored at –80 °C until they were tested at Chulalongkorn University to identify additional pathogens. Results: We were able to identify the etiologic agents in 24.6% of the 463 enrolled patients. Zoonotic and vector borne agents were confirmed in 59 cases (12.7%. Dengue virus (7.3% was the most frequently detected disease followed by scrub typhus (3.2%. There were two cases of comorbidities of scrub typhus and dengue fever. The other six cases of zoonoses were leptospirosis, melioidosis, and Streptococcus suis infections. Patients with zoonotic/vector borne agents noticed rats in their houses and reported having contact with livestock feces more frequently than those patients without zoonotic/vector borne agents. Conclusions: Dengue virus and scrub typhus were mostly detected in the rainy season. During this specific season, clinicians should raise awareness of those diseases when any patients are admitted to the hospital with fever of an unidentified source.

  14. Clustering of modifiable biobehavioral risk factors for chronic disease in US adults: a latent class analysis.

    Leventhal, Adam M; Huh, Jimi; Dunton, Genevieve F

    2014-11-01

    Examining the co-occurrence patterns of modifiable biobehavioral risk factors for deadly chronic diseases (e.g. cancer, cardiovascular disease, diabetes) can elucidate the etiology of risk factors and guide disease-prevention programming. The aims of this study were to (1) identify latent classes based on the clustering of five key biobehavioral risk factors among US adults who reported at least one risk factor and (2) explore the demographic correlates of the identified latent classes. Participants were respondents of the National Epidemiologic Survey of Alcohol and Related Conditions (2004-2005) with at least one of the following disease risk factors in the past year (N = 22,789), which were also the latent class indicators: (1) alcohol abuse/dependence, (2) drug abuse/dependence, (3) nicotine dependence, (4) obesity, and (5) physical inactivity. Housing sample units were selected to match the US National Census in location and demographic characteristics, with young adults oversampled. Participants were administered surveys by trained interviewers. Five latent classes were yielded: 'obese, active non-substance abusers' (23%); 'nicotine-dependent, active, and non-obese' (19%); 'active, non-obese alcohol abusers' (6%); 'inactive, non-substance abusers' (50%); and 'active, polysubstance abusers' (3.7%). Four classes were characterized by a 100% likelihood of having one risk factor coupled with a low or moderate likelihood of having the other four risk factors. The five classes exhibited unique demographic profiles. Risk factors may cluster together in a non-monotonic fashion, with the majority of the at-risk population of US adults expected to have a high likelihood of endorsing only one of these five risk factors. © Royal Society for Public Health 2013.

  15. PDZD7 is a modifier of retinal disease and a contributor to digenic Usher syndrome

    Ebermann, Inga; Phillips, Jennifer B.; Liebau, Max C.; Koenekoop, Robert K.; Schermer, Bernhard; Lopez, Irma; Schäfer, Ellen; Roux, Anne-Francoise; Dafinger, Claudia; Bernd, Antje; Zrenner, Eberhart; Claustres, Mireille; Blanco, Bernardo; Nürnberg, Gudrun; Nürnberg, Peter; Ruland, Rebecca; Westerfield, Monte; Benzing, Thomas; Bolz, Hanno J.

    2010-01-01

    Usher syndrome is a genetically heterogeneous recessive disease characterized by hearing loss and retinitis pigmentosa (RP). It frequently presents with unexplained, often intrafamilial, variability of the visual phenotype. Although 9 genes have been linked with Usher syndrome, many patients do not have mutations in any of these genes, suggesting that there are still unidentified genes involved in the syndrome. Here, we have determined that mutations in PDZ domain–containing 7 (PDZD7), which encodes a homolog of proteins mutated in Usher syndrome subtype 1C (USH1C) and USH2D, contribute to Usher syndrome. Mutations in PDZD7 were identified only in patients with mutations in other known Usher genes. In a set of sisters, each with a homozygous mutation in USH2A, a frame-shift mutation in PDZD7 was present in the sister with more severe RP and earlier disease onset. Further, heterozygous PDZD7 mutations were present in patients with truncating mutations in USH2A, G protein–coupled receptor 98 (GPR98; also known as USH2C), and an unidentified locus. We validated the human genotypes using zebrafish, and our findings were consistent with digenic inheritance of PDZD7 and GPR98, and with PDZD7 as a retinal disease modifier in patients with USH2A. Pdzd7 knockdown produced an Usher-like phenotype in zebrafish, exacerbated retinal cell death in combination with ush2a or gpr98, and reduced Gpr98 localization in the region of the photoreceptor connecting cilium. Our data challenge the view of Usher syndrome as a traditional Mendelian disorder and support the reclassification of Usher syndrome as an oligogenic disease. PMID:20440071

  16. PDZD7 is a modifier of retinal disease and a contributor to digenic Usher syndrome.

    Ebermann, Inga; Phillips, Jennifer B; Liebau, Max C; Koenekoop, Robert K; Schermer, Bernhard; Lopez, Irma; Schäfer, Ellen; Roux, Anne-Francoise; Dafinger, Claudia; Bernd, Antje; Zrenner, Eberhart; Claustres, Mireille; Blanco, Bernardo; Nürnberg, Gudrun; Nürnberg, Peter; Ruland, Rebecca; Westerfield, Monte; Benzing, Thomas; Bolz, Hanno J

    2010-06-01

    Usher syndrome is a genetically heterogeneous recessive disease characterized by hearing loss and retinitis pigmentosa (RP). It frequently presents with unexplained, often intrafamilial, variability of the visual phenotype. Although 9 genes have been linked with Usher syndrome, many patients do not have mutations in any of these genes, suggesting that there are still unidentified genes involved in the syndrome. Here, we have determined that mutations in PDZ domain-containing 7 (PDZD7), which encodes a homolog of proteins mutated in Usher syndrome subtype 1C (USH1C) and USH2D, contribute to Usher syndrome. Mutations in PDZD7 were identified only in patients with mutations in other known Usher genes. In a set of sisters, each with a homozygous mutation in USH2A, a frame-shift mutation in PDZD7 was present in the sister with more severe RP and earlier disease onset. Further, heterozygous PDZD7 mutations were present in patients with truncating mutations in USH2A, G protein-coupled receptor 98 (GPR98; also known as USH2C), and an unidentified locus. We validated the human genotypes using zebrafish, and our findings were consistent with digenic inheritance of PDZD7 and GPR98, and with PDZD7 as a retinal disease modifier in patients with USH2A. Pdzd7 knockdown produced an Usher-like phenotype in zebrafish, exacerbated retinal cell death in combination with ush2a or gpr98, and reduced Gpr98 localization in the region of the photoreceptor connecting cilium. Our data challenge the view of Usher syndrome as a traditional Mendelian disorder and support the reclassification of Usher syndrome as an oligogenic disease.

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

    Salter, Amber R; Marrie, Ruth Ann; Agashivala, Neetu; Belletti, Daniel A; Kim, Edward; Cutter, Gary R; Cofield, Stacey S; Tyry, Tuula

    2014-01-01

    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. To investigate the reasons patients switch DMTs and identify characteristics associated with the decision to switch. 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. 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%). Participants frequently initiated the discussion regarding changing DMT, although physician recommendations regarding the specific therapy were still weighed highly. Long-term follow-up of these participants will provide valuable information on their disease trajectory, satisfaction with, and effectiveness of their new medication.

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

    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

  19. Poly(vinyl chloride) catheters modified with pH-responsive poly(methacrylic acid) with affinity for antimicrobial agents

    Zuñiga-Zamorano, Ivette; Meléndez-Ortiz, H. Iván; Costoya, Alejandro; Alvarez-Lorenzo, Carmen; Concheiro, Angel; Bucio, Emilio

    2018-01-01

    Radiation-grafting of pH-responsive methacrylic acid (MAA) onto poly(vinyl chloride) (PVC) was carried out by the pre-irradiation method using gamma rays, which demonstrated to be an efficient and fast procedure for obtaining PVC-g-MAA copolymers. The influence of preparation conditions, such as absorbed dose, monomer concentration, reaction time, and reaction temperature on the grafting yield was studied. The grafting of MAA onto PVC catheters was confirmed by means of Fourier transform infrared spectroscopy (FT-IR), thermogravimetry analysis (TGA), and differential scanning calorimetry (DSC). The pH-responsiveness of the grafted copolymers (critical point 8.5) was measured by swelling under cyclic changes in the pH of the medium. Interestingly, PVC-g-MAA showed enhanced capability to immobilize benzalkonium chloride and, particularly, ciprofloxacin and to sustain the release this antimicrobial agent at both acid and alkaline pH. Tests carried out with Escherichia coli, Pseudomonas aeruginosa, and Staphylococcus aureus point out that the developed functionalized catheters may play a role in the prevention/management of urinary tract infections.

  20. Serological studies on the infection of dogs in Ontario with Borrelia burgdorferi, the etiological agent of Lyme disease

    Artsob, Harvey; Barker, Ian K.; Fister, Richard; Sephton, Gregory; Dick, Daryl; Lynch, John A.; Key, Doug

    1993-01-01

    A serological study was undertaken to determine whether dogs in Ontario are being exposed to Borrelia burgdorferi, the etiological agent of Lyme disease. This study consisted of a survey of randomly selected dogs and testing of diagnostic submissions from candidate Lyme disease cases. The survey of 1,095 dogs, bled between January 1988 and August 1989, revealed a total of 65 (5.9%) enzyme-linked immunosorbent assay (ELISA) reactors, of which 22 had immuno-fluorescent antibody assay (IFA) tite...

  1. Concepts, problems and the role of modifying agents in the relationship between recovery of cells' survival ability and mechanisms of repair of radiation lesions

    Orr, J.S.

    1984-01-01

    The two strands of the problem are the shapes and changes with time of cell survival curves on the one hand and the responses of cell constituents to radiation on the other. Evidence of correlations between results of studies of these two types of phenomena under the influence of a wide range of modifying agents is required to establish mechanisms. Recovery may be defined as referring to the whole cell, while repair should be regarded as a process carried out by one substance on another. The degrees of usefulness and possible deficiencies of a multi-hit/target model and a repair model for explaining cell survival curves and cell recovery are compared in a range of circumstances. A fully satisfactory model is not yet available. (author)

  2. Evidence for a close phylogenetic relationship between Melissococcus pluton, the causative agent of European foulbrood disease, and the genus Enterococcus.

    Cai, J; Collins, M D

    1994-04-01

    The 16S rRNA gene sequence of Melissococcus pluton, the causative agent of European foulbrood disease, was determined in order to investigate the phylogenetic relationships between this organism and other low-G + C-content gram-positive bacteria. A comparative sequence analysis revealed that M. pluton is a close phylogenetic relative of the genus Enterococcus.

  3. Does Animal Behavior Underlie Covariation Between Hosts' Exposure to Infectious Agents and Susceptibility to Infection? Implications for Disease Dynamics

    Hawley, Dana M.; Etienne, Rampal S.; Ezenwa, Vanessa O.; Jolles, Anna E.

    2011-01-01

    Animal behavior is unique in influencing both components of the process of transmission of disease: exposure to infectious agents, and susceptibility to infection once exposed. To date, the influence of behavior on exposure versus susceptibility has largely been considered separately. Here, we ask

  4. Disease-modifying effect of anthraquinone prodrug with boswellic acid on collagenase-induced osteoarthritis in Wistar rats.

    Dhaneshwar, Suneela; Dipmala, Patil; Abhay, Harsulkar; Prashant, Bhondave

    2013-08-01

    Diacerein and its active metabolite rhein are promising disease modifying agents for osteoarthritis (OA). Boswellic acid is an active ingredient of Gugglu; a herbal medicine commonly administered in osteoarthritis. Both of them possess excellent anti-inflammatory and anti-arthritic activities. It was thought interesting to conjugate rhein and boswellic acid into a mutual prodrug (DSRB) and evaluate its efficacy on collagenase-induced osteoarthritis in rats wherein the conjugate, rhein, boswellic acid and their physical mixture, were tested based on various parameters. Oral administration of 3.85 mg of rhein, 12.36 mg of boswellic acid and 15.73 mg of DSRB which would release equimolar amounts of rhein and boswellic acid, exhibited significant restoration in rat body weight as compared to the untreated arthritic control group. Increase in knee diameter (mm), due to edema was observed in group injected with collagenase, which reduced significantly with the treatment of conjugate. The hematological parameters (Hb, RBC, WBC and ESR) and biochemical parameters (CRP, SALP, SGOT and SGPT) in the osteoarthritic rats were significantly brought back to normal values on treatment with conjugate. It also showed better anti-ulcer activity than rhein. Further the histopathological studies revealed significant anti-arthritic activity of conjugate when compared with the arthritic control group. In conclusion, the conjugate at the specified dose level of 15.73 mg/kg, p. o. (BID) showed reduction in knee diameter and it could significantly normalize the hematological and biochemical abnormalities in collagenase-induced osteoarthritis in rats. Further the histopathological studies confirmed the additive anti-arthritic effect of DSRB as compared to plain rhein.

  5. The preventive Control of White Root Rot Disease in Small Holder Rubber Plantation Using Botanical, Biological and Chemical Agents

    Joko Prasetyo

    2014-03-01

    Full Text Available The preventive control of white root rot disease in small holder plantation using botanical, biological, and chemical agents. A field and laboratory experiment were conducted from June 2008 to December 2009 in Panumangan, Tulang Bawang - Lampung. The  field experiment was intended to evaluate the effect of  botanical plants (Alpinia galanga, Sansiviera auranthii, and Marantha arundinacea, biological agents (organic matter and Trichoderma spp., and chemical agents (lime and natural sulphur on the incidence of white root rot disease and population of some soil microbes. The laboratory experiment was conducted  to observe the mechanism of botanical agents  in controlling white root rot disease. In the field experiment, the treatments were applied  in the experimental plot with cassava plant infection as the indicator. The variables  examined were the incidence of  white root rot and population of soil microbes. In the laboratory experiment, culture of R. microporus was grown in PDA containing root exudate of the antagonistic plant (botanical agent. The variable examined was colony diameter of R. microporus growing in the PDA plates. The results of the  field experiment  showed that planting of the botanical agents, and application of Trichoderma spp., as well as natural sulphur, decreased the incidence of white root rot disease. The effectiveness of M. arundinacea and Trichoderma spp. was comparable to natural  sulphur. The laboratory experiment showed only root exudate of  A. galanga and  S. auranthii that were significantly inhibit the growth of R. microporus.

  6. D-Glucose as a modifying agent in gelatin/collagen matrix and reservoir nanoparticles for Calendula officinalis delivery.

    Lam, P-L; Kok, S H-L; Bian, Z-X; Lam, K-H; Tang, J C-O; Lee, K K-H; Gambari, R; Chui, C-H

    2014-05-01

    Gelatin/Collagen-based matrix and reservoir nanoparticles require crosslinkers to stabilize the formed nanosuspensions, considering that physical instability is the main challenge of nanoparticulate systems. The use of crosslinkers improves the physical integrity of nanoformulations under the-host environment. Aldehyde-based fixatives, such as formaldehyde and glutaraldehyde, have been widely applied to the crosslinking process of polymeric nanoparticles. However, their potential toxicity towards human beings has been demonstrated in many previous studies. In order to tackle this problem, D-glucose was used during nanoparticle formation to stabilize the gelatin/collagen-based matrix wall and reservoir wall for the deliveries of Calendula officinalis powder and oil, respectively. In addition, therapeutic selectivity between malignant and normal cells could be observed. The C. officinalis powder loaded nanoparticles significantly strengthened the anti-cancer effect towards human breast adenocarcinoma MCF7 cells and human hepatoma SKHep1 cells when compared with the free powder. On the contrary, the nanoparticles did not show significant cytotoxicity towards normal esophageal epithelial NE3 cells and human skin keratinocyte HaCaT cells. On the basis of these evidences, D-glucose modified gelatin/collagen matrix nanoparticles containing C. officinalis powder might be proposed as a safer alternative vehicle for anti-cancer treatments. Copyright © 2014 Elsevier B.V. All rights reserved.

  7. Antioxidant agents for delaying diabetic kidney disease progression: A systematic review and meta-analysis.

    Davide Bolignano

    Full Text Available Oxidative stress is a key player in the genesis and worsening of diabetic kidney disease (DKD. We aimed at collecting all available information on possible benefits of chronic antioxidant supplementations on DKD progression.Systematic review and meta-analysis.Adults with DKD (either secondary to type 1 or 2 diabetes mellitus.Cochrane CENTRAL, Ovid-MEDLINE and PubMed were searched for randomized controlled trials (RCTs or quasi-RCTs without language or follow-up restriction.Any antioxidant supplementation (including but not limited to vitamin A, vitamin C, vitamin E, selenium, zinc, methionine or ubiquinone alone or in combination.Primary outcome was progression to end-stage kidney disease (ESKD. Secondary outcomes were change in albuminuria, proteinuria, serum creatinine and renal function.From 13519 potentially relevant citations retrieved, 15 articles referring to 14 full studies (4345 participants met the inclusion criteria. Antioxidant treatment significantly decreased albuminuria as compared to control (8 studies, 327 participants; SMD: -0.47; 95% CI -0.78, -0.16 but had apparently no tangible effects on renal function (GFR (3 studies, 85 participants; MD -0.12 ml/min/1.73m2; 95% CI -0.06, 0.01. Evidence of benefits on the other outcomes of interest was inconclusive or lacking.Small sample size and limited number of studies. Scarce information available on hard endpoints (ESKD. High heterogeneity among studies with respect to DKD severity, type and duration of antioxidant therapy.In DKD patients, antioxidants may improve early renal damage. Future studies targeting hard endpoints and with longer follow-up and larger sample size are needed to confirm the usefulness of these agents for retarding DKD progression.

  8. Co-feeding transmission facilitates strain coexistence in Borrelia burgdorferi, the Lyme disease agent

    S.L. States

    2017-06-01

    Full Text Available Coexistence of multiple tick-borne pathogens or strains is common in natural hosts and can be facilitated by resource partitioning of the host species, within-host localization, or by different transmission pathways. Most vector-borne pathogens are transmitted horizontally via systemic host infection, but transmission may occur in the absence of systemic infection between two vectors feeding in close proximity, enabling pathogens to minimize competition and escape the host immune response. In a laboratory study, we demonstrated that co-feeding transmission can occur for a rapidly-cleared strain of Borrelia burgdorferi, the Lyme disease agent, between two stages of the tick vector Ixodes scapularis while feeding on their dominant host, Peromyscus leucopus. In contrast, infections rapidly became systemic for the persistently infecting strain. In a field study, we assessed opportunities for co-feeding transmission by measuring co-occurrence of two tick stages on ears of small mammals over two years at multiple sites. Finally, in a modeling study, we assessed the importance of co-feeding on R0, the basic reproductive number. The model indicated that co-feeding increases the fitness of rapidly-cleared strains in regions with synchronous immature tick feeding. Our results are consistent with increased diversity of B. burgdorferi in areas of higher synchrony in immature feeding – such as the midwestern United States. A higher relative proportion of rapidly-cleared strains, which are less human pathogenic, would also explain lower Lyme disease incidence in this region. Finally, if co-feeding transmission also occurs on refractory hosts, it may facilitate the emergence and persistence of new pathogens with a more limited host range.

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

    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.

  10. [Therapeutic Concepts for Treatment of Patients with Non-infectious Uveitis Biologic Disease Modifying Antirheumatic Drugs].

    Walscheid, Karoline; Pleyer, Uwe; Heiligenhaus, Arnd

    2018-04-12

    Biologic disease modifying antirheumatic drugs (bDMARDs) can be highly efficient in the treatment of various non-infectious uveitis entities. Currently, the TNF-α-inhibitor Adalimumab is the only in-label therapeutic option, whereas, all other bDMARDs need to be given as an off-label therapy. bDMARDs are indicated in diseases refractory to conventional synthetic DMARD therapy and/or systemic steroids, or in patients in whom treatment with those is not possible due to side effects. Therapeutic mechanisms currently employed are cytokine-specific (interferons, inhibition of TNF-α or of interleukin [IL]-1-, IL-6- or IL-17-signalling), inhibit T cell costimulation (CTLA-4 fusion protein), or act via depletion of B cells (anti-CD20). All bDMARDs need to be administered parenterally, and therapy is initiated by the treating internal specialist only after interdisciplinary coordination of all treating subspecialties and after exclusion of contraindications. Regular clinical and laboratory monitoring is mandatory for all patients while under bDMARD therapy. Georg Thieme Verlag KG Stuttgart · New York.

  11. Total oxidant status, total antioxidant capacity and ischemia modified albumin levels in children with celiac disease.

    Sayar, Ersin; Özdem, Sebahat; Uzun, Gülbahar; İşlek, Ali; Yılmaz, Aygen; Artan, Reha

    2015-01-01

    In our study, we aimed to investigate ischemia modified albumin (IMA) as an oxidative stress marker, as well as other oxidant and antioxidant markers that have not been evaluated in children with celiac disease. A total of 37 pediatric patients who were diagnosed with celiac disease (CD) and 29 healthy children were enrolled in this prospective study. We evaluated the IMA, total oxidant status, total antioxidant capacity, sulfhydryl, and advanced oxidation protein products in all of the subjects. We also compared the levels at the time of the diagnosis, and following a gluten-free diet (GFD) in the children with CD. While the IMA and the other oxidant marker levels were significantly higher in the patient group compared to the control group, the antioxidant marker levels were found to be significantly lower in the patient group, compared to the control group. We also determined that the tissue transglutaminase IgA showed a highly positive correlation, and that the IMA showed a moderately positive correlation with the Marsh-Oberhuber histopathological stage. Additionally, the IMA and other oxidant marker levels were significantly lower, while the antioxidant marker levels were significantly higher after the GFD, compared to the pre-diet period. We detected that oxidative stress played a role in the pathogenesis of CD, and that this could be evaluated using oxidative stress markers, which would regress after the GFD. We also detected that IMA is a marker that shows a correlation with the histopathological stage, and may be used in the diagnosis.

  12. Fertility, pregnancy and childbirth in patients with multiple sclerosis: impact of disease-modifying drugs.

    Amato, Maria Pia; Portaccio, Emilio

    2015-03-01

    In recent decades, pregnancy-related issues in multiple sclerosis (MS) have received growing interest. MS is more frequent in women than in men and typically starts during child-bearing age. An increasing number of disease-modifying drugs (DMDs) for the treatment of MS are becoming available. Gathering information on their influences on pregnancy-related issues is of crucial importance for the counselling of MS patients. As for the immunomodulatory drugs (interferons and glatiramer acetate), accumulating evidence points to the relative safety of pregnancy exposure in terms of maternal and foetal outcomes. In case of higher clinical disease activity before pregnancy, these drugs could be continued until conception. As for the 'newer' drugs (fingolimod, natalizumab, teriflunomide, dimethyl fumarate and alemtuzumab), the information is more limited. Whereas fingolimod and teriflunomide are likely associated with an increased risk of foetal malformations, the effects of natalizumab, dimethyl fumarate and alemtuzumab still need to be ascertained. This article provides a review of the available information on the use of DMDs during pregnancy, with a specific focus on fertility, foetal development, delivery and breast-feeding.

  13. Design of fuzzy classifier for diabetes disease using Modified Artificial Bee Colony algorithm.

    Beloufa, Fayssal; Chikh, M A

    2013-10-01

    In this study, diagnosis of diabetes disease, which is one of the most important diseases, is conducted with artificial intelligence techniques. We have proposed a novel Artificial Bee Colony (ABC) algorithm in which a mutation operator is added to an Artificial Bee Colony for improving its performance. When the current best solution cannot be updated, a blended crossover operator (BLX-α) of genetic algorithm is applied, in order to enhance the diversity of ABC, without compromising with the solution quality. This modified version of ABC is used as a new tool to create and optimize automatically the membership functions and rules base directly from data. We take the diabetes dataset used in our work from the UCI machine learning repository. The performances of the proposed method are evaluated through classification rate, sensitivity and specificity values using 10-fold cross-validation method. The obtained classification rate of our method is 84.21% and it is very promising when compared with the previous research in the literature for the same problem. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  14. Agent of whirling disease meets orphan worm: phylogenomic analyses firmly place Myxozoa in Cnidaria.

    Maximilian P Nesnidal

    Full Text Available Myxozoa are microscopic obligate endoparasites with complex live cycles. Representatives are Myxobolus cerebralis, the causative agent of whirling disease in salmonids, and the enigmatic "orphan worm" Buddenbrockia plumatellae parasitizing in Bryozoa. Originally, Myxozoa were classified as protists, but later several metazoan characteristics were reported. However, their phylogenetic relationships remained doubtful. Some molecular phylogenetic analyses placed them as sister group to or even within Bilateria, whereas the possession of polar capsules that are similar to nematocysts of Cnidaria and of minicollagen genes suggest a close relationship between Myxozoa and Cnidaria. EST data of Buddenbrockia also indicated a cnidarian origin of Myxozoa, but were not sufficient to reject a closer relationship to bilaterians. Phylogenomic analyses of new genomic sequences of Myxobolus cerebralis firmly place Myxozoa as sister group to Medusozoa within Cnidaria. Based on the new dataset, the alternative hypothesis that Myxozoa form a clade with Bilateria can be rejected using topology tests. Sensitivity analyses indicate that this result is not affected by long branch attraction artifacts or compositional bias.

  15. Biological Evaluation of Double Point Modified Analogues of 1,25-Dihydroxyvitamin D2 as Potential Anti-Leukemic Agents

    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.

  16. Cholesterol as a modifying agent of the neurovascular unit structure and function under physiological and pathological conditions.

    Czuba, Ewelina; Steliga, Aleksandra; Lietzau, Grażyna; Kowiański, Przemysław

    2017-08-01

    The brain, demanding constant level of cholesterol, precisely controls its synthesis and homeostasis. The brain cholesterol pool is almost completely separated from the rest of the body by the functional blood-brain barrier (BBB). Only a part of cholesterol pool can be exchanged with the blood circulation in the form of the oxysterol metabolites such, as 27-hydroxycholesterol (27-OHC) and 24S-hydroxycholesterol (24S-OHC). Not only neurons but also blood vessels and neuroglia, constituting neurovascular unit (NVU), are crucial for the brain cholesterol metabolism and undergo precise regulation by numerous modulators, metabolites and signal molecules. In physiological conditions maintaining the optimal cholesterol concentration is important for the energetic metabolism, composition of cell membranes and myelination. However, a growing body of evidence indicates the consequences of the cholesterol homeostasis dysregulation in several pathophysiological processes. There is a causal relationship between hypercholesterolemia and 1) development of type 2 diabetes due to long-term high-fat diet consumption, 2) significance of the oxidative stress consequences for cerebral amyloid angiopathy and neurodegenerative diseases, 3) insulin resistance on progression of the neurodegenerative brain diseases. In this review, we summarize the current state of knowledge concerning the cholesterol influence upon functioning of the NVU under physiological and pathological conditions.

  17. State and development of new clinical contrast agents for MR diagnosis of liver diseases

    Rummeny, E.J.; Peters, P.E.

    1992-01-01

    MR contrast agents are developed for pharmaceutical manipulation of tissue signal intensities. Today it is widely recognized that MR contrast agents will play an increasingly important role in MR imaging of the liver. Contrast-enhanced MR-imaging allows to obtain simultaneously dynamic physiologic information and high anatomci detail. Up to now three major classes of MR contrast agents are available for clinical MR-imaging of the liver. These include paramagnetic perfusion agents, hepatobiliary agents, and superparamagnetic RES-specific iron oxide particles. A fourth class of contrast agents now in use for animal experiments includes ultrasmall superparamagnetic particles which can be targeted to extrareticuloendothelial structures such as asialoglycoprotein receptors of hepatocytes. In this article, we review recent advances in the development of MR contrast media and the clinical of contrast-enhanced MR imaging of the liver. (orig.) [de

  18. Toxicology Studies on Lewisite and Sulfur Mustard Agents: Modified Dominant Lethal Study of Sulfur Mustard in Rats Final Report

    Sasser, L. B.; Cushing, J. A.; Kalkwarf, D. R.; Buschbom, R. L.

    1989-05-01

    Occupational health standards have not been established for sulfur mustard (HD) [bis{2-chloroethyl)-sulfide) ' a strong alkylating agent with known mutagenic properties. Little, however, is known about the mutagenic activity of HD in mammalian species and data regarding the dominant lethal effects of HD are ambiguous. The purpose of this study was to determine the dominant lethal effect in male and female rats orally exposed to HD. The study was conducted in two phases; a female dominant lethal phase and a male dominant lethal phase. Sprague-Dawley rats of each sex were administered 0.08, 0.20, or 0.50 mg/kg HD in sesame oil 5 days/week for 10 weeks. For the female phase, treated or untreated males were mated with treated females and their fetuses were evaluated at approximately 14 days after copulation. For the male dominant lethal phase, treated males cohabited with untreated femal (during 5 days of each week for 10 weeks) and females were sacrificed for fetal evaluation 14 days after the midweek of cohabitation during each of the 10 weeks. The appearance and behavior of the rats were unremarkable throughout the experiment and there were no treatment-related deaths. Growth rates were reduced in both female and male rats treated with 0.50 mg/kg HD. Indicators of reproductive performance did not demonstrate significant female dominant lethal effects, although significant male dominant lethal effects were observed at 2 and 3 week post-exposure. These effects included increases of early fetal resorptions and preimplantation losses and decreases of total live embryo implants. These effects were most consistently observed at a dose of 0.50 mg/kg, but frequently occurred at the lower doses. Although no treatment-related effects on male reproductive organ weights or sperm motility were found, a significant increase in the percentage of abnormal sperm was detected in males exposed to 0. 50 mg/kg HD. The timing of these effects is consistent with an effect during the

  19. Subclinical chronic kidney disease modifies the diagnosis of experimental acute kidney injury.

    Succar, Lena; Pianta, Timothy J; Davidson, Trent; Pickering, John W; Endre, Zoltán H

    2017-09-01

    Extensive structural damage within the kidney must be present before serum creatinine increases. However, a subclinical phase of chronic kidney disease (CKD) usually goes undetected. Here we tested whether experimental subclinical CKD would modify functional and damage biomarker profiles of acute kidney injury (AKI). Subclinical CKD was induced in rats by adenine or aristolochic acid models but without increasing serum creatinine. After prolonged recovery (three to six weeks), AKI was induced with a subnephrotoxic dose of cisplatin. Urinary levels of kidney injury molecule-1 (KIM-1), cytochrome C, monocyte chemotactic protein-1 (MCP-1), clusterin, and interleukin-18 increased during CKD induction, without an increase in serum creatinine. After AKI in adenine-induced CKD, serum creatinine increased more rapidly, while increased urinary KIM-1, clusterin, and MCP-1 were delayed and reduced. Increased serum creatinine and biomarker excretion were associated with diffuse tubulointerstitial injury in the outer stripe of outer medulla coupled with over 50% cortical damage. Following AKI in aristolochic acid-induced CKD, increased serum creatinine, urinary KIM-1, clusterin, MCP-1, cytochrome C, and interleukin-18 concentrations and excretion were greater at day 21 than day 42 and inversely correlated with cortical injury. Subclinical CKD modified functional and damage biomarker profiles in diametrically opposite ways. Functional biomarker profiles were more sensitive, while damage biomarker diagnostic thresholds and increases were diminished and delayed. Damage biomarker concentrations and excretion were inversely linked to the extent of prior cortical damage. Thus, thresholds for AKI biomarkers may need to be lower or sampling delayed in the known presence of CKD. Crown Copyright © 2017. Published by Elsevier Inc. All rights reserved.

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

    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

  1. The Prevalence of Trypanosoma cruzi, the Causal Agent of Chagas Disease, in Texas Rodent Populations.

    Aleman, Adriana; Guerra, Trina; Maikis, Troy J; Milholland, Matthew T; Castro-Arellano, Ivan; Forstner, Michael R J; Hahn, Dittmar

    2017-03-01

    Rodent species were assessed as potential hosts of Trypanosoma cruzi, the etiologic agent of Chagas disease, from five sites throughout Texas in sylvan and disturbed habitats. A total of 592 rodents were captured, resulting in a wide taxonomic representation of 11 genera and 15 species. Heart samples of 543 individuals were successfully analyzed by SybrGreen-based quantitative PCR (qPCR) targeting a 166 bp fragment of satellite DNA of T. cruzi. Eight rodents representing six species from six genera and two families were infected with T. cruzi. This is the first report of T. cruzi in the pygmy mouse (Baiomys taylori) and the white-footed mouse (Peromyscus leucopus) for the USA. All infected rodents were from the southernmost site (Las Palomas Wildlife Management Area). No differences in pathogen prevalence existed between disturbed habitats (5 of 131 tested; 3.8%) and sylvan habitats (3 of 40 tested; 7.5%). Most positives (n = 6, 16% prevalence) were detected in late winter with single positives in both spring (3% prevalence) and fall (1% prevalence). Additionally, 30 Triatoma insects were collected opportunistically from sites in central Texas. Fifty percent of these insects, i.e., 13 T. gerstaeckeri (68%), and two T. lecticularia (100%) were positive for T. cruzi. Comparative sequence analyses of 18S rRNA of samples provided identical results with respect to detection of the presence or absence of T. cruzi and assigned T. cruzi from rodents collected in late winter to lineage TcI. T. cruzi from Triatoma sp. and rodents from subsequent collections in spring and fall were different, however, and could not be assigned to other lineages with certainty.

  2. New Tacrines as Anti-Alzheimer's Disease Agents. The (Benzo)Chromeno- PyranoTacrines.

    Oset-Gasque, Maria Jesus; Marco-Contelles, Jose

    2017-01-01

    Tacrine was the first drug approved by FDA (US) for the treatment of Alzheimer's disease suffering patients. Nowadays, this agent has been withdrawn from the clinics due to secondary effects, which, most importantly, include hepatotoxicity. However, the research on new tacrine analogues devoid of these therapeutically undesirable effects, but benefiting of their high and well known positive cholinergic power, has produced a number of new non-hepatotoxic tacrines. In this context, our laboratory has recently prepared a new set of heterocyclic tacrines by changing the benzene ring present in tacrine by appropriate heterocyclic motifs. Based on this approach, in this review we summarize the results that we have found in the ChromenoPyranoTacrines, one of the families of tacrine analogues. This highlights their pharmacological profile, such as their cholinesterase inhibition power, calcium channel blockade, antioxidant capacity, Aβ-anti-aggregating, and neuroprotective properties. As a result of this work we have identified permeable, neuroprotective MTD tacrines racemic hit-tacrines 11-amino-12-(3,4,5-trimethoxyphenyl)-7,9,10,12-tetrahydro-8H-chromeno[2,3- b]quinolin-3-ol (6g) and 14-(3,4-dimethoxyphenyl)-9,11,12,14-tetrahydro-10H-benzo[5,6] chromeno [2,3-b] quinolin-13-amine (7i),devoid of toxic effects and showing potent anti-cholinesterasic properties, that deserve attention and further development in order to find new, and more efficient drugs, for AD therapy. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  3. Treatment patterns in disease-modifying therapy for patients with multiple sclerosis in the United States.

    Bonafede, Machaon M; Johnson, Barbara H; Wenten, Madé; Watson, Crystal

    2013-10-01

    Patients with multiple sclerosis (MS) whose disease activity is inadequately controlled with a platform therapy (interferon beta or glatiramer acetate [GA]) may switch to another platform therapy or escalate therapy to natalizumab or fingolimod, which were approved in the US in 2006 and 2010, respectively. The objective of this study was to describe treatment patterns in patients with multiple sclerosis (MS) in the United States who were followed for 2 years after initiating a disease-modifying therapy (DMT). A retrospective observational cohort study was conducted to examine treatment patterns of initial DMT use (on initial therapy for 2 years with and without gaps of ≥ 60 days, medication switching, and discontinuation) among patients with MS who initiated a platform therapy (interferon-β or glatiramer acetate) or natalizumab between January 1, 2007, and September 30, 2009; the first DMT claim was the index. Eligible patients were identified in the MarketScan Commercial and Medicare Supplemental databases based on continuous enrollment for 6 months before (preindex period) and 24 months after their index date, with a diagnosis of MS and no claim for a previous DMT in the 6-month preindex period. Demographics at index and clinical characteristics during the preindex period were also analyzed. A total of 6181 MS patients were included, with 5735 (92.8%) starting on platform therapy. Natalizumab initiators were more likely to stay on index therapy (32.3% vs 16.9%, P treatment gaps of ≥ 60 days (44.8% vs 55.3%, P treatment (13.9% vs 19.1%, P = 0.007) and took longer to switch (400.9 days vs 330.7 days, P treatment gaps, and switch less than platform initiators in the 2 years after treatment initiation. Switching between platform therapies is common despite evidence that MS patients on platform therapy may benefit from switching to natalizumab. © 2013 Elsevier HS Journals, Inc. All rights reserved.

  4. ANALYSIS OF DISEASE MODIFYING DRUGS ADMINISTRATION FREGUENCY AND CAUSES OF THEIR WITHDRAWAL IN RHEUMATOID ARTHRITIS

    E V Pavlova

    2000-01-01

    Full Text Available Aim of studdy: To assess the frequency of practical application of different basic drugs in rheumatoid arthritis (RA. Material and methods: Tlxe study was conducted basing of questionner of pts and analysis of ycases by randomized sampling among 103 consequent pts (M:F= 13:90 with reliable RA (ARA, 1987 in rheumatologic department of Clinical Hospital Nol in Ekaterinburg. 74% of pts under study demonstrated systemic manifestations: anemia (in 47 pts, lymphadenopathy (in 34, rheumatoid nodules (in 15, Sjogren s syndrome (in 4, nephropathy (in 4, vascular disturbances including Raynaud s phenomenon, capillarites (by 1 pt. Results: In the course of disease basic therapy was prescribed to 88 out of103 (85.4% pts and one and the same patient could take different basic drugs. Aminochinoline drugs prevailed, after them more frequent were immunodepressants and gold preparations. More rarely pts had sulfasalazin, cuprenil and wobenzym. In general, in 133 out of 184 cases of prescribing basic drugs they were canceled. The reason for cancellation were: prevalently absence of the drug in the pharmaceutical stores (in 48 cases averagely in 8 months of taking the drug; then they insufficient efficacy (44 cases averagely in 1.3 year. In 18 cases pts themselves stopped treatment averagely in 3.5 months of drug taking. Conclusion: In the majority of cases of basic drugs cancellation in RA the cause is their absence in sail especially on free of charge prescription. Cases ofself-cancellation of the drug demonstrate the need of explaining to pts the necessity> of long-term taking disease-modifying drugs.

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

    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.

  6. Baseline predictors of persistence to first disease-modifying treatment in multiple sclerosis.

    Zettl, U K; Schreiber, H; Bauer-Steinhusen, U; Glaser, T; Hechenbichler, K; Hecker, M

    2017-08-01

    Patients with multiple sclerosis (MS) require lifelong therapy. However, success of disease-modifying therapies is dependent on patients' persistence and adherence to treatment schedules. In the setting of a large multicenter observational study, we aimed at assessing multiple parameters for their predictive power with respect to discontinuation of therapy. We analyzed 13 parameters to predict discontinuation of interferon beta-1b treatment during a 2-year follow-up period based on data from 395 patients with MS who were treatment-naïve at study onset. Besides clinical characteristics, patient-related psychosocial outcomes were assessed as well. Among patients without clinically relevant fatigue, males showed a higher persistence rate than females (80.3% vs 64.7%). Clinically relevant fatigue scores decreased the persistence rate in men and especially in women (71.4% and 51.2%). Besides gender and fatigue, univariable and multivariable analyses revealed further factors associated with interferon beta-1b therapy discontinuation, namely lower quality of life, depressiveness, and higher relapse rate before therapy initiation, while higher education, living without a partner, and higher age improved persistence. Patients with higher grades of fatigue and depressiveness are at higher risk to prematurely discontinue MS treatment; especially, women suffering from fatigue have an increased discontinuation rate. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  7. 10-minute delayed recall from the modified mini-mental state test predicts Alzheimer's disease pathology.

