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Sample records for anti-anxiety agents

  1. Anti-anxiety effect of methanol extract of Pericarpium zanthoxyli ...

    African Journals Online (AJOL)

    Purpose: To determine if the methanol extract of Pericarpium zanthoxyli exerts anti-anxiety effects and also to explore any probable anti-anxiety mechanism in vivo. Methods: The staircase test, elevated plus maze test, rota-rod treadmill test and convulsions induced by strychnine and picrotoxin on mice were tested to identify ...

  2. Anti-Infectious Agents against MRSA

    Directory of Open Access Journals (Sweden)

    Nobuhiro Koyama

    2012-12-01

    Full Text Available Clinically useful antibiotics, β-lactams and vancomycin, are known to inhibit bacterial cell wall peptidoglycan synthesis. Methicillin-resistant Staphylococcus aureus (MRSA has a unique cell wall structure consisting of peptidoglycan and wall teichoic acid. In recent years, new anti-infectious agents (spirohexaline, tripropeptin C, DMPI, CDFI, cyslabdan, 1835F03, and BPH-652 targeting MRSA cell wall biosynthesis have been discovered using unique screening methods. These agents were found to inhibit important enzymes involved in cell wall biosynthesis such as undecaprenyl pyrophosphate (UPP synthase, FemA, flippase, or UPP phosphatase. In this review, the discovery, the mechanism of action, and the future of these anti-infectious agents are described.

  3. Anti-anxiety activity of hydro alcoholic extract of Scoparia dulcis Linn. assessed using different experimental anxiety models In rodents

    Directory of Open Access Journals (Sweden)

    Arasan Elayaraja

    2015-03-01

    Full Text Available Scoparia dulcis belonging to the family Scrophulariaceae is an valuable medicinal herb, had showed antiviral, antimalarial, anticancer and antidiabetic activities. The present study was aimed to investigate the anti-anxiety activity of crude ethanolic extract of S.dulcis L by various behavioural models. Preliminary phytochemical investigation revealed the presence of  phenols and flavonoids. The extract at 100mg/kg and 200mg/kg was evaluated for anti anxiety activity by  Open-field test [OFT], Elevated plus-maze test [EPM], Elevated Zero-maze test [EZM],, Social interaction test [SI] And  Novelty induced suppressed feeling latency test [FL]   and the results of behavioral tests indicated the dose dependent anti-anxiety activity of  Scoparia dulcis which is comparable to standard. It was concluded that crude ethanolic extract showed anti anxiety activity.Further studies are needed to identify the anxiolytic mechanism(s and the phytochemicals responsible for the observed anxiolytic effect  of the hydroalcoholic extract of Scoparia dulcis. 

  4. Anti-anxiety activity of hydro alcoholic extract of Scoparia dulcis Linn. assessed using different experimental anxiety models In rodents

    OpenAIRE

    Arasan Elayaraja; S. A. Rahaman; Prem kumar P.; Phani Kumar K.

    2015-01-01

    Scoparia dulcis belonging to the family Scrophulariaceae is an valuable medicinal herb, had showed antiviral, antimalarial, anticancer and antidiabetic activities. The present study was aimed to investigate the anti-anxiety activity of crude ethanolic extract of S.dulcis L by various behavioural models. Preliminary phytochemical investigation revealed the presence of  phenols and flavonoids. The extract at 100mg/kg and 200mg/kg was evaluated for anti anxiety activity by  Open-field test [OFT]...

  5. Novel agents for anti-platelet therapy

    Directory of Open Access Journals (Sweden)

    Ji Xuebin

    2011-11-01

    Full Text Available Abstract Anti-platelet therapy plays an important role in the treatment of patients with thrombotic diseases. The most commonly used anti-platelet drugs, namely, aspirin, ticlopidine, and clopidogrel, are effective in the prevention and treatment of cardio-cerebrovascular diseases. Glycoprotein IIb/IIIa antagonists (e.g., abciximab, eptifibatide and tirofiban have demonstrated good clinical benefits and safety profiles in decreasing ischemic events in acute coronary syndrome. However, adverse events related to thrombosis or bleeding have been reported in cases of therapy with glycoprotein IIb/IIIa antagonists. Cilostazol is an anti-platelet agent used in the treatment of patients with peripheral ischemia, such as intermittent claudication. Presently, platelet adenosine diphosphate P2Y(12 receptor antagonists (e.g., clopidogrel, prasugrel, cangrelor, and ticagrelor are being used in clinical settings for their pronounced protective effects. The new protease-activated receptor antagonists, vorapaxar and atopaxar, potentially decrease the risk of ischemic events without significantly increasing the rate of bleeding. Some other new anti-platelet drugs undergoing clinical trials have also been introduced. Indeed, the number of new anti-platelet drugs is increasing. Consequently, the efficacy of these anti-platelet agents in actual patients warrants scrutiny, especially in terms of the hemorrhagic risks. Hopefully, new selective platelet inhibitors with high anti-thrombotic efficiencies and low hemorrhagic side effects can be developed.

  6. Effect of Anti-Parasite Chemotherapeutic Agents on Immune Reactions.

    Science.gov (United States)

    1980-08-01

    observations). Similar effects of a number of other alkylating agents have been noticed (9, and personal observa- tions). Similarly, corticosteroids inhibit...Wellham, L. L., and Sigel, M. M. Ef- fect of anti-cancer chemotherapeutic agents on immune reactions of mice. I. Comparison of two nitrosoureas . J...7 D-Ri138 852 EFFECT OF ANTI-PARASITE CHEMOTHERAPEUTIC AGENTS ON i/i IMMUNE REACTIONS(U) SOUTH CAROLINA UNIV COLUMBIA DEPT OF MICROBIOLOGY AND

  7. Anti-anxiety effect of methanol extract of Pericarpium zanthoxyli ...

    African Journals Online (AJOL)

    the elevated plus maze test, suggesting that it has significant anti-anxiety activity. Furthermore, the ... Kyung-Dong Oriental Market, Seoul, Republic of. Korea. They were ... on which the mouse placed all four paws; rearing was defined as each ...

  8. Anti-Obesity Agents and the US Food and Drug Administration.

    Science.gov (United States)

    Casey, Martin F; Mechanick, Jeffrey I

    2014-09-01

    Despite the growing market for obesity care, the US Food and Drug Administration (FDA) has approved only two new pharmaceutical agents-lorcaserin and combination phentermine/topiramate-for weight reduction since 2000, while removing three agents from the market in the same time period. This article explores the FDA's history and role in the approval of anti-obesity medications within the context of a public health model of obesity. Through the review of obesity literature and FDA approval documents, we identified two major barriers preventing fair evaluation of anti-obesity agents including: (1) methodological pitfalls in clinical trials and (2) misaligned values in the assessment of anti-obesity agents. Specific recommendations include the use of adaptive (Bayesian) design protocols, value-based analyses of risks and benefits, and regulatory guidance based on a comprehensive, multi-platform obesity disease model. Positively addressing barriers in the FDA approval process of anti-obesity agents may have many beneficial effects within an obesity disease model.

  9. Curcumin: An age-old anti-inflammatory and anti-neoplastic agent

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    Matthew C. Fadus

    2017-07-01

    Full Text Available Curcumin is a natural anti-inflammatory agent that has been used for treating medical conditions for many years. Several experimental and pharmacologic trials have demonstrated its efficacy in the role as an anti-inflammatory agent. Curcumin has been shown to be effective in treating chronic conditions like rheumatoid arthritis, inflammatory bowel disease, Alzheimer's and common malignancies like colon, stomach, lung, breast, and skin cancers. As treatments in medicine become more and more complex, the answer may be something simpler. This is a review article written with the objective to systematically analyze the wealth of information regarding the medical use of curcumin, the “curry spice”, and to understand the existent gaps which have prevented its widespread application in the medical community.

  10. Pharmacological interactions of anti-microbial agents in odontology.

    Science.gov (United States)

    Gómez-Moreno, Gerardo; Guardia, Javier; Cutando, Antonio; Calvo-Guirado, José-Luis

    2009-03-01

    In this third article we describe the pharmacological interactions resulting from the use of anti-microbial agents. Although the antimicrobials prescribed in odontology are generally safe they can produce interactions with other medicaments which can give rise to serious adverse reactions which are well documented in clinical studies. Antibiotics with grave and dangerous life threatening consequences are erythromycin, clarithromycin and metronidazol and the anti-fungal agents are ketoconazol and itraconazol. Regarding the capacity of the anti-microbials to reduce the efficacy of oral anti-contraceptives the clinical studies to date are inconclusive, however, it would be prudent for the oral cavity specialist to point out the risk of a possible interaction. Therefore the specialist should be aware of possible interactions as a consequence of administering an antibiotic together with other medicaments the patient may be taking.

  11. Identification of Molecular Substrate for the Attenuation of Anxiety: A Step Toward the Development of Better Anti-Anxiety Drugs

    Directory of Open Access Journals (Sweden)

    Uwe Rudolph

    2001-01-01

    Full Text Available Anxiety disorders affect some 19 million people in the U.S. alone, costing $46.6 billion, or one third of the nation’s total mental health bill in 1990. Benzodiazepine tranquilizers like the prototypic diazepam are among the most widely used anti-anxiety agents. In addition to their anxiolytic action, they also induce sedation and may impair motor coordination, both of which are undesired side effects when they are used as anxiolytics. Not surprisingly, road traffic accidents may be increased for patients on classical benzodiazepines. In addition, these drugs carry the risk of dependence liability. Benzodiazepines augment the action of the inhibitory neurotransmitter g-aminobutyric acid (GABA at contact points between two nerve cells called synapses, points at which information is transmitted from one nerve cell to the next. Synaptically released GABA binds to postsynaptic GABAA receptors, thus causing an influx of negatively charged chloride ions into the postsynaptic neuron. This leads to a hyperpolarization and thus functional inhibition of the postsynaptic cell. Benzodiazepines bind to a site on the GABAA receptor which is different from the GABA binding site, thus increasing the chloride current. Benzodiazepines like diazepam bind to GABAA receptors containing the α subunits α1, α2, α3, or α5, most likely in abgabg combinations.

  12. Screening of Anti-Obesity Agent from Herbal Mixtures

    Directory of Open Access Journals (Sweden)

    Sung-Kee Jo

    2012-03-01

    Full Text Available Globally, one in three of the World’s adults are overweight and one in 10 is obese. By 2015, World Health Organization (WHO estimates the number of chubby adults will balloon to 2.3 billion—Equal to the combined populations of China, Europe and the United States. The discovery of bioactive compounds from herbs is one possible way to control obesity and to prevent or reduce the risks of developing various obesity-related diseases. In this study, we screened anti-obesity agents such as methyl gallate from the herbal composition known as HemoHIM that actively inhibits lipid formation as evidenced by Oil Red O staining and triglyceride (TG contents in 3T3-L1 adipocytes, suggesting their use as an anti-obesity agent. Furthermore, the amount of glycerol released from cells into the medium had increased by treatment of methyl gallate in a concentration-dependent manner. The present study suggests that a promising anti-obesity agent like methyl gallate might be of therapeutic interest for the treatment of obesity.

  13. Screening of anti-obesity agent from herbal mixtures.

    Science.gov (United States)

    Roh, Changhyun; Jung, Uhee; Jo, Sung-Kee

    2012-03-23

    Globally, one in three of the World's adults are overweight and one in 10 is obese. By 2015, World Health Organization (WHO) estimates the number of chubby adults will balloon to 2.3 billion--Equal to the combined populations of China, Europe and the United States. The discovery of bioactive compounds from herbs is one possible way to control obesity and to prevent or reduce the risks of developing various obesity-related diseases. In this study, we screened anti-obesity agents such as methyl gallate from the herbal composition known as HemoHIM that actively inhibits lipid formation as evidenced by Oil Red O staining and triglyceride (TG) contents in 3T3-L1 adipocytes, suggesting their use as an anti-obesity agent. Furthermore, the amount of glycerol released from cells into the medium had increased by treatment of methyl gallate in a concentration-dependent manner. The present study suggests that a promising anti-obesity agent like methyl gallate might be of therapeutic interest for the treatment of obesity.

  14. Marine Algae as a Potential Source for Anti-Obesity Agents

    Directory of Open Access Journals (Sweden)

    Chu Wan-Loy

    2016-12-01

    Full Text Available Obesity is a major epidemic that poses a worldwide threat to human health, as it is also associated with metabolic syndrome, type 2 diabetes and cardiovascular disease. Therapeutic intervention through weight loss drugs, accompanied by diet and exercise, is one of the options for the treatment and management of obesity. However, the only approved anti-obesity drug currently available in the market is orlistat, a synthetic inhibitor of pancreatic lipase. Other anti-obesity drugs are still being evaluated at different stages of clinical trials, while some have been withdrawn due to their severe adverse effects. Thus, there is a need to look for new anti-obesity agents, especially from biological sources. Marine algae, especially seaweeds are a promising source of anti-obesity agents. Four major bioactive compounds from seaweeds which have the potential as anti-obesity agents are fucoxanthin, alginates, fucoidans and phlorotannins. The anti-obesity effects of such compounds are due to several mechanisms, which include the inhibition of lipid absorption and metabolism (e.g., fucoxanthin and fucoidans, effect on satiety feeling (e.g., alginates, and inhibition of adipocyte differentiation (e.g., fucoxanthin. Further studies, especially testing bioactive compounds in long-term human trials are required before any new anti-obesity drugs based on algal products can be developed.

  15. Carnosol: a promising anti-cancer and anti-inflammatory agent.

    Science.gov (United States)

    Johnson, Jeremy J

    2011-06-01

    The Mediterranean diet and more specifically certain meats, fruits, vegetables, and olive oil found in certain parts of the Mediterranean region have been associated with a decreased cardiovascular and diabetes risk. More recently, several population based studies have observed with these lifestyle choices have reported an overall reduced risk for several cancers. One study in particular observed an inverse relationship between consumption of Mediterranean herbs such as rosemary, sage, parsley, and oregano with lung cancer. In light of these findings there is a need to explore and identify the anti-cancer properties of these medicinal herbs and to identify the phytochemicals therein. One agent in particular, carnosol, has been evaluated for anti-cancer property in prostate, breast, skin, leukemia, and colon cancer with promising results. These studies have provided evidence that carnosol targets multiple deregulated pathways associated with inflammation and cancer that include nuclear factor kappa B (NFκB), apoptotic related proteins, phosphatidylinositol-3-kinase (PI3 K)/Akt, androgen and estrogen receptors, as well as molecular targets. In addition, carnosol appears to be well tolerated in that it has a selective toxicity towards cancer cells versus non-tumorigenic cells and is well tolerated when administered to animals. This mini-review reports on the pre-clinical studies that have been performed to date with carnosol describing mechanistic, efficacy, and safety/tolerability studies as a cancer chemoprevention and anti-cancer agent. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  16. Novel anti-inflammatory agents in COPD

    DEFF Research Database (Denmark)

    Loukides, Stelios; Bartziokas, Konstantinos; Vestbo, Jørgen

    2013-01-01

    Inflammation plays a central role in chronic obstructive pulmonary disease (COPD). COPD related inflammation is less responsive to inhaled steroids compared to asthma. There are three major novel anti-inflammatory approaches to the management of COPD. The first approach is phosphodiesterase...... on these strategies exist at the moment. A third potential approach involves novel agents whose mechanism of action is closely related to COPD mechanisms and pathophysiology. Such novel treatments are of great interest since they may treat both COPD and co-morbidities. Several novel agents are currently under...

  17. Anti-herpesvirus agents: a patent and literature review (2003 to present).

    Science.gov (United States)

    Skoreński, Marcin; Sieńczyk, Marcin

    2014-08-01

    The standard therapy used to treat herpesvirus infections is based on the application of DNA polymerase inhibitors such as ganciclovir or aciclovir. Unfortunately, all of these compounds exhibit relatively high toxicity and the mutation of herpesviruses results in the appearance of new drug-resistant strains. Consequently, there is a great need for the development of new, effective and safe anti-herpesvirus agents that employ different patterns of therapeutic action at various stages of the virus life cycle. Patents and patent applications concerning the development of anti-herpesvirus agents displaying different mechanisms of action that have been published since 2003 are reviewed. In addition, major discoveries in this field that have been published in academic papers have also been included. Among all the anti-herpesvirus agents described in this article, the inhibitors of viral serine protease seem to present one of the most effective/promising therapeutics. Unfortunately, the practical application of these antiviral agents has not yet been proven in any clinical trials. Nevertheless, the dynamic and extensive work on this subject gives hope that a new class of anti-herpesvirus agents aimed at the enzymatic activity of herpesvirus serine protease may be developed.

  18. An overview of the current methodologies used for evaluation of anti-fertility agents

    Directory of Open Access Journals (Sweden)

    Manisha Shah

    2016-05-01

    Full Text Available Discoveries in the past two decades have continued to improve our understanding of the mechanism of fertilization and animal models have played a significant role to define the basic mechanism of anti-fertility agents. In vivo models have been developed in the past years to study the anti-fertility agents. Methods that are used in anti-fertility study can be categorized into method including estimation of sex hormones, assessment of sperm motility and count, assessment of sperm viability and morphology, mating trial test body, sex organ weights, abortifacient activity, post-coital anti-fertility activity, effect on estrous cycle, anti-estrogenic activity, anti-gonadotrophic effect and quantification of fructose in seminal vesicle, histopathology, and biochemical methods. This review aims to highlight some of the new and currently, used experimental models that are used for the evaluation of anti-fertility agents.

  19. Radiation protective agents possessing anti-oxidative properties

    Energy Technology Data Exchange (ETDEWEB)

    Anzai, Kazunori; Ueno, Emi; Yoshida, Akira; Furuse, Masako; Ikota, Nobuo [National Inst. of Radiological Sciences, Research Center for Radiation Safety, Chiba, Chiba (Japan)

    2005-11-15

    The purpose of studies is to see mechanisms of radiation protection of agents possessing anti-oxidative properties because the initial step resulting in radiation hazard is the formation of radicals by water radiolysis. Agents were commercially available or synthesized proxyl derivatives (spin prove agents), commercially available spin-trapping agents, edaravone and TMG (a tocopherol glycoside). Mice and cultured cells were X-irradiated by Shimadzu Pantak HF-320 or 320S. Survivals of cells were determined by colony assay and of mice, to which the agents were given intraperitoneally before or after X-irradiation, within 30 days post irradiation. Plasma and marrow concentrations of proxyls were estimated by electron spin resonance (ESR) spectrometry. Mechanisms of their radiation protective effects were shown different from agent to agent. TMG was found effective even post irradiation, which suggests a possibility for a new drug development. Some (spin trapping agents and TMG), virtually ineffective at the cell level, were found effective in the whole body, suggesting the necessity of studies on their disposition and metabolism. (S.I.)

  20. Radiation protective agents possessing anti-oxidative properties

    International Nuclear Information System (INIS)

    Anzai, Kazunori; Ueno, Emi; Yoshida, Akira; Furuse, Masako; Ikota, Nobuo

    2005-01-01

    The purpose of studies is to see mechanisms of radiation protection of agents possessing anti-oxidative properties because the initial step resulting in radiation hazard is the formation of radicals by water radiolysis. Agents were commercially available or synthesized proxyl derivatives (spin prove agents), commercially available spin-trapping agents, edaravone and TMG (a tocopherol glycoside). Mice and cultured cells were X-irradiated by Shimadzu Pantak HF-320 or 320S. Survivals of cells were determined by colony assay and of mice, to which the agents were given intraperitoneally before or after X-irradiation, within 30 days post irradiation. Plasma and marrow concentrations of proxyls were estimated by electron spin resonance (ESR) spectrometry. Mechanisms of their radiation protective effects were shown different from agent to agent. TMG was found effective even post irradiation, which suggests a possibility for a new drug development. Some (spin trapping agents and TMG), virtually ineffective at the cell level, were found effective in the whole body, suggesting the necessity of studies on their disposition and metabolism. (S.I.)

  1. Limited-sampling strategies for anti-infective agents: systematic review.

    Science.gov (United States)

    Sprague, Denise A; Ensom, Mary H H

    2009-09-01

    Area under the concentration-time curve (AUC) is a pharmacokinetic parameter that represents overall exposure to a drug. For selected anti-infective agents, pharmacokinetic-pharmacodynamic parameters, such as AUC/MIC (where MIC is the minimal inhibitory concentration), have been correlated with outcome in a few studies. A limited-sampling strategy may be used to estimate pharmacokinetic parameters such as AUC, without the frequent, costly, and inconvenient blood sampling that would be required to directly calculate the AUC. To discuss, by means of a systematic review, the strengths, limitations, and clinical implications of published studies involving a limited-sampling strategy for anti-infective agents and to propose improvements in methodology for future studies. The PubMed and EMBASE databases were searched using the terms "anti-infective agents", "limited sampling", "optimal sampling", "sparse sampling", "AUC monitoring", "abbreviated AUC", "abbreviated sampling", and "Bayesian". The reference lists of retrieved articles were searched manually. Included studies were classified according to modified criteria from the US Preventive Services Task Force. Twenty studies met the inclusion criteria. Six of the studies (involving didanosine, zidovudine, nevirapine, ciprofloxacin, efavirenz, and nelfinavir) were classified as providing level I evidence, 4 studies (involving vancomycin, didanosine, lamivudine, and lopinavir-ritonavir) provided level II-1 evidence, 2 studies (involving saquinavir and ceftazidime) provided level II-2 evidence, and 8 studies (involving ciprofloxacin, nelfinavir, vancomycin, ceftazidime, ganciclovir, pyrazinamide, meropenem, and alpha interferon) provided level III evidence. All of the studies providing level I evidence used prospectively collected data and proper validation procedures with separate, randomly selected index and validation groups. However, most of the included studies did not provide an adequate description of the methods or

  2. Menahydroquinone-4 Prodrug: A Promising Candidate Anti-Hepatocellular Carcinoma Agent.

    Science.gov (United States)

    Enjoji, Munechika; Watase, Daisuke; Matsunaga, Kazuhisa; Kusuda, Mariko; Nagata-Akaho, Nami; Karube, Yoshiharu; Takata, Jiro

    2015-07-22

    Recently, new therapeutics have been developed for hepatocellular carcinoma (HCC). However, the overall survival rate of HCC patients is still unsatisfactory; one of the reasons for this is the high frequency of recurrence after radical treatment. Consequently, to improve prognosis, it will be important to develop a novel anti-tumor agent that is especially effective against HCC recurrence. For clinical application, long-term safety, together with high anti-tumor efficacy, is desirable. Recent studies have proposed menahydroquinone-4 1,4-bis- N,N -dimethylglycinate hydrochloride (MKH-DMG), a prodrug of menahydroquinone-4 (MKH), as a promising candidate for HCC treatment including the inhibition of recurrence; MKH-DMG has been shown to achieve good selective accumulation of MKH in tumor cells, resulting in satisfactory inhibition of cell proliferation in des-γ-carboxyl prothrombin (DCP)-positive and DCP-negative HCC cell lines. In a spleen-liver metastasis mouse model, MKH-DMG has been demonstrated to have anti-proliferation and anti-metastatic effects in vivo . The characteristics of MKH-DMG as a novel anti-HCC agent are presented in this review article.

  3. Impact of the Number of Anti-Thrombosis Agents in Hemodialysis Patients: BOREAS-HD2 Study

    Directory of Open Access Journals (Sweden)

    Marenao Tanaka

    2017-09-01

    Full Text Available Background/Aims: Relationships between the number of anti-thrombosis agents, clinical benefits and adverse events in hemodialysis (HD patients are unclear. Methods: All patients on HD in 22 institutes (n = 1,071 were enrolled and followed up for 3 years. After exclusion of patients with missing data, kidney transplantation or retraction of consent during the follow-up period (n = 204, mortality rate and ischemic and hemorrhagic events were compared between different regimens of anti-thrombosis agents. Results: The use of dual or triple antiplatelet (AP agents (HR:2.03, 95% CI:1.01-4.13, p = 0.04 and the combination of an AP agent and warfarin (WF (HR:4.84, 95%CI 1.96-11.96, p < 0.001 were associated with an increase in hemorrhagic events compared with no use of anti-thrombosis agents. No anti-thrombosis regimen was associated with a significant change in risk of ischemic stroke. The use of dual or triple AP agents, but not WF, was associated with an increase in cardiovascular mortality (HR:2.48, 95% CI:1.24-4.76, p = 0.01. Conclusion: A significant increase in hemorrhagic events by the use of dual or more AP agents and by co-administration of an AP agent and WF in patients on HD should be considered in planning their anti-thrombosis regimen.

  4. Birth Outcomes in Children Fathered by Men Treated with Anti-TNF-α Agents Before Conception

    DEFF Research Database (Denmark)

    Larsen, Michael Due; Friedman, Sonia; Magnussen, Bjarne

    2016-01-01

    OBJECTIVES: The safety of paternal use of anti-tumor necrosis factor-α (TNF-α) agents immediately prior to conception is practically unknown. On the basis of nationwide data from Danish health registries, we examined the association between paternal use of anti-TNF-α agents within 3 months before...... the safety of paternal preconceptional use of anti-TNF-α agents. The result regarding SGA should, however, be interpreted with caution as we found an increased risk, although not significantly increased....

  5. Resistance to cytotoxic and anti-angiogenic anticancer agents: similarities and differences.

    NARCIS (Netherlands)

    Broxterman, H.J.; Lankelma, J.; Hoekman, K.

    2003-01-01

    Intrinsic resistance to anticancer drugs, or resistance developed during chemotherapy, remains a major obstacle to successful treatment. This is the case both for resistance to cytotoxic agents, directed at malignant cells, and for resistance to anti-angiogenic agents, directed at non-malignant

  6. Are anti-inflammatory agents effective in treating gingivitis as solo or adjunct therapies? A systematic review.

    Science.gov (United States)

    Polak, David; Martin, Conchita; Sanz-Sánchez, Ignacio; Beyth, Nurit; Shapira, Lior

    2015-04-01

    Systematically review the scientific evidence for efficiency of anti-inflammatory agents against gingivitis, either as solo treatments or adjunctive therapies. A protocol was developed aimed to answer the following focused question: "Are anti-inflammatory agents effective in treating gingivitis as solo or adjunct therapies?" RCTs and cohort studies on anti-inflammatory agents against gingivitis studies were searched electronically. Screening, data extraction and quality assessment were conducted. The primary outcome measures were indices of gingival inflammation. A sub-analysis was performed dividing the active agents into anti-inflammatory and other drugs. The search identified 3188 studies, of which 14 RCTs met the inclusion criteria. The use of anti-inflammatory or other agents, in general showed a higher reduction in the test than in the control in terms of gingival indexes and bleeding scores. Only two RCTs on inflammatory drugs could be meta-analysed, showing a statistically significant reduction in the GI in the experimental group [WMD = -0.090; 95% CI (-0.105; -0.074); p = 0.000]. However, the contribution of both studies to the global result was unbalanced (% weight: 99.88 and 0.12 respectively). Most of the tested material showed beneficial effect as anti-inflammatory agents against gingivitis, either as a single treatment modality or as an adjunctive therapy. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  7. Repeated systemic administration of the cinnamon essential oil possesses anti-anxiety and anti-depressant activities in mice.

    Science.gov (United States)

    Sohrabi, Reyhaneh; Pazgoohan, Nasim; Seresht, Hasan Rezaei; Amin, Bahareh

    2017-06-01

    The present study aimed to evaluate the putative antidepressant and anti-anxiety effects of the cinnamon essential oil when administered acute (for 3 doses) and sub-acute (for 14 days) to mice. In an acute experimental study, forced swim test (FST) was conducted to evaluate the antidepressant-like behavior of animals treated with the intraperitoneal (IP) essential oil of cinnamon in triple doses (0.5, 1, and 2 mg/kg). In a sub-acute study (14 days in 24-hr intervals) antidepressant-like effects of essential oil (0.5, 1, and 2 mg/kg) with the same route were assessed in FST and tail suspension test (TST). Anti-anxiety and motor activities were evaluated using elevated plus-maze (EPM) and open field tests, respectively. Determination of different constituents within the sample oil was via gas chromatography-mass spectrometry (GC-MS) analysis. Repetitive administration of cinnamon essential oil (0.5, 1, 2 mg/kg) during 14 days significantly decreased the time of immobility in both FST and TST as compared to the control group. Mice treated with oil at the dose of 2 mg/kg spent a longer time and had more entries into the open arms of EPM as compared with the vehicle-treated ones. According to GC-MS analysis, 46 chemical compounds were identified in the studied cinnamon essential oil with the main constituent being trans-cinnamaldehyde (87.32%). Cinnamon essential oil might be used as an adjunctive therapy in improving symptoms of depressive and anxiety disorders. However, dose-response effects need further evaluation. Trans-cinnamaldehyde might be responsible for the beneficial effect observed.

  8. An update on anti-TNF agents in ulcerative colitis

    NARCIS (Netherlands)

    Samaan, Mark A.; Bagi, Preet; Vande Casteele, Niels; D'Haens, Geert R.; Levesque, Barrett G.

    2014-01-01

    Anti-tumor necrosis factor-α agents are key therapeutic options for the treatment of ulcerative colitis. Their efficacy and safety have been shown in large randomized controlled trials. The key evidence gained from these trials of infliximab, adalimumab, and golimumab is reviewed along with their

  9. Anti-inflammatory agents in the treatment of bipolar depression: a systematic review and meta-analysis.

    Science.gov (United States)

    Rosenblat, Joshua D; Kakar, Ron; Berk, Michael; Kessing, Lars V; Vinberg, Maj; Baune, Bernhard T; Mansur, Rodrigo B; Brietzke, Elisa; Goldstein, Benjamin I; McIntyre, Roger S

    2016-03-01

    Inflammation has been implicated in the risk, pathophysiology, and progression of mood disorders and, as such, has become a target of interest in the treatment of bipolar disorder (BD). Therefore, the objective of the current qualitative and quantitative review was to determine the overall antidepressant effect of adjunctive anti-inflammatory agents in the treatment of bipolar depression. Completed and ongoing clinical trials of anti-inflammatory agents for BD published prior to 15 May 15 2015 were identified through searching the PubMed, Embase, PsychINFO, and Clinicaltrials.gov databases. Data from randomized controlled trials (RCTs) assessing the antidepressant effect of adjunctive mechanistically diverse anti-inflammatory agents were pooled to determine standard mean differences (SMDs) compared with standard therapy alone. Ten RCTs were identified for qualitative review. Eight RCTs (n = 312) assessing adjunctive nonsteroidal anti-inflammatory drugs (n = 53), omega-3 polyunsaturated fatty acids (n = 140), N-acetylcysteine (n = 76), and pioglitazone (n = 44) in the treatment of BD met the inclusion criteria for quantitative analysis. The overall effect size of adjunctive anti-inflammatory agents on depressive symptoms was -0.40 (95% confidence interval -0.14 to -0.65, p = 0.002), indicative of a moderate and statistically significant antidepressant effect. The heterogeneity of the pooled sample was low (I² = 14%, p = 0.32). No manic/hypomanic induction or significant treatment-emergent adverse events were reported. Overall, a moderate antidepressant effect was observed for adjunctive anti-inflammatory agents compared with conventional therapy alone in the treatment of bipolar depression. The small number of studies, diversity of agents, and small sample sizes limited interpretation of the current analysis. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  10. Can We Predict the Efficacy of Anti-TNF-α Agents?

    Science.gov (United States)

    Lopetuso, Loris Riccardo; Gerardi, Viviana; Papa, Valerio; Scaldaferri, Franco; Rapaccini, Gian Lodovico; Gasbarrini, Antonio; Papa, Alfredo

    2017-09-14

    The use of biologic agents, particularly anti-tumor necrosis factor (TNF)-α, has revolutionized the treatment of inflammatory bowel diseases (IBD), modifying their natural history. Several data on the efficacy of these agents in inducing and maintaining clinical remission have been accumulated over the past two decades: their use avoid the need for steroids therapy, promote mucosal healing, reduce hospitalizations and surgeries and therefore dramatically improve the quality of life of IBD patients. However, primary non-response to these agents or loss of response over time mainly due to immunogenicity or treatment-related side-effects are a frequent concern in IBD patients. Thus, the identification of predicting factors of efficacy is crucial to allow clinicians to efficiently use these therapies, avoiding them when they are ineffective and eventually shifting towards alternative biological therapies with the end goal of optimizing the cost-effectiveness ratio. In this review, we aim to identify the predictive factors of short- and long-term benefits of anti-TNF-α therapy in IBD patients. In particular, multiple patient-, disease- and treatment-related factors have been evaluated.

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

    DEFF Research Database (Denmark)

    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....

  12. Evaluation of GABAergic neuroactive steroid 3alpha-hydroxy-5alpha-pregnane-20-one as a neurobiological substrate for the anti-anxiety effect of ethanol in rats.

    Science.gov (United States)

    Hirani, Khemraj; Sharma, Ajay N; Jain, Nishant S; Ugale, Rajesh R; Chopde, Chandrabhan T

    2005-07-01

    Acute systemic ethanol administration is known to elevate plasma and cerebral levels of neuroactive steroid 3alpha-hydroxy-5alpha-pregnane-20-one (3alpha, 5alpha-THP; allopregnanolone) to a concentration sufficient to potentiate GABA(A) receptors. We have earlier demonstrated that 3alpha, 5alpha-THP mediates the antidepressant-like effect of ethanol in Porsolt forced swim test. The aim of the present study is to explain the relationship between endogenous GABAergic neurosteroids and anxiolytic effect of ethanol in Sprague-Dawley rats. The mediation of 3alpha, 5alpha-THP in the anti-anxiety effect of ethanol was assessed by pharmacological interactions of ethanol with various endogenous neurosteroidal modulators and using simulated physiological conditions of altered neurosteroid content in elevated plus maze (EPM) test. Pretreatment of 3alpha, 5alpha-THP (0.5-2.5 mug/rat, i.c.v.) or neurosteroidogenic agents such as 3alpha, 5alpha-THP precursor progesterone (5 or 10 mg/kg, i.p.), 11-beta hydroxylase inhibitor metyrapone (50 or 100 mg/kg, i.p.) or the GABA(A) receptor agonist muscimol (25 ng/rat, i.c.v.) significantly potentiated the anti-anxiety effect of ethanol (1 g/kg, i.p.). On the other hand, the GABAergic antagonistic neurosteroid dehydroepiandrosterone sulphate (DHEAS) (1 mg/kg, i.p.), the GABA(A) receptor blocker bicuculline (1 mg/kg, i.p.), the 5alpha-reductase inhibitor finasteride (50 x 2 mg/kg, s.c.) or the mitochondrial diazepam binding inhibitory receptor antagonist PK11195 (1 mg/kg, i.p.) reduced ethanol-induced preference of time spent and number of entries into open arms. Anti-anxiety effect of ethanol was abolished in adrenalectomized (ADX) rats as compared to sham-operated control. This ADX-induced blockade was restored by prior systemic injection of progesterone, signifying the contribution of peripheral steroidogenesis in ethanol anxiolysis. Socially isolated animals known to exhibit decreased brain 3alpha, 5alpha-THP and GABA(A) receptor

  13. Anti-anxiety and anti-depressant like effects of murraya koenigii in experimental models of anxiety and depression

    Directory of Open Access Journals (Sweden)

    Snigdha Sharma

    2017-01-01

    Full Text Available Background: Presence of free radical scavenging activity in Murraya koenigii, commonly known as Curry leaves, has been shown in previous studies. Oxidative stress plays an important role in the development of various neurobehavioral disorders including anxiety and depression. Aim: The present study aimed to evaluate the effects of Murraya koenigii in animal models of depression and anxiety. Materials and Methods: The effect of incremental doses of Murraya koenigii aqueous leaf extract was evaluated on spontaneous motor activity (SMA, open arm incursions in elevated plus maze, and despair behaviour in forced swim (FST and tail suspension (TST tests as compared to control groups in Swiss albino mice. Results: Murraya koenigii 300 mg/kg, p.o. (MK300 and 400 mg/kg, p.o. (MK400 reduced the SMA count from 754 ± 64.9 to 540 ± 29 and 295 ± 34 respectively, which was statistically significant. MK300 and MK400 reduced significantly the open arm count from 29 ± 8.6 to 16 ± 7 and 10 ± 3.9, respectively. On FST, MK400 reduced the duration of immobility from 145.5 ± 29 to 91 ± 17.3, which was statistically significant. On TST, MK produced a dose-dependent decrease in the duration of immobility; however, it was statistically significant only with MK400. Conclusion: Murraya koenigii aqueous leaf extract reduced the despair behavior in experimental animal models, suggesting an anti-depressant like activity. Murraya koenigii extract also reduced spontaneous locomotor activity in a dose-dependent manner suggesting a sedative and/or anxiolytic effect though there wasn't any anxiolytic effect in the elevated plus maze test.

  14. Evaluation of pawpaw leaves extract as anti-corrosion agent for ...

    African Journals Online (AJOL)

    Pawpaw leaves extract was examined as anti-corrosion agent for aluminium in hydrochloric acid medium. The extract and corrosion product were analyzed using Fourier transform infrared spectrophotometer (FTIR). Thermometric, gravimetric, potentiodynamic polarization and scanning electron microscopic methods were ...

  15. Dentists' approach to patients on anti-platelet agents and warfarin: a survey of practice.

    LENUS (Irish Health Repository)

    Murphy, James

    2010-04-23

    In everyday practice, dentists are confronted with the dilemma of patients on anti-platelet agents and warfarin who require invasive dental procedures and, more pertinently, dental extractions. There may be a divergence of opinion among dentists regarding how they manage these patients. AIMS: To assess general dental practitioners\\' approach to the management of patients taking anti-platelet agents and\\/or warfarin who are undergoing invasive dental procedures. METHODS AND DATA: A semi-structured questionnaire was designed to survey general dental practitioners in a large Irish urban area. RESULTS: A response rate of 89% was achieved in a study population of 54 general dental practitioners. A total of 25% of respondents who carry out extractions on warfarinised patients do not check the INR prior to invasive dental procedures. Some 90% of respondents stop anti-platelet agents prior to extractions. CONCLUSIONS: A significant proportion of respondents fail to check warfarinised patients\\' INR prior to invasive dental procedures. Furthermore, a trend of stopping anti-platelet agents was noted, which is in contrast with current recommendations in the dental literature. Certain practices in this small study population proved alarming and highlight the need for improved awareness of current guidelines. A further large-scale study may be justified, as variation in practice may have clinical and medico-legal repercussions.

  16. Dermatomyositis-like syndrome induced by nonsteroidal anti-inflammatory agents.

    Science.gov (United States)

    Grob, J J; Collet, A M; Bonerandi, J J

    1989-01-01

    A dermatomyositis-like syndrome developed in a patient treated with a nonsteroidal anti-inflammatory agent (NSAI), niflumic acid, and regressed after the cessation of treatment. Previously an eruption had occurred under treatment with another NSAI, diclofenac. Our report shows that NSAI can induce not only lupus-like syndromes but also other connective tissue disorders.

  17. Concanavalin A: A potential anti-neoplastic agent targeting apoptosis, autophagy and anti-angiogenesis for cancer therapeutics

    International Nuclear Information System (INIS)

    Li, Wen-wen; Yu, Jia-ying; Xu, Huai-long; Bao, Jin-ku

    2011-01-01

    Highlights: → ConA induces cancer cell death targeting apoptosis and autophagy. → ConA inhibits cancer cell angiogenesis. → ConA is utilized in pre-clinical and clinical trials. -- Abstract: Concanavalin A (ConA), a Ca 2+ /Mn 2+ -dependent and mannose/glucose-binding legume lectin, has drawn a rising attention for its remarkable anti-proliferative and anti-tumor activities to a variety of cancer cells. ConA induces programmed cell death via mitochondria-mediated, P73-Foxo1a-Bim apoptosis and BNIP3-mediated mitochondrial autophagy. Through IKK-NF-κB-COX-2, SHP-2-MEK-1-ERK, and SHP-2-Ras-ERK anti-angiogenic pathways, ConA would inhibit cancer cell survival. In addition, ConA stimulates cell immunity and generates an immune memory, resisting to the same genotypic tumor. These biological findings shed light on new perspectives of ConA as a potential anti-neoplastic agent targeting apoptosis, autophagy and anti-angiogenesis in pre-clinical or clinical trials for cancer therapeutics.

  18. Rational drug design for anti-cancer chemotherapy: multi-target QSAR models for the in silico discovery of anti-colorectal cancer agents.

    Science.gov (United States)

    Speck-Planche, Alejandro; Kleandrova, Valeria V; Luan, Feng; Cordeiro, M Natália D S

    2012-08-01

    The discovery of new and more potent anti-cancer agents constitutes one of the most active fields of research in chemotherapy. Colorectal cancer (CRC) is one of the most studied cancers because of its high prevalence and number of deaths. In the current pharmaceutical design of more efficient anti-CRC drugs, the use of methodologies based on Chemoinformatics has played a decisive role, including Quantitative-Structure-Activity Relationship (QSAR) techniques. However, until now, there is no methodology able to predict anti-CRC activity of compounds against more than one CRC cell line, which should constitute the principal goal. In an attempt to overcome this problem we develop here the first multi-target (mt) approach for the virtual screening and rational in silico discovery of anti-CRC agents against ten cell lines. Here, two mt-QSAR classification models were constructed using a large and heterogeneous database of compounds. The first model was based on linear discriminant analysis (mt-QSAR-LDA) employing fragment-based descriptors while the second model was obtained using artificial neural networks (mt-QSAR-ANN) with global 2D descriptors. Both models correctly classified more than 90% of active and inactive compounds in training and prediction sets. Some fragments were extracted from the molecules and their contributions to anti-CRC activity were calculated using mt-QSAR-LDA model. Several fragments were identified as potential substructural features responsible for the anti-CRC activity and new molecules designed from those fragments with positive contributions were suggested and correctly predicted by the two models as possible potent and versatile anti-CRC agents. Copyright © 2012 Elsevier Ltd. All rights reserved.

  19. Decreasing Skin Graft Contraction through Topical Wound Bed Preparation with Anti-Inflammatory Agents

    Science.gov (United States)

    2017-10-01

    Award Number: W81XWH-14-2-0153 TITLE: Decreasing Skin Graft Contraction through Topical Wound Bed Preparation with Anti-Inflammatory Agents...09/14/2017 4. TITLE AND SUBTITLE “Decreasing Skin Graft Contraction through Topical Wound Bed Preparation with Anti-Inflammatory Agents” 5a...of a specific topical anti-inflammatory drug that will reduce and shorten the inflammatory state of the recipient wound bed and thus, skin graft

  20. Anxiety Distorders: Types, Diagnosis and Treatment | NIH MedlinePlus the Magazine

    Science.gov (United States)

    ... medications used for anxiety disorders are antidepressants, anti-anxiety drugs, and beta-blockers. Be aware that some medications are effective only ... anxiety disorders. Benzodiazepines (anti-anxiety medications) The anti-anxiety medications called benzodiazepines ... control some of the physical symptoms ...

  1. Towards identifying novel anti-Eimeria agents: trace elements, vitamins, and plant-based natural products.

    Science.gov (United States)

    Wunderlich, Frank; Al-Quraishy, Saleh; Steinbrenner, Holger; Sies, Helmut; Dkhil, Mohamed A

    2014-10-01

    Eimeriosis, a widespread infectious disease of livestock, is caused by coccidian protozoans of the genus Eimeria. These obligate intracellular parasites strike the digestive tract of their hosts and give rise to enormous economic losses, particularly in poultry, ruminants including cattle, and rabbit farming. Vaccination, though a rational prophylactic measure, has not yet been as successful as initially thought. Numerous broad-spectrum anti-coccidial drugs are currently in use for treatment and prophylactic control of eimeriosis. However, increasing concerns about parasite resistance, consumer health, and environmental safety of the commercial drugs warrant efforts to search for novel agents with anti-Eimeria activity. This review summarizes current approaches to prevent and treat eimeriosis such as vaccination and commercial drugs, as well as recent attempts to use dietary antioxidants as novel anti-Eimeria agents. In particular, the trace elements selenium and zinc, the vitamins A and E, and natural products extracted from garlic, barberry, pomegranate, sweet wormwood, and other plants are discussed. Several of these novel anti-Eimeria agents exhibit a protective role against oxidative stress that occurs not only in the intestine of Eimeria-infected animals, but also in their non-parasitized tissues, in particular, in the first-pass organ liver. Currently, it appears to be promising to identify safe combinations of low-cost natural products with high anti-Eimeria efficacy for a potential use as feed supplementation in animal farming.

  2. Non-operative anti-caries agents and dental caries increment among adults at high caries risk: a retrospective cohort study.

    Science.gov (United States)

    Chaffee, Benjamin W; Cheng, Jing; Featherstone, John D B

    2015-09-24

    Consensus guidelines support non-operative preventives for dental caries management; yet, their use in practice is far from universal. The purpose of this study was to evaluate the effectiveness of non-operative anti-caries agents in caries prevention among high caries risk adults at a university clinic where risk-based caries management is emphasized. This retrospective observational study drew data from the electronic patient records of non-edentulous adult patients deemed to be at high risk for dental caries during baseline oral evaluations that were completed between July 1, 2007 and December 31, 2012 at a dental university in the United States. We calculated and compared adjusted mean estimates for the number of new decayed or restored teeth (DFT increment) from baseline to the next completed oral evaluation (N = 2,724 patients with follow-up) across three categories of delivery of non-operative anti-caries agents (e.g., high-concentration fluoride toothpaste, chlorhexidine rinse, xylitol products): never, at a single appointment, or at ≥2 appointments ≥4 weeks apart. Estimates were adjusted for patient and provider characteristics, baseline dental status, losses-to-follow-up, and follow-up time. Approximately half the patients did not receive any form of non-operative anti-caries agent. Most that received anti-caries agents were given more than one type of product in combination. One-time delivery of anti-caries agents was associated with a similar DFT increment as receiving no such therapy (difference in increment: -0.04; 95% CI: -0.28, 0.21). However, repeated, spaced delivery of anti-caries agents was associated with approximately one decayed or restored tooth prevented over 18 months for every three patients treated (difference in increment: -0.35; 95% CI: -0.65, -0.08). These results lend evidence that repeatedly receiving anti-caries agents can reduce tooth decay among high-risk patients engaged in regular dental care.

  3. Macrolides decrease the minimal inhibitory concentration of anti-pseudomonal agents against Pseudomonas aeruginosa from cystic fibrosis patients in biofilm

    Directory of Open Access Journals (Sweden)

    Lutz Larissa

    2012-09-01

    Full Text Available Abstract Background Biofilm production is an important mechanism for bacterial survival and its association with antimicrobial resistance represents a challenge for the patient treatment. In this study we evaluated the in vitro action of macrolides in combination with anti-pseudomonal agents on biofilm-grown Pseudomonas aeruginosa recovered from cystic fibrosis (CF patients. Results A total of 64 isolates were analysed. The biofilm inhibitory concentration (BIC results were consistently higher than those obtained by the conventional method, minimal inhibitory concentration, (MIC for most anti-pseudomonal agents tested (ceftazidime: P = 0.001, tobramycin: P = 0.001, imipenem: P P = 0.005. When macrolides were associated with the anti-pseudomonal agents, the BIC values were reduced significantly for ceftazidime (P  0.001 and tobramycin (P  0.001, regardless the concentration of macrolides. Strong inhibitory quotient was observed when azithromycin at 8 mg/L was associated with all anti-pseudomonal agents tested in biofilm conditions. Conclusions P. aeruginosa from CF patients within biofilms are highly resistant to antibiotics but macrolides proved to augment the in vitro activity of anti-pseudomonal agents.

  4. Comparative Efficacy and Acceptability of Anti-Diabetic Agents for Alzheimer's Disease and Mild Cognitive Impairment: A Systematic Review and Network Meta-analysis.

    Science.gov (United States)

    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.

  5. Screening of Anti-Obesity Agent from Herbal Mixtures

    OpenAIRE

    Sung-Kee Jo; Uhee Jung; Changhyun Roh

    2012-01-01

    Globally, one in three of the World’s adults are overweight and one in 10 is obese. By 2015, World Health Organization (WHO) estimates the number of chubby adults will balloon to 2.3 billion—Equal to the combined populations of China, Europe and the United States. The discovery of bioactive compounds from herbs is one possible way to control obesity and to prevent or reduce the risks of developing various obesity-related diseases. In this study, we screened anti-obesity agents such as methyl ...

  6. The Anti-Anxiety Curriculum: Combating Math Anxiety in the Classroom

    Science.gov (United States)

    Geist, Eugene

    2010-01-01

    Negative attitudes toward mathematics and what has come to be know as "math anxiety" are serious obstacles for children in all levels of schooling today. In this paper, the literature is reviewed and critically assessed in regards to the roots of math anxiety and its especially detrimental effect on children in "at-risk" populations such as low…

  7. Mitochondrial complex II, a novel target for anti-cancer agents

    Czech Academy of Sciences Publication Activity Database

    Klučková, Katarína; Bezawork-Geleta, A.; Rohlena, Jakub; Dong, L.; Neužil, Jiří

    2013-01-01

    Roč. 1827, č. 5 (2013), s. 552-564 ISSN 0005-2728 R&D Projects: GA ČR(CZ) GAP301/10/1937; GA ČR GAP301/12/1851 Institutional research plan: CEZ:AV0Z50520701 Keywords : Mitochondrion * Complex II * Anti-cancer agent Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 4.829, year: 2013

  8. 21 CFR 178.3130 - Antistatic and/or anti-fogging agents in food-packaging materials.

    Science.gov (United States)

    2010-04-01

    ...-packaging materials. 178.3130 Section 178.3130 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF.../or anti-fogging agents in food-packaging materials. The substances listed in paragraph (b) of this section may be safely used as antistatic and/or antifogging agents in food-packaging materials, subject to...

  9. Current progress and future perspectives in the development of anti-polo-like kinase 1 therapeutic agents [version 1; referees: 4 approved

    Directory of Open Access Journals (Sweden)

    Jung-Eun Park

    2017-06-01

    Full Text Available Although significant levels of side effects are often associated with their use, microtubule-directed agents that primarily target fast-growing mitotic cells have been considered to be some of the most effective anti-cancer therapeutics. With the hope of developing new-generation anti-mitotic agents with reduced side effects and enhanced tumor specificity, researchers have targeted various proteins whose functions are critically required for mitotic progression. As one of the highly attractive mitotic targets, polo-like kinase 1 (Plk1 has been the subject of an extensive effort for anti-cancer drug discovery. To date, a variety of anti-Plk1 agents have been developed, and several of them are presently in clinical trials. Here, we will discuss the current status of generating anti-Plk1 agents as well as future strategies for designing and developing more efficacious anti-Plk1 therapeutics.

  10. Genome Mining of the Marine Actinomycete Streptomyces sp. DUT11 and Discovery of Tunicamycins as Anti-complement Agents

    Directory of Open Access Journals (Sweden)

    Xiao-Na Xu

    2018-06-01

    Full Text Available Marine actinobacteria are potential producers of various secondary metabolites with diverse bioactivities. Among various bioactive compounds, anti-complement agents have received great interest for drug discovery to treat numerous diseases caused by inappropriate activation of the human complement system. However, marine streptomycetes producing anti-complement agents are still poorly explored. In this study, a marine-derived strain Streptomyces sp. DUT11 showing superior anti-complement activity was focused, and its genome sequence was analyzed. Gene clusters showing high similarities to that of tunicamycin and nonactin were identified, and their corresponding metabolites were also detected. Subsequently, tunicamycin I, V, and VII were isolated from Streptomyces sp. DUT11. Anti-complement assay showed that tunicamycin I, V, VII inhibited complement activation through the classic pathway, whereas no anti-complement activity of nonactin was detected. This is the first time that tunicamycins are reported to have such activity. In addition, genome analysis indicates that Streptomyces sp. DUT11 has the potential to produce novel lassopeptides and lantibiotics. These results suggest that marine Streptomyces are rich sources of anti-complement agents for drug discovery.

  11. Oncocalyxone A functions as an anti-glycation agent in vitro.

    Directory of Open Access Journals (Sweden)

    Ingrid Sofia Vieira de Melo

    Full Text Available Advanced glycation endproducts (AGE are the result of post-translational changes to proteins, which ultimately compromise their structure and/or function. The identification of methods to prevent the formation of these compounds holds great promise in the development of alternative therapies for diseases such as diabetes. Plants used in traditional medicine are often rich sources of anti-glycation agents. Therefore, in this study, we investigated the anti-glycation activity of one such compound, Oncocalyxone A (Onco A. Using spectrofluorimetric techniques, we determined that Onco A inhibits AGE formation in a concentration-dependent manner. Its IC50 value (87.88 ± 3.08 μM was almost two times lower than the standard anti-glycation compound aminoguanidine (184.68 ± 4.85 μM. The excellent anti-glycation activity of Onco A makes it an exciting candidate for the treatment of diseases associated with excessive accumulation of AGE. However, additional studies are necessary to identify its mechanism of action, as well as the in vivo response in suitable model organisms.

  12. Calcination of Rod-like Hydroxyapatite Nanocrystals with an Anti-sintering Agent Surrounding the Crystals

    International Nuclear Information System (INIS)

    Okada, M.; Furuzono, T.

    2007-01-01

    Sintering-free nanocrystals of calcined hydroxyapatite (HAp) having a rod-like morphology were fabricated by calcination at 800 deg. C for 1 h with an anti-sintering agent surrounding original HAp particles and the agent was subsequently removed after calcination. The original HAp particles having a rod-like morphology with a size ranging from 30 to 80 nm (short axis) and 300 to 500 nm (long axis) were prepared by wet chemical process, and poly(acrylic acid, calcium salt) (PAA-Ca) was used as the anti-sintering agent. In the case of calcination without additives, the mean size of HAp crystals dispersed in an ethanol medium increased by about 4 times and the specific surface area of the crystals exhibited a 25% decrease compared to those of the original HAp particles because of calcination-induced sintering among the crystals. On the other hand, the HAp crystals calcined with the anti-sintering agent, PAA-Ca, could be dispersed in an ethanol medium at the same size as the original particles, and they preserved the specific surface area after calcination. These results indicate that PAA-Ca and/or its thermally decomposed product, CaO, surrounded the HAp particles and protected them against calcination-induced sintering during calcination. The HAp crystals calcined with PAA-Ca showed high crystallinity, and no other calcium phosphate phases could be detected after washing with water

  13. Drug-induced liver injury due to antimicrobials, central nervous system agents, and nonsteroidal anti-inflammatory drugs.

    Science.gov (United States)

    Devarbhavi, Harshad; Andrade, Raúl J

    2014-05-01

    Antimicrobial agents including antituberculosis (anti-TB) agents are the most common cause of idiosyncratic drug-induced liver injury (DILI) and drug-induced liver failure across the world. Better molecular and genetic biomarkers are acutely needed to help identify those at risk of liver injury particularly for those needing antituberculosis therapy. Some antibiotics such as amoxicillin-clavulanate and isoniazid consistently top the lists of agents in retrospective and prospective DILI databases. Central nervous system agents, particularly antiepileptics, account for the second most common class of agents implicated in DILI registries. Hepatotoxicity from older antiepileptics such as carbamazepine, phenytoin, and phenobarbital are often associated with hypersensitivity features, whereas newer antiepileptic drugs have a more favorable safety profile. Antidepressants and nonsteroidal anti-inflammatory drugs carry very low risk of significant liver injury, but their prolific use make them important causes of DILI. Early diagnosis and withdrawal of the offending agent remain the mainstays of minimizing hepatotoxicity. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

  14. Novel histone deacetylase inhibitors in clinical trials as anti-cancer agents

    Directory of Open Access Journals (Sweden)

    Petrillo Richard L

    2010-02-01

    Full Text Available Abstract Histone deacetylases (HDACs can regulate expression of tumor suppressor genes and activities of transcriptional factors involved in both cancer initiation and progression through alteration of either DNA or the structural components of chromatin. Recently, the role of gene repression through modulation such as acetylation in cancer patients has been clinically validated with several inhibitors of HDACs. One of the HDAC inhibitors, vorinostat, has been approved by FDA for treating cutaneous T-cell lymphoma (CTCL for patients with progressive, persistent, or recurrent disease on or following two systemic therapies. Other inhibitors, for example, FK228, PXD101, PCI-24781, ITF2357, MGCD0103, MS-275, valproic acid and LBH589 have also demonstrated therapeutic potential as monotherapy or combination with other anti-tumor drugs in CTCL and other malignancies. At least 80 clinical trials are underway, testing more than eleven different HDAC inhibitory agents including both hematological and solid malignancies. This review focuses on recent development in clinical trials testing HDAC inhibitors as anti-tumor agents.

  15. Biosynthesis of ilamycins featuring unusual building blocks and engineered production of enhanced anti-tuberculosis agents.

    Science.gov (United States)

    Ma, Junying; Huang, Hongbo; Xie, Yunchang; Liu, Zhiyong; Zhao, Jin; Zhang, Chunyan; Jia, Yanxi; Zhang, Yun; Zhang, Hua; Zhang, Tianyu; Ju, Jianhua

    2017-08-30

    Tuberculosis remains one of the world's deadliest communicable diseases, novel anti-tuberculosis agents are urgently needed due to severe drug resistance and the co-epidemic of tuberculosis/human immunodeficiency virus. Here, we show the isolation of six anti-mycobacterial ilamycin congeners (1-6) bearing rare L-3-nitro-tyrosine and L-2-amino-4-hexenoic acid structural units from the deep sea-derived Streptomyces atratus SCSIO ZH16. The biosynthesis of the rare L-3-nitrotyrosine and L-2-amino-4-hexenoic acid units as well as three pre-tailoring and two post-tailoring steps are probed in the ilamycin biosynthetic machinery through a series of gene inactivation, precursor chemical complementation, isotope-labeled precursor feeding experiments, as well as structural elucidation of three intermediates (6-8) from the respective mutants. Most impressively, ilamycins E 1 /E 2 , which are produced in high titers by a genetically engineered mutant strain, show very potent anti-tuberculosis activity with an minimum inhibitory concentration value ≈9.8 nM to Mycobacterium tuberculosis H37Rv constituting extremely potent and exciting anti-tuberculosis drug leads.Tuberculosis (TB) remains one of the world's deadliest communicable diseases, novel anti-TB agents are urgently needed due to severe drug resistance and the co-epidemic of TB/HIV. Here, the authors show that anti-mycobacterial ilamycin congeners bearing unusual structural units possess extremely potent anti-tuberculosis activities.

  16. Oleuropein, a non-toxic olive iridoid, is an anti-tumor agent and cytoskeleton disruptor

    International Nuclear Information System (INIS)

    Hamdi, Hamdi K.; Castellon, Raquel

    2005-01-01

    Oleuropein, a non-toxic secoiridoid derived from the olive tree, is a powerful antioxidant and anti-angiogenic agent. Here, we show it to be a potent anti-cancer compound, directly disrupting actin filaments in cells and in a cell-free assay. Oleuropein inhibited the proliferation and migration of advanced-grade tumor cell lines in a dose-responsive manner. In a novel tube-disruption assay, Oleuropein irreversibly rounded cancer cells, preventing their replication, motility, and invasiveness; these effects were reversible in normal cells. When administered orally to mice that developed spontaneous tumors, Oleuropein completely regressed tumors in 9-12 days. When tumors were resected prior to complete regression, they lacked cohesiveness and had a crumbly consistency. No viable cells could be recovered from these tumors. These observations elevate Oleuropein from a non-toxic antioxidant into a potent anti-tumor agent with direct effects against tumor cells. Our data may also explain the cancer-protective effects of the olive-rich Mediterranean diet

  17. Synthesis and exploration of novel curcumin analogues as anti-malarial agents.

    Science.gov (United States)

    Mishra, Satyendra; Karmodiya, Krishanpal; Surolia, Namita; Surolia, Avadhesha

    2008-03-15

    Curcumin, a major yellow pigment and active component of turmeric, has been shown to possess anti-inflammatory and anti-cancer activities. Recent studies have indicated that curcumin inhibits chloroquine-sensitive (CQ-S) and chloroquine-resistant (CQ-R) Plasmodium falciparum growth in culture with an IC(50) of approximately 3.25 microM (MIC=13.2 microM) and IC(50) 4.21 microM (MIC=14.4 microM), respectively. In order to expand their potential as anti-malarials a series of novel curcumin derivatives were synthesized and evaluated for their ability to inhibit P. falciparum growth in culture. Several curcumin analogues examined show more effective inhibition of P. falciparum growth than curcumin. The most potent curcumin compounds 3, 6, and 11 were inhibitory for CQ-S P. falciparum at IC(50) of 0.48, 0.87, 0.92 microM and CQ-R P. falciparum at IC(50) of 0.45 microM, 0.89, 0.75 microM, respectively. Pyrazole analogue of curcumin (3) exhibited sevenfold higher anti-malarial potency against CQ-S and ninefold higher anti-malarial potency against CQ-R. Curcumin analogues described here represent a novel class of highly selective P. falciparum inhibitors and promising candidates for the design of novel anti-malarial agents.

  18. Peripapillary Choroidal Neovascularization Associated with Optic Nerve Head Drusen Treated with Anti-VEGF Agents

    Directory of Open Access Journals (Sweden)

    Norman A. Saffra

    2015-02-01

    Full Text Available Optic nerve head drusen can be associated with peripapillary choroidal neovascularization, in both the pediatric and adult population. These membranes can involve the macula, causing significant visual loss. Herein, we present a case that required treatment with an anti-VEGF agent. The patient failed to respond to the initial agent, but subsequently responded to a change of agent. Adult patients with macular degeneration involving peripapillary choroidal neovascularization associated with optic nerve head drusen may require individualized treatment plans.

  19. Efficacy and safety of combining intra-articular methylprednisolone and anti-TNF agent to achieve prolonged remission in patients with recurrent inflammatory monoarthritis.

    LENUS (Irish Health Repository)

    Haroon, Muhammad

    2012-02-01

    OBJECTIVE: To control local inflammation, the role of intra-articular corticosteroid is well established; similarly, with time there are more reports on the experience of intra-articular anti-TNF agent for localized joint inflammation. The aim of this study was to assess the safety, local tolerability and clinical response after combining intra-articular administration of corticosteroids and anti-TNF agents for recurrent inflammatory monoarthritis. METHODS: Patients with recurrent monoarthritis of the knee were recruited from our inflammatory arthritis clinics. These patients required intra-articular corticosteroids every 8-12 weeks, with good short-term results. Five such consecutive patients were invited to partake in this study. Patients were maintained on their baseline immunosuppressive therapy. After aspiration of knee joint, the involved joint was injected with 80mg of methylprednisolone mixed with 5ml of lignocaine 1%; this was followed by the injection of an anti-TNF agent. RESULTS: In majority of our patients (three out of five), combining anti-TNF agent and methylprednisolone led to prolonged anti-inflammatory response, and these patients remain in remission to date (mean follow-up of 12 months). These responders were noted to be naive to anti-TNF therapy. Conversely, the remaining two patients were found to be on baseline systemic anti-TNF therapy, and both of them failed to respond either partly or completely. CONCLUSION: Combining intra-articular corticosteroid and anti-TNF agent has proved to be safe in our cohort of patients. We conclude that in particular subset of patients who suffer from recurrent inflammatory monoarthritis or oligoarthritis, combination therapy of intra-articular corticosteroids and anti-TNF agents appears attractive and promising.

  20. Surgical choroidal neovascular membrane removal in the era of anti-vascular endothelial growth factor agents

    Directory of Open Access Journals (Sweden)

    Nagpal Manish

    2009-01-01

    Full Text Available Intravitreal anti-vascular endothelial growth factor (VEGF agents have obtained acceptance as the mainstay in the management strategy of subfoveal choroidal neovascular membranes (CNVM due to varying etiologies. Few drawbacks include need for repeated intravitreal injections, with its adjunct risks, and the lack of a predefined treatment end point, which can cause doubts and uncertainty in the mind of the patient. Furthermore, it remains a significant financial burden for the patient. Herein we report our data of three patients who were reluctant for further re-injections of anti-VEGF agents and were therefore offered surgical removal of the CNVM by submacular surgery as an alternative treatment plan.

  1. Biotechnical paving of recombinant enterocin A as the candidate of anti-Listeria agent.

    Science.gov (United States)

    Hu, Xiaoyuan; Mao, Ruoyu; Zhang, Yong; Teng, Da; Wang, Xiumin; Xi, Di; Huang, Jianzhong; Wang, Jianhua

    2014-08-28

    Enterocin A is a classic IIa bacteriocin isolated firstly from Enterococcus faecium CTC492 with selective antimicrobial activity against Listeria strains. However, the application of enterocin A as an anti-Listeria agent has been limited due to its very low native yield. The present work describes high production of enterocin A through codon optimization strategy and its character study. The gene sequence of enterocin A was optimized based on preferential codon usage in Pichia pastoris to increase its expression efficiency. The highest anti-Listeria activity reached 51,200 AU/ml from 180 mg/l of total protein after 24 h of induction in a 5-L fermenter. Recombinant enterocin A (rEntA), purified by gel filtration chromatography, showed very strong activity against Listeria ivanovii ATCC 19119 with a low MIC of 20 ng/ml. In addition, the rEntA killed over 99% of tested L. ivanovii ATCC19119 within 4 h when exposed to 4 × MIC (80 ng/ml). Moreover, it showed high stability under a wide pH range (2-10) and maintained full activity after 1 h of treatment at 80°C within a pH range of 2-8. Its antimicrobial activity was enhanced at 25 and 50 mM NaCl, while 100-400 mM NaCl had little effect on the bactericidal ability of rEntA. The EntA was successfully expressed in P. pastoris, and this feasible system could pave the pre-industrial technological path of rEntA as a competent candidate as an anti-Listeria agent. Furthermore, it showed high stability under wide ranges of conditions, which could be potential as the new candidate of anti-Listeria agent.

  2. Benzimidazole derivatives: search for GI-friendly anti-inflammatory analgesic agents

    Directory of Open Access Journals (Sweden)

    Monika Gaba

    2015-07-01

    Full Text Available Non-steroidal anti-inflammatory drugs (NSAIDs have been successfully used for the alleviation of pain and inflammation in the past and continue to be used daily by millions of patients worldwide. However, gastrointestinal (GI toxicity associated with NSAIDs is an important medical and socioeconomic problem. Local generation of various reactive oxygen species plays a significant role in the formation of gastric ulceration associated with NSAIDs therapy. Co-medication of antioxidants along with NSAIDs has been found to be beneficial in the prevention of GI injury. This paper describes the synthesis and biological evaluation of N-1-(phenylsulfonyl-2-methylamino-substituted-1H-benzimidazole derivatives as anti-inflammatory analgesic agents with lower GI toxicity. Studies in vitro and in vivo demonstrated that the antioxidant activity of the test compounds decreased GI toxicity.

  3. Risk of Lymphoma in Patients With Inflammatory Bowel Disease Treated With Anti-Tumor Necrosis Factor Alpha Agents: A Systematic Review and Meta-analysis.

    Science.gov (United States)

    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.

  4. Pre-operative use of anti-TNF-α agents and the risk of post-operative complications in patients with ulcerative colitis - a nationwide cohort study

    DEFF Research Database (Denmark)

    Nørgård, B M; Nielsen, J; Qvist, N

    2012-01-01

    It is still controversial whether pre-operative anti-tumour necrosis factor-alpha (anti-TNF-α) agents increase post-operative complications in patients with ulcerative colitis (UC).......It is still controversial whether pre-operative anti-tumour necrosis factor-alpha (anti-TNF-α) agents increase post-operative complications in patients with ulcerative colitis (UC)....

  5. Duloxetine versus other anti-depressive agents for depression

    Science.gov (United States)

    Cipriani, Andrea; Koesters, Markus; Furukawa, Toshi A; Nosè, Michela; Purgato, Marianna; Omori, Ichiro M; Trespidi, Carlotta; Barbui, Corrado

    2014-01-01

    Background Although pharmacological and psychological interventions are both effective for major depression, in primary and secondary care settings antidepressant drugs remain the mainstay of treatment. Amongst antidepressants many different agents are available. Duloxetine hydrochloride is a dual reuptake inhibitor of serotonin and norepinephrine and has been licensed by the Food and Drug Administration in the US for major depressive disorder (MDD), generalised anxiety disorder, diabetic peripheral neuropathic pain, fibromyalgia and chronic musculoskeletal pain. Objectives To assess the evidence for the efficacy, acceptability and tolerability of duloxetine in comparison with all other antidepressant agents in the acute-phase treatment of major depression. Search methods MEDLINE (1966 to 2012), EMBASE (1974 to 2012), the Cochrane Collaboration Depression, Anxiety and Neurosis Controlled Trials Register and the Cochrane Central Register of Controlled Trials up to March 2012. No language restriction was applied. Reference lists of relevant papers and previous systematic reviews were hand-searched. Pharmaceutical company marketing duloxetine and experts in this field were contacted for supplemental data. Selection criteria Randomised controlled trials allocating patients with major depression to duloxetine versus any other antidepressive agent. Data collection and analysis Two review authors independently extracted data and a double-entry procedure was employed. Information extracted included study characteristics, participant characteristics, intervention details and outcome measures in terms of efficacy, acceptability and tolerability. Main results A total of 16 randomised controlled trials (overall 5735 participants) were included in this systematic review. Of these, three trials were unpublished. We found 11 studies (overall 3304 participants) comparing duloxetine with one selective serotonin reuptake inhibitor (SSRI) (six studies versus paroxetine, three studies

  6. Intra-antral application of an anti-fungal agent for recurrent maxillary fungal rhinosinusitis: a case report

    Directory of Open Access Journals (Sweden)

    Dunmade Adekunle D

    2012-08-01

    Full Text Available Abstract Introduction Fungal infection of the paranasal sinuses is an increasingly recognized entity both in immunocompetent and immunocompromised individuals. Treatment has been via use of either surgical or medical modalities, or a combination of the two. Here, we present a case of utilization of intra-antral application of an anti-fungal agent in the management of recurrent fungal sinusitis in an indigent Nigerian patient. Case presentation We present the case of a 30-year-old West African Yoruba man, an indigent Nigerian clergyman, who presented to our facility with a history of recurrent nasal discharge (about one year, recurrent nasal blockage (about five months, and right facial swelling (about one week. After intra-nasal antrostomy for debulking with a systemic anti-fungal agent, our patient had a recurrence after four months. Our patient subsequently had an intra-antral application of flumetasone and clioquinol (Locacorten®-Vioform® weekly for six weeks with improvement of symptoms and no recurrence after six months of follow-up. Conclusions We conclude that topical intra-antral application of anti-fungal agents is effective in patients with recurrent fungal maxillary sinusitis after surgical debulking.

  7. Fabric tensile strength as affected by different anti pilling agents at various concentration and ph levels

    International Nuclear Information System (INIS)

    Tusief, M.Q.; Mahmood, N.; Saleem, M.

    2013-01-01

    Pilling is a phenomenon that has a long cause trouble in textile industry. It is the formation of pills or knops on the surface of woven or knitted fabrics caused by friction and abrasion. If fabric has a pronounced tendency to pilling, their appearances suffer severely after a short period of use. The pilling of fabrics is a serious problem for the apparel industry. The use of anti pilling finishes is one of the best techniques to control the pilling of the fabric. In this method fabric is treated with special anti pilling agents to prevent pilling that promote adhesion of the fibres in the yarn or the fabric. This paper endeavors to optimize the application of different anti pilling agents at different concentration and pH levels on the Tensile Strength of P/C fabric for best results. The results exposed that different anti pilling finishes have significant effects on the Tensile Strength of fabric at different concentration level however different pH levels have no considerable effects. (author)

  8. PS3-18: Use of Antidepressant and Anti-Anxiety Medications Among Breast Cancer Survivors in a HMO

    Science.gov (United States)

    Avila, Chantal; Haque, Reina; Quinn, Virginia; Schottinger, Joanne; Fisher, Alice

    2010-01-01

    Background: Almost 200,000 U.S. women are diagnosed each year with breast cancer and over 40,000 women will die of the disease. In addition to the medical and functional consequences of the diagnosis and treatment, women experience worry, persistent anxiety, fear and depressive disorders. Overall, 30% of women diagnosed with breast cancer suffer significant distress at some point in their illness trajectory. National health organizations including the Institute of Medicine and National Cancer Institute call for treatment of common symptoms among breast cancer patients such as depression and anxiety. To date, there are only limited reports on the prevalence of treatment, and even fewer studies have examined potential differences by race/ethnicity, age, or tumor characteristics. Aim: To describe the prevalence of pharmacotherapy for depressive symptoms/anxiety among patients diagnosed with breast cancer in a large HMO. Methods: We identified all women diagnosed with primary breast cancer between 2000–2006 (n=10,408) who had been members of Kaiser Permanente Southern California (KPSC) for 1+ years prior to diagnosis. KPSC is a nonprofit comprehensive prepaid health plan serving 3.2 million socioeconomically diverse members. Data was obtained from the KPSC SEER-affiliated cancer registry and automated clinical, pharmacy, and membership databases. We examined patient and tumor characteristics associated with new use of pharmacotherapy for depression/anxiety. Univariate odds ratios (OR) and 95% confidence intervals (CI) were estimated using logistic regression. Results: We found 35% of women (3,611 of 10,408) were newly prescribed either anti-depressant or anti-anxiety medications within a year of breast cancer diagnosis. Younger women (e.g., OR=1.44, CI=1.28–1.63 for 40–49 year olds v. 60–69) and women with higher stage (e.g., OR=3.40, CI=2.87–4.04 for Stage 3 v. Stage 0) were more likely to be prescribed these medications, while African-American (OR=0.81, CI

  9. Harnessing the potential clinical use of medicinal plants as anti-diabetic agents

    Directory of Open Access Journals (Sweden)

    Campbell-Tofte JI

    2012-08-01

    Full Text Available Joan IA Campbell-Tofte,1 Per Mølgaard,2 Kaj Winther11Department of Clinical Biochemistry, Frederiksberg University Hospital, Frederiksberg, Denmark; 2Department of Medicinal Chemistry, Faculty of Pharmaceutical Sciences, University of Copenhagen, Copenhagen, DenmarkAbstract: Diabetes is a metabolic disorder arising from complex interactions between multiple genetic and/or environmental factors. The characteristic high blood sugar levels result from either lack of the hormone insulin (type 1 diabetes, T1D, or because body tissues do not respond to the hormone (type 2 diabetes, T2D. T1D patients currently need exogenous insulin for life, while for T2D patients who do not respond to diet and exercise regimes, oral anti-diabetic drugs (OADs and sometimes insulin are administered to help keep their blood glucose as normal as possible. As neither the administration of insulin nor OADs is curative, many patients develop tissue degenerative processes that result in life-threatening diabetes comorbidities. Several surveys of medicinal plants used as anti-diabetic agents amongst different peoples have been published. Some of this interest is driven by the ongoing diabetes pandemic coupled with the inadequacies associated with the current state of-the-art care and management of the syndrome. However, there is a huge cleft between traditional medicine and modern (Western medicine, with the latter understandably demanding meaningful and scientific validation of anecdotal evidence for acceptance of the former. The main problems for clinical evaluation of medicinal plants with promising anti-diabetic properties reside both with the complexity of components of the plant materials and with the lack of full understanding of the diabetes disease etiology. This review is therefore focused on why research activities involving an integration of Systems Biology-based technologies of pharmacogenomics, metabolomics, and bioinformatics with standard clinical data

  10. Infections and exposure to anti-infective agents and the risk of severe mental disorders

    DEFF Research Database (Denmark)

    Köhler, Ole; Petersen, Liselotte; Mors, O

    2017-01-01

    OBJECTIVE: Severe infections are associated with increased risks of mental disorders; however, this is the first large-scale study investigating whether infections treated with anti-infective agents in the primary care setting increase the risks of schizophrenia and affective disorders. METHOD: We...

  11. Intravenous Versus Subcutaneous Anti-TNF-Alpha Agents for Crohn's Disease: A Comparison of Effectiveness and Safety.

    Science.gov (United States)

    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

  12. Radiation proctitis in the rat. Sequential changes and effects of anti-inflammatory agents

    Energy Technology Data Exchange (ETDEWEB)

    Northway, M.G.; Scobey, M.W.; Geisinger, K.R.

    1988-11-01

    Female Wistar rats were treated with single exposure irradiation to 2 cm of distal colon to cause radiation proctitis. All animals were evaluated by examination, colonoscopy and histologic evaluation for changes post-irradiation. Exposures of 10, 12.5, 15, 17.5, 20, 22.5, 25, 27.5 and 30 Gy caused dose-related clinical and histologic changes peaking at 7 to 15 days post-exposure. Rats treated with 20 Gy were colonoscoped and biopsied daily and showed sequential post-irradiation endoscopic changes ranging from mucosal edema and mild inflammatory changes to erosion and ulcers. Histologically, crypt abscess and mural wall necrosis similar to changes found in the human rectum after radiotherapy were noted. Treatment with nonsteroidal anti-inflammatory agents, (aspirin, indomethacin, piroxicam), misoprostol (a prostaglandin E1 analogue), or sucralfate (an anti-ulcer agent) did not ameliorate nor exacerbate radiation proctitis in rats exposed to 22.5 Gy. We conclude from these data that the female Wistar rat is a good model for studying radiation proctitis because endoscopic, histologic, and clinical changes seen post-exposure closely resemble those found in man.

  13. Radiation proctitis in the rat. Sequential changes and effects of anti-inflammatory agents

    International Nuclear Information System (INIS)

    Northway, M.G.; Scobey, M.W.; Geisinger, K.R.