    Lyness, Scott A; Lee, Ae Young; Zarow, Chris; Teng, Evelyn L; Chui, Helena C

    2014-01-01

    We compared the sensitivity and specificity of two delayed recall scores from the Modified Mini-Mental State (3MS) test with consensus clinical diagnosis to differentiate cognitive impairment due to Alzheimer's disease (AD) versus non-AD pathologies. At a memory disorders clinic, 117 cognitively impaired patients were administered a baseline 3MS test and received a contemporaneous consensus clinical diagnosis. Their brains were examined after death about 5 years later. Using logistic regression with forward selection to predict pathologically defined AD versus non-AD, 10-min delayed recall entered first (p = 0.001), followed by clinical diagnosis (p = 0.02); 1-min delayed recall did not enter. 10-min delayed recall scores ≤4 (score range = 0-9) were 87% sensitive and 47% specific in predicting AD pathology; consensus clinical diagnosis was 82% sensitive and 45% specific. For the 57 patients whose initial Mini-Mental State Examination scores were ≥19 (the median), 3MS 10-min delayed recall scores ≤4 showed some loss of sensitivity (80%) but a substantial gain in specificity (77%). In conclusion, 10-min delayed recall score on the brief 3MS test distinguished between AD versus non-AD pathology about 5 years before death at least as well as consensus clinical diagnosis that requires much more comprehensive information and complex deliberation.

  8. Adherence to synthetic disease-modifying Antirheumatic Drugs in Rheumatoid Arthritis: Results of the OBSERVAR Study.

    Juan Mas, Antonio; Castañeda, Santos; Cantero Santamaría, José I; Baquero, José L; Del Toro Santos, Francisco J

    2017-12-27

    Treatment compliance with disease-modifying antirheumatic drugs (DMARD) is essential to achieve the therapeutic goals in rheumatoid arthritis (RA). However, despite the need for good compliance, there is evidence that patients with RA frequently fail to use DMARD for the control of RA. Thus, the main objective of the OBSERVAR study is to evaluate the reasons for the lack of therapeutic adherence to synthetic DMARD in these patients. A Delphi process involving 18 randomly selected Spanish rheumatologists determined the level of agreement with 66 causes of noncompliance selected from the literature in relation to synthetic DMARD in RA. The reasons for noncompliance were consistent in 75.7%, although 3 reasons (4.5%) were highly consistent: 1) not knowing what to do in the case of an adverse event with DMARD; 2) not having undergone adherence screening by health personnel for early detection of "noncompliant patients"; and 3) not having undergone interventions or strategies that improve adherence. In order to improve adherence to RA treatment with synthetic DMARD, the patient should be adequately informed of each new treatment introduced, the patient's compliance profile should be incorporated into the clinical routine and the patient's motivation for therapeutic compliance be reinforced through the methods available to us. Copyright © 2017 Elsevier España, S.L.U. and Sociedad Española de Reumatología y Colegio Mexicano de Reumatología. All rights reserved.

  9. In vitro evaluation of the effects of some plant essential oils on Ascosphaera apis, the causative agent of Chalkbrood disease

    Mohammad Javed Ansari

    2017-07-01

    Full Text Available Ascosphaera apis is one of the major fungal pathogens of honey bee broods and the causative agent of Chalkbrood disease. The factors responsible for the pathogenesis of Chalkbrood disease are still not fully understood, and the increasing resistance of A. apis to commonly used antifungal agents necessitates a search for new agents to control this disease. The in vitro antifungal activities of 27 plant essential oils against two isolates of A. apis (Aksu-4 and Aksu-9 were evaluated. Out of the 27 plant essential oils tested, 21 were found to be effective in killing both isolates of A. apis. Based on their minimum fungicidal concentration (MFC values, the effective oils were grouped into three categories: highly effective, moderately effective and minimally effective. Mountain pepper oil, Kala Bhangra oil, spearmint oil, babuna oil, betel leaf oil, carrot seed oil, cumin seed oil and clove bud oil were highly effective, with MBC values between 50.0 μg/mL and 600.0 μg/mL. Mountain pepper was the most effective essential oil, with an MBC value of 50.0 μg/mL. Citral and caryophyllene containing oils were the most effective with MIC 50 ppm. The essential oils tested exhibited significant antimicrobial activities against both strains of A. apis, and they may contain compounds that could play an important role in the treatment or prevention of Chalkbrood disease of honeybee.

  10. Perspectives and experiences of Dutch multiple sclerosis patients and multiple sclerosis-specialized neurologists on injectable disease-modifying treatment

    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

  11. Patients' considerations in the decision-making process of initiating disease-modifying anti-rheumatic drugs

    Nota, Ingrid; Drossaert, Constance H.C.; Taal, Erik; van de Laar, Mart A F J

    2015-01-01

    Objectives To explore what considerations patients have when deciding about disease-modifying anti-rheumatic drugs (DMARDs) and what information patients need to participate in the decision-making process. Methods In-depth face-to-face interviews were conducted with 32 inflammatory arthritis

  12. Health-Related Quality of Life in Patients with Multiple Sclerosis : Impact of Disease-Modifying Drugs

    Jongen, Peter Joseph

    Multiple sclerosis (MS) has a profound impact on health-related quality of life (HRQoL), a comprehensive subjective measure of the patient's health status. Assessment of HRQoL informs on the potential advantages and disadvantages of disease-modifying drugs (DMDs) beyond their effects on

  13. Radiographic assessment of disease progression in rheumatoid arthritis patients undergoing early disease-modifying anti-rheumatic drug treatment

    Wick, M.C.

    2002-04-01

    Rheumatoid arthritis (RA) is a common systemic disease predominantly involving the joints. Since the pathogenesis, etiology and pathophysiological mechanisms of RA have only been partially elucidated, a definitive therapy has not been established. Precise diagnosis and follow-up therapy requires objective quantification, and radiological analyses are considered to be the most appropriate method. The aim of this study was to retrospectively determine the time-dependent progression of joint damage in patients with pharmacologically-treated RA, and to determine which therapeutic agents demonstrate the highest efficacy. Outpatient records, laboratory values, therapy schemes and radiographs from hands and feet of 150 RA patients were collected, analyzed and statistically evaluated. Radiographs were quantified using the Larsen score and supportively using the 'RheumaCoach-Rheumatology' computer software. Our observations reveal that radiologically-detectable damage is most pronounced during the first year of disease, while mitigated and generally progressing linearly thereafter. Overall Larsen scores linearly increased from year 0 to 10 (r=0.853), during which the mean Larsen score increased 7.93 ± 0.76 per year. During the first year, RA progression was similar regardless of the medication administered (gold-compounds, AU; chloroquine, CQ; methotrexate, MTX; sulfasalazine SSZ). While MTX and CQ treatment showed no difference when examined as mean 5-year increment of Larsen score, AU and SSZ showed up to 3 fold higher RA progression compared with MTX. The Larsen score in year 1 did not correlate with that of years 2 to 5. In contrast, Larsen scores in year 2 were linearly related to each of the subsequent 3 years. Despite similar ESR values in various medication groups, cumulative ESR correlated with RA progression, and its reduction with therapeutic efficacy. In conclusion, this study found that, (i) early DMARD-treated RA progressed more rapidly during the first than

  14. Bacillus spp as a biological control agent against panama disease in banana

    Gumede, WHN

    2006-02-01

    Full Text Available The decreased productivity levels in crop production as a consequence of disease infection have been a great concern amongst agricultural communities. A similar threat is facing the banana-cultivating community due to Panama disease. Panama disease...

  15. Effect of Plant Antimicrobial Agents Containing Marinades on Storage Stability and Microbiological Quality of Broiler Chicken Cuts Packed with Modified Atmosphere Packaging.

    Alakomi, H-L; Maukonen, J; Honkapää, K; Storgårds, E; Quirin, K-W; Yang, B; Saarela, M

    2017-10-01

    The food industry, including the meat industry, is currently looking for natural preservatives to prevent the growth of harmful microbes in foods. The potential of plant-derived antimicrobial extracts to increase the shelf life and to delay the microbiological spoilage of marinated broiler chicken cuts in modified atmosphere packages during cold storage was investigated in this study. We evaluated the impact of aqueous ethanolic extracts of Finnish sea buckthorn berries and lingonberries and supercritical CO 2 -extracted herbal extracts from an antimicrobial blend and oregano leaves on the shelf life of broiler meat. The commercial antimicrobial blend extract and the oregano extract inhibited the growth of lactic acid bacteria (LAB) and Brochothrix thermosphacta in the marinated samples. The antimicrobial blend extract also reduced the growth of psychrotrophic aerobic bacteria, whereas the sea buckthorn and lingonberry extracts did not. Only minor antimicrobial activity against Enterobacteriaceae by all the extracts was observed. Plate count analysis, denaturing gradient gel electrophoresis, and quantitative real-time PCR indicated that LAB, which are the major spoilage group in marinated modified atmosphere-packaged poultry products, were not significantly affected by the berry extracts studied. During this shelf-life study, LAB isolates of Lactobacillus and Leuconostoc were identified in the marinated samples. Antimicrobial blends and oregano leaf extracts can act as antimicrobial agents in marinade blends, although tailoring of the dose is needed because of their strong taste. Further studies for exploiting synergistic effects of plant extracts could contribute to the development of potential and more effective antimicrobial blends. Studies are needed in meat matrices and in product applications to demonstrate the efficacy of these compounds.

  16. Towards the concept of disease-modifier in post-stroke or vascular cognitive impairment: a consensus report.

    Bordet, Régis; Ihl, Ralf; Korczyn, Amos D; Lanza, Giuseppe; Jansa, Jelka; Hoerr, Robert; Guekht, Alla

    2017-05-24

    Vascular cognitive impairment (VCI) is a complex spectrum encompassing post-stroke cognitive impairment (PSCI) and small vessel disease-related cognitive impairment. Despite the growing health, social, and economic burden of VCI, to date, no specific treatment is available, prompting the introduction of the concept of a disease modifier. Within this clinical spectrum, VCI and PSCI remain advancing conditions as neurodegenerative diseases with progression of both vascular and degenerative lesions accounting for cognitive decline. Disease-modifying strategies should integrate both pharmacological and non-pharmacological multimodal approaches, with pleiotropic effects targeting (1) endothelial and brain-blood barrier dysfunction; (2) neuronal death and axonal loss; (3) cerebral plasticity and compensatory mechanisms; and (4) degenerative-related protein misfolding. Moreover, pharmacological and non-pharmacological treatment in PSCI or VCI requires valid study designs clearly stating the definition of basic methodological issues, such as the instruments that should be used to measure eventual changes, the biomarker-based stratification of participants to be investigated, and statistical tests, as well as the inclusion and exclusion criteria that should be applied. A consensus emerged to propose the development of a disease-modifying strategy in VCI and PSCI based on pleiotropic pharmacological and non-pharmacological approaches.

  17. A tick mannose-binding lectin inhibits the vertebrate complement cascade to enhance transmission of the Lyme disease agent

    Schuijt, Tim J.; Coumou, Jeroen; Narasimhan, Sukanya; Dai, Jianfeng; DePonte, Kathleen; Wouters, Diana; Brouwer, Mieke; Oei, Anneke; Roelofs, Joris J.T.H.; van Dam, Alje P.; van der Poll, Tom; van ’t Veer, Cornelis; Hovius, Joppe W.; Fikrig, Erol

    2011-01-01

    The Lyme disease agent, Borrelia burgdorferi, is primarily transmitted to vertebrates by Ixodes ticks. The classical and alternative complement pathways are important in Borrelia eradication by the vertebrate host. We recently identified a tick salivary protein, designated P8 that reduced complement-mediated killing of Borrelia. We now discover that P8 interferes with the human lectin complement cascade resulting in impaired neutrophil phagocytosis and chemotaxis, and diminished Borrelia lysi...

  18. Infectious agents and inflammation in donated hearts and dilated cardiomyopathies related to cardiovascular diseases, Chagas' heart disease, primary and secondary dilated cardiomyopathies.

    Mangini, Sandrigo; Higuchi, Maria de Lourdes; Kawakami, Joyce Tiyeko; Reis, Marcia Martins; Ikegami, Renata Nishiyama; Palomino, Suely Aparecida Pinheiro; Pomerantzeff, Pablo Maria Alberto; Fiorelli, Alfredo Inácio; Marcondes-Braga, Fabiana Goulart; Bacal, Fernando; Ferreira, Sílvia Moreira Ayub; Issa, Victor Sarli; Souza, Germano Emílio Conceição; Chizzola, Paulo Roberto; Bocchi, Edimar Alcides

    2015-01-15

    Clinical and experimental conflicting data have questioned the relationship between infectious agents, inflammation and dilated cardiomyopathy (DCM). The aim of this study was to determine the frequency of infectious agents and inflammation in endomyocardial biopsy (EMB) specimens from patients with idiopathic DCM, explanted hearts from different etiologies, including Chagas' disease, compared to donated hearts. From 2008 to 2011, myocardial samples from 29 heart donors and 55 patients with DCMs from different etiologies were studied (32 idiopathic, 9 chagasic, 6 ischemic and 8 other specific etiologies). Inflammation was investigated by immunohistochemistry and infectious agents by immunohistochemistry, molecular biology, in situ hybridization and electron microscopy. There were no differences regarding the presence of macrophages, expression of HLA class II and ICAM-I in donors and DCM. Inflammation in Chagas' disease was predominant. By immunohistochemistry, in donors, there was a higher expression of antigens of enterovirus and Borrelia, hepatitis B and C in DCMs. By molecular biology, in all groups, the positivity was elevated to microorganisms, including co-infections, with a higher positivity to adenovirus and HHV6 in donors towards DCMs. This study was the first to demonstrate the presence of virus in the heart tissue of chagasic DCM. The presence of inflammation and infectious agents is frequent in donated hearts, in the myocardium of patients with idiopathic DCM, myocardial dysfunction related to cardiovascular diseases, and primary and secondary cardiomyopathies, including Chagas' disease. The role of co-infection in Chagas' heart disease physiopathology deserves to be investigated in future studies. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  19. Detection of Crohn's disease: Comparison of CT and MR enterography without anti-peristaltic agents performed on the same day

    Grand, David J.; Beland, Michael D.; Machan, Jason T.; Mayo-Smith, William W.

    2012-01-01

    Objective: To directly compare CT enterography (CTE) and MR enterography (MRE) without antiperistaltic agents. Materials/methods: 26 patients referred for CTE underwent CTE immediately followed by MRE without use of an anti-peristaltic agent. Each study was evaluated on a 10 point scale for exam quality, level of diagnostic confidence, and presence of Crohn's disease. Kappa analysis was performed to determine the degree of agreement between the CTE and MRE of each patient. Results: 25 patients completed the MRE. The quality of the CTEs was judged as excellent by both readers (reader 1 = average 9.5/10, reader 2 = average 9.1/10). The quality of the MREs was ranked lower than the CTEs by both readers (reader 1 = average 8.9/10, reader 2 = average 7.2/10), which was statistically significant (p < 0.05). The level of confidence in interpretation was not significantly different between CTE and MRE for reader 1 or 2 (p = 0.3). There was substantial agreement between readers for the presence or absence of Crohn's disease on both CTE (kappa = 0.75) and MRE (kappa = 0.67). Conclusion: MR enterography without anti-peristaltic agents results in high diagnostic confidence and excellent agreement for the presence of Crohn's disease.

  20. Influence of Anti-TNF and Disease Modifying Antirheumatic Drugs Therapy on Pulmonary Forced Vital Capacity Associated to Ankylosing Spondylitis: A 2-Year Follow-Up Observational Study

    Alberto Daniel Rocha-Muñoz

    2015-01-01

    Full Text Available Objective. To evaluate the effect of anti-TNF agents plus synthetic disease modifying antirheumatic drugs (DMARDs versus DMARDs alone for ankylosing spondylitis (AS with reduced pulmonary function vital capacity (FVC%. Methods. In an observational study, we included AS who had FVC% <80% at baseline. Twenty patients were taking DMARDs and 16 received anti-TNF + DMARDs. Outcome measures: changes in FVC%, BASDAI, BASFI, 6-minute walk test (6MWT, Borg scale after 6MWT, and St. George’s Respiratory Questionnaire at 24 months. Results. Both DMARDs and anti-TNF + DMARDs groups had similar baseline values in FVC%. Significant improvement was achieved with anti-TNF + DMARDs in FVC%, at 24 months, when compared to DMARDs alone (P=0.04. Similarly, patients in anti-TNF + DMARDs group had greater improvement in BASDAI, BASFI, Borg scale, and 6MWT when compared to DMARDs alone. After 2 years of follow-up, 14/16 (87.5% in the anti-TNF + DMARDs group achieved the primary outcome: FVC% ≥80%, compared with 11/20 (55% in the DMARDs group (P=0.04. Conclusions. Patients with anti-TNF + DMARDs had a greater improvement in FVC% and cardiopulmonary scales at 24 months compared with DMARDs. This preliminary study supports the fact that anti-TNF agents may offer additional benefits compared to DMARDs in patients with AS who have reduced FVC%.

  1. Do Genetic Markers of Inflammation Modify the Relationship between Periodontitis and Nonalcoholic Fatty Liver Disease? Findings from the SHIP Study.

    Akinkugbe, A A; Avery, C L; Barritt, A S; Cole, S R; Lerch, M; Mayerle, J; Offenbacher, S; Petersmann, A; Nauck, M; Völzke, H; Slade, G D; Heiss, G; Kocher, T; Holtfreter, B

    2017-11-01

    An association between periodontitis and nonalcoholic fatty liver disease (NAFLD) has been reported by experimental animal and epidemiologic studies. This study investigated whether circulating levels of serum C-reactive protein (CRP) and a weighted genetic CRP score representing markers of inflammatory burden modify the association between periodontitis and NAFLD. Data came from 2,481 participants of the Study of Health in Pomerania who attended baseline examination that occurred between 1997 and 2001. Periodontitis was defined as the percentage of sites (0%, 3 mg/L. Periodontitis was positively associated with higher prevalence odds of NAFLD, and this relationship was modified by serum CRP levels.

  2. Therapeutic compliance of first line disease-modifying therapies in patients with multiple sclerosis. COMPLIANCE Study.

    Saiz, A; Mora, S; Blanco, J

    2015-05-01

    Non-adherence to disease-modifying therapies (DMTs) in multiple sclerosis may be associated with reduced efficacy. We assessed compliance, the reasons for non-compliance, treatment satisfaction, and quality of life (QoL) of patients treated with first-line therapies. A cross-sectional, multicenter study was conducted that included relapsing multiple sclerosis patients. Compliance in the past month was assessed using Morisky-Green test. Seasonal compliance and reasons for non-compliance were assessed by an ad-hoc questionnaire. Treatment satisfaction and QoL were evaluated by means of TSQM and PRIMUS questionnaires. A total of 220 patients were evaluated (91% relapsing-remitting); the mean age was 39.1 years, 70% were female, and the average time under treatment was 5.4 years. Subcutaneous interferon (IFN) β-1b was used in 23% of the patients, intramuscular IFN β-1a in 21%, subcutaneous IFN β-1a in 37%, and with glatiramer acetate in 19%. The overall compliance was 75%, with no significant differences related to the therapy, and 81% did not report any seasonal variation. Compliant patients had significantly lower disability scores and time of diagnosis, and greater satisfaction with treatment and its effectiveness. Discomfort and flu-like symptoms were the most frequent reasons for non-compliance. The satisfaction and QoL were associated with less disability and number of therapeutic switches. The rate of compliance, satisfaction and QoL in multiple sclerosis patients under DMTs is high, especially for those newly diagnosed, less disabled, and with fewer therapeutic switches. Discomfort and flu-like symptoms associated with injected therapies significantly affect adherence. Copyright © 2013 Sociedad Española de Neurología. Published by Elsevier España, S.L.U. All rights reserved.

  3. Functional paraoxonase 1 variants modify the risk of Parkinson's disease due to organophosphate exposure.

    Lee, Pei-Chen; Rhodes, Shannon L; Sinsheimer, Janet S; Bronstein, Jeff; Ritz, Beate

    2013-06-01

    We previously demonstrated that carriers of the "slower metabolizer" MM genotype of paraoxonase (PON1) who were also exposed to ambient organophosphate (OP) pesticides at their residences were at increased risk of developing Parkinson's disease (PD). Here, with a larger sample size, we extend our previous investigation to consider additional sources of ambient exposure and examined two additional functional PON1 variants. From 2001 to 2011, we enrolled incident cases of idiopathic PD and population controls living in central California. We genotyped three well-known functional PON1 SNPs: two exonic polymorphisms (PON1L55M and PON1Q192R) and the promoter region variant (PON1C-108T). Ambient exposures to diazinon, chlorpyrifos, and parathion at residential and workplace addresses were assessed using a validated geographic information system-based model incorporating records of agricultural pesticide applications in California. The odds ratio (OR) for Caucasians exposed to OPs at either residential or workplace addresses varied by PON1 genotype; for exposed carriers of the "faster" metabolizer genotypes, ML or LL, we estimated lower odds ratios (range, 1.20-1.39) than for exposed carriers of the "slower" metabolizer genotype MM (range, 1.78-2.45) relative to unexposed carriers of the faster genotypes. We observed similarly increased ORs for exposure across PON1Q192R genotypes, but no differences across PON1C-108T genotypes. The largest ORs were estimated for exposed carriers of both PON1192QQ and PON155MM (OR range, 2.84-3.57). Several functional PON1 variants may act together to modify PD risk for ambient OP exposures. While either PON1L55M or PON1Q192R may be sufficient to identify increased susceptibility, carriers of both slow metabolizer variants seem most susceptible to OP exposures. Copyright © 2013 Elsevier Ltd. All rights reserved.

  4. Environmental enrichment imparts disease-modifying and transgenerational effects on genetically-determined epilepsy and anxiety.

    Dezsi, Gabi; Ozturk, Ezgi; Salzberg, Michael R; Morris, Margaret; O'Brien, Terence J; Jones, Nigel C

    2016-09-01

    The absence epilepsies are presumed to be caused by genetic factors, but the influence of environmental exposures on epilepsy development and severity, and whether this influence is transmitted to subsequent generations, is not well known. We assessed the effects of environmental enrichment on epilepsy and anxiety outcomes in multiple generations of GAERS - a genetic rat model of absence epilepsy that manifests comorbid elevated anxiety-like behaviour. GAERS were exposed to environmental enrichment or standard housing beginning either prior to, or after epilepsy onset, and underwent EEG recordings and anxiety testing. Then, we exposed male GAERS to early enrichment or standard housing and generated F1 progeny, which also underwent EEG recordings. Hippocampal CRH mRNA expression and DNA methylation were assessed using RT-PCR and pyrosequencing, respectively. Early environmental enrichment delayed the onset of epilepsy in GAERS, and resulted in fewer seizures in adulthood, compared with standard housed GAERS. Enrichment also reduced the frequency of seizures when initiated in adulthood. Anxiety levels were reduced by enrichment, and these anti-epileptogenic and anxiolytic effects were heritable into the next generation. We also found reduced expression of CRH mRNA in GAERS exposed to enrichment, but this was not due to changes in DNA methylation. Environmental enrichment produces disease-modifying effects on genetically determined absence epilepsy and anxiety, and these beneficial effects are transferable to the subsequent generation. Reduced CRH expression was associated with these phenotypic improvements. Environmental stimulation holds promise as a naturalistic therapy for genetically determined epilepsy which may benefit subsequent generations. Copyright © 2016 Elsevier Inc. All rights reserved.

  5. Does Caffeine Consumption Modify Cerebrospinal Fluid Amyloid-β Levels in Patients with Alzheimer's Disease?

    Travassos, Maria; Santana, Isabel; Baldeiras, Inês; Tsolaki, Magda; Gkatzima, Olymbia; Sermin, Genc; Yener, Görsev G; Simonsen, Anja; Hasselbalch, Steen G; Kapaki, Elisabeth; Mara, Bourbouli; Cunha, Rodrigo A; Agostinho, Paula; Blennow, Kaj; Zetterberg, Henrik; Mendes, Vera M; Manadas, Bruno; de Mendon, Alexandreça

    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 in the CSF. However, a significant positive correlation was found between the concentrations of theobromine, both in the CSF and in the plasma, with Aβ42 in the CSF. Theobromine in the CSF was positively correlated with the levels of other xanthines in the CSF, but not in the plasma, suggesting that it may be formed by central metabolic pathways. In conclusion, caffeine consumption does not modify the levels of CSF biomarkers, and does not require to be controlled for when measuring CSF biomarkers in a clinical setting. Since theobromine is associated with a favorable Aβ profile in the CSF, the possibility that it might have a protective role in AD should be further investigated.

  6. The Burden of Cardiovascular Disease Attributable to Major Modifiable Risk Factors in Indonesia

    Mohammad Akhtar Hussain

    2016-10-01

    Full Text Available Background: In Indonesia, coronary heart disease (CHD and stroke are estimated to cause more than 470 000 deaths annually. In order to inform primary prevention policies, we estimated the sex- and age-specific burden of CHD and stroke attributable to five major and modifiable vascular risk factors: cigarette smoking, hypertension, diabetes, elevated total cholesterol, and excess body weight. Methods: Population attributable risks for CHD and stroke attributable to these risk factors individually were calculated using summary statistics obtained for prevalence of each risk factor specific to sex and to two age categories (<55 and ≥55 years from a national survey in Indonesia. Age- and sex-specific relative risks for CHD and stroke associated with each of the five risk factors were derived from prospective data from the Asia-Pacific region. Results: Hypertension was the leading vascular risk factor, explaining 20%–25% of all CHD and 36%–42% of all strokes in both sexes and approximately one-third of all CHD and half of all strokes across younger and older age groups alike. Smoking in men explained a substantial proportion of vascular events (25% of CHD and 17% of strokes. However, given that these risk factors are likely to be strongly correlated, these population attributable risk proportions are likely to be overestimates and require verification from future studies that are able to take into account correlation between risk factors. Conclusions: Implementation of effective population-based prevention strategies aimed at reducing levels of major cardiovascular risk factors, especially blood pressure, total cholesterol, and smoking prevalence among men, could reduce the growing burden of CVD in the Indonesian population.

  7. Disease modifying and antiangiogenic activity of 2-Methoxyestradiol in a murine model of rheumatoid arthritis

    Moore Elizabeth G

    2009-05-01

    study parameters and prevented neovascularization into the joint. Examination of gene expression on dissected hind limbs from mice treated for 5 or 14 days with 2ME2 showed inhibition of inflammatory cytokine message for IL-1β, TNF-α, IL-6 and IL-17, as well as the angiogenic cytokines, VEGF and FGF-2. Conclusion These data demonstrate that in the CAIA mouse model of RA, 2ME2 has disease modifying activity that is at least partially attributable to the inhibition of neovascular development. Further, the data suggests new mechanistic points of intervention for 2ME2 in RA, specifically inhibition of inflammatory mediators and osteoclast activity.

  8. Study on the structure-properties relationship of natural rubber/SiO2 composites modified by a novel multi-functional rubber agent

    S. Y. Yang

    2014-06-01

    Full Text Available Vulcanization property and structure-properties relationship of natural rubber (NR/silica (SiO2 composites modified by a novel multi-functional rubber agent, N-phenyl- N'-(γ-triethoxysilane-propyl thiourea (STU, are investigated in detail. Results from the infrared spectroscopy (IR and X-ray photoelectron spectroscopy (XPS show that STU can graft to the surface of SiO2 under heating, resulting in a fine-dispersed structure in the rubber matrix without the connectivity of SiO2 particles as revealed by transmission electron microscopy (TEM. This modification effect reduces the block vulcanization effect of SiO2 for NR/SiO2/STU compounds under vulcanization process evidently. The 400% modulus and tensile strength of NR/SiO2/STU composites are much higher than that of NR/SiO2/TU composites, although the crystal index at the stretching ratio of 4 and crosslinking densities of NR/SiO2 composites are almost the same at the same dosage of SiO2. Consequently, a structure-property relationship of NR/SiO2/STU composites is proposed that the silane chain of STU can entangle with NR molecular chains to form an interfacial region, which is in accordance with the experimental observations quite well.

  9. Green Preparation of Epoxy/Graphene Oxide Nanocomposites Using a Glycidylamine Epoxy Resin as the Surface Modifier and Phase Transfer Agent of Graphene Oxide.

    Tang, Xinlei; Zhou, Yang; Peng, Mao

    2016-01-27

    In studies of epoxy/graphene oxide (GO) nanocomposites, organic solvents are commonly used to disperse GO, and vigorous mechanical processes and complicated modification of GO are usually required, increasing the cost and hindering the development and application of epoxy nanocomposites. Here, we report a green, facile, and efficient method of preparing epoxy/GO nanocomposites. When triglycidyl para-aminophenol (TGPAP), a commercially available glycidyl amine epoxy resin with one tertiary amine group per molecule, is used as both the surface modifier and phase transfer agent of GO, GO can be directly and rapidly transferred from water to diglycidyl ether of bisphenol A and other types of epoxy resins by manual stirring under ambient conditions, whereas GO cannot be transferred to these epoxy resins in the absence of TGPAP. The interaction between TGPAP and GO and the effect of the TGPAP content on the dispersion of GO in the epoxy matrix were investigated systematically. Superior dispersion and exfoliation of GO nanosheets and remarkably improved mechanical properties, including tensile and flexural properties, toughness, storage modulus, and microhardness, of the epoxy/GO nanocomposites with a suitable amount of TGPAP were demonstrated. This method is organic-solvent-free and technically feasible for large-scale preparation of high-performance nanocomposites; it opens up new opportunities for exploiting the unique properties of graphene or even other nanofillers for a wide range of applications.

  10. Developing framework for agent- based diabetes disease management system: user perspective.

    Mohammadzadeh, Niloofar; Safdari, Reza; Rahimi, Azin

    2014-02-01

    One of the characteristics of agents is mobility which makes them very suitable for remote electronic health and tele medicine. The aim of this study is developing a framework for agent based diabetes information management at national level through identifying required agents. The main tool is a questioner that is designed in three sections based on studying library resources, performance of major organizations in the field of diabetes in and out of the country and interviews with experts in the medical, health information management and software fields. Questionnaires based on Delphi methods were distributed among 20 experts. In order to design and identify agents required in health information management for the prevention and appropriate and rapid treatment of diabetes, the results were analyzed using SPSS 17 and Results were plotted with FREEPLANE mind map software. ACCESS TO DATA TECHNOLOGY IN PROPOSED FRAMEWORK IN ORDER OF PRIORITY IS: mobile (mean 1/80), SMS, EMAIL (mean 2/80), internet, web (mean 3/30), phone (mean 3/60), WIFI (mean 4/60). In delivering health care to diabetic patients, considering social and human aspects is essential. Having a systematic view for implementation of agent systems and paying attention to all aspects such as feedbacks, user acceptance, budget, motivation, hierarchy, useful standards, affordability of individuals, identifying barriers and opportunities and so on, are necessary.

  11. MMP-2 is a disease-modifying gene in primary sclerosing cholangitis

    Korkmaz, Kerem Sebib; de Rooij, Bert-Jan F.; van Hoek, Bart; Janse, Marcel; Coenraad, Minneke J.; van der Reijden, Johan J.; Weersma, Rinse K.; Porte, Robert J.; Voorneveld, Philip W.; Baranski, Andrzej G.; Verspaget, Hein W.

    BackgroundPrimary sclerosing cholangitis (PSC) is a chronic inflammatory disease of the bile ducts, frequently necessitating orthotopic liver transplantation (OLT), often accompanied by inflammatory bowel disease (IBD). Matrix metalloproteinases (MMPs) are associated with fibrotic diseases caused by

  12. Information to prevent human exposure to disease agents associated with wildlife—U.S. Geological Survey circulars on zoonotic disease

    Meteyer, Carol U.; Moede Rogall, Gail

    2018-03-05

    The U.S. Geological Survey in collaboration with the U.S. Fish and Wildlife Service and others have published reports with information about geographic distribution, specific pathogens, disease ecology, and strategies to avoid exposure and infection for a selection of zoonotic diseases. Zoonotic diseases are diseases that can be passed from animals to humans, such as rabies and plague. This summary factsheet highlights the reports on plague, bat rabies, and raccoon roundworm with links to all seven zoonotic diseases covered in this series.

  13. A SNP in the HTT promoter alters NF-κB binding and is a bidirectional genetic modifier of Huntington disease

    Bečanović, Kristina; Nørremølle, Anne; Neal, Scott J

    2015-01-01

    Cis-regulatory variants that alter gene expression can modify disease expressivity, but none have previously been identified in Huntington disease (HD). Here we provide in vivo evidence in HD patients that cis-regulatory variants in the HTT promoter are bidirectional modifiers of HD age of onset....

  14. Serological studies on the infection of dogs in Ontario with Borrelia burgdorferi, the etiological agent of Lyme disease

    Artsob, Harvey; Barker, Ian K.; Fister, Richard; Sephton, Gregory; Dick, Daryl; Lynch, John A.; Key, Doug

    1993-01-01

    A serological study was undertaken to determine whether dogs in Ontario are being exposed to Borrelia burgdorferi, the etiological agent of Lyme disease. This study consisted of a survey of randomly selected dogs and testing of diagnostic submissions from candidate Lyme disease cases. The survey of 1,095 dogs, bled between January 1988 and August 1989, revealed a total of 65 (5.9%) enzyme-linked immunosorbent assay (ELISA) reactors, of which 22 had immuno-fluorescent antibody assay (IFA) titers ≥1:32. All but one of the IFA-positive and 10 of the ELISA-positive, IFA-negative sera were further tested by western blot. Eight western blot positive and three equivocal reactors were obtained. Three of the eight confirmed reactors had visited areas known to be endemic for Lyme disease, leaving five reactors that might have been infected in previously undocumented areas for B. burgdorferi activity in Ontario. Diagnostic submissions of sera from 223 dogs were received between August 1987 and February 1992. Test results revealed 21 (9.4%) IFA reactors, of which only six had significant titers (≥1:256) and were reactive by an immunodot Borrelia test. All six dogs had travelled to known Lyme endemic areas. Based on results obtained from this study, it seems likely that the agent of Lyme disease is not widespread in Ontario. PMID:17424284

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

    Xie Peng; Liu Xiaomei; Huang Jianmin; Zhang Fang; Pan Liping; Wu Weijie; Gao Jianqing

    2013-01-01

    Objective: To compare the accuracy of 99 Tc m -diethylene triamine pentaacetic acid ( 99 Tc m -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)

  16. 77 FR 47795 - Disease Associated With Exposure to Certain Herbicide Agents: Peripheral Neuropathy

    2012-08-10

    ...) Whether there is a statistical association between exposure to herbicide agents and the illness, taking.... Redesignating Note 3 as Note 2. 4. Amend Sec. 3.816(b)(2) by: a. In the introductory text, removing ``before October 1, 2002.'' b. In the introductory text, removing the period after ``chloracne'' and all that...

  17. Genetic Factors Interact With Tobacco Smoke to Modify Risk for Inflammatory Bowel Disease in Humans and Mice

    Yadav, Pankaj; Ellinghaus, David; Rémy, Gaëlle

    2017-01-01

    BACKGROUND & AIMS: The role of tobacco smoke in the etiology of inflammatory bowel disease (IBD) is unclear. We investigated interactions between genes and smoking (gene-smoking interactions) that affect risk for Crohn's disease (CD) and ulcerative colitis (UC) in a case-only study of patients...... chamber, or ambient air (controls). Intestines were collected and analyzed histologically and by reverse transcription polymerase chain reaction. RESULTS: We identified 64 single nucleotide polymorphisms (SNPs) for which the association between the SNP and IBD were modified by smoking behavior (meta...... to smoke. CONCLUSIONS: In an analysis of 55 Immunochip-wide datasets, we identified 64 SNPs whose association with risk for IBD is modified by tobacco smoking. Gene-smoking interactions were confirmed in mice with disruption of Il10 and Nod2-variants of these genes have been associated with risk for IBD...

  18. Disease-modifying effect of atipamezole in a model of post-traumatic epilepsy.

    Nissinen, Jari; Andrade, Pedro; Natunen, Teemu; Hiltunen, Mikko; Malm, Tarja; Kanninen, Katja; Soares, Joana I; Shatillo, Olena; Sallinen, Jukka; Ndode-Ekane, Xavier Ekolle; Pitkänen, Asla

    2017-10-01

    Treatment of TBI remains a major unmet medical need, with 2.5 million new cases of traumatic brain injury (TBI) each year in Europe and 1.5 million in the USA. This single-center proof-of-concept preclinical study tested the hypothesis that pharmacologic neurostimulation with proconvulsants, either atipamezole, a selective α 2 -adrenoceptor antagonist, or the cannabinoid receptor 1 antagonist SR141716A, as monotherapy would improve functional recovery after TBI. A total of 404 adult Sprague-Dawley male rats were randomized into two groups: sham-injured or lateral fluid-percussion-induced TBI. The rats were treated with atipamezole (started at 30min or 7 d after TBI) or SR141716A (2min or 30min post-TBI) for up to 9 wk. Total follow-up time was 14 wk after treatment initiation. Outcome measures included motor (composite neuroscore, beam-walking) and cognitive performance (Morris water-maze), seizure susceptibility, spontaneous seizures, and cortical and hippocampal pathology. All injured rats exhibited similar impairment in the neuroscore and beam-walking tests at 2 d post-TBI. Atipamezole treatment initiated at either 30min or 7 d post-TBI and continued for 9 wk via subcutaneous osmotic minipumps improved performance in both the neuroscore and beam-walking tests, but not in the Morris water-maze spatial learning and memory test. Atipamezole treatment initiated at 7 d post-TBI also reduced seizure susceptibility in the pentylenetetrazol test 14 wk after treatment initiation, although it did not prevent the development of epilepsy. SR141716A administered as a single dose at 2min post-TBI or initiated at 30min post-TBI and continued for 9 wk had no recovery-enhancing or antiepileptogenic effects. Mechanistic studies to assess the α 2 -adrenoceptor subtype specificity of the disease-modifying effects of atipametzole revealed that genetic ablation of α 2A -noradrenergic receptor function in Adra2A mice carrying an N79P point mutation had antiepileptogenic effects

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

    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

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

    Østergaard, Søren D; Mukherjee, Shubhabrata; Sharp, Stephen J; Proitsi, Petroula; Lotta, Luca A; Day, Felix; Perry, John R B; Boehme, Kevin L; Walter, Stefan; Kauwe, John S; Gibbons, Laura E; Larson, Eric B; Powell, John F; Langenberg, Claudia; Crane, Paul K; Wareham, Nicholas J; Scott, Robert A

    2015-06-01

    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

  1. [Alkylating agents].

    Pourquier, Philippe

    2011-11-01

    With the approval of mechlorethamine by the FDA in 1949 for the treatment of hematologic malignancies, alkylating agents are the oldest class of anticancer agents. Even though their clinical use is far beyond the use of new targeted therapies, they still occupy a major place in specific indications and sometimes represent the unique option for the treatment of refractory diseases. Here, we are reviewing the major classes of alkylating agents and their mechanism of action, with a particular emphasis for the new generations of alkylating agents. As for most of the chemotherapeutic agents used in the clinic, these compounds are derived from natural sources. With a complex but original mechanism of action, they represent new interesting alternatives for the clinicians, especially for tumors that are resistant to conventional DNA damaging agents. We also briefly describe the different strategies that have been or are currently developed to potentiate the use of classical alkylating agents, especially the inhibition of pathways that are involved in the repair of DNA lesions induced by these agents. In this line, the development of PARP inhibitors is a striking example of the recent regain of interest towards the "old" alkylating agents.

  2. Antimicrobial agents of plant origin for the treatment of phlogistic-infectious diseases of the lower female genital tract

    Francesco Gon

    2012-12-01

    Full Text Available The phlogistic-infectious diseases of the lower female genital tract are one of the most widespread obstetricgynecologic issues, due to treatment failures that cause frequent relapses and to the adverse effects of some commonly used drugs.The most common vaginal syndromes are due to uncontrolled growth of bacteria or fungi which replace the normal vaginal flora, causing phlogistic and infectious based diseases. These infections are treated with anti-inflammatory and antibiotic therapy; however, the emergence of resistant strains and the ability of many microorganisms to grow inside biofilms severely reduce the repertoire of useful agents.Thus, in the last years increasing interest has been focused toward compounds of plant origin with anti-microbial properties. In the present work, we studied the antimicrobial activity of fractions obtained from endemic plants of Sardinia towards microorganisms that frequently are involved in vaginal infectious diseases: Streptococcus agalactiae, Gardnerella vaginalis and Candida albicans.