    1988-01-01

    Female Wistar rats were treated with single exposure irradiation to 2 cm of distal colon to cause radiation proctitis. All animals were evaluated by examination, colonoscopy and histologic evaluation for changes post-irradiation. Exposures of 10, 12.5, 15, 17.5, 20, 22.5, 25, 27.5 and 30 Gy caused dose-related clinical and histologic changes peaking at 7 to 15 days post-exposure. Rats treated with 20 Gy were colonoscoped and biopsied daily and showed sequential post-irradiation endoscopic changes ranging from mucosal edema and mild inflammatory changes to erosion and ulcers. Histologically, crypt abscess and mural wall necrosis similar to changes found in the human rectum after radiotherapy were noted. Treatment with nonsteroidal anti-inflammatory agents, (aspirin, indomethacin, piroxicam), misoprostol (a prostaglandin E1 analogue), or sucralfate (an anti-ulcer agent) did not ameliorate nor exacerbate radiation proctitis in rats exposed to 22.5 Gy. We conclude from these data that the female Wistar rat is a good model for studying radiation proctitis because endoscopic, histologic, and clinical changes seen post-exposure closely resemble those found in man

  14. Visualization of Tumor Angiogenesis Using MR Imaging Contrast Agent Gd-DTPA-anti-VEGF Receptor 2 Antibody Conjugate in a Mouse Tumor Model

    International Nuclear Information System (INIS)

    Jun, Hong Young; Yin, Hong Hua; Kim, Sun Hee; Park, Seong Hoon; Kim, Hun Soo; Yoon Kwon Ha Yoon

    2010-01-01

    To visualize tumor angiogenesis using the MRI contrast agent, Gd- DTPA-anti-VEGF receptor 2 antibody conjugate, with a 4.7-Tesla MRI instrument in a mouse model. We designed a tumor angiogenesis-targeting T1 contrast agent that was prepared by the bioconjugation of gadolinium diethylenetriaminepentaacetic acid (Gd-DTPA) and an anti-vascular endothelial growth factor receptor-2 (VEGFR2) antibody. The specific binding of the agent complex to cells that express VEGFR2 was examined in cultured murine endothelial cells (MS-1 cells) with a 4.7-Tesla magnetic resonance imaging scanner. Angiogenesis-specific T1 enhancement was imaged with the Gd-DTPA-anti-VEGFR2 antibody conjugate using a CT-26 adenocarcinoma tumor model in eight mice. As a control, the use of the Gd-DTPA-anti-rat immunoglobulin G (Gd-DTPA-anti-rat IgG) was imaged with a tumor model in eight mice. Statistical significance was assessed using the Mann-Whitney test. Tumor tissue was examined by immunohistochemical analysis. The Gd-DTPA-anti-VEGFR2 antibody conjugate showed predominant binding to cultured endothelial cells that expressed a high level of VEGFR2. Signal enhancement was approximately three-fold for in vivo T1-weighted MR imaging with the use of the Gd-DTPA-anti-VEGFR2 antibody conjugate as compared with the Gd-DTPA-rat IgG in the mouse tumor model (p < 0.05). VEGFR2 expression in CT-26 tumor vessels was demonstrated using immunohistochemical staining. MR imaging using the Gd-DTPA-anti-VEGFR2 antibody conjugate as a contrast agent is useful in visualizing noninvasively tumor angiogenesis in a murine tumor model

  15. Visualization of Tumor Angiogenesis Using MR Imaging Contrast Agent Gd-DTPA-anti-VEGF Receptor 2 Antibody Conjugate in a Mouse Tumor Model

    Energy Technology Data Exchange (ETDEWEB)

    Jun, Hong Young; Yin, Hong Hua; Kim, Sun Hee; Park, Seong Hoon; Kim, Hun Soo; Yoon Kwon Ha Yoon [Wonkwang University School of Medicine, Iksan (Korea, Republic of)

    2010-08-15

    To visualize tumor angiogenesis using the MRI contrast agent, Gd- DTPA-anti-VEGF receptor 2 antibody conjugate, with a 4.7-Tesla MRI instrument in a mouse model. We designed a tumor angiogenesis-targeting T1 contrast agent that was prepared by the bioconjugation of gadolinium diethylenetriaminepentaacetic acid (Gd-DTPA) and an anti-vascular endothelial growth factor receptor-2 (VEGFR2) antibody. The specific binding of the agent complex to cells that express VEGFR2 was examined in cultured murine endothelial cells (MS-1 cells) with a 4.7-Tesla magnetic resonance imaging scanner. Angiogenesis-specific T1 enhancement was imaged with the Gd-DTPA-anti-VEGFR2 antibody conjugate using a CT-26 adenocarcinoma tumor model in eight mice. As a control, the use of the Gd-DTPA-anti-rat immunoglobulin G (Gd-DTPA-anti-rat IgG) was imaged with a tumor model in eight mice. Statistical significance was assessed using the Mann-Whitney test. Tumor tissue was examined by immunohistochemical analysis. The Gd-DTPA-anti-VEGFR2 antibody conjugate showed predominant binding to cultured endothelial cells that expressed a high level of VEGFR2. Signal enhancement was approximately three-fold for in vivo T1-weighted MR imaging with the use of the Gd-DTPA-anti-VEGFR2 antibody conjugate as compared with the Gd-DTPA-rat IgG in the mouse tumor model (p < 0.05). VEGFR2 expression in CT-26 tumor vessels was demonstrated using immunohistochemical staining. MR imaging using the Gd-DTPA-anti-VEGFR2 antibody conjugate as a contrast agent is useful in visualizing noninvasively tumor angiogenesis in a murine tumor model

  16. Comparison of anxiety between smokers and nonsmokers with acute myocardial infarction.

    Science.gov (United States)

    Sheahan, Sharon L; Rayens, Mary K; An, Kyungeh; Riegel, Barbara; McKinley, Sharon; Doering, Lynn; Garvin, Bonnie J; Moser, Debra K

    2006-11-01

    Increased anxiety correlates with increased complications after acute myocardial infarction. Anxiety levels and use of anxiolytic agents have not been compared between smokers and nonsmokers hospitalized because of acute myocardial infarction. To compare anxiety level, sociodemographic factors, and clinical variables between smokers and nonsmokers hospitalized with acute myocardial infarction and to examine predictors of use of beta-blockers and anxiolytic agents among smokers and nonsmokers. Secondary data analysis of a prospective multisite study on anxiety in 181 smokers and 351 nonsmokers with acute myocardial infarction. Anxiety was measured by using the State Trait Anxiety Inventory and the anxiety subscale of the Basic Symptom Inventory within 72 hours of admission. Smokers reported higher anxiety levels than nonsmokers reported on both anxiety scales. Female smokers reported the highest anxiety and peak pain levels of all, yet women were the least likely to receive anxiolytic agents. Smoking status was not a predictor for anxiety level when sex, peak pain, use of beta-blockers in the hospital, and age were controlled for. However, smokers were twice as likely as nonsmokers to receive an anxiolytic agent and 60% more likely to receive a beta-blocker in the emergency department, and smokers were 80% more likely than nonsmokers to receive an anxiolytic agent during hospitalization when these variables were controlled. Older female smokers are at risk for complications because they are older than their male counterparts and less likely to receive beta-blockers and antianxiety medications in the emergency department.

  17. Protective effects of phosphodiesterase 2 inhibitor on depression- and anxiety-like behaviors: involvement of antioxidant and anti-apoptotic mechanisms.

    Science.gov (United States)

    Ding, Lianshu; Zhang, Chong; Masood, Anbrin; Li, Jianxin; Sun, Jiao; Nadeem, Ahmed; Zhang, Han-Ting; O' Donnell, James M; Xu, Ying

    2014-07-15

    Stress occurs in everyday life, but the relationship between stress and the onset or development of depression/anxiety remains unknown. Increasing evidence suggests that the impairment of antioxidant defense and the neuronal cell death are important in the process of emotional disorders. Chronic stress impairs the homeostasis of antioxidants/oxidation, which results in the aberrant stimulation of the cell cycle proteins where cGMP-PKG signaling is thought to have an inhibitory role. Phosphodiesterase 2 (PDE2) is linked to cGMP-PKG signaling and highly expressed in the limbic brain regions including hippocampus and amygdala, which may play important roles in the treatment of depression and anxiety. To address the possible effects of PDE2 inhibitors on depression-/anxiety-like behaviors and the underlying mechanisms, Bay 60-7550 (0.75, 1.5 and 3 mg/kg, i.p.) was administered 30 min before chronic stress. The results suggested that Bay 60-7550 not only restored the behavioral changes but also regulated Cu/Zn superoxide dismutase (SOD) levels differentially in hippocampus and amygdala, which were increased in the hippocampus while decreased in the amygdala. It was also significant that Bay 60-7550 regulated the abnormalities of pro- and anti-apoptotic components, such as Bax, Caspase 3 and Bcl-2, and the indicator of PKG signaling characterized by pVASP(ser239), in these two brain regions. The results suggested that Bay 60-7550 is able to alleviate oxidative stress and mediate part of the apoptotic machinery in neuronal cells possibly through SOD-cGMP/PKG-anti-apoptosis signaling and that inhibition of PDE2 may represent a novel therapeutic target for psychiatric disorders, such as depression and anxiety. Copyright © 2014 Elsevier B.V. All rights reserved.

  18. Potential Use of Phenolic Acids as Anti-Candida Agents: A Review

    Science.gov (United States)

    Teodoro, Guilherme R.; Ellepola, Kassapa; Seneviratne, Chaminda J.; Koga-Ito, Cristiane Y.

    2015-01-01

    There has been a sharp rise in the occurrence of Candida infections and associated mortality over the last few years, due to the growing body of immunocompromised population. Limited number of currently available antifungal agents, undesirable side effects and toxicity, as well as emergence of resistant strains pose a considerable clinical challenge for the treatment of candidiasis. Therefore, molecules that derived from natural sources exhibiting considerable antifungal properties are a promising source for the development of novel anti-candidal therapy. Phenolic compounds isolated from natural sources possess antifungal properties of interest. Particularly, phenolic acids have shown promising in vitro and in vivo activity against Candida species. However, studies on their mechanism of action alone or in synergism with known antifungals are still scarce. This review attempts to discuss the potential use, proposed mechanisms of action and limitations of the phenolic acids in anti-candidal therapy. PMID:26733965

  19. Synthesis and Biological Evaluation of Novel Furozan-Based Nitric Oxide-Releasing Derivatives of Oridonin as Potential Anti-Tumor Agents

    Directory of Open Access Journals (Sweden)

    Hao Cai

    2012-06-01

    Full Text Available To search for novel nitric oxide (NO releasing anti-tumor agents, a series of novel furoxan/oridonin hybrids were designed and synthesized. Firstly, the nitrate/nitrite levels in the cell lysates were tested by a Griess assay and the results showed that these furoxan-based NO-releasing derivatives could produce high levels of NO in vitro. Then the anti-proliferative activity of these hybrids against four human cancer cell lines was also determined, among which, 9h exhibited the most potential anti-tumor activity with IC50 values of 1.82 µM against K562, 1.81 µM against MGC-803 and 0.86 µM against Bel-7402, respectively. Preliminary structure-activity relationship was concluded based on the experimental data obtained. These results suggested that NO-donor/natural product hybrids may provide a promising approach for the discovery of novel anti-tumor agents.

  20. 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

    DEFF Research Database (Denmark)

    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...

  1. Synthesis of mutual azo prodrugs of anti-inflammatory agents and peptides facilitated by α-aminoisobutyric acid.

    Science.gov (United States)

    Kennedy, David A; Vembu, Nagarajan; Fronczek, Frank R; Devocelle, Marc

    2011-12-02

    Reported is the synthesis of azo mutual prodrugs of the nonsteroidal anti-inflammatory agents (NSAIDs) 4-aminophenylacetic acid (4-APAA) or 5-aminosalicylic acid (5-ASA) with peptides, including an antibiotic peptide temporin analogue modified at the amino terminal by an α-aminoisobutyric acid (Aib) residue. These prodrugs are designed for colonic delivery of two agents to treat infection and inflammation by the bacterial pathogen Clostridium difficile . © 2011 American Chemical Society

  2. Screening of chemical compound libraries identified new anti-Toxoplasma gondii agents.

    Science.gov (United States)

    Adeyemi, Oluyomi Stephen; Sugi, Tatsuki; Han, Yongmei; Kato, Kentaro

    2018-02-01

    Toxoplasma gondii is the etiological agent of toxoplasmosis, a common parasitic disease that affects nearly one-third of the human population. The primary infection can be asymptomatic in healthy individuals but may prove fatal in immunocompromised individuals. Available treatment options for toxoplasmosis patients are limited, underscoring the urgent need to identify and develop new therapies. Non-biased screening of libraries of chemical compounds including the repurposing of well-characterized compounds is emerging as viable approach to achieving this goal. In the present investigation, we screened libraries of natural product and FDA-approved compounds to identify those that inhibited T. gondii growth. We identified 32 new compounds that potently inhibit T. gondii growth. Our findings are new and promising, and further strengthen the prospects of drug repurposing as well as the screening of a wide range of chemical compounds as a viable source of alternative anti-parasitic therapeutic agents.

  3. Secapin, a bee venom peptide, exhibits anti-fibrinolytic, anti-elastolytic, and anti-microbial activities.

    Science.gov (United States)

    Lee, Kwang Sik; Kim, Bo Yeon; Yoon, Hyung Joo; Choi, Yong Soo; Jin, Byung Rae

    2016-10-01

    Bee venom contains a variety of peptide constituents that have various biological, toxicological, and pharmacological actions. However, the biological actions of secapin, a venom peptide in bee venom, remain largely unknown. Here, we provide the evidence that Asiatic honeybee (Apis cerana) secapin (AcSecapin-1) exhibits anti-fibrinolytic, anti-elastolytic, and anti-microbial activities. The recombinant mature AcSecapin-1 peptide was expressed in baculovirus-infected insect cells. AcSecapin-1 functions as a serine protease inhibitor-like peptide that has inhibitory effects against plasmin, elastases, microbial serine proteases, trypsin, and chymotrypsin. Consistent with these functions, AcSecapin-1 inhibited the plasmin-mediated degradation of fibrin to fibrin degradation products, thus indicating the role of AcSecapin-1 as an anti-fibrinolytic agent. AcSecapin-1 also inhibited both human neutrophil and porcine pancreatic elastases. Furthermore, AcSecapin-1 bound to bacterial and fungal surfaces and exhibited anti-microbial activity against fungi and gram-positive and gram-negative bacteria. Taken together, our data demonstrated that the bee venom peptide secapin has multifunctional roles as an anti-fibrinolytic agent during fibrinolysis and an anti-microbial agent in the innate immune response. Copyright © 2016 Elsevier Ltd. All rights reserved.

  4. GTP depletion synergizes the anti-proliferative activity of chemotherapeutic agents in a cell type-dependent manner

    International Nuclear Information System (INIS)

    Lin, Tao; Meng, Lingjun; Tsai, Robert Y.L.

    2011-01-01

    Highlights: → Strong synergy between mycophenolic acid (MPA) and 5-FU in MDA-MB-231 cells. → Cell type-dependent synergy between MPA and anti-proliferative agents. → The synergy of MPA on 5-FU is recapitulated by RNA polymerase-I inhibition. → The synergy of MPA on 5-FU requires the expression of nucleostemin. -- Abstract: Mycophenolic acid (MPA) depletes intracellular GTP by blocking de novo guanine nucleotide synthesis. GTP is used ubiquitously for DNA/RNA synthesis and as a signaling molecule. Here, we made a surprising discovery that the anti-proliferative activity of MPA acts synergistically with specific chemotherapeutic agents in a cell type-dependent manner. In MDA-MB-231 cells, MPA shows an extremely potent synergy with 5-FU but not with doxorubicin or etoposide. The synergy between 5-FU and MPA works most effectively against the highly tumorigenic mammary tumor cells compared to the less tumorigenic ones, and does not work in the non-breast cancer cell types that we tested, with the exception of PC3 cells. On the contrary, MPA shows the highest synergy with paclitaxel but not with 5-FU in SCC-25 cells, derived from oral squamous cell carcinomas. Mechanistically, the synergistic effect of MPA on 5-FU in MDA-MB-231 cells can be recapitulated by inhibiting the RNA polymerase-I activity and requires the expression of nucleostemin. This work reveals that the synergy between MPA and anti-proliferative agents is determined by cell type-dependent factors.

  5. Development and Sequential Analysis of a New Multi-Agent, Anti-Acne Formulation Based on Plant-Derived Antimicrobial and Anti-Inflammatory Compounds

    Directory of Open Access Journals (Sweden)

    Crina Saviuc

    2017-01-01

    Full Text Available The antibacterial and anti-inflammatory potential of natural, plant-derived compounds has been reported in many studies. Emerging evidence indicates that plant-derived essential oils and/or their major compounds may represent a plausible alternative treatment for acne, a prevalent skin disorder in both adolescent and adult populations. Therefore, the purpose of this study was to develop and subsequently analyze the antimicrobial activity of a new multi-agent, synergic formulation based on plant-derived antimicrobial compounds (i.e., eugenol, β-pinene, eucalyptol, and limonene and anti-inflammatory agents for potential use in the topical treatment of acne and other skin infections. The optimal antimicrobial combinations selected in this study were eugenol/β-pinene/salicylic acid and eugenol/β-pinene/2-phenoxyethanol/potassium sorbate. The possible mechanisms of action revealed by flow cytometry were cellular permeabilization and inhibition of efflux pumps activity induced by concentrations corresponding to sub-minimal inhibitory (sub-MIC values. The most active antimicrobial combination represented by salycilic acid/eugenol/β-pinene/2-phenoxyethanol/potassium sorbate was included in a cream base, which demonstrated thermodynamic stability and optimum microbiological characteristics.

  6. Ristocetin induces phosphorylated-HSP27 (HSPB1) release from the platelets of type 2 DM patients: Anti-platelet agent-effect on the release.

    Science.gov (United States)

    Tokuda, Haruhiko; Kuroyanagi, Gen; Onuma, Takashi; Enomoto, Yukiko; Doi, Tomoaki; Iida, Hiroki; Otsuka, Takanobu; Ogura, Shinji; Iwama, Toru; Kojima, Kumi; Kozawa, Osamu

    2018-04-01

    It has been previously reported that HSP27 is released from platelets in type 2 diabetes mellitus (DM) patients according to phosphorylation. In the present study, we investigated the effect of ristocetin, a glycoprotein (GP)Ib/IX/V activator, on the release of HSP27 and the effect of anti-platelet agents, such as acetylsalicylic acid (ASA), on this release. Forty-six patients with type 2 DM were recruited, and classified into two groups depending on administration of anti-platelet agents, resulting in 31 patients without these agents (control group) and 15 patients with them (anti-platelet group). Ristocetin potently induced the aggregation of platelets in the two groups. Ristocetin-induced changes of the area under the curve of light transmittance and the ratio of the size of platelet aggregates in the anti-platelet group were slightly different from those in the control group. On the other hand, the levels of phosphorylated-HSP27 induced by ristocetin in the platelets from a patient of the anti-platelet group taking ASA were significantly lower than those from a patient of the control group. The levels of HSP27 release from the ristocetin-stimulated platelets were significantly correlated with the levels of phosphorylated-HSP27 in the platelets from patients in the two groups. The levels of HSP27 release and those of platelet-derived growth factor-AB (PDGF-AB) secretion stimulated by ristocetin in the anti-platelet group were lower than those in the control group. In addition, the levels of HSP27 release and those of PDGF-AB secretion stimulated by ADP in the anti-platelet group were lower than those in the control group. These results strongly suggest that anti-platelet agents inhibit the HSP27 release from platelets stimulated by ristocetin but not the aggregation in type 2 DM patients.

  7. Increased risk of post-operative complications in patients with Crohn's disease treated with anti-tumour necrosis factor α agents - a systematic review

    DEFF Research Database (Denmark)

    El-Hussuna, Alaa; Theede, Klaus; Olaison, Gunnar

    2014-01-01

    INTRODUCTION: Tumour necrosis factor α (TNF-α) plays a role in the immune defence, angiogenesis and collagen synthesis. Inhibition of these pathways may increase the risk of infections and impair wound healing in patients after surgery. Biologic treatments including anti-TNF-α agents are increasi......INTRODUCTION: Tumour necrosis factor α (TNF-α) plays a role in the immune defence, angiogenesis and collagen synthesis. Inhibition of these pathways may increase the risk of infections and impair wound healing in patients after surgery. Biologic treatments including anti-TNF-α agents...... are increasingly used in the treatment of inflammatory bowel disease. Taking into consideration the biologics' mechanism of action, fears have been expressed that they might increase the rate of post-operative complications. Results from 18 retrospective studies were conflicting, and meta-analyses based...... an increased risk of overall post-operative complications and an increased rate of infectious or anastomosis-related complications in patients receiving anti-TNF-α. CONCLUSION: The use of anti-TNF-α agents in Crohn's disease patients is associated with an increased risk of post-operative complications after...

  8. Polyphenols from Cymbopogon citratus leaves as topical anti-inflammatory agents.

    Science.gov (United States)

    Costa, Gustavo; Ferreira, João Pinto; Vitorino, Carla; Pina, Maria Eugénia; Sousa, João José; Figueiredo, Isabel Vitória; Batista, Maria Teresa

    2016-02-03

    A variety of plant polyphenols have been reported to have anti-inflammatory, frequently associated with erythema, edema, hyperplasia, skin photoaging and photocarcinogenesis. Cymbopogon citratus (DC). Stapf (Poaceae) is a worldwide known medicinal plant, used in traditional medicine in inflammation-related conditions. In this work, the anti-inflammatory potential of C. citratus infusion (CcI) and its polyphenols as topical agents was evaluated in vivo. The plant extract was prepared and its fractioning led two polyphenol-rich fractions: flavonoids fraction (CcF) and tannins fraction (CcT). An oil/water emulsion was developed with each active (CcI, CcF+CcT and diclofenac), pH and texture having been evaluated. Release tests were further performed using static Franz diffusion cells and all collected samples were monitored by HPLC-PDA. In vivo topical anti-inflammatory activity evaluation was performed by the carrageenan-induced rat paw edema model. The texture analysis revealed statistically significant differences for all tested parameters to CcF+CcT, supporting its topical application. Release experiments lead to the detection of the phenolic compounds from each sample in the receptor medium and the six major flavonoids were quantified, by HPLC-PDA: carlinoside, isoorientin, cynaroside, luteolin 7-O-neohesperidoside, kurilesin A and cassiaoccidentalin B. The CcF+CcT formulation prompted to the higher release rate for all these flavonoids. CcI4%, CcI1% and CcF+CcT exhibited an edema reduction of 43.18, 29.55 and 59.09%, respectively. Our findings highlight that CcI, containing luteolin 7-O-neohesperidoside, cassiaoccidentalin B, carlinoside, cynaroside and tannins have a potential anti-inflammatory topical activity, suggesting their promising application in the treatment of skin inflammatory pathologies. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  9. Synthesis and Characterization of Celecoxib Derivatives as Possible Anti-Inflammatory, Analgesic, Antioxidant, Anticancer and Anti-HCV Agents

    Directory of Open Access Journals (Sweden)

    Amartya Basu

    2013-03-01

    Full Text Available A series of novel N-(3-substituted aryl/alkyl-4-oxo-1,3-thiazolidin-2-ylidene-4-[5-(4-methylphenyl-3-(trifluoromethyl-1H-pyrazol-1-yl]benzenesulfonamides 2a–e were synthesized by the addition of ethyl a-bromoacetate and anhydrous sodium acetate in dry ethanol to N-(substituted aryl/alkylcarbamothioyl-4-[5-(4-methylphenyl-3-(trifluoro-methyl-1H-pyrazol-1-yl]benzene sulfonamides 1a–e, which were synthesized by the reaction of alkyl/aryl isothiocyanates with celecoxib. The structures of the isolated products were determined by spectral methods and their anti-inflammatory, analgesic, antioxidant, anticancer and anti-HCV NS5B RNA-dependent RNA polymerase (RdRp activities evaluated. The compounds were also tested for gastric toxicity and selected compound 1a was screened for its anticancer activity against 60 human tumor cell lines. These investigations revealed that compound 1a exhibited anti-inflammatory and analgesic activities and further did not cause tissue damage in liver, kidney, colon and brain compared to untreated controls or celecoxib. Compounds 1c and 1d displayed modest inhibition of HCV NS5B RdRp activity. In conclusion, N-(ethylcarbamothioyl-4-[5-(4-methylphenyl-3-(trifluoromethyl-1H-pyrazol-1-yl]benzenesulfonamide (1a may have the potential to be developed into a therapeutic agent.

  10. Anti-SEMA3A Antibody: A Novel Therapeutic Agent to Suppress GBM Tumor Growth.

    Science.gov (United States)

    Lee, Jaehyun; Shin, Yong Jae; Lee, Kyoungmin; Cho, Hee Jin; Sa, Jason K; Lee, Sang-Yun; Kim, Seok-Hyung; Lee, Jeongwu; Yoon, Yeup; Nam, Do-Hyun

    2017-11-10

    Glioblastoma (GBM) is classified as one of the most aggressive and lethal brain tumor. Great strides have been made in understanding the genomic and molecular underpinnings of GBM, which translated into development of new therapeutic approaches to combat such deadly disease. However, there are only few therapeutic agents that can effectively inhibit GBM invasion in a clinical framework. In an effort to address such challenges, we have generated anti-SEMA3A monoclonal antibody as a potential therapeutic antibody against GBM progression. We employed public glioma datasets, Repository of Molecular Brain Neoplasia Data and The Cancer Genome Atlas, to analyze SEMA3A mRNA expression in human GBM specimens. We also evaluated for protein expression level of SEMA3A via tissue microarray (TMA) analysis. Cell migration and proliferation kinetics were assessed in various GBM patient-derived cells (PDCs) and U87-MG cell-line for SEMA3A antibody efficacy. GBM patient-derived xenograft (PDX) models were generated to evaluate tumor inhibitory effect of anti-SEMA3A antibody in vivo. By combining bioinformatics and TMA analysis, we discovered that SEMA3A is highly expressed in human GBM specimens compared to non-neoplastic tissues. We developed three different anti-SEMA3A antibodies, in fully human IgG form, through screening phage-displayed synthetic antibody library using a classical panning method. Neutralization of SEMA3A significantly reduced migration and proliferation capabilities of PDCs and U87-MG cell-line in vitro. In PDX models, treatment with anti-SEMA3A antibody exhibited notable tumor inhibitory effect through down-regulation of cellular proliferative kinetics and tumor-associated macrophages recruitment. In present study, we demonstrated tumor inhibitory effect of SEMA3A antibody in GBM progression and present its potential relevance as a therapeutic agent in a clinical framework.

  11. Quercetin as an Emerging Anti-Melanoma Agent: A four-focus area therapeutic development strategy

    Directory of Open Access Journals (Sweden)

    Zoey Harris

    2016-10-01

    Full Text Available Replacing current refractory treatments for melanoma with new prevention and therapeutic approaches is crucial in order to successfully treat this aggressive cancer form. Melanoma develops from neural crest cells, which express tyrosinase -- a key enzyme in the pigmentation pathway. The tyrosinase enzyme is highly active in melanoma cells and metabolizes polyphenolic compounds; tyrosinase expression thus makes a feasible a target for polyphenol-based therapies. For example, quercetin (3,3′,4′,5,7-pentahydroxyflavone is a highly ubiquitous and well-classified dietary polyphenol found in various fruits, vegetables and other plant products including onions, broccoli, kale, oranges, blueberries, apples, and tea. Quercetin has demonstrated anti-proliferative and pro-apoptotic activity in various cancer cell types. Quercetin is readily metabolized by tyrosinase into various compounds that promote anti-cancer activity; additionally, given that tyrosinase expression increases during tumorigenesis, and its activity is associated with pigmentation changes in both early- and late-stage melanocytic lesions, it suggests that quercetin can be used to target melanoma. In this review we explore the potential of Quercetin as an anti-melanoma agent utilizing and extrapolating on evidence from previous in vitro studies in various human malignant cell lines and propose a four-focus area strategy to develop quercetin as a targeted anti-melanoma compound for use as either a preventative or therapeutic agent. The four areas of focus include utilizing quercetin to i modulate cellular bioreduction potential and associated signaling cascades, ii affect transcription of relevant genes, iii regulate epigenetic processes, and iv develop effective combination therapies and delivery modalities/protocols. In general, quercetin could be used to exploit tyrosinase activity to prevent, and/or treat, melanoma with minimal additional side effects.

  12. The status of rheumatoid factor and anti-cyclic citrullinated peptide antibody are not associated with the effect of anti-TNFα agent treatment in patients with rheumatoid arthritis: a meta-analysis.

    Directory of Open Access Journals (Sweden)

    Qianwen Lv

    Full Text Available OBJECTIVES: This meta-analysis was conducted to investigate whether the status of rheumatoid factor (RF and anti-cyclic citrullinated peptide (anti-CCP antibody are associated with the clinical response to anti-tumor necrosis factor (TNF alpha treatment in rheumatoid arthritis (RA. METHODS: A systemic literature review was performed using the MEDLINE, SCOPUS, Cochrane Library, ISI Web of Knowledge, and Clinical Trials Register databases, and Hayden's criteria of quality assessment for prognostic studies were used to evaluate all of the studies. The correlation between the RF and anti-CCP antibody status with the treatment effect of anti-TNFα agents was analyzed separately using the Mantel Haenszel method. A fixed-effects model was used when there was no significant heterogeneity; otherwise, a random-effects model was applied. Publication bias was assessed using Egger's linear regression and a funnel plot. RESULTS: A total of 14 studies involving 5561 RA patients meeting the inclusion criteria were included. The overall analysis showed that the pooled relative risk for the predictive effects of the RF and anti-CCP antibody status on patient response to anti-TNFα agents was 0.98 (95% CI: 0.91-1.05, p=0.54 and 0.88 (95% CI: 0.76-1.03, p=0.11, respectively, with I(2 values of 43% (p=0.05 and 67% (p<0.01, respectively. Subgroup analyses of different anti-TNFα treatments (infliximab vs. etanercept vs. adalimumab vs. golimumab, response criteria (DAS28 vs. ACR20 vs. EULAR response, follow-up period (≥ 6 vs. <6 months, and ethnic group did not reveal a significant association for the status of RF and anti-CCP. CONCLUSIONS: Neither the RF nor anti-CCP antibody status in RA patients is associated with a clinical response to anti-TNFα treatment.

  13. Increased risk of post-operative complications in patients with Crohn’s disease treated with anti-tumour necrosis factor α agents - a systematic review

    DEFF Research Database (Denmark)

    El-Hussuna, Alaa; Theede, Klaus; Olaison, Per Olov Gunnar

    2014-01-01

    INTRODUCTION: Tumour necrosis factor α (TNF-α) plays a role in the immune defence, angiogenesis and collagen synthesis. Inhibition of these pathways may increase the risk of infections and impair wound healing in patients after surgery. Biologic treatments including anti-TNF-α agents are increasi......INTRODUCTION: Tumour necrosis factor α (TNF-α) plays a role in the immune defence, angiogenesis and collagen synthesis. Inhibition of these pathways may increase the risk of infections and impair wound healing in patients after surgery. Biologic treatments including anti-TNF-α agents...... are increasingly used in the treatment of inflammatory bowel disease. Taking into consideration the biologics' mechanism of action, fears have been expressed that they might increase the rate of post-operative complications. Results from 18 retrospective studies were conflicting, and meta-analyses based...... an increased risk of overall post-operative complications and an increased rate of infectious or anastomosis-related complications in patients receiving anti-TNF-α. CONCLUSION: The use of anti-TNF-α agents in Crohn's disease patients is associated with an increased risk of post-operative complications after...

  14. An overview of structure-activity relationship studies of curcumin analogs as antioxidant and anti-inflammatory agents.

    Science.gov (United States)

    Arshad, Laiba; Haque, Md Areeful; Abbas Bukhari, Syed Nasir; Jantan, Ibrahim

    2017-04-01

    Curcumin, extracted mainly from Curcuma longa rhizomes, has been reported to possess potent anti-inflammatory and anti-oxidant activities. Although safe at higher doses and exhibiting multiple biological activities, curcumin still has the problem of poor bioavailability which has been an attractive area of research over the last few years. A number of efforts have been made by modifying structural features of curcumin. This review highlights the structurally modified and more stable newly synthesized curcumin analogs that have been screened against antioxidant and anti-inflammatory activities. Also the structure-activity relationship to gain insight into future guidelines for scheming new compounds has been discussed, and further these analogs being more stable may serve as promising agents for use in different pathological conditions.

  15. Design, synthesis and development of novel indolocarbazole derivatives as potential anti-cancer agents

    OpenAIRE

    Pierce, Laurence Thomas

    2011-01-01

    This thesis describes work carried out on the design of new routes to a range of bisindolylmaleimide and indolo[2,3-a]carbazole analogs, and investigation of their potential as successful anti-cancer agents. Following initial investigation of classical routes to indolo[2,3-a]pyrrolo[3,4-c]carbazole aglycons, a new strategy employing base-mediated condensation of thiourea and guanidine with a bisindolyl β-ketoester intermediate afforded novel 5,6-bisindolylpyrimidin-4(3H)-ones in moderat...

  16. Radiolabelled anti-human fibrin antibody: a new thrombus-detecting agent

    International Nuclear Information System (INIS)

    Bosnjakovic, V.; Jankovic, B.D.; Horvat, J.; Cvoric, J.

    1977-01-01

    Rabbit anti-human fibrin globulin (A.F.G.) was labelled with iodine ( 131 I) and used as a thrombus-detecting agent. 131 I-A.F.G. labelled thrombi were displayed by means of a gamma scintillation camera. Normal subjects and patients with thrombo-phlebitis of legs, acute fibrin depositions other than thrombi, and chronic varicosities were examined. The 131 I-A.F.G. technique detected both formed thrombi and those that were forming and could discriminate between acute thrombosis and chronic varicosities. Thrombo-phlebitis and extravascular fibrin depositions were best demonstrated between 24 and 72 hours after 131 I-A.F.G. injection. Radiolabelled A.F.G. in normal veins and chronic varicosities was best displayed within 6 hours of injection. (author)

  17. Targeting Bacterial Dsb Proteins for the Development of Anti-Virulence Agents

    Directory of Open Access Journals (Sweden)

    Roxanne P. Smith

    2016-07-01

    Full Text Available Recent years have witnessed a dramatic increase in bacterial antimicrobial resistance and a decline in the development of novel antibiotics. New therapeutic strategies are urgently needed to combat the growing threat posed by multidrug resistant bacterial infections. The Dsb disulfide bond forming pathways are potential targets for the development of antimicrobial agents because they play a central role in bacterial pathogenesis. In particular, the DsbA/DsbB system catalyses disulfide bond formation in a wide array of virulence factors, which are essential for many pathogens to establish infections and cause disease. These redox enzymes are well placed as antimicrobial targets because they are taxonomically widespread, share low sequence identity with human proteins, and many years of basic research have provided a deep molecular understanding of these systems in bacteria. In this review, we discuss disulfide bond catalytic pathways in bacteria and their significance in pathogenesis. We also review the use of different approaches to develop inhibitors against Dsb proteins as potential anti-virulence agents, including fragment-based drug discovery, high-throughput screening and other structure-based drug discovery methods.

  18. Efficacy of intravitreal injection of anti-vascular endothelial growth factor agents for stage 4 retinopathy of prematurity.

    Science.gov (United States)

    Cheng, Hui-Chen; Lee, Shui-Mei; Hsieh, Yi-Ting; Lin, Po-Kang

    2015-04-01

    To investigate the efficacy of intravitreal injection of anti-vascular endothelial growth factor agents for Stage 4 retinopathy of prematurity. Retrospective case series study. The medical records of patients receiving intravitreal injection of anti-vascular endothelial growth factor agents for Stage 4 retinopathy of prematurity from January 2007 to May 2012 in Taipei Veterans General Hospital were reviewed. A total of 13 eyes of 7 patients (3 boys and 4 girls) with Stage 4 retinopathy of prematurity were included. The mean gestational age and birth weight were 27.6 ± 2.6 weeks (range, 24.5-30.5 weeks) and 893.1 ± 293.2 g (range, 550-1422 g), respectively. The mean age at the time of injection was 38.2 ± 1.9 weeks (range, 36.0-41.5 weeks) postmenstrual age, and the mean follow-up period was 37.8 ± 19.5 months (range, 11.0-67.5 months). The active neovascularization regressed rapidly, and the anatomical outcomes were favorable in all patients. One eye developed recurrent retinal hemorrhage with localized retinal detachment 21 weeks after initial treatment, which resolved after a second injection. There were no ocular or systemic complications in these patients. Intravitreal injection of anti-vascular endothelial growth factor agents may be effective as monotherapy or as supplement to failed laser treatment for patients with Stage 4 retinopathy of prematurity without additional surgical intervention. Further randomized controlled trials are necessary to compare the clinical efficacy and safety with other conventional interventions.

  19. Investigating Sedative, Preanaesthetic & Anti-anxiety Effects of Herbal Extract of Cannabis Sativa in Comparison with Diazepam in Rats

    Directory of Open Access Journals (Sweden)

    A rezaei

    2014-04-01

    Full Text Available Introduction: Cannabis sativa is a plant that is Called Cannabis in Persian and has diversity all over the world. This plant grows in North region, Arak and Kashan in Iran. Chemical compounds of this plant are cannabidiol, cannabidiolic acid and tetra hydro cannabinol that cause the increase in duration of anesthesia via injection of anesthesia drugs. This effect shows the effectiveness of this plant extraction for sedation and smoothing. It is claimed that the usage of this drug for preanesthesia causes the reduction of anesthesia duration induction and increases anesthesia persistency. It seems that Cannabis and its compounds have effects on sleep through hypothalamus and posterior nucleus hemisphere. Methods: herbal extract of Cannabis Sativa (with doses of 150, 300, 450mg/kg, IP, Diazepam (with dose of 1.2mg/kg, IP, and Di-methyl sulphoxide with the equal volume was injected intraperitoneally into two different groups of male wistar rats 30 minutes before assessing the relief sedative and preanaesthetic effects (induced sleep duration by ketamine 40mg/kg, ip & anti-anxiety effects (using elevated plus maze. Results: The results showed a meaningful increase in the period of the sleep time that had been induced with Ketamine and also a meaningful increase was observed in the time spent at open arms in the treatment groups with high and low dose of extract. Conclusion: The results showed that the Cannabis Sativa extract with dose of 350mg/kg has sedative, preanaesthetic & anti-anxiety effects.

  20. Effects of some nonsteroidal anti-inflammatory agents on experimental radiation pneumonitis

    Energy Technology Data Exchange (ETDEWEB)

    Gross, N.J.; Holloway, N.O.; Narine, K.R. (Medical Radiology Service, Hines VA Hospital, Maywood, IL (United States))

    1991-09-01

    Corticosteroids have previously been found to be protective against the mortality of radiation pneumonitis in mice, even when given well after lethal lung irradiation. The authors explored the possibility that this effect was due to their well-known anti-inflammatory actions by giving various nonsteroidal inhibitors of arachidonate metabolism to groups of mice that had received 19 Gy to the thorax (bilaterally). Treatments of four cyclooxygenase inhibitors, one lipoxygenase inhibitor, and one leukotriene receptor antagonist, given by various routes in various doses, were commenced 10 weeks after irradiation or sham irradiation and continued throughout the period when death from radiation pneumonitis occurs, 11-26 weeks after irradiation. Each of the treatments had the appropriate effect on arachidonate metabolism in the lungs as assessed by LTB4 and PGE2 levels in lung lavage fluid. The principal end point was mortality. The 5-lipoxygenase inhibitor diethylcarbamazine and the LTD4/LTE4 receptor antagonist LY 171883 markedly reduced mortality in dose-response fashion. The effects of cyclooxygenase inhibitors were divergent; piroxicam and ibuprofen were marginally protective, indomethacin in all doses accelerated mortality, and aspirin reduced mortality in a dose-response fashion. These results suggest that the protective effect of corticosteroids in radiation pneumonitis can be tentatively attributed to their anti-inflammatory actions, and that nonsteroidal anti-inflammatory agents, particularly those that affect lipoxygenase products, may offer equal or better protection than corticosteroids against mortality due to radiation pneumonitis.

  1. Effects of some nonsteroidal anti-inflammatory agents on experimental radiation pneumonitis

    International Nuclear Information System (INIS)

    Gross, N.J.; Holloway, N.O.; Narine, K.R.

    1991-01-01

    Corticosteroids have previously been found to be protective against the mortality of radiation pneumonitis in mice, even when given well after lethal lung irradiation. The authors explored the possibility that this effect was due to their well-known anti-inflammatory actions by giving various nonsteroidal inhibitors of arachidonate metabolism to groups of mice that had received 19 Gy to the thorax (bilaterally). Treatments of four cyclooxygenase inhibitors, one lipoxygenase inhibitor, and one leukotriene receptor antagonist, given by various routes in various doses, were commenced 10 weeks after irradiation or sham irradiation and continued throughout the period when death from radiation pneumonitis occurs, 11-26 weeks after irradiation. Each of the treatments had the appropriate effect on arachidonate metabolism in the lungs as assessed by LTB4 and PGE2 levels in lung lavage fluid. The principal end point was mortality. The 5-lipoxygenase inhibitor diethylcarbamazine and the LTD4/LTE4 receptor antagonist LY 171883 markedly reduced mortality in dose-response fashion. The effects of cyclooxygenase inhibitors were divergent; piroxicam and ibuprofen were marginally protective, indomethacin in all doses accelerated mortality, and aspirin reduced mortality in a dose-response fashion. These results suggest that the protective effect of corticosteroids in radiation pneumonitis can be tentatively attributed to their anti-inflammatory actions, and that nonsteroidal anti-inflammatory agents, particularly those that affect lipoxygenase products, may offer equal or better protection than corticosteroids against mortality due to radiation pneumonitis

  2. Marketed nonsteroidal anti-inflammatory agents, antihypertensives, and human immunodeficiency virus protease inhibitors: as-yet-unused weapons of the oncologists’ arsenal

    Directory of Open Access Journals (Sweden)

    Papanagnou P

    2015-05-01

    Full Text Available Panagiota Papanagnou,1 Panagiotis Baltopoulos,2 Maria Tsironi1 1Department of Nursing, Faculty of Human Movement and Quality of Life Sciences, University of Peloponnese, Sparta, 2Department of Sports Medicine and Biology of Physical Activity, Faculty of Physical Education and Sport Science, National and Kapodistrian University of Athens, Athens, Greece Abstract: Experimental data indicate that several pharmacological agents that have long been used for the management of various diseases unrelated to cancer exhibit profound in vitro and in vivo anticancer activity. This is of major clinical importance, since it would possibly aid in reassessing the therapeutic use of currently used agents for which clinicians already have experience. Further, this would obviate the time-consuming process required for the development and the approval of novel antineoplastic drugs. Herein, both pre-clinical and clinical data concerning the antineoplastic function of distinct commercially available pharmacological agents that are not currently used in the field of oncology, ie, nonsteroidal anti-inflammatory drugs, antihypertensive agents, and anti-human immunodeficiency virus agents inhibiting viral protease, are reviewed. The aim is to provide integrated information regarding not only the molecular basis of the antitumor function of these agents but also the applicability of the reevaluation of their therapeutic range in the clinical setting. Keywords: repositioning, tumorigenesis, pleiotropy, exploitation

  3. Betaxolol in anxiety disorders.

    Science.gov (United States)

    Swartz, C M

    1998-03-01

    Betaxolol, a long-acting beta-adrenergic blocker that enters the central nervous system, was examined for therapeutic effects on the persistent anxiety of anxiety disorders. Prior studies of beta-blockers examined only agents that were short-acting or did not enter the brain. Betaxolol was administered to 31 patients in open trials. Of 13 outpatients, 11 had generalized anxiety disorder (GAD) and 2 had adjustment disorder with anxiety. Five with GAD had concurrent panic disorder. Of 18 inpatients, 16 had GAD and 2 had adjustment disorder with anxiety. Betaxolol doses were increased until the patient responded or declined further dosage. Severity was rated on a 4-point global scale. Before betaxolol, all were moderately or severely ill. In all patients with panic disorder panic attacks stopped within 2 days (pAnxiety decreased to no more than marginally ill in 85% of outpatients (panxiety and obsessive-compulsive personality disorder. Preliminary observations in posttraumatic stress disorder are similar.

  4. Synthesis and pharmacological evaluation of pyrazolo[4,3-c]cinnoline derivatives as potential anti-inflammatory and antibacterial agents.

    Science.gov (United States)

    Tonk, Rajiv Kumar; Bawa, Sandhya; Chawla, Gita; Deora, Girdhar Singh; Kumar, Suresh; Rathore, Vandana; Mulakayala, Naveen; Rajaram, Azad; Kalle, Arunasree M; Afzal, Obaid

    2012-11-01

    A series of pyrazolo[4,3-c]cinnoline derivatives was synthesized, characterized and evaluated for anti-inflammatory and antibacterial activity. Test compounds that exhibited good anti-inflammatory activity were further screened for their ulcerogenic and lipid peroxidation activity. Compounds 4d and 4l showed promising anti-inflammatory activity with reduced ulcerogenic and lipid peroxidation activity when compared to naproxen. Docking results of these two compounds with COX-2 (PDB ID: 1CX2) also exhibited a strong binding profile. Among the test derivatives, compound 4i displayed significant antibacterial property against gram-negative (Escherichia coli and Pseudomonas aeruginosa) and gram-positive (Staphylococcus aureus) bacteria. However, compound 4b emerged as the best dual anti-inflammatory-antibacterial agent in the present study. Copyright © 2012 Elsevier Masson SAS. All rights reserved.

  5. POOLED ESTIMATES OF INCIDENCE OF ENDOPHTHALMITIS AFTER INTRAVITREAL INJECTION OF ANTI-VASCULAR ENDOTHELIAL GROWTH FACTOR AGENTS WITH AND WITHOUT TOPICAL ANTIBIOTIC PROPHYLAXIS.

    Science.gov (United States)

    Reibaldi, Michele; Pulvirenti, Alfredo; Avitabile, Teresio; Bonfiglio, Vincenza; Russo, Andrea; Mariotti, Cesare; Bucolo, Claudio; Mastropasqua, Rodolfo; Parisi, Guglielmo; Longo, Antonio

    2018-01-01

    To assess the effect of topical antibiotic prophylaxis on postoperative endophthalmitis after intravitreal injection of anti-vascular endothelial growth factor agents. A systematic literature search was performed from inception to March 2016 using PubMed, Medline, Web of Science, Embase, and the Cochrane Library, to identify articles that reported cases of endophthalmitis after intravitreal injection of anti-vascular endothelial growth factor agents. We used a pooled analysis to estimate the incidence of cases of endophthalmitis who developed after injections performed with and without topical antibiotic prophylaxis. We used regression analysis to explore the effects of study characteristics on heterogeneity. From our search of electronic databases, we identified and screened 4,561 unique records. We judged 60 articles to have reported findings for cohorts of patients who met our inclusion criteria, (12 arms of randomized clinical trials, 11 prospective cohort studies, and 37 retrospective cohort studies), which included 244 cases of endophthalmitis and 639,391 intravitreal injections of anti-vascular endothelial growth factor agents. The final pooled estimate endophthalmitis proportions were 9/10,000 (95% confidence interval, 7/10,000-12/10,000) in the antibiotic-treated group and 3/10,000 (95% confidence interval, 2/10,000-5/10,000) in the untreated group. The estimated incidence of endophthalmitis with topical antibiotic prophylaxis was approximated three times the incidence without prophylaxis. Random effects regression showed that none of the study characteristics significantly affected the effect size in either group. Topical antibiotic after intravitreal injection of anti-vascular endothelial growth factor agents is associated with a higher risk of endophthalmitis.

  6. Sustained release of a novel anti-quorum-sensing agent against oral fungal biofilms.

    Science.gov (United States)

    Feldman, Mark; Shenderovich, Julia; Al-Quntar, Abed Al Aziz; Friedman, Michael; Steinberg, Doron

    2015-04-01

    Thiazolidinedione-8 (S-8) has recently been identified as a potential anti-quorum-sensing/antibiofilm agent against bacteria and fungi. Based on these results, we investigated the possibility of incorporating S-8 in a sustained-release membrane (SRM) to increase its pharmaceutical potential against Candida albicans biofilm. We demonstrated that SRM containing S-8 inhibits fungal biofilm formation in a time-dependent manner for 72 h, due to prolonged release of S-8. Moreover, the SRM effectively delivered the agent in its active form to locations outside the membrane reservoir. In addition, eradication of mature biofilm by the SRM containing S-8 was also significant. Of note, S-8-containing SRM affected the characteristics of mature C. albicans biofilm, such as thickness, exopolysaccharide (EPS) production, and morphogenesis of fungal cells. The concept of using an antibiofilm agent with no antifungal activity incorporated into a sustained-release delivery system is new in medicine and dentistry. This concept of an SRM containing a quorum-sensing quencher with an antibiofilm effect could pave the way for combating oral fungal infectious diseases. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  7. Misoprostol, an anti-ulcer agent and PGE2 receptor agonist, protects against cerebral ischemia

    OpenAIRE

    Li, Jun; Liang, Xibin; Wang, Qian; Breyer, Richard M.; McCullough, Louise; Andreasson, Katrin

    2008-01-01

    Induction of COX-2 activity in cerebral ischemia results in increased neuronal injury and infarct size. Recent studies investigating neurotoxic mechanisms of COX-2 demonstrate both toxic and paradoxically protective effects of downstream prostaglandin receptor signaling pathways. We tested whether misoprostol, a PGE2 receptor agonist that is utilized clinically as an anti-ulcer agent and signals through the protective PGE2 EP2, EP3, and EP4 receptors, would reduce brain injury in the murine m...

  8. Screening for potential anti-infective agents towards Burkholderia pseudomallei infection

    Science.gov (United States)

    Eng, Su Anne; Nathan, Sheila

    2014-09-01

    The established treatment for melioidosis is antibiotic therapy. However, a constant threat to this form of treatment is resistance development of the causative agent, Burkholderia pseudomallei, towards antibiotics. One option to circumvent this threat of antibiotic resistance is to search for new alternative anti-infectives which target the host innate immune system and/or bacterial virulence. In this study, 29 synthetic compounds were evaluated for their potential to increase the lifespan of an infected host. The nematode Caenorhabditis elegans was adopted as the infection model as its innate immune pathways are homologous to humans. Screens were performed in a liquid-based survival assay containing infected worms exposed to individual compounds and survival of untreated and compound-treated worms were compared. A primary screen identified nine synthetic compounds that extended the lifespan of B. pseudomallei-infected worms. Subsequently, a disc diffusion test was performed on these selected compounds to delineate compounds into those that enhanced the survival of worms via antimicrobial activity i.e. reducing the number of infecting bacteria, or into those that did not target pathogen viability. Out of the nine hits selected, two demonstrated antimicrobial effects on B. pseudomallei. Therefore, the findings from this study suggest that the other seven identified compounds are potential anti-infectives which could protect a host against B. pseudomallei infection without developing the risk of drug resistance.

  9. How should immunomodulators be optimized when used as combination therapy with anti-tumor necrosis factor agents in the management of inflammatory bowel disease?

    Science.gov (United States)

    Ward, Mark G; Irving, Peter M; Sparrow, Miles P

    2015-10-28

    In the last 15 years the management of inflammatory bowel disease has evolved greatly, largely through the increased use of immunomodulators and, especially, anti-tumor necrosis factor (anti-TNF) biologic agents. Within this time period, confidence in the use of anti-TNFs has increased, whilst, especially in recent years, the efficacy and safety of thiopurines has been questioned. Yet despite recent concerns regarding the risk: benefit profile of thiopurines, combination therapy with an immunomodulator and an anti-TNF has emerged as the recommended treatment strategy for the majority of patients with moderate-severe disease, especially those who are recently diagnosed. Concurrently, therapeutic drug monitoring has emerged as a means of optimizing the dosage of both immunomodulators and anti-TNFs. However the recommended therapeutic target levels for both drug classes were largely derived from studies of monotherapy with either agent, or studies underpowered to analyze outcomes in combination therapy patients. It has been assumed that these target levels are applicable to patients on combination therapy also, however there are few data to support this. Similarly, the timing and duration of treatment with immunomodulators when used in combination therapy remains unknown. Recent attention, including post hoc analyses of the pivotal registration trials, has focused on the optimization of anti-TNF agents, when used as either monotherapy or combination therapy. This review will instead focus on how best to optimize immunomodulators when used in combination therapy, including an evaluation of recent data addressing unanswered questions regarding the optimal timing, dosage and duration of immunomodulator therapy in combination therapy patients.

  10. Reproductive studies with the anti-inflammatory agent, piroxicam: modification of classical protocols.

    Science.gov (United States)

    Perraud, J; Stadler, J; Kessedjian, M J; Monro, A M

    1984-02-14

    Reproductive toxicology studies were conducted in rabbits and rats given piroxicam, a non-steroidal anti-inflammatory agent (NSAI), orally at 2, 5 and 10 mg/kg/day. In teratology studies there was neither drug-related embryotoxicity nor teratogenicity. As piroxicam, like other NSAI, affects parturition in rats and leads to a progressive toxicity in lactating females, standard protocols were modified: dams of the female fertility study were treated from 2 weeks prior to mating until day 6 of gestation and females of the post-natal toxicity study were treated from parturition until day 12 of lactation. No other adverse effects on reproduction, fertility and postnatal development were observed.

  11. Comparative effectiveness of fourth-line anti-hypertensive agents in resistant hypertension: A systematic review and meta-analysis.

    Science.gov (United States)

    Sinnott, Sarah-Jo; Tomlinson, Laurie A; Root, Adrian A; Mathur, Rohini; Mansfield, Kathryn E; Smeeth, Liam; Douglas, Ian J

    2017-02-01

    Aim We assessed the effectiveness of fourth-line mineralocorticoid receptor antagonists in comparison with other fourth-line anti-hypertensive agents in resistant hypertension. Methods and results We systematically searched Medline, EMBASE and the Cochrane library from database inception until January 2016. We included randomised and non-randomised studies that compared mineralocorticoid receptor antagonists with other fourth-line anti-hypertensive agents in patients with resistant hypertension. The outcome was change in systolic blood pressure, measured in the office, at home or by ambulatory blood pressure monitoring. Secondary outcomes were changes in serum potassium and occurrence of hyperkalaemia. We used random effects models and assessed statistical heterogeneity using the I 2 test and corresponding 95% confidence intervals. From 2,506 records, 5 studies met our inclusion criteria with 755 included patients. Two studies were randomised and three were non-randomised. Comparative fourth-line agents included bisoprolol, doxazosin, furosemide and additional blockade of the renin angiotensin-aldosterone system. Using data from randomised studies, mineralocorticoid receptor antagonists reduced blood pressure by 7.4 mmHg (95%CI 3.2 - 11.6) more than the active comparator. When limited to non-randomised studies, mineralocorticoid receptor antagonists reduced blood pressure by 11.9 mmHg (95% CI 9.3 - 14.4) more than the active comparator. Conclusion On the basis of this meta-analysis, mineralocorticoid receptor antagonists reduce blood pressure more effectively than other fourth-line agents in resistant hypertension. Effectiveness stratified by ethnicity and comorbidities, in addition to information on clinical outcomes such as myocardial infarction and stroke, now needs to be determined.

  12. Risk of venous and arterial thromboembolic events associated with anti-VEGF agents in advanced non-small-cell lung cancer: a meta-analysis and systematic review

    Directory of Open Access Journals (Sweden)

    Zhang D

    2016-06-01

    Full Text Available Dianbao Zhang,1,* Xianfen Zhang,2,* Chunling Zhao1 1Department of Medical Oncology, 2Department of Cardiac Surgery, The First Affiliated Hospital of Henan University of Science and Technology, Luoyang, Henan Province, People’s Republic of China *These authors contributed equally to this work Aims: To assess the incidence and risk of arterial and venous thromboembolic events (ATEs and VTEs associated with antivascular endothelial growth factor (VEGF agents, including VEGF receptor-tyrosine kinase inhibitors and VEGF monoclonal antibodies, in advanced non-small-cell lung cancer (NSCLC patients. Methods: We performed a broad search of PubMed for relevant trials. Prospective randomized trials evaluating therapy with or without anti-VEGF agents in patients with advanced NSCLC were included for analysis. Data on VTEs and ATEs were extracted. The overall incidence, Peto odds ratio (Peto OR, and 95% confidence intervals (CIs were pooled according to the heterogeneity of included trials. Results: A total of 13,436 patients from 23 trials were included for analysis. Our results showed that anti-VEGF agents significantly increased the risk of developing high-grade ATEs (Peto OR: 1.44, 95% CI: 1.00–2.07, P=0.048, but not for all-grade ATEs (Peto OR: 0.94, 95% CI: 0.56–1.59, P=0.82 compared with controls. Additionally, no increased risk of all-grade and high-grade VTEs (Peto OR: 0.94, 95% CI: 0.67–1.31, P=0.71 and Peto OR: 0.95, 95% CI: 0.73–1.22, P=0.67, respectively was observed in advanced NSCLC patients receiving anti-VEGF agents. Conclusion: The use of anti-VEGF agents in advanced NSCLC patients significantly increased the risk of high-grade ATEs, but not for VTEs. Clinicians should be aware of the risk of severe ATEs with administration of these drugs in advanced NSCLC patients. Keywords: anti-VEGF agents, toxicity, arterial thromboembolic events, venous thromboembolic events, meta-analysis

  13. Miracle Fruit (Synsepalum dulcificum Exhibits as a Novel Anti-Hyperuricaemia Agent

    Directory of Open Access Journals (Sweden)

    Yeu-Ching Shi

    2016-01-01

    Full Text Available Miracle fruit (Synsepalum dulcificum belongs to the Sapotaceae family. It can change flavors on taste buds, transforming acidic tastes to sweet. We evaluated various miracle fruit extracts, including water, butanol, ethyl acetate (EA, and hexane fractions, to determine its antioxidant effects. These extracts isolated from miracle fruit exerted potential for reduction of uric acid and inhibited xanthine oxidase activity in vitro and in monosodiumurate (MSU-treated RAW264.7 macrophages. Moreover, we also found that the butanol extracts of miracle fruit attenuated oxonic acid potassium salt-induced hyperuricaemia in ICR mice by lowering serum uric acid levels and activating hepatic xanthine oxidase. These effects were equal to those of allopurinol, suggesting that the butanol extract of miracle fruit could be developed as a novel anti-hyperuricaemia agent or health food.

  14. Moringa oleifera as an Anti-Cancer Agent against Breast and Colorectal Cancer Cell Lines.

    Science.gov (United States)

    Al-Asmari, Abdulrahman Khazim; Albalawi, Sulaiman Mansour; Athar, Md Tanwir; Khan, Abdul Quaiyoom; Al-Shahrani, Hamoud; Islam, Mozaffarul

    2015-01-01

    In this study we investigated the anti-cancer effect of Moringa oleifera leaves, bark and seed extracts. When tested against MDA-MB-231 and HCT-8 cancer cell lines, the extracts of leaves and bark showed remarkable anti-cancer properties while surprisingly, seed extracts exhibited hardly any such properties. Cell survival was significantly low in both cells lines when treated with leaves and bark extracts. Furthermore, a striking reduction (about 70-90%) in colony formation as well as cell motility was observed upon treatment with leaves and bark. Additionally, apoptosis assay performed on these treated breast and colorectal cancer lines showed a remarkable increase in the number of apoptotic cells; with a 7 fold increase in MD-MB-231 to an increase of several fold in colorectal cancer cell lines. However, no significant apoptotic cells were detected upon seeds extract treatment. Moreover, the cell cycle distribution showed a G2/M enrichment (about 2-3 fold) indicating that these extracts effectively arrest the cell progression at the G2/M phase. The GC-MS analyses of these extracts revealed numerous known anti-cancer compounds, namely eugenol, isopropyl isothiocynate, D-allose, and hexadeconoic acid ethyl ester, all of which possess long chain hydrocarbons, sugar moiety and an aromatic ring. This suggests that the anti-cancer properties of Moringa oleifera could be attributed to the bioactive compounds present in the extracts from this plant. This is a novel study because no report has yet been cited on the effectiveness of Moringa extracts obtained in the locally grown environment as an anti-cancer agent against breast and colorectal cancers. Our study is the first of its kind to evaluate the anti-malignant properties of Moringa not only in leaves but also in bark. These findings suggest that both the leaf and bark extracts of Moringa collected from the Saudi Arabian region possess anti-cancer activity that can be used to develop new drugs for treatment of breast

  15. Anti-Enterovirus 71 Agents of Natural Products.

    Science.gov (United States)

    Wang, Liyan; Wang, Junfeng; Wang, Lishu; Ma, Shurong; Liu, Yonghong

    2015-09-09

    This review, with 42 references, presents the fascinating area of anti-enterovirus 71 natural products over the last three decades for the first time. It covers literature published from 2005-2015 and refers to compounds isolated from biogenic sources. In total, 58 naturally-occurring anti-EV71 compounds are recorded.

  16. Berberine as a promising safe anti-cancer agent - is there a role for mitochondria?

    Science.gov (United States)

    Diogo, Catia V; Machado, Nuno G; Barbosa, Inês A; Serafim, Teresa L; Burgeiro, Ana; Oliveira, Paulo J

    2011-06-01

    Metabolic regulation is largely dependent on mitochondria, which play an important role in energy homeostasis. Imbalance between energy intake and expenditure leads to mitochondrial dysfunction, characterized by a reduced ratio of energy production (ATP production) to respiration. Due to the role of mitochondrial factors/events in several apoptotic pathways, the possibility of targeting that organelle in the tumor cell, leading to its elimination is very attractive, although the safety issue is problematic. Berberine, a benzyl-tetra isoquinoline alkaloid extracted from plants of the Berberidaceae family, has been extensively used for many centuries, especially in the traditional Chinese and Native American medicine. Several evidences suggest that berberine possesses several therapeutic uses, including anti-tumoral activity. The present review supplies evidence that berberine is a safe anti-cancer agent, exerting several effects on mitochondria, including inhibition of mitochondrial Complex I and interaction with the adenine nucleotide translocator which can explain several of the described effects on tumor cells.

  17. Complicações Imediatas de 3.555 aplicações de agentes anti-TNFα Immediate complications of 3,555 injections of anti-TNFα

    Directory of Open Access Journals (Sweden)

    Júlio César Bertacini de Moraes

    2010-04-01

    Full Text Available OBJETIVO: Avaliar as complicações imediatas da aplicação de agentes anti-TNFα no Centro de Dispensação de Medicação deAlto Custo do HC-FMUSP. PACIENTES E MÉTODOS: Foram incluídos todos os pacientes que receberam agentes anti-TNFα entre agosto/2007 e março/2009.As complicações imediatas (até 1 hora após o término da aplicação foram classificadas em leves (cefaleia, rash, tontura, prurido, náuseas, moderadas (febre, urticária, palpitação, dor torácica, dispneia, variação da pressão arterial de 20 a 40 mmHg ou graves (febre com calafrios, dispneia com sibilância, variação da pressão arterial > 40 mmHg. RESULTADOS: Foram avaliados 242 pacientes: 94 (39% com artrite reumatoide, 64 (26% com espondilite anquilosante, 32 (13% com artrite psoriásica, 26 (11% com artrite idiopática juvenil e 27 (11% com outros diagnósticos. O número total de aplicações foi de 3.555, sendo 992 (28% de adalimumabe, 1.546 (43% de etanercepte e 1.017 (29% de infliximabe. Complicações imediatas foram observadas em 39/242 (16% pacientes. As complicações ocorreram em 45/3.555 (1,2% aplicações. Estas foram mais frequentes com infliximabe comparado com adalimumabe (3,7% vs. 0,5%, P OBJECTIVE: To evaluate the immediate complications of anti-TNFα drugs at the "Center for Dispensation of High Cost Medications" of HC-FMUSP. PATIENTS AND METHODS: All patients who received anti-TNFα agents between August 2007 and March 2009 were included in this study. Immediate complications (up to 1 hour after the injection were classified as mild (headache, rash, dizziness, itching, nausea, moderate (fever, urticaria, palpitation, chest pain, dyspnea, blood pressure variations between 20 and 40 mmHg, or severe (fever with chills, dyspnea with wheezing, variations in blood pressure > 40 mmHg. RESULTS: Two hundred and forty-two patients were evaluated: 94 (39% with rheumatoid arthritis, 64 (26% with ankylosing spondylitis, 32 (13% with psoriatic arthritis

  18. Anti-Enterovirus 71 Agents of Natural Products

    Directory of Open Access Journals (Sweden)

    Liyan Wang

    2015-09-01

    Full Text Available This review, with 42 references, presents the fascinating area of anti-enterovirus 71 natural products over the last three decades for the first time. It covers literature published from 2005–2015 and refers to compounds isolated from biogenic sources. In total, 58 naturally-occurring anti-EV71 compounds are recorded.

  19. Sources of information on lymphoma associated with anti-tumour necrosis factor agents: comparison of published case reports and cases reported to the French pharmacovigilance system.

    Science.gov (United States)

    Théophile, Hélène; Schaeverbeke, Thierry; Miremont-Salamé, Ghada; Abouelfath, Abdelilah; Kahn, Valentine; Haramburu, Françoise; Bégaud, Bernard

    2011-07-01

    Anti-tumour necrosis factor (TNF) agents, through their intense immunoregulatory effect, have been suspected to increase the risk of malignant lymphoma. However, the classical epidemiological approaches conducted over about the last 10 years have not totally succeeded in addressing the question of a causal or artifactual association. Therefore, the analysis of a substantial set of case reports, although usually considered as poorly generalizable to the general population, could be particularly informative. Two main sources of case reports in postmarketing settings are available; publications in medical journals and reports to pharmacovigilance systems. The aim of the study was to compare the characteristics of case reports from both these sources in order to understand whether they provided the same information for the investigation of the causal link between lymphoma and anti-TNF agents. All case reports of malignant lymphoma in patients treated with an anti-TNF agent published in MEDLINE and all reports to the French pharmacovigilance system up to 1 February 2010 were identified. Cases of malignant lymphoma identified in postmarketing surveillance from both sources were compared regarding the following variables: age, sex, anti-TNF agent involved, indication for use, type of lymphoma, prior or concomitant immunosuppressive drugs and time to onset of lymphoma. A total of 81 published case reports and 61 cases reported to the French pharmacovigilance system were compared. In published reports, patients were younger (p = 0.03) and more frequently receiving a first anti-TNF treatment (p = 0.03), particularly infliximab (p = 0.03). Conversely, in the pharmacovigilance system reports, a succession of different anti-TNFs (p = 0.03) and adalimumab (p French pharmacovigilance system differed markedly for all characteristics tested, except sex and the use of prior or concomitant immunosuppressive drugs. Published case reports favoured convincing arguments

  20. The effect of anti-tumor necrosis factor alpha agents on the outcome in pediatric uveitis of diverse etiologies.

    Science.gov (United States)

    Deitch, Iris; Amer, Radgonde; Tomkins-Netzer, Oren; Habot-Wilner, Zohar; Friling, Ronit; Neumann, Ron; Kramer, Michal

    2018-04-01

    This study aimed to report the clinical outcome of children with uveitis treated with anti-tumor necrosis factor alpha (TNF-α) agents. This included a retrospective cohort study. Children with uveitis treated with infliximab or adalimumab in 2008-2014 at five dedicated uveitis clinics were identified by database search. Their medical records were reviewed for demographic data, clinical presentation, ocular complications, and visual outcome. Systemic side effects and the steroid-sparing effect of treatment were documented. The cohort included 24 patients (43 eyes) of whom 14 received infliximab and 10 received adalimumab after failing conventional immunosuppression therapy. Mean age was 9.3 ± 4.0 years. The most common diagnosis was juvenile idiopathic arthritis-related uveitis (n = 10), followed by Behçet's disease (n = 4), sarcoidosis (n = 1), and ankylosing spondylitis (n = 1); eight had idiopathic uveitis. Ocular manifestations included panuveitis in 20 eyes (46.5%), chronic anterior uveitis in 19 (44.2%), and intermediate uveitis in 4 (9.3%). The duration of biologic treatment ranged from 6 to 72 months. During the 12 months prior to biologic treatment, while on conventional immunosuppressive therapy, mean visual acuity deteriorated from 0.22 to 0.45 logMAR, with a trend of recovery to 0.25 at 3 months after initiation of biologic treatment, remaining stable thereafter. A full corticosteroid-sparing effect was demonstrated in 16 of the 19 patients (84.2%) for whom data were available. Treatment was well tolerated. Treatment of pediatric uveitis with anti-TNF-α agents may improve outcome while providing steroid-sparing effect, when conventional immunosuppression fails. The role of anti-TNF-α agents as first-line treatment should be further investigated in controlled prospective clinical trials.

  1. Delivering Cognitive Behavior Therapy to Young Adults With Symptoms of Depression and Anxiety Using a Fully Automated Conversational Agent (Woebot): A Randomized Controlled Trial.

    Science.gov (United States)

    Fitzpatrick, Kathleen Kara; Darcy, Alison; Vierhile, Molly

    2017-06-06

    Web-based cognitive-behavioral therapeutic (CBT) apps have demonstrated efficacy but are characterized by poor adherence. Conversational agents may offer a convenient, engaging way of getting support at any time. The objective of the study was to determine the feasibility, acceptability, and preliminary efficacy of a fully automated conversational agent to deliver a self-help program for college students who self-identify as having symptoms of anxiety and depression. In an unblinded trial, 70 individuals age 18-28 years were recruited online from a university community social media site and were randomized to receive either 2 weeks (up to 20 sessions) of self-help content derived from CBT principles in a conversational format with a text-based conversational agent (Woebot) (n=34) or were directed to the National Institute of Mental Health ebook, "Depression in College Students," as an information-only control group (n=36). All participants completed Web-based versions of the 9-item Patient Health Questionnaire (PHQ-9), the 7-item Generalized Anxiety Disorder scale (GAD-7), and the Positive and Negative Affect Scale at baseline and 2-3 weeks later (T2). Participants were on average 22.2 years old (SD 2.33), 67% female (47/70), mostly non-Hispanic (93%, 54/58), and Caucasian (79%, 46/58). Participants in the Woebot group engaged with the conversational agent an average of 12.14 (SD 2.23) times over the study period. No significant differences existed between the groups at baseline, and 83% (58/70) of participants provided data at T2 (17% attrition). Intent-to-treat univariate analysis of covariance revealed a significant group difference on depression such that those in the Woebot group significantly reduced their symptoms of depression over the study period as measured by the PHQ-9 (F=6.47; P=.01) while those in the information control group did not. In an analysis of completers, participants in both groups significantly reduced anxiety as measured by the GAD-7 (F 1

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

    International Nuclear Information System (INIS)

    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.

  3. Identification and reconstitution of the polyketide synthases responsible for biosynthesis of the anti-malarial agent, cladosporin

    OpenAIRE

    Cochrane, Rachel V. K.; Sanichar, Randy; Lambkin, Gareth R.; Reiz, Béla; Xu, Wei; Tang, Yi; Vederas, John C.

    2015-01-01

    The anti-malarial agent cladosporin is a nanomolar inhibitor of Plasmodium falciparum lysyl-tRNA synthetase, and exhibits activity against both blood and liver stage infection. Cladosporin can be isolated from the fungus Cladosporium cladosporioides, where it was believed to be biosynthesized by a highly reducing (HR) and non-reducing (NR) iterative type I polyketide synthase (PKS) pair. Genome sequencing of the host organism, and subsequent heterologous expression of these enzymes in Sacchar...

  4. Studies on the Synthesis of Etodolac Derivatives as Potential Anti-inflammatory Agents

    Energy Technology Data Exchange (ETDEWEB)

    Cho, H.; Chung, Y.S. [Department of Chemistry, Chungbuk Natiojal University (Korea); Jang, H.D. [Department of Chemical Engineering, Seoul National Polytechnic University (Korea); Ryu, S.R. [Department of Chemical Engineering, Dae Bul University (Korea)

    1999-02-01

    For the synthesis of new anti-inflammatory agents as indol derivatives, we have synthesized a-benzoyl-1-ethyl-1,3,4,9-tetrahydro-8-ethyl-9-(N-benzoyl)pyrano[3,4-b]indole-= 1-acetic acid methyl ester. It was a new method for a-substituted etodolac carboxylic acid. The synthetic process was composed of four steps, and 7-ethylindole and oxalyl chloride were used as starting materials. The third step, cyclization was carried out by addition of borontrifluoride diethyl etherate in 66% yield. The step of reduction and cyclization were simplified successfully. The final product, a-benzoyl-1-ethyl-1,3,4,9-tetrahydropyrano[3,4-b]indole-1-acetate (etodollic acid methyl ester) and benzoyl chloride. 14 refs., 3 figs.

  5. Current evidence on the use of anti-RAAS agents in congenital or acquired solitary kidney.

    Science.gov (United States)

    Simeoni, Mariadelina; Armeni, Annarita; Summaria, Chiara; Cerantonio, Annamaria; Fuiano, Giorgio

    2017-11-01

    The inhibition of renin-angiotensin-aldosterone system (RAAS) is a major strategy for slowing the progression of chronic kidney disease (CKD). The utility of anti-RAAS agents in patients with congenital or acquired solitary kidney is still controversial. A systematic literature review was conducted. The conclusions of the few available studies on the topic are homogeneously in agreement with a long-term reno-protective activity of anti-RAAS drugs in patients with solitary kidney, especially if patients are hypertensive or proteinuric. However, angiotensin 2 (ANG2) levels permit a functional adaptation to a reduced renal mass in adults and is crucial for sustaining complete kidney development and maturation in children. A hormonal interference on ANG2 levels has been supposed in women. Consequently, at least in children and women, the use of ARBs appears more appropriate. Principle conclusions: Available data on this topic are limited; however, by their overall assessment, it would appear that anti-RAAS drugs might also be reno-protective in patients with solitary kidney. The use of ARBs, especially in children and in women, seems to be more appropriate. However, more experimental data would be strictly necessary to confirm this hypothesis.

  6. Effects of Mimosa pudica L. leaves extract on anxiety, depression and memory

    Directory of Open Access Journals (Sweden)

    Ganesh Patro

    2016-11-01

    Full Text Available Objective: The present study was carried out to investigate the neuropharmacological activities of ethyl acetate extract of Mimosa pudica (EAMP leaves on anxiety, depression and memory in a mouse model. Materials and Methods: Anti-anxiety potential of EAMP was evaluated by elevated plus maze (EPM, light-dark box (LDB and social interaction (SI tests in mice.Anti-depressant potential of EAMP was evaluated by forced swimming (FST, tail suspension (TST, and open field tests (OFT. The behavioral findings were further corroborated with estimation of neurotransmitters and their metabolites from mouse brain homogenate. Effect on learning and memory was evaluated by EPM, passive avoidance (PA tests. Further, it was confirmed with assessment of acetylcholinesterase and caspase-3 activity in brain homogenate. Results: EAMP showed significant anti-anxiety activity by increasing the time spent in open arm of EPM, light box of LDB. Social interaction time was increased significantly (p

  7. Targeting cancer chemotherapeutic agents by use of lipiodol contrast medium

    International Nuclear Information System (INIS)

    Konno, T.

    1990-01-01

    Arterially administered Lipiodol Ultrafluid contrast medium selectively remained in various malignant solid tumors because of the difference in time required for the removal of Lipiodol contrast medium from normal capillaries and tumor neovasculature. Although blood flow was maintained in the tumor, even immediately after injection Lipiodol contrast medium remained in the neovasculature of the tumor. To target anti-cancer agents to tumors by using Lipiodol contrast medium as a carrier, the characteristics of the agents were examined. Anti-cancer agents had to be soluble in Lipiodol, be stable in it, and separate gradually from it so that the anti-cancer agents would selectively remain in the tumor. These conditions were found to be necessary on the basis of the measurement of radioactivity in VX2 tumors implanted in the liver of 16 rabbits that received arterial injections of 14C-labeled doxorubicin. Antitumor activities and side effects of arterial injections of two types of anti-cancer agents were compared in 76 rabbits with VX2 tumors. Oily anti-cancer agents that had characteristics essential for targeting were compared with simple mixtures of anti-cancer agents with Lipiodol contrast medium that did not have these essential characteristics. Groups of rabbits that received oily anti-cancer agents responded significantly better than groups that received simple mixtures, and side effects were observed more frequently in the groups that received the simple mixtures. These results suggest that targeting of the anti-cancer agent to the tumor is important for treatment of solid malignant tumors

  8. Anti-Anxiety Effect of (-)-Syringaresnol-4-O-β-d-apiofuranosyl-(1→2)-β-d-glucopyranoside from Albizzia julibrissin Durazz (Leguminosae).

    Science.gov (United States)

    Liu, Jie; Lv, Yue-Wei; Shi, Jin-Li; Ma, Xiao-Jie; Chen, Yi; Zheng, Zhi-Quan; Wang, Sheng-Nan; Guo, Jian-You

    2017-08-11

    Albizzia julibrissin Durazz, a Chinese Medicine, is commonly used for its anti-anxiety effects. (-)-syringaresnol-4- O -β-d-apiofuranosyl-(1→2)-β-d-glucopyranoside (SAG) is the main ingredient of Albizzia julibrissin Durazz. The present study investigated the anxiolytic effect and potential mechanisms on the HPA axis and monoaminergic systems of SAG on acute restraint-stressed rats. The anxiolytic effect of SAG was examined through an open field test and an elevated plus maze test. The concentration of CRF, ACTH, and CORT in plasma was examined by an enzyme-linked immune sorbent assay (ELISA) kit while neurotransmitters in the cerebral cortex and hippocampus of the brain were examined by High Performance Liquid Chromatography (HPLC). We show that repeated treatment with SAG (3.6 mg/kg, p.o.) significantly increased the number and time spent on the central entries in the open-field test when compared to the vehicle/stressed group. In the elevated plus maze test, 3.6 mg/kg SAG could increase the percentage of entries into and time spent on the open arms of the elevated plus maze. In addition, the concentration of CRF, ACTH, and CORT in plasma and neurotransmitters (NE, 5-HT, DA and their metabolites 5-HIAA, DOPAC, and HVA) in the cerebral cortex and hippocampus of the brain were decreased after SAG treatment, as compared to the repeated acute restraint-stressed rats. These results suggest that SAG is a potential anti-anxiety drug candidate.