  3. Recovery of divergent avian bornaviruses from cases of proventricular dilatation disease: Identification of a candidate etiologic agent

    Greninger Alexander

    2008-07-01

    Full Text Available Abstract Background Proventricular dilatation disease (PDD is a fatal disorder threatening domesticated and wild psittacine birds worldwide. It is characterized by lymphoplasmacytic infiltration of the ganglia of the central and peripheral nervous system, leading to central nervous system disorders as well as disordered enteric motility and associated wasting. For almost 40 years, a viral etiology for PDD has been suspected, but to date no candidate etiologic agent has been reproducibly linked to the disease. Results Analysis of 2 PDD case-control series collected independently on different continents using a pan-viral microarray revealed a bornavirus hybridization signature in 62.5% of the PDD cases (5/8 and none of the controls (0/8. Ultra high throughput sequencing was utilized to recover the complete viral genome sequence from one of the virus-positive PDD cases. This revealed a bornavirus-like genome organization for this agent with a high degree of sequence divergence from all prior bornavirus isolates. We propose the name avian bornavirus (ABV for this agent. Further specific ABV PCR analysis of an additional set of independently collected PDD cases and controls yielded a significant difference in ABV detection rate among PDD cases (71%, n = 7 compared to controls (0%, n = 14 (P = 0.01; Fisher's Exact Test. Partial sequence analysis of a total of 16 ABV isolates we have now recovered from these and an additional set of cases reveals at least 5 distinct ABV genetic subgroups. Conclusion These studies clearly demonstrate the existence of an avian reservoir of remarkably diverse bornaviruses and provide a compelling candidate in the search for an etiologic agent of PDD.

  4. High-resolution motion compensated MRA in patients with congenital heart disease using extracellular contrast agent at 3 Tesla

    Dabir Darius

    2012-10-01

    Full Text Available Abstract Background Using first-pass MRA (FP-MRA spatial resolution is limited by breath-hold duration. In addition, image quality may be hampered by respiratory and cardiac motion artefacts. In order to overcome these limitations an ECG- and navigator-gated high-resolution-MRA sequence (HR-MRA with slow infusion of extracellular contrast agent was implemented at 3 Tesla for the assessment of congenital heart disease and compared to standard first-pass-MRA (FP-MRA. Methods 34 patients (median age: 13 years with congenital heart disease (CHD were prospectively examined on a 3 Tesla system. The CMR-protocol comprised functional imaging, FP- and HR-MRA, and viability imaging. After the acquisition of the FP-MRA sequence using a single dose of extracellular contrast agent the motion compensated HR-MRA sequence with isotropic resolution was acquired while injecting the second single dose, utilizing the timeframe before viability imaging. Qualitative scores for image quality (two independent reviewers as well as quantitative measurements of vessel sharpness and relative contrast were compared using the Wilcoxon signed-rank test. Quantitative measurements of vessel diameters were compared using the Bland-Altman test. Results The mean image quality score revealed significantly better image quality of the HR-MRA sequence compared to the FP-MRA sequence in all vessels of interest (ascending aorta (AA, left pulmonary artery (LPA, left superior pulmonary vein (LSPV, coronary sinus (CS, and coronary ostia (CO; all p  Conclusions An ECG- and navigator-gated HR-MRA-protocol with infusion of extracellular contrast agent at 3 Tesla is feasible. HR-MRA delivers significantly better image quality and vessel sharpness compared to FP-MRA. It may be integrated into a standard CMR-protocol for patients with CHD without the need for additional contrast agent injection and without any additional examination time.

  5. Pre-operative use of anti-TNF-alpha agents and the risk of post-operative complications in patients with Crohn's disease--a nationwide cohort study

    Nørgård, Bente Mertz; Nielsen, J.; Qvist, N.

    2013-01-01

    BACKGROUND: A possible negative role of pre-operative use of antitumour necrosis factor-alpha (anti-TNF-alpha) agents on post-operative outcomes in Crohn's disease (CD) patients is still debated. AIM: To examine the impact of pre-operative anti-TNF-alpha agents on post-operative outcomes 30 and 6...

  6. Quantitative susceptibility of Streptococcus suis strains isolated from diseased pigs in seven European countries to antimicrobial agents licenced in veterinary medicine

    Wisselink, H.J.; Veldman, K.T.; Salmon, S.A.; Mevius, D.J.

    2006-01-01

    The susceptibility of Streptococcus suis strains (n = 384) isolated from diseased pigs in seven European countries to 10 antimicrobial agents was determined. For that purpose a microbroth dilution method was used according to CLSI recommendations. The following antimicrobial agents were tested:

  7. Efficacy of cyclin dependent kinase 4 inhibitors as potent neuroprotective agents against insults relevant to Alzheimer's disease.

    Priyankar Sanphui

    Full Text Available Alzheimer's disease (AD is a progressive neurodegenerative disease with no cure till today. Aberrant activation of cell cycle regulatory proteins is implicated in neurodegenerative diseases including AD. We and others have shown that Cyclin dependent kinase 4 (Cdk4 is activated in AD brain and is required for neuron death. In this study, we tested the efficiency of commercially available Cdk4 specific inhibitors as well as a small library of synthetic molecule inhibitors targeting Cdk4 as neuroprotective agents in cellular models of neuron death. We found that several of these inhibitors significantly protected neuronal cells against death induced by nerve growth factor (NGF deprivation and oligomeric beta amyloid (Aβ that are implicated in AD. These neuroprotective agents inhibit specifically Cdk4 kinase activity, loss of mitochondrial integrity, induction of pro-apoptotic protein Bim and caspase3 activation in response to NGF deprivation. The efficacies of commercial and synthesized inhibitors are comparable. The synthesized molecules are either phenanthrene based or naphthalene based and they are synthesized by using Pschorr reaction and Buchwald coupling respectively as one of the key steps. A number of molecules of both kinds block neurodegeneration effectively. Therefore, we propose that Cdk4 inhibition would be a therapeutic choice for ameliorating neurodegeneration in AD and these synthetic Cdk4 inhibitors could lead to development of effective drugs for AD.

  8. Antihypertensive agents and risk of Parkinson's disease, essential tremor and dementia: a population-based prospective study (NEDICES).

    Louis, Elan D; Benito-León, Julián; Bermejo-Pareja, Félix

    2009-01-01

    Recent interest in antihypertensive agents, especially calcium channel blockers, has been sparked by the notion that these medications may be neuroprotective. A modest literature, with mixed results, has examined whether these medications might lower the odds or risk of Parkinson's disease (PD) or dementia. There are no data for essential tremor (ET). To examine the association between antihypertensive use (defined broadly and by individual subclasses) and ET, PD and dementia. For each disorder, we used cross-sectional data (association with prevalent disease) and prospective data (association with incident disease). Prospective population-based study in Spain enrolling 5,278 participants at baseline. Use of antihypertensive medications (aside from beta-blockers) was similar in prevalent ET cases and controls. Baseline use of antihypertensive agents was not associated with reduced risk of incident ET. Antihypertensive medication use was not associated with prevalent or incident PD. Calcium channel blocker use was marginally reduced in prevalent dementia cases (OR(adjusted) = 0.63, p = 0.06) but was not associated with reduced risk of incident dementia (RR(adjusted) = 1.02, p = 0.95). We did not find evidence of a protective effect of antihypertensive medications in these three neurodegenerative disorders. Copyright 2009 S. Karger AG, Basel.

  9. Evaluation of a Modified Italian European Prospective Investigation into Cancer and Nutrition Food Frequency Questionnaire for Individuals with Celiac Disease.

    Mazzeo, Teresa; Roncoroni, Leda; Lombardo, Vincenza; Tomba, Carolina; Elli, Luca; Sieri, Sabina; Grioni, Sara; Bardella, Maria T; Agostoni, Carlo; Doneda, Luisa; Brighenti, Furio; Pellegrini, Nicoletta

    2016-11-01

    To date, it is unclear whether individuals with celiac disease following a gluten-free (GF) diet for several years have adequate intake of all recommended nutrients. Lack of a food frequency questionnaire (FFQ) for individuals with celiac disease could be partly responsible for this still-debated issue. The aim of the study is to evaluate the performance of a modified European Prospective Investigation into Cancer and Nutrition (EPIC) FFQ in estimating nutrient and food intake in a celiac population. In a cross-sectional study, the dietary habits of individuals with celiac disease were reported using a modified Italian EPIC FFQ and were compared to a 7-day weighed food record as a reference method. A total of 200 individuals with histologically confirmed celiac disease were enrolled in the study between October 2012 and August 2014 at the Center for Prevention and Diagnosis of Celiac Disease (Milan, Italy). Nutrient and food category intake were calculated by 7-day weighed food record using an Italian food database integrated with the nutrient composition of 60 GF foods and the modified EPIC FFQ, in which 24 foods were substituted with GF foods comparable for energy and carbohydrate content. An evaluation of the modified FFQ compared to 7-day weighed food record in assessing the reported intake of nutrient and food groups was conducted using Spearman's correlation coefficients and weighted κ. One hundred individuals completed the study. The Spearman's correlation coefficients of FFQ and 7-day weighed food record ranged from .13 to .73 for nutrients and from .23 to .75 for food groups. A moderate agreement, which was defined as a weighted κ value of .40 to .60, was obtained for 30% of the analyzed nutrients, and 40% of the nutrients showed values between .30 and .40. The weighted κ exceeded .40 for 60% of the 15 analyzed food groups. The modified EPIC FFQ demonstrated moderate congruence with a weighed food record in ranking individuals by dietary intakes

  10. Safety and effectiveness of collagenase clostridium histolyticum in the treatment of Peyronie's disease using a new modified shortened protocol.

    Abdel Raheem, Amr; Capece, Marco; Kalejaiye, Odunayo; Abdel-Raheem, Tarek; Falcone, Marco; Johnson, Mark; Ralph, Oliver G; Garaffa, Giulio; Christopher, Andrew N; Ralph, David J

    2017-11-01

    To evaluate the efficacy and safety of collagenase clostridium histolyticum (CCH; Xiapex ® , Xiaflex ® ) in the treatment of Peyronie's disease (PD) using a new modified treatment protocol that aims at reducing the number of injections needed and reducing patient visits, thus reducing the duration and cost of treatment. A prospective study of 53 patients with PD who had treatment with CCH at a single centre using a new modified protocol. The angle of curvature assessment after an intracavernosal injection of prostaglandin E1, the International Index of Erectile Function (IIEF) and Peyronie's Disease Questionnaire (PDQ) were completed at baseline and at week 12 (4 weeks after the last injection). The Global Assessment of Peyronie's disease (GAPD) questionnaire was completed at week 12. Under a penile block of 10 mL plain lignocaine 1%, a total of three intralesional injections of CCH (0.9 mg) were given at 4-weekly intervals using a new modified injection technique. In between injections patients used a combination of home modelling, stretching and a vacuum device on a daily basis to mechanically stretch the plaque. Investigator modelling was not performed. The mean (range) penile curvature at baseline was 54 (30-90)°. Of the 53 patients in the study, 51 patients (96.2%) had an improvement in the angel of curvature by a mean (range) of 17.36 (0-40)° or 31.4 (0-57)% from baseline after three CCH injections. The final mean (range) curvature was 36.9 (12-75)° (P effective, and cost efficient. The results of using only three CCH injections according to this modified protocol are comparable to those of the clinical trials that used eight CCH injections. © 2017 The Authors BJU International © 2017 BJU International Published by John Wiley & Sons Ltd.

  11. De novo genome assembly of Geosmithia morbida, the causal agent of thousand cankers disease

    Taruna A. Schuelke; Anthony Westbrook; Kirk Broders; Keith Woeste; Matthew D. MacManes

    2016-01-01

    Geosmithia morbida is a filamentous ascomycete that causes thousand cankers disease in the eastern black walnut tree. This pathogen is commonly found in the western U.S.; however, recently the disease was also detected in several eastern states where the black walnut lumber industry is concentrated. G. morbida is one of two...

  12. 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

    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.

  13. Global Association of Air Pollution and Cardiorespiratory Diseases: A Systematic Review, Meta-Analysis, and Investigation of Modifier Variables

    Adams, Matthew D.; Arain, Altaf; Papatheodorou, Stefania; Koutrakis, Petros; Mahmoud, Moataz

    2018-01-01

    Background. Little is known about the health risks of air pollution and cardiorespiratory diseases, globally, across regions and populations, which may differ because of external factors. Objectives. We systematically reviewed the evidence on the association between air pollution and cardiorespiratory diseases (hospital admissions and mortality), including variability by energy, transportation, socioeconomic status, and air quality. Search Methods. We conducted a literature search (PubMed and Web of Science) for studies published between 2006 and May 11, 2016. Selection Criteria. We included studies if they met all of the following criteria: (1) considered at least 1 of these air pollutants: carbon monoxide, sulfur dioxide, nitrogen dioxide, ozone, or particulate matter (PM2.5 or PM10); (2) reported risk for hospital admissions, mortality, or both; (3) presented individual results for respiratory diseases, cardiovascular diseases, or both; (4) considered the age groups younger than 5 years, older than 65 years, or all ages; and (5) did not segregate the analysis by gender. Data Collection and Analysis. We extracted data from each study, including location, health outcome, and risk estimates. We performed a meta-analysis to estimate the overall effect and to account for both within- and between-study heterogeneity. Then, we applied a model selection (least absolute shrinkage and selection operator) to assess the modifier variables, and, lastly, we performed meta-regression analyses to evaluate the modifier variables contributing to heterogeneity among studies. Main Results. We assessed 2183 studies, of which we selected 529 for in-depth review, and 70 articles fulfilled our study inclusion criteria. The 70 studies selected for meta-analysis encompass more than 30 million events across 28 countries. We found positive associations between cardiorespiratory diseases and different air pollutants. For example, when we considered only the association between PM2.5 and

  14. Whole-Genome Sequences of Two Borrelia afzelii and Two Borrelia garinii Lyme Disease Agent Isolates

    Casjens, S.R.; Dunn, J.; Mongodin, E. F.; Qiu, W.-G.; Luft, B. J.; Fraser-Liggett, C. M.; Schutzer, S. E.

    2011-12-01

    Human Lyme disease is commonly caused by several species of spirochetes in the Borrelia genus. In Eurasia these species are largely Borrelia afzelii, B. garinii, B. burgdorferi, and B. bavariensis sp. nov. Whole-genome sequencing is an excellent tool for investigating and understanding the influence of bacterial diversity on the pathogenesis and etiology of Lyme disease. We report here the whole-genome sequences of four isolates from two of the Borrelia species that cause human Lyme disease, B. afzelii isolates ACA-1 and PKo and B. garinii isolates PBr and Far04.

  15. Microtubule-Targeting Agents Enter the Central Nervous System (CNS): Double-edged Swords for Treating CNS Injury and Disease.

    Hur, Eun-Mi; Lee, Byoung Dae

    2014-12-01

    Microtubules have been among the most successful targets in anticancer therapy and a large number of microtubule-targeting agents (MTAs) are in various stages of clinical development for the treatment of several malignancies. Given that injury and diseases in the central nervous system (CNS) are accompanied by acute or chronic disruption of the structural integrity of neurons and that microtubules provide structural support for the nervous system at cellular and intracellular levels, microtubules are emerging as potential therapeutic targets for treating CNS disorders. It has been postulated that exogenous application of MTAs might prevent the breakdown or degradation of microtubules after injury or during neurodegeneration, which will thereby aid in preserving the structural integrity and function of the nervous system. Here we review recent evidence that supports this notion and also discuss potential risks of targeting microtubules as a therapy for treating nerve injury and neurodegenerative diseases.

  16. Microtubule-Targeting Agents Enter the Central Nervous System (CNS: Double-edged Swords for Treating CNS Injury and Disease

    Eun-Mi Hur

    2014-12-01

    Full Text Available Microtubules have been among the most successful targets in anticancer therapy and a large number of microtubule-targeting agents (MTAs are in various stages of clinical development for the treatment of several malignancies. Given that injury and diseases in the central nervous system (CNS are accompanied by acute or chronic disruption of the structural integrity of neurons and that microtubules provide structural support for the nervous system at cellular and intracellular levels, microtubules are emerging as potential therapeutic targets for treating CNS disorders. It has been postulated that exogenous application of MTAs might prevent the breakdown or degradation of microtubules after injury or during neurodegeneration, which will thereby aid in preserving the structural integrity and function of the nervous system. Here we review recent evidence that supports this notion and also discuss potential risks of targeting microtubules as a therapy for treating nerve injury and neurodegenerative diseases.

  17. 75 FR 53202 - Diseases Associated With Exposure to Certain Herbicide Agents (Hairy Cell Leukemia and Other...

    2010-08-31

    ... ICD-9-CM Medical Terminology and Codes One commenter expressed concern that VA regulations do not... Chapter of the American Parkinson Disease Association, Froedtert & The Medical College of Wisconsin, and...

  18. Treatment of gastric candidiasis in patients with gastric ulcer disease: are antifungal agents necessary?

    Jung, Min Kyu; Jeon, Seong Woo; Cho, Chang Min; Tak, Won Young; Kweon, Young Oh; Kim, Sung Kook; Choi, Yong Hwan

    2009-03-01

    The inadequacy of information on the treatment of gastric candidiasis with antifungal agents promoted us to evaluate patients with fungal infections who had gastric ulcers and assess the need for proton-pump inhibitors or antifungal agents. Sixteen patients were included in the study. The criterion for the diagnosis of candidiasis was finding yeast and hyphae in the tissue or an ulcer on histological sections of biopsy samples. Surface fungi were not considered infections. In all cases with benign ulcers, follow-up endoscopy performed 6 weeks after proton-pump-inhibitor treatment revealed that the ulcer had improved without antifungal medication. However, in patients with malignant ulcers, surgical resection was necessary for a definitive cure. Two patients with lymphoma received combined chemotherapy and a proton-pump inhibitor, which improved their condition. The results of this study suggest that benign ulcers with candidiasis can be effectively treated by a proton-pump inhibitor without antifungal medication. However, surgical resection should be considered for malignant ulcers with candidiasis.

  19. Prevalence of selected infectious disease agents in stray cats in Catalonia, Spain

    Sara Ravicini

    2016-02-01

    Full Text Available Objectives The objective of the current study was to investigate the prevalence rates of the following infectious agents in 116 stray cats in the Barcelona area of Spain: Anaplasma phagocytophilum, Bartonella species, Borrelia burgdorferi, Chlamydia felis, Dirofilaria immitis, Ehrlichia species, feline calicivirus (FCV, feline herpesvirus-1 (FHV-1, feline leukaemia virus (FeLV, feline immunodeficiency virus (FIV, haemoplasmas, Mycoplasma species and Rickettsia species. Methods Serum antibodies were used to estimate the prevalence of exposure to A phagocytophilum, Bartonella species, B burgdorferi, Ehrlichia species and FIV; serum antigens were used to assess for infection by D immitis and FeLV; and molecular assays were used to amplify nucleic acids of Anaplasma species, Bartonella species, C felis, D immitis, Ehrlichia species, FCV, FHV-1, haemoplasmas, Mycoplasma species and Rickettsia species from blood and nasal or oral swabs. Results Of the 116 cats, 63 (54.3% had evidence of infection by Bartonella species, FeLV, FIV or a haemoplasma. Anaplasma species, Ehrlichia species or Rickettsia species DNA was not amplified from these cats. A total of 18/116 cats (15.5% were positive for FCV RNA (six cats, Mycoplasma species DNA (six cats, FHV-1 DNA (three cats or C felis DNA (three cats. Conclusions and relevance This study documents that shelter cats in Catalonia are exposed to many infectious agents with clinical and zoonotic significance, and that flea control is indicated for cats in the region.

  20. Richard Bradley: a unified, living agent theory of the cause of infectious diseases of plants, animals, and humans in the first decades of the 18th century.

    Santer, Melvin

    2009-01-01

    During the years 1714 to 1721, Richard Bradley, who was later to become the first Professor of Botany at Cambridge University, proposed a unified, unique, living agent theory of the cause of infectious diseases of plants and animals and the plague of humans. Bradley's agents included microscopic organisms, revealed by the studies of Robert Hooke and Antony van Leeuwenhoek. His theory derived from his experimental studies of plants and their diseases and from microscopic observation of animalcules in different naturally occurring and artificial environments. He concluded that there was a microscopic world of "insects" that lived and reproduced under the appropriate conditions, and that infectious diseases of plants were caused by such "insects." Since there are structural and functional similarities between plants and animals, Bradley concluded that microscopic organisms caused human and animal infectious diseases as well. However, his living agent cause of infectious diseases was not accepted by the contemporary scientific society.

  1. Immunomodulation and disease resistance in postyearling rainbow trout infected with Myxobolus cerebralis, the causative agent of whirling disease

    Densmore, Christine L.; Ottinger, C.A.; Blazer, V.S.; Iwanowicz, L.R.; Smith, D.R.

    2004-01-01

    Myxobolus cerebralis, the myxosporean parasite that causes whirling disease, has a number of deleterious effects on its salmonid host. Although it is well established that juvenile salmonids in the active stages of whirling disease mount an immune response to the pathogen, the occurrence and longevity of any related immunomodulatory effects are unknown. In this study, postyearling rainbow trout Oncorhynchus mykiss infected with M. cerebralis were examined for leukocyte functions and for resistance to Yersinia ruckeri, a bacterial pathogen of salmonids. Compared with uninfected controls, M. cerebralis-infected fish showed lower proliferative lymphocyte responses to four mitogens (concanavalin A, pokeweed mitogen, phytohemagglutinin, and lipopolysaccharide). Conversely, M. cerebralis-infected fish displayed greater bactericidal activity of anterior kidney macrophages than did uninfected fish. After bath challenges with K. ruckeri, M. cerebralis-infected fish had slightly lower survival and a more rapid onset of mortality than did the control fish. Renal tissue and fecal samples from M. cerebralis-infected and uninfected survivors were cultured for the presence of K. ruckeri, and no difference in prevalence was noted between the two groups. Because immunomodulatory changes in the M. cerebralis-infected fish involved functional enhancement and suppression of different leukocyte populations, disease resistance among M. cerebralis-infected fish in the later stages of whirling disease will probably vary with the secondary pathogen and the nature of immune response the pathogen evokes.

  2. Potential Therapeutic Effects of Curcumin, the Anti-inflammatory Agent, Against Neurodegenerative, Cardiovascular, Pulmonary, Metabolic, Autoimmune and Neoplastic Diseases

    Aggarwal, Bharat B.; Harikumar, Kuzhuvelil B.

    2009-01-01

    Although safe in most cases, ancient treatments are ignored because neither their active component nor their molecular targets are well defined. This is not the case, however, with curcumin, a yellow-pigment substance and component of turmeric (Curcuma longa), which was identified more than a century ago. For centuries it has been known that turmeric exhibits anti-inflammatory activity, but extensive research performed within the past two decades has shown that the this activity of turmeric is due to curcumin, a diferuloylmethane. This agent has been shown to regulate numerous transcription factors, cytokines, protein kinases, adhesion molecules, redox status and enzymes that have been linked to inflammation. The process of inflammation has been shown to play a major role in most chronic illnesses, including neurodegenerative, cardiovascular, pulmonary, metabolic, autoimmune and neoplastic diseases. In the current review, we provide evidence for the potential role of curcumin in the prevention and treatment of various pro-inflammatory chronic diseases. These features, combined with the pharmacological safety and negligible cost, render curcumin an attractive agent to explore further. PMID:18662800

  3. Aquaculture in Cameroon and potential of lactic acid bacteria to be used as diseases controlling agents. A Review

    Kaktchan, Pierre Marie

    2015-08-01

    Full Text Available Aquaculture is the world’s fastest growing food production sector and can be a great solution to the massive demand for protein of animal due to increase in the Cameroonian population. This review summarizes the past and present status of fish aquaculture in Cameroon, the new challenges for intensifying fish production and evaluates the possibility of using lactic acid bacteria as disease control agents in order to overcome these challenges. Fish farming started in Cameroon in the late 1940s, and has seen little progress since the last ten years, but the production is still insufficient to meet the demand of the population estimated at 400 000 tons in 2015. In order to reduce massive fish imports, Cameroon plans to produce 100 000 tons of fish by commercial aquaculture. Achieving this task needs quality and quantity of fingerlings, and probiotic lactic acid bacteria instead of antibiotics could be used as disease control agents in young fish hatching and ponds in order to boost and ensure quality and quantity production.

  4. Modifiable Risk Factors for Common Ragweed (Ambrosia artemisiifolia Allergy and Disease in Children: A Case-Control Study

    Maureen Agnew

    2018-06-01

    Full Text Available Ragweed allergy is a major public health concern. Within Europe, ragweed is an introduced species and research has indicated that the amounts of ragweed pollen are likely to increase over Europe due to climate change, with corresponding increases in ragweed allergy. To address this threat, improving our understanding of predisposing factors for allergic sensitisation to ragweed and disease is necessary, specifically focusing upon factors that are potentially modifiable (i.e., environmental. In this study, a total of 4013 children aged 2–13 years were recruited across Croatia to undergo skin prick tests to determine sensitisation to ragweed and other aeroallergens. A parental questionnaire collected home environment, lifestyle, family and personal medical history, and socioeconomic information. Environmental variables were obtained using Geographical Information Systems and data from nearby pollen, weather, and air pollution stations. Logistic regression was performed (clustered on school focusing on risk factors for allergic sensitisation and disease. Ragweed sensitisation was strongly associated with ragweed pollen at levels over 5000 grains m–3 year−1 and, above these levels, the risk of sensitisation was 12–16 times greater than in low pollen areas with about 400 grains m–3 year−1. Genetic factors were strongly associated with sensitisation but nearly all potentially modifiable factors were insignificant. This included measures of local land use and proximity to potential sources of ragweed pollen. Rural residence was protective (odds ratio (OR 0.73, 95% confidence interval (CI 0.55–0.98, but the factors underlying this association were unclear. Being sensitised to ragweed doubled (OR 2.17, 95% CI 1.59–2.96 the risk of rhinoconjunctivitis. No other potentially modifiable risk factors were associated with rhinoconjunctivitis. Ragweed sensitisation was strongly associated with ragweed pollen, and sensitisation was significantly

  5. [Temperature that modifies the effect of air pollution on emergency room visits for circulatory and respiratory diseases in Beijing, China].

    Wang, L L; Zhang, Q; Bai, R H; Mi, B B; Yan, H

    2017-08-10

    Objective: To analyze the temperature modification effect on emergency room visits for circulatory and respiratory diseases caused by air pollution, in Beijing. Methods: Data on both circulatory and respiratory diseases in 2010 and 2011 were collected, Both meteorological and air pollutants related data were obtained from the National Scientific Data Sharing Platform for Population and Health. By using the stratified time-series models, we analyzed the effects of air pollution on emergency room visits for circulatory and respiratory diseases under different temperature zones, from 2010 to 2011, in Beijing. Results: Low temperature (daily average temperatureeffect of air pollution index (API) on emergency room visits for circulatory diseases, Under 10 units of API, the relative risks and confidence interval appeared as 1.067 (1.054-1.080). However, high (daily average temperature between 24.4 ℃ and 28.5 ℃) and extra-high temperature (daily average temperature >28.5 ℃) could enhance the effect of API on emergency room visits for respiratory diseases, Under 10 units of API, the relative risks and confidence interval were 1.021 (1.015-1.028) and 1.006 (1.003-1.008), respectively. Conclusion: Temperature seemed to have modified the association between air pollution and both circulatory and respiratory diseases.

  6. Does wheat genetically modified for disease resistance affect root-colonizing pseudomonads and arbuscular mycorrhizal fungi?

    Meyer, Joana Beatrice; Song-Wilson, Yi; Foetzki, Andrea; Luginbühl, Carolin; Winzeler, Michael; Kneubühler, Yvan; Matasci, Caterina; Mascher-Frutschi, Fabio; Kalinina, Olena; Boller, Thomas; Keel, Christoph; Maurhofer, Monika

    2013-01-01

    This study aimed to evaluate the impact of genetically modified (GM) wheat with introduced pm3b mildew resistance transgene, on two types of root-colonizing microorganisms, namely pseudomonads and arbuscular mycorrhizal fungi (AMF). Our investigations were carried out in field trials over three field seasons and at two locations. Serial dilution in selective King's B medium and microscopy were used to assess the abundance of cultivable pseudomonads and AMF, respectively. We developed a denatu...

  7. Overexpression of a modified plant thionin enhances disease resistance to citrus canker and Huanglongbing (HLB)

    Huanglongbing (HLB or citrus greening disease) caused by Candidatus Liberibacter asiaticus (Las) is a great threat to the United States 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 ec...

  8. Radicinin from Cochliobolus sp. inhibits Xylella fastidiosa, the causal agent of Pierce's Disease of grapevine.

    Aldrich, Thomas J; Rolshausen, Philippe E; Roper, M Caroline; Reader, Jordan M; Steinhaus, Matthew J; Rapicavoli, Jeannette; Vosburg, David A; Maloney, Katherine N

    2015-08-01

    The fastidious phytopathogenic bacterium, Xylella fastidiosa, poses a substantial threat to many economically important crops, causing devastating diseases including Pierce's Disease of grapevine. Grapevines (Vitis vinifera L.) planted in an area under Pierce's Disease pressure often display differences in disease severity and symptom expression, with apparently healthy vines growing alongside the dying ones, despite the fact that all the vines are genetic clones of one another. Under the hypothesis that endophytic microbes might be responsible for this non-genetic resistance to X. fastidiosa, endophytic fungi were isolated from vineyard cvs. 'Chardonnay' and 'Cabernet Sauvignon' grown under high Pierce's Disease pressure. A Cochliobolus sp. isolated from a Cabernet Sauvignon grapevine inhibited the growth of X. fastidiosa in vitro. Bioassay-guided isolation of an organic extract of Cochliobolus sp. yielded the natural product radicinin as the major active compound. Radicinin also inhibited proteases isolated from the culture supernatant of X. fastidiosa. In order to assess structure-activity relationships, three semi-synthetic derivatives of radicinin were prepared and tested for activity against X. fastidiosa in vitro. Assay results of these derivatives are consistent with enzyme inactivation by conjugate addition to carbon-10 of radicinin, as proposed previously. Copyright © 2015 Elsevier Ltd. All rights reserved.

  9. Modifiable life style associated risk factors for non communicable diseases among students of pre-university college of Udupi taluk

    Shradha S Parsekar

    2015-01-01

    Full Text Available Background Non-communicable diseases are diseases of longer period and are increasing. This study was intended to find out the proportion of adolescents having modifiable life style associated risk factors. Materials and methods A cross sectional study was carried out in 15 pre-university colleges (PUC of Udupi taluk, which were randomly selected, a class from each PUC was randomly chosen. WHO stepwise approach was used to collect data. A total of 838 adolescents in the age group 15 to 19 years were included. Data was analysed using SPSS software version 15. Chi square test was used to find the association. Results Current smoking was found in 1.67% of the participants. Nearly 16.94% participants were exposed to second hand smoke. About 2.15% of the participants were current alcohol drinkers. Junk food consumption was found in 64.08% of the participants. About 89.86% of the participants were physically inactive. Nearly 31.98% of the participants reported adding extra salt to the diet. Conclusion The behavioural risk factors investigated in the present study are potentially modifiable; identifying subgroups having one or multiple risk factors at an early age is of extreme importance for preventing risk of acquiring chronic diseases in adult life.

  10. Immunomodulators as Therapeutic Agents in Mitigating the Progression of Parkinson’s Disease

    Bethany Grimmig

    2016-09-01

    Full Text Available Parkinson’s disease (PD is a common neurodegenerative disorder that primarily afflicts the elderly. It is characterized by motor dysfunction due to extensive neuron loss in the substantia nigra pars compacta. There are multiple biological processes that are negatively impacted during the pathogenesis of PD, and are implicated in the cell death in this region. Neuroinflammation is evidently involved in PD pathology and mitigating the inflammatory cascade has been a therapeutic strategy. Age is the number one risk factor for PD and thus needs to be considered in the context of disease pathology. Here, we discuss the role of neuroinflammation within the context of aging as it applies to the development of PD, and the potential for two representative compounds, fractalkine and astaxanthin, to attenuate the pathophysiology that modulates neurodegeneration that occurs in Parkinson’s disease.

  11. CLINICAL CASE OF RUSSIAN THROMBOLYTIC AGENT FORTELYZIN® USE IN PATIENTS WITH ACUTE CORONARY ARTERY DISEASE

    K. A. Kireev

    2015-01-01

    Full Text Available One of the three clinical examples of hospital thrombolysis using Russian thrombolytic agent recombinant protein comprising an amino acid sequence of staphylokinase is described. The trial was held in Chelyabinsk Regional Vascular Centre of specialized medical care for patients with acute coronary syndromes. Each of the three patients had similar reasons for systemic intravenous thrombolysis: hospitalization with ST-segment elevation myocardial infarction, unavailability of coronary interventions due to the X-ray operating room occupancy, high need for the reperfusion therapy in the setting of significant acute myocardial ischemia. In all the cases the pharmacologic reperfusion with recombinant protein comprising an amino acid sequence of staphylokinase was successful, hereafter percutaneous coronary interventions were performed. There were no complications registered.

  12. Efficacy of genetically engineered biological agents in the treatment of uveitis associated with rheumatic diseases in children

    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.

  13. FOXP3+ T Regulatory Cell Modifications in Inflammatory Bowel Disease Patients Treated with Anti-TNFα Agents

    Luisa Guidi

    2013-01-01

    Full Text Available Treg modulation has been hypothesized as one of the mechanisms by which antitumor necrosis factor α (TNFα agents exert their action in rheumatoid arthritis (RA and inflammatory bowel disease (IBD. However, data in IBD are still conflicting. We evaluated CD4+CD25+FOXP3+ (Tregs by flow cytometry in peripheral blood from 32 adult IBD patient before (T0 and after the induction of anti-TNFα therapy (T1. Eight healthy controls (HCs were included. We also evaluated the number of FOXP3+ cells in the lamina propria (LP in biopsies taken in a subset of patients and controls. Treg frequencies were significantly increased in peripheral blood from our patients after anti-TNFα therapy compared to T0. T1 but not T0 levels were higher than HC. The increase was detectable only in clinical responders to the treatment. A negative correlation was found among delta Treg levels and the age of patients or disease duration and with the activity score of Crohn’s disease (CD. No significant differences were found in LP FOXP3+ cells. Our data suggest the possibility that in IBD patients the treatment with anti-TNFα may affect Treg percentages and that Treg modifications may correlate with clinical response, but differently in early versus late disease.

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

    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.

  15. Microglial TNF and IL-1 as early disease-modifiers in Alzheimer's-like disease in mice

    Ilkjær, Laura; Babcock, Alicia; Finsen, Bente

    2015-01-01

    In Alzheimer's disease (AD) signs of microglial activation is evident already in prodromal and early AD. This and other evidence suggest that neuroinflammation contributes to the progression of the early disease development in AD. Microglial cells have the capacity to produce cytokines such as TNF...... 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...

  16. K/DOQI Clinical Practice Guidelines on Hypertension and Antihypertensive Agents in Chronic Kidney Disease

    Levey, Andrew S.; Rocco, Michael V.; Anderson, Sharon; Andreoli, Sharon P.; Bailie, George R.; Bakris, George L.; Callahan, Mary Beth; Greene, Jane H.; Johnson, Cynda Ann; Lash, James P.; McCullough, Peter A.; Miller III, Edgar R.; Nally, Joseph V.; Pirsch, John D.; Portman, Ronald J.; Sevick, Mary Ann; Sica, Domenic; Wesson, Donald E.; Agodoa, Lawrence; Bolton, Kline; Cutler, Jeffrey A.; Hostetter, Tom; Lau, Joseph; Uhlig, Katrin; Chew, Priscilla; Kausz, Annamaria; Kupelnick, Bruce; Raman, Gowri; Sarnak, Mark; Wang, Chenchen; Astor, Brad C.; Eknoyan, Garabed; Levin, Adeera; Levin, Nathan; Bailie, George; Becker, Bryan; Becker, Gavin; Burrowes, Jerrilynn; Carrera, Fernando; Churchill, David; Collins, Allan; Crooks, Peter W.; de Zeeuw, Dick; Golper, Thomas; Gotch, Frank; Gotto, Antonio; Greenwood, Roger; Greer, Joel W.; Grimm Jr., Richard; Haley, William E.; Hogg, Ronald; Hull, Alan R.; Hunsicker, Lawrence; Klag, Michael; Klahr, Saulo; Lameire, Norbert; Locatelli, Francesco; McCulloch, Sally; Michael, Maureen; Newmann, John M.; Nissenson, Allen; Norris, Keith; Obrador, Gregorio; Owen Jr., William; Patel, Thakor G.; Payne, Glenda; Ronco, Claudio; Rivera-Mizzoni, Rosa A.; Schoolwerth, Anton C.; Star, Robert; Steffes, Michael; Steinman, Theodore; Wauters, John-Pierre; Wenger, Nanette; Briggs, Josephine; Burrows-Hudson, Sally; Latos, Derrick; Mapes, Donna; Oberley, Edith; Pereira, Brian J.G.; Willis, Kerry; Gucciardo, Anthony; Fingerhut, Donna; Klette, Margaret; Schachne, Elicia

    2004-01-01

    INTRODUCTION: CHRONIC KIDNEY disease (CKD) is a worldwide public health issue. In the United States, there is a rising incidence and prevalence of kidney failure (Fig 1), with poor outcomes and high cost. The prevalence of earlier stages of CKD is approximately 100 times greater than the prevalence

  17. Curcumin: Reintroduced Therapeutic Agent from Traditional Medicine for Alcoholic Liver Disease

    Hamid Reza Rahimi

    2015-03-01

    Full Text Available Alcoholic liver disease (ALD is the main cause of chronic liver disease across the world and can lead to fibrosis and cirrhosis. The etiopathogenesis of ALD is related to ethanol-induced oxidative stress, glutathione reduction, abnormal methionine metabolism, malnutrition, and production of endotoxins that activate Kupffer cells. Curcumin is an active ingredient of the rhizome of turmeric. The substance is shown to have minor adverse effects. As the substance possess low bioavailability in free formulation, different strategies has been conducted to improve its bioavailability which resulted in production of nanomiscels and nanoparticles. Curcumin can provide protection for the liver against toxic effects of alcohol use. Several studies showed curcumin blocks endotoxin-mediated activation of NF-κB and suppresses the expression of cytokines, chemokines, COX-2, and iNOS in Kupffer cells. According to the molecular studies, curcumin inhibits NF-κB signaling pathway, regulates cytokines production and modulates immune response. It has been shown that curcumin can suppress gene expression, especially cytokines genes resulting in down-regulation of tumor necrosis factor-α (TNF-α, interleukin 1 (IL-1, IL-6, IL-8, adhesion molecules (ICAM, VCAM and C-reactive protein. Hence, curcumin can have therapeutic effects on the majority of chronic inflammatory diseases such as asthma, bronchitis, inflammatory bowel disease, rheumatoid arthritis, ALD, fatty liver, and allergy.

  18. Tree disease and wood decay as agents of environmental and social change

    Kevin T. Smith

    2018-01-01

    The breakdown or decay of wood is a prominent process in landscape health and disease. The bulk of the energy captured and stored by natural woodlands, orchards, and agroforestry operations is allocated to produce wood. The release of that stored energy and the cycling of the constituent mineral elements into environmental pools and other organisms is through processes...

  19. 75 FR 14391 - Diseases Associated With Exposure to Certain Herbicide Agents (Hairy Cell Leukemia and Other...

    2010-03-25

    ... blood and oxygen to a portion of the myocardium; it typically occurs when there is an imbalance between... include hypertension or peripheral manifestations of arteriosclerosis such as peripheral vascular disease... mirror that average. Only the benefit costs of the presumptive conditions listed. Secondary conditions...

  20. Alzheimer's disease: pathophysiology and applications of magnetic nanoparticles as MRI theranostic agents.

    Amiri, H.; Saeidi, K.; Borhani, P.; Manafirad, A.; Ghavami, M.; Zerbi, V.

    2013-01-01

    Alzheimer's disease (AD) is the most common form of dementia. During the recent decade, nanotechnology has been widely considered, as a promising tool, for theranosis (diagnosis and therapy) of AD. Here we first discuss pathophysiology and characteristics of AD with a focus on the amyloid cascade

  1. Sex-dimorphic adverse drug reactions to immune suppressive agents in inflammatory bowel disease

    Z. Zelinkova (Zuzana); E. Bultman (Evelien); L. Vogelaar (Lauran); C. Bouziane (Cheima); E.J. Kuipers (Ernst); C.J. van der Woude (Janneke)

    2012-01-01

    textabstractAIM: To analyze sex differences in adverse drug reactions (ADR) to the immune suppressive medication in inflammatory bowel disease (IBD) patients. METHODS: All IBD patients attending the IBD outpatient clinic of a referral hospital were identifed through the electronic diagnosis

  2. An analytic method for agent-based modeling of spatially inhomogeneous disease dynamics

    Bock, W.; Fattler, T.; Rodiah, I.; Tse, O.T.C.; Villagonzalo, C.D.; Esguerra, J.P.H.; Soriano, M.N.; Bornales, J.B.; Carpio-Bernido, M.V.; Bernido, C.C.