  9. Treating Anxiety Disorders | NIH MedlinePlus the Magazine

    Science.gov (United States)

    ... Benzodiazepines are the most common class of anti-anxiety drugs. Commonly prescribed: Xanax, Klonopin, Valium, and Ativan. Beta blockers. These drugs block norepinephrine, the body's "fight-or- ...

  10. Anti-microbial and anti-biofilm compounds from Indonesian medicinal plants

    NARCIS (Netherlands)

    Pratiwi, Sylvia U.T.

    2015-01-01

    Microbial biofilms causing elevated resistance to both most anti-microbial drugs and the host defense systems, which often results in persistent and difficult-to-treat infections. The discovery of anti-infective agents which are active against planktonic and biofilm microorganisms are therefore

  11. Nanofiber mats composed of a chitosan-poly(d,l-lactic-co-glycolic acid)-poly(ethylene oxide) blend as a postoperative anti-adhesion agent.

    Science.gov (United States)

    Ko, Jae Eok; Ko, Young-Gwang; Kim, Won Il; Kwon, Oh Kyoung; Kwon, Oh Hyeong

    2017-10-01

    Postoperative tissue adhesion causes serious complications and suffering in 90% of patients after peritoneum surgery, while commercial anti-adhesion agents cannot completely prevent postoperative peritoneal adhesions. This study demonstrates electrospining of a blended solution of chitosan, poly(d,l-lactic-co-glycolic acid) (PLGA), and poly(ethylene oxide) (PEO) to fabricate a chitosan-based nanofibrous mat as a postoperative anti-adhesion agent. Rheological studies combined with scanning electron microscopy reveal that the spinnability of the chitosan-PLGA solution could be controlled by adjusting the blend ratio and concentration with average fiber diameter from 634 to 913 nm. Biodegradation of the nanofiber specimens showed accelerated hydrolysis by chitosan. Proliferation of fibroblasts and antimicrobial activity of nanofibers containing chitosan was analyzed. Abdominal defects with cecum adhesion in rats demonstrated that the blend nanofiber mats were effective in preventing tissue adhesion as a barrier (4 weeks after abdominal surgery) by coverage of exfoliated peritoneum and insufficient wound sites at the beginning of the wound healing process. Chitosan-PLGA-PEO blend nanofiber mats will provide a promising key as a postoperative anti-adhesion agent. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 1906-1915, 2017. © 2016 Wiley Periodicals, Inc.

  12. Anti-anxiety activity of successive extracts of Angelica archangelica Linn. on the elevated T-maze and forced swimming tests in rats.

    Science.gov (United States)

    Kumar, Dinesh; Bhat, Zulfiqar Ali; Shah, M Y

    2012-09-01

    Angelica archangelica Linn. is widely used in food and liquor preparations and also in Kashmiri folk medicine to reduce anxiety. We evaluated the anxiolytic effect of successive extracts of A. archangelica linn. (SAE) on rats tested in the elevated T-maze test (an animal model of generalized anxiety) at doses that exhibit antidepressant-like activity in humans. A. archangelica (1 kg) was subjected to successive extraction in a soxhlet apparatus with solvents [petroleum ether (40-60 degrees C), chloroform, ethyl acetate, methanol and decoction with water] in order of increasing polarity (yield: 6.9%, 7.3%, 5.1%, 11.88% and 8.2% w/w, respectively). SAE were evaluated for anxiolytic effects using the elevated T-maze and forced swimming tests in rats. Oral dosing of diazepam (1 mg/kg) and extracts (50, 100 and 200 mg/kg) clearly showed an anxiolytic-like profile in the elevated T-maze test: it increased one-way escape and decreased inhibitory avoidance on the first, third and seventh day. In the forced swimming test, imipramine and SAE showed antidepressant- and anxiolytic-like effects as reflected by increased climbing time, swimming time and decreased immobility time on the first, third and seventh day. Aqueous and methanol extracts showed the most, petroleum ether (40-60 degrees C) and chloroform intermediate, and ethyl acetate the least anxiolytic activity (*P<0.05, **P<0.01, ***P< 0.001) in both models. These results suggest the anti-anxiety activity of various extracts of A. archangelica and strongly justify its use in traditional Indian medicine for the treatment of anxiety.

  13. MASS TRANSFER COEFFICIENTS FOR A NON-NEWTONIAN FLUID AND WATER WITH AND WITHOUT ANTI-FOAM AGENTS

    Energy Technology Data Exchange (ETDEWEB)

    Leishear, R.

    2009-09-09

    Mass transfer rates were measured in a large scale system, which consisted of an 8.4 meter tall by 0.76 meter diameter column containing one of three fluids: water with an anti-foam agent, water without an anti-foam agent, and AZ101 simulant, which simulated a non-Newtonian nuclear waste. The testing contributed to the evaluation of large scale mass transfer of hydrogen in nuclear waste tanks. Due to its radioactivity, the waste was chemically simulated, and due to flammability concerns oxygen was used in lieu of hydrogen. Different liquids were used to better understand the mass transfer processes, where each of the fluids was saturated with oxygen, and the oxygen was then removed from solution as air bubbled up, or sparged, through the solution from the bottom of the column. Air sparging was supplied by a single tube which was co-axial to the column, the decrease in oxygen concentration was recorded, and oxygen measurements were then used to determine the mass transfer coefficients to describe the rate of oxygen transfer from solution. Superficial, average, sparging velocities of 2, 5, and 10 mm/second were applied to each of the liquids at three different column fill levels, and mass transfer coefficient test results are presented here for combinations of superficial velocities and fluid levels.

  14. MASS TRANSFER COEFFICIENTS FOR A NON-NEWTONIAN FLUID AND WATER WITH AND WITHOUT ANTI-FOAM AGENTS

    International Nuclear Information System (INIS)

    Leishear, R.

    2009-01-01

    Mass transfer rates were measured in a large scale system, which consisted of an 8.4 meter tall by 0.76 meter diameter column containing one of three fluids: water with an anti-foam agent, water without an anti-foam agent, and AZ101 simulant, which simulated a non-Newtonian nuclear waste. The testing contributed to the evaluation of large scale mass transfer of hydrogen in nuclear waste tanks. Due to its radioactivity, the waste was chemically simulated, and due to flammability concerns oxygen was used in lieu of hydrogen. Different liquids were used to better understand the mass transfer processes, where each of the fluids was saturated with oxygen, and the oxygen was then removed from solution as air bubbled up, or sparged, through the solution from the bottom of the column. Air sparging was supplied by a single tube which was co-axial to the column, the decrease in oxygen concentration was recorded, and oxygen measurements were then used to determine the mass transfer coefficients to describe the rate of oxygen transfer from solution. Superficial, average, sparging velocities of 2, 5, and 10 mm/second were applied to each of the liquids at three different column fill levels, and mass transfer coefficient test results are presented here for combinations of superficial velocities and fluid levels

  15. Inhibition of biofilm development of uropathogens by curcumin - an anti-quorum sensing agent from Curcuma longa.

    Science.gov (United States)

    Packiavathy, Issac Abraham Sybiya Vasantha; Priya, Selvam; Pandian, Shunmugiah Karutha; Ravi, Arumugam Veera

    2014-04-01

    Urinary tract infection is caused primarily by the quorum sensing (QS)-dependent biofilm forming ability of uropathogens. In the present investigation, an anti-quorum sensing (anti-QS) agent curcumin from Curcuma longa (turmeric) was shown to inhibit the biofilm formation of uropathogens, such as Escherichia coli, Pseudomonas aeruginosa PAO1, Proteus mirabilis and Serratia marcescens, possibly by interfering with their QS systems. The antibiofilm potential of curcumin on uropathogens as well as its efficacy in disturbing the mature biofilms was examined under light microscope and confocal laser scanning microscope. The treatment with curcumin was also found to attenuate the QS-dependent factors, such as exopolysaccharide production, alginate production, swimming and swarming motility of uropathogens. Furthermore, it was documented that curcumin enhanced the susceptibility of a marker strain and uropathogens to conventional antibiotics. Copyright © 2012 Elsevier Ltd. All rights reserved.

  16. In vitro, in silico and in vivo studies of ursolic acid as an anti-filarial agent.

    Directory of Open Access Journals (Sweden)

    Komal Kalani

    Full Text Available As part of our drug discovery program for anti-filarial agents from Indian medicinal plants, leaves of Eucalyptus tereticornis were chemically investigated, which resulted in the isolation and characterization of an anti-filarial agent, ursolic acid (UA as a major constituent. Antifilarial activity of UA against the human lymphatic filarial parasite Brugia malayi using in vitro and in vivo assays, and in silico docking search on glutathione-s-transferase (GST parasitic enzyme were carried out. The UA was lethal to microfilariae (mf; LC100: 50; IC50: 8.84 µM and female adult worms (LC100: 100; IC50: 35.36 µM as observed by motility assay; it exerted 86% inhibition in MTT reduction potential of the adult parasites. The selectivity index (SI of UA for the parasites was found safe. This was supported by the molecular docking studies, which showed adequate docking (LibDock scores for UA (-8.6 with respect to the standard antifilarial drugs, ivermectin (IVM -8.4 and diethylcarbamazine (DEC-C -4.6 on glutathione-s-transferase enzyme. Further, in silico pharmacokinetic and drug-likeness studies showed that UA possesses drug-like properties. Furthermore, UA was evaluated in vivo in B. malayi-M. coucha model (natural infection, which showed 54% macrofilaricidal activity, 56% female worm sterility and almost unchanged microfilaraemia maintained throughout observation period with no adverse effect on the host. Thus, in conclusion in vitro, in silico and in vivo results indicate that UA is a promising, inexpensive, widely available natural lead, which can be designed and developed into a macrofilaricidal drug. To the best of our knowledge this is the first ever report on the anti-filarial potential of UA from E. tereticornis, which is in full agreement with the Thomson Reuter's 'Metadrug' tool screening predictions.

  17. High-throughput identification of chemical inhibitors of E. coli Group 2 capsule biogenesis as anti-virulence agents.

    Directory of Open Access Journals (Sweden)

    Carlos C Goller

    Full Text Available Rising antibiotic resistance among Escherichia coli, the leading cause of urinary tract infections (UTIs, has placed a new focus on molecular pathogenesis studies, aiming to identify new therapeutic targets. Anti-virulence agents are attractive as chemotherapeutics to attenuate an organism during disease but not necessarily during benign commensalism, thus decreasing the stress on beneficial microbial communities and lessening the emergence of resistance. We and others have demonstrated that the K antigen capsule of E. coli is a preeminent virulence determinant during UTI and more invasive diseases. Components of assembly and export are highly conserved among the major K antigen capsular types associated with UTI-causing E. coli and are distinct from the capsule biogenesis machinery of many commensal E. coli, making these attractive therapeutic targets. We conducted a screen for anti-capsular small molecules and identified an agent designated "C7" that blocks the production of K1 and K5 capsules, unrelated polysaccharide types among the Group 2-3 capsules. Herein lies proof-of-concept that this screen may be implemented with larger chemical libraries to identify second-generation small-molecule inhibitors of capsule biogenesis. These inhibitors will lead to a better understanding of capsule biogenesis and may represent a new class of therapeutics.

  18. Cognitive impairment in anxiety disorders

    Directory of Open Access Journals (Sweden)

    B. A. Volel

    2018-01-01

    Full Text Available Anxiety disorders are an important biomedical problem due to the high prevalence and significant negative impact on the quality of life and the course of concomitant somatic and neurological diseases. Cognitive impairment (CI is one of the most intensively studied aspects of pathological anxiety. Impairments in attention, executive functions, memory, cognitive deficit, as well as abnormal cognitions and metacognitions are identified in anxiety disorders. Moreover, the treatment of the latter with the most frequently used drugs (antidepressants, atypical antipsychotics, anticonvulsants, tranquilizers does not lead to a significant improvement in cognitive functions, and often contributes to their worsening. In this connection, in addition to psychotherapy, cognitive function-improving agents play a large role in treating anxiety diseases associated with cognitive dysfunction. Ginkgo Biloba extract (EGb 761, Tanakan® that positively affects cognitive functions, especially in the domains of memory, concentration and attention deserves special attention.

  19. Depression and anxiety disorder among epileptic people at Amanuel Specialized Mental Hospital, Addis Ababa, Ethiopia.

    Science.gov (United States)

    Tegegne, Minale Tareke; Mossie, Tilahun Belete; Awoke, Andargie Abate; Assaye, Ashagre Molla; Gebrie, Belete Temitm; Eshetu, Desalegn Asmare

    2015-09-02

    Although depression and anxiety disorders are very common in people with epilepsy; there are no studies that assessed the magnitude and associated factors among epileptic people in Ethiopia. Therefore, this study determined prevalence and associated factors of depression and anxiety disorders in people with epilepsy. An institution based cross-sectional study was conducted from April to May, 2013, among 423 people with epilepsy from the outpatient department of Amanuel Mental Specialized Hospital. Depression and anxiety were assessed using the Hospital Anxiety and Depression Scale. Logistic regression analysis was used to assess predictors of depression and anxiety. The prevalence of anxiety and depression among epileptic people were 33.5 and 32.8%, respectively. Monthly income, frequency of seizure and side effects of anti convulsants were found to be significantly associated with both depression and anxiety. Being divorced/widowed was associated with anxiety while using poly-therapy of anti convulsants, perceived stigma, and inability to read or write were associated with depression. The prevalence of co-morbid anxiety and depression was found to be high among people with epilepsy. Early identification of co-morbid depression and anxiety in people with epilepsy and managing epilepsy to become seizure free should be of great concern for health care providers.

  20. MEK Inhibitors Reverse cAMP-Mediated Anxiety in Zebrafish

    DEFF Research Database (Denmark)

    Lundegaard, Pia R.; Anastasaki, Corina; Grant, Nicola J.

    2015-01-01

    Altered phosphodiesterase (PDE)-cyclic AMP (cAMP) activity is frequently associated with anxiety disorders, but current therapies act by reducing neuronal excitability rather than targeting PDE-cAMP-mediated signaling pathways. Here, we report the novel repositioning of anti-cancer MEK inhibitors...... as anxiolytics in a zebrafish model of anxiety-like behaviors. PDE inhibitors or activators of adenylate cyclase cause behaviors consistent with anxiety in larvae and adult zebrafish. Small-molecule screening identifies MEK inhibitors as potent suppressors of cAMP anxiety behaviors in both larvae and adult...... zebrafish, while causing no anxiolytic behavioral effects on their own. The mechanism underlying cAMP-induced anxiety is via crosstalk to activation of the RAS-MAPK signaling pathway. We propose that targeting crosstalk signaling pathways can be an effective strategy for mental health disorders, and advance...

  1. Alternative Agents to Prevent Fogging in Head and Neck Endoscopy

    Directory of Open Access Journals (Sweden)

    Patorn Piromchai

    2011-01-01

    Full Text Available Background The essential factor for diagnosis and treatment of diseases in head and neck endoscopy is the visibility of the image. An anti-fogging agent can reduce this problem by minimizing surface tension to prevent the condensation of water in the form of small droplets on a surface. There is no report on the use of hibiscrub ® or baby shampoo to reduce fogging in the literature. The objective of this study was to compare the efficacy between commercial anti-fogging agent, hibiscrub ® and baby shampoo to reduce fogging for the use in head and neck endoscopy. Methods The study was conducted at the Department of Otorhinolaryngology, Faculty of Medicine, Khon Kaen University in August 2010. Commercial anti-fogging agent, baby shampoo and hibiscrub ® were applied on rigid endoscope lens before putting them into a mist generator. The images were taken at baseline, 15 seconds, 30 seconds and 1 minute. The images' identifiers were removed before they were sent to two evaluators. A visual analogue scale (VAS was used to rate the image quality from 0 to 10. Results The difference in mean VAS score between anti-fogging agent, baby shampoo and hibiscrub ® versus no agent were 5.46, 4.45 and 2.1 respectively. The commercial anti-fogging agent and baby shampoo had most protective benefit and performed significantly better than no agent ( P < 0.05. Conclusions Baby shampoo is an effective agent to prevent fogging during head and neck endoscopy and compares favourably with commercial anti-fogging agent.

  2. Ganoderma lucidum Polysaccharides as An Anti-cancer Agent.

    Science.gov (United States)

    Sohretoglu, Didem; Huang, Shile

    2017-11-13

    The mushroom Ganoderma lucidum (G. lucidum) has been used for centuries in Asian countries to treat various diseases and to promote health and longevity. Clinical studies have shown beneficial effects of G. lucidum as an alternative adjuvant therapy in cancer patients without obvious toxicity. G. lucidum polysaccharides (GLP) is the main bioactive component in the water soluble extracts of this mushroom. Evidence from in vitro and in vivo studies has demonstrated that GLP possesses potential anticancer activity through immunomodulatory, anti-proliferative, pro-apoptotic, anti-metastatic and anti-angiogenic effects. Here, we briefly summarize these anticancer effects of GLP and the underlying mechanisms. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  3. Study of phytochemical, anti-microbial, anti-oxidant, and anti-cancer properties of Allium wallichii.

    Science.gov (United States)

    Bhandari, Jaya; Muhammad, BushraTaj; Thapa, Pratiksha; Shrestha, Bhupal Govinda

    2017-02-08

    There is growing interest in the use of plants for the treatment and prevention of cancer. Medicinal plants are currently being evaluated as source of promising anticancer agents. In this paper, we have investigated the anticancer potential of plant Allium wallichii, a plant native to Nepal and growing at elevations of 2300-4800 m. This is the first study of its kind for the plant mentioned. The dried plant was extracted in aqueous ethanol. Phytochemical screening, anti-microbial assay, anti-oxidant assay, cytotoxicity assay and the flow-cytometric analysis were done for analyzing different phytochemicals present, anti-microbial activity, anti-oxidant activity and anti-cancer properties of Allium wallichii. We observed the presence of steroids, terpenoids, flavonoids, reducing sugars and glycosides in the plant extract and the plant showed moderate anti-microbial and anti-oxidant activity. The IC 50 values of Allium wallichii in different cancer cell lines are 69.69 μg/ml for Prostate cancer (PC3) cell line, 55.29 μg/ml for Breast Cancer (MCF-7) cell line and 46.51 μg/ml for cervical cancer (HeLa) cell line as compared to Doxorubicin (0.85 μg/ml). The cell viability assay using FACS showed that the IC 50 value of Allium wallichii for Burkitt's lymphoma (B-Lymphoma) cell line was 3.817 ± 1.99 mg/ml. Allium wallichii can be an important candidate to be used as an anticancer agent. Separation of pure compounds with bioassay guided extraction, spectrometric analysis and subsequent cytotoxicity assay of the pure bioactive compounds from Allium wallichii is highly recommended as the crude extract itself showed promising cytotoxicity.

  4. Identification of novel anti-inflammatory agents from Ayurvedic medicine for prevention of chronic diseases: "reverse pharmacology" and "bedside to bench" approach.

    Science.gov (United States)

    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.

  5. Development of anti-infectives using phage display: biological agents against bacteria, viruses, and parasites.

    Science.gov (United States)

    Huang, Johnny X; Bishop-Hurley, Sharon L; Cooper, Matthew A

    2012-09-01

    The vast majority of anti-infective therapeutics on the market or in development are small molecules; however, there is now a nascent pipeline of biological agents in development. Until recently, phage display technologies were used mainly to produce monoclonal antibodies (MAbs) targeted against cancer or inflammatory disease targets. Patent disputes impeded broad use of these methods and contributed to the dearth of candidates in the clinic during the 1990s. Today, however, phage display is recognized as a powerful tool for selecting novel peptides and antibodies that can bind to a wide range of antigens, ranging from whole cells to proteins and lipid targets. In this review, we highlight research that exploits phage display technology as a means of discovering novel therapeutics against infectious diseases, with a focus on antimicrobial peptides and antibodies in clinical or preclinical development. We discuss the different strategies and methods used to derive, select, and develop anti-infectives from phage display libraries and then highlight case studies of drug candidates in the process of development and commercialization. Advances in screening, manufacturing, and humanization technologies now mean that phage display can make a significant contribution in the fight against clinically important pathogens.

  6. The Usage of Oral Anti Hyperglycemic Agent in Gestational Diabetes: Pros and Cons

    Directory of Open Access Journals (Sweden)

    Bram Pradipta

    2014-06-01

    Full Text Available The prevalence of gestational diabetes mellitus (GDM  is increasing as the pregnant population becomes older and more obese. Fifteen percent of GDM patients require medical intervention. Insulin is still the drug of choice because it has not been implicated as a teratogen in human pregnancies.Insulin has its disadvantages such as the need for injections, the risk of hypoglycaemia, excessive weight gain and the costs. The use of oral anti hyperglicemic agent (OAHA, traditionally contraindicated, now can be considered as an alternative for insulin which can be beneficial in developing countries. From four groups of OAHA, sulfonylurea and biguanides can be used during pregnancy. Studies and randomized controlled trial (RCT have been done and most summarized that it does not increase any maternal and perinatal morbidity. Most data also show that thereare also no differences in glycemic control or pregnancy outcomes compared with insulin. There are conflicting data shows metformin increase prevalence of preeclampsia patient and perinatal morbidity. OAHA usage, although not yet recommended internationally, can be considered in GDMpatients with uncontrolled blood sugar levels that require medical intervention but can not use insulin. Wellconducted, prospective, controlled studies regarding itsfeasibility in pregnant women with diabetes are still needed.Keywords:oral antihyperglycemic agent, gestational, diabetes

  7. Antimicrobial and anti-inflammatory activities of endophytic fungi Talaromyces wortmannii extracts against acne-inducing bacteria.

    Directory of Open Access Journals (Sweden)

    Alexander Pretsch

    Full Text Available Acne vulgaris is the most common skin disease, causing significant psychosocial problems such as anxiety and depression similar to a chronic illness for those afflicted. Currently, obtainable agents for acne treatment have limited use. Thus, development of novel agents to treat this disease is a high medical need. The anaerobic bacterium Propionibacterium acnes has been implicated in the inflammatory phase of acne vulgaris by activating pro-inflammatory mediators such as the interleukin-8 (IL-8 via the NF-κB and MAPK pathways. Talaromyces wortmannii is an endophytic fungus, which is known to produce high bioactive natural compounds. We hypothesize that compound C but also the crude extract from T. wortmannii may possess both antibacterial activity especially against P. acnes and also anti-inflammatory properties by inhibiting TNF-α-induced ICAM-1 expression and P. acnes-induced IL-8 release. Treatment of keratinocytes (HaCaT with P. acnes significantly increased NF-κB and activator protein-1 (AP-1 activation, as well as IL-8 release. Compound C inhibited P. acnes-mediated activation of NF-κB and AP-1 by inhibiting IκB degradation and the phosphorylation of ERK and JNK MAP kinases, and IL-8 release in a dose-dependent manner. Based on these results, compound C has effective antimicrobial activity against P. acnes and anti-inflammatory activity, and we suggest that this substance or the crude extract are alternative treatments for antibiotic/anti-inflammatory therapy for acne vulgaris.

  8. Antimicrobial and Anti-Inflammatory Activities of Endophytic Fungi Talaromyces wortmannii Extracts against Acne-Inducing Bacteria

    Science.gov (United States)

    Schwendinger, Katja; Kreiseder, Birgit; Wiederstein, Martina; Pretsch, Dagmar; Genov, Miroslav; Hollaus, Ralph; Zinssmeister, Daniela; Debbab, Abdesamad; Hundsberger, Harald; Eger, Andreas; Proksch, Peter; Wiesner, Christoph

    2014-01-01

    Acne vulgaris is the most common skin disease, causing significant psychosocial problems such as anxiety and depression similar to a chronic illness for those afflicted. Currently, obtainable agents for acne treatment have limited use. Thus, development of novel agents to treat this disease is a high medical need. The anaerobic bacterium Propionibacterium acnes has been implicated in the inflammatory phase of acne vulgaris by activating pro-inflammatory mediators such as the interleukin-8 (IL-8) via the NF-κB and MAPK pathways. Talaromyces wortmannii is an endophytic fungus, which is known to produce high bioactive natural compounds. We hypothesize that compound C but also the crude extract from T. wortmannii may possess both antibacterial activity especially against P. acnes and also anti-inflammatory properties by inhibiting TNF-α-induced ICAM-1 expression and P. acnes-induced IL-8 release. Treatment of keratinocytes (HaCaT) with P. acnes significantly increased NF-κB and activator protein-1 (AP-1) activation, as well as IL-8 release. Compound C inhibited P. acnes-mediated activation of NF-κB and AP-1 by inhibiting IκB degradation and the phosphorylation of ERK and JNK MAP kinases, and IL-8 release in a dose-dependent manner. Based on these results, compound C has effective antimicrobial activity against P. acnes and anti-inflammatory activity, and we suggest that this substance or the crude extract are alternative treatments for antibiotic/anti-inflammatory therapy for acne vulgaris. PMID:24887557

  9. Contribution of Helicobacter pylori infection to the risk of peptic ulcer bleeding in patients on nonsteroidal anti-inflammatory drugs, antiplatelet agents, anticoagulants, corticosteroids and selective serotonin reuptake inhibitors.

    Science.gov (United States)

    Venerito, M; Schneider, C; Costanzo, R; Breja, R; Röhl, F-W; Malfertheiner, P

    2018-06-01

    Nonsteroidal anti-inflammatory drugs, low-dose aspirin, non-aspirin antiplatelet agents, anticoagulants, selective serotonin reuptake inhibitors and corticosteroids increase the risk of gastroduodenal bleeding. To determine in a retrospective cohort study the contribution of Helicobacter pylori infection to the risk of peptic ulcer bleeding in patients taking these drugs. Among patients with peptic ulcer disease diagnosed by endoscopy from 01/2004 to 12/2014 (N = 1719, 60% males, age 65.8 ± 14.5), 56.9% had peptic ulcer bleeding (cases) and 43.1% uncomplicated peptic ulcer disease (controls). Demographics, intake of nonsteroidal anti-inflammatory drugs, aspirin, non-aspirin antiplatelet agents, anticoagulants, selective serotonin reuptake inhibitors, proton pump inhibitors and corticosteroids were documented. H. pylori status was determined by histology, rapid urease test or serology. Adjusted odds ratios (OR) were estimated by logistic regression analysis. Helicobacter pylori infection increased the risk of peptic ulcer bleeding in nonsteroidal anti-inflammatory drug and aspirin users (OR = 2.91, 95% CI = 1.71-4.98 and OR = 2.23, 95% CI = 1.52-3.28, respectively), but not in patients on anticoagulants, selective serotonin reuptake inhibitor or corticosteroid therapy. H. pylori-positive status substantially increased the risk of peptic ulcer bleeding in patients on non-aspirin antiplatelet agents (OR = 4.37, 95% CI = 1.28-14.99), concomitant aspirin/nonsteroidal anti-inflammatory drug intake (OR = 5.85, 95% CI = 1.68-20.36) and combined antiplatelet therapy (OR = 8.43, 95% CI = 1.09-65.17). After further adjustment for proton pump inhibitor intake, H. pylori infection was still a risk factor for peptic ulcer bleeding in nonsteroidal anti-inflammatory drug and aspirin users. Helicobacter pylori infection increases the risk of peptic ulcer bleeding in peptic ulcer disease patients on nonsteroidal anti-inflammatory drugs, aspirin and non

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

    Directory of Open Access Journals (Sweden)

    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.

  11. Intermittent fasting combined with supplementation with Ayurvedic herbs reduces anxiety in middle aged female rats by anti-inflammatory pathways.

    Science.gov (United States)

    Singh, Harpal; Kaur, Taranjeet; Manchanda, Shaffi; Kaur, Gurcharan

    2017-08-01

    Intermittent fasting-dietary restriction (IF-DR) is an increasingly popular intervention to promote healthy aging and delay age associated decline in brain functions. Also, the use of herbal interventions is gaining attention due to their non-pharmacological approach to treat several abnormalities and promote general health with least side effects. The present study was aimed to investigate the synergistic effects of IF-DR regimen with herbal supplementation on anxiety-like behavior and neuroinflammation in middle aged female rats. We used dried leaf powder of Withania somnifera and dried stem powder of Tinospora cordifolia for our study. The rats were divided into three groups: (1) Control group fed ad libitum (AL); (2) rats deprived of food for full day and fed ad libitum on every alternate day (IF-DR); and (3) IF-DR and herbal extract (DRH) group in which rats were fed ad libitum with herbal extract supplemented diet, every alternate day. Post regimen, the rats were tested for anxiety-like behavior and further used for study of key inflammatory molecules (NFκB, Iba1, TNFα, IL-1β, IL-6) and glial marker (GFAP) in hippocampus and piriform cortex regions of brain. The study was further extended to explore the effect of DRH regimen on stress response protein (HSP70) and calcium dependent regulators of synaptic plasticity (CaMKIIα, Calcineurin). Our data demonstrated that DRH regimen reduced anxiety-like behavior in middle age female rats and associated neuroinflammation by ameliorating key inflammatory cytokines and modulated stress response. The present data may provide scientific validation for anxiolytic and anti-inflammatory potential of herbal intervention combined with short term IF-DR regimen.

  12. Rational design, synthesis, and biological evaluation of third generation α-noscapine analogues as potent tubulin binding anti-cancer agents.

    Directory of Open Access Journals (Sweden)

    Naresh Kumar Manchukonda

    Full Text Available Systematic screening based on structural similarity of drugs such as colchicine and podophyllotoxin led to identification of noscapine, a microtubule-targeted agent that attenuates the dynamic instability of microtubules without affecting the total polymer mass of microtubules. We report a new generation of noscapine derivatives as potential tubulin binding anti-cancer agents. Molecular modeling experiments of these derivatives 5a, 6a-j yielded better docking score (-7.252 to -5.402 kCal/mol than the parent compound, noscapine (-5.505 kCal/mol and its existing derivatives (-5.563 to -6.412 kCal/mol. Free energy (ΔG bind calculations based on the linear interaction energy (LIE empirical equation utilizing Surface Generalized Born (SGB continuum solvent model predicted the tubulin-binding affinities for the derivatives 5a, 6a-j (ranging from -4.923 to -6.189 kCal/mol. Compound 6f showed highest binding affinity to tubulin (-6.189 kCal/mol. The experimental evaluation of these compounds corroborated with theoretical studies. N-(3-brormobenzyl noscapine (6f binds tubulin with highest binding affinity (KD, 38 ± 4.0 µM, which is ~ 4.0 times higher than that of the parent compound, noscapine (KD, 144 ± 1.0 µM and is also more potent than that of the first generation clinical candidate EM011, 9-bromonoscapine (KD, 54 ± 9.1 µM. All these compounds exhibited substantial cytotoxicity toward cancer cells, with IC50 values ranging from 6.7 µM to 72.9 µM; compound 6f showed prominent anti-cancer efficacy with IC50 values ranging from 6.7 µM to 26.9 µM in cancer cells of different tissues of origin. These compounds perturbed DNA synthesis, delayed the cell cycle progression at G2/M phase, and induced apoptotic cell death in cancer cells. Collectively, the study reported here identified potent, third generation noscapinoids as new anti-cancer agents.

  13. Anti-Bacterial and Anti-Fungal Activity of Xanthones Obtained via Semi-Synthetic Modification of α-Mangostin from Garcinia mangostana

    Directory of Open Access Journals (Sweden)

    Srinivasan Narasimhan

    2017-02-01

    Full Text Available The microbial contamination in food packaging has been a major concern that has paved the way to search for novel, natural anti-microbial agents, such as modified α-mangostin. In the present study, twelve synthetic analogs were obtained through semi-synthetic modification of α-mangostin by Ritter reaction, reduction by palladium-carbon (Pd-C, alkylation, and acetylation. The evaluation of the anti-microbial potential of the synthetic analogs showed higher bactericidal activity than the parent molecule. The anti-microbial studies proved that I E showed high anti-bacterial activity whereas I I showed the highest anti-fungal activity. Due to their microbicidal potential, modified α-mangostin derivatives could be utilized as active anti-microbial agents in materials for the biomedical and food industry.

  14. Novel 3-Nitro-1H-1,2,4-triazole-based Amides and Sulfonamides as Potential anti-Trypanosomal Agents

    Science.gov (United States)

    Papadopoulou, Maria V.; Bloomer, William D.; Rosenzweig, Howard S.; Chatelain, Eric; Kaiser, Marcel; Wilkinson, Shane R.; McKenzie, Caroline; Ioset, Jean-Robert

    2012-01-01

    A series of novel 3-nitro-1H-1,2,4-triazole-(and in some cases 2-nitro-1H-imidazole)-based amides and sulfonamides were characterized for their in vitro anti-trypanosomal and antileishmanial activities as well as mammalian toxicity. Out of 36 compounds tested, 29 (mostly 3-nitro-1H-1,2,4-triazoles) displayed significant activity against T. cruzi intracellular amastigotes (IC50 ranging from 28 nM to 3.72 μM) without concomitant toxicity to L6 host cells (selectivity 66 to 2782). Twenty three of these active compounds were more potent (up to 58 fold) than the reference drug benznidazole, tested in parallel. In addition, 9 nitrotriazoles which were moderately active (0.5 μM ≤ IC50 amides and sulfonamides are potent anti-trypanosomal agents. PMID:22550999

  15. Inhibition of human polimorfonuclear leucocyte migration by clofazimine: a new pro-oxidative anti-inflammatory agent

    International Nuclear Information System (INIS)

    Jansen van Rensburg, C.E.

    1986-10-01

    Preliminary studies on the in vitro and in vivo effects of clofazimine on the function of polymorphonuclear leucocytes (PMNL) from normal individuals and patients with lepromatous leprosy showed that clofazimine caused a progressive dose-dependent inhibition of both random mortality of PMNL as well as migration of PMNL induced by the leucoattractant endotoxin-activated serum (EAS). The drug also increased chemiluminescence as well as hexose monophosphate shunt (HMS). These studies on clofazimine include the use of radiolabelling with 14 C, 125 I and 3 H. Clofazimine-mediated inhibition of PMNL migration is dependent on intact membrane-associated oxidative metabolism. Clofazimine is therefore a pro-oxidative anti-inflammatory agent

  16. Evaluation of combinations of putative anti-biofilm agents and antibiotics to eradicate biofilms of Staphylococcus aureus and Pseudomonas aeruginosa.

    Science.gov (United States)

    Belfield, Katherine; Bayston, Roger; Hajduk, Nadzieja; Levell, Georgia; Birchall, John P; Daniel, Matija

    2017-09-01

    To evaluate potential anti-biofilm agents for their ability to enhance the activity of antibiotics for local treatment of localized biofilm infections. Staphylococcus aureus and Pseudomonas aeruginosa in vitro biofilm models were developed. The putative antibiotic enhancers N-acetylcysteine, acetylsalicylic acid, sodium salicylate, recombinant human deoxyribonuclease I, dispersin B, hydrogen peroxide and Johnson's Baby Shampoo (JBS) were tested for their anti-biofilm activity alone and their ability to enhance the activity of antibiotics for 7 or 14 days, against 5 day old biofilms. The antibiotic enhancers were paired with rifampicin and clindamycin against S. aureus and gentamicin and ciprofloxacin against P. aeruginosa. Isolates from biofilms that were not eradicated were tested for antibiotic resistance. Antibiotic levels 10× MIC and 100× MIC significantly reduced biofilm, but did not consistently eradicate it. Antibiotics at 100× MIC with 10% JBS for 14 days was the only treatment to eradicate both staphylococcal and pseudomonal biofilms. Recombinant human deoxyribonuclease I significantly reduced staphylococcal biofilm. Emergence of resistance of surviving isolates was minimal and was often associated with the small colony variant phenotype. JBS enhanced the activity of antibiotics and several other promising anti-biofilm agents were identified. Antibiotics with 10% JBS eradicated biofilms produced by both organisms. Such combinations might be useful in local treatment of localized biofilm infections. © The Author 2017. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  17. Gastroduodenal mucosal defence mechanisms and the action of non-steroidal anti-inflammatory agents.

    Science.gov (United States)

    Garner, A; Allen, A; Rowe, P H

    1987-01-01

    This review summarises gastroduodenal protective mechanisms, the actions of non-steroidal anti-inflammatory (NSAI) agents on mucus and HCO3 secretions, and the basis of gastric mucosal injury induced by acetylsalicylic and salicylic acids (ASA and SA). Resistance to autodigestion by acid and pepsin present in gastric juice is multifactorial involving pre-epithelial (mucus-bicarbonate barrier) and post-epithelial (blood flow, acid-base balance) factors in addition to properties of the surface cell layer per se. The latter includes mucosal re-epithelialisation, a property which appears particularly important with respect to recovery from acute injury. A range of NSAI agents (ASA, fenclofenac, ibuprofen and indomethacin) inhibit gastric HCO3 transport in isolated mucosal preparations. Inhibition of duodenal HCO3 transport has been demonstrated in response to indomethacin in vitro and in vivo. These effects on secretion can be antagonised by exogenous prostaglandins of the E series. The layer of secreted mucus gel overlying the epithelial surface is not affected by NSAI drugs in the short term. However a number of these agents have been shown to inhibit glycoprotein biosynthesis by the epithelial cells. Thus loss of this protective coat could be anticipated during chronic drug exposure since erosion of adherent mucus by luminal shear and proteolysis would not be compensated by continued secretion. Detailed analysis of the gastric mucosal injury induced by salicylates both in vitro and in vivo reveals that much of the damage previously attributed to ASA is in fact due to the metabolic product SA. In this respect it is concluded that mucosal injury caused by ASA is due to a combination of two factors.(ABSTRACT TRUNCATED AT 250 WORDS)

  18. Anti-vascular agent Combretastatin A-4-P modulates Hypoxia Inducible Factor-1 and gene expression

    Directory of Open Access Journals (Sweden)

    Currie Margaret J

    2006-12-01

    Full Text Available Abstract Background A functional vascular network is essential for the survival, growth and spread of solid tumours, making blood vessels a key target for therapeutic strategies. Combretastatin A-4 phosphate (CA-4-P is a tubulin-depolymerising agent in Phase II clinical trials as a vascular disrupting agent. Not much is known of the molecular effect of CA-4-P under tumour conditions. The tumour microenvironment differs markedly from that in normal tissue, specifically with respect to oxygenation (hypoxia. Gene regulation under tumour conditions is governed by hypoxia inducible factor 1 (HIF-1, controlling angiogenic and metastatic pathways. Methods We investigated the effect of CA-4-P on factors of the upstream and downstream signalling pathway of HIF-1 in vitro. Results CA-4-P treatment under hypoxia tended to reduce HIF-1 accumulation in a concentration-dependent manner, an effect which was more prominent in endothelial cells than in cancer cell lines. Conversely, CA-4-P increased HIF-1 accumulation under aerobic conditions in vitro. At these concentrations of CA-4-P under aerobic conditions, nuclear factor κB was activated via the small GTPase RhoA, and expression of the HIF-1 downstream angiogenic effector gene, vascular endothelial growth factor (VEGF-A, was increased. Conclusion Our findings advance the understanding of signal transduction pathways involved in the actions of the anti-vascular agent CA-4-P.