    2017-01-01

    In this article we set up a microscopic model for the spread of an infectious disease based on configuration space analysis. Using the so-called Vlasov scaling we obtained the corresponding mesoscopic (kinetic) equations, describing the density of susceptible and infected individuals (particles) in

  3. An overview of the aetiologic agents of diarrhoea diseases in children

    Diarrhoea disease is the second leading cause of death amongst Nigerian children (after malaria) with a prevalence rate in Nigeria of 18.8% which is one of the worst in sub-Sahara Africa. A major contributor to childhood morbidity and mortality, causes 4 million deaths each year in under-fives with each child experiencing ...

  4. Stimulation or Inhibition: Conflicting evidence for (+/-)-catechin's role as a chemical facilitator and disease protecting agent.

    Bais, Harsh P; Venkatachalam, L; Biedrzycki, Meredith L

    2010-03-01

    The occurrence of plant hormesis is a poorly understood phenomenon, wherein low doses of phytotoxins unusually promote growth responses in higher plants. In contrast, negative plant-plant interactions mediated through secreted small molecular weight compounds initiate growth inhibitory responses. Studies related to (+/-)-catechin mediated allelopathy have transpired both novel information and generated significant controversy. Specifically, studies related to the phytotoxicity responses mediated by (+/-)-catechins have been seriously debated. The pronged opinion that (+/-)-catechin is phytotoxic versus non-phytotoxic relies more on the target plant systems and the conditions used to test phytotoxic responses. It is reported that lower than MIC dosage supplementation of (+/-)-catechin could promote growth responses in the model plant Arabidopsis thaliana. Furthermore, it was shown that sub-MIC levels of (+/-)-catechin supplementation leads to elicitation of disease resistance against Pseudomonas syringae DC3000 (hereafter DC3000). Intrigued by the unique hormesis response observed, we tested whether (+/-)-catechin indeed promotes growth responses in A. thaliana. In our hands, we observed no growth promotion responses of (+/-)-catechin against A. thaliana under in vitro or in soil conditions. We also evaluated the previously reported disease protecting properties of (+/-)-catechin in A. thaliana against DC3000. The systematic observations to evaluate disease protecting properties entailing colony counts, disease incidences and loss of chlorophyll studies showed no disease protecting properties of (+/-)-catechin. The transcriptional response for a marker pathogenesis related PR1 defense gene showed no induction post (+/-)-catechin supplementation. The cell death genes (ACD2 and CAD1) associated with programmed cell death revealed unchanged expression levels in plants treated with sub-MIC levels of (+/-)-catechin. Further, we report supplementation of sub-MIC levels of

  5. Disease-modifying anti-rheumatic drugs til behandling af ankyloserende spondylitis

    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...

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

    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).

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

    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

  8. Resorbable electrospun polydioxanone fibres modify the behaviour of cells from both healthy and diseased human tendons

    A Kendal

    2017-02-01

    Full Text Available Chronic tendinopathy in an active and ageing population represents an increasing burden to healthcare systems. Rotator cuff tendinopathy alone accounts for approximately 70 % of all shoulder pain. Tendinopathic tissue has a disorganised extracellular matrix, altered vasculature, and infiltration of fibroblasts and inflammatory cells. This altered biology may contribute to the limited success of surgical repair strategies. Electrospun resorbable scaffolds can potentially enhance endogenous repair mechanisms by influencing the tissue microenvironment. Polydioxanone (PDO has an established safety profile in patients. We compared the response of healthy and diseased human tendon cells to electrospun PDO fibres using live cell imaging, proliferation, flow cytometry, and gene expression studies. Within 4 h of initial contact with electrospun PDO, healthy tendon cells underwent a marked transformation; elongating along the fibres in a fibre density dependent manner. Diseased tendon cells initially responded at a slower rate, but ultimately underwent a similar morphological change. Electrospun fibres increased the proliferation rate of diseased tendon cells and increased the ratio of type I:IIIcollagenmRNA expression. Flow cytometry revealed decreased expression of CD106, a marker of mesenchymal stem cells, and increased expression of CD10 on healthy versus diseased tendon cells. PDO electrospun scaffolds further promoted CD106negCD10pos expression of healthy tendon cells. Despite their behavioural differences, both healthy and diseased human tendon cells responded to electrospun PDO fibres. This encourages further work establishing their efficacy in augmenting surgical repair of diseased tendons.

  9. Sequencing of disease-modifying therapies for relapsing-remitting multiple sclerosis: a theoretical approach to optimizing treatment.

    Grand'Maison, Francois; Yeung, Michael; Morrow, Sarah A; Lee, Liesly; Emond, Francois; Ward, Brian J; Laneuville, Pierre; Schecter, Robyn

    2018-04-18

    Multiple sclerosis (MS) is a chronic disease which usually begins in young adulthood and is a lifelong condition. Individuals with MS experience physical and cognitive disability resulting from inflammation and demyelination in the central nervous system. Over the past decade, several disease-modifying therapies (DMTs) have been approved for the management of relapsing-remitting MS (RRMS), which is the most prevalent phenotype. The chronic nature of the disease and the multiple treatment options make benefit-risk-based sequencing of therapy essential to ensure optimal care. The efficacy and short- and long-term risks of treatment differ for each DMT due to their different mechanism of action on the immune system. While transitioning between DMTs, in addition to immune system effects, factors such as age, disease duration and severity, disability status, monitoring requirements, preference for the route of administration, and family planning play an important role. Determining a treatment strategy is therefore challenging as it requires careful consideration of the differences in efficacy, safety and tolerability, while at the same time minimizing risks of immune modulation. In this review, we discuss a sequencing approach for treating RRMS, with importance given to the long-term risks and individual preference when devising a treatment plan. Evidence-based strategies to counter breakthrough disease are also addressed.

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

    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.

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

    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.

  12. Bio-protective microbial agents from rhizosphere eco-systems trigger plant defense responses provide protection against sheath blight disease in rice (Oryza sativa L.).

    Singh, Udai B; Malviya, Deepti; Wasiullah; Singh, Shailendra; Pradhan, Jatindra K; Singh, Bhanu P; Roy, Manish; Imram, Mohd; Pathak, Neelam; Baisyal, B M; Rai, Jai P; Sarma, B K; Singh, Rajiv K; Sharma, P K; Kaur, Saman Deep; Manna, M C; Sharma, Sushil K; Sharma, Arun K

    2016-11-01

    Sheath blight of rice (Oryza sativa L.) caused by Rhizoctonia solani is a major disease and attempts are being made to develop microbe based technologies for biocontrol of this pathogen. However, the mechanisms of biocontrol are not fully understood and still require indepth study in the backdrop of emerging concepts in biological systems. The present investigation was aimed at deciphering the mechanisms of biocontrol of sheath blight of rice employing Pseudomonas fluorescens and Trichoderma harzianum as model agents for biocontrol. Initially 25, 5 and 5 strains of P. fluorescens, T. viride and T. harzianum, respectively, were screened for their biocontrol potential. Out of which, six strains with higher value of percent inhibition of fungal mycelium in dual plate assay were selected. The role of P. fluorescens, T. viride and T. harzianum were investigated in induction and bioaccumulation of natural antioxidants, defence-related biomolecules and other changes in plant which lead not only to growth promotion but also protection from pathogenic stress conditions in rice. The two most promising strains, P. fluorescens PF-08 and T. harzianum UBSTH-501 selected on the basis of in planta evaluation, when applied individually or in combination, significantly enhanced the accumulation of defence-related biomolecules, enzymes and exhibited biocontrol potential against R. solani. A modified/newly developed delivery system was applied for the first time in the experiments involving inoculation of plants with both bioagents, viz. P. fluorescens PF-08 and T. harzianum UBSTH-501. Results suggested that application of P. fluorescens PF-08 and T. harzianum UBSTH-501 alone or in combination, not only helps in control of the disease but also increases plant growth along with reduction in application of toxic chemical pesticides. Copyright © 2016 Elsevier GmbH. All rights reserved.

  13. Risk of Lymphoma in Patients With Inflammatory Bowel Disease Treated With Anti-Tumor Necrosis Factor Alpha Agents: A Systematic Review and Meta-analysis.

    Yang, Chen; Huang, Junlin; Huang, Xiaowen; Huang, Shaozhuo; Cheng, Jiaxin; Liao, Weixin; Chen, Xuewen; Wang, Xueyi; Dai, Shixue

    2018-05-12

    The association between anti-tumor necrosis factor alpha agents and the risk of lymphoma in patients with inflammatory bowel disease has already been sufficiently reported. However, the results of these studies are inconsistent. Hence, this analysis was conducted to investigate whether anti-tumor necrosis factor alpha agents can increase the risk of lymphoma in inflammatory bowel disease patients. MEDLINE, EMBASE and the Cochrane Library were searched to identify relevant studies which evaluated the risk of lymphoma in inflammatory bowel disease patients treated with anti-tumor necrosis factor alpha agents. A random-effects meta-analysis was performed to calculate the pooled incidence rate ratios as well as risk ratios. Twelve studies comprising 285811 participants were included. The result showed that there was no significantly increased risk of lymphoma between anti-tumor necrosis factor alpha agents exposed and anti-tumor necrosis factor alpha agents unexposed groups (random effects: incidence rate ratio [IRR], 1.43 95%CI, 0.91-2.25, p= 0.116; random effects: risk ratio [RR], 0.83 95%CI, 0.47-1.48, p=0.534). However, monotherapy of anti-tumor necrosis factor alpha agents (random effects: IRR=1.65, 95%CI, 1.16-2.35; p=0.006; random effects: RR=1.00, 95%CI, 0.39-2.59; p=0.996) or combination therapy (random effects: IRR=3.36, 95%CI, 2.23-5.05; ptumor necrosis factor alpha agents in patients with inflammatory bowel disease is not associated with a higher risk of lymphoma. Combination therapy and anti-tumor necrosis factor alpha agents monotherapy can significantly increase the risk of lymphoma in patients with inflammatory bowel disease.

  14. Coronary artery disease reporting and data system (CAD-RADSTM): Inter-observer agreement for assessment categories and modifiers.

    Maroules, Christopher D; Hamilton-Craig, Christian; Branch, Kelley; Lee, James; Cury, Roberto C; Maurovich-Horvat, Pál; Rubinshtein, Ronen; Thomas, Dustin; Williams, Michelle; Guo, Yanshu; Cury, Ricardo C

    The Coronary Artery Disease Reporting and Data System (CAD-RADS) provides a lexicon and standardized reporting system for coronary CT angiography. To evaluate inter-observer agreement of the CAD-RADS among an panel of early career and expert readers. Four early career and four expert cardiac imaging readers prospectively and independently evaluated 50 coronary CT angiography cases using the CAD-RADS lexicon. All readers assessed image quality using a five-point Likert scale, with mean Likert score ≥4 designating high image quality, and CAD-RADS assessment categories and modifiers were assessed using intra-class correlation (ICC) and Fleiss' Kappa (κ).The impact of reader experience and image quality on inter-observer agreement was also examined. Inter-observer agreement for CAD-RADS assessment categories was excellent (ICC 0.958, 95% CI 0.938-0.974, p CAD-RADS assessment categories and modifiers is excellent, except for high-risk plaque (modifier V) which demonstrates fair agreement. These results suggest CAD-RADS is feasible for clinical implementation. Copyright © 2017. Published by Elsevier Inc.

  15. Protective glove use and hygiene habits modify the associations of specific pesticides with Parkinson’s disease

    Furlong, Melissa; Tanner, Caroline M; Goldman, Samuel M; Bhudhikanok, Grace S.; Blair, Aaron; Chade, Anabel; Comyns, Kathleen; Hoppin, Jane A.; Kasten, Meike; Korell, Monica; Langston, J William; Marras, Connie; Meng, Cheryl; Richards, Marie; Ross, G Webster; Umbach, David M; Sandler, Dale P; Kamel, Freya

    2014-01-01

    Pesticides have been associated with Parkinson’s disease (PD), and protective gloves and workplace hygiene can reduce pesticide exposure. We assessed whether use of gloves and workplace hygiene modified associations between pesticides and PD. The Farming and Movement Evaluation (FAME) Study is a nested case-control study within the Agricultural Health Study. Use of protective gloves, other PPE, and hygiene practices were determined by questionnaire (69 cases and 237 controls were included). We considered interactions of gloves and hygiene with ever-use of pesticides for all pesticides with ≥ 5 exposed and unexposed cases and controls in each glove-use stratum (paraquat, permethrin, rotenone, and trifluralin). 61% of respondents consistently used protective gloves and 87% consistently used ≥ 2 hygiene practices. Protective glove use modified the associations of paraquat and permethrin with PD: neither pesticide was associated with PD among protective glove users, while both pesticides were associated with PD among non-users (paraquat OR 3.9 [95% CI 1.3, 11.7], interaction p=0.15; permethrin OR 4.3 [95% CI 1.2, 15.6] interaction p=0.05). Rotenone was associated with PD regardless of glove use. Trifluralin was associated with PD among people who used glove use and hygiene practices appeared to be important modifiers of the association between pesticides and PD and may reduce risk of PD associated with certain pesticides. PMID:25461423

  16. Serosurvey of infectious disease agents of carnivores in captive red pandas (Ailurus fulgens) in China.

    Qin, Qin; Wei, Fuwen; Li, Ming; Dubovi, Edward J; Loeffler, I Kati

    2007-03-01

    The future of the endangered red panda (Ailurusfulgens) depends in part on the development of protective measures against infectious diseases. The present study is a first step toward improved understanding of infectious diseases in the species' home regions. Serum samples obtained from 73 red pandas in 10 captive facilities in southwest, east, and northeast China from October to December 2004 were tested for antibodies against nine common infectious pathogens of carnivores. Antibody titers against canine distemper virus (CDV), canine parvovirus (CPV), and canine adenovirus (CAV) in the three facilities in which red pandas were vaccinated were highly variable. The CAV titer in one vaccinated red panda was high enough to suggest infection with the field virus following vaccination. Together with anecdotal reports of vaccine-associated morbidity and mortality, our results suggest that the Chinese vaccine is not suitable for this species. In the seven unvaccinated groups, CDV titers were low and occurred in 20-100% of the animals; antibody titers against CPV were found in seven of eight areas. Only one of 61 and two of 61 unvaccinated red pandas had CAV and canine coronavirus titers, respectively, and these titers were all low. Positive titers to Toxoplasma gondii were found in four locations (33-94% seropositive); the titers in 52% of seropositive individuals were of a magnitude consistent with active disease in other species (1:1,024 to > or = 1:4,096). One red panda in each of three locations was seropositive for Neospora caninum. Antibodies against canine herpesvirus and Brucella canis were not detected in any of the samples. Only one of the 73 red pandas had a weak positive influenza A titer. The results of this study emphasize the need for research on and protection against infectious diseases of red pandas and other endangered species in China.

  17. Antibodies against a tick protein, Salp15, protect mice from the Lyme disease agent

    Dai, Jianfeng; Wang, Penghua; Adusumilli, Sarojini; Booth, Carmen J.; Narasimhan, Sukanya; Anguita, Juan; Fikrig, Erol

    2009-01-01

    Traditionally, vaccines directly target a pathogen or microbial toxin. Lyme disease, caused by Borrelia burgdorferi, is a tick-borne illness for which a human vaccine is not currently available. B. burgdorferi binds a tick salivary protein, Salp15, during transmission from the vector, and this interaction facilitates infection of mice. We now show that Salp15-antiserum significantly protected mice from B. burgdorferi infection. Salp15-antiserum also markedly enhanced the protective capacity o...

  18. The Impact of Conventional and Biological Disease Modifying Antirheumatic Drugs on Bone Biology. Rheumatoid Arthritis as a Case Study.

    Barreira, Sofia Carvalho; Fonseca, João Eurico

    2016-08-01

    The bone and the immune system have a very tight interaction. Systemic immune-mediated inflammatory diseases, such as rheumatoid arthritis (RA), induce bone loss, leading to a twofold increase in osteoporosis and an increase of fragility fracture risk of 1.35-2.13 times. This review focuses on the effects of conventional and biological disease modifying antirheumatic drugs (DMARDs) on bone biology, in the context of systemic inflammation, with a focus on RA. Published evidence supports a decrease in osteoclastic activity induced by DMARDs, which leads to positive effects on bone mineral density (BMD). It is unknown if this effect could be translated into fracture risk reduction. The combination with antiosteoclastic drugs can have an additional benefit.

  19. Current and developing therapeutic agents in the treatment of Chagas disease

    Werner Apt

    2010-09-01

    Full Text Available Werner AptUniversity of Chile, Faculty of Medicine, Santiago, ChileAbstract: Chagas disease must be treated in all its stages: acute, indeterminate, chronic, and initial and middle determinant chronic, due to the fact that DNA of the parasite can be demonstrated by PCR in chronic cases, where optical microscopy does not detect parasites. Nifurtimox (NF and benznidazole (BNZ are the drugs accepted to treat humans based upon ethical considerations and efficiency. However, both the drugs produce secondary effects in 30% of the cases, and the treatment must be given for at least 30–60 days. Other useful drugs are itraconazole and posaconazole. The latter may be the drug to treat Chagas disease in the future when all the investigations related to it are finished. At present, there is no criterion of cure for chronic cases since in the majority, the serology remains positive, although it may decrease. In acute cases, 70% cure with NF and 75% with BNZ is achieved. In congenital cases, 100% cure is obtained if the treatment is performed during the first year of life. In chronic acquired cases, 20% cure and 50% improvement of the electrocardiographic changes are obtained with itraconazole.Keywords: Chagas disease, treatment, nifurtimox, benznidazole, allopurinol, itraconazole, posaconazole

  20. Antibacterial Effect of Potassium Tetraborate Tetrahydrate against Soft Rot Disease Agent Pectobacterium carotovorum in Tomato

    Firas A. Ahmed

    2017-09-01

    Full Text Available Soft rot caused by Pectobacterium carotovorum is one of most common bacterial diseases occurring in fruits and vegetables worldwide, yet consumer-acceptable options for post-harvest disease management are still insufficient. We evaluated the effect of potassium tetraborate tetrahydrate (B4K2O7.4H2O (PTB on the growth of P. carotovorum using strain BA17 as a representative of high virulence. Complete inhibition of bacterial growth was achieved by treatment with PTB at 100 mM both at pH 9.2 and after adjustment to pH 7.0. Bactericidal activity was quantified and validated by counting fluorescently labeled live and dead bacterial cells using flow cytometry, and reconfirmed using qPCR with high-affinity photoreactive DNA binding dye propidium monoazide (PMA. The results of flow cytometry, qPCR, and culturing confirmed that bacterial cells were killed following exposure to PTB at 100 mM. Bacterial cell membranes were damaged following a 5-min treatment and extrusion of cytoplasmic material from bacterial cells was observed using electronic transmission microscopy. Soft rot incidence on inoculated tomato fruit was significantly reduced by dipping infected fruits in PTB at 100 mM for 5 min and no lesions developed following a 10-min treatment. PTB does not pose a hazard to human health and is an effective alternative to other bactericides and antibiotics for controlling soft rot disease of tomato caused by P. carotovorum.

  1. Glucocerebroside: an evolutionary advantage for patients with Gaucher disease and a new immunomodulatory agent.

    Ilan, Yaron; Elstein, Deborah; Zimran, Ari

    2009-10-01

    Gaucher disease (GD) is caused by the reduced activity of a lysosomal enzyme, glucocerebrosidase, leading to the accumulation of glucocerebroside (GC). The relatively high prevalence of this disease within an ethnic group is believed to reflect a selective advantage. Treatment with enzyme replacement therapy (ERT) is safe and effective in ameliorating the primary symptoms of the disease, yet there have been reports that some patients on ERT have developed type 2 diabetes or metabolic syndrome, malignancies and central nervous system disorders. A series of animal studies suggest that these complications may be related to the reduction of GC levels by the enzyme administered. GC has been shown to have an immunomodulatory effect through the promotion of dendritic cells, natural killer T cells, and regulatory T cells. The break down of GC to ceramide can underline part of these findings. Clinical trials suggested a beneficial effect of GC in type 2 diabetes or nonalcoholic steatohepatitis. This review of the data from animal models and humans proposes that the increased level of GC may provide an evolutionary advantage for patients with GD. Indirectly, these data support treating symptomatic patients with mild/moderate GD with low-dose ERT and re-evaluating the use of ERT in asymptomatic patients.

  2. Isolation and evaluation of biocontrol agents in controlling anthracnose disease of mango in Thailand

    Rungjindamai Nattawut

    2016-07-01

    Full Text Available The agricultural based economy is a core business in Thailand and food export is one of the main sources of income for the Thai population. However, pesticides are overused and misused. As a result there is an urgent need to reduce the use of synthetic chemicals. Biological control offers an alternative to the use of pesticides. Mango (Mangifera indica L. is widely planted in Thailand and is one of the major cash crops for international export. However, mango suffers from various diseases especially anthracnose, a fungal disease caused by Colletotrichum gloeosporioides. One hundred and twelve isolates of epiphytic microbes were isolated from healthy leaves and fruits of mangoes; this included 93 and 19 isolates of epiphytic bacteria and yeasts, respectively. They were screened for bioactivity against a pathogenic strain of C. gloeosporioides isolated from diseased mangoes using a dual culture technique. Out of 112 isolates, eight isolates exhibited at least 60% inhibition. These isolates were further screened for their inhibition on mango using fruit inoculation. Two isolates reduced the lesion sizes caused by C. gloeosporioides compared to control treatment. These two isolates, based on phenotypical and biochemical tests, were identified as Bacillus sp. MB61 and Bacillus sp. LB72.

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

    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.

  4. Treating respiratory viral diseases with chemically modified, second generation intranasal siRNAs.

    Barik, Sailen

    2009-01-01

    Chemically synthesized short interfering RNA (siRNA) of pre-determined sequence has ushered a new era in the application of RNA interference (RNAi) against viral genes. We have paid particular attention to respiratory viruses that wreak heavy morbidity and mortality worldwide. The clinically significant ones include respiratory syncytial virus (RSV), parainfluenza virus (PIV) and influenza virus. As the infection by these viruses is clinically restricted to the respiratory tissues, mainly the lungs, the logical route for the application of the siRNA was also the same, i.e., via the nasal route. Following the initial success of intranasal siRNA against RSV, second-generation siRNAs were made against the viral polymerase large subunit (L) that were chemically modified and screened for improved stability, activity and pharmacokinetics. 2'-O-methyl (2'-O-Me) and 2'-deoxy-2'-fluoro (2'-F) substitutions in the ribose ring were incorporated in different positions of the sense and antisense strands and the resultant siRNAs were tested with various transfection reagents intranasally against RSV. Based on these results, we propose the following consensus for designing intranasal antiviral siRNAs: (i) modified 19-27 nt long double-stranded siRNAs are functional in the lung, (ii) excessive 2'-OMe and 2'-F modifications in either or both strands of these siRNAs reduce efficacy, and (iii) limited modifications in the sense strand are beneficial, although their precise efficacy may be position-dependent.

  5. Bacterial and protozoal agents of feline vector-borne diseases in domestic and stray cats from southern Portugal

    2014-01-01

    Background Feline vector-borne diseases (FVBD) have emerged in recent years, showing a wider geographic distribution and increased global prevalence. In addition to their veterinary importance, domestic cats play a central role in the transmission cycles of some FVBD agents by acting as reservoirs and sentinels, a circumstance that requires a One Health approach. The aim of the present work was to molecularly detect feline vector-borne bacteria and protozoa with veterinary and zoonotic importance, and to assess associated risk factors in cats from southern Portugal. Methods Six hundred and forty-nine cats (320 domestic and 329 stray), from veterinary medical centres and animal shelters in southern Portugal, were studied. Anaplasma spp./Ehrlichia spp., Babesia spp., Bartonella spp., Borrelia burgdorferi sensu lato, Hepatozoon spp. and Leishmania spp. infections were evaluated by polymerase chain reaction (PCR) in blood samples. Results One hundred and ninety-four (29.9%) cats were PCR-positive to at least one of the tested genera or complex of FVBD agents. Sixty-four (9.9%) cats were positive to Leishmania spp., 56 (8.6%) to Hepatozoon spp., 43 (6.6%) to Babesia spp., 35 (5.4%) to Anaplasma spp./Ehrlichia spp., 19 (2.9%) to Bartonella spp. and 14 (2.2%) to B. burgdorferi s.l. Thirty-three (5.1%) cats were positive to two (n = 29) or three (n = 4) genera/complex. Babesia vogeli, Bartonella clarridgeiae, Bartonella henselae, Ehrlichia canis, Hepatozoon felis and Leishmania infantum were identified by DNA sequencing. Conclusions The occurrence of FVBD agents in southern Portugal, some of them with zoonotic character, emphasizes the need to alert the veterinary community, owners and public health authorities for the risk of infection. Control measures should be implemented to prevent the infection of cats, other vertebrate hosts and people. PMID:24655431

  6. Intravenous Versus Subcutaneous Anti-TNF-Alpha Agents for Crohn's Disease: A Comparison of Effectiveness and Safety.

    Liu, Jinan; Sylwestrzak, Gosia; Ruggieri, Alexander P; DeVries, Andrea

    2015-07-01

    In recent years, there have been a number of pharmacological innovations for Crohn's disease (CD), a difficult-to-treat condition, including new treatment philosophies (e.g., top-down therapy) and new therapeutic options in terms of the agent and the route of administration. Three anti-tumor necrosis factor (anti-TNF-alpha) agents are available for use among CD patients in the United States: infliximab, an intravenous agent, and adalimumab and certolizumab pegol, 2 newer subcutaneous products. Infliximab is considered the "gold standard" because it has the longest clinical experience, and adalimumab and certolizumab pegol have each gained significant market share. To examine differences in effectiveness and safety between currently available intravenous and subcutaneous anti-TNF-alpha agents used to treat patients with CD. Data for this retrospective, administrative claims analysis were obtained from pharmacy and medical claims from major U.S. health plans geographically dispersed across 14 states during 2007-2011. Patients had at least 1 ICD-9-CM diagnosis for CD, 6 months pre-index eligibility, and initiated anti-TNF-alpha therapy on the index date. Patients in each cohort were propensity score matched on pre-index demographics, clinical characteristics, and baseline health care use. During the post-index period, age-sex adjusted incidence rate ratios (IRRs) of CD-related symptoms, infections, cancers, and hepatic-related conditions were compared using Cox (PH) models. The matched cohorts included 515 patients in each group, with an average age of 39 years. Median follow-up was 17.5 months in the intravenous cohort and 17.7 months in the subcutaneous cohort. In terms of effectiveness outcomes, age-sex adjusted IRRs for the subcutaneous group, with the intravenous cohort as a reference, were as follows: 0.61 (95% CI = 0.32-1.18, P = 0.14) for anal fissures; 0.97 (95% CI = 0.72-1.30, P = 0.85) for abscess; 1.08 (95% CI = 0.79-1.04, P = 0

  7. Social exclusion modifies climate and deforestation impacts on a vector-borne disease.

    Chaves, Luis Fernando; Cohen, Justin M; Pascual, Mercedes; Wilson, Mark L

    2008-02-06

    The emergence of American Cutaneous Leishmaniasis (ACL) has been associated with changes in the relationship between people and forests, leading to the view that forest ecosystems increase infection risk and subsequent proposal that deforestation could reduce re-emergence of this disease. We analyzed county-level incidence rates of ACL in Costa Rica (1996-2000) as a function of social and environmental variables relevant to transmission ecology with statistical models that incorporate breakpoints. Once social marginality was taken into account, the effect of living close to a forest on infection risk was small, and diminished exponentially above a breakpoint. Forest cover was associated with the modulation of temporal effects of El Niño Southern Oscillation (ENSO) at small spatial scales, revealing an additional complex interplay of environmental forces and disease patterns. Social factors, which previously have not been evaluated rigorously together with environmental and climatic factors, appear to play a critical role that may ultimately determine disease risk.

  8. Functional and biophysical studies on four ceratoplatanins from the fungus Moniliophthora perniciosa, causal agent of the Witche's broom disease

    Barsottini, M.; Zaparoli, G.; Garcia, O.; Pereira, G.A.G.; Oliveira, J.F.; Tiezzi, H.O.; Ambrosio, A.L.B.; Dias, S.M.G.

    2012-01-01

    Full text: Ceratoplatanin (CP) is a secreted protein of 12.4 kDa initially identified in culture filtrates of the disease ascomycete Ceratocystis fimbriata f. sp. platani, etiological agent of the canker stain disease. CP is also the founding member of the namesake protein family, which contains fungal-secreted proteins involved in various stages of the host-fungus interaction and may act as phytotoxins or elicitors of defense response. Besides the low molecular weight, CPs have a high percentage of hydrophobic residues and share two conserved intramolecular disulfide bonds. It has been suggested that CPs have important physiological functions, including interaction with cell wall or cell membrane and manipulation of the host's defense system. Furthermore, a recent work showed that the ceratoplatanin from C. fimbriata has some degree of affinity for the saccharide 4-N-acetylglucosamine. However, its precise molecular function remains elusive. Five putative CPs have been identified in Moniliophthora perniciosa a basidiomycete fungus responsible for great economic losses in cocoa industry in the form of Witches' broom disease (WBD) , four of which had their crystal structures resolved by our group. In this work we report biophysical and functional studies on these MpCPs aiming at understanding their role and importance during the WBD progression. (author)

  9. Genetic diversity of the causative agent of ice-ice disease of the seaweed Kappaphycus alvarezii from Karimunjawa island, Indonesia

    Syafitri, E.; Prayitno, S. B.; Ma'ruf, W. F.; Radjasa, O. K.

    2017-02-01

    An essential step in investigating the bacterial role in the occurrence of diseases in Kappaphycus alvarezii is the characterization of bacteria associated with this seaweed. A molecular characterization was conducted on the genetic diversity of the causative agents of ice-ice disease associated with K. alvarezii widely known as the main source of kappa carrageenan. K. alvrezii infected with ice-ice were collected from the Karimunjawa island, North Java Sea, Indonesia. Using Zobell 2216E marine agar medium, nine bacterial species were isolated from the infected seaweed. The molecular characterizations revealed that the isolated bacteria causing ice-ice disease were closely related to the genera of Alteromonas, Bacillus, Pseudomonas, Pseudoalteromonas, Glaciecola, Aurantimonas, and Rhodococcus. In order to identify the symptoms causative organisms, the isolated bacterial species were cultured and were evaluated for their pathogenity. Out of 9 species, only 3 isolates were able to cause the ice-ice symptoms and consisted of Alteromonas macleodii, Pseudoalteromonas issachenkonii and Aurantimonas coralicida. A. macleodii showed the highest pathogenity.

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

    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; Gómez-Tortosa, Estrella; Mayo Cabrero, David; Jones, Randi; Zanko, Andrea; Nance, Martha; Abramson, Ruth K.; Suchowersky, Oksana; Paulsen, Jane S.; Harrison, Madaline B.; Yang, Qiong; Cupples, L. Adrienne; Mysore, Jayalakshmi; Gusella, James F.; MacDonald, Marcy E.

    2007-01-01

    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 (Drosophila homeo box homologue 1, formerly known as homeo box 7, HOX7), Δ2642 (within the HD coding sequence), and BJ56 (D4S127). Suggestive evidence for an association was seen between MSX1 alleles and AO, after adjustment for normal CAG repeat, expanded repeat, and their product term (model P value 0.079). Of the variance of AO that was not accounted for by HD and normal CAG repeats, 0.8% could be attributed to the MSX1 genotype. Individuals with MSX1 genotype 3/3 tended to have younger AO. No association was found between Δ2642 (P=0.44) and BJ56 (P=0.73) and AO. This study supports previous studies suggesting that there may be a significant genetic modifier for AO in HD in the 4p16 region. Furthermore, the modifier may be present on both HD and normal chromosomes bearing the 3 allele of the MSX1 marker. PMID:15029481

  11. Climate variability and change in the United States: potential impacts on water- and foodborne diseases caused by microbiologic agents.

    Rose, J B; Epstein, P R; Lipp, E K; Sherman, B H; Bernard, S M; Patz, J A

    2001-05-01

    Exposure to waterborne and foodborne pathogens can occur via drinking water (associated with fecal contamination), seafood (due to natural microbial hazards, toxins, or wastewater disposal) or fresh produce (irrigated or processed with contaminated water). Weather influences the transport and dissemination of these microbial agents via rainfall and runoff and the survival and/or growth through such factors as temperature. Federal and state laws and regulatory programs protect much of the U.S. population from waterborne disease; however, if climate variability increases, current and future deficiencies in areas such as watershed protection, infrastructure, and storm drainage systems will probably increase the risk of contamination events. Knowledge about transport processes and the fate of microbial pollutants associated with rainfall and snowmelt is key to predicting risks from a change in weather variability. Although recent studies identified links between climate variability and occurrence of microbial agents in water, the relationships need further quantification in the context of other stresses. In the marine environment as well, there are few studies that adequately address the potential health effects of climate variability in combination with other stresses such as overfishing, introduced species, and rise in sea level. Advances in monitoring are necessary to enhance early-warning and prevention capabilities. Application of existing technologies, such as molecular fingerprinting to track contaminant sources or satellite remote sensing to detect coastal algal blooms, could be expanded. This assessment recommends incorporating a range of future scenarios of improvement plans for current deficiencies in the public health infrastructure to achieve more realistic risk assessments.

  12. Disease-modifying anti-rheumatic drug use in pregnant women with rheumatic diseases: a systematic review of the risk of congenital malformations.

    Baldwin, Corisande; Avina-Zubieta, Antonio; Rai, Sharan K; Carruthers, Erin; De Vera, Mary A

    2016-01-01

    Despite the high incidence of rheumatic diseases during the reproductive years, little is known about the impact of disease-modifying anti-rheumatic drug (DMARD) use during pregnancy. Our objective was to systematically review and appraise evidence in women with rheumatic disease on the use of traditional and biologic DMARDs during pregnancy and the risk of congenital malformation outcomes. We conducted a systematic search of MEDLINE, EMBASE, and INTERNATIONAL PHARMACEUTICAL ABSTRACTS databases. Inclusion criteria were: 1) study sample including women with rheumatic disease; 2) use of traditional and/or biologic DMARDs during pregnancy; and 3) congenital malformation outcome(s) reported. We extracted information on study design, data source, number of exposed pregnancies, type of DMARD, number of live births, and number of congenital malformations. Altogether, we included 79 studies; the majority were based on designs that did not involve a comparison group, including 26 case reports, 17 case series, 20 cross-sectional studies, and 4 surveys. Studies that had a comparator group included 1 case control, 10 cohort studies, and 1 controlled trial. Hydroxychloroquine and azathioprine represent the most studied traditional DMARD exposures and, among biologics, most of the reports were on infliximab and etanercept. This is the first systematic review on the use of both traditional and biologic DMARDs during pregnancy among women with rheumatic diseases and congenital malformation outcomes, with a focus on study design and quality. Findings confirm the limited number of studies, as well as the need to improve study designs.

  13. The potential of a fluorescent-based approach for bioassay of antifungal agents against chili anthracnose disease in Thailand.

    Chutrakul, Chanikul; Khaokhajorn, Pratoomporn; Auncharoen, Patchanee; Boonruengprapa, Tanapong; Mongkolporn, Orarat

    2013-01-01

    Severe chili anthracnose disease in Thailand is caused by Colletotrichum gloeosporioides and C. capsici. To discover anti-anthracnose substances we developed an efficient dual-fluorescent labeling bioassay based on a microdilution approach. Indicator strains used in the assay were constructed by integrating synthetic green fluorescent protein (sGFP) and Discosoma sp. red fluorescent protein (DsRedExp) genes into the genomes of C. gloeosporioides or C. capsici respectively. Survival of co-spore cultures in the presence of inhibitors was determined by the expression levels of these fluorescent proteins. This developed assay has high potential for utilization in the investigation of selective inhibition activity to either one of the pathogens as well as the broad-range inhibitory effect against both pathogens. The value of using the dual-fluorescent assay is rapid, reliable, and consistent identification of anti-anthracnose agents. Most of all, the assay enables the identification of specific inhibitors under the co-cultivation condition.

  14. Alemtuzumab for patients with relapsing multiple sclerosis after disease-modifying therapy

    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....

  15. 4p16.3 haplotype modifying age at onset of Huntington disease

    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, ...

  16. Human apolipoprotein E genotypes differentially modify house dust mite-induced airway disease in mice

    Yao, Xianglan; Dai, Cuilian; Fredriksson, Karin

    2012-01-01

    Apolipoprotein E (apoE) is an endogenous negative regulator of airway hyperreactivity (AHR) and mucous cell metaplasia in experimental models of house dust mite (HDM)-induced airway disease. The gene encoding human apoE is polymorphic, with three common alleles (e2, e3, and e4) reflecting single ...

  17. Epigenetic histone acetylation modifiers in vascular remodelling : New targets for therapy in cardiovascular disease

    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

  18. Nanoparticles as potential clinical therapeutic agents in Alzheimer's disease: focus on selenium nanoparticles.

    Nazıroğlu, Mustafa; Muhamad, Salina; Pecze, Laszlo

    2017-07-01

    In etiology of Alzheimer's disease (AD), involvement of amyloid β (Aβ) plaque accumulation and oxidative stress in the brain have important roles. Several nanoparticles such as titanium dioxide, silica dioxide, silver and zinc oxide have been experimentally using for treatment of neurological disease. In the last decade, there has been a great interest on combination of antioxidant bioactive compounds such as selenium (Se) and flavonoids with the oxidant nanoparticles in AD. We evaluated the most current data available on the physiological effects of oxidant and antioxidant nanoparticles. Areas covered: Oxidative nanoparticles decreased the activities of reactive oxygen species (ROS) scavenging enzymes such as glutathione peroxidase (GSH-Px), superoxide dismutase (SOD) and catalase in the brain of rats and mice. However, Se-rich nanoparticles in small size (5-15 nm) depleted Aβ formation through decreasing ROS production. Reports on low levels of Se in blood and tissue samples and the low activities of GSH-Px, catalase and SOD enzymes in AD patients and animal models support the proposed crucial role of oxidative stress in the pathogenesis of AD. Expert commentary: In conclusion, present literature suggests that Se-rich nanoparticles appeared to be a potential therapeutic compound for the treatment of AD.

  19. Naturally Inspired Molecules as Multifunctional Agents for Alzheimer’s Disease Treatment

    Angela Rampa

    2016-05-01

    Full Text Available Alzheimer’s disease (AD has been defined as a multi-factorial disorder resulting from a complex array of networked cellular and molecular mechanisms. In particular, elevated levels of Aβ protein and its aggregation products in the presence of metal ions proved to be highly neurotoxic and therapeutic strategies aimed at preventing Aβ generation and oxidative stress may represent an effective approach for AD treatment. A recent paradigm for the treatment of complex diseases such as AD suggests the employment of multifunctional compounds, single chemical entities capable of simultaneously modulating different targets involved in the pathology. In this paper, the “pharmacophores combination” strategy was applied, connecting the main scaffold of the BACE-1 ligand 1 to that of the chalcone 2, as metal chelating pharmacophore, to obtain a small library of compounds. Conjugate 5 emerged as the most interesting derivative, proving to inhibit BACE-1 with low-micromolar potency, and showing neuroprotective effects. In particular, 5 proved to be able to protect from metal-associated oxidative stress by hampering intracellular Cu2+-induced ROS formation without any direct neurotoxic effect.

  20. Nanotechnology solutions for Alzheimer's disease: advances in research tools, diagnostic methods and therapeutic agents.

    Nazem, Amir; Mansoori, G Ali

    2008-03-01

    A century of research has passed since the discovery and definition of Alzheimer's disease (AD), the primary common dementing disorder worldwide. However, AD lacks definite diagnostic approaches and effective cure at the present. Moreover, the currently available diagnostic tools are not sufficient for an early screening of AD in order to start preventive approaches. Recently the emerging field of nanotechnology has promised new techniques to solve some of the AD challenges. Nanotechnology refers to the techniques of designing and manufacturing nanosize (1-100 nm) structures through controlled positional and/or self-assembly of atoms and molecules. In this report, we present the promises that nanotechnology brings in research on the AD diagnosis and therapy. They include its potential for the better understanding of the AD root cause molecular mechanisms, AD's early diagnoses, and effective treatment. The advances in AD research offered by the atomic force microscopy, single molecule fluorescence microscopy and NanoSIMS microscopy are examined here. In addition, the recently proposed applications of nanotechnology for the early diagnosis of AD including bio-barcode assay, localized surface plasmon resonance nanosensor, quantum dot and nanomechanical cantilever arrays are analyzed. Applications of nanotechnology in AD therapy including neuroprotections against oxidative stress and anti-amyloid therapeutics, neuroregeneration and drug delivery beyond the blood brain barrier (BBB) are discussed and analyzed. All of these applications could improve the treatment approach of AD and other neurodegenerative diseases. The complete cure of AD may become feasible by a combination of nanotechnology and some other novel approaches, like stem cell technology.

  1. Implementation of a Tool to Modify Behavior in a Chronic Disease Management Program

    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.

  2. Lifestyle modifies obesity-associated risk of cardiovascular disease in a genetically homogeneous population

    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 of 2311...... Inuit living in Denmark (n = 995) or Greenland (n = 1316). The participants received an oral-glucose-tolerance test. Blood tests were supplemented by structured interviews and anthropometric and blood pressure measurements. RESULTS: The trend in the association between obesity and metabolic effects...

  3. Modified Lipids and Lipoproteins in Chronic Kidney Disease: A New Class of Uremic Toxins

    Nans Florens

    2016-12-01

    Full Text Available Chronic kidney disease (CKD is associated with an enhanced oxidative stress and deep modifications in lipid and lipoprotein metabolism. First, many oxidized lipids accumulate in CKD and were shown to exert toxic effects on cells and tissues. These lipids are known to interfere with many cell functions and to be pro-apoptotic and pro-inflammatory, especially in the cardiovascular system. Some, like F2-isoprostanes, are directly correlated with CKD progression. Their accumulation, added to their noxious effects, rendered their nomination as uremic toxins credible. Similarly, lipoproteins are deeply altered by CKD modifications, either in their metabolism or composition. These impairments lead to impaired effects of HDL on their normal effectors and may strongly participate in accelerated atherosclerosis and failure of statins in end-stage renal disease patients. This review describes the impact of oxidized lipids and other modifications in the natural history of CKD and its complications. Moreover, this review focuses on the modifications of lipoproteins and their impact on the emergence of cardiovascular diseases in CKD as well as the appropriateness of considering them as actual mediators of uremic toxicity.

  4. DISEASE MODIFYING THERAPY AND OUTCOME OF RHEUMATOID ARTHRITIS: RETROSPECTIVE ASSESSMENT OF LONG-TERM RESULTS

    D. E. Karateyev

    2000-01-01

    Full Text Available Aim of study: To investigate the relation between patterns of basic treatment and the outcome of disease in patients with rheumatoid arthritis (RA. Material and methods: We studied retrospectively two groups of patients with RA (1987 ACR criteria: 1 main group - died (72 patients, mean duration of disease from the onset to death 12.8±0.9 years; 2 control group - alive to 1999 with duration of disease at least 15 years (90 patients, mean follow-up period 19.4±0.47 years. Results: Some patterns of basic treatment were observed: 1 "passive ” strategy - only hydroxychloroquine or sulphasalazine during many years; 2 "inteirupted " treatment - early treatment gold or cytotoxics, but when improvement occurred, therapy with DMARD was interrupted for 1-2 years or more, after that re-started etc.; 3 “emergency” strategy’ - 7-10years of "passive" treatment, after that se\\>ere destruction and/or amyloidosis appeared, and cytotoxics started; 4 typical "pyramid " strategy; 5 "active " strategy - early start of treatment with active DMARD (melotrexate, gold with consecutive change of DMARDs without interruption of basic treatment (very close to "sawtooth ” strategy. The most of died patients were treated with "passive ” and "interrupted" strategies, but the most of patients in control group were treated with "pyramid” and "active" strategies. Conclusion: active strategy of basic treatment has a positive influence on the survival ofpatients with R.A.

  5. Modified Lipids and Lipoproteins in Chronic Kidney Disease: A New Class of Uremic Toxins.

    Florens, Nans; Calzada, Catherine; Lyasko, Egor; Juillard, Laurent; Soulage, Christophe O

    2016-12-16

    Chronic kidney disease (CKD) is associated with an enhanced oxidative stress and deep modifications in lipid and lipoprotein metabolism. First, many oxidized lipids accumulate in CKD and were shown to exert toxic effects on cells and tissues. These lipids are known to interfere with many cell functions and to be pro-apoptotic and pro-inflammatory, especially in the cardiovascular system. Some, like F2-isoprostanes, are directly correlated with CKD progression. Their accumulation, added to their noxious effects, rendered their nomination as uremic toxins credible. Similarly, lipoproteins are deeply altered by CKD modifications, either in their metabolism or composition. These impairments lead to impaired effects of HDL on their normal effectors and may strongly participate in accelerated atherosclerosis and failure of statins in end-stage renal disease patients. This review describes the impact of oxidized lipids and other modifications in the natural history of CKD and its complications. Moreover, this review focuses on the modifications of lipoproteins and their impact on the emergence of cardiovascular diseases in CKD as well as the appropriateness of considering them as actual mediators of uremic toxicity.

  6. Smoking modifies the associated increased risk of future cardiovascular disease by genetic variation on chromosome 9p21.

    Viktor Hamrefors

    Full Text Available AIMS: Genetic predisposition for cardiovascular disease (CVD is likely to be modified by environmental exposures. We tested if the associated risk of CVD and CVD-mortality by the single nucleotide polymorphism rs4977574 on chromosome 9p21 is modified by life-style factors. METHODS AND RESULTS: A total of 24,944 middle-aged subjects (62% females from the population-based Malmö-Diet-and-Cancer-Cohort were genotyped. Smoking, education and physical activity-levels were recorded. Subjects were followed for 15 years for incidence of coronary artery disease (CAD; N = 2309, ischemic stroke (N = 1253 and CVD-mortality (N = 1156. Multiplicative interactions between rs4977574 and life-style factors on endpoints were tested in Cox-regression-models. We observed an interaction between rs4977574 and smoking on incident CAD (P = 0.035 and CVD-mortality (P = 0.012. The hazard ratios (HR per risk allele of rs4977574 were highest in never smokers (N = 9642 for CAD (HR = 1.26; 95% CI 1.13-1.40; P<0.001 and for CVD-mortality (HR = 1.40; 95% CI 1.20-1.63; P<0.001, whereas the risk increase by rs4977574 was attenuated in current smokers (N = 7000 for both CAD (HR = 1.05; 95%CI 0.95-1.16; P = 0.326 and CVD-mortality (HR = 1.08; 95%CI 0.94-1.23; P = 0.270. A meta-analysis supported the finding that the associated increased risk of CAD by the risk-allele was attenuated in smokers. Neither education nor physical activity-levels modified the associated risk of CAD, ischemic stroke and CVD mortality conferred by rs4977574. CONCLUSION: Smoking may modify the associated risk of CAD and CVD-mortality conferred by genetic variation on chromosome 9p21. Whether the observed attenuation of the genetic risk reflects a pathophysiological mechanism or is a result of smoking being such a strong risk-factor that it may eliminate the associated genetic effect, requires further investigation.

  7. Plant latex: a promising antifungal agent for post harvest disease control.

    Sibi, G; Wadhavan, Rashmi; Singh, Sneha; Shukla, Abhilasha; Dhananjaya, K; Ravikumar, K R; Mallesha, H

    2013-12-01

    Bioactive compounds from plant latex are potential source of antifungic against post harvest pathogens. Latex from a total of seven plant species was investigated for its phytochemical and antifungal properties. Six fungi namely Aspergillus fumigatus, A. niger, A. terreus, F. solani, P. digitatum and R. arrhizus were isolated from infected fruits and vegetables and tested against various solvent extracts of latex. Analysis of latex extracts with phytochemical tests showed the presence of alkaloids, flavonoids, glycosides, phenols, saponins, steroids, tannins and terpenoids. Antifungal assay revealed the potential inhibitory activity of petroleum ether extracts against the postharvest fungal isolates. Various degree of sensitivity was observed irrespective of plant species studied with A. terreus and P. digitatum as the most susceptible ones. F. solani and A. fumigatus were moderately sensitive to the latex extracts tested. Among the plants, latex of Thevetia peruviana (75.2%) and Artocarpus heterophyllus (64.8%) were having potential antifungal activity against the isolates followed by Manilkara zapota (51.1%). In conclusion, use of plant latex makes interest to control postharvest fungal diseases and is fitting well with the concept of safety for human health and environment.

  8. Inhibitory effect of indole analogs against Paenibacillus larvae, the causal agent of American foulbrood disease.

    Alvarado, Israel; Margotta, Joseph W; Aoki, Mai M; Flores, Fernando; Agudelo, Fresia; Michel, Guillermo; Elekonich, Michelle M; Abel-Santos, Ernesto

    2017-09-01

    Paenibacillus larvae, a Gram-positive bacterium, causes American foulbrood (AFB) in honey bee larvae (Apis mellifera Linnaeus [Hymenoptera: Apidae]). P. larvae spores exit dormancy in the gut of bee larvae, the germinated cells proliferate, and ultimately bacteremia kills the host. Hence, spore germination is a required step for establishing AFB disease. We previously found that P. larvae spores germinate in response to l-tyrosine plus uric acid in vitro. Additionally, we determined that indole and phenol blocked spore germination. In this work, we evaluated the antagonistic effect of 35 indole and phenol analogs and identified strong inhibitors of P. larvae spore germination in vitro. We further tested the most promising candidate, 5-chloroindole, and found that it significantly reduced bacterial proliferation. Finally, feeding artificial worker jelly containing anti-germination compounds to AFB-exposed larvae significantly decreased AFB infection in laboratory-reared honey bee larvae. Together, these results suggest that inhibitors of P. larvae spore germination could provide another method to control AFB. © The Authors 2017. Published by Oxford University Press on behalf of Entomological Society of America.

  9. Bee venom and its component apamin as neuroprotective agents in a Parkinson disease mouse model.

    Alvarez-Fischer, Daniel; Noelker, Carmen; Vulinović, Franca; Grünewald, Anne; Chevarin, Caroline; Klein, Christine; Oertel, Wolfgang H; Hirsch, Etienne C; Michel, Patrick P; Hartmann, Andreas

    2013-01-01

    Bee venom has recently been suggested to possess beneficial effects in the treatment of Parkinson disease (PD). For instance, it has been observed that bilateral acupoint stimulation of lower hind limbs with bee venom was protective in the acute 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of PD. In particular, a specific component of bee venom, apamin, has previously been shown to have protective effects on dopaminergic neurons in vitro. However, no information regarding a potential protective action of apamin in animal models of PD is available to date. The specific goals of the present study were to (i) establish that the protective effect of bee venom for dopaminergic neurons is not restricted to acupoint stimulation, but can also be observed using a more conventional mode of administration and to (ii) demonstrate that apamin can mimic the protective effects of a bee venom treatment on dopaminergic neurons. Using the chronic mouse model of MPTP/probenecid, we show that bee venom provides sustained protection in an animal model that mimics the chronic degenerative process of PD. Apamin, however, reproduced these protective effects only partially, suggesting that other components of bee venom enhance the protective action of the peptide.

  10. Nattokinase: An Oral Antithrombotic Agent for the Prevention of Cardiovascular Disease.

    Weng, Yunqi; Yao, Jian; Sparks, Sawyer; Wang, Kevin Yueju

    2017-02-28

    Natto, a fermented soybean product, has been consumed as a traditional food in Japan for thousands of years. Nattokinase (NK), a potent blood-clot dissolving protein used for the treatment of cardiovascular diseases, is produced by the bacterium Bacillus subtilis during the fermentation of soybeans to produce Natto. NK has been extensively studied in Japan, Korea, and China. Recently, the fibrinolytic (anti-clotting) capacity of NK has been recognized by Western medicine. The National Science Foundation in the United States has investigated and evaluated the safety of NK. NK is currently undergoing a clinical trial study (Phase II) in the USA for atherothrombotic prevention. Multiple NK genes have been cloned, characterized, and produced in various expression system studies. Recombinant technology represents a promising approach for the production of NK with high purity for its use in antithrombotic applications. This review covers the history, benefit, safety, and production of NK. Opportunities for utilizing plant systems for the large-scale production of NK, or for the production of edible plants that can be used to provide oral delivery of NK without extraction and purification are also discussed.

  11. Nattokinase: An Oral Antithrombotic Agent for the Prevention of Cardiovascular Disease

    Yunqi Weng

    2017-02-01

    Full Text Available Natto, a fermented soybean product, has been consumed as a traditional food in Japan for thousands of years. Nattokinase (NK, a potent blood-clot dissolving protein used for the treatment of cardiovascular diseases, is produced by the bacterium Bacillus subtilis during the fermentation of soybeans to produce Natto. NK has been extensively studied in Japan, Korea, and China. Recently, the fibrinolytic (anti-clotting capacity of NK has been recognized by Western medicine. The National Science Foundation in the United States has investigated and evaluated the safety of NK. NK is currently undergoing a clinical trial study (Phase II in the USA for atherothrombotic prevention. Multiple NK genes have been cloned, characterized, and produced in various expression system studies. Recombinant technology represents a promising approach for the production of NK with high purity for its use in antithrombotic applications. This review covers the history, benefit, safety, and production of NK. Opportunities for utilizing plant systems for the large-scale production of NK, or for the production of edible plants that can be used to provide oral delivery of NK without extraction and purification are also discussed.

  12. Synthetic oligonucleotide antigens modified with locked nucleic acids detect disease specific antibodies

    Samuelsen, Simone V; Solov'yov, Ilia A.; Balboni, Imelda M.

    2016-01-01

    New techniques to detect and quantify antibodies to nucleic acids would provide a significant advance over current methods, which often lack specificity. We investigate the potential of novel antigens containing locked nucleic acids (LNAs) as targets for antibodies. Particularly, employing...... molecular dynamics we predict optimal nucleotide composition for targeting DNA-binding antibodies. As a proof of concept, we address a problem of detecting anti-DNA antibodies that are characteristic of systemic lupus erythematosus, a chronic autoimmune disease with multiple manifestations. We test the best...... that the novel method is a promising tool to create antigens for research and point-of-care monitoring of anti-DNA antibodies....

  13. Coronary Heart Disease Alters Intercellular Communication by Modifying Microparticle-Mediated MicroRNA Transport

    Finn, Nnenna A.; Eapen, Danny; Manocha, Pankaj; Kassem, Hatem Al; Lassegue, Bernard; Ghasemzadeh, Nima; Quyyumi, Arshed; Searles, Charles D.

    2013-01-01

    Coronary heart disease (CHD) is characterized by abnormal intercellular communication and circulating microRNAs (miRNAs) are likely involved in this process. Here, we show that CHD was associated with changes in the transport of circulating miRNA, particularly decreased miRNA enrichment in microparticles (MPs). Additionally, MPs from CHD patients were less efficient at transferring miRNA to cultured HUVECs, which correlated with their diminished capacity to bind developmental endothelial locus-1 (Del-1). In summary, CHD was associated with distinct changes in circulating miRNA transport and these changes may contribute to the abnormal intercellular communication that underlies CHD initiation and progression. PMID:24042051

  14. SAT2 Foot-and-Mouth Disease Virus Structurally Modified for Increased Thermostability.

    Scott, Katherine A; Kotecha, Abhay; Seago, Julian; Ren, Jingshan; Fry, Elizabeth E; Stuart, David I; Charleston, Bryan; Maree, Francois F

    2017-05-15

    Foot-and-mouth disease virus (FMDV), particularly strains of the O and SAT serotypes, is notoriously unstable. Consequently, vaccines derived from heat-labile SAT viruses have been linked to the induction of immunity with a poor duration and hence require more frequent vaccinations to ensure protection. In silico calculations predicted residue substitutions that would increase interactions at the interpentamer interface, supporting increased stability. We assessed the stability of the 18 recombinant mutant viruses in regard to their growth kinetics, antigenicity, plaque morphology, genetic stability, and temperature, ionic, and pH stability by using Thermofluor and inactivation assays in order to evaluate potential SAT2 vaccine candidates with improved stability. The most stable mutant for temperature and pH stability was the S2093Y single mutant, while other promising mutants were the E3198A, L2094V, and S2093H single mutants and the F2062Y-H2087M-H3143V triple mutant. Although the S2093Y mutant had the greatest stability, it exhibited smaller plaques, a reduced growth rate, a change in monoclonal antibody footprint, and poor genetic stability properties compared to those of the wild-type virus. However, these factors affecting production can be overcome. The addition of 1 M NaCl was found to further increase the stability of the SAT2 panel of viruses. The S2093Y and S2093H mutants were selected for future use in stabilizing SAT2 vaccines. IMPORTANCE Foot-and-mouth disease virus (FMDV) causes a highly contagious acute vesicular disease in cloven-hoofed livestock and wildlife. The control of the disease by vaccination is essential, especially at livestock-wildlife interfaces. The instability of some serotypes, such as SAT2, affects the quality of vaccines and therefore the duration of immunity. We have shown that we can improve the stability of SAT2 viruses by mutating residues at the capsid interface through predictive modeling. This is an important finding for

  15. Identification of actinomycetes from plant rhizospheric soils with inhibitory activity against Colletotrichum spp., the causative agent of anthracnose disease.

    Intra, Bungonsiri; Mungsuntisuk, Isada; Nihira, Takuya; Igarashi, Yasuhiro; Panbangred, Watanalai

    2011-04-01

    Colletotrichum is one of the most widespread and important genus of plant pathogenic fungi worldwide. Various species of Colletotrichum are the causative agents of anthracnose disease in plants, which is a severe problem to agricultural crops particularly in Thailand. These phytopathogens are usually controlled using chemicals; however, the use of these agents can lead to environmental pollution. Potential non-chemical control strategies for anthracnose disease include the use of bacteria capable of producing anti-fungal compounds such as actinomycetes spp., that comprise a large group of filamentous, Gram positive bacteria from soil. The aim of this study was to isolate actinomycetes capable of inhibiting the growth of Colletotrichum spp, and to analyze the diversity of actinomycetes from plant rhizospheric soil. A total of 304 actinomycetes were isolated and tested for their inhibitory activity against Colletotrichum gloeosporioides strains DoA d0762 and DoA c1060 and Colletotrichum capsici strain DoA c1511 which cause anthracnose disease as well as the non-pathogenic Saccharomyces cerevisiae strain IFO 10217. Most isolates (222 out of 304, 73.0%) were active against at least one indicator fungus or yeast. Fifty four (17.8%) were active against three anthracnose fungi and 17 (5.6%) could inhibit the growth of all three fungi and S. cerevisiae used in the test. Detailed analysis on 30 selected isolates from an orchard at Chanthaburi using the comparison of 16S rRNA gene sequences revealed that most of the isolates (87%) belong to the genus Streptomyces sp., while one each belongs to Saccharopolyspora (strain SB-2) and Nocardiopsis (strain CM-2) and two to Nocardia (strains BP-3 and LK-1). Strains LC-1, LC-4, JF-1, SC-1 and MG-1 exerted high inhibitory activity against all three anthracnose fungi and yeast. In addition, the organic solvent extracts prepared from these five strains inhibited conidial growth of the three indicator fungi. Preliminary analysis of crude

  16. Computer-Aided Drug Design Applied to Marine Drug Discovery: Meridianins as Alzheimer's Disease Therapeutic Agents.

    Llorach-Pares, Laura; Nonell-Canals, Alfons; Sanchez-Martinez, Melchor; Avila, Conxita

    2017-11-27

    Computer-aided drug discovery/design (CADD) techniques allow the identification of natural products that are capable of modulating protein functions in pathogenesis-related pathways, constituting one of the most promising lines followed in drug discovery. In this paper, we computationally evaluated and reported the inhibitory activity found in meridianins A-G, a group of marine indole alkaloids isolated from the marine tunicate Aplidium , against various protein kinases involved in Alzheimer's disease (AD), a neurodegenerative pathology characterized by the presence of neurofibrillary tangles (NFT). Balance splitting between tau kinase and phosphate activities caused tau hyperphosphorylation and, thereby, its aggregation and NTF formation. Inhibition of specific kinases involved in its phosphorylation pathway could be one of the key strategies to reverse tau hyperphosphorylation and would represent an approach to develop drugs to palliate AD symptoms. Meridianins bind to the adenosine triphosphate (ATP) binding site of certain protein kinases, acting as ATP competitive inhibitors. These compounds show very promising scaffolds to design new drugs against AD, which could act over tau protein kinases Glycogen synthetase kinase-3 Beta (GSK3β) and Casein kinase 1 delta (CK1δ, CK1D or KC1D), and dual specificity kinases as dual specificity tyrosine phosphorylation regulated kinase 1 (DYRK1A) and cdc2-like kinases (CLK1). This work is aimed to highlight the role of CADD techniques in marine drug discovery and to provide precise information regarding the binding mode and strength of meridianins against several protein kinases that could help in the future development of anti-AD drugs.

  17. Development of criteria for evaluating clinical response in thyroid eye disease (CRI-TED) using a modified Delphi technique

    Douglas, Raymond S.; Tsirbas, Angelo; Gordon, Mark; Lee, Diana; Khadavi, Nicole; Garneau, Helene Chokron; Goldberg, Robert A.; Cahill, Kenneth; Dolman, Peter J.; Elner, Victor; Feldon, Steve; Lucarelli, Mark; Uddin, Jimmy; Kazim, Michael; Smith, Terry J.; Khanna, Dinesh

    2014-01-01

    To identify components of a provisional clinical response index for thyroid eye disease (CRI-TED) using a modified Delphi technique. The International Thyroid Eye Disease Society (ITEDS) conducted a structured, 3-round Delphi exercise establishing consensus for a core set of measures for clinical trials in TED. The steering committee discussed the results in a face-to-face meeting (nominal group technique) and evaluated each criterion with respect to its feasibility, reliability, redundancy, and validity. Redundant measures were consolidated or excluded. Criteria were 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 eight 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 due to 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. Using a Delphi exercise, we developed provisional core measures for assessing disease activity and severity in clinical trials of therapies for TED. These measures will be iteratively refined for use in multicenter clinical trials. PMID:19752424

  18. Does wheat genetically modified for disease resistance affect root-colonizing pseudomonads and arbuscular mycorrhizal fungi?

    Meyer, Joana Beatrice; Song-Wilson, Yi; Foetzki, Andrea; Luginbühl, Carolin; Winzeler, Michael; Kneubühler, Yvan; Matasci, Caterina; Mascher-Frutschi, Fabio; Kalinina, Olena; Boller, Thomas; Keel, Christoph; Maurhofer, Monika

    2013-01-01

    This study aimed to evaluate the impact of genetically modified (GM) wheat with introduced pm3b mildew resistance transgene, on two types of root-colonizing microorganisms, namely pseudomonads and arbuscular mycorrhizal fungi (AMF). Our investigations were carried out in field trials over three field seasons and at two locations. Serial dilution in selective King's B medium and microscopy were used to assess the abundance of cultivable pseudomonads and AMF, respectively. We developed a denaturing gradient gel electrophoresis (DGGE) method to characterize the diversity of the pqqC gene, which is involved in Pseudomonas phosphate solubilization. A major result was that in the first field season Pseudomonas abundances and diversity on roots of GM pm3b lines, but also on non-GM sister lines were different from those of the parental lines and conventional wheat cultivars. This indicates a strong effect of the procedures by which these plants were created, as GM and sister lines were generated via tissue cultures and propagated in the greenhouse. Moreover, Pseudomonas population sizes and DGGE profiles varied considerably between individual GM lines with different genomic locations of the pm3b transgene. At individual time points, differences in Pseudomonas and AMF accumulation between GM and control lines were detected, but they were not consistent and much less pronounced than differences detected between young and old plants, different conventional wheat cultivars or at different locations and field seasons. Thus, we conclude that impacts of GM wheat on plant-beneficial root-colonizing microorganisms are minor and not of ecological importance. The cultivation-independent pqqC-DGGE approach proved to be a useful tool for monitoring the dynamics of Pseudomonas populations in a wheat field and even sensitive enough for detecting population responses to altered plant physiology.

  19. Does wheat genetically modified for disease resistance affect root-colonizing pseudomonads and arbuscular mycorrhizal fungi?

    Joana Beatrice Meyer

    Full Text Available This study aimed to evaluate the impact of genetically modified (GM wheat with introduced pm3b mildew resistance transgene, on two types of root-colonizing microorganisms, namely pseudomonads and arbuscular mycorrhizal fungi (AMF. Our investigations were carried out in field trials over three field seasons and at two locations. Serial dilution in selective King's B medium and microscopy were used to assess the abundance of cultivable pseudomonads and AMF, respectively. We developed a denaturing gradient gel electrophoresis (DGGE method to characterize the diversity of the pqqC gene, which is involved in Pseudomonas phosphate solubilization. A major result was that in the first field season Pseudomonas abundances and diversity on roots of GM pm3b lines, but also on non-GM sister lines were different from those of the parental lines and conventional wheat cultivars. This indicates a strong effect of the procedures by which these plants were created, as GM and sister lines were generated via tissue cultures and propagated in the greenhouse. Moreover, Pseudomonas population sizes and DGGE profiles varied considerably between individual GM lines with different genomic locations of the pm3b transgene. At individual time points, differences in Pseudomonas and AMF accumulation between GM and control lines were detected, but they were not consistent and much less pronounced than differences detected between young and old plants, different conventional wheat cultivars or at different locations and field seasons. Thus, we conclude that impacts of GM wheat on plant-beneficial root-colonizing microorganisms are minor and not of ecological importance. The cultivation-independent pqqC-DGGE approach proved to be a useful tool for monitoring the dynamics of Pseudomonas populations in a wheat field and even sensitive enough for detecting population responses to altered plant physiology.

  20. A modified elliptical formula to estimate kidney collagen content in a model of chronic kidney disease.

    Nieto, Jake A; Zhu, Janice; Duan, Bin; Li, Jingsong; Zhou, Ping; Paka, Latha; Yamin, Michael A; Goldberg, Itzhak D; Narayan, Prakash

    2018-01-01

    The extent of scarring or renal interstitial collagen deposition in chronic kidney disease (CKD) can only be ascertained by highly invasive, painful and sometimes risky, tissue biopsy. Interestingly, while CKD-related abnormalities in kidney size can often be visualized using ultrasound, not only does the ellipsoid formula used today underestimate true renal size, but the calculated renal size does not inform tubulointerstitial collagen content. We used coronal kidney sections from healthy mice and mice with kidney disease to develop a new formula for estimating renal parenchymal area. While treating the kidney as an ellipse with the major axis (a) the polar distance, this technique involves extending the minor axis (b) into the renal pelvis to obtain a new minor axis, be. The calculated renal parenchymal area is remarkably similar to the true or measured area. Biochemically determined kidney collagen content revealed a strong and positive correlation with the calculated renal parenchymal area. Picrosirius red staining for tubulointerstitial collagen also correlated with calculated renal parenchymal area. The extent of renal scarring, i.e. kidney interstitial collagen content, can now be computed by making just two axial measurements which can easily be accomplished via noninvasive imaging of this organ.

  1. Oxidatively modified glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and Alzheimer's disease: many pathways to neurodegeneration.

    Butterfield, D Allan; Hardas, Sarita S; Lange, Miranda L Bader

    2010-01-01

    Recently, the oxidoreductase, glyceraldehyde-3-phosphate dehydrogenase (GAPDH), has become a subject of interest as more and more studies reveal a surfeit of diverse GAPDH functions, extending beyond traditional aerobic metabolism of glucose. As a result of multiple isoforms and cellular locales, GAPDH is able to come in contact with a variety of small molecules, proteins, membranes, etc., that play important roles in normal and pathologic cell function. Specifically, GAPDH has been shown to interact with neurodegenerative disease-associated proteins, including the amyloid-beta protein precursor (AbetaPP). Studies from our laboratory have shown significant inhibition of GAPDH dehydrogenase activity in Alzheimer's disease (AD) brain due to oxidative modification. Although oxidative stress and damage is a common phenomenon in the AD brain, it would seem that inhibition of glycolytic enzyme activity is merely one avenue in which AD pathology affects neuronal cell development and survival, as oxidative modification can also impart a toxic gain-of-function to many proteins, including GAPDH. In this review, we examine the many functions of GAPDH with respect to AD brain; in particular, the apparent role(s) of GAPDH in AD-related apoptotic cell death is emphasized.

  2. Modifying Eating Behavior: Novel Approaches for Reducing Body Weight, Preventing Weight Regain, and Reducing Chronic Disease Risk123

    Gletsu-Miller, Nana; McCrory, Megan A

    2014-01-01

    This article is a summary of the symposium “Modifying Eating Behavior: Novel Approaches for Reducing Body Weight, Preventing Weight Regain, and Reducing Chronic Disease Risk” held 29 April 2014 at the ASN Scientific Sessions and Annual Meeting at Experimental Biology 2014 in San Diego, CA. In this symposium, novel approaches to modifying eating behavior were highlighted, including 1) alteration of meal timing and macronutrient composition and 2) retraining and provision of feedback about eating behavior. Dr. Ciampolini discussed a method for teaching individuals to recognize a decrease in blood glucose concentration, and therefore the need for energy, by learning the associated physical sensations (signifying hunger). Dr. Madar and Sigal Sofer presented their work on reducing hunger during energy reduction by feeding carbohydrate only in the evening. Dr. Hamilton-Shield reviewed studies on the Mandometer (Mikrodidakt), a device for training individuals to slow eating rate. Finally, Dr. Sazonov presented information on a wearable device, the Automatic Ingestion Monitor, which senses jaw motion and/or hand-to-mouth gestures to detect and characterize food intake. His goal is to use the instrument to prevent overeating by providing feedback to the user to stop ingestion at a predetermined limit. PMID:25398742

  3. Updated genome assembly and annotation of Paenibacillus larvae, the agent of American foulbrood disease of honey bees

    de Graaf Dirk C

    2011-09-01

    Full Text Available Abstract Background As scientists continue to pursue various 'omics-based research, there is a need for high quality data for the most fundamental 'omics of all: genomics. The bacterium Paenibacillus larvae is the causative agent of the honey bee disease American foulbrood. If untreated, it can lead to the demise of an entire hive; the highly social nature of bees also leads to easy disease spread, between both individuals and colonies. Biologists have studied this organism since the early 1900s, and a century later, the molecular mechanism of infection remains elusive. Transcriptomics and proteomics, because of their ability to analyze multiple genes and proteins in a high-throughput manner, may be very helpful to its study. However, the power of these methodologies is severely limited without a complete genome; we undertake to address that deficiency here. Results We used the Illumina GAIIx platform and conventional Sanger sequencing to generate a 182-fold sequence coverage of the P. larvae genome, and assembled the data using ABySS into a total of 388 contigs spanning 4.5 Mbp. Comparative genomics analysis against fully-sequenced soil bacteria P. JDR2 and P. vortex showed that regions of poor conservation may contain putative virulence factors. We used GLIMMER to predict 3568 gene models, and named them based on homology revealed by BLAST searches; proteases, hemolytic factors, toxins, and antibiotic resistance enzymes were identified in this way. Finally, mass spectrometry was used to provide experimental evidence that at least 35% of the genes are expressed at the protein level. Conclusions This update on the genome of P. larvae and annotation represents an immense advancement from what we had previously known about this species. We provide here a reliable resource that can be used to elucidate the mechanism of infection, and by extension, more effective methods to control and cure this widespread honey bee disease.

  4. Does influence at work modify the relation between high occupational physical activity and risk of heart disease in women?

    Allesøe, Karen; Holtermann, Andreas; Rugulies, Reiner

    2017-01-01

    .6 years by individual linkage to incident IHD in the Danish National Patient Registry. Information on OPA, influence at work, other occupational factors and known risk factors for IHD was collected by self-report in 1993. Results: During follow-up 869 nurses were hospitalised with incident IHD. Nurses......Purpose: To investigate whether influence at work modifies the association between demanding and strenuous occupational physical activity (OPA) and risk of ischaemic heart disease (IHD). Methods: A sample of 12,093 nurses aged 45–64 years from the Danish Nurse Cohort Study was followed for 20...... exposed to strenuous OPA and low influence at work had a 46% increased risk of IHD [hazard ratio (HR) 1.46 (95% confidence interval (CI) 1.02–2.09)] compared to the reference group of nurses with moderate OPA and high influence at work. Nurses exposed to strenuous OPA and high influence at work were...

  5. Efficacy of VX-509 (decernotinib) in combination with a disease-modifying antirheumatic drug in patients with rheumatoid arthritis

    Genovese, Mark C.; Yang, Fang; Østergaard, Mikkel

    2016-01-01

    Objective To assess early effects on joint structures of VX-509 in combination with stable disease-modifying antirheumatic drug (DMARD) therapy using MRI in adults with rheumatoid arthritis (RA). Methods This phase II, placebo-controlled, double-blind, dose-ranging study randomised patients with RA......), and the RA MRI scoring (RAMRIS) system. Results ACR20 response at week 12 was 63.6%, 60.0% and 60.0% in the VX-509 100-mg, 200-mg and 300-mg groups, respectively, compared with 25.0% in the placebo group. DAS28-CRP scores decreased in a dose-dependent manner with increasing VX-509 doses. Decreases in RAMRIS...... to a DMARD alone. MRI responses were detected at week 12. Treatment was generally well tolerated. Trial registration number NCT01754935; results....

  6. Sex modifies the APOE-related risk of developing Alzheimer disease.

    Altmann, Andre; Tian, Lu; Henderson, Victor W; Greicius, Michael D

    2014-04-01

    The APOE4 allele is the strongest genetic risk factor for sporadic Alzheimer disease (AD). Case-control studies suggest the APOE4 link to AD is stronger in women. We examined the APOE4-by-sex interaction in conversion risk (from healthy aging to mild cognitive impairment (MCI)/AD or from MCI to AD) and cerebrospinal fluid (CSF) biomarker levels. Cox proportional hazards analysis was used to compute hazard ratios (HRs) for an APOE-by-sex interaction on conversion in controls (n = 5,496) and MCI patients (n = 2,588). The interaction was also tested in CSF biomarker levels of 980 subjects from the Alzheimer's Disease Neuroimaging Initiative. Among controls, male and female carriers were more likely to convert to MCI/AD, but the effect was stronger in women (HR = 1.81 for women; HR = 1.27 for men; interaction: p = 0.011). The interaction remained significant in a predefined subanalysis restricted to APOE3/3 and APOE3/4 genotypes. Among MCI patients, both male and female APOE4 carriers were more likely to convert to AD (HR = 2.16 for women; HR = 1.64 for men); the interaction was not significant (p = 0.14). In the subanalysis restricted to APOE3/3 and APOE3/4 genotypes, the interaction was significant (p = 0.02; HR = 2.17 for women; HR = 1.51 for men). The APOE4-by-sex interaction on biomarker levels was significant for MCI patients for total tau and the tau-to-Aβ ratio (p = 0.009 and p = 0.02, respectively; more AD-like in women). APOE4 confers greater AD risk in women. Biomarker results suggest that increased APOE-related risk in women may be associated with tau pathology. These findings have important clinical implications and suggest novel research approaches into AD pathogenesis. © 2014 American Neurological Association.

  7. Identification of novel anti-inflammatory agents from Ayurvedic medicine for prevention of chronic diseases: "reverse pharmacology" and "bedside to bench" approach.

    Aggarwal, Bharat B; Prasad, Sahdeo; Reuter, Simone; Kannappan, Ramaswamy; Yadev, Vivek R; Park, Byoungduck; Kim, Ji Hye; Gupta, Subash C; Phromnoi, Kanokkarn; Sundaram, Chitra; Prasad, Seema; Chaturvedi, Madan M; Sung, Bokyung

    2011-10-01

    Inflammation, although first characterized by Cornelius Celsus, a physician in first Century Rome, it was Rudolf Virchow, a German physician in nineteenth century who suggested a link between inflammation and cancer, cardiovascular diseases, diabetes, pulmonary diseases, neurological diseases and other chronic diseases. Extensive research within last three decades has confirmed these observations and identified the molecular basis for most chronic diseases and for the associated inflammation. The transcription factor, Nuclear Factor-kappaB (NF-kappaB) that controls over 500 different gene products, has emerged as major mediator of inflammation. Thus agents that can inhibit NF-kappaB and diminish chronic inflammation have potential to prevent or delay the onset of the chronic diseases and further even treat them. In an attempt to identify novel anti-inflammatory agents which are safe and effective, in contrast to high throughput screen, we have turned to "reverse pharmacology" or "bed to benchside" approach. We found that Ayurveda, a science of long life, almost 6,000 years old, can serve as a "goldmine" for novel anti-inflammatory agents used for centuries to treat chronic diseases. The current review is an attempt to provide description of various Ayurvedic plants currently used for treatment, their active chemical components, and the inflammatory pathways that they inhibit.

  8. The effect of tofacitinib on function and quality of life indicators in patients with rheumatoid arthritis resistant to synthetic and biological disease-modifying antirheumatic drugs in real clinical practice: Results of a multicenter observational study

    D. E. Karateev

    2017-01-01

    Full Text Available Tofacitinib (TOFA, a representative of a new class of targeted synthetic disease-modifying antirheumatic drugs (s-DMARD, is a promising drug for treating rheumatoid arthritis (RA and other immune inflammatory diseases.Objective: to evaluate the efficiency and safety of therapy with TOFA in combination with methotrexate (MTX and other s-DMARDs in real clinical practice in patients with active RA and previous ineffective therapy.Patients and methods. A 6-month Russian multicenter study of function and quality of life enrolled 101 patients with resistant RA: 18 men and 83 women; mean age, 51.03±11.28 years; mean disease duration, 105.4±81.43 months; rheumatoid factor-positive individuals (89.1%; and anticyclic citrullinated peptide antibody-positive ones (74.7%. 93 (92,1% of these patients completed a 24-week study. TOFA was used as both second-line drug (after failure of therapy with s-DMARD (n=74 and as a third-line drug (after failure of therapy with s-DMARDs and biological agents (BAs (n=74. The tools RAPID3, HAQ, and EQ-5D were used to determine disease outcomes from a patient's assessment.Results. All the three tools demonstrated significant positive changes at 3–6 months following therapy initiation. RAPID3 scores for the status of a patient achieving a low disease activity or remission coincided with the mean DAS28-ESR and SDAI scores in 60% and 68% of cases, respectively. The achievement rates of the minimally clinically significant improvement (ΔHAQ≥0.22 and functional remission (HAQ≤0.5 at 6 months of TOFA therapy were 79.6 and 30.1%, respectively. The mean change value in EQ-5D scores over 6 months was -0.162±0.21. There were no significant between the groups of patients who used TOFA as a second- or third-line agent in the majority of indicators, except EQ-5D scores at 6 months.Conclusions. The results of our multicenter study using considerable Russian material confirmed the pronounced positive effect of TOFA used

  9. Feasibility of a Modified E-PASS and POSSUM System for Postoperative Risk Assessment in Patients with Spinal Disease.

    Chun, Dong Hyun; Kim, Do Young; Choi, Sun Kyu; Shin, Dong Ah; Ha, Yoon; Kim, Keung Nyun; Yoon, Do Heum; Yi, Seong

    2018-04-01

    This retrospective case control study aimed to evaluate the feasibility of using Estimation of Physiological Ability and Surgical Stress (E-PASS) and Physiological and Operative Severity Score for the enumeration of Mortality and Morbidity (POSSUM) systems in patients undergoing spinal surgical procedures. Degenerative spine disease has increased in incidence in aging societies, as has the number of older adult patients undergoing spinal surgery. Many older adults are at a high surgical risk because of comorbidity and poor general health. We retrospectively reviewed 217 patients who had undergone spinal surgery at a single tertiary care. We investigated complications within 1 month after surgery. Criteria for both skin incision in E-PASS and operation magnitude in the POSSUM system were modified to fit spine surgery. We calculated the E-PASS and POSSUM scores for enrolled patients, and investigated the relationship between postoperative complications and both surgical risk scoring systems. To reinforce the predictive ability of the E-PASS system, we adjusted equations and developed modified E-PASS systems. The overall complication rate for spinal surgery was 22.6%. Forty-nine patients experienced 58 postoperative complications. Nineteen major complications, including hematoma, deep infection, pleural effusion, progression of weakness, pulmonary edema, esophageal injury, myocardial infarction, pneumonia, reoperation, renal failure, sepsis, and death, occurred in 17 patients. The area under the receiver operating characteristic curve (AUC) for predicted postoperative complications after spine surgery was 0.588 for E-PASS and 0.721 for POSSUM. For predicted major postoperative complications, the AUC increased to 0.619 for E-PASS and 0.842 for POSSUM. The AUC of the E-PASS system increased from 0.588 to 0.694 with the Modified E-PASS equation. The POSSUM system may be more useful than the E-PASS system for estimating postoperative surgical risk in patients undergoing

  10. Evaluation of the antimicrobial and physical properties of an orthodontic photo-activated adhesive modified with an antiplaque agent: An in vitro study

    Chanjyot Singh

    2013-01-01

    Results: The findings indicated that (1 addition of chlorhexidine to the orthodontic composite resin enhanced its antimicrobial properties, (2 there was no significant difference between the bond strengths of the control and the experimental resins tested after 24 h and 25 days and (3 maximum release of chlorhexidine from the modified resin was much higher than the minimum inhibitory concentration level.