  19. Application of quercetin and its bio-inspired nanoparticles as anti-adhesive agents against Bacillus subtilis attachment to surface

    Energy Technology Data Exchange (ETDEWEB)

    Raie, Diana S., E-mail: raiediana@yahoo.com [Process Design and Development Department, Egyptian Petroleum Research Institute (EPRI), Nasr City, Cairo (Egypt); Mhatre, Eisha [Terrestrial Biofilms Group, Institute of Microbiology, Friedrich Schiller University Jena (FSU), Jena (Germany); Thiele, Matthias [Nanobiophotonic Department, Leibniz Institute of Photonic Technology Jena (IPHT), Jena (Germany); Labena, A. [Process Design and Development Department, Egyptian Petroleum Research Institute (EPRI), Nasr City, Cairo (Egypt); El-Ghannam, Gamal [National Institute of Laser Enhanced Sciences (NILES), Cairo University, Giza (Egypt); Farahat, Laila A. [Process Design and Development Department, Egyptian Petroleum Research Institute (EPRI), Nasr City, Cairo (Egypt); Youssef, Tareq [National Institute of Laser Enhanced Sciences (NILES), Cairo University, Giza (Egypt); Fritzsche, Wolfgang [Nanobiophotonic Department, Leibniz Institute of Photonic Technology Jena (IPHT), Jena (Germany); Kovács, Ákos T., E-mail: akos-tibor.kovacs@uni-jena.de [Terrestrial Biofilms Group, Institute of Microbiology, Friedrich Schiller University Jena (FSU), Jena (Germany)

    2017-01-01

    The aim of this study was directed to reveal the repulsive effect of coated glass slides by quercetin and its bio-inspired titanium oxide and tungsten oxide nanoparticles on physical surface attachment of Bacillus subtilis as an ab-initio step of biofilm formation. Nanoparticles were successfully synthesized using sol–gel and acid precipitation methods for titanium oxide and tungsten oxide, respectively (in the absence or presence of quercetin). The anti-adhesive impact of the coated-slides was tested through the physical attachment of B. subtilis after 24 h using Confocal Laser Scanning Microscopy (CLSM). Here, quercetin was presented as a bio-route for the synthesis of tungsten mixed oxides nano-plates at room temperature. In addition, quercetin had an impact on zeta potential and adsorption capacity of both bio-inspired amorphous titanium oxide and tungsten oxide nano-plates. Interestingly, our experiments indicated a contrary effect of quercetin as an anti-adhesive agent than previously reported. However, its bio-inspired metal oxide proved their repulsive efficiency. In addition, quercetin-mediated nano-tungsten and quercetin-mediated amorphous titanium showed anti-adhesive activity against B. subtilis biofilm. - Highlights: • Novel quercetin-mediated nanoparticles were tested for anti-adhesion against attachment of cells forming biofilms. • Quercetin showed a low-grade of protection level against bacterial attachment. • Bio-inspired nano-anatase showed a lower efficiency than amorphous titanium. • Thermally treated bio-inspired nano-tungsten gets an improved anti-adhesive activity.

  20. Targeting Phosphatidylinositol 4-Kinase IIIα for Radiosensitization: A Potential Model of Drug Repositioning Using an Anti-Hepatitis C Viral Agent

    Energy Technology Data Exchange (ETDEWEB)

    Kwon, Jeanny [Department of Radiation Oncology, Graduate School of Medicine, Seoul National University, Seoul (Korea, Republic of); Kim, Dan Hyo; Park, Ji Min [Medical Science Research Institute, Seoul National University Bundang Hospital, Seongnam (Korea, Republic of); Park, Young Hee [Department of Radiation Oncology, Graduate School of Medicine, Seoul National University, Seoul (Korea, Republic of); Hwang, Yeo Hyun [Medical Science Research Institute, Seoul National University Bundang Hospital, Seongnam (Korea, Republic of); Wu, Hong-Gyun [Department of Radiation Oncology, Graduate School of Medicine, Seoul National University, Seoul (Korea, Republic of); Institute of Radiation Medicine, Seoul National University, Seoul (Korea, Republic of); Shin, Kyung Hwan [Department of Radiation Oncology, Graduate School of Medicine, Seoul National University, Seoul (Korea, Republic of); Kim, In Ah, E-mail: inah228@snu.ac.kr [Department of Radiation Oncology, Graduate School of Medicine, Seoul National University, Seoul (Korea, Republic of); Medical Science Research Institute, Seoul National University Bundang Hospital, Seongnam (Korea, Republic of); Institute of Radiation Medicine, Seoul National University, Seoul (Korea, Republic of); Cancer Research Institute, Seoul National University, Seoul (Korea, Republic of)

    2016-11-15

    Purpose: To investigate which isotype of phosphatidylinositol 4-kinase (PI4K) may affect radiosensitivity and examine whether anti–hepatitis C viral (HCV) agents, some of which have been shown to inhibit PI4K IIIα activity, could be repositioned as a radiosensitizer in human cancer cells. Methods and Materials: U251, BT474, and HepG2 cell lines and normal human astrocyte were used. Ribonucleic acid interference, clonogenic assays, Western blotting, immunofluorescence, annexin V assay, lysotracker staining, and β-galactosidase assay were performed. Results: Of the 4 PI4K isotypes, specific inhibition of IIIα increased radiosensitivity. For pharmacologic inhibition of PI4K IIIα, we screened 9 anti-HCV agents by half-maximal inhibitory concentration assay. Simeprevir was selected, and its inhibition of PI4K IIIα activity was confirmed. Combination of simeprevir treatment and radiation significantly attenuated expression of phospho-phospho-PKC and phospho-Akt and increased radiation-induced cell death in tested cell lines. Pretreatment with simeprevir prolonged γH2AX foci formation and down-regulation of phospho-DNA-PKcs, indicating impairment of nonhomologous end-joining repair. Cells pretreated with simeprevir exhibited mixed modes of cell death, including apoptosis and autophagy. Conclusion: These data demonstrate that targeting PI4K IIIα using an anti-HCV agent is a viable approach to enhance the therapeutic efficacy of radiation therapy in various human cancers, such as glioma, breast, and hepatocellular carcinoma.

  1. Embolization biomaterial reinforced with nanotechnology for an in-situ release of anti-angiogenic agent in the treatment of hyper-vascularized tumors and arteriovenous malformations.

    Science.gov (United States)

    Jubeli, E; Yagoubi, N; Pascale, F; Bédouet, L; Slimani, K; Labarre, D; Saint-Maurice, J P; Laurent, A; Moine, L

    2015-10-01

    A polymer based material was developed to act as an embolic agent and drug reservoir for the treatment of arteriovenous malformations (AVM) and hyper vascularized solid tumors. The aim was to combine the blocking of blood supply to the target region and the inhibition of the embolization-stimulated angiogenesis. The material is composed of an ethanolic solution of a linear acrylate based copolymer and acrylate calibrated microparticles containing nanospheres loaded with sunitinib, an anti-angiogenic agent. The precipitation of the linear copolymer in aqueous environment after injection through microcatheter results in the formation of an in-situ embolization gel whereas the microparticles serve to increase the cohesive properties of the embolization agent and to form a reservoir from which the sunitinib-loaded nanospheres are released post-embolization. The swollen state of the microparticles in contact with aqueous medium results in the release of the nanospheres out of microparticles macromolecular structure. After the synthesis, the formulation and the characterization of the different components of the material, anti-angiogenic activity was evaluated in vitro using endothelial cells and in vivo using corneal neovascularization model in rabbit. The efficiency of the arterial embolization was tested in vivo in a sheep model. Results proved the feasibility of this new system for vascular embolization in association with an in situ delivery of anti-angiogenic drug. This combination is a promising strategy for the management of arteriovenous malformations and solid tumors. Copyright © 2015 Elsevier B.V. All rights reserved.

  2. Premedication with melatonin vs midazolam: efficacy on anxiety and compliance in paediatric surgical patients.

    Science.gov (United States)

    Impellizzeri, Pietro; Vinci, Enrica; Gugliandolo, Maria Cristina; Cuzzocrea, Francesca; Larcan, Rosalba; Russo, Tiziana; Gravina, Maria Rosaria; Arena, Salvatore; D'Angelo, Gabriella; Gitto, Eloisa; Montalto, Angela Simona; Alibrandi, Angela; Marseglia, Lucia; Romeo, Carmelo

    2017-07-01

    Preoperative anxiety is a major problem in paediatric surgical patients. Melatonin has been used as a premedicant agent and data regarding effectiveness are controversial. The primary outcome of this randomized clinical trial was to evaluate the effectiveness of oral melatonin premedication, in comparison to midazolam, in reducing preoperative anxiety in children undergoing elective surgery. As secondary outcome, compliance to intravenous induction anaesthesia was assessed. There were 80 children undergoing surgery randomly assigned, 40 per group, to receive oral midazolam (0.5 mg/kg, max 20 mg) or oral melatonin (0.5 mg/kg, max 20 mg). Trait anxiety of children and their mothers (State-Trait Anxiety Inventory) at admission, preoperative anxiety and during anaesthesia induction (Modified Yale Pre-operative Anxiety Scale), and children's compliance with anaesthesia induction (Induction Compliance Checklist) were all assessed. Children premedicated with melatonin and midazolam did not show significant differences in preoperative anxiety levels, either in the preoperative room or during anaesthesia induction. Moreover, compliance during anaesthesia induction was similar in both groups. This study adds new encouraging data, further supporting the potential use of melatonin premedication in reducing anxiety and improving compliance to induction of anaesthesia in children undergoing surgery. Nevertheless, further larger controlled clinical trials are needed to confirm the real effectiveness of melatonin as a premedicant agent in paediatric population. What is Known: • Although midazolam represents the preferred treatment as a premedication for children before induction of anaesthesia, it has several side effects. • Melatonin has been successfully used as a premedicant agent in adults, while data regarding effectiveness in children are controversial. What is New: • In this study, melatonin was as effective as midazolam in reducing children's anxiety in both

  3. Xanthone and Flavone Derivatives as Dual Agents with Acetylcholinesterase Inhibition and Antioxidant Activity as Potential Anti-Alzheimer Agents

    Directory of Open Access Journals (Sweden)

    Inês Cruz

    2017-01-01

    Full Text Available Alzheimer’s disease (AD is a multifactorial neurodegenerative disorder that is associated with the elderly. The current therapy that is used to treat AD is based mainly on the administration of acetylcholinesterase (AChE inhibitors. Due to their low efficacy there is a considerable need for other therapeutic strategies. Considering that the malfunctions of different, but interconnected, biochemical complex pathways play an important role in the pathogenesis of this disease, a promising therapy may consist in administration of drugs that act on more than a target on biochemical scenery of AD. In this work, the synthesis and evaluation of xanthone and flavone derivatives as antioxidants with AChE inhibitory activity were accomplished. Among the obtained compounds, Mannich bases 3 and 14 showed capacity to inhibit AChE and antioxidant property, exerting dual activity. Moreover, for the most promising AChE inhibitors, docking studies on the target have been performed aiming to predict the binding mechanism. The results presented here may help to identify new xanthone and flavone derivatives as dual anti-Alzheimer agents with AChE inhibitory and antioxidant activities.

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

    Science.gov (United States)

    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.

  5. Fear Appeal in Traffic Safety Advertising: The moderating role of medium context, trait anxiety, and differences between drivers and non-drivers

    OpenAIRE

    Janssens, Wim; De Pelsmacker, Patrick

    2007-01-01

    The impact was investigated of the intensity of a fear appeal, the valence of the medium context, and the individuals' trait anxiety and personal relevance on the responses of 197 individuals to anti-speeding advertisements. A high level of fear attracts more attention. A negative valence context leads to a more positive anti-speeding attitude. The most important moderating effect of trait anxiety is that the attitude is more positive when low-anxiety individuals are exposed to high fear appe...

  6. Synthesis and Biological Evaluation of 2H-Indazole Derivatives: Towards Antimicrobial and Anti-Inflammatory Dual Agents

    Directory of Open Access Journals (Sweden)

    Jaime Pérez-Villanueva

    2017-10-01

    Full Text Available Indazole is considered a very important scaffold in medicinal chemistry. It is commonly found in compounds with diverse biological activities, e.g., antimicrobial and anti-inflammatory agents. Considering that infectious diseases are associated to an inflammatory response, we designed a set of 2H-indazole derivatives by hybridization of cyclic systems commonly found in antimicrobial and anti-inflammatory compounds. The derivatives were synthesized and tested against selected intestinal and vaginal pathogens, including the protozoa Giardia intestinalis, Entamoeba histolytica, and Trichomonas vaginalis; the bacteria Escherichia coli and Salmonella enterica serovar Typhi; and the yeasts Candida albicans and Candida glabrata. Biological evaluations revealed that synthesized compounds have antiprotozoal activity and, in most cases, are more potent than the reference drug metronidazole, e.g., compound 18 is 12.8 times more active than metronidazole against G. intestinalis. Furthermore, two 2,3-diphenyl-2H-indazole derivatives (18 and 23 showed in vitro growth inhibition against Candida albicans and Candida glabrata. In addition to their antimicrobial activity, the anti-inflammatory potential for selected compounds was evaluated in silico and in vitro against human cyclooxygenase-2 (COX-2. The results showed that compounds 18, 21, 23, and 26 display in vitro inhibitory activity against COX-2, whereas docking calculations suggest a similar binding mode as compared to rofecoxib, the crystallographic reference.

  7. How action researchers use anxiety to facilitate change in health care.

    Science.gov (United States)

    Evans, Nicola; Hopkinson, Jane

    2016-06-01

    The aim of this paper is to report on the role of an action researcher in a study investigating the change process in a health service context where a new assessment clinic was developed to manage the excessive waiting list for that service. For effective organisational change in health, there is a suggestion that change agents need to be emotionally intelligent; recognising the emotional state of individuals, reconciling that with the organisational drivers and making an assessment of readiness for organisational change. Anxiety features throughout this literature and there is a suggestion that being aware of anxiety and managing anxiety is within the emotionally intelligent change agent's repertoire, but there is a gap in the literature that explains this relationship in detail. Data were generated to investigate the discrete nature of the role of the action researcher during this organisational change that spanned two years, through three methods: participant observations in the field captured in field notes (n = 72); observations of team meetings that had been recorded and transcribed (n = 13); interviews with key informants pre- and postintervention (n = 14); a reflexive diary one document of 8920 words (n = 1). The data illuminating the interaction between the action researcher and participants were synthesised into two broad themes: how the action researcher introduced anxiety into the system; how the action researcher facilitated the participants to tolerate change anxiety. The findings from this study can be applied in clinical practice where change in practice is planned. Part of the requirement of a change agent in the NHS might be to be sufficiently emotionally literate to understand anxiety in the participant system and manage it to effect change. © 2016 John Wiley & Sons Ltd.

  8. Non-operative anti-caries agents and dental caries increment among adults at high caries risk: a retrospective cohort study

    OpenAIRE

    Chaffee, Benjamin W.; Cheng, Jing; Featherstone, John DB

    2015-01-01

    Background Consensus guidelines support non-operative preventives for dental caries management; yet, their use in practice is far from universal. The purpose of this study was to evaluate the effectiveness of non-operative anti-caries agents in caries prevention among high caries risk adults at a university clinic where risk-based caries management is emphasized. Methods This retrospective observational study drew data from the electronic patient records of non-edentulous adult patients deeme...

  9. Discovery and Evaluation of Thiazinoquinones as Anti-Protozoal Agents

    Directory of Open Access Journals (Sweden)

    Marcel Kaiser

    2013-09-01

    Full Text Available Pure compound screening has identified the dioxothiazino-quinoline-quinone ascidian metabolite ascidiathiazone A (2 to be a moderate growth inhibitor of Trypanosoma brucei rhodesiense (IC50 3.1 μM and Plasmodium falciparum (K1 dual drug resistant strain (IC50 3.3 μM while exhibiting low levels of cytotoxicity (L6, IC50 167 μM. A series of C-7 amide and Δ2(3 analogues were prepared that explored the influence of lipophilicity and oxidation state on observed anti-protozoal activity and selectivity. Little variation in anti-malarial potency was observed (IC50 0.62–6.5 μM, and no correlation was apparent between anti-malarial and anti-T. brucei activity. Phenethylamide 7e and Δ2(3-glycine analogue 8k exhibited similar anti-Pf activity to 2 but with slightly enhanced selectivity (SI 72 and 93, respectively, while Δ2(3-phenethylamide 8e (IC50 0.67 μM, SI 78 exhibited improved potency and selectivity towards T. brucei rhodesiense compared to the natural product hit. A second series of analogues were prepared that replaced the quinoline ring of 2 with benzofuran or benzothiophene moieties. While esters 10a/10b and 15 were once again found to exhibit cytotoxicity, carboxylic acid analogues exhibited potent anti-Pf activity (IC50 0.34–0.035 μM combined with excellent selectivity (SI 560–4000. In vivo evaluation of a furan carboxylic acid analogue against P. berghei was undertaken, demonstrating 85.7% and 47% reductions in parasitaemia with ip or oral dosing respectively.

  10. Emerging Drugs for the Treatment of Anxiety

    Science.gov (United States)

    Murrough, James W.; Yaqubi, Sahab; Sayed, Sehrish; Charney, Dennis S.

    2016-01-01

    Introduction Anxiety disorders are among the most prevalent and disabling psychiatric disorders in the United States and worldwide. Basic research has provided critical insights into the mechanism regulating fear behavior in animals and a host of animal models have been developed in order to screen compounds for anxiolytic properties. Despite this progress, no mechanistically novel agents for the treatment of anxiety have come to market in more than two decades. Areas covered The current review will provide a critical summary of current pharmacological approaches to the treatment of anxiety and will examine the pharmacotherapeutic pipeline for treatments in development. Anxiety and related disorders considered herein include panic disorder, social anxiety disorder, generalized anxiety disorder and posttraumatic stress disorder. The glutamate, neuropeptide and endocannabinoid systems show particular promise as future targets for novel drug development. Expert opinion In the face of an ever-growing understanding of fear related behavior, the field awaits the translation of this research into mechanistically novel treatments. Obstacles will be overcome through close collaboration between basic and clinical researchers with the goal of aligning valid endophenotypes of human anxiety disorders with improved animal models. Novel approaches are needed to move basic discoveries into new, more effective treatments for our patients. PMID:26012843

  11. Misoprostol, an anti-ulcer agent and PGE2 receptor agonist, protects against cerebral ischemia.

    Science.gov (United States)

    Li, Jun; Liang, Xibin; Wang, Qian; Breyer, Richard M; McCullough, Louise; Andreasson, Katrin

    2008-06-20

    Induction of COX-2 activity in cerebral ischemia results in increased neuronal injury and infarct size. Recent studies investigating neurotoxic mechanisms of COX-2 demonstrate both toxic and paradoxically protective effects of downstream prostaglandin receptor signaling pathways. We tested whether misoprostol, a PGE(2) receptor agonist that is utilized clinically as an anti-ulcer agent and signals through the protective PGE(2) EP2, EP3, and EP4 receptors, would reduce brain injury in the murine middle cerebral artery occlusion-reperfusion (MCAO-RP) model. Administration of misoprostol, at the time of MCAO or 2h after MCAO, resulted in significant rescue of infarct volume at 24 and 72h. Immunocytochemistry demonstrated dynamic regulation of the EP2 and EP4 receptors during reperfusion in neurons and endothelial cells of cerebral cortex and striatum, with limited expression of EP3 receptor. EP3-/- mice had no significant changes in infarct volume compared to control littermates. Moreover, administration of misoprostol to EP3+/+ and EP3-/- mice showed similar levels of infarct rescue, indicating that misoprostol protection was not mediated through the EP3 receptor. Taken together, these findings suggest a novel function for misoprostol as a protective agent in cerebral ischemia acting via the PGE(2) EP2 and/or EP4 receptors.

  12. Tumor vascular-targeted co-delivery of anti-angiogenesis and chemotherapeutic agents by mesoporous silica nanoparticle-based drug delivery system for synergetic therapy of tumor

    Directory of Open Access Journals (Sweden)

    Li X

    2015-12-01

    Full Text Available Xiaoyu Li, Meiying Wu, Limin Pan, Jianlin Shi State Key Laboratory of High Performance Ceramics and Superfine Microstructure, Shanghai Institute of Ceramics, Chinese Academy of Sciences, Shanghai, People’s Republic of China Abstract: To overcome the drawback of drug non-selectivity in traditional chemotherapy, the construction of multifunctional targeting drug delivery systems is one of the most effective and prevailing approaches. The intratumoral anti-angiogenesis and the tumor cell-killing are two basic approaches in fighting tumors. Herein we report a novel tumor vascular-targeting multidrug delivery system using mesoporous silica nanoparticles as carrier to co-load an antiangiogenic agent (combretastatin A4 and a chemotherapeutic drug (doxorubicin and conjugate with targeting molecules (iRGD peptide for combined anti-angiogenesis and chemotherapy. Such a dual-loaded drug delivery system is capable of delivering the two agents at tumor vasculature and then within tumors through a differentiated drug release strategy, which consequently results in greatly improved antitumor efficacy at a very low doxorubicin dose of 1.5 mg/kg. The fast release of the antiangiogenic agent at tumor vasculatures led to the disruption of vascular structure and had a synergetic effect with the chemotherapeutic drug slowly released in the following delivery of chemotherapeutic drug into tumors. Keywords: mesoporous silica nanoparticles, drug delivery, tumor vasculatures targeting, antiangiogenic agent

  13. Identification of Bioactive Agents and Immunomodulatory Factors from Seashells of the Persian Gulf

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    Arezoo Najafi

    2010-09-01

    Full Text Available Background: Research in marine pharmacology will promise new bioactive agents. The marine bioenvironment is the unique resource for bioactive agents that could not be found in terrestrial organisms. Methods: A total of known 611 seashells species in the Persian Gulf were investigated for synonymy in OBIS database. Then, all the species, including their synonymy were searched in PubMed database to find their isolated bioactive agents. Results: From 611 known seashells in the Persian Gulf, 172 genera/species had bioactive compounds. Bioactive agents were isolated and purified for 16 genera/ species. The crude or purified extracts from these seashells had immunomodulatory effects (6 seashells, anti-toxicologic effects (4 seashells, analgesic (1 seashell, cardiotonic and vasoactive agents (2 seashells, hypolipidemic agents (4 seashells, anti-osteoporotic and osteoblastic agents (2 seashells and anti-dermatitis effect (1 seashell. Conclusion: The known seashells from the Persian Gulf have bioactive and immunomodulatory compounds and increase in the efforts to isolate these agents will promise a treasure for novel anti-infective agents.

  14. Anti-inflammatory and anti-oxidative effects of herbal preparation EM 1201 in adjuvant arthritic rats

    Directory of Open Access Journals (Sweden)

    Laimis Akramas

    2015-01-01

    Conclusions: The present study suggests that EM 1201 has protective activity against arthritis and demonstrated its potential beneficiary effect analogical to diclofenac. Anti-inflammatory and anti-oxidative effect of EM 1201 in rats with AA support the need of further investigations by using it as supplementary agent alone or together with other anti-arthritic drugs in the treatment of rheumatoid arthritis.

  15. Electron beam processed transdermal delivery system for administration of an anti-anginal agent

    Science.gov (United States)

    Kotiyan, P. N.; Vavia, P. R.; Bharadwaj, Y. K.; Sabarwal, S.; Majali, A. B.

    2002-12-01

    Electron beam irradiation was used to synthesize a matrix type transdermal system of isosorbide dinitrate, an effective anti-anginal agent. The drug was dissolved in two monomeric systems, 2-ethylhexyl acrylate (EHA) and 2-ethylhexyl acrylate : methyl methacrylate (9 : 1). The solutions were then directly irradiated on a backing membrane (Scotchpak ®1006) at different doses to get transdermal patches. The developed systems were evaluated for residual monomer content, equilibrium weight swelling ratio, weight uniformity, thickness uniformity, drug content, peel strength, in vitro release and skin permeation kinetics. They possessed excellent tack and adhesive properties. In the case of isosorbide dinitrate-EHA systems, an increase in the peel strength values with respect to the skin was observed with increasing radiation doses. The systems exhibited promising skin permeation kinetics favorable for transdermal drug delivery. The radiation stability of the drug in the pure solid state form was also assessed.

  16. Electron beam processed transdermal delivery system for administration of an anti-anginal agent

    Energy Technology Data Exchange (ETDEWEB)

    Kotiyan, P.N. E-mail: pramila-kotiyan@uiowa.edu; Vavia, P.R.; Bharadwaj, Y.K.; Sabarwal, S.; Majali, A.B

    2002-12-01

    Electron beam irradiation was used to synthesize a matrix type transdermal system of isosorbide dinitrate, an effective anti-anginal agent. The drug was dissolved in two monomeric systems, 2-ethylhexyl acrylate (EHA) and 2-ethylhexyl acrylate : methyl methacrylate (9 : 1). The solutions were then directly irradiated on a backing membrane (Scotchpak[reg]1006) at different doses to get transdermal patches. The developed systems were evaluated for residual monomer content, equilibrium weight swelling ratio, weight uniformity, thickness uniformity, drug content, peel strength, in vitro release and skin permeation kinetics. They possessed excellent tack and adhesive properties. In the case of isosorbide dinitrate-EHA systems, an increase in the peel strength values with respect to the skin was observed with increasing radiation doses. The systems exhibited promising skin permeation kinetics favorable for transdermal drug delivery. The radiation stability of the drug in the pure solid state form was also assessed.

  17. A screen to identify drug resistant variants to target-directed anti-cancer agents

    Directory of Open Access Journals (Sweden)

    Azam Mohammad

    2003-01-01

    Full Text Available The discovery of oncogenes and signal transduction pathways important for mitogenesis has triggered the development of target-specific small molecule anti-cancer compounds. As exemplified by imatinib (Gleevec, a specific inhibitor of the Chronic Myeloid Leukemia (CML-associated Bcr-Abl kinase, these agents promise impressive activity in clinical trials, with low levels of clinical toxicity. However, such therapy is susceptible to the emergence of drug resistance due to amino acid substitutions in the target protein. Defining the spectrum of such mutations is important for patient monitoring and the design of next-generation inhibitors. Using imatinib and BCR/ABL as a paradigm for a drug-target pair, we recently reported a retroviral vector-based screening strategy to identify the spectrum of resistance-conferring mutations. Here we provide a detailed methodology for the screen, which can be generally applied to any drug-target pair.

  18. Electron beam processed transdermal delivery system for administration of an anti-anginal agent

    International Nuclear Information System (INIS)

    Kotiyan, P.N.; Vavia, P.R.; Bharadwaj, Y.K.; Sabarwal, S.; Majali, A.B.

    2002-01-01

    Electron beam irradiation was used to synthesize a matrix type transdermal system of isosorbide dinitrate, an effective anti-anginal agent. The drug was dissolved in two monomeric systems, 2-ethylhexyl acrylate (EHA) and 2-ethylhexyl acrylate : methyl methacrylate (9 : 1). The solutions were then directly irradiated on a backing membrane (Scotchpak[reg]1006) at different doses to get transdermal patches. The developed systems were evaluated for residual monomer content, equilibrium weight swelling ratio, weight uniformity, thickness uniformity, drug content, peel strength, in vitro release and skin permeation kinetics. They possessed excellent tack and adhesive properties. In the case of isosorbide dinitrate-EHA systems, an increase in the peel strength values with respect to the skin was observed with increasing radiation doses. The systems exhibited promising skin permeation kinetics favorable for transdermal drug delivery. The radiation stability of the drug in the pure solid state form was also assessed

  19. The challenge of treating hepatitis C virus-associated cryoglobulinemic vasculitis in the era of anti-CD20 monoclonal antibodies and direct antiviral agents.

    Science.gov (United States)

    Roccatello, Dario; Sciascia, Savino; Rossi, Daniela; Solfietti, Laura; Fenoglio, Roberta; Menegatti, Elisa; Baldovino, Simone

    2017-06-20

    Mixed cryoglobulinemia syndrome (MC) is a systemic vasculitis involving kidneys, joints, skin, and peripheral nerves. While many autoimmune, lymphoproliferative, and neoplastic disorders have been associated with this disorder, hepatitis C virus (HCV) is known to be the etiologic agent in the majority of patients. Therefore, clinical research has focused on anti-viral drugs and, more recently, on the new, highly potent Direct-acting Antiviral Agents (DAAs). These drugs assure sustained virologic response (SVR) rates >90%. Nevertheless, data on their efficacy in patients with HCV-associated cryoglobulinemic vasculitis are disappointing, possibly due to the inability of the drugs to suppress the immune-mediated process once it has been triggered.Despite the potential risk of exacerbation of the infection, immunosuppression has traditionally been regarded as the first-line intervention in cryoglobulinemic vasculitis, especially if renal involvement is severe. Biologic agents have raised hopes for more manageable therapeutic approaches, and Rituximab (RTX), an anti CD20 monoclonal antibody, is the most widely used biologic drug. It has proved to be safer than conventional immunosuppressants, thus substantially changing the natural history of HCV-associated cryoglobulinemic vasculitis by providing long-term remission, especially with intensive regimens.The present review focuses on the new therapeutic opportunities offered by the combination of biological drugs, mainly Rituximab, with DAAs.

  20. A Novel Role of Serotonin Receptor 2B Agonist as an Anti-Melanogenesis Agent

    Directory of Open Access Journals (Sweden)

    Eun Ju Oh

    2016-04-01

    Full Text Available BW723C86, a serotonin receptor 2B agonist, has been investigated as a potential therapeutic for various conditions such as anxiety, hyperphagia and hypertension. However, the functional role of BW723C86 against melanogenesis remains unclear. In this study, we investigate the effect of serotonin receptor 2B (5-HTR2B agonist on melanogenesis and elucidate the mechanism involved. BW723C86 reduced melanin synthesis and intracellular tyrosinase activity in melan-A cells and normal human melanocytes. The expression of melanogenesis-related proteins (tyrosinase, TRP-1 and TRP-2 and microphthalmia-associated transcription factor (MITF in melan-A cells decreased after BW723C86 treatment. The promoter activity of MITF was also reduced by BW723C86 treatment. The reduced level of MITF was associated with inhibition of protein kinase A (PKA and cAMP response element-binding protein (CREB activation by BW723C86 treatment. These results suggest that the serotonin agonist BW723C86 could be a potential therapeutic agent for skin hyperpigmentation disorders.

  1. Anti-vascular endothelial growth factor for neovascular glaucoma.

    Science.gov (United States)

    Simha, Arathi; Braganza, Andrew; Abraham, Lekha; Samuel, Prasanna; Lindsley, Kristina

    2013-10-02

    Neovascular glaucoma (NVG) is a potentially blinding secondary glaucoma. It is caused by the formation of abnormal new blood vessels which prevent normal drainage of aqueous from the anterior segment of the eye. Anti-vascular endothelial growth factor (anti-VEGF) agents are specific inhibitors of the primary mediators of neovascularization. Studies have reported the effectiveness of anti-VEGFs for the control of intraocular pressure (IOP) in NVG. To compare the IOP lowering effects of intraocular anti-VEGF agents to no anti-VEGF treatment, as an adjunct to existing modalities for the treatment of NVG. We searched CENTRAL (which contains the Cochrane Eyes and Vision Group Trials Register) (The Cochrane Library 2012, Issue 12), Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily, Ovid OLDMEDLINE, (January 1950 to January 2013), EMBASE (January 1980 to January 2013), Latin American and Caribbean Literature on Health Sciences (LILACS) (January 1982 to January 2013), the metaRegister of Controlled Trials (mRCT) (www.controlled-trials.com), ClinicalTrials.gov (www.clinicaltrials.gov/) and the WHO International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). We did not use any date or language restrictions in the electronic searches for trials. We last searched the electronic databases on 11 January 2013. We included randomized controlled trials (RCTs) and quasi-RCTs of people treated with anti-VEGF agents for NVG. Two authors independently assessed the search results for trials to be included in the review. Discrepancies were resolved by discussion with a third author. Since no trial met our inclusion criteria, no assessment of risk of bias or meta-analysis was undertaken. No RCTs were found that met the inclusion criteria for this review. Two RCTs of anti-VEGF agents for treating NVG were not included in the review due to the heterogeneity and uncontrolled assignment of adjunct treatments received by the

  2. Therapeutic potential of a non-steroidal bifunctional anti-inflammatory and anti-cholinergic agent against skin injury induced by sulfur mustard

    Energy Technology Data Exchange (ETDEWEB)

    Chang, Yoke-Chen; Wang, James D.; Hahn, Rita A.; Gordon, Marion K.; Joseph, Laurie B. [Department of Pharmacology and Toxicology, Rutgers University, Piscataway, NJ (United States); Heck, Diane E. [Department of Environmental Science, New York Medical College, Valhalla, NY (United States); Heindel, Ned D. [Department of Chemistry, Lehigh University, Bethlehem, PA (United States); Young, Sherri C. [Department of Chemistry, Muhlenberg College, Allentown, PA (United States); Sinko, Patrick J. [Department of Pharmaceutics, Rutgers University, Piscataway, NJ (United States); Casillas, Robert P. [MRIGlobal, Kansas City, MO (United States); Laskin, Jeffrey D. [Environmental and Occupational Medicine, Robert Wood Johnson Medical School, Rutgers University, Piscataway, NJ (United States); Laskin, Debra L. [Department of Pharmacology and Toxicology, Rutgers University, Piscataway, NJ (United States); Gerecke, Donald R., E-mail: gerecke@eohsi.rutgers.edu [Department of Pharmacology and Toxicology, Rutgers University, Piscataway, NJ (United States)

    2014-10-15

    Sulfur mustard (bis(2-chloroethyl) sulfide, SM) is a highly reactive bifunctional alkylating agent inducing edema, inflammation, and the formation of fluid-filled blisters in the skin. Medical countermeasures against SM-induced cutaneous injury have yet to be established. In the present studies, we tested a novel, bifunctional anti-inflammatory prodrug (NDH 4338) designed to target cyclooxygenase 2 (COX2), an enzyme that generates inflammatory eicosanoids, and acetylcholinesterase, an enzyme mediating activation of cholinergic inflammatory pathways in a model of SM-induced skin injury. Adult SKH-1 hairless male mice were exposed to SM using a dorsal skin vapor cup model. NDH 4338 was applied topically to the skin 24, 48, and 72 h post-SM exposure. After 96 h, SM was found to induce skin injury characterized by edema, epidermal hyperplasia, loss of the differentiation marker, keratin 10 (K10), upregulation of the skin wound marker keratin 6 (K6), disruption of the basement membrane anchoring protein laminin 322, and increased expression of epidermal COX2. NDH 4338 post-treatment reduced SM-induced dermal edema and enhanced skin re-epithelialization. This was associated with a reduction in COX2 expression, increased K10 expression in the suprabasal epidermis, and reduced expression of K6. NDH 4338 also restored basement membrane integrity, as evidenced by continuous expression of laminin 332 at the dermal–epidermal junction. Taken together, these data indicate that a bifunctional anti-inflammatory prodrug stimulates repair of SM induced skin injury and may be useful as a medical countermeasure. - Highlights: • Bifunctional anti-inflammatory prodrug (NDH4338) tested on SM exposed mouse skin • The prodrug NDH4338 was designed to target COX2 and acetylcholinesterase. • The application of NDH4338 improved cutaneous wound repair after SM induced injury. • NDH4338 treatment demonstrated a reduction in COX2 expression on SM injured skin. • Changes of skin repair

  3. Impact of transgenic potatoes expressing anti-bacterial agents on bacterial endophytes is comparable with the effects of plant genotype, soil type and pathogen infection

    NARCIS (Netherlands)

    Rasche, F; Velvis, H; Zachow, C; Berg, G; Van Elsas, JD; Sessitsch, A

    1. Blackleg and soft rot disease of potatoes Solanum tuberosum L., mainly caused by the bacterial pathogen Erwinia carotovora ssp. atrospetica (Eca), lead to enormous yield losses world-wide. Genetically modified (GM) potatoes producing anti-bacterial agents, such as cecropin/attacin and T4

  4. Impact of transgenic potatoes expressing anti-bacterial agents on bacterial endophytes is comparable with the effects of plant genotype, soil type and pathogen infection

    NARCIS (Netherlands)

    Rasche, F.; Velvis, H.; Zachow, C.; Berg, G.; Elsas, van J.D.; Sessitsch, A.

    2006-01-01

    1. Blackleg and soft rot disease of potatoes Solanum tuberosum L., mainly caused by the bacterial pathogen Erwinia carotovora ssp. atrospetica (Eca), lead to enormous yield losses world-wide. Genetically modified (GM) potatoes producing anti-bacterial agents, such as cecropin/attacin and T4

  5. Anti-cancer activities of Ganoderma lucidum: active ingredients and pathways

    Directory of Open Access Journals (Sweden)

    Chi H.J. Kao

    2013-02-01

    Full Text Available ABSTRACTGanoderma lucidum, commonly referred to as Lingzhi, has been used in Asia for health promotion for centuries. The anti-cancer effects of G. lucidum have been demonstrated in both in vitro and in vivo studies. In addition, the observed anti-cancer activities of Ganoderma have prompted its usage by cancer patients alongside chemotherapy.The main two bioactive components of G. lucidum can be broadly grouped into triterpenes and polysaccharides. Despite triterpenes and polysaccharides being widely known as the major active ingredients, the different biological pathways by which they exert their anti-cancer effect remain poorly defined. Therefore, understanding the mechanisms of action may lead to more widespread use of Ganoderma as an anti-cancer agent.The aim of this paper is to summarise the various bioactive mechanisms that have been proposed for the anti-cancer properties of triterpenes and polysaccharides extracted from G. lucidum. A literature search of published papers on NCBI with keywords “Ganoderma” and “cancer” was performed. Among those, studies which specifically examined the anti-cancer activities of Ganoderma triterpenes and polysaccharides were selected to be included in this paper.We have found five potential mechanisms which are associated with the anti-cancer activities of Ganoderma triterpenes and three potential mechanisms for Ganoderma polysaccharides. In addition, G. lucidum has been used in combination with known anti-cancer agents to improve the anti-cancer efficacies. This suggests Ganoderma’s bioactive pathways may compliment that of anti-cancer agents. In this paper we present several potential anti-cancer mechanisms of Ganoderma triterpenes and polysaccharides which can be used for the development of Ganoderma as an anti-cancer agent.