  11. Comparative Efficacy and Acceptability of Anti-Diabetic Agents for Alzheimer's Disease and Mild Cognitive Impairment: A Systematic Review and Network Meta-analysis.

    Cao, Bing; Rosenblat, Joshua D; Brietzke, Elisa; Park, Caroline; Lee, Yena; Musial, Natalie; Pan, Zihang; Mansur, Rodrigo B; McIntyre, Roger S

    2018-05-23

    The current meta-analysis compares the efficacy (i.e., pro-cognitive effects) and acceptability of anti-diabetic agents for Alzheimer's disease (AD) and mild cognitive impairment (MCI). Cochrane Library (CENTRAL), PubMed/MEDLINE, EMBASE and PsycINFO were searched from inception to January 15, 2018 for randomized controlled trials (RCTs) comparing anti-diabetic agents with placebo and/or another active anti-diabetic agent for the treatment of AD or MCI. Nineteen eligible studies (n = 4,855) evaluating the effects of six different anti-diabetic drugs (i.e., intranasal insulin, pioglitazone, rosiglitazone, metformin, sitagliptin and liraglutide) were included. The results of 29 pairwise comparisons indicated that cognition was significantly improved in subjects treated with anti-diabetic agents compared to placebo. Pioglitazone 15-30 mg demonstrated the greatest efficacy compared to placebo in network meta-analysis. No significant differences in acceptability were identified when comparing agents with each other and with placebo. The current findings indicate a pro-cognitive class effect of anti-diabetic agents in AD/MCI. Other anti-diabetic agents should also be investigated in future studies. This study is registered with PROSPERO (CRD42018085967). This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  12. Risk of therapy-related leukaemia and preleukaemia after Hodgkin's disease. Relation to age, cumulative dose of alkylating agents, and time from chemotherapy

    Pedersen-Bjergaard, J.; Specht, L.; Larsen, S.O.

    1987-01-01

    391 patients treated intensively for Hodgkin's disease were followed for up to 15 years to evaluate the risk of therapy-related acute non-lymphocytic leukaemia (t-ANLL) and preleukaemia. Only two independent factors, patient age and cumulative dose of alkylating agents, were related to the risk...... of t-ANLL. The hazard rate of t-ANLL was roughly proportional to the square of patient age and to the total cumulative dose of alkylating agents. In 320 patients treated with alkylating agents the cumulative risk of t-ANLL increased steadily from 1 year after the start of treatment and reached 13.......0% (SE 3.0) at 10 years after which time there were no further cases. Calculated from cessation of therapy with alkylating agents, however, the cumulative risk curve increased steeply during the first 1-2 years then gradually levelled out and no new cases were observed beyond 7 years. With a 15-year...

  13. Light and heavy touch reduces postural sway and modifies axial tone in Parkinson's disease.

    Franzén, Erika; Paquette, Caroline; Gurfinkel, Victor; Horak, Fay

    2012-10-01

    Light touch with a stable object reduces postural sway by increasing axial postural tone in healthy subjects. However, it is unknown whether subjects with Parkinson's disease (PD), who have more postural sway and higher axial postural tone than healthy subjects, can benefit from haptic touch. To investigate the effect of light and heavy touch on postural stability and hip tone in subjects with PD. Fourteen subjects with mid-stage PD and 14 healthy control subjects were evaluated during quiet standing with eyes closed with their arms (a) crossed, (b) lightly touching a fixed rigid bar in front of them, and (c) firmly gripping the bar. Postural sway was measured with a forceplate, and axial hip tone was quantified using a unique device that measures the resistance of the hips to yaw rotation while maintaining active stance. Subjects with PD significantly decreased their postural sway with light or heavy touch (P touch, hip tone was larger in PD subjects. With touch, however, tone values were similar in both groups. This change in hip tone with touch was highly correlated with the initial amount of tone (PD, r = -.72 to -.95; controls, r = -.74 to -.85). The authors showed, for the first time, that subjects with PD benefit from touch similarly to control subjects and that despite higher axial postural tone, PD subjects are able to modulate their tone with touch. Future studies should investigate the complex relationship between touch and postural tone.

  14. Does Caffeine Consumption Modify Cerebrospinal Fluid Amyloid-β Levels in Patients with Alzheimer's Disease?

    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...

  15. Development of a biocontrol agent for plant disease control with special emphasis on the near commercial fungal antagonist Clonostachys rosea strain "IK726"

    Jensen, Dan Funck; Knudsen, Inge M.B.; Lübeck, Mette

    2007-01-01

    Numerous experiments demonstrating potential biocontrol effects on soilborne diseases have been reported in the scientific literature. However, from the lists of approved and registered biocontrol agents, it is striking how few have been commercialised and are used in practise for plant disease c...... with in such a development. Australasian Plant Pathology 36(2) 95-101 Submitted: 12 January 2006 Accepted: 15 January 2007 Published: 6 March 2007 Full text DOI: 10.1071/AP07009 © Australasian Plant Pathology Society 2007...

  16. Light and heavy touch reduces postural sway and modifies axial tone in Parkinson’s disease

    Franzén, Erika; Paquette, Caroline; Gurfinkel, Victor; Horak, Fay

    2014-01-01

    Background Light touch with a stable object reduces postural sway by increasing axial postural tone in healthy subjects. However, it is unknown whether subjects with Parkinson’s disease (PD), who have more postural sway and higher axial postural tone than healthy subjects, can benefit from haptic touch. Objective To investigate the effect of light and heavy touch on postural stability and hip tone in subjects with PD. Methods Fourteen subjects with mid-stage PD, and 14 healthy control subjects were evaluated during quiet standing with eyes closed with their arms: 1) crossed, 2) lightly touching a fixed rigid bar in front of them and 3) firmly gripping the bar. Postural sway was measured with a forceplate and axial hip tone was quantified using a unique device that measures the resistance of the hips to yaw rotation while maintaining active stance. Results Subjects with PD significantly decreased their postural sway with light or heavy touch (ptouch, hip tone was larger in PD subjects. With touch, however, tone values were similar in both groups. This change in hip tone with touch was highly correlated with the initial amount of tone (PD: r=− 0.72 to −0.95 and controls: r=−0.74 to−0.85). Conclusions We showed, for the first time, that subjects with PD benefit from touch similarly to control subjects and that despite higher axial postural tone, PD subjects are able to modulate their tone with touch. Future studies should investigate the complex relationship between touch and postural tone. PMID:22415944

  17. Psychosocial predictors of patient adherence to disease-modifying therapies for multiple sclerosis

    Alosaimi FD

    2017-03-01

    Full Text Available Fahad D Alosaimi,1 Alaa AlMulhem,2 Hanan AlShalan,2 Mohammad Alqazlan,3 Abdulgader Aldaif,4 Matthew Kowgier,5 Janooshsheya Balasundaram,6 Sanjeev Sockalingam6,7 1Department of Psychiatry, 2College of Medicine, King Saud University, 3Department of Mental Health, King Faisal Specialist Hospital and Research Centre, 4Department of Neurology, King Saud University, Riyadh, Saudi Arabia; 5Dalla Lana School of Public Health, University of Toronto, 6Centre for Mental Health, University Health Network, 7Department of Psychiatry, University of Toronto, Toronto, ON, Canada Objectives: Our aim was to identify the impact of psychosocial predictors, specifically relationship style, depressive symptoms, anxiety symptoms, cognitive impairment, and culture-specific disease beliefs, on treatment adherence for multiple sclerosis (MS patients.Methods: In this cross-sectional observational study, patients from two MS clinics in Saudi Arabia completed self-reported questionnaires focused on MS treatment adherence, physical symptom burden, relationship style, cultural beliefs, depressive symptoms, anxiety, and cognitive impairment.Results: A total of 163 MS patients participated, 81.6% of them were female, and the mean age of the patients was 31.6 years. Mean patient-reported adherence to their MS treatment regimen was 79.47%±25.26%. Multivariate linear regression analysis only identified patients’ belief that their MS was due to “supernatural” forces as being significantly negatively associated with MS medication adherence.Conclusion: This study demonstrates the importance of cultural interpretations to MS medication adherence in comparison to psychosocial factors. Education and family involvement in the treatment planning may address this issue and warrant further research. Keywords: multiple sclerosis, adherence, depression, attachment style, culture

  18. Modified impact of emotion on temporal discrimination in a transgenic rat model of Huntington disease

    Alexis eFaure

    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.

  19. Systematic review and meta-analysis of serious infections with tofacitinib and biologic disease-modifying antirheumatic drug treatment in rheumatoid arthritis clinical trials.

    Strand, Vibeke; Ahadieh, Sima; French, Jonathan; Geier, Jamie; Krishnaswami, Sriram; Menon, Sujatha; Checchio, Tina; Tensfeldt, Thomas G; Hoffman, Elaine; Riese, Richard; Boy, Mary; Gómez-Reino, Juan J

    2015-12-15

    were 2.21 (0.60, 8.14) and 2.02 (0.56, 7.28), respectively. Risk differences (95% CIs) versus placebo for tofacitinib 5 and 10 mg BID were 0.38% (-0.24%, 0.99%) and 0.40% (-0.22%, 1.02%), respectively. In interventional studies, the risk of serious infections with tofacitinib is comparable to published rates for biologic disease-modifying antirheumatic drugs in patients with moderate to severely active RA.

  20. Melatonin Receptor Agonists as the "Perioceutics" Agents for Periodontal Disease through Modulation of Porphyromonas gingivalis Virulence and Inflammatory Response.

    Zhou, Wei; Zhang, Xuan; Zhu, Cai-Lian; He, Zhi-Yan; Liang, Jing-Ping; Song, Zhong-Chen

    2016-01-01

    A, and ragA), while increasing the mRNA expression of ferritin (ftn) or hemolysin (hem). They did not show obvious cytotoxicity toward HGFs. They inhibited Pg-LPS-induced IL-6 and IL-8 secretion, which was reversed by luzindole, the melatonin receptor antagonist. Melatonin receptor agonists can inhibit planktonic and biofilm growth of Porphyromonas gingivalis by affecting the virulent properties, as well as Pg-LPS-induced inflammatory response. Our study provides new evidence that melatonin receptor agonists might be useful as novel "perioceutics" agents to prevent and treat Porphyromonas gingivalis-associated periodontal diseases.

  1. Melatonin Receptor Agonists as the "Perioceutics" Agents for Periodontal Disease through Modulation of Porphyromonas gingivalis Virulence and Inflammatory Response.

    Wei Zhou

    A, rgpB, hagA, and ragA, while increasing the mRNA expression of ferritin (ftn or hemolysin (hem. They did not show obvious cytotoxicity toward HGFs. They inhibited Pg-LPS-induced IL-6 and IL-8 secretion, which was reversed by luzindole, the melatonin receptor antagonist.Melatonin receptor agonists can inhibit planktonic and biofilm growth of Porphyromonas gingivalis by affecting the virulent properties, as well as Pg-LPS-induced inflammatory response. Our study provides new evidence that melatonin receptor agonists might be useful as novel "perioceutics" agents to prevent and treat Porphyromonas gingivalis-associated periodontal diseases.

  2. Isolation and characterization of the mating type locus of Mycosphaerella fijiensis, the causal agent of black leaf streak disease of banana

    Conde, L.; Waalwijk, C.; Canto-Canché, B.B.; Kema, G.H.J.; Crous, P.W.; James, A.C.; Abeln, E.C.A.

    2007-01-01

    Idiomorphs mat1-1 and mat1-2 from Mycosphaerella fijiensis, the causal agent of black leaf streak disease of banana, were isolated. Degenerate oligos were used to amplify the HMG box of the mat1-2 idiomorph from M. fijiensis, showing homology with the HMG box of Mycosphaerella graminicola. Using a

  3. Variable number of tandem repeat markers in the genome sequence of Mycosphaerella fijiensis, the causal agent of black leaf streak disease of banana (Musa spp)

    Garcia, S.A.L.; Lee, van der T.A.J.; Ferreira, C.F.; Lintel Hekkert, te B.; Zapater, M.F.; Goodwin, S.B.; Guzmán, M.; Kema, G.H.J.; Souza, M.T.

    2010-01-01

    ABSTRACT. We searched the genome of Mycosphaerella fijiensis for molecular markers that would allow population genetics analysis of this plant pathogen. M. fijiensis, the causal agent of banana leaf streak disease, also known as black Sigatoka, is the most devastating pathogen attacking bananas

  4. A tick mannose-binding lectin inhibitor interferes with the vertebrate complement cascade to enhance transmission of the lyme disease agent

    Schuijt, Tim J.; Coumou, Jeroen; Narasimhan, Sukanya; Dai, Jianfeng; Deponte, Kathleen; Wouters, Diana; Brouwer, Mieke; Oei, Anneke; Roelofs, Joris J. T. H.; van Dam, Alje P.; van der Poll, Tom; van't Veer, Cornelis; Hovius, Joppe W.; Fikrig, Erol

    2011-01-01

    The Lyme disease agent Borrelia burgdorferi is primarily transmitted to vertebrates by Ixodes ticks. The classical and alternative complement pathways are important in Borrelia eradication by the vertebrate host. We recently identified a tick salivary protein, designated P8, which reduced

  5. Development of VNTR Markers to Assess Genetic Diversity of Mycosphaerella Fijiensis, the Causal Agent of Black Leaf Streak Disease in Bananas (Musa spp.)

    Mycosphaerella fijiensis is the causal agent of black leaf streak (BLS) disease in bananas. This pathogen threatens global banana production as the main export cultivars are highly susceptible. As a consequence, commercial banana plantations must be protected chemically with fungicides; up to 40 app...

  6. Variable Number of Tandem Repeat Markers in the Genome Sequence of Mycosphaerella Fijiensis, the Causal Agent of Black Leaf Streak Disease of Banana (Musa spp.)

    Mycosphaerella fijiensis, the causal agent of banana leaf streak disease (commonly known as black Sigatoka), is the most devastating pathogen attacking bananas (Musa spp). Recently the whole genome sequence of M. fijiensis became available. This sequence was screened for the presence of Variable Num...

  7. ReMindMe : Agent-Based Support for Self-Disclosure of Personal Memories in People with Alzheimer’s Disease

    Peeters, M.M.M.

    2016-01-01

    This paper presents work on the design rationale and architecture of ReMindMe. ReMindMe aims to provide agent-based support for people with Alzheimer’s disease and their social environment by playing music with a strong personal meaning to the patient so as to activate personal memory recall.

  8. Pregnancy and the Use of Disease-Modifying Therapies in Patients with Multiple Sclerosis: Benefits versus Risks

    Raed Alroughani

    2016-01-01

    Full Text Available The burden of multiple sclerosis (MS in women of childbearing potential is increasing, with peak incidence around the age of 30 years, increasing incidence and prevalence, and growing female : male ratio. Guidelines recommend early use of disease-modifying therapies (DMTs, which are contraindicated or recommended with considerable caution, during pregnancy/breastfeeding. Many physicians are reluctant to prescribe them for a woman who is/is planning to be pregnant. Interferons are not absolutely contraindicated during pregnancy, since interferon-β appears to lack serious adverse effects in pregnancy, despite a warning in its labelling concerning risk of spontaneous abortion. Glatiramer acetate, natalizumab, and alemtuzumab also may not induce adverse pregnancy outcomes, although natalizumab may induce haematologic abnormalities in newborns. An accelerated elimination procedure is needed for teriflunomide if pregnancy occurs on treatment or if pregnancy is planned. Current evidence supports the contraindication for fingolimod during pregnancy; data on other DMTs remains limited. Increased relapse rates following withdrawal of some DMTs in pregnancy are concerning and require further research. The postpartum period brings increased risk of disease reactivation that needs to be carefully addressed through effective communication between treating physicians and mothers intending to breastfeed. We address the potential for use of the first- and second-line DMTs in pregnancy and lactation.

  9. Cognitive enhancers (nootropics). Part 3: drugs interacting with targets other than receptors or enzymes. disease-modifying drugs.

    Froestl, Wolfgang; Pfeifer, Andrea; Muhs, Andreas

    2013-01-01

    Cognitive enhancers (nootropics) are drugs to treat cognition deficits in patients suffering from Alzheimer's disease, schizophrenia, stroke, attention deficit hyperactivity disorder, or aging. Cognition refers to a capacity for information processing, applying knowledge, and changing preferences. It involves memory, attention, executive functions, perception, language, and psychomotor functions. The term nootropics was coined in 1972 when memory enhancing properties of piracetam were observed in clinical trials. In the meantime, hundreds of drugs have been evaluated in clinical trials or in preclinical experiments. To classify the compounds, a concept is proposed assigning drugs to 19 categories according to their mechanism(s) of action, in particular drugs interacting with receptors, enzymes, ion channels, nerve growth factors, re-uptake transporters, antioxidants, metal chelators, and disease modifying drugs, meaning small molecules, vaccines, and monoclonal antibodies interacting with amyloid-β and tau. For drugs, whose mechanism of action is not known, they are either classified according to structure, e.g., peptides, or their origin, e.g., natural products. The review covers the evolution of research in this field over the last 25 years.

  10. UKPDS 59: hyperglycemia and other potentially modifiable risk factors for peripheral vascular disease in type 2 diabetes.

    Adler, Amanda I; Stevens, Richard J; Neil, Andrew; Stratton, Irene M; Boulton, Andrew J M; Holman, Rury R

    2002-05-01

    To determine the role of hyperglycemia in prospective analyses of peripheral vascular disease (PVD) in type 2 diabetes, taking into account other potential risk factors. Potential risk factors for the development of PVD were examined in 3,834 of 5,102 individuals enrolled in the U.K. Prospective Diabetes Study (UKPDS) without PVD at diagnosis of diabetes, followed for 6 years, and for whom relevant data were available. PVD was defined as two of the following: ankle-arm blood pressure index < 0.8, absence of both dorsalis pedis and posterior tibial pulses to palpation in one or both legs, and intermittent claudication. Logistic regression was used to estimate the association between potential risk factors measured 3-4 months after diagnosis of diabetes and incident PVD. The prevalence of PVD at 3-year intervals to 18 years was determined. Hyperglycemia, assessed as HbA(1c), was associated with an increased risk for incident PVD, independent of other risk factors including age, increased systolic blood pressure, reduced HDL cholesterol, smoking, prior cardiovascular disease, peripheral sensory neuropathy, and retinopathy. Each 1% increase in HbA(1c) was associated with a 28% increased risk of PVD (95% CI 12-46), and each 10-mmHg increase in systolic blood pressure with a 25% increase in risk (95% CI 10-43). Hyperglycemia, as well as smoking, dyslipidemia, and blood pressure are potentially modifiable risk factors for the development of PVD.

  11. Chronic obstructive pulmonary disease (COPD) assessment test scores corresponding to modified Medical Research Council grades among COPD patients.

    Lee, Chang-Hoon; Lee, Jinwoo; Park, Young Sik; Lee, Sang-Min; Yim, Jae-Joon; Kim, Young Whan; Han, Sung Koo; Yoo, Chul-Gyu

    2015-09-01

    In assigning patients with chronic obstructive pulmonary disease (COPD) to subgroups according to the updated guidelines of the Global Initiative for Chronic Obstructive Lung Disease, discrepancies have been noted between the COPD assessment test (CAT) criteria and modified Medical Research Council (mMRC) criteria. We investigated the determinants of symptom and risk groups and sought to identify a better CAT criterion. This retrospective study included COPD patients seen between June 20, 2012, and December 5, 2012. The CAT score that can accurately predict an mMRC grade ≥ 2 versus COPD patients, the percentages of patients classified into subgroups A, B, C, and D were 24.5%, 47.2%, 4.2%, and 24.1% based on CAT criteria and 49.3%, 22.4%, 8.9%, and 19.4% based on mMRC criteria, respectively. More than 90% of the patients who met the mMRC criteria for the 'more symptoms group' also met the CAT criteria. AUROC and CART analyses suggested that a CAT score ≥ 15 predicted an mMRC grade ≥ 2 more accurately than the current CAT score criterion. During follow-up, patients with CAT scores of 10 to 14 did not have a different risk of exacerbation versus those with CAT scores COPD patients.

  12. Modifiable lifestyle and social factors affect chronic kidney disease in high-risk individuals with type 2 diabetes mellitus.

    Dunkler, Daniela; Kohl, Maria; Heinze, Georg; Teo, Koon K; Rosengren, Annika; Pogue, Janice; Gao, Peggy; Gerstein, Hertzel; Yusuf, Salim; Oberbauer, Rainer; Mann, Johannes F E

    2015-04-01

    This observational study examined the association between modifiable lifestyle and social factors on the incidence and progression of early chronic kidney disease (CKD) among those with type 2 diabetes. All 6972 people from the Ongoing Telmisartan Alone and in Combination with Ramipril Global Endpoint Trial (ONTARGET) with diabetes but without macroalbuminuria were studied. CKD progression was defined as decline in GFR of more than 5% per year, progression to end-stage renal disease, microalbuminuria, or macroalbuminuria at 5.5 years. Lifestyle/social factors included tobacco and alcohol use, physical activity, stress, financial worries, the size of the social network and education. Adjustments were made for known risks such as age, diabetes duration, GFR, albuminuria, gender, body mass index, blood pressure, fasting plasma glucose, and angiotensin-converting enzyme inhibitors/angiotensin-receptor blockers use. Competing risk of death was considered. At study end, 31% developed CKD and 15% had died. The social network score (SNS) was a significant independent risk factor of CKD and death, reducing the risk by 11 and 22% when comparing the third to the first tertile of the SNS (odds ratios of CKD 0.89 and death 0.78). Education showed a significant association with CKD but stress and financial worries did not. Those with moderate alcohol consumption had a significantly decreased CKD risk compared with nonusers. Regular physical activity significantly decreased the risk of CKD. Thus, lifestyle is a determinant of kidney health in people at high cardiovascular risk with diabetes.

  13. Oral disease-modifying therapies for multiple sclerosis in the Middle Eastern and North African (MENA) region: an overview.

    Deleu, Dirk; Mesraoua, Boulenouar; Canibaño, Beatriz; Melikyan, Gayane; Al Hail, Hassan; El-Sheikh, Lubna; Ali, Musab; Al Hussein, Hassan; Ibrahim, Faiza; Hanssens, Yolande

    2018-06-18

    The introduction of new disease-modifying therapies (DMTs) for remitting-relapsing multiple sclerosis (RRMS) has considerably transformed the landscape of therapeutic opportunities for this chronic disabling disease. Unlike injectable drugs, oral DMTs promote patient satisfaction and increase therapeutic adherence. This article reviews the salient features about the mode of action, efficacy, safety, and tolerability profile of approved oral DMTs in RRMS, and reviews their place in clinical algorithms in the Middle East and North Africa (MENA) region. A systematic review was conducted using a comprehensive search of MEDLINE, PubMed, Cochrane Database of Systematic Reviews (period January 1, 1995-January 31, 2018). Additional searches of the American Academy of Neurology and European Committee for Treatment and Research in Multiple Sclerosis abstracts from 2012-2017 were performed, in addition to searches of the Food and Drug Administration and European Medicines Agency websites, to obtain relevant safety information on these DMTs. Four oral DMTs: fingolimod, teriflunomide, dimethyl fumarate, and cladribine have been approved by the regulatory agencies. Based on the number needed to treat (NNT), the potential role of these DMTs in the management of active and highly active or rapidly evolving RRMS is assessed. Finally, the place of the oral DMTs in clinical algorithms in the MENA region is reviewed.

  14. The impact of adjusted work conditions and disease-modifying drugs on work ability in multiple sclerosis.

    Wickström, Anne; Fagerström, Maria; Wickström, Lucas; Granåsen, Gabriel; Dahle, Charlotte; Vrethem, Magnus; Sundström, Peter

    2017-07-01

    Multiple sclerosis (MS) is a neurological disorder that causes significantly reduced ability to work, and the Expanded Disability Status Scale (EDSS) is one of the main predictors for reduced work ability. To investigate how work requirements, flexible work conditions and disease-modifying drugs (DMDs) influence the work ability in relation to different EDSS grades in two MS populations. Work ability was studied in two MS populations: one in the southern and one in the northern part of Sweden, both demographically similar. In the latter population, more active work-promoting interventions have been practised and second-generation DMDs have been widely used from the onset of disease for several years. The proportion of MS patients who participated in the workforce or studied was significantly higher in the northern compared with the southern population ( p work conditions and were able to work more hours per week. Higher EDSS was associated with lower reduction in number of worked hours per week in the northern population ( p = 0.042). Our data indicated that treatment strategy and adjusted work conditions have impact on work ability in MS.

  15. Cost-effectiveness of magnetic resonance imaging with a new contrast agent for the early diagnosis of Alzheimer's disease.

    Maria Biasutti

    Full Text Available Used as contrast agents for brain magnetic resonance imaging (MRI, markers for beta-amyloid deposits might allow early diagnosis of Alzheimer's disease (AD. We evaluated the cost-effectiveness of such a diagnostic test, MRI+CLP (contrastophore-linker-pharmacophore, should it become clinically available.We compared the cost-effectiveness of MRI+CLP to that of standard diagnosis using currently available cognition tests and of standard MRI, and investigated the impact of a hypothetical treatment efficient in early AD. The primary analysis was based on the current French context for 70-year-old patients with Mild Cognitive Impairment (MCI. In alternative "screen and treat" scenarios, we analyzed the consequences of systematic screenings of over-60 individuals (either population-wide or restricted to the ApoE4 genotype population. We used a Markov model of AD progression; model parameters, as well as incurred costs and quality-of-life weights in France were taken from the literature. We performed univariate and probabilistic multivariate sensitivity analyses. The base-case preferred strategy was the standard MRI diagnosis strategy. In the primary analysis however, MRI+CLP could become the preferred strategy under a wide array of scenarios involving lower cost and/or higher sensitivity or specificity. By contrast, in the "screen and treat" analyses, the probability of MRI+CLP becoming the preferred strategy remained lower than 5%.It is thought that anti-beta-amyloid compounds might halt the development of dementia in early stage patients. This study suggests that, even should such treatments become available, systematically screening the over-60 population for AD would only become cost-effective with highly specific tests able to diagnose early stages of the disease. However, offering a new diagnostic test based on beta-amyloid markers to elderly patients with MCI might prove cost-effective.

  16. Elucidating the life cycle of Marteilia sydneyi, the aetiological agent of QX disease in the Sydney rock oyster (Saccostrea glomerata).

    Adlard, Robert D; Nolan, Matthew J

    2015-05-01

    Marteilia sydneyi (Phylum Paramyxea, Class Marteiliidea, Order Marteiliida) (the causative agent of QX disease) is recognised as the most severe parasite to infect Saccostrea glomerata, the Sydney rock oyster, on the east coast of Australia. Despite its potential impact on industry (>95% mortality), research towards lessening these effects has been hindered by the lack of an experimental laboratory model of infection as a consequence of our incomplete understanding of the life cycle of this parasite. Here, we explored the presence of this parasite in hosts other than a bivalve mollusc from two study sites on the Hawkesbury River, New South Wales, Australia. We employed PCR-based in situ hybridisation and sequence analysis of a portion of the first internal transcribed spacer of rDNA in an attempt to detect M. sydneyi DNA in 21 species of polychaete worm. Marteilia DNA was detected in 6% of 1247 samples examined by PCR; the analysis of all amplicons defined one distinct sequence type for first internal transcribed spacer, representing M. sydneyi. Of the polychaete operational taxonomic units test-positive in PCR, we examined 116 samples via in situ hybridisation DNA probe staining and identified M. sydneyi DNA in the epithelium of the intestine of two specimens of Nephtys australiensis. Two differing morphological forms were identified: a 'primordial' cell that contained a well-defined nucleus but had little differentiation in the cytoplasm, and a 'plasmodial' cell that showed an apparent syncytial structure. This finding represents the first known record of the identification of M. sydneyi being parasitic in an organism other than an oyster, and only the third record of any species of Marteilia identified from non-molluscan hosts. Future work aims at determining if N. australiensis and S. glomerata are the only hosts in the life cycle of this paramyxean, and the development of experimental models to aid the production of QX disease-resistant oysters. Copyright

  17. Simultaneous Response in Several Domains in Patients with Psoriatic Disease Treated with Etanercept as Monotherapy or in Combination with Conventional Synthetic Disease-modifying Antirheumatic Drugs.

    Behrens, Frank; Meier, Lothar; Prinz, Jörg C; Jobst, Jürgen; Lippe, Ralph; Löschmann, Peter-Andreas; Lorenz, Hanns-Martin

    2018-04-01

    To evaluate patients with psoriatic arthritis (PsA) receiving etanercept (ETN) monotherapy or ETN plus conventional synthetic disease-modifying antirheumatic drugs (csDMARD) to determine the proportion achieving a clinically meaningful response in arthritis, psoriasis, and quality of life simultaneously. A prospective, multicenter, 52-week observational study in patients with active PsA evaluated treatment with ETN in clinical practice (ClinicalTrials.gov: NCT00293722). This analysis assessed simultaneous achievement of 3 treatment targets: low disease activity (LDA) based on 28-joint count Disease Activity Score (DAS28); body surface area (BSA) involvement ≤ 3%; and a score > 45 on the Medical Outcomes Study Short Form-12 (SF-12) physical component summary. Of 579 patients, 380 received ETN monotherapy and 199 received combination ETN plus csDMARD. At 52 weeks, data for all 3 disease domains were available for 251 patients receiving monotherapy and 151 receiving combination therapy. In the monotherapy and combination therapy groups, 61 (24.3%) and 37 (24.5%) patients, respectively, achieved all 3 treatment targets simultaneously. A significantly greater proportion of patients receiving monotherapy versus combination therapy achieved SF-12 > 45 (43.0% vs 31.8%; p < 0.05) and DAS28 LDA (72.5% vs 62.3%; p < 0.05). Conversely, BSA ≤ 3% was reached by a significantly greater proportion receiving combination therapy (75.5% vs 56.6%; p < 0.001). However, baseline BSA involvement was higher for the monotherapy group. While nearly half the patients achieved arthritis and psoriasis treatment targets simultaneously and one-fourth reached all 3 treatment targets, combining ETN and csDMARD did not substantially improve clinical response compared with ETN monotherapy in this real-world PsA patient population.

  18. Potential therapeutic agents for circulatory diseases from Bauhinia glauca Benth.subsp. pernervosa. (Da Ye Guan Men).

    Tang, Yingzhan; Ling, Junhong; Zhang, Peng; Zhang, Xiangrong; Zhang, Na; Wang, Wenli; Li, Jiayuan; Li, Ning

    2015-08-15

    Because of platelets as critical factor in the formation of pathogenic thrombi, anti-platelet activities have been selected as therapeutic target for various circulatory diseases. In order to find potential therapeutic agents, bioassay-directed separation of Bauhinia glauca Benth.subsp. pernervosa. (called Da Ye Guan Men as a traditional Chinese medicine) was performed to get 29 main components (compounds 1-29) from the bioactive part of this herbal. It was the first time to focus on the composition with anti-platelet aggregation activities for this traditional Chinese medicine. The constituents, characterized from the effective extract, were established on the basis of extensive spectral data analysis. Then their anti-platelet aggregation effects were evaluated systematically. On the basis of the chemical profile and biological assay, it was suggested that the flavonoid composition (5 and 18) should be responsible for the anti-platelet aggregation of the herbal because of their significant activities. The primary structure and activity relationship was also discussed briefly. Copyright © 2015. Published by Elsevier Ltd.

  19. Inhibitory action of essential oils against proteases activity of Paenibacillus larvae, the etiological agent of American Foulbrood disease

    Pellegrini, M.C.; Zalazar, L.; Fuselli, S.L.; Ponce, A.G.

    2017-01-01

    American foulbrood (AFB) is a disease affecting the larva of Apis mellifera. The etiological agent is Paenibacillus larvae, which releases metalloproteases involved in the degradation of larval tissues. Through quorum sensing (QS) mechanism, bacteria are able to activate specific genes such as virulence factors. The exoproteases regulation of P. larvae could be associated with QS. A promising mechanism of AFB control is to block QS mechanism with essential oils (EO). The aim of this study was to investigate the potential presence of QS signals in the regulation of P. larvae proteases and the effect of seven EOs on the exoproteases activity of P. larvae. From growth curves and evaluation of the presence of proteases by milk agar plates assay, it was observed protease activity during the late exponential phase of growth. Early production of protease activity (15 hours earlier than control) was observed when a low density culture was incubated with late exponential spent medium (SM) suggesting the presence of factor(s) inducing this activity. SM was obtained by the ultrafiltration of P. larvae cultures on late growth phase and was free of proteases. Proteolytic activity was quantified on P. larvae cultures in presence of sublethal concentration of EO by azocasein method. The EOs, except S. chilensis EO, reduced significantly protease activity (more than 50%). We report for the first time evidence on the possible role of QS on P. larvae and the antiproteolytic activity of EOs (except for S. chilensis) on exoproteases, an interesting therapeutic strategy to control AFB.

  20. Evaluation of antimicrobial activity of glycerol monolaurate nanocapsules against American foulbrood disease agent and toxicity on bees.

    Lopes, Leonardo Q S; Santos, Cayane G; de Almeida Vaucher, Rodrigo; Gende, Liesel; Raffin, Renata P; Santos, Roberto C V

    2016-08-01

    The American Foulbrood Disease (AFB) is a fatal larval bee infection. The etiologic agent is the bacterium Paenibacillus larvae. The treatment involves incineration of all contaminated materials, leading to high losses. The Glycerol Monolaurate (GML) is a known antimicrobial potential compound, however its use is reduced due to its low solubility in water and high melting point. The nanoencapsulation of some drugs offers several advantages like improved stability and solubility in water. The present study aimed to evaluate the antimicrobial activity against P. larvae and the toxicity in bees of GML nanoparticles. The nanocapsules were produced and presented mean diameter of 210 nm, polydispersity index of 0.044, and zeta potential of -23.4 mV demonstrating the acceptable values to predict a stable system. The microdilution assay showed that it is necessary 142 and 285 μg/mL of GML nanocapsules to obtain a bacteriostatic and bactericidal effect respectively. The time-kill curve showed the controlled release of compound, exterminating the microorganism after 24 h. The GML nanocapsules were able to kill the spore form of Paenibacillus larvae while the GML do not cause any effect. The assay in bees showed that the GML has a high toxicity while the GML nanoparticles showed a decrease on toxic effects. Concluding, the formulation shows positive results in the action to combat AFB besides not causing damage to bees. Copyright © 2016 Elsevier Ltd. All rights reserved.

  1. Inhibitory action of essential oils against proteases activity of Paenibacillus larvae, the etiological agent of American Foulbrood disease

    Pellegrini, M.C.; Zalazar, L.; Fuselli, S.L.; Ponce, A.G.

    2017-07-01

    American foulbrood (AFB) is a disease affecting the larva of Apis mellifera. The etiological agent is Paenibacillus larvae, which releases metalloproteases involved in the degradation of larval tissues. Through quorum sensing (QS) mechanism, bacteria are able to activate specific genes such as virulence factors. The exoproteases regulation of P. larvae could be associated with QS. A promising mechanism of AFB control is to block QS mechanism with essential oils (EO). The aim of this study was to investigate the potential presence of QS signals in the regulation of P. larvae proteases and the effect of seven EOs on the exoproteases activity of P. larvae. From growth curves and evaluation of the presence of proteases by milk agar plates assay, it was observed protease activity during the late exponential phase of growth. Early production of protease activity (15 hours earlier than control) was observed when a low density culture was incubated with late exponential spent medium (SM) suggesting the presence of factor(s) inducing this activity. SM was obtained by the ultrafiltration of P. larvae cultures on late growth phase and was free of proteases. Proteolytic activity was quantified on P. larvae cultures in presence of sublethal concentration of EO by azocasein method. The EOs, except S. chilensis EO, reduced significantly protease activity (more than 50%). We report for the first time evidence on the possible role of QS on P. larvae and the antiproteolytic activity of EOs (except for S. chilensis) on exoproteases, an interesting therapeutic strategy to control AFB.

  2. Inhibitory action of essential oils against proteases activity of Paenibacillus larvae, the etiological agent of American Foulbrood disease

    María C. Pellegrini

    2018-02-01

    Full Text Available American foulbrood (AFB is a disease affecting the larva of Apis mellifera. The etiological agent is Paenibacillus larvae, which releases metalloproteases involved in the degradation of larval tissues. Through quorum sensing (QS mechanism, bacteria are able to activate specific genes such as virulence factors. The exoproteases regulation of P. larvae could be associated with QS. A promising mechanism of AFB control is to block QS mechanism with essential oils (EO. The aim of this study was to investigate the potential presence of QS signals in the regulation of P. larvae proteases and the effect of seven EOs on the exoproteases activity of P. larvae. From growth curves and evaluation of the presence of proteases by milk agar plates assay, it was observed protease activity during the late exponential phase of growth. Early production of protease activity (15 hours earlier than control was observed when a low density culture was incubated with late exponential spent medium (SM suggesting the presence of factor(s inducing this activity. SM was obtained by the ultrafiltration of P. larvae cultures on late growth phase and was free of proteases. Proteolytic activity was quantified on P. larvae cultures in presence of sublethal concentration of EO by azocasein method. The EOs, except S. chilensis EO, reduced significantly protease activity (more than 50%. We report for the first time evidence on the possible role of QS on P. larvae and the antiproteolytic activity of EOs (except for S. chilensis on exoproteases, an interesting therapeutic strategy to control AFB.

  3. Effect of nutrition and environmental factors on the endoparasitic fungus Esteya vermicola, a biocontrol agent against pine wilt disease.

    Xue, Jianjie; Zhang, Yongan; Wang, Chunyan; Wang, Yuzhu; Hou, Jingang; Wang, Zhen; Wang, Yunbo; Gu, Lijuan; Sung, Changkeun

    2013-09-01

    The nematophagous fungus Esteya vermicola has tremendous potential for biological control. This species exhibits strong infectious activity against pinewood nematodes, whereas the study on the effect of nutrition and environmental factors is still of paucity. Carbon (C), nitrogen (N), pH value, temperature, and water activity have great impact on the fungal growth, sporulation, and germination. In nutrition study, the greatest number of conidia (2.36 × 10(9) per colony) was obtained at the C:N ratio of 100:1 with a carbon concentration 32 g l(-1). In addition, the germination rate and radial growth of E. vermicola were used to evaluate the effects of environmental conditions and they were optimized as following: pH 5.5, 26 °C and water activity of 0.98. Our results also confirmed that variation of environmental factors has a detrimental influence on the efficacy of active conidia and growth of fungus. Moreover, under above optimal condition, the biocontrol efficacy was significantly improved in regard to the increase of adhesive and mortality rate, which highlight the study on the application of E. vermicola as pine wilt disease biocontrol agent.

  4. Potential of a new strain of Bacillus amyloliquefaciens BUZ-14 as a biocontrol agent of postharvest fruit diseases.

    Calvo, H; Marco, P; Blanco, D; Oria, R; Venturini, M E

    2017-05-01

    The biocontrol potential of the Bacillus amyloliquefaciens strain BUZ-14 was tested against the main postharvest diseases of orange, apple, grape and stone fruit. After characterizing the temperature and pH growth curves of strain BUZ-14, its in vitro antifungal activity was determined against Botrytis cinerea, Monilinia fructicola, M. laxa, Penicillium digitatum, P. expansum and P. italicum. Subsequently, in vivo activity was tested against these pathogens by treating fruit with cells, endospores and cell-free supernatants. The in vitro results showed that BUZ-14 inhibited the growth of all the pathogens tested corresponding to the least susceptible species, P. italicum, and the most susceptible, M. laxa. In vivo tests corroborated these results as most of the treatments decreased the incidence of brown rot in stone fruit from 100% to 0%, establishing 10 7  CFU mL -1 as the minimum inhibitory concentration. For the Penicillium species a preventive treatment inhibited P. digitatum and P. italicum growth in oranges and reduced P. expansum incidence in apples from 100% to 20%. Finally, it has been demonstrated that BUZ-14 was able to survive and to control brown rot in peaches stored at cool temperatures, making it a very suitable biocontrol agent for application during the post-harvest storage and marketing of horticultural products. Copyright © 2016 Elsevier Ltd. All rights reserved.