  6. Protective effects of antioxidants and anti-inflammatory agents against manganese-induced oxidative damage and neuronal injury

    International Nuclear Information System (INIS)

    Milatovic, Dejan; Gupta, Ramesh C.; Yu, Yingchun; Zaja-Milatovic, Snjezana; Aschner, Michael

    2011-01-01

    Exposure to excessive manganese (Mn) levels leads to neurotoxicity, referred to as manganism, which resembles Parkinson's disease (PD). Manganism is caused by neuronal injury in both cortical and subcortical regions, particularly in the basal ganglia. The basis for the selective neurotoxicity of Mn is not yet fully understood. However, several studies suggest that oxidative damage and inflammatory processes play prominent roles in the degeneration of dopamine-containing neurons. In the present study, we assessed the effects of Mn on reactive oxygen species (ROS) formation, changes in high-energy phosphates and associated neuronal dysfunctions both in vitro and in vivo. Results from our in vitro study showed a significant (p 2 -isoprostanes (F 2 -IsoPs), as well as the depletion of ATP in primary rat cortical neurons following exposure to Mn (500 μM) for 2 h. These effects were protected when neurons were pretreated for 30 min with 100 of an antioxidant, the hydrophilic vitamin E analog, trolox (6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid), or an anti-inflammatory agent, indomethacin. Results from our in vivo study confirmed a significant increase in F 2 -IsoPs levels in conjunction with the progressive spine degeneration and dendritic damage of the striatal medium spiny neurons (MSNs) of mice exposed to Mn (100 mg/kg, s.c.) 24 h. Additionally, pretreatment with vitamin E (100 mg/kg, i.p.) or ibuprofen (140 μg/ml in the drinking water for two weeks) attenuated the Mn-induced increase in cerebral F 2 -IsoPs? and protected the MSNs from dendritic atrophy and dendritic spine loss. Our findings suggest that the mediation of oxidative stress/mitochondrial dysfunction and the control of alterations in biomarkers of oxidative injury, neuroinflammation and synaptodendritic degeneration may provide an effective, multi-pronged therapeutic strategy for protecting dysfunctional dopaminergic transmission and slowing of the progression of Mn-induced neurodegenerative

  7. Application of Mesenchymal Stem Cells for Therapeutic Agent Delivery in Anti-tumor Treatment

    Directory of Open Access Journals (Sweden)

    Daria S. Chulpanova

    2018-03-01

    Full Text Available Mesenchymal stem cells (MSCs are non-hematopoietic progenitor cells, which can be isolated from different types of tissues including bone marrow, adipose tissue, tooth pulp, and placenta/umbilical cord blood. There isolation from adult tissues circumvents the ethical concerns of working with embryonic or fetal stem cells, whilst still providing cells capable of differentiating into various cell lineages, such as adipocytes, osteocytes and chondrocytes. An important feature of MSCs is the low immunogenicity due to the lack of co-stimulatory molecules expression, meaning there is no need for immunosuppression during allogenic transplantation. The tropism of MSCs to damaged tissues and tumor sites makes them a promising vector for therapeutic agent delivery to tumors and metastatic niches. MSCs can be genetically modified by virus vectors to encode tumor suppressor genes, immunomodulating cytokines and their combinations, other therapeutic approaches include MSCs priming/loading with chemotherapeutic drugs or nanoparticles. MSCs derived membrane microvesicles (MVs, which play an important role in intercellular communication, are also considered as a new therapeutic agent and drug delivery vector. Recruited by the tumor, MSCs can exhibit both pro- and anti-oncogenic properties. In this regard, for the development of new methods for cancer therapy using MSCs, a deeper understanding of the molecular and cellular interactions between MSCs and the tumor microenvironment is necessary. In this review, we discuss MSC and tumor interaction mechanisms and review the new therapeutic strategies using MSCs and MSCs derived MVs for cancer treatment.

  8. A Hamster Model of Diet-Induced Obesity for Preclinical Evaluation of Anti-Obesity, Anti-Diabetic and Lipid Modulating Agents.

    Directory of Open Access Journals (Sweden)

    Louise S Dalbøge

    Full Text Available Unlike rats and mice, hamsters develop hypercholesterolemia, and hypertriglyceridemia when fed a cholesterol-rich diet. Because hyperlipidemia is a hallmark of human obesity, we aimed to develop and characterize a novel diet-induced obesity (DIO and hypercholesterolemia Golden Syrian hamster model.Hamsters fed a highly palatable fat- and sugar-rich diet (HPFS for 12 weeks showed significant body weight gain, body fat accumulation and impaired glucose tolerance. Cholesterol supplementation to the diet evoked additional hypercholesterolemia. Chronic treatment with the GLP-1 analogue, liraglutide (0.2 mg/kg, SC, BID, 27 days, normalized body weight and glucose tolerance, and lowered blood lipids in the DIO-hamster. The dipeptidyl peptidase-4 (DPP-4 inhibitor, linagliptin (3.0 mg/kg, PO, QD also improved glucose tolerance. Treatment with peptide YY3-36 (PYY3-36, 1.0 mg/kg/day or neuromedin U (NMU, 1.5 mg/kg/day, continuously infused via a subcutaneous osmotic minipump for 14 days, reduced body weight and energy intake and changed food preference from HPFS diet towards chow. Co-treatment with liraglutide and PYY3-36 evoked a pronounced synergistic decrease in body weight and food intake with no lower plateau established. Treatment with the cholesterol uptake inhibitor ezetimibe (10 mg/kg, PO, QD for 14 days lowered plasma total cholesterol with a more marked reduction of LDL levels, as compared to HDL, indicating additional sensitivity to cholesterol modulating drugs in the hyperlipidemic DIO-hamster. In conclusion, the features of combined obesity, impaired glucose tolerance and hypercholesterolemia in the DIO-hamster make this animal model useful for preclinical evaluation of novel anti-obesity, anti-diabetic and lipid modulating agents.

  9. Diastereoisomers of 2-benzyl-2, 3-dihydro-2-(1H-inden-2-yl)-1H-inden-1-ol: potential anti-inflammatory agents.

    Science.gov (United States)

    Sheridan, Helen; Walsh, John J; Cogan, Carina; Jordan, Michael; McCabe, Tom; Passante, Egle; Frankish, Neil H

    2009-10-15

    The synthesis and biological activity of the novel diastereoisomers of 2-benzyl-2,3-dihydro-2-(1H-inden-2-yl)-1H-inden-1-ol is reported. The 2,2-coupled indane dimers were synthesised by coupling of the silyl enol ether of 1-indanone with the dimethyl ketal of 2-indanone. The coupled product was directly alkylated to give the racemic ketone which was reduced to the diastereoisomeric alcohols. The alcohols were separated and their relative stereochemistry was established by X-ray crystallography. These molecules demonstrate significant anti-inflammatory activity in vivo and in vitro and may represent a new class of anti-inflammatory agent.

  10. Incidence and complications of interstitial lung disease in users of tocilizumab, rituximab, abatacept and anti-tumor necrosis factor α agents, a retrospective cohort study.

    Science.gov (United States)

    Curtis, Jeffrey R; Sarsour, Khaled; Napalkov, Pavel; Costa, Laurie A; Schulman, Kathy L

    2015-11-11

    Interstitial lung disease (ILD) is a common extra-articular condition in rheumatoid arthritis (RA), but few studies have systematically investigated its incidence and risk factors in patients receiving anti-tumor necrosis factor-alpha (anti-TNFα) agents or alternate mechanisms of action (MOAs) (e.g., T-cell, B-cell, and interleukin-6 inhibitors). RA patients at least 18 years old were selected from the MarketScan databases (2010-2012) if they had at least one prescription/administration of abatacept, rituximab, tocilizumab, or anti-TNF after having discontinued a different biologic agent and meeting enrollment criteria. Cox models estimated the risk of incident ILD and ILD-related hospitalization. Sensitivity analyses used an alternate ILD case definition. We identified 13,795 episodes of biologic exposure in 11,219 patients. Mean (standard deviation) follow-up was 0.7 (0.5) years. Patients receiving alternate MOA agents were more likely to have had recent exposure to steroids, prior exposure to a greater number of biologics, and history of ILD, anemia, chronic obstructive pulmonary disease, and other pulmonary conditions. When the sensitive definition was used, unadjusted ILD incidence rates (95% confidence interval, or CI) ranged from 4.0 (1.6-8.2, abatacept) to 12.2 (5.6-23.2, infliximab) per 1000 person-years. Being older (hazard ratio (HR) 3.5; 95% CI 2.1-6.0), being male (HR 3.1; 95% CI 1.2-8.4), and having another pulmonary condition (HR 4.8; 95% CI 1.7-13.7) were associated with increased ILD incidence in either sensitive and/or specific models. There were no significant differences by biologic class. Hospitalization rates (95% CI) when the sensitive definition was used ranged from 55.6 (6.7-200.7, tocilizumab) to 262.5 (71.5-672.2, infliximab). In Cox models, recent methotrexate exposure was associated with reduced ILD hospitalization (HR 0.16; 95% CI 0.06-0.46), whereas being male (HR 2.5; 95% CI 1.3-4.8) and having had a hospitalization for asthma (HR 3

  11. Sea Cucumbers Metabolites as Potent Anti-Cancer Agents

    Directory of Open Access Journals (Sweden)

    Naveena B. Janakiram

    2015-05-01

    Full Text Available Sea cucumbers and their extracts have gained immense popularity and interest among researchers and nutritionists due to their nutritive value, potential health benefits, and use in the treatment of chronic inflammatory diseases. Many areas of the world use sea cucumbers in traditional foods and folk medicine. Though the actual components and their specific functions still remain to be investigated, most sea cucumber extracts are being studied for their anti-inflammatory functions, immunostimulatory properties, and for cancer prevention and treatment. There is large scope for the discovery of additional bioactive, valuable compounds from this natural source. Sea cucumber extracts contain unique components, such as modified triterpene glycosides, sulfated polysaccharides, glycosphingolipids, and esterified phospholipids. Frondanol A5, an isopropyl alcohol/water extract of the enzymatically hydrolyzed epithelia of the edible North Atlantic sea cucumber, Cucumaria frondosa, contains monosulfated triterpenoid glycoside Frondoside A, the disulfated glycoside Frondoside B, the trisulfated glycoside Frondoside C, 12-methyltetradecanoic acid, eicosapentaenoic acid, and fucosylated chondroitin sulfate. We have extensively studied the efficacy of this extract in preventing colon cancer in rodent models. In this review, we discuss the anti-inflammatory, immunostimulatory, and anti-tumor properties of sea cucumber extracts.

  12. Synthesis of coumarin-theophylline hybrids as a new class of anti-tubercular and anti-microbial agents.

    Science.gov (United States)

    Mangasuli, Sumitra N; Hosamani, Kallappa M; Devarajegowda, Hirihalli C; Kurjogi, Mahantesh M; Joshi, Shrinivas D

    2018-02-25

    A series of novel coumarin-theophylline hybrids were synthesized and examined for their anti-tubercular activity in vitro against Mycobacterium tuberculosis H 37 Rv, anti-microbial activity in vitro against gram-positive bacteria (Staphylococcus aureus) and gram-negative bacterias (Escherichia coli, Salmonella typhi) as well as fungi (Candida albicans). The compound (3a) has shown excellent anti-tubercular activity with MIC of 0.12 μg/mL. Electron donating compounds (3a, 3f) have displayed significant anti-microbial activity. The compounds have also been precisely elucidated using single crystal X-ray diffraction techniques. Molecular docking study has been performed against 4DQU enzyme of Mycobacterium tuberculosis showed good binding interactions and is in agreement with the in vitro results. Copyright © 2018. Published by Elsevier Masson SAS.

  13. Growth of MCF-7 breast cancer cells and efficacy of anti-angiogenic agents in a hydroxyethyl chitosan/glycidyl methacrylate hydrogel.

    Science.gov (United States)

    Wang, Hejing; Qian, Junmin; Zhang, Yaping; Xu, Weijun; Xiao, Juxiang; Suo, Aili

    2017-01-01

    Breast cancer negatively affects women's health worldwide. The tumour microenvironment plays a critical role in tumour initiation, proliferation, and metastasis. Cancer cells are traditionally grown in two-dimensional (2D) cultures as monolayers on a flat solid surface lacking cell-cell and cell-matrix interactions. These experimental conditions deviate from the clinical situation. Improved experimental systems that can mimic the in vivo situation are required to discover new therapies, particularly for anti-angiogenic agents that mainly target intercellular factors and play an essential role in treating some cancers. Chitosan can be modified to construct three-dimensional (3D) tumour models. Here, we report an in vitro 3D tumour model using a hydroxyethyl chitosan/glycidyl methacrylate (HECS-GMA) hydrogel produced by a series of chitosan modifications. Parameters relating to cell morphology, viability, proliferation, and migration were analysed using breast cancer MCF-7 cells. In a xenograft model, secretion of angiogenesis-related growth factors and the anti-angiogenic efficacy of Endostar and Bevacizumab in cells grown in HECS-GMA hydrogels were assessed by immunohistochemistry. Hydroxyethyl chitosan/glycidyl methacrylate hydrogels had a highly porous microstructure, mechanical properties, swelling ratio, and morphology consistent with a 3D tumour model. Compared with a 2D monolayer culture, breast cancer MCF-7 cells residing in the HECS-GMA hydrogels grew as tumour-like clusters in a 3D formation. In a xenograft model, MCF-7 cells cultured in the HECS-GMA hydrogels had increased secretion of angiogenesis-related growth factors. Recombinant human endostatin (Endostar), but not Bevacizumab (Avastin), was an effective anti-angiogenic agent in HECS-GMA hydrogels. The HECS-GMA hydrogel provided a 3D tumour model that mimicked the in vivo cancer microenvironment and supported the growth of MCF7 cells better than traditional tissue culture plates. The HECS

  14. Enhancement of the photo-electric effect with pharmacological agents in synchrotron radiation based anti-cancer radiotherapy: a methodological study

    International Nuclear Information System (INIS)

    Corde, Stephanie

    2002-01-01

    Anti-cancer therapy rests on three main principles: 1) anatomic confinement of irradiation; 2) temporal fractioning of treatment; 3) treatment of tissues that are more sensitive to radiation than surrounding healthy tissue. Under those principles hides the goal of radiotherapy: to deposit more of the X-ray energy in the tumor while preserving the surrounding healthy tissues. This goal is hard to reach since one of the causes of the failures in radiotherapy is the continuing evolution of the tumor. Could synchrotron radiation be more effective as an X-ray source for radiotherapy? The variation of the radiation-matter interaction cross-sections as a function of X-ray energy and atomic number of the medium show that certain energies and certain elements are more suitable to obtain the largest number of interactions and the largest amount of deposited energy. Synchrotron radiation allows to select precisely those energies because of its high spectral intensity. Its spectral characteristics (energy of the photons between 10 and 100 keV) allow to trigger the photoelectric effect with a maximum of probability on heavy elements introduced close to cancerous cells. It has been shown that: 1) synchrotron radiation based tomodensitometry is a quantitative imaging technique, potentially powerful for radiotherapy since it insures in-vivo the measurement of intra-tumoral concentration of contrast agent (I or Gd); 2) in the presence of iodinated contrast agent the lethal effect of X-rays on cell survival is increased and the gain in radio sensitivity depends on X-ray energy; 3) at the cellular scale the lethality of irradiation can be optimised again by transporting heavy atoms (I, Pt) inside the DNA, which is the biological target of the irradiation. This reinforcement of the killing efficiency of low energy X-rays using a physical mechanism aimed at a pharmacological agent is an original concept in anti-cancer radiotherapy. (author) [fr

  15. Fear Appeal in Traffic Safety Advertising: The moderating role of medium context, trait anxiety, and differences between drivers and non-drivers

    Directory of Open Access Journals (Sweden)

    Wim Janssens

    2007-10-01

    Full Text Available The impact was investigated of the intensity of a fear appeal, the valence of the medium context, and the individuals' trait anxiety and personal relevance on the responses of 197 individuals to anti-speeding advertisements. A high level of fear attracts more attention. A negative valence context leads to a more positive anti-speeding attitude. The most important moderating effect of trait anxiety is that the attitude is more positive when low-anxiety individuals are exposed to high fear appeals in a context with negative valence than in a positive context. These results were largely replicated for drivers, but not for non-drivers for whom there was only an attention-getting effect of high fear appeal. Theoretical and practical implications for anti-speeding campaigning are discussed.

  16. Antimicrobial peptides: Possible anti-infective agents.

    Science.gov (United States)

    Lakshmaiah Narayana, Jayaram; Chen, Jyh-Yih

    2015-10-01

    Multidrug-resistant bacterial, fungal, viral, and parasitic infections are major health threats. The Infectious Diseases Society of America has expressed concern on the decrease of pharmaceutical companies working on antibiotic research and development. However, small companies, along with academic research institutes, are stepping forward to develop novel therapeutic methods to overcome the present healthcare situation. Among the leading alternatives to current drugs are antimicrobial peptides (AMPs), which are abundantly distributed in nature. AMPs exhibit broad-spectrum activity against a wide variety of bacteria, fungi, viruses, and parasites, and even cancerous cells. They also show potential immunomodulatory properties, and are highly responsive to infectious agents and innate immuno-stimulatory molecules. In recent years, many AMPs have undergone or are undergoing clinical development, and a few are commercially available for topical and other applications. In this review, we outline selected anion and cationic AMPs which are at various stages of development, from preliminary analysis to clinical drug development. Moreover, we also consider current production methods and delivery tools for AMPs, which must be improved for the effective use of these agents. Copyright © 2015 Elsevier Inc. All rights reserved.

  17. Meditation therapy for anxiety disorders.

    Science.gov (United States)

    Krisanaprakornkit, T; Krisanaprakornkit, W; Piyavhatkul, N; Laopaiboon, M

    2006-01-25

    Anxiety disorders are characterised by long term worry, tension, nervousness, fidgeting and symptoms of autonomic system hyperactivity. Meditation is an age-old self regulatory strategy which is gaining more interest in mental health and psychiatry. Meditation can reduce arousal state and may ameliorate anxiety symptoms in various anxiety conditions. To investigate the effectiveness of meditation therapy in treating anxiety disorders Electronic databases searched include CCDANCTR-Studies and CCDANCTR-References, complementary and alternative medicine specific databases, Science Citation Index, Health Services/Technology Assessment Text database, and grey literature databases. Conference proceedings, book chapters and references were checked. Study authors and experts from religious/spiritual organisations were contacted. Types of studies: Randomised controlled trials. patients with a diagnosis of anxiety disorders, with or without another comorbid psychiatric condition. Types of interventions: concentrative meditation or mindfulness meditation. Comparison conditions: one or combination of 1) pharmacological therapy 2) other psychological treatment 3) other methods of meditation 4) no intervention or waiting list. Types of outcome: 1) improvement in clinical anxiety scale 2) improvement in anxiety level specified by triallists, or global improvement 3) acceptability of treatment, adverse effects 4) dropout. Data were independently extracted by two reviewers using a pre-designed data collection form. Any disagreements were discussed with a third reviewer, and the authors of the studies were contacted for further information. Two randomised controlled studies were eligible for inclusion in the review. Both studies were of moderate quality and used active control comparisons (another type of meditation, relaxation, biofeedback). Anti-anxiety drugs were used as standard treatment. The duration of trials ranged from 3 months (12 weeks) to 18 weeks. In one study

  18. [Response of Pharmaceutical Companies to the Crisis of Post-Marketing Clinical Trials of Anti-Cancer Agents -- Results of Questionnaires to Pharmaceutical Companies].

    Science.gov (United States)

    Nakajima, Toshifusa

    2016-04-01

    Investigator-oriented post-marketing clinical trials of anti-cancer agents are faced to financial crisis due to drastic decrease in research-funds from pharmaceutical companies caused by a scandal in 2013. In order to assess the balance of research funds between 2012 and 2014, we made queries to 26 companies manufacturing anti-cancer agents, and only 10 of 26 responded to our queries. Decrease in the fund was observed in 5 of 10, no change in 1, increase in 3 and no answer in 1. Companies showed passive attitude to carry out doctor-oriented clinical trials of off-patent drugs or unapproved drugs according to advanced medical care B program, though some companies answered to proceed approved routines of these drugs if clinical trials showed good results. Most companies declined to make comments on the activity of Japan Agency for Medical Research and Development (AMED), but some insisted to produce good corroboration between AMED and pharmaceutical companies in order to improve the quality of trials. Further corroboration must be necessary for this purpose among researchers, governmental administrative organs, pharmaceutical companies, patients' groups, and mass-media.

  19. Elevated mazes as animal models of anxiety: effects of serotonergic agents

    Directory of Open Access Journals (Sweden)

    Simone H. Pinheiro

    2007-03-01

    Full Text Available This article reviews reported results about the effects of drugs that act upon the serotonergic neurotransmission measured in three elevated mazes that are animal models of anxiety. A bibliographic search has been performed in MEDLINE using different combinations of the key words X-maze, plus-maze, T-maze, serotonin and 5-HT, present in the title and/or the abstract, with no time limit. From the obtained abstracts, several publications were excluded on the basis of the following criteria: review articles that did not report original results, species other than the rat, intracerebral drug administration alone, genetically manipulated rats, and animals having any kind of experimental pathology. The reported results indicate that the effect of drugs on the inhibitory avoidance task performed in the elevated T-maze and on the spatio temporal indexes of anxiety measured in the X and plus mazes correlate with their effect in patients diagnosed with generalized anxiety disorder. In contrast, the drug effects on the one-way escape task in the elevated T-maze predict the drug response of panic disorder patients. Overall, the drug effects assessed with the avoidance task in the T-maze are more consistent than those measured through the anxiety indexes of the X and plus mazes. Therefore, the elevated T-maze is a promising animal model of generalized anxiety and panic disorder.No presente artigo, revisamos resultados publicados relatando efeitos de drogas que atuam na neurotransmissão serotonérgica medidos em três labirintos elevados, que são modelos animais de ansiedade. Realizamos uma busca bibliográfica no MEDLINE, usando diferentes combinações das palavras-chave: X-maze, plus-maze, T-maze, serotonin e 5-HT, presentes no título ou no resumo, sem limite de tempo. Dos resumos obtidos, vários foram excluídos com base nos seguintes critérios: artigos de revisão que não continham resultados originais, espécies diferentes do rato, apenas inje

  20. Clinical judgment, moral anxiety, and the limits of psychiatry.

    Science.gov (United States)

    Murray, Bradley

    2017-12-01

    It is common for clinicians working in psychiatry and related clinical disciplines to be called on to make diagnostic clinical judgments concerning moral anxiety, which is a kind of anxiety that is closely bound up with decisions individuals face as moral agents. To make such a judgment, it is necessary to make a moral judgment. Although it has been common to acknowledge that there are ways in which moral and clinical judgment interact, this type of interaction has remained unacknowledged. This raises questions as to the nature and limits of psychiatry-particularly concerning the extent to which psychiatric discourse ought to incorporate moral discourse, and the role of the clinician as an expert in identifying problematic anxiety.

  1. A desirability-based multi objective approach for the virtual screening discovery of broad-spectrum anti-gastric cancer agents.

    Directory of Open Access Journals (Sweden)

    Yunierkis Perez-Castillo

    Full Text Available Gastric cancer is the third leading cause of cancer-related mortality worldwide and despite advances in prevention, diagnosis and therapy, it is still regarded as a global health concern. The efficacy of the therapies for gastric cancer is limited by a poor response to currently available therapeutic regimens. One of the reasons that may explain these poor clinical outcomes is the highly heterogeneous nature of this disease. In this sense, it is essential to discover new molecular agents capable of targeting various gastric cancer subtypes simultaneously. Here, we present a multi-objective approach for the ligand-based virtual screening discovery of chemical compounds simultaneously active against the gastric cancer cell lines AGS, NCI-N87 and SNU-1. The proposed approach relays in a novel methodology based on the development of ensemble models for the bioactivity prediction against each individual gastric cancer cell line. The methodology includes the aggregation of one ensemble per cell line using a desirability-based algorithm into virtual screening protocols. Our research leads to the proposal of a multi-targeted virtual screening protocol able to achieve high enrichment of known chemicals with anti-gastric cancer activity. Specifically, our results indicate that, using the proposed protocol, it is possible to retrieve almost 20 more times multi-targeted compounds in the first 1% of the ranked list than what is expected from a uniform distribution of the active ones in the virtual screening database. More importantly, the proposed protocol attains an outstanding initial enrichment of known multi-targeted anti-gastric cancer agents.

  2. Zfp462 deficiency causes anxiety-like behaviors with excessive self-grooming in mice.

    Science.gov (United States)

    Wang, B; Zheng, Y; Shi, H; Du, X; Zhang, Y; Wei, B; Luo, M; Wang, H; Wu, X; Hua, X; Sun, M; Xu, X

    2017-02-01

    Zfp462 is a newly identified vertebrate-specific zinc finger protein that contains nearly 2500 amino acids and 23 putative C2H2-type zinc finger domains. So far, the functions of Zfp462 remain unclear. In our study, we showed that Zfp462 is expressed predominantly in the developing brain, especially in the cerebral cortex and hippocampus regions from embryonic day 7.5 to early postnatal stage. By using a piggyBac transposon-generated Zfp462 knockout (KO) mouse model, we found that Zfp462 KO mice exhibited prenatal lethality with normal neural tube patterning, whereas heterozygous (Het) Zfp462 KO (Zfp462 +/- ) mice showed developmental delay with low body weight and brain weight. Behavioral studies showed that Zfp462 +/- mice presented anxiety-like behaviors with excessive self-grooming and hair loss, which were similar to the pathological grooming behaviors in Hoxb8 KO mice. Further analysis of grooming microstructure showed the impairment of grooming patterning in Zfp462 +/- mice. In addition, the mRNA levels of Pbx1 (pre-B-cell leukemia homeobox 1, an interacting protein of Zfp462) and Hoxb8 decreased in the brains of Zfp462 +/- mice, which may be the cause of anxiety-like behaviors. Finally, imipramine, a widely used and effective anti-anxiety medicine, rescued anxiety-like behaviors and excessive self-grooming in Zfp462 +/- mice. In conclusion, Zfp462 deficiency causes anxiety-like behaviors with excessive self-grooming in mice. This provides a novel genetic mouse model for anxiety disorders and a useful tool to determine potential therapeutic targets for anxiety disorders and screen anti-anxiety drugs. © 2016 John Wiley & Sons Ltd and International Behavioural and Neural Genetics Society.

  3. Plants of Zimbabwe used as anti-fertility agents. | Sewani-Rusike ...

    African Journals Online (AJOL)

    Ethnomedicine has gained a lot of recognition in post-independence Zimbabwe and yet little research on anti-fertility medicines has been done. Information on plants used as anti-fertility medicines was obtained by interviewing women, men, traditional healers and traditional midwives in urban Harare and surrounding rural ...

  4. Bacterial biosynthesis and maturation of the didemnin anti-cancer agents

    KAUST Repository

    Xü , Ying; Kersten, Roland D.; Nam, Sang Jip; Lu, Liang; Al-Suwailem, Abdulaziz M.; Zheng, Huajun; Fenical, William H.; Dorrestein, Pieter C.; Moore, Bradley S.; Qian, Peiyuan

    2012-01-01

    The anti-neoplastic agent didemnin B from the Caribbean tunicate Trididemnum solidum was the first marine drug to be clinically tested in humans. Because of its limited supply and its complex cyclic depsipeptide structure, considerable challenges were encountered during didemnin B's development that continue to limit aplidine (dehydrodidemnin B), which is currently being evaluated in numerous clinical trials. Herein we show that the didemnins are bacterial products produced by the marine α-proteobacteria Tistrella mobilis and Tistrella bauzanensis via a unique post-assembly line maturation process. Complete genome sequence analysis of the 6,513,401 bp T. mobilis strain KA081020-065 with its five circular replicons revealed the putative didemnin biosynthetic gene cluster (did) on the 1,126,962 bp megaplasmid pTM3. The did locus encodes a 13-module hybrid non-ribosomal peptide synthetase-polyketide synthase enzyme complex organized in a collinear arrangement for the synthesis of the fatty acylglutamine ester derivatives didemnins X and Y rather than didemnin B as first anticipated. Imaging mass spectrometry of T. mobilis bacterial colonies captured the time-dependent extracellular conversion of the didemnin X and Y precursors to didemnin B, in support of an unusual post-synthetase activation mechanism. Significantly, the discovery of the didemnin biosynthetic gene cluster may provide a long-term solution to the supply problem that presently hinders this group of marine natural products and pave the way for the genetic engineering of new didemnin congeners. © 2012 American Chemical Society.

  5. Bacterial biosynthesis and maturation of the didemnin anti-cancer agents

    KAUST Repository

    Xü, Ying

    2012-05-23

    The anti-neoplastic agent didemnin B from the Caribbean tunicate Trididemnum solidum was the first marine drug to be clinically tested in humans. Because of its limited supply and its complex cyclic depsipeptide structure, considerable challenges were encountered during didemnin B\\'s development that continue to limit aplidine (dehydrodidemnin B), which is currently being evaluated in numerous clinical trials. Herein we show that the didemnins are bacterial products produced by the marine α-proteobacteria Tistrella mobilis and Tistrella bauzanensis via a unique post-assembly line maturation process. Complete genome sequence analysis of the 6,513,401 bp T. mobilis strain KA081020-065 with its five circular replicons revealed the putative didemnin biosynthetic gene cluster (did) on the 1,126,962 bp megaplasmid pTM3. The did locus encodes a 13-module hybrid non-ribosomal peptide synthetase-polyketide synthase enzyme complex organized in a collinear arrangement for the synthesis of the fatty acylglutamine ester derivatives didemnins X and Y rather than didemnin B as first anticipated. Imaging mass spectrometry of T. mobilis bacterial colonies captured the time-dependent extracellular conversion of the didemnin X and Y precursors to didemnin B, in support of an unusual post-synthetase activation mechanism. Significantly, the discovery of the didemnin biosynthetic gene cluster may provide a long-term solution to the supply problem that presently hinders this group of marine natural products and pave the way for the genetic engineering of new didemnin congeners. © 2012 American Chemical Society.

  6. The Phytochemical Constituents, Analgesic and Anti-inflammatory ...

    African Journals Online (AJOL)

    This effect was comparable to the observed effect with Piroxicam (0.5mg/kg) which was used as a standard. The effect was also dose- dependent. Furthermore, Jatropha ... This also supports its use traditionally as an anti-snake bite, rheumatism and anti- cancer or anti-tumor agent. Further study is on the way to find out the ...

  7. Assessment of topical non-steroidal anti-inflammatory drugs in animal models.

    Science.gov (United States)

    Hiramatsu, Y; Akita, S; Salamin, P A; Maier, R

    1990-10-01

    Four commercial gel preparations of topical anti-inflammatory agents have been assessed in six animal models commonly used to determine the biological activity of non-steroidal anti-inflammatory agents for systemic administration. Only UV-induced erythema of the skin, adjuvant induced arthritis and the measurement of vascular permeability proved suitable for differentiation of the potency of the four topical agents. Carrageenin-induced paw oedema, the cotton pellet test and the assessment of the pain threshold according to Randall and Selitto were of little value. The effects of the gel preparation of diclofenac (CAS 15307-86-5) diethylammonium (Voltaren Emulgel) were comparable to two preparations containing 1% and 5% active ingredient, respectively. Gel 4 showed low overall activity. The experiments demonstrated that some of the models used for the assessment of anti-inflammatory agent for systemic administration proved suitable for the testing of topical preparations and that percutaneous absorption was insufficient to elicit anti-inflammatory effect in the animals at sites remote from the site of application.

  8. Protective effects of antioxidants and anti-inflammatory agents against manganese-induced oxidative damage and neuronal injury

    Energy Technology Data Exchange (ETDEWEB)

    Milatovic, Dejan, E-mail: dejan.milatovic@vanderbilt.edu [Vanderbilt University School of Medicine, Department of Pediatrics, Nashville, TN (United States); Gupta, Ramesh C. [Murray State University, Breathitt Veterinary Center, Hopkinsville, KY (United States); Yu, Yingchun; Zaja-Milatovic, Snjezana [Vanderbilt University School of Medicine, Department of Pediatrics, Nashville, TN (United States); Aschner, Michael [Vanderbilt University School of Medicine, Department of Pediatrics, Nashville, TN (United States); Pharmacology and the Kennedy Center for Research on Human Development, Nashville, TN (United States)

    2011-11-15

    Exposure to excessive manganese (Mn) levels leads to neurotoxicity, referred to as manganism, which resembles Parkinson's disease (PD). Manganism is caused by neuronal injury in both cortical and subcortical regions, particularly in the basal ganglia. The basis for the selective neurotoxicity of Mn is not yet fully understood. However, several studies suggest that oxidative damage and inflammatory processes play prominent roles in the degeneration of dopamine-containing neurons. In the present study, we assessed the effects of Mn on reactive oxygen species (ROS) formation, changes in high-energy phosphates and associated neuronal dysfunctions both in vitro and in vivo. Results from our in vitro study showed a significant (p < 0.01) increase in biomarkers of oxidative damage, F{sub 2}-isoprostanes (F{sub 2}-IsoPs), as well as the depletion of ATP in primary rat cortical neurons following exposure to Mn (500 {mu}M) for 2 h. These effects were protected when neurons were pretreated for 30 min with 100 of an antioxidant, the hydrophilic vitamin E analog, trolox (6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid), or an anti-inflammatory agent, indomethacin. Results from our in vivo study confirmed a significant increase in F{sub 2}-IsoPs levels in conjunction with the progressive spine degeneration and dendritic damage of the striatal medium spiny neurons (MSNs) of mice exposed to Mn (100 mg/kg, s.c.) 24 h. Additionally, pretreatment with vitamin E (100 mg/kg, i.p.) or ibuprofen (140 {mu}g/ml in the drinking water for two weeks) attenuated the Mn-induced increase in cerebral F{sub 2}-IsoPs? and protected the MSNs from dendritic atrophy and dendritic spine loss. Our findings suggest that the mediation of oxidative stress/mitochondrial dysfunction and the control of alterations in biomarkers of oxidative injury, neuroinflammation and synaptodendritic degeneration may provide an effective, multi-pronged therapeutic strategy for protecting dysfunctional

  9. Screening of proteins based on macro-algae from West Java coast in Indonesian marine as a potential anti-aging agent

    Science.gov (United States)

    Putri, Arlina Prima; Dewi, Rizna Triana; Handayani, Aniek Sri; Harjanto, Sri; Chalid, Mochamad

    2018-02-01

    Algae has been known as one of the potential marine bio-resources that have been used in many fields such as bio-energy, food, pharmaceutical and medical applications. Study of macro-algae or seaweed for medicine application, in particular, highlights to empower their ingredients as a promising antioxidant like anti-aging agent due to their diversity in biological activity. The tropical climate of Indonesia with the highest marine biodiversity puts this country an auspicious source of numerous alga species as a novel antioxidant source. A Sample of 29 species of macroalgae has been collected from Coast of Pari Island as a part of Seribu Islands, Indonesia. Screening and extracting of aqueous tropical marine alga protein as a potential source for an antioxidant agent has been done by using 2,2-diphenyl-1-picrylhydrazyl scavenging method, and protein contents have been determined by Lowry method. Sample number 26 of the phylum Rhodophyta have 9.00±0.03 % protein content, which is potential for nutritional food in form of nutraceutical. That sample demonstrated the maximum DPPH scavenging activity 79.27±1.81 %. Moreover, crude extract from another species from phylum Rhodophyta had the very lower IC50 (3.4333±0.29 mg/ml) followed by Chlorophyta species (7.1069±1.78 mg/ml). In general, this study found that algae from phylum Rhodophyta possess a high content of protein, high activity towards free radical. Nevertheless, algae acquire the lowest IC50 value not only dominated by Rhodophyta but also from phylum Chlorophyta. The conclusion of this study leads to empowering high antioxidant activity algae as an anti-aging agent, which can be used in pharmaceutical applications. Therefore, the next study should be concerned on the properties of the algae which has been known to be suitable for pharmaceutical fields.

  10. Russian olive (Elaeagnus angustifolia L.: From a variety of traditional medicinal applications to its novel roles as active antioxidant, anti-inflammatory, anti-mutagenic and analgesic agent

    Directory of Open Access Journals (Sweden)

    Rafie Hamidpour

    2017-01-01

    Full Text Available Elaeagnus angustifolia L., which is commonly known as oleaster or Russian olive, is a deciduous plant from Elaeagnacea family. This plant can tolerate and survive a wide variety of environmental conditions. Different parts of E. angustifolia plant, especially the fruits and flowers, have been used traditionally in treating a variety of common illnesses such as nausea, cough, asthma, fever, jaundice, and diarrhea. The use of fruit powder and extract of E. angustifolia L. have shown to be effective in alleviating pain in patients with rheumatoid arthritis and also in reducing the healing time of wounds in injured person. In addition, some recent reports have indicated the anti-oxidant, anti-inflammatory, antimicrobial, anticancer and some other properties of oleaster plant. The other important property of this plant would be its role in bio-monitoring the environment for some toxic elements and also its action as a bio-fertilizer agent in distressed lands. It seems that with more advanced studies on E. angustifolia L. and its bioactive components, this plant might be potentially effective and can be used as a natural alternative resource in pharmaceutical industries for treating chronic and serious problems, Fig. 1.