  5. Utilization Patterns of IV Iron and Erythropoiesis Stimulating Agents in Anemic Chronic Kidney Disease Patients: A Multihospital Study

    Avani D. Joshi

    2012-01-01

    Full Text Available Intravenous (IV iron and Erythropoiesis Stimulating Agents (ESAs are recommended for anemia management in chronic kidney disease (CKD. This retrospective cohort study analyzed utilization patterns of IV iron and ESA in patients over 18 years of age admitted to University Health System Hospitals with a primary or secondary diagnosis of CKD between January 1, 2006 to December 31, 2008. A clustered binomial logistic regression using the GEE methodology was used to identify predictors of IV iron utilization. Only 8% (n = 6678 of CKD patients on ESA therapy received IV iron supplementation in university hospitals. Those receiving iron used significantly less amounts of ESAs. Patient demographics (age, race, primary payer, patient clinical conditions (admission status, severity of illness, dialysis status, and physician specialty were identified as predictors of IV iron use in CKD patients. Use of IV iron with ESAs was low despite recommendations from consensus guidelines. The low treatment rate of IV iron represents a gap in treatment practices and signals an opportunity for healthcare improvement in CKD anemic patients.

  6. Synthetic Curcumin Analogs as Inhibitors of β -Amyloid Peptide Aggregation: Potential Therapeutic and Diagnostic Agents for Alzheimer's Disease.

    Bukhari, Syed Nasir Abbas; Jantan, Ibrahim

    2015-01-01

    There is a crucial need to develop new effective drugs for Alzheimer's disease (AD) as the currently available AD treatments provide only momentary and incomplete symptomatic relief. Amongst natural products, curcumin, a major constituent of turmeric, has been intensively investigated for its neuroprotective effect against β-amyloid (Aβ)-induced toxicity in cultured neuronal cells. The ability of curcumin to attach to Aβ peptide and prevent its accumulation is attributed to its three structural characteristics such as the presence of two aromatic end groups and their co-planarity, the length and rigidity of the linker region and the substitution conformation of these aromatics. However, curcumin failed to reach adequate brain levels after oral absorption in AD clinical trials due to its low water solubility and poor oral bioavailability. A number of new curcumin analogs that mimic the active site of the compound along with analogs that mimic the curcumin anti-amyloid effect combined with anticholinesterase effect have been developed to enhance the bioavailability, pharmacokinetics, water solubility, stability at physiological conditions and delivery of curcumin. In this article, we have summarized all reported synthetic analogs of curcumin showing effects on β-amyloid and discussed their potential as therapeutic and diagnostic agents for AD.

  7. [In vitro early detection of amyloid plaques in Alzheimer's disease by Pittsburgh compound B-modified magnetic nanoparticles].

    Zeng, J Q; Wu, J Q; Li, M H; Wang, P J

    2017-11-07

    Objective: To construct magnetic nanoparticles targeting β-amyloid (Aβ) plaques, the pathological biomarker of Alzheimer's disease (AD) and to study their binding capability in vitro . Methods: Superparamagnetic nanoparticles Mn(0.6)Zn(0.4)Fe(2)O(4) (MZF) were coated with amphiphilic star-block copolymeric micelles and modified with Aβ-specific probe Pittsburgh compound B (PiB) to construct a novel magnetic nanoparticle MZF-PiB, which specifically targeted amyloid plaques. Transmission electron microscope was used to study the morphological features of MZF-PiB. Superparamagnetism of MZF-PiB was assessed by its r(2) relaxation rate by using 3.0 T MRI scanner. Cytotoxic test was applied to determine biosafety of MZF-PiB nanoparticles in differentiated human neuroblastoma cells (SH-SY5Y) and Madin-Darby canine kidney (MDCK). In vitro binding tests were conducted via immunohistochemistry on 6-month old AD mice brain sections. Differences of cell viability between groups were compared with one-way analysis of variance. Results: MZF-PiB nanoparticles were successfully constructed. Transmission electron microscope images showed that the nanoparticles were about 100 nm in size. The r(2) relaxation rate was 163.11 mMS(-1). No differences were found in cell viability of SH-SY5Y and MDCK incubated with MZF-PiB suspension for 24 h or 48 h when compared with those of untreated cells ( F =2.336, 2.539, 0.293, 1.493, all P >0.05). In vitro binding tests indicated that the MZF-PiB were specifically bound to amyloid plaques. The smallest size of detected plaques was 27 μm. Conclusion: PiB-modified nanoparticles targeting Aβ are biologically safe and highly superparamagnetic, possessing the capability to detect amyloid plaques early in vitro and the potential for early diagnosis of AD.

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

    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. Magnesium modifies the association between serum phosphate and the risk of progression to end-stage kidney disease in patients with non-diabetic chronic kidney disease.

    Sakaguchi, Yusuke; Iwatani, Hirotsugu; Hamano, Takayuki; Tomida, Kodo; Kawabata, Hiroaki; Kusunoki, Yasuo; Shimomura, Akihiro; Matsui, Isao; Hayashi, Terumasa; Tsubakihara, Yoshiharu; Isaka, Yoshitaka; Rakugi, Hiromi

    2015-10-01

    It is known that magnesium antagonizes phosphate-induced apoptosis of vascular smooth muscle cells and prevents vascular calcification. Here we tested whether magnesium can also counteract other pathological conditions where phosphate toxicity is involved, such as progression of chronic kidney disease (CKD). We explored how the link between the risk of CKD progression and hyperphosphatemia is modified by magnesium status. A post hoc analysis was run in 311 non-diabetic CKD patients who were divided into four groups according to the median values of serum magnesium and phosphate. During a median follow-up of 44 months, 135 patients developed end-stage kidney disease (ESKD). After adjustment for relevant clinical factors, patients in the lower magnesium-higher phosphate group were at a 2.07-fold (95% CI: 1.23-3.48) risk for incident ESKD and had a significantly faster decline in estimated glomerular filtration rate compared with those in the higher magnesium-higher phosphate group. There were no significant differences in the risk of these renal outcomes among the higher magnesium-higher phosphate group and both lower phosphate groups. Incubation of tubular epithelial cells in high phosphate and low magnesium medium in vitro increased apoptosis and the expression levels of profibrotic and proinflammatory cytokine; these changes were significantly suppressed by increasing magnesium concentration. Thus, magnesium may act protectively against phosphate-induced kidney injury.

  10. Evaluation of the effects of chemical versus biological control on Botrytis cinerea agent of gray mould disease of strawberry.

    Alizadeh, H R; Sharifi-Tehrani, A; Hedjaroude, Gh A

    2007-01-01

    This study investigates on effects of four fungicide and six isolate from Trichoderma and Gliocladium on Botrytis cinerea agent grey mold of strawberry under library and greenhouse condition. The effect of four fungicides i.e. benomyl, dichlofluanid, captan and triadimenol on B. cinerea was studied in the laboratory condition by method mixed poison to culture medium. It was shown that the fungicide including benomyl, triadimenol, dichlofluanid and captan were able to inhibit mycelial growth of B. cinerea on PDA plate with EC50 of 0.16, 1.42, 3.40 and 7.73 ppm respectively. These fungicides delayed myceliogenic germination of sclerotia at 1000 ppm, while exhibiting no fungicidal effect. Moreover, the antagonistic effects of six fungi including Trichoderma koningii (T21), T. viride (T4), T. harzionum (T5), T. viride (T2), G. virens (G2), G. virens (G8) on B. cinerea were assessed. This assessment was done under library condition and its results as follows: The antagonistic mechanism occurred through branching at the end of B. cinerea hyphae, hyphal contact, coiling, vacuolization and lyses. Volatile metabolites of T. koningii (T21) and non-volatile metabolites of G. virens (G2 and G8) and T. koningii (T21) caused maximum inhibition of the fungal growth. Trichoderma spp and G. virens were able to colonize and sporulate on sclerotia and caused their lysis within 7-21 days. In greenhouse, a completely randomized design with 11 treatments (4 chemical and 6 biological and one untreated control) each replicated five times were used for the comparison. Greenhouse studies revealed that application of fungicides i.e. captan, dichlofluanid, triadimenol and benomyl reduces disease severity by 42, 45, 48 and 52% respectively. The fungal antagonists reduce the grey mold disease severity between 5-42%. All treatments caused a decline in post harvest disease, as the most effective treatment of chemical control was benomyl with 68.33% and for the biological treatment this was T

  11. Validation of a model to investigate the effects of modifying cardiovascular disease (CVD) risk factors on the burden of CVD: the rotterdam ischemic heart disease and stroke computer simulation (RISC) model

    van Kempen, Bob J. H.; Ferket, Bart S.; Hofman, Albert; Steyerberg, Ewout W.; Colkesen, Ersen B.; Boekholdt, S. Matthijs; Wareham, Nicholas J.; Khaw, Kay-Tee; Hunink, M. G. Myriam

    2012-01-01

    Background: We developed a Monte Carlo Markov model designed to investigate the effects of modifying cardiovascular disease (CVD) risk factors on the burden of CVD. Internal, predictive, and external validity of the model have not yet been established. Methods: The Rotterdam Ischemic Heart Disease

  12. 99mTc-MAG3 as a single modality investigative agent for evaluation of renal diseases in children

    Bal, C.S.; Padhy, A.K.; Handa, R.; Bajpai, M.

    1998-01-01

    Optimal assessment of a child with congenital or acquired renal disease consists of quantitation of renal cortical and excretory function. This at present is routinely done with a 99m Tc-GHA/DMSA and 99m Tc-DTPA scans, respectively. This study was undertaken to assess if 99m Tc-MAG 3 can be utilized as a single modality investigation to provide adequate information about these functions. Sixteen children attending the pediatric urology clinic at All India Institute of Medical Sciences (AIIMS), New Delhi with a variety of renal disorders like posterior urethral valves, hydronephrosis vesicoureteral reflux etc. were included in the study. All the cases were subjected to 99m Tc-MAG 3 , 99m -DTPA and 99m Tc-GHA scans on separate occasions, but as close to one other as possible. The time required for the completion of a 99m Tc-MAG 3 renogram was only twenty minutes. 99m Tc-MAG 3 produced significantly better scintigraphic images of the kidneys and ureters, enabling differentiation between pelviureteric and vesicoureteric junction obstruction. Because of the abundance of photons in 99m Tc-MAG 3 , antegrade ureteric visualization was possible in nine renal units with active ureteric peristalsis appreciable in three renal units. Being a renal tubular agent, it gave a better assessment of renal health of the involved renal unit as compared to 99m Tc-DTPA, a glomerular filtration agent. Detection of renal scars as compared to 99m Tc-GHA showed a sensitivity of 69% and specificity of 93%. Amount of radioactivity required was consistently less than either GHA or DTPA scans. Use of 99m Tc-MAG 3 for renal functional evaluation may result in decreased radiation exposure and optional gamma camera utilization. Besides it is more cost-effective and may reduce the number of investigations that a child needs to be subjected to. It may be of immense value in a country like India where patients have to travel long distances to avail such investigations in a few, overworked nuclear

  13. Sialic acid (SA)-modified selenium nanoparticles coated with a high blood-brain barrier permeability peptide-B6 peptide for potential use in Alzheimer's disease.

    Yin, Tiantian; Yang, Licong; Liu, Yanan; Zhou, Xianbo; Sun, Jing; Liu, Jie

    2015-10-01

    The blood-brain barrier (BBB) is a formidable gatekeeper toward exogenous substances, playing an important role in brain homeostasis and maintaining a healthy microenvironment for complex neuronal activities. However, it also greatly hinders drug permeability into the brain and limits the management of brain diseases. The development of new drugs that show improved transport across the BBB represents a promising strategy for Alzheimer's disease (AD) intervention. Whereas, previous study of receptor-mediated endogenous BBB transport systems has focused on a strategy of using transferrin to facilitate brain drug delivery system, a system that still suffers from limitations including synthesis procedure, stability and immunological response. In the present study, we synthetised sialic acid (SA)-modified selenium (Se) nanoparticles conjugated with an alternative peptide-B6 peptide (B6-SA-SeNPs, a synthetic selenoprotein analogue), which shows high permeability across the BBB and has the potential to serve as a novel nanomedicine for disease modification in AD. Laser-scanning confocal microscopy, flow cytometry analysis and inductively coupled plasma-atomic emission spectroscopy ICP-AES revealed high cellular uptake of B6-SA-SeNPs by cerebral endothelial cells (bEnd.3). The transport efficiency of B6-SA-SeNPs was evaluated in a Transwell experiment based on in vitro BBB model. It provided direct evidence for B6-SA-SeNPs crossing the BBB and being absorbed by PC12 cells. Moreover, inhibitory effects of B6-SA-SeNPs on amyloid-β peptide (Aβ) fibrillation could be demonstrated in PC12 cells and bEnd3 cells. B6-SA-SeNPs could not only effectively inhibit Aβ aggregation but could disaggregate preformed Aβ fibrils into non-toxic amorphous oligomers. These results suggested that B6-SA-SeNPs may provide a promising platform, particularly for the application of nanoparticles in the treatment of brain diseases. Alzheimer's disease (AD) is the world's most common form of

  14. Comparative Studies on Thermal, Mechanical, and Flame Retardant Properties of PBT Nanocomposites via Different Oxidation State Phosphorus-Containing Agents Modified Amino-CNTs.

    Zhu, San-E; Wang, Li-Li; Chen, Hao; Yang, Wei; Yuen, Anthony Chun-Yin; Chen, Timothy Bo-Yuan; Luo, Cheng; Bi, Wen-Mei; Hu, En-Zhu; Zhang, Jian; Si, Jing-Yu; Lu, Hong-Dian; Hu, Kun-Hong; Chan, Qing Nian; Yeoh, Guan Heng

    2018-01-26

    High-performance poly(1,4-butylene terephthalate) (PBT) nanocomposites have been developed via the consideration of phosphorus-containing agents and amino-carbon nanotube (A-CNT). One-pot functionalization method has been adopted to prepare functionalized CNTs via the reaction between A-CNT and different oxidation state phosphorus-containing agents, including chlorodiphenylphosphine (DPP-Cl), diphenylphosphinic chloride (DPP(O)-Cl), and diphenyl phosphoryl chloride (DPP(O₃)-Cl). These functionalized CNTs, DPP(O x )-A-CNTs ( x = 0, 1, 3), were, respectively, mixed with PBT to obtain the CNT-based polymer nanocomposites through a melt blending method. Scanning electron microscope observations demonstrated that DPP(O x )-A-CNT nanoadditives were homogeneously distributed within PBT matrix compared to A-CNT. The incorporation of DPP(O x )-A-CNT improved the thermal stability of PBT. Moreover, PBT/DPP(O₃)-A-CNT showed the highest crystallization temperature and tensile strength, due to the superior dispersion and interfacial interactions between DPP(O₃)-A-CNT and PBT. PBT/DPP(O)-A-CNT exhibited the best flame retardancy resulting from the excellent carbonization effect. The radicals generated from decomposed polymer were effectively trapped by DPP(O)-A-CNT, leading to the reduction of heat release rate, smoke production rate, carbon dioxide and carbon monoxide release during cone calorimeter tests.

  15. Cerivastatin Nano-Liposome as a Potential Disease Modifying Approach for the Treatment of Pulmonary Arterial Hypertension.

    Lee, Young; Pai, S Balakrishna; Bellamkonda, Ravi V; Thompson, David H; Singh, Jaipal

    2018-04-25

    In this study, we have investigated nano-liposome as an approach to tailor the pharmacology of cerivastatin as a disease modifying drug for pulmonary arterial hypertension (PAH). Cerivastatin encapsulated liposomes with an average diameter of 98±27 nm were generated by thin film and freeze-thaw process. The nano-liposomes demonstrated sustained drug release kinetics in vitro and inhibited proliferation of pulmonary artery smooth muscle cells with significantly less cellular cytotoxicity as compared to free cerivastatin. When delivered by inhalation to a rat model of monocrotalin induced PAH, cerivastatin significantly reduced pulmonary artery pressure from 55.13±9.82 mmHg to 35.56±6.59 mmHg (P < 0.001) and diminished pulmonary artery wall thickening. Echocardiography showed that cerivastatin significantly reduced right ventricle thickening (0.34±0.02 cm monocrotalin vs. 0.26±0.02 cm cerivastatin; P < 0.001) and increased pulmonary artery acceleration time (13.98±1.14 ms monocrotalin vs. 21.07±2.80 ms cerivastatin; P < 0.001). Nano-liposomal cerivastatin was equally effective or slightly better than cerivastatin in reducing pulmonary artery pressure (67.06±13.64 mmHg monocrotalin; 46.31±7.64 mmHg cerivastatin vs. 37.32±9.50 mmHg liposomal cerivastatin) and improving parameters of right ventricular function as measured by increasing pulmonary artery acceleration time (24.68±3.92 ms monocrotalin; 32.59±6.10 ms cerivastatin vs. 34.96±7.51 ms liposomal cerivastatin). More importantly, the rate and magnitude of toxic cerivastatin metabolite lactone generation from the intratracheally administered nano-liposomes was significantly lower as compared to intravenously administered free cerivastatin. These studies show that nano-liposome encapsulation improved in vitro and in vivo pharmacological and safety profile of cerivastatin and may represent a safer approach as a disease modifying therapy for PAH. The American Society for Pharmacology and Experimental

  16. The V471A polymorphism in autophagy-related gene ATG7 modifies age at onset specifically in Italian Huntington disease patients

    Metzger, Silke; Walter, Carolin; Riess, Olaf

    2013-01-01

    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......, 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...... 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...

  17. CARACTERIZACIÓN MORFOLÓGICA DE PELÍCULAS BIODEGRADABLES A PARTIR DE ALMIDÓN MODIFICADO DE YUCA, AGENTE ANTIMICROBIANO Y PLASTIFICANTE CARACTERIZAÇÃO MORFOLÓGICA DE FILMES BIODEGRADÁVEIS A PARTIR DE AMIDO MODIFICADO DE MANDIOCA, AGENTE ANTIMICROBIANO E PLASTIFICANTE MORPHOLOGICAL CHARACTERIZATION OF BIODEGRADABLE FILMS MADE FROM MODIFIED CASSAVA STARCH, ANTIMICROBIAL AGENT AND PLASTICIZER

    REINALDO VELASCO M

    2012-12-01

    propriedades microestruturais e mecânicas dos amidos termoplásticos, que são essenciais para a continuidade no estudo de filmes biodegradáveisIt was evaluated the morphological surface of thermoplastic starch (TPS obtained from three modified cassava starch varieties, plasticizer and an antimicrobial agent. The films was made by blown extrusion and extended over a slide and then was taken photomicrographs with 4x and 10x objectives. It was used High Resolution Optical Microscopy to image characterization. The technique showed the effect of plasticizer addition over the starch films microstructure, it was found some inhomogeneity; however was identified some smooth regions related to form and size of starch granule, plasticizer concentration and extrusion variables process like velocity screw and temperature profile. This research contributed to characterize microstructural properties and gave some insights about the mechanical behaviour of TPS films, needed to study and make biodegradable films.

  18. Synthesis and antimicrobial evaluation of two peptide LyeTx I derivatives modified with the chelating agent HYNIC for radiolabeling with technetium-99m.

    Fuscaldi, Leonardo Lima; Dos Santos, Daniel Moreira; Pinheiro, Natália Gabriela Silva; Araújo, Raquel Silva; de Barros, André Luís Branco; Resende, Jarbas Magalhães; Fernandes, Simone Odília Antunes; de Lima, Maria Elena; Cardoso, Valbert Nascimento

    2016-01-01

    Current diagnostic methods and imaging techniques are not able to differentiate septic and aseptic inflammation. Thus, reliable methods are sought to provide this distinction and scintigraphic imaging is an interesting option, since it is based on physiological changes. In this context, radiolabeled antimicrobial peptides have been investigated as they accumulate in infectious sites instead of aseptic inflammation. The peptide LyeTx I, from the venom of Lycosa erythrognatha, has potent antimicrobial activity. Therefore, this study aimed to synthesize LyeTx I derivatives with the chelating compound HYNIC, to evaluate their antimicrobial activity and to radiolabel them with (99m)Tc. Two LyeTx I derivatives, HYNIC-LyeTx I (N-terminal modification) and LyeTx I-K-HYNIC (C-terminal modification), were synthesized by Fmoc strategy and purified by RP-HPLC. The purified products were assessed by RP-HPLC and MALDI-ToF-MS analysis. Microbiological assays were performed against S. aureus (ATCC® 6538) and E. coli (ATCC® 10536) in liquid medium to calculate the MIC. The radiolabeling procedure of LyeTx I-K-HYNIC with (99m)Tc was performed in the presence of co-ligands (tricine and EDDA) and reducing agent (SnCl2 (.) 2H2O), and standardized taking into account the amount of peptide, reducing agent, pH and heating. Radiochemical purity analysis was performed by thin-layer chromatography on silica gel strips and the radiolabeled compound was assessed by RP-HPLC and radioactivity measurement of the collected fractions. Data were analyzed by ANOVA, followed by Tukey test (p-values EDDA). The binding of HYNIC to the N-terminal portion of LyeTx I seems to affect its activity against bacteria. Nevertheless, the radiolabeling of the C-terminal derivative, LyeTx I-K-HYNIC, must be better investigated to optimize the radiolabeled compound, in order to use it as a specific imaging agent to distinguish septic and aseptic inflammation.

  19. The mosaic of environment involvement in autoimmunity: the abrogation of viral latency by stress, a non-infectious environmental agent, is an intrinsic prerequisite prelude before viruses can rank as infectious environmental agents that trigger autoimmune diseases.

    Temajo, Norbert O; Howard, Neville

    2014-06-01

    An autoimmune disease (AD), organ-specific or systemic, results from an aberrant response in which the protective immune system normally schooled to recognize and destroy invading infectious agents (viruses, etc.) instead fails to distinguish self-antigens and proceeds to attack and destroy the host's organs. There can be familial aggregation in which a single AD may occur in members of a family, or a single family may be afflicted with multiple ADs. Finally, sometimes multiple ADs co-occur in a single individual: the kaleidoscope of autoimmunity. Autoimmunity is a multifactorial process in which genetic, hormonal, immunological and environmental factors act in concert to materialize the mosaic of autoimmunity phenomenon. A genetically primed individual may yet not develop an AD: the contribution by an environmental factor (non-infectious or infectious) is essential for completion of the act. Of the non-infectious factors, stress plays a determinative step in autoimmunity in that it abrogates viral latency and thereby ordains the viruses to qualify as infectious environmental factors that trigger ADs. This is note-worthy as viruses rank first as the most important environmental triggers of ADs. Furthermore, all these viruses experience going through latency. Hence the hypothesis: "The abrogation of viral latency by stress, a non-infectious environmental agent, is an intrinsic prerequisite prelude before viruses can rank as infectious environmental agents that trigger autoimmune diseases". There is collaboration here between non-infectious- and infectious-agent to achieve the cause of autoimmunity. We say viral latency and stress have a covenant: continued perpetration of autoimmunity is dependent on the intervention by stress to reactivate latent infections. Crown Copyright © 2014. Published by Elsevier B.V. All rights reserved.

  20. Clinically isolated syndrome. Prognostic markers for conversion to multiple sclerosis and initiation of disease-modifying therapy

    Kohriyama, Tatsuo

    2011-01-01

    Eighty-five percent of patients with multiple sclerosis (MS) initially present with a single demyelinating event, referred to as a clinically isolated syndrome (CIS) of the optic nerves, brainstem, or spinal cord. Following the onset of CIS, 38 to 68% of patients develop clinically definite MS (CDMS). Clinically silent brain lesions are seen on MRI in 50 to 80% of patients with CIS at first clinical presentation and 56 to 88% of CIS patients with abnormal MRI are at high risk of conversion to CDMS. Axonal damage, that is considered to underlie the development of persistent disability in MS, occurs in the CIS stage. Treatment with disease-modifying therapies (DMTs), that might prevent axonal damage and result in slowing the progression of disability, should be initiated early during the disease course. Clinical trials demonstrated that early treatment of CIS patients with the standard dose of interferon beta (IFNβ) significantly reduced the risk of progression to CDMS by 44 to 50%. After 5 years of follow-up, the results of the IFNβ treatment extension studies confirmed that the risk of conversion to CDMS was significantly reduced by 35 to 37% in patients receiving early treatment compared to that in those receiving delayed treatment. However, not every patient with CIS will progress to CDMS; the IFNβ treatment is appropriately indicated for CIS patients who are diagnosed with MS by McDonald diagnostic criteria based on MRI findings of dissemination in space and time and are at high risk for conversion to CDMS. Development of more reliable prognostic markers will enable DMTs to be targeted for those who are most likely to benefit. (author)

  1. Association between perfluoroalkyl substance exposure and asthma and allergic disease in children as modified by MMR vaccination.

    Timmermann, Clara Amalie Gade; Budtz-Jørgensen, Esben; Jensen, Tina Kold; Osuna, Christa Elyse; Petersen, Maria Skaalum; Steuerwald, Ulrike; Nielsen, Flemming; Poulsen, Lars K; Weihe, Pál; Grandjean, Philippe

    2017-12-01

    Perfluoroalkyl substances (PFASs) are highly persistent chemicals that might be associated with asthma and allergy, but the associations remain unclear. Therefore, this study examined whether pre- and postnatal PFAS exposure was associated with childhood asthma and allergy. Measles, mumps, and rubella (MMR) vaccination in early life may have a protective effect against asthma and allergy, and MMR vaccination is therefore taken into account when evaluating these associations. In a cohort of Faroese children whose mothers were recruited during pregnancy, serum concentrations of five PFASs - Perfluorohexane sulfonic acid (PFHxS), perfluorooctane sulfonic acid (PFOS), perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA), and perfluorodecanoic acid (PFDA) - were measured at three timepoints (maternal serum in pregnancy week 34-36 and child serum at ages 5 and 13 years) and their association with immunoglobulin E (IgE) (cord blood and at age 7 years) and asthma/allergic diseases (questionnaires at ages 5 and 13 years and skin prick test at age 13 years) was determined. A total of 559 children were included in the analyses. Interactions with MMR vaccination were evaluated. Among 22 MMR-unvaccinated children, higher levels of the five PFASs at age 5 years were associated with increased odds of asthma at ages 5 and 13. The associations were reversed among MMR-vaccinated children. Prenatal PFAS exposure was not associated with childhood asthma or allergic diseases regardless of MMR vaccination status. In conclusion, PFAS exposure at age 5 was associated with increased risk of asthma among a small subgroup of MMR-unvaccinated children but not among MMR-vaccinated children. While PFAS exposure may impact immune system functions, this study suggests that MMR vaccination might be a potential effect-modifier.

  2. Diagnostic value of β amyloid plaques imaging agent 131I-IMPY brain imaging in early Alzheimer's disease

    Ye Wanzhong; Lu Chunxiong; Yang Min; Bao Jiandong; Cheng Zhaohuo; Cai Deliang; Wang Zhiqiang; Yang Bixiu

    2012-01-01

    Objective: To evaluate the diagnostic value of β-amyloid plaques imaging agent [ 131 I] 2( 4-dimethylaminop henyl)-6-iodoimidazo [1, 2-α] pyridine ( 131 I-IMPY) SPECT imaging in early Alzheimer's Disease. Methods: 24 cases of AD (7 males, 17 females, aged 48∼79 years) and 14 normal (6 males, 8 females, aged 42∼67 years) control subjects were selected for this study. 131 I-IMPY SPECT imaging was carried out 2-3 h post injection. 131 I-IMPY uptake defined as the ratio of each brain gyrus and cerebellum uptake on fixed region of interest (ROI) (Rcl/cb) was calculated. Comparative analysis between the two groups was carried out using t-test. Results: In patients with early AD (MCI), 131 I-IMPY was increased in parietal gyrus, temporal gyrus and frontal gyrus compared with normal control group and it were found to be statistically significant (t = 1.3967∼2.8757, all P 0.05). In patients with AD, increase in 131 I-IMPY were observed in parietal, temporal, occipital lobes and basal ganglia compared with normal control group and it were found to be statistically significant (t=2.1001∼6.2789, all P 0.05), and 131 I-IMPY was increased in occipital lobes and basal ganglia compared with MCI group and it were found to be statistically significant (t=2.0850∼3.6772, all P 131 I-IMPY was lightly increased in each brain of left side gyrus compared with right but without statistically significant difference (t=0.1273∼0.5571, all P>0.05). Conclusions: 131 I-IMPY SPECT Imaging was helpful for early diagnosis of AD. (authors)

  3. Genome Sequence, Assembly and Characterization of Two Metschnikowia fructicola Strains Used as Biocontrol Agents of Postharvest Diseases

    Edoardo Piombo

    2018-04-01

    Full Text Available The yeast Metschnikowia fructicola was reported as an efficient biological control agent of postharvest diseases of fruits and vegetables, and it is the bases of the commercial formulated product “Shemer.” Several mechanisms of action by which M. fructicola inhibits postharvest pathogens were suggested including iron-binding compounds, induction of defense signaling genes, production of fungal cell wall degrading enzymes and relatively high amounts of superoxide anions. We assembled the whole genome sequence of two strains of M. fructicola using PacBio and Illumina shotgun sequencing technologies. Using the PacBio, a high-quality draft genome consisting of 93 contigs, with an estimated genome size of approximately 26 Mb, was obtained. Comparative analysis of M. fructicola proteins with the other three available closely related genomes revealed a shared core of homologous proteins coded by 5,776 genes. Comparing the genomes of the two M. fructicola strains using a SNP calling approach resulted in the identification of 564,302 homologous SNPs with 2,004 predicted high impact mutations. The size of the genome is exceptionally high when compared with those of available closely related organisms, and the high rate of homology among M. fructicola genes points toward a recent whole-genome duplication event as the cause of this large genome. Based on the assembled genome, sequences were annotated with a gene description and gene ontology (GO term and clustered in functional groups. Analysis of CAZymes family genes revealed 1,145 putative genes, and transcriptomic analysis of CAZyme expression levels in M. fructicola during its interaction with either grapefruit peel tissue or Penicillium digitatum revealed a high level of CAZyme gene expression when the yeast was placed in wounded fruit tissue.

  4. Identification and application of biocontrol agents against Cotton leaf curl virus disease in Gossypium hirsutum under greenhouse conditions

    Memoona Ramzan

    2016-05-01

    Full Text Available Biological control is a novel approach in crop protection. Bacteria, such as Bacillus spp. and Pseudomonas spp., are reported for this purpose and some of their products are already commercially available. In this study, the rhizosphere and phyllosphere of healthy cotton plants were used as a source of bacterial isolates with properties of potential biocontrol agents. The isolates were screened for phosphate solubilization activity, indole acetic acid (IAA production and antifungal activity. Two isolates, S1HL3 and S1HL4, showed phosphate solubilization and IAA production simultaneously, while another two, JS2HR4 and JS3HR2, demonstrated potential to inhibit fungal pathogens. These bacteria were identified as Pseudomonas aeruginosa (S1HL3, Burkholderia sp. (S1HL4 and Bacillus sp. (JS2HR4 and JS3HR2 based on biochemical and molecular characteristics. The isolates were tested against Cotton leaf curl virus (CLCuV in greenhouse conditions, both as individual bacterial isolates and consortia. Treated plants were healthy as compared to control plants, where up to 74% of the plants were symptomatic for CLCuV infection. Maximum inhibition of CLCuV was observed in the plants treated with a mixture of bacterial isolates: the viral load in the treated plants was only 0.4% vs. up to 74% in controls. This treatment consortium included P. aeruginosa S1HL3, Burkholderia sp. S1HL4 and Bacillus spp. isolates, JS2HR4 and JS3HR2. The principal-component biplot showed a highly significant correlation between the viral load percentage and the disease incidence.

  5. Radiation sensitizations at DNA-level by chemical and biological agents. Coordinated programme on improvement of radiotherapy of cancer using modifiers of radiosensitivity of cells

    Altmann, H.

    1982-01-01

    Radiation sensitization by chemical agents at DNA level is discussed. Procaine, Halothan and Metronidazole showed no significant effect on unscheduled DNA synthesis (UDS) in mouse spleen cells, investigated by autoradiography and no effect on rejoining of DNA single strand breaks after gamma or UV irradiation. Oxyphenbutazon and prednisolone reduced the replicative DNA synthesis in vitro and in vivo but there was only little effect on DNA repair in the in vivo experiments. These two substances showed also a small reduction in poly(ADP-ribose) synthesis (PAR synthesis). 5-methoxypsoralen (5-MOP) and 8-methoxypsoralen (8-MOP) in combination with UV irradiation showed that 5-MOP was more toxic than mutagen, but induced much less DNA crosslinks than 8-MOP. Autoradiographic studies of radiation sensitization by biological agents showed significant inhibition of UDS in Yoshida tumor cells after acute mycoplasma infection in rats. Nucleoid sedimentation studies showed only in the case of Yoshida tumor cells after mycoplasma infection a dramatic effect in the sedimentation behaviour. Sensitization of cells by changing chromatin structure was also studied. Benzamide, 3-NH 2 -benzamide, 3-Methoxybenzamide, Spermine, Theophyllin and Caffeine were tested in different concentrations on replicative DNA synthesis, UDS after UV irradiation and PAR synthesis Chinese hamster ovary cells. 5-Methoxybenzamide was the strongest sensitizer and inhibitor of the PAR synthesis, and was used in further experiments. Results of KFA Juelich on sensitization of a mamma-adenocarcinoma EO 771 on C57 B1 mice are given. Replicative DNA synthesis, DNA repair and PAR synthesis were compared in spleen cells and adenocarcinoma cells after treatment with 5-Methoxybenzamide. An inhibitory effect on UDS could be shown only in adenocarcinoma cells but not in the mice spleen cells

  6. Needle-free and microneedle drug delivery in children: a case for disease-modifying antirheumatic drugs (DMARDs).

    Shah, Utpal U; Roberts, Matthew; Orlu Gul, Mine; Tuleu, Catherine; Beresford, Michael W

    2011-09-15

    Parenteral routes of drug administration have poor acceptability and tolerability in children. Advances in transdermal drug delivery provide a potential alternative for improving drug administration in this patient group. Issues with parenteral delivery in children are highlighted and thus illustrate the scope for the application of needle-free and microneedle technologies. This mini-review discusses the opportunities and challenges for providing disease-modifying antirheumatic drugs (DMARDs) currently prescribed to paediatric rheumatology patients using such technologies. The aim is to raise further awareness of the need for age-appropriate formulations and drug delivery systems and stimulate exploration of these options for DMARDs, and in particular, rapidly emerging biologics on the market. The ability of needle-free and microneedle technologies to deliver monoclonal antibodies and fusion proteins still remains largely untested. Such an understanding is crucial for future drug design opportunities. The bioavailability, safety and tolerance of delivering biologics into the viable epidermis also need to be studied. Copyright © 2011 Elsevier B.V. All rights reserved.

  7. A Modified ELISA Accurately Measures Secretion of High Molecular Weight Hyaluronan (HA) by Graves' Disease Orbital Cells

    Krieger, Christine C.

    2014-01-01

    Excess production of hyaluronan (hyaluronic acid [HA]) in the retro-orbital space is a major component of Graves' ophthalmopathy, and regulation of HA production by orbital cells is a major research area. In most previous studies, HA was measured by ELISAs that used HA-binding proteins for detection and rooster comb HA as standards. We show that the binding efficiency of HA-binding protein in the ELISA is a function of HA polymer size. Using gel electrophoresis, we show that HA secreted from orbital cells is primarily comprised of polymers more than 500 000. We modified a commercially available ELISA by using 1 million molecular weight HA as standard to accurately measure HA of this size. We demonstrated that IL-1β-stimulated HA secretion is at least 2-fold greater than previously reported, and activation of the TSH receptor by an activating antibody M22 from a patient with Graves' disease led to more than 3-fold increase in HA production in both fibroblasts/preadipocytes and adipocytes. These effects were not consistently detected with the commercial ELISA using rooster comb HA as standard and suggest that fibroblasts/preadipocytes may play a more prominent role in HA remodeling in Graves' ophthalmopathy than previously appreciated. PMID:24302624

  8. Long-term changes in ADAS-cog: what is clinically relevant for disease modifying trials in Alzheimer?

    Vellas, B; Andrieu, S; Cantet, C; Dartigues, J F; Gauthier, S

    2007-01-01

    With the development of long-term disease modifying trials, changes in ADAS-Cog at 18 months will rise certainly many questions. We decided to look in the Real.fr study at the links between changes in cognition, ADAS-Cog and function. A total of 346 Alzheimer's patients with ADAS-cog at entry and at 18 months. were eligible for this analysis. These patients were on average 77.44 years old and 254 (72.36%) were women. The great majority lived at home and about 93% were treated with a cholinesterase inhibitor at baseline. Thirty three patients (9%) had a gain of more than 2 points at the ADAS-cog at 18 months (Group I, improvement); 130 (38%) were considered as stable, the reference group (Group II ) characterized by a stability at the ADAS-cog: decline of 2 points to gain of 2 points, 112 subjects (32%) had a moderate decline between 2 and 7 at the ADAScog (Group III) and finally 71 subjects (21%) had a severe impairment more than seven points at the ADAS-cog. A loss of one Basic ADL is certainly highly relevant, and such a change was found at 18 months in more than half of the subjects, which is not surprising for a long-term evolution in mild to moderate AD. An impairment of more than 7 points at the ADAS-cog was found in 21% of the subjects at 18 months and was associated with loss.

  9. Antidepressant Drug Treatment in Association with Multiple Sclerosis Disease-Modifying Therapy: Using Explorys in the MS Population.

    Mirsky, Matthew M; Marrie, Ruth Ann; Rae-Grant, Alexander

    2016-01-01

    Background: The Explorys Enterprise Performance Management (EPM) database contains de-identified clinical data for 50 million patients. Multiple sclerosis (MS) disease-modifying therapies (DMTs), specifically interferon beta (IFNβ) treatments, may potentiate depression. Conflicting data have emerged, and a large-scale claims-based study by Patten et al. did not support such an association. This study compares the results of Patten et al. with those using the EPM database. Methods: "Power searches" were built to test the relationship between antidepressant drug use and DMT in the MS population. Searches were built to produce a cohort of individuals diagnosed as having MS in the past 3 years taking a specific DMT who were then given any antidepressant drug. The antidepressant drug therapy prevalence was tested in the MS population on the following DMTs: IFNβ-1a, IFNβ-1b, combined IFNβ, glatiramer acetate, natalizumab, fingolimod, and dimethyl fumarate. Results: In patients with MS, the rate of antidepressant drug use in those receiving DMTs was 40.60% to 44.57%. The rate of antidepressant drug use for combined IFNβ DMTs was 41.61% (males: 31.25%-39.62%; females: 43.10%-47.33%). Antidepressant drug use peaked in the group aged 45 to 54 years for five of six DMTs. Conclusions: We found no association between IFNβ treatment and antidepressant drug use in the MS population compared with other DMTs. The EPM database has been validated against the Patten et al. data for future use in the MS population.

  10. Anakinra as first-line disease-modifying therapy in systemic juvenile idiopathic arthritis: report of forty-six patients from an international multicenter series

    Nigrovic, Peter A.; Mannion, Melissa; Prince, Femke H. M.; Zeft, Andrew; Rabinovich, C. Egla; van Rossum, Marion A. J.; Cortis, Elisabetta; Pardeo, Manuela; Miettunen, Paivi M.; Janow, Ginger; Birmingham, James; Eggebeen, Aaron; Janssen, Erin; Shulman, Andrew I.; Son, Mary Beth; Hong, Sandy; Jones, Karla; Ilowite, Norman T.; Cron, Randy Q.; Higgins, Gloria C.

    2011-01-01

    To examine the safety and efficacy of the interleukin-1 (IL-1) receptor antagonist anakinra as first-line therapy for systemic juvenile idiopathic arthritis (JIA). Patients with systemic JIA receiving anakinra as part of initial disease-modifying antirheumatic drug (DMARD) therapy were identified

  11. Efficacy of biological disease-modifying antirheumatic drugs: a systematic literature review informing the 2013 update of the EULAR recommendations for the management of rheumatoid arthritis

    Nam, Jackie L.; Ramiro, Sofia; Gaujoux-Viala, Cecile; Takase, Kaoru; Leon-Garcia, Mario; Emery, Paul; Gossec, Laure; Landewe, Robert; Smolen, Josef S.; Buch, Maya H.

    2014-01-01

    To update the evidence for the efficacy of biological disease-modifying antirheumatic drugs (bDMARD) in patients with rheumatoid arthritis (RA) to inform the European League Against Rheumatism(EULAR) Task Force treatment recommendations. Medline, Embase and Cochrane databases were searched for

  12. Uso de EVA Modificado com Grupos Mercaptana na Compatibilização de Misturas NBR/EPDM The Use of Mercapto-Modified EVA as Compatibilizing Agent for NBR/EPDM Blends

    Marcia G. Oliveira

    2002-10-01

    Full Text Available Copolímeros de etileno - acetato de vinila com diferentes teores de acetato de vinila - foram funcionalizados com grupos mercaptana e utilizados como agentes compatibilizantes reativos em misturas envolvendo borracha nitrílica e copolímeros de etileno-propileno-dieno (EPDM. Foi investigada a influência das características estruturais dos copolímeros funcionalizados no processo de vulcanização, propriedades mecânicas e dinâmico-mecânicas bem como resistência ao envelhecimento. A adição de pequena porção desses copolímeros resultou em tempos de cura menores. Copolímeros funcionalizados, obtidos a partir da transesterificação de EVA com ácido mercaptoacético (EVASH, apresentaram desempenho melhor como compatibilizante do que aquele obtido a partir da esterificação de EVA hidrolisado com o mesmo ácido (EVALSH. As misturas compatibilizadas com o primeiro sistema apresentaram melhores propriedades mecânicas além de uma morfologia mais refinada e uniforme. A presença dos grupos mercaptana nesses agentes compatibilizantes resultou em uma melhora na resistência ao envelhecimento das misturas.Ethylene-vinyl acetate (EVA copolymers with different amounts of vinyl acetate have been functionalized with mercapto groups and these reactive compounds were used as compatibilizing agent for nitrile rubber (NBR/ ethylene-propylene-diene rubber (EPDM blends. The effects from the structural properties of mercapto-modified EVA compounds on the vulcanizing characteristics, mechanical properties, aging resistance and dynamic-mechanical properties were investigated. The addition of low amounts of mercapto-modified EVA resulted in a decrease of curing time. The functionalized copolymer obtained through transesterification reaction between mercaptoacetic acid and EVA (EVASH presented better compatibilizing action than that obtained from esterification of hydrolyzed EVA and mercaptoacetic acid (EVALSH. Blends compatibilized with the former

  13. Study of CaCl2 as an agent that modifies the surface of activated carbon used in sorption/treatment cycles for nitrate removal

    O. Zanella

    2014-03-01

    Full Text Available The efficiency of the application of a chemically-modified activated carbon surface was investigated. The purpose of this study was to examine the effect of treatment with CaCl2 solution at a concentration of 2000 mg.L-1 on the sorption of nitrate ions from aqueous solutions in successive sorption/t reatment cycles. The sorbent was initially subjected to chemical treatment with CaCl2 and subsequently to the sorption process. Nine sorption cycles were performed. The concentrations of nitrate ions in the solution were measured by UV-Vis spectrophotometry before and after sorption. The results show that treatment with CaCl2 caused a significant increase in the percentage removal for each treatment step, reaching a removal rate of 80% of nitrate in the solution after nine cycles.

  14. Diabetes and kidney disease: the role of sodium-glucose cotransporter-2 (SGLT-2) and SGLT-2 inhibitors in modifying disease outcomes.

    Mende, Christian W

    2017-03-01

    Patients with type 2 diabetes (T2D) often have coexisting chronic kidney disease (CKD). However, healthy renal function is crucial in maintaining glucose homeostasis, assuring that almost all of the filtered glucose is reabsorbed by the sodium glucose cotransporters (SGLTs) SGLT-1 and SGLT-2. In diabetes, an increased amount of glucose is filtered by the kidneys and SGLT-2 is upregulated, leading to increased glucose absorption and worsening hyperglycemia. Prolonged hyperglycemia contributes to the development of CKD by inducing metabolic and hemodynamic changes in the kidneys. Due to the importance of SGLT-2 in regulating glucose levels, investigation into SGLT-2 inhibitors was initiated as a glucose-dependent mechanism to control hyperglycemia, and there are three agents currently approved for use in the United States: dapagliflozin, canagliflozin, and empagliflozin. SGLT-2 inhibitors have been shown to reduce glycated hemoglobin (A1C), weight, and blood pressure, which not only affects glycemic control, but may also help slow the progression of renal disease by impacting the underlying mechanisms of kidney injury. In addition, SGLT-2 inhibitors have shown reductions in albuminuria, uric acid, and an increase in magnesium. Caution is advised when prescribing SGLT-2 inhibitors to patients with moderately impaired renal function and those at risk for volume depletion and hypotension. Published data on slowing of the development, as well as progression of CKD, is a hopeful indicator for the possible renal protection potential of this drug class. This narrative review provides an in-depth discussion of the interplay between diabetes, SGLT-2 inhibitors, and factors that affect kidney function.

  15. Synthesis and antimicrobial evaluation of two peptide LyeTx I derivatives modified with the chelating agent HYNIC for radiolabeling with technetium-{sup 99m}

    Fuscaldi, Leonardo Lima; Santos, Daniel Moreira dos; Pinheiro, Natalia Gabriela Silva; Araujo, Raquel Silva; Barros, Andre Luis Branco de; Resende, Jarbas Magalhaes; Fernandes, Simone Odilia Antunes; Lima, Maria Elena de; Cardoso, Valbert Nascimento, E-mail: valbertncardoso@gmail.com [Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, MG (Brazil). Departamento de Analises Clinicas Toxicologica

    2016-11-01

    Background: Current diagnostic methods and imaging techniques are not able to differentiate septic and aseptic inflammation. Thus, reliable methods are sought to provide this distinction and scintigraphic imaging is an interesting option, since it is based on physiological changes. In this context, radiolabeled antimicrobial peptides have been investigated as they accumulate in infectious sites instead of aseptic inflammation. The peptide LyeTx I, from the venom of Lycosa erythrognatha, has potent antimicrobial activity. Therefore, this study aimed to synthesize LyeTx I derivatives with the chelating compound HYNIC, to evaluate their antimicrobial activity and to radiolabel them with {sup 99m}Tc. Methods: Two LyeTx I derivatives, HYNIC-LyeTx I (N-terminal modification) and LyeTx I-K-HYNIC (C-terminal modification), were synthesized by Fmoc strategy and purified by RP-HPLC. The purified products were assessed by RP-HPLC and MALDI-ToF-MS analysis. Microbiological assays were performed against S. aureus (ATCC® 6538) and E. coli (ATCC® 10536) in liquid medium to calculate the MIC. The radiolabeling procedure of LyeTx I-K-HYNIC with {sub 99m}Tc was performed in the presence of co-ligands (tricine and EDDA) and reducing agent (SnCl{sub 2} . 2H{sub 2}O), and standardized taking into account the amount of peptide, reducing agent, pH and heating. Radiochemical purity analysis was performed by thin-layer chromatography on silica gel strips and the radiolabeled compound was assessed by RP-HPLC and radioactivity measurement of the collected fractions. Data were analyzed by ANOVA, followed by Tukey test (p-values < 0.05). Results: Both LyeTx I derivatives were suitably synthesized and purified, as shown by RP-HPLC and MALDI-ToF-MS analysis. The microbiological test showed that HYNIC-LyeTx I (N-terminal modification) did not inhibit bacterial growth, whereas LyeTx I-K-HYNIC (C-terminal modification) showed a MIC of 5.05 μmol. L−1 (S. aureus) and 10.10 μmol. L−1 (E. coli

  16. Barriers and facilitators to disease-modifying antirheumatic drug use in patients with inflammatory rheumatic diseases: a qualitative theory-based study.

    Voshaar, Marieke; Vriezekolk, Johanna; van Dulmen, Sandra; van den Bemt, Bart; van de Laar, Mart

    2016-10-21

    Although disease-modifying anti-rheumatic drugs (DMARDs) are the cornerstone of treatment for inflammatory rheumatic diseases, medication adherence to DMARDs is often suboptimal. Effective interventions to improve adherence to DMARDs are lacking, and new targets are needed to improve adherence. The aim of the present study was to explore patients' barriers and facilitators of optimal DMARD use. These factors might be used as targets for adherence interventions. In a mixed method study design, patients (n = 120) with inflammatory arthritis (IA) completed a questionnaire based on an existing adapted Theoretical Domains Framework (TDF) to identify facilitators and barriers of DMARD use. A subgroup of these patients (n = 21) participated in focus groups to provide insights into their facilitators and barriers. The answers to the questionnaires and responses of the focus groups were thematically coded by three researchers independently and subsequently categorized. The barriers and facilitators that were reported by IA patients presented large inter-individual variations. The identified barriers and facilitators could be captured in the following domains based on an adapted TDF: (i) knowledge, (ii) emotions, (iii) attention, memory, and decision processes, (iv) social influences, (v) beliefs about capability, (vi) beliefs about consequences, (vii) motivation and goals, (viii) goal conflict, (ix) environmental context and resources, and (x) skills. Patients with IA have a variety of barriers and facilitators with regard to their DMARD use. All of these barriers and facilitators could be categorized into adapted domains of the TDF. Interventions that address individual facilitators and barriers, based on capability, opportunity, and motivation, are needed to develop strategies for medication adherence that are tailored to individual patient needs.

  17. Enhancement of wound closure by modifying dual release patterns of stromal-derived cell factor-1 and a macrophage recruitment agent from gelatin hydrogels.

    Kim, Yang-Hee; Tabata, Yasuhiko

    2017-11-01

    The objective of the present study is to evaluate the effects of the release patterns of stromal derived factor (SDF)-1 and sphingosine-1 phosphate agonist (SEW2871), used as MSC and macrophage recruitment agents, on the wound closure of diabetic mouse skin defects. To achieve different release patterns, hydrogels were prepared using two types of gelatin with isoelectric points (IEP) of 5 and 9, into which SDF-1 and SEW2871 were then incorporated in various combinations. When the hydrogels incorporating SDF-1 and SEW2871 were applied into wound defects of diabetic mice, the number of MSCs and macrophages recruited to the defects and the levels of pro- and anti- inflammatory cytokines were found to be dependent on the release profiles of SDF-1 and SEW2871. Of particular interest was the case of a rapid release of SDF-1 combined with a controlled release of SEW2871. This resulted in a higher number of M2 macrophages and gene expression levels of anti-inflammatory cytokines 3 days after implantation and faster wound closure than when pairing the controlled release of SDF-1 with a rapid release of SEW2871. Therefore, the present study demonstrates that different release patterns of SDF-1 and SEW2871 can enhance the in vivo recruitment of MSCs and macrophages, and can promote skin wound closure through the modulation of inflammation. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

  18. Mechanical properties of chemically modified Sansevieria trifasciata/natural rubber/high density polyethylene (STF/NR/HDPE) composites: Effect of silane coupling agent

    Zakaria, Nurzam Ezdiani; Baharum, Azizah; Ahmad, Ishak

    2018-04-01

    The main objective of this research is to study the effects of chemical modification on the mechanical properties of treated Sansevieria trifasciata fiber/natural rubber/high density polyethylene (TSTF/NR/HDPE) composites. Processing of STF/NR/HDPE composites was done by using an internal mixer. The processing parameters used were 135°C for temperature and a mixing rotor speed of 55 rpm for 15 minutes. Filler loading was varied from 10% to 40% of STF and the fiber size used was 125 µm. The composite blends obtained then were pressed with a hot press machine to get test samples of 1 mm and 3 mm of thickness. Samples were evaluated via tensile tests, Izod impact test and scanning electron microscopy (SEM). Results showed that tensile strength and strain value decreased while tensile modulus increased when filler loading increased. Impact strength increased when filler loading increased and began to decrease after 10% of filler amount for treated composites. For untreated composites, impact strength began to decrease after 20% of filler loading. Chemical modification by using silane coupling agent has improved certain mechanical properties of the composites such as tensile strength, strain value and tensile modulus. Adding more amount of filler will also increase the viscosity and the stiffness of the materials.

  19. Validation of modified World Health Organization classification for pregnant women with heart disease in a tertiary care center in southern Thailand

    Suwanrath C

    2018-01-01

    Full Text Available Chitkasaem Suwanrath,1 Putthaporn Thongphanang,1 Sutham Pinjaroen,1 Saranyou Suwanugsorn2 1Department of Obstetrics and Gynecology, 2Department of Internal Medicine, Faculty of Medicine, Prince of Songkla University, Hat Yai, Songkhla, Thailand Purpose: To validate the modified World Health Organization (WHO classification in pregnant women with congenital and acquired heart diseases. Patients and methods: The database of pregnant women with heart disease, who delivered at Songklanagarind Hospital between January 1995 and December 2016, was retrieved from the Statistical Unit, Department of Obstetrics and Gynecology, along with the Hospital Information System of Songklanagarind Hospital, Faculty of Medicine, Prince of Songkla University. Each patient was retrospectively classified according to the modified WHO classification of maternal cardiovascular risk. Comparison of maternal and fetal outcomes among the modified WHO classes were analyzed using the chi-square test or Fisher’s exact test and one-way ANOVA test. A p-value of <0.05 was considered statistically significant. Results: A total of 331 cases were studied: 157 cases with congenital heart disease and 174 cases with acquired heart disease. There were 48, 173, 32 and 78 cases in the modified WHO class I, II, III and IV, respectively. Congestive heart failure was the most common complication. The overall maternal mortality rate was 3.6%, all of which were in the modified WHO class IV. Maternal cardiovascular events occurred in 24.2% of cases, increasing rates with higher modified WHO class: 4.2%, 15.0%, 25.0% and 56.4% in class I, II, III and IV, respectively (p<0.001. Adverse fetal outcomes including preterm delivery, low birth weight, small for gestational age and neonatal intensive care unit admission were also significantly increased in class III and IV (p<0.05. Conclusion: The modified WHO classification is useful not only for obtaining a cardiovascular risk assessment in pregnant

  20. Metastatic Extramammary Paget’s Disease of Scrotum Responds Completely to Single Agent Trastuzumab in a Hemodialysis Patient: Case Report, Molecular Profiling and Brief Review of the Literature

    Peter Barth

    2015-01-01

    metastatic the prognosis of EMPD is poor and treatment options are limited. We report a case of a complete response to single agent trastuzumab in a hemodialysis patient with metastatic Her2/neu overexpressed EMPD of the scrotum. Molecular profiling of his case as well as 12 other EMPD and 8 mammary Paget disease (MPD cases was completed and revealed multiple biomarker aberrations. Overexpression of Her2 was frequently noted (30%–40% in both EMPD and MPD patients and when present can be effectively treated with Her2 targeted agents. Trastuzumab therapy can be safely utilized in a hemodialysis patient. In addition, multiple protein overexpression and loss were seen in EMPD including PD-1, PD-L1, PTEN, and AR as well as PIK3CA mutation. These findings may lead to possible therapeutic interventions targeting these pathways in a disease with few effective treatment options.

  1. Modifying an Active Compound’s Release Kinetic Using a Supercritical Impregnation Process to Incorporate an Active Agent into PLA Electrospun Mats

    Carol López de Dicastillo

    2018-04-01

    Full Text Available The main objective of this work was to study the release of cinnamaldehyde (CIN from electrospun poly lactic acid (e-PLA mats obtained through two techniques: (i direct incorporation of active compound during the electrospinning process (e-PLA-CIN; and (ii supercritical carbon dioxide (scCO2 impregnation of CIN within electrospun PLA mats (e-PLA/CINimp. The development and characterization of both of these active electrospun mats were investigated with the main purpose of modifying the release kinetic of this active compound. Morphological, structural, and thermal properties of these materials were also studied, and control mats e-PLA and e- PLA CO 2 were developed in order to understand the effect of electrospinning and scCO2 impregnation, respectively, on PLA properties. Both strategies of incorporation of this active compound into PLA matrix resulted in different morphologies that influenced chemical and physical properties of these composites and in different release kinetics of CIN. The electrospinning and scCO2 impregnation processes and the presence of CIN altered PLA thermal and structural properties when compared to an extruded PLA material. The incorporation of CIN through scCO2 impregnation resulted in higher release rate and lower diffusion coefficients when compared to active electrospun mats with CIN incorporated during the electrospinning process.

  2. Correlation between the Modified Systemic Lupus Erythematosus Disease Activity Index 2000 and the European Consensus Lupus Activity Measurement in juvenile systemic lupus erythematosus.

    Sato, J O; Corrente, J E; Saad-Magalhães, C

    2016-11-01

    Objective The objective of this study was to assess Modified Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) and European Consensus Lupus Activity Measurement (ECLAM) disease activity correlation in addition to their respective correlation to Pediatric Systemic Lupus International Collaborative Clinics/American College of Rheumatology (SLICC/ACR) Damage Index (Ped-SDI), in juvenile systemic lupus erythematosus (JSLE). Methods The activity indices were scored retrospectively and summarized by adjusted means during follow-up. The Ped-SDI was scored during the last visit for those with more than six months follow-up. Pearson correlation between the Modified SLEDAI-2K and ECLAM, as well as Spearman correlations between the Modified SLEDAI-2K, ECLAM, and Ped-SDI were calculated. The receiver operating characteristic (ROC) curve was calculated for both activity indices discriminating damage measured by Ped-SDI. Results Thirty-seven patients with mean age at diagnosis 11 ± 2.9 years and mean follow-up time 3.2 ± 2.4 years were studied. The Modified SLEDAI-2K and ECLAM adjusted means were highly correlated ( r = 0.78, p  0.7, p < 0.001), but Modified SLEDAI-2K and ECLAM correlation with Ped-SDI was only moderate. ROC analysis discriminant performance for both activity indices resulted in area under curve (AUC) of 0.74 and 0.73 for Modified SLEDAI-2K and ECLAM, respectively. Conclusion The high correlation found between the Modified SLEDAI-2K and ECLAM adjusted means indicated that both tools can be equally useful for longitudinal estimates of JSLE activity.

  3. Comparison of independent screens on differentially vulnerable motor neurons reveals alpha-synuclein as a common modifier in motor neuron diseases.

    Kline, Rachel A; Kaifer, Kevin A; Osman, Erkan Y; Carella, Francesco; Tiberi, Ariana; Ross, Jolill; Pennetta, Giuseppa; Lorson, Christian L; Murray, Lyndsay M

    2017-03-01

    The term "motor neuron disease" encompasses a spectrum of disorders in which motor neurons are the primary pathological target. However, in both patients and animal models of these diseases, not all motor neurons are equally vulnerable, in that while some motor neurons are lost very early in disease, others remain comparatively intact, even at late stages. This creates a valuable system to investigate the factors that regulate motor neuron vulnerability. In this study, we aim to use this experimental paradigm to identify potential transcriptional modifiers. We have compared the transcriptome of motor neurons from healthy wild-type mice, which are differentially vulnerable in the childhood motor neuron disease Spinal Muscular Atrophy (SMA), and have identified 910 transcriptional changes. We have compared this data set with published microarray data sets on other differentially vulnerable motor neurons. These neurons were differentially vulnerable in the adult onset motor neuron disease Amyotrophic Lateral Sclerosis (ALS), but the screen was performed on the equivalent population of neurons from neurologically normal human, rat and mouse. This cross species comparison has generated a refined list of differentially expressed genes, including CELF5, Col5a2, PGEMN1, SNCA, Stmn1 and HOXa5, alongside a further enrichment for synaptic and axonal transcripts. As an in vivo validation, we demonstrate that the manipulation of a significant number of these transcripts can modify the neurodegenerative phenotype observed in a Drosophila line carrying an ALS causing mutation. Finally, we demonstrate that vector-mediated expression of alpha-synuclein (SNCA), a transcript decreased in selectively vulnerable motor neurons in all four screens, can extend life span, increase weight and decrease neuromuscular junction pathology in a mouse model of SMA. In summary, we have combined multiple data sets to identify transcripts, which are strong candidates for being phenotypic modifiers

  4. Trends in Modifiable Risk Factors Are Associated With Declining Incidence of Hospitalized and Nonhospitalized Acute Coronary Heart Disease in a Population.

    Mannsverk, Jan; Wilsgaard, Tom; Mathiesen, Ellisiv B; Løchen, Maja-Lisa; Rasmussen, Knut; Thelle, Dag S; Njølstad, Inger; Hopstock, Laila Arnesdatter; Bønaa, Kaare Harald

    2016-01-05

    Few studies have used individual person data to study whether contemporary trends in the incidence of coronary heart disease are associated with changes in modifiable coronary risk factors. We identified 29 582 healthy men and women ≥25 years of age who participated in 3 population surveys conducted between 1994 and 2008 in Tromsø, Norway. Age- and sex-adjusted incidence rates were calculated for coronary heart disease overall, out-of-hospital sudden death, and hospitalized ST-segment-elevation and non-ST-segment-elevation myocardial infarction. We measured coronary risk factors at each survey and estimated the relationship between changes in risk factors and changes in incidence trends. A total of 1845 participants had an incident acute coronary heart disease event during 375 064 person-years of follow-up from 1994 to 2010. The age- and sex-adjusted incidence of total coronary heart disease decreased by 3% (95% confidence interval, 2.0-4.0; Pcoronary risk factors accounted for 66% (95% confidence interval, 48-97; Pcoronary heart disease. Favorable changes in cholesterol contributed 32% to the decline, whereas blood pressure, smoking, and physical activity each contributed 14%, 13%, and 9%, respectively. We observed a substantial decline in the incidence of coronary heart disease that was driven by reductions in out-of-hospital sudden death and hospitalized ST-segment-elevation myocardial infarction. Changes in modifiable coronary risk factors accounted for 66% of the decline in coronary heart disease events. © 2015 American Heart Association, Inc.

  5. Antimicrobial activities of the essential oils of various plants against tomato late blight disease agent Phytophthora infestans.

    Soylu, E Mine; Soylu, Soner; Kurt, Sener

    2006-02-01

    The aim of this study was to find an alternative to synthetic fungicides currently used in the control of devastating oomycete pathogen Phytophthora infestans, causal agent of late blight disease of tomato. Antifungal activities of essential oils obtained from aerial parts of aromatic plants such as oregano (Origanum syriacum var. bevanii), thyme (Thymbra spicata subsp. spicata), lavender (Lavandula stoechas subsp. stoechas), rosemary (Rosmarinus officinalis), fennel (Foeniculum vulgare), and laurel (Laurus nobilis), were investigated against P. infestans. Both contact and volatile phase effects of different concentrations of the essential oils used were determined by using two in vitro methods. Chemical compositions of the essential oils were also determined by GC-MS analysis. Major compounds found in essential oils of thyme, oregano, rosemary, lavender, fennel and laurel were carvacrol (37.9%), carvacrol (79.8), borneol (20.4%), camphor (20.2%), anethole (82.8%) and 1,8-cineole (35.5%), respectively. All essential oils were found to inhibit the growth of P. infestans in a dose-dependent manner. Volatile phase effect of oregano and thyme oils at 0.3 microg/ml air was found to completely inhibit the growth of P. infestans. Complete growth inhibition of pathogen by essential oil of fennel, rosemary, lavender and laurel was, however, observed at 0.4-2.0 microg/ml air concentrations. For the determination of the contact phase effects of the tested essential oils, oregano, thyme and fennel oils at 6.4 microg/ml were found to inhibit the growth of P. infestans completely. Essential oils of rosemary, lavender and laurel were inhibitory at relatively higher concentrations (12.8, 25.6, 51.2 microg/ml respectively). Volatile phase effects of essential oils were consistently found to be more effective on fungal growth than contact phase effect. Sporangial production was also inhibited by the essential oil tested. Light and scanning electron microscopic (SEM) observation on

  6. [Acupuncture Therapy versus Disease-modifying Antirheumatic Drugs for the Treatment of Ankylosing Spondylitis--a Meta-analysis].

    Lv, Zheng-tao; Zhou, Xiang; Chen, An-min

    2015-01-01

    We conducted a meta-analysis evaluating the efficacy and safety of acupuncture compared to disease-modifying antirheumatic drugs in patients with ankylosing spondylitis. Four databases including Pubmed, EMBASE, Cochrane library, and ISI Web of Science were searched in December 2014, taking also the reference section into account. Randomized controlled trials that aimed to assess the efficacy of acupuncture therapy were identified. The inclusion criteria for the outcome measurements were the clinical effect, ESR, occipital wall test, chest expansion, CRP and finger ground distance. Finally, six studies met these inclusion criteria. Two reviewers screened each article independently and were blinded to the findings of each other. We analyzed data from 6 RCTs involving 541 participants. Acupuncture therapy could further improve the clinical effect (OR = 3.01; 95% CI, 1.48-6.13; P = 0.002) and reduce ESR level (SMD = -0.77; 95% CI, -1.46 to -0.08; P = 0.03) compared to DMARDs; a combination of acupuncture and DMARDs could further improve clinical effect (OR = 3.20, 95% CI, 1.36-7.54; P = 0.008), occipital-wall distance (SMD = -0.84; 95% CI, -1.37 to -0.31; P = 0.002), chest expansion (SMD = 0.38; 95% CI, 0.16-0.60; P = 0.0009), and finger-ground distance (SMD = -0.48; 95% CI, -0.87 to -0.09; P = 0.02) as compared to DMARDs treatment alone. Our findings support that acupuncture therapy could be an option to relieve symptoms associated with AS. These results should be interpreted cautiously due to the generally poor methodological qualities of the included trials. © 2015 S. Karger GmbH, Freiburg.

  7. Does influence at work modify the relation between high occupational physical activity and risk of heart disease in women?

    Allesøe, Karen; Holtermann, Andreas; Rugulies, Reiner; Aadahl, Mette; Boyle, Eleanor; Søgaard, Karen

    2017-07-01

    To investigate whether influence at work modifies the association between demanding and strenuous occupational physical activity (OPA) and risk of ischaemic heart disease (IHD). A sample of 12,093 nurses aged 45-64 years from the Danish Nurse Cohort Study was followed for 20.6 years by individual linkage to incident IHD in the Danish National Patient Registry. Information on OPA, influence at work, other occupational factors and known risk factors for IHD was collected by self-report in 1993. During follow-up 869 nurses were hospitalised with incident IHD. Nurses exposed to strenuous OPA and low influence at work had a 46% increased risk of IHD [hazard ratio (HR) 1.46 (95% confidence interval (CI) 1.02-2.09)] compared to the reference group of nurses with moderate OPA and high influence at work. Nurses exposed to strenuous OPA and high influence at work were not at an increased risk of IHD [HR 1.10 (95% CI 0.59-2.06)]. An additive hazards model showed there were 18.0 (95% CI -0.01 to 36.0) additional cases of IHD per 10,000 person years among nurses with strenuous OPA and low influence at work compared to nurses with moderate OPA and high influence at work. A detrimental additive interaction between strenuous OPA and low influence at work that could explain the additional cases of IHD among nurses with strenuous OPA and low influence at work was indicated. The findings suggest that high influence at work may buffer some of the adverse effects of strenuous OPA on risk of IHD.

  8. Ethnicity Modifies Associations between Cardiovascular Risk Factors and Disease Severity in Parallel Dutch and Singapore Coronary Cohorts.

    Crystel M Gijsberts

    Full Text Available In 2020 the largest number of patients with coronary artery disease (CAD will be found in Asia. Published epidemiological and clinical reports are overwhelmingly derived from western (White cohorts and data from Asia are scant. We compared CAD severity and all-cause mortality among 4 of the world's most populous ethnicities: Whites, Chinese, Indians and Malays.The UNIted CORoNary cohort (UNICORN simultaneously enrolled parallel populations of consecutive patients undergoing coronary angiography or intervention for suspected CAD in the Netherlands and Singapore. Using multivariable ordinal regression, we investigated the independent association of ethnicity with CAD severity and interactions between risk factors and ethnicity on CAD severity. Also, we compared all-cause mortality among the ethnic groups using multivariable Cox regression analysis.We included 1,759 White, 685 Chinese, 201 Indian and 224 Malay patients undergoing coronary angiography. We found distinct inter-ethnic differences in cardiovascular risk factors. Furthermore, the associations of gender and diabetes with severity of CAD were significantly stronger in Chinese than Whites. Chinese (OR 1.3 [1.1-1.7], p = 0.008 and Malay (OR 1.9 [1.4-2.6], p<0.001 ethnicity were independently associated with more severe CAD as compared to White ethnicity. Strikingly, when stratified for diabetes status, we found a significant association of all three Asian ethnic groups as compared to White ethnicity with more severe CAD among diabetics, but not in non-diabetics. Crude all-cause mortality did not differ, but when adjusted for covariates mortality was higher in Malays than the other ethnic groups.In this population of individuals undergoing coronary angiography, ethnicity is independently associated with the severity of CAD and modifies the strength of association between certain risk factors and CAD severity. Furthermore, mortality differs among ethnic groups. Our data provide insight in

  9. Efficacy and safety of tofacitinib following inadequate response to conventional synthetic or biological disease-modifying antirheumatic drugs.

    Charles-Schoeman, Christina; Burmester, Gerd; Nash, Peter; Zerbini, Cristiano A F; Soma, Koshika; Kwok, Kenneth; Hendrikx, Thijs; Bananis, Eustratios; Fleischmann, Roy

    2016-07-01

    Biological disease-modifying antirheumatic drugs (bDMARDs) have shown diminished clinical response following an inadequate response (IR) to ≥1 previous bDMARD. Here, tofacitinib was compared with placebo in patients with an IR to conventional synthetic DMARDs (csDMARDs; bDMARD-naive) and in patients with an IR to bDMARDs (bDMARD-IR). Data were taken from phase II and phase III studies of tofacitinib in patients with rheumatoid arthritis (RA). Patients received tofacitinib 5 or 10 mg twice daily, or placebo, as monotherapy or with background methotrexate or other csDMARDs. Efficacy endpoints and incidence rates of adverse events (AEs) of special interest were assessed. 2812 bDMARD-naive and 705 bDMARD-IR patients were analysed. Baseline demographics and disease characteristics were generally similar between treatment groups within subpopulations. Across subpopulations, improvements in efficacy parameters at month 3 were generally significantly greater for both tofacitinib doses versus placebo. Clinical response was numerically greater with bDMARD-naive versus bDMARD-IR patients (overlapping 95% CIs). Rates of safety events of special interest were generally similar between tofacitinib doses and subpopulations; however, patients receiving glucocorticoids had more serious AEs, discontinuations due to AEs, serious infection events and herpes zoster. Numerically greater clinical responses and incidence rates of AEs of special interest were generally reported for tofacitinib 10 mg twice daily versus tofacitinib 5 mg twice daily (overlapping 95% CIs). Tofacitinib demonstrated efficacy in both bDMARD-naive and bDMARD-IR patients with RA. Clinical response to tofacitinib was generally numerically greater in bDMARD-naive than bDMARD-IR patients. The safety profile appeared similar between subpopulations. (NCT00413660, NCT00550446, NCT00603512, NCT00687193, NCT00960440, NCT00847613, NCT00814307, NCT00856544, NCT00853385). Published by the BMJ Publishing Group Limited

  10. The Effect of Disease-Modifying Drugs on Brain Atrophy in Relapsing-Remitting Multiple Sclerosis: A Meta-Analysis.

    Pierre Branger

    Full Text Available The quantification of brain atrophy in relapsing-remitting multiple sclerosis (RRMS may serve as a marker of disease progression and treatment response. We compared the association between first-line (FL or second-line (SL disease-modifying drugs (DMDs and brain volume changes over time in RRMS.We reviewed clinical trials in RRMS between January 1, 1995 and June 1, 2014 that assessed the effect of DMDs and reported data on brain atrophy in Medline, Embase, the Cochrane database and meeting abstracts. First, we designed a meta-analysis to directly compare the percentage brain volume change (PBVC between FLDMDs and SLDMDs at 24 months. Second, we conducted an observational and longitudinal linear regression analysis of a 48-month follow-up period. Sensitivity analyses considering PBVC between 12 and 48 months were also performed.Among the 272 studies identified, 117 were analyzed and 35 (18,140 patients were included in the analysis. Based on the meta-analysis, atrophy was greater for the use of an FLDMD than that of an SLDMD at 24 months (primary endpoint mean difference, -0.86; 95% confidence interval: -1.57--0.15; P = 0.02. Based on the linear regression analysis, the annual PBVC significantly differed between SLDMDs and placebo (-0.27%/y and -0.50%/y, respectively, P = 0.046 but not between FLDMDs (-0.33%/y and placebo (P = 0.11 or between FLDMDs and SLDMDs (P = 0.49. Based on sensitivity analysis, the annual PBVC was reduced for SLDMDs compared with placebo (-0.14%/y and -0.56%/y, respectively, P<0.001 and FLDMDs (-0.46%/y, P<0.005, but no difference was detected between FLDMDs and placebo (P = 0.12.SLDMDs were associated with reduced PBVC slope over time in RRMS, regardless of the period considered. These results provide new insights into the mechanisms underlying atrophy progression in RRMS.

  11. Real-World Adherence and Persistence to Oral Disease-Modifying Therapies in Multiple Sclerosis Patients Over 1 Year.

    Johnson, Kristen M; Zhou, Huanxue; Lin, Feng; Ko, John J; Herrera, Vivian

    2017-08-01

    Disease-modifying therapies (DMTs) are indicated to reduce relapse rates and slow disease progression for relapsing-remitting multiple sclerosis (MS) patients when taken as prescribed. Nonadherence or non-persistence in the real-world setting can lead to greater risk for negative clinical outcomes. Although previous research has demonstrated greater adherence and persistence to oral DMTs compared with injectable DMTs, comparisons among oral DMTs are lacking. To compare adherence, persistence, and time to discontinuation among MS patients newly prescribed the oral DMTs fingolimod, dimethyl fumarate, or teriflunomide. This retrospective study used MarketScan Commercial and Medicare Supplemental claims databases. MS patients with ≥ 1 claim for specified DMTs from April 1, 2013, to June 30, 2013, were identified. The index drug was defined as the first oral DMT within this period. To capture patients newly initiating index DMTs, patients could not have a claim for their index drugs in the previous 12 months. Baseline characteristics were described for patients in each treatment cohort. Adherence, as measured by medication possession ratio (MPR) and proportion of days covered (PDC); persistence (30-day gap allowed); and time to discontinuation over a 12-month follow-up period were compared across treatment cohorts. Adjusted logistic regression models were used to examine adherence, and Cox regression models estimated risk of discontinuation. 1,498 patients newly initiated oral DMTs and met study inclusion criteria: fingolimod (n = 185), dimethyl fumarate (n = 1,160), and teriflunomide (n = 143). Patients were similar across most baseline characteristics, including region, relapse history, and health care resource utilization. Statistically significant differences were observed across the treatment cohorts for age, gender, previous injectable/infused DMT use, and comorbidities. Adherence and time to discontinuation were adjusted for age, gender, region, previous oral

  12. RNA interference of endochitinases in the sugarcane endophyte Trichoderma virens 223 reduces its fitness as a biocontrol agent of pineapple disease.

    Aline S Romão-Dumaresq

    Full Text Available The sugarcane root endophyte Trichoderma virens 223 holds enormous potential as a sustainable alternative to chemical pesticides in the control of sugarcane diseases. Its efficacy as a biocontrol agent is thought to be associated with its production of chitinase enzymes, including N-acetyl-ß-D-glucosaminidases, chitobiosidases and endochitinases. We used targeted gene deletion and RNA-dependent gene silencing strategies to disrupt N-acetyl-ß-D-glucosaminidase and endochitinase activities of the fungus, and to determine their roles in the biocontrol of soil-borne plant pathogens. The loss of N-acetyl-ß-D-glucosaminidase activities was dispensable for biocontrol of the plurivorous damping-off pathogens Rhizoctonia solani and Sclerotinia sclerotiorum, and of the sugarcane pathogen Ceratocystis paradoxa, the causal agent of pineapple disease. Similarly, suppression of endochitinase activities had no effect on R. solani and S. sclerotiorum disease control, but had a pronounced effect on the ability of T. virens 223 to control pineapple disease. Our work demonstrates a critical requirement for T. virens 223 endochitinase activity in the biocontrol of C. paradoxa sugarcane disease, but not for general antagonism of other soil pathogens. This may reflect its lifestyle as a sugarcane root endophyte.

  13. Modified structural and magnetic properties of nanocrystalline MnFe{sub 2}O{sub 4} by pH in capping agent free co-precipitation method

    Iranmanesh, P., E-mail: p.iranmanesh@vru.ac.ir [Department of Physics, Vali-e-Asr University of Rafsanjan, 77139-36417 Rafsanjan (Iran, Islamic Republic of); Saeednia, S. [Department of Chemistry, Vali-e-Asr University of Rafsanjan, 77139-36417 Rafsanjan (Iran, Islamic Republic of); Mehran, M.; Dafeh, S. Rashidi [Department of Physics, Vali-e-Asr University of Rafsanjan, 77139-36417 Rafsanjan (Iran, Islamic Republic of)

    2017-03-01

    Nano-sized manganese ferrite (MnFe{sub 2}O{sub 4}) particles were prepared using co-precipitation method in two different pH (9 and 11). The structural, morphological, optical and magnetic properties of as-synthesized nanoparticles were characterized by Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), transmission electron microscopy (TEM), UV–vis absorption and vibrating sample magnetometer (VSM). The FTIR spectra revealed two strong peaks at about 600 and 400 cm{sup −1} that can be attributed to the vibration mode of octahedral and tetrahedral sites of spinel structure of MnFe{sub 2}O{sub 4}, respectively. The XRD results showed that the nanocrystalline MnFe{sub 2}O{sub 4} has pure cubic spinel crystal structure with average crystallite size of 11 nm. The cation distribution of these nanoparticles was estimated by X-ray analysis data. The blue shift was observed in the band gap when compared with bulk sample which is due to the quantum size effect. The absence of hysteresis for MnFe{sub 2}O{sub 4} nanoparticles indicated the superparamagnetic behaviour, as expected for single domain nanoparticles. The obtained value for saturation magnetization being less than its value of bulk ones and larger pH is due to surface effects. The calculated magnetic particle size was smaller than crystallite size estimated from the XRD results; which indicate the presence of dead layer on particle surface. - Highlights: • We study effect of pH on the size and magnetic properties of MnFe{sub 2}O{sub 4} nanoparticles. • MnFe{sub 2}O{sub 4} were synthesized by co-precipitation method without any capping agent. • The physical properties are affected by cation contribution and surface effects. • The smaller nanoparticles with larger pH show a red shift in the band gap energy. • The M{sub s} is less than its value of bulk ones due to surface effects.

  14. Evaluation of glycodendron and synthetically-modified dextran clearing agents for multi-step targeting of radioisotopes for molecular imaging and radioimmunotherapy

    Cheal, Sarah M.; Yoo, Barney; Boughdad, Sarah; Punzalan, Blesida; Yang, Guangbin; Dilhas, Anna; Torchon, Geralda; Pu, Jun; Axworthy, Don B.; Zanzonico, Pat; Ouerfelli, Ouathek; Larson, Steven M.

    2014-01-01

    A series of N-acetylgalactosamine-dendrons (NAG-dendrons) and dextrans bearing biotin moieties were compared for their ability to complex with and sequester circulating bispecific anti-tumor antibody (scFv4) streptavidin (SA) fusion protein (scFv4-SA) in vivo, to improve tumor to normal tissue concentration ratios for targeted radioimmunotherapy and diagnosis. Specifically, a total of five NAG-dendrons employing a common synthetic scaffold structure containing 4, 8, 16, or 32 carbohydrate residues and a single biotin moiety were prepared (NAGB), and for comparative purposes, a biotinylated-dextran with average molecular weight (MW) of 500 kD was synthesized from amino-dextran (DEXB). One of the NAGB compounds, CA16, has been investigated in humans; our aim was to determine if other NAGB analogs (e.g. CA8 or CA4) were bioequivalent to CA16 and/or better suited as MST reagents. In vivo studies included dynamic positron-emission tomography (PET) imaging of 124I-labelled-scFv4-SA clearance and dual-label biodistribution studies following multi-step targeting (MST) dire