  11. Occurrence of anti-Neospora caninum and anti-Toxoplasma gondii IgG antibodies in goats and sheep in western Maranhão, Brazil Ocorrência de anticorpos IgG anti-Neospora caninum e anti-Toxoplasma gondii em caprinos e ovinos do oeste do Maranhão, Brasil

    Directory of Open Access Journals (Sweden)

    Larissa Martins de Brito Moraes

    2011-12-01

    Full Text Available Neosporosis and toxoplasmosis are parasitic diseases which can cause reproductive problems in goats and sheep. The current study aimed to determine the occurrence of anti-Neospora caninum and anti-Toxoplasma gondii IgG antibodies in goats and sheep from the districts of Amarante do Maranhão and Buritirana, Imperatriz microregion, western area of Maranhão State, northeastern Brazil, and to assess factors associated to infection by these etiologic agents. Blood samples from 110 animals (46 goats and 64 sheep from five herds were collected, and indirect immunofluorescence assay was used for serological testing. Of 46 goat samples, 17.39% (n = 8 showed anti-N. caninum antibodies and 4.35% (n = 2 anti-T. gondii, while of 64 sheep samples 4.69% (n = 3 and 18.75% (n = 12 showed anti-N. caninum and anti-T. gondii antibodies, respectively. No significant difference regarding the presence of domestic cats and/or dogs on the property and veterinary care was seen for both etiologic agents studied. However, food supplementation and animal reproductive failure were significantly (p A neosporose e a toxoplasmose são doenças parasitárias que podem causar problemas reprodutivos em caprinos e ovinos. O objetivo deste estudo foi determinar a ocorrência de anticorpos IgG anti-Neospora caninum e anti-Toxoplasma gondii em caprinos e ovinos dos municípios de Amarante do Maranhão e Buritirana, microrregião de Imperatriz, Oeste maranhense, Nordeste do Brasil, bem como avaliar fatores associados à infecção por esses agentes etiológicos. Amostras de sangue de 110 animais (46 caprinos e 64 ovinos, provenientes de cinco propriedades, foram coletadas, e a reação de imunofluorescência indireta utilizada para o diagnóstico sorológico. Das 46 amostras de caprinos, 17,39% (n = 8 apresentaram anticorpos anti-N. caninum e 4,35% (n = 2 anti-T. gondii, enquanto das 64 amostras de ovinos, 4,69% (n = 3 e 18,75% (n = 12 apresentaram anticorpos anti-N. caninum e anti

  12. Preliminary screening of some traditional zulu medicinal plants for anti-inflammatory and anti-microbial activities.

    Science.gov (United States)

    Lin, J; Opoku, A R; Geheeb-Keller, M; Hutchings, A D; Terblanche, S E; Jäger, A K; van Staden, J

    1999-12-15

    Aqueous and methanolic extracts from different parts of nine traditional Zulu medicinal plants, of the Vitaceae from KwaZulu-Natal, South Africa were evaluated for therapeutic potential as anti-inflammatory and anti-microbial agents. Of the twenty-nine crude extracts assayed for prostaglandin synthesis inhibitors, only five methanolic extracts of Cyphostemma natalitium-root, Rhoicissus digitata-leaf, R. rhomboidea-root, R. tomentosa-leaf/stem and R. tridentata-root showed significant inhibition of cyclo-oxygenase (COX-1). The extracts of R. digitata-leaf and of R. rhomboidea-root exhibited the highest inhibition of prostaglandin synthesis with 53 and 56%, respectively. The results suggest that Rhoicissus digitata leaves and of Rhoicissus rhomboidea roots may have the potential to be used as anti-inflammatory agents. All the screened plant extracts showed some degrees of anti-microbial activity against gram-positive and gram-negative microorganisms. The methanolic extracts of C. natalitium-stem and root, R. rhomboidea-root, and R. tomentosa-leaf/stem, showed different anti-microbial activities against almost all micro-organisms tested. Generally, these plant extracts inhibited the gram-positive micro-organisms more than the gram-negative ones. Several plant extracts inhibited the growth of Candida albicans while only one plant extract showed inhibitory activity against Saccharomyces cerevisiae. All the plant extracts which demonstrated good anti-inflammatory activities also showed better inhibitory activity against Candida albicans.

  13. Tamsulosin Monotherapy versus Combination Therapy with Antibiotics or Anti-Inflammatory Agents in the Treatment of Chronic Pelvic Pain Syndrome

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    Tae Hyo Kim

    2011-06-01

    Full Text Available Purpose Chronic pelvic pain syndrome (CPPS is treated by use of various protocols. We compared tamsulosin monotherapy with tamsulosin in combination with antibiotics or anti-inflammatory agents and evaluated the efficacy of these treatments in patients with CPPS. Methods Patients (n=107 who were younger than 55 years and diagnosed with CPPS were randomly assigned to treatment with tamsulosin at 0.2 mg (group A, tamsulosin at 0.2 mg plus anti-inflammatory drugs (group B or tamsulosin at 0.2 mg plus antibiotics (group C daily. We applied the National Institutes of Health-Chronic Prostatitis Symptom Index (NIH-CPSI and the International Prostate Symptom Score (IPSS to evaluate 100 patients who were treated for 12 weeks (7 withdrew. Scores of the three groups were compared by analysis of variance and we also evaluated subscores, which included pain, voiding and quality of life (QoL. Results All three groups showed statistically significant decreases in NIH-CPSI score, IPSS and subscore scores (P<0.05. There were no statistically significant differences between the groups except for the QoL domain of the IPSS (group A vs. C; P<0.01. Conclusions Tamsulosin monotherapy for 12 weeks was effective for treating patients with CPPS, compared with combination therapy with antibiotics or anti-inflammatory drugs.

  14. Direct anti-HCV agents

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    Xingquan Zhang

    2016-01-01

    Full Text Available Unlike human immunodeficiency virus (HIV and hepatitis B virus (HBV, hepatitis C virus (HCV infection is a curable disease. Current direct antiviral agent (DAA targets are focused on HCV NS3/4A protein (protease, NS5B protein (polymerase and NS5A protein. The first generation of DAAs includes boceprevir and telaprevir, which are protease inhibitors and were approved for clinical use in 2011. The cure rate for genotype 1 patients increased from 45% to 70% when boceprevir or telaprevir was added to standard PEG-IFN/ribavirin. More effective and less toxic second generation DAAs supplanted these drugs by 2013. The second generation of DAAs includes sofosbuvir (Sovaldi, simeprevir (Olysio, and fixed combination medicines Harvoni and Viekira Pak. These drugs increase cure rates to over 90% without the need for interferon and effectively treat all HCV genotypes. With these drugs the “cure HCV” goal has become a reality. Concerns remain about drug resistance mutations and the high cost of these drugs. The investigation of new HCV drugs is progressing rapidly; fixed dose combination medicines in phase III clinical trials include Viekirax, asunaprevir+daclatasvir+beclabuvir, grazoprevir+elbasvir and others.

  15. Farmer to Pharmacist: Curcumin as an Anti-invasive and Antimetastatic Agent for the Treatment of Cancer

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    Bandyopadhyay, Debasish

    2014-12-01

    A huge number of compounds are widely distributed in nature and many of these possess medicinal/biological/pharmacological activity. Curcumin, a polyphenol derived from the rhizomes (underground stems) of Curcuma longa Linn (a member of the ginger family, commonly known as turmeric) is a culinary spice and therapeutic used in India for thousands of years to induce color and flavor in food as well as to treat a wide array of diseases. The origin of turmeric as spice and folklore medicine is so old that it is lost in legend. Curcumin has many beneficial pharmacological effects which includes, but are not limited with, antimicrobial, anti-inflammatory, antioxidant, antiviral, antiangiogenic, and antidiabetic activities. Most importantly curcumin possesses immense antitumorigenic effect. It prevents tumor invasion and metastasis in a number of animal models, including models of lung, liver, stomach, colon, breast, esophageal cancer etc. Invasion and metastasis are considered as one of the hallmarks in cancer biology. The pertinent recent applications of curcumin as anti-invasive and antimetastatic agent in in vitro and in vivo and ex vivo studies as well as associated molecular mechanisms have been discussed in this review. Curcumin has also demonstrated the ability to improve patient outcomes in clinical trials.

  16. Farmer to Pharmacist: Curcumin as an Anti-invasive and Antimetastatic Agent for the Treatment of Cancer

    Directory of Open Access Journals (Sweden)

    Debasish eBandyopadhyay

    2014-12-01

    Full Text Available A huge number of compounds are widely distributed in nature and many of these possess medicinal/biological/pharmacological activity. Curcumin, a polyphenol derived from the rhizomes (underground stems of Curcuma longa Linn (a member of the ginger family, commonly known as turmeric is a culinary spice and therapeutic used in India for thousands of years to induce color and flavor in food as well as to treat a wide array of diseases. The origin of turmeric as spice and folklore medicine is so old that it is lost in legend. Curcumin has many beneficial pharmacological effects which includes, but are not limited with, antimicrobial, anti-inflammatory, antioxidant, antiviral, antiangiogenic, and antidiabetic activities. Most importantly curcumin possesses immense antitumorigenic effect. It prevents tumor invasion and metastasis in a number of animal models, including models of lung, liver, stomach, colon, breast, esophageal cancer etc. Invasion and metastasis are considered as one of the hallmarks in cancer biology. The pertinent recent applications of curcumin as anti-invasive and antimetastatic agent in in vitro and in vivo and ex vivo studies as well as associated molecular mechanisms have been discussed in this review. Curcumin has also demonstrated the ability to improve patient outcomes in clinical trials.

  17. Characterization of a Newly Isolated Marine Fungus Aspergillus dimorphicus for Optimized Production of the Anti-Tumor Agent Wentilactones

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    Rui Xu

    2015-11-01

    Full Text Available The potential anti-tumor agent wentilactones were produced by a newly isolated marine fungus Aspergillus dimorphicus. This fungus was derived from deep-sea sediment and identified by polyphasic approach, combining phenotypic, molecular, and extrolite profiles. However, wentilactone production was detected only under static cultures with very low yields. In order to improve wentilactone production, culture conditions were optimized using the response surface methodology. Under the optimal static fermentation conditions, the experimental values were closely consistent with the prediction model. The yields of wentilactone A and B were increased about 11-fold to 13.4 and 6.5 mg/L, respectively. The result was further verified by fermentation scale-up for wentilactone production. Moreover, some small-molecule elicitors were found to have capacity of stimulating wentilactone production. To our knowledge, this is first report of optimized production of tetranorlabdane diterpenoids by a deep-sea derived marine fungus. The present study might be valuable for efficient production of wentilactones and fundamental investigation of the anti-tumor mechanism of norditerpenoids.

  18. Genotoxicity studies on DNA-interactive telomerase inhibitors with application as anti-cancer agents.

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    Harrington, Dean J; Cemeli, Eduardo; Carder, Joanna; Fearnley, Jamie; Estdale, Sian; Perry, Philip J; Jenkins, Terence C; Anderson, Diana

    2003-01-01

    Telomerase-targeted strategies have aroused recent interest in anti-cancer chemotherapy, because DNA-binding drugs can interact with high-order tetraplex rather than double-stranded (duplex) DNA targets in tumour cells. However, the protracted cell-drug exposure times necessary for clinical application require that telomerase inhibitory efficacy must be accompanied by both low inherent cytotoxicity and the absence of mutagenicity/genotoxicity. For the first time, the genotoxicity of a number of structurally diverse DNA-interactive telomerase inhibitors is examined in the Ames test using six Salmonella typhimurium bacterial strains (TA1535, TA1537, TA1538, TA98, TA100, and TA102). DNA damage induced by each agent was also assessed using the Comet assay with human lymphocytes. The two assay procedures revealed markedly different genotoxicity profiles that are likely to reflect differences in metabolism and/or DNA repair between bacterial and mammalian cells. The mutational spectrum for a biologically active fluorenone derivative, shown to be mutagenic in the TA100 strain, was characterised using a novel and rapid assay method based upon PCR amplification of a fragment of the hisG46 allele, followed by RFLP analysis. Preliminary analysis indicates that the majority (84%) of mutations induced by this compound are C --> A transversions at position 2 of the missense proline codon of the hisG46 allele. However, despite its genotoxic bacterial profile, this fluorenone agent gave a negative response in the Comet assay, and demonstrates how unwanted systemic effects (e.g., cytotoxicity and genotoxicity) can be prevented or ameliorated through suitable molecular fine-tuning of a candidate drug in targeted human tumour cells. Copyright 2003 Wiley-Liss, Inc.

  19. Soft-tissue wound healing by anti-advanced glycation end-products agents.

    Science.gov (United States)

    Chang, P-C; Tsai, S-C; Jheng, Y-H; Lin, Y-F; Chen, C-C

    2014-04-01

    The blocking of advanced glycation end-products (AGE) has been shown to reduce diabetic complications and control periodontitis. This study investigated the pattern of palatal wound-healing after graft harvesting under the administration of aminoguanidine (AG), an AGE inhibitor, or N-phenacylthiazolium bromide (PTB), a glycated cross-link breaker. Full-thickness palatal excisional wounds (5.0 x 1.5 mm(2)) were created in 72 Sprague-Dawley rats. The rats received daily intraperitoneal injections of normal saline (control), AG, or PTB and were euthanized after 4 to 28 days. The wound-healing pattern was assessed by histology, histochemistry for collagen matrix deposition, immunohistochemistry for AGE and the AGE receptor (RAGE), and the expression of RAGE, as well as inflammation- and recovery-associated genes. In the first 14 days following AG or PTB treatments, wound closure, re-epithelialization, and collagen matrix deposition were accelerated, whereas AGE deposition, RAGE-positive cells, and inflammation were reduced. RAGE and tumor necrosis factor-alpha were significantly down-regulated at day 7, and heme oxygenase-1 was persistently down-regulated until day 14. The levels of vascular endothelial growth factor, periostin, type I collagen, and fibronectin were all increased at day 14. In conclusion, anti-AGE agents appeared to facilitate palatal wound-healing by reducing AGE-associated inflammation and promoting the recovery process.

  20. Anti-Inflammatory Agent Indomethacin Reduces Invasion and Alters Metabolism in a Human Breast Cancer Cell Line

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    Ellen Ackerstaff

    2007-03-01

    Full Text Available Hostile physiological environments such as hypoxia and acidic extracellular pH, which exist in solid tumors, may promote invasion and metastasis through inflammatory responses and formation of eicosanoids. Here, we have investigated the effects of the antiinflammatory agent indomethacin on the invasion and metabolism of the human breast cancer cell line MDAMB-435 in Dulbecco's Modified Eagles (DME-based or Roswell Park Memorial Institute (RPMI-based cell medium, using a magnetic resonance-compatible invasion assay. Indomethacin treatment significantly reduced the invasion of MDA-MB-435 cells independent of the culture and perfusion conditions examined. Significant changes were detected in levels of intracellular choline phospholipid metabolites and in triglyceride (TG concentrations of these cells, depending on indomethacin treatment and basal cell medium used. Additionally, genetic profiling of breast cancer cells, grown and treated with low-dose indomethacin in cell culture using an RPMI-based medium, revealed the upregulation of several genes implicating cyclooxygenaseindependent targets of indomethacin. These data confirm the ability of an anti-inflammatory agent to reduce breast cancer invasion and demonstrate, depending on cell culture and perfusion conditions, that the indomethacin-induced decrease in invasion is associated with changes in choline phospholipid metabolism, TG metabolism, and gene expression.

  1. Restoration of dietary-fat induced blood–brain barrier dysfunction by anti-inflammatory lipid-modulating agents

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    Pallebage-Gamarallage Menuka

    2012-09-01

    Full Text Available Abstract Background Several studies have identified use of non-steroidal-anti-inflammatory drugs and statins for prevention of dementia, but their efficacy in slowing progression is not well understood. Cerebrovascular disturbances are common pathological feature of Alzheimer’s disease. We previously reported chronic ingestion of saturated fatty acids (SFA compromises blood–brain barrier (BBB integrity resulting in cerebral extravasation of plasma proteins and inflammation. However, the SFA-induced parenchymal accumulation of plasma proteins could be prevented by co-administration of some cholesterol lowering agents. Restoration of BBB dysfunction is clinically relevant, so the purpose of this study was to explore lipid-lowering agents could reverse BBB disturbances induced by chronic ingestion of SFA’s. Methods Wild-type mice were fed an SFA diet for 12 weeks to induce BBB dysfunction, and then randomised to receive atorvastatin, pravastatin or ibuprofen in combination with the SFA-rich diet for 2 or 8 weeks. Abundance of plasma-derived immunoglobulin-G (IgG and amyloid-β enriched apolipoprotein (apo-B lipoproteins within brain parenchyme were quantified utilising immunofluorescence microscopy. Results Atorvastatin treatment for 2 and 8 weeks restored BBB integrity, indicated by a substantial reduction of IgG and apo B, particularly within the hippocampus. Pravastatin, a water-soluble statin was less effective than atorvastatin (lipid-soluble. Statin effects were independent of changes in plasma lipid homeostasis. Ibuprofen, a lipid-soluble cyclooxygenase inhibitor attenuated cerebral accumulation of IgG and apo B as effectively as atorvastatin. Our findings are consistent with the drug effects being independent of plasma lipid homeostasis. Conclusion Our findings suggest that BBB dysfunction induced by chronic ingestion of SFA is reversible with timely introduction and sustained treatment with agents that suppress inflammation.

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

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    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. Changing paradigms of anti-VEGF in the Indian scenario

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    P Mahesh Shanmugam

    2014-01-01

    Full Text Available Anti-vascular endothelial growth factors (VEGF agents have revolutionized the treatment of retinal diseases. Use of anti-VEGF agents in the Indian Scenario present some unique challenges considering the absence of compounding pharmacies, poor penetrance of health insurance and limited affordability of the citizens of a developing economy. To study the changing paradigms of anti-VEGF use in the Indian scenario, all articles published by Indian authors, data from web-based surveys amongst Indian vitreo-retinal specialists were reviewed. In the paucity of compounding pharmacies in India, fractionation and injection techniques differ from those of developed countries. Frequent anti-VEGF monotherapy offers the best anatomical and visual results, but economics of scale do not allow the same in the Indian scenario, resulting in PRN dosing and combination of anti-VEGF with laser photocoagulation, being the commonly employed treatment protocols.

  4. External influences and priority-setting for anti-cancer agents: a case study of media coverage in adjuvant trastuzumab for breast cancer

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    Fralick John

    2007-06-01

    Full Text Available Abstract Background Setting priorities for the funding of new anti-cancer agents is becoming increasingly complex. The funding of adjuvant trastuzumab for breast cancer has brought this dilemma to the fore. In this paper we review external factors that may influence decision-making bodies and present a case study of media response in Ontario, Canada to adjuvant trastuzumab for breast cancer. Methods A comprehensive search of the databases of Canadian national and local newspapers and television was performed. Articles pertaining to trastuzumab in adjuvant breast cancer as well as 17 other anti-cancer drugs and indications were retrieved. The search period was from the date when individual trial results were announced to the date funding was made available in Ontario. Results During the 2.6 months between the release of the trastuzumab results to funding approval in Ontario, we identified 51 episodes of media coverage. For the 17 other drugs/indications (7 breast and 10 non-breast, the median time to funding approval was 31 months (range 14–46. Other recent major advances in oncology such as adjuvant vinorelbine/cisplatin for resected NSCLC and docetaxel for advanced prostate cancer received considerably less media attention (17 media reports for each than trastuzumab. The median number of media reports for breast cancer drugs was 4.5 compared to 2.5 for non-breast cancer drugs (p = 0.56. Conclusion Priority-setting for novel anti-cancer agents is a complex process that tries to ensure fair use of constrained resources to fund therapies with the best evidence of clinical benefit. However, this process is subject to external factors including the influence of media, patient advocates, politicians, and industry. The data in this case study serve to illustrate the significant involvement one (or all of these external factors may play in the debate over priority-setting.

  5. Anti-influenza M2e antibody

    Science.gov (United States)

    Bradbury, Andrew M [Santa Fe, NM

    2011-12-20

    Humanized recombinant and monoclonal antibodies specific for the ectodomain of the influenza virus M2 ion channel protein are disclosed. The antibodies of the invention have anti-viral activity and may be useful as anti-viral therapeutics and/or prophylactic/vaccine agents for inhibiting influenza virus replication and for treating individuals infected with influenza.

  6. Rational Design and Synthesis of Biologically Active Disubstituted 2(3H) Furanones and Pyrrolone Derivatives as Potent and Safer Non Steroidal Anti-inflammatory Agents.

    Science.gov (United States)

    Khokra, S L; Khan, S A; Choudhary, D; Hasan, S M; Ahmad, A; Husain, Asif

    2016-01-01

    Furanone and pyrrolone heterocyclic ring system represent important and interesting classes of bioactive compounds. Medicinal chemists use these heterocycyclic moieties as scaffolds in drug design and discovery. A series of 3-arylidene-5-(naphthalene-2-yl)-furan-2(3H)-ones (2a-j) were synthesized by incorporating pharmacophore of COX-2 inhibitor rofecoxib and naphthyl ring of naproxen as potential non steroidal anti-inflammatory agents. These furanone derivatives were subsequently reacted with dry ammonia gas and benzylamine to furnish corresponding 3-arylidene-5-(naphthlen-2-yl)-1H-pyrrol-2(3H)-ones (3a-e) and 3-arylidene-1-benzyl-5- (naphthalene-2-yl)-1H-pyrrol-2(3H)-ones (4a-e), respectively. The newly prepared heterocyclics were screened for their expected in-vivo biological activities including anti-inflammatory, analgesic and ulcerogenic actions in rodents. The COX-2 inhibitory behavior of synthesized compounds was also assessed via automated docking studies. The chemical structure of the synthesized compounds was characterized by using modern spectroscopic techniques. Result of in-vivo pharmacological studies demonstrated that almost all N-Benzyl-pyrrol-2(3H)-ones (4a-e) showed better anti-inflammatory and analgesic activities in comparison with the other two series of furan-2(3H)-ones and pyrrol- 2(3H)-ones. The moldock score value of the tested compounds was found in the range of -116.66 to -170.328 and was better than the standard drug. Among all the synthesized compounds, only nine compounds (2d, 2g, 2h, 3d, 4a, 4b, 4c, 4d and 4e) exhibited potent anti-inflammatory and analgesic activities with significantly reduced gastrointestinal toxicity in various animal models in comparison to standard drug, diclofenac. Therefore, it is recommended to explore the potential of the synthesized compounds as lead candidates for the development of new therapeutic agents.

  7. The cerebral neurobiology of anxiety, anxiety displacement, and anxiety denial.

    Science.gov (United States)

    Gottschalk, L A; Fronczek, J; Abel, L; Buchsbaum, M S; Fallon, J H

    2001-01-01

    Previous studies examining the relationship of anxiety scores, derived from the content analysis of speech of normal individuals, have revealed that the anxiety scores occurring in the dreams associated with rapid eye movement (REM) sleep are significantly correlated with localized cerebral glucose metabolic rates assessed by positron emission tomography (PET) scanning. These significant intercorrelations occur in different cerebral areas when the anxiety scores are obtained from mental experiences reported during non-REM sleep or during wakeful silent mentation. The purpose of the present study was to examine the intercorrelations found between anxiety attributed to the self, anxiety-displacement, and anxiety denial measured from computerized content analysis of 5-min verbal reports of subjective thoughts and feelings obtained from wakeful normal subjects and localized cerebral glucose metabolic rates during PET scanning. The subjects were 10 wakeful young males. Their anxiety scores were derived from computerized content analysis of 5-min reports they gave of their subjective thoughts, feelings and fantasies during a 30-min period following an intravenous injection of F D-deoxyglucose (FDG). The subjects were moved 32--45 min after this injection to obtain a PET scan, which records all of the localized cerebral glucose metabolic rates during the 30 min following the FDG injection. Significant intercorrelations of localized cerebral glucose metabolic rates with the scores of self-anxiety, anxiety displacement, and anxiety-denial were found in dissimilar cerebral locations depending on the type of anxiety involved. The significant correlations occurred in brain regions known to be associated with the functions of emotions, cognition, memory, and vision. Specific combinations of cerebral areas, based on glucose metabolic rates, appear to distinguish and be associated with different verbal expressions of anxiety. Replication of this preliminary research will be

  8. Advancements in anti-inflammatory therapy for dry eye syndrome.

    Science.gov (United States)

    McCabe, Erin; Narayanan, Srihari

    2009-10-01

    The goal of this literature review is to discuss recent discoveries in the pathophysiology of dry eye and the subsequent evolution of diagnostic and management techniques. The mechanisms of various anti-inflammatory treatments are reviewed, and the efficacy of common pharmacologic agents is assessed. Anti-inflammatory therapy is evaluated in terms of its primary indications, target population, and utility within a clinical setting. The Medline PubMed database and the World Wide Web were searched for current information regarding dry eye prevalence, pathogenesis, diagnosis, and management. After an analysis of the literature, major concepts were integrated to generate an updated portrayal of the status of dry eye syndrome. Inflammation appears to play a key role in perpetuating and sustaining dry eye. Discoveries of inflammatory markers found within the corneal and conjunctival epithelium of dry eye patients have triggered recent advancements in therapy. Pharmacologic anti-inflammatory therapy for dry eye includes 2 major categories: corticosteroids and immunomodulatory agents. Fatty acid and androgen supplementation and oral antibiotics have also shown promise in dry eye therapy because of their anti-inflammatory effects. Anti-inflammatory pharmacologic agents have shown great success in patients with moderate to severe dry eye when compared with alternative treatment modalities. A deeper understanding of the link between inflammation and dry eye validates the utilization of anti-inflammatory therapy in everyday optometric practice.

  9. General study of pyridazine compounds against cyclooxygenase enzyme and their relation with analgesic, anti-inflammatory and anti-arthritic activities

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    Mohammad Asif

    2010-01-01

    Full Text Available There is increased focus on developed non-steroidal anti-inflammatory drugs (NSAIDs containing a pyridazine nucleus. The NSAIDs are one of the most commonly used medications worldwide to inhibit cyclooxygenase (COX-1 and COX-2 enzyme in varying extent by inhibiting prostaglandin (PGEs synthesis for the treatment of pain, inflammation, arthritis and edema. Their routine and long-term use causes gastrointestinal (GIT and renal toxicities. In order to minimize these side-effects, selective COX-2 inhibitors are prepared with an improved GIT and renal safety profile relative to other NSAIDs. The recent development toward the effective NSAIDs agents causes dual COX and lipooxygenase inhibitory effects because COX-2 inhibitors cause cardiovascular problems. The literature stimulated these above findings. Our attention has been focused on the series of pyridazine or other derivatives that were reported or will be reported in the future as anti-inflammatory, analgesic, anti-arthritic as well as anti-edemic agent.

  10. Pro-oxidant activity of dietary chemopreventive agents: an under-appreciated anti-cancer property [v1; ref status: indexed, http://f1000r.es/15s

    Directory of Open Access Journals (Sweden)

    Asfar S Azmi

    2013-06-01

    Full Text Available “Let food be thy medicine and medicine be thy food” was quoted by Hippocrates more than two thousand years ago and since ancient times the health benefits of different natural agents have been exploited. In modern research, the disease preventive benefits of many such natural agents, particularly dietary compounds and their derivatives, has been attributed to their well recognized activity as the regulators of redox state of the cell. Nevertheless, most of these studies have focused on their antioxidant activity. A large body of evidence indicates that a major fraction of these agents can elicit pro-oxidant (radical generating behavior which has been linked to their anti-cancer effects. This editorial provides an overview of the under-appreciated pro-oxidant activity of natural products, with a special focus on their ability to generate reactive oxygen species in the presence of transition metal ions, and discusses their possible use as cancer chemotherapeutic agents.

  11. High trait anxiety: a challenge for disrupting fear memory reconsolidation.

    Science.gov (United States)

    Soeter, Marieke; Kindt, Merel

    2013-01-01

    Disrupting reconsolidation may be promising in the treatment of anxiety disorders but the fear-reducing effects are thus far solely demonstrated in the average organism. A relevant question is whether disrupting fear memory reconsolidation is less effective in individuals who are vulnerable to develop an anxiety disorder. By collapsing data from six previous human fear conditioning studies we tested whether trait anxiety was related to the fear-reducing effects of a pharmacological agent targeting the process of memory reconsolidation--n = 107. Testing included different phases across three consecutive days each separated by 24 h. Fear responding was measured by the eye-blink startle reflex. Disrupting the process of fear memory reconsolidation was manipulated by administering the β-adrenergic receptor antagonist propranolol HCl either before or after memory retrieval. Trait anxiety uniquely predicted the fear-reducing effects of disrupting memory reconsolidation: the higher the trait anxiety, the less fear reduction. Vulnerable individuals with the propensity to develop anxiety disorders may need higher dosages of propranolol HCl or more retrieval trials for targeting and changing fear memory. Our finding clearly demonstrates that we cannot simply translate observations from fundamental research on fear reduction in the average organism to clinical practice.

  12. [Effect of anti-inflammatory therapy on the treatment of dry eye syndrome].

    Science.gov (United States)

    Mrukwa-Kominek, Ewa; Rogowska-Godela, Anna; Gierek-Ciaciura, Stanisława

    2007-01-01

    Dry eye syndrome is a common chronic disease; agents and strategies for its effective management are still lacking. The syndrome tends to be accompanied by ocular surface inflammation; therefore, the use of anti-inflammatory agents might prove beneficial. The authors present up-to-date guidelines, strategies, and efficacy of dry eye syndrome management, including anti-inflammatory treatment. As no diagnostic tests are now available to assess ocular surface inflammation severity, the right timing to launch an anti-inflammatory agent is difficult to determine. Patients with mild intermittent bouts of symptoms which can be alleviated with ophthalmic lubricants do not typically require anti-inflammatory therapy. The latter should be considered in those who do not respond to lubricating drops, obtain poor results on clinical tests, and show symptoms of ocular surface irritation (eg. conjunctivae redness). Anti-inflammatory treatment of dry eye syndrome may include short-term corticosteroids, cyclosporine A emulsion, oral tetracycline therapy, oral omega-3 fatty acid supplements, and autologous serum eye drops. Anti-inflammatory treatment should be safe and effective; potential benefits should be evaluated for each individual patient. The authors have reviewed the advantages of anti-inflammatory treatment in dry eye syndrome, presented in literature.

  13. Phytochemistry and pharmacology of anti-depressant medicinal plants: A review.

    Science.gov (United States)

    Martins, Jeanette; S, Brijesh

    2018-05-16

    Stress renders an individual to experience mental pressure and exhaustion which brings about feelings of anxiety, depression, anger and/or other negative emotions. Depression affects a person's state of mind, behaviour, health and is often associated with suicide. The use of anti-depressant drugs as therapeutic agents is associated with symptoms such as, delayed onset of action, side-effects, drug-drug and dietary interactions, sexual dysfunction, cardiac toxicity, etc. Thus, there is need to target these issues and improve current treatment options. Medicinal plants have long been used in discovering novel treatment strategies and compounds with promising roles in treating various disease conditions. There has been an increase, worldwide, in the use of medicinal plants and herbs for developing nutraceuticals for treatment of depression and other psychiatric disorders. Medicinal plants in their natural forms are valuable as they are rich in various phytochemical compounds. These phytochemical compounds have pharmacological roles in treating various diseases conditions; apart from being widely available in nature and commercially beneficial. The phytochemical compounds in plants are constantly being explored through various experimental studies to determine the molecular basis of how medicinal plants work in relation to drugs and diseases and to develop neutraceuticals for improving conditions. This review summarizes 110 medicinal plants and their phytochemical constituents that have been shown to possess anti-depressant activity. This review also highlights the various mechanisms of anti-depressant action of some of these plants and their plant parts like roots, stem, leaves, flowers, fruit or whole plant; phytochemical compounds showing anti-depressant activity such flavanoids, steroids, saponins, sugars, lectins, alkaloids, etc.; and various anti-depressant screening models used such as tail suspension test, forced swim test, chronic unpredictable stress test

  14. Depression- and anxiety-like behaviour is related to BDNF/TrkB signalling in a mouse model of psoriasis.

    Science.gov (United States)

    JiaWen, W; Hong, S; ShengXiang, X; Jing, L

    2018-04-01

    The prevalence of anxiety and depression is significantly higher in individuals with psoriasis than in the general population. Clinical data also show that anti-anxiety and antidepression drugs can reduce skin lesions in patients with psoriasis, but the actual mechanism is still poorly understood. To investigate whether brain-derived neurotrophic factor (BDNF) and tropomyosin receptor kinase B (TrKB) signalling plays a role in the mechanism underlying psoriasis with depression and anxiety behaviours. Expression of BDNF and tropomyosin receptor kinase B (TrKB) in the K5.Stat3C mouse, an animal model of psoriasis, were investigated by reverse transcription PCR and Western blotting. Anxiety-like behaviours in the elevated-plus maze test and changes in BDNF/TrkB that have been implicated in depression and anxiety behaviours were measured. Skin lesions induced by 12-O-tetradecanoyl phorbol-13-acetate (TPA) were also measured when the mice were administered fluoxetine and K252a, an antagonist of TrkB. The antidepression and anti-anxiety drug fluoxetine reduced TPA-induced skin lesions and increased expression of BDNF and TrkB in K5.Stat3C mice. More importantly, the effects of fluoxetine were reversed by the TrkB antagonist K252a. BDNF/TrkB signalling participates in the pathological mechanism of depression and anxiety behaviours in psoriasis. Our findings provide a new therapeutic strategy for the treatment of skin lesions in psoriasis. © 2018 British Association of Dermatologists.

  15. [Upper gastrointestinal hemorrhage caused by anti-inflammatory agents].

    Science.gov (United States)

    Duhamel, C; Czernichow, P; Dechelotte, P; Ducrotte, P; Lerebours, E; Colin, R

    1989-03-01

    The aim of this study was to describe the clinical and evolutive characteristics of gastroduodenal bleeding occurring in patients receiving nonsteroidal anti-inflammatory (NSAI) drugs, containing salicylates or not, and to determine the relative toxicity of the NSAI drugs without salicylates. Eight hundred and fourty-five consecutive patients with upper gastrointestinal bleeding related to endoscopically proven peptic ulcer or gastroduodenal erosions were admitted between 1983 and June 1987 to an intensive care unit for digestive tract hemorrhage. Of these, 267 were using anti-inflammatory drugs; 151 (56 p. 100) were taking NSAI drugs other than salicylates, 97 salicylates (36 p. 100) and 10, steroids (4 p. 100). Patients taking nonsteroidal drugs without or with salicylates were compared with patients bleeding from gastroduodenal ulcer or erosion not receiving anti-inflammatory therapy. Patients receiving nonsteroidal drugs not containing salicylates were older (70 p. 100 over 65 years of age vs 46 p. 100, p less than 0.001) and the proportion of female patients was greater (54 p. 100 vs 33 p. 100, p less than 0.001) than in the other group. No significant difference was observed with regard to the following parameters: percentage of gastric lesions, concomitant anticoagulant therapy, need for surgical hemostasis, or mortality. Patients taking aspirin had more gastric lesions (75 p. 100 vs 64 p. 100, p less than 0.05) and less need for surgical hemostasis (7 p. 100 vs 15 p. 100, p less than 0.05); the other parameters did not differ. NSAI drugs other than salicylates were taken more often for osteoarthritis than salicylates (33.6 p. 100 vs 17.4 p. 100, p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

  16. Identification of novel 3,5-diarylpyrazoline derivatives containing salicylamide moiety as potential anti-melanoma agents.

    Science.gov (United States)

    Li, Qing-Shan; Lv, Xian-Hai; Zhang, Yan-Bin; Dong, Jing-Jun; Zhou, Wen-Ping; Yang, Yang; Zhu, Hai-Liang

    2012-11-01

    There is an accumulating body of experimental evidences validating oncogenic BRAF(V600E) as a therapeutic target and offering opportunities for anti-melanoma drug development. Encouraged by the positive results of pyrazole derivatives as BRAF(V600E) inhibitors, we sought to design diverse novel potential BRAF(V600E) inhibitors as antitumor agents based on pyrazole skeleton. In silico and in vitro screening of our designed pyrazole derivatives has identified Hit 1 as BRAF(V600E) inhibitor. Based on its structure and through further structure modification, compound 25, which exhibited the most potent inhibitory activity with an IC(50) value of 0.16 μM for BRAF(V600E) and GI(50) value of 0.24 μM for mutant BRAF-dependent melanoma cells, was obtained. The 3D-QSAR models and the molecular docking simulation were introduced to analyze the structure-activity relationship. Copyright © 2012 Elsevier Ltd. All rights reserved.

  17. In vitro anti-Malassezia activity and potential use in anti-dandruff formulation of Asparagus racemosus.

    Science.gov (United States)

    Onlom, C; Khanthawong, S; Waranuch, N; Ingkaninan, K

    2014-02-01

    Malassezia species are frequently associated with dandruff and seborrhoeic dermatitis. The study was conducted to evaluate anti-fungal activities of the extracts obtained from the roots of Asparagus racemosus Willd against Malassezia furfur and M. globosa. Asparagus racemosus roots were successively extracted with the series of solvents, that is, hexane, ethanol and water, and also a saponin-enriched fraction was prepared. The amounts of saponin (equivalent to shatavarin IV) in the extracts were determined using ELISA. The extracts were tested for anti-fungal activity by disc diffusion and broth microdilution methods. By disc diffusion, only the ethanolic and saponin-enriched extracts demonstrated anti-fungal activity against M. furfur and M. globosa at the concentration of 1 mg per disc whereas the extracts with other solvents were ineffective. Multiple concentrations using the broth microdilution method against M. furfur and M. globosa yielded minimum inhibitory concentrations (MICs) of 25 mg mL(-1) for the ethanolic extract but much higher potency for the saponin-enriched extract: MICs to 0.20 and 0.40 mg mL(-1) for M. furfur and M. globosa, respectively. These extracts showed no antagonist effect with the anti-fungal agents, ketoconazole and zinc pyrithione. These studies revealed the antifungal activity of A. racemosus roots extracts. Because A. racemosus is also anti-inflammatory agent, it has the potential use as an active ingredient in an anti-dandruff formulation. © 2013 Society of Cosmetic Scientists and the Société Française de Cosmétologie.

  18. Alpha-1 antitrypsin: a potent anti-inflammatory and potential novel therapeutic agent.

    LENUS (Irish Health Repository)

    Bergin, David A

    2012-04-01

    Alpha-1 antitrypsin (AAT) has long been thought of as an important anti-protease in the lung where it is known to decrease the destructive effects of major proteases such as neutrophil elastase. In recent years, the perception of this protein in this simple one dimensional capacity as an anti-protease has evolved and it is now recognised that AAT has significant anti-inflammatory properties affecting a wide range of inflammatory cells, leading to its potential therapeutic use in a number of important diseases. This present review aims to discuss the described anti-inflammatory actions of AAT in modulating key immune cell functions, delineate known signalling pathways and specifically to identify the models of disease in which AAT has been shown to be effective as a therapy.

  19. Evaluation of a curcumin analog as an anti-cancer agent inducing ER stress-mediated apoptosis in non-small cell lung cancer cells

    International Nuclear Information System (INIS)

    Liu, Zhiguo; Wang, Yi; Sun, Yusheng; Ren, Luqing; Huang, Yi; Cai, Yuepiao; Weng, Qiaoyou; Shen, Xueqian; Li, Xiaokun; Liang, Guang

    2013-01-01

    Recent advances have highlighted the importance of the endoplasmic reticulum (ER) in cell death processes. Pharmacological interventions that effectively enhance tumor cell death through activating ER stress have attracted a great deal of attention for anti-cancer therapy. A bio-evaluation on 113 curcumin analogs against four cancer cell lines was performed through MTT assay. Furthermore, real time cell assay and flow cytometer were used to evaluate the apoptotic induction of (1E,4E)-1,5-bis(5-bromo-2-ethoxyphenyl)penta-1,4-dien-3-one (B82). Western blot, RT-qPCR, and siRNA were then utilized to confirm whether B82-induced apoptosis is mediated through activating ER stress pathway. Finally, the in vivo anti-tumor effect of B82 was evaluated. B82 exhibited strong anti-tumor activity in non-small cell lung cancer (NSCLC) H460 cells. Treatment with B82 significantly induced apoptosis in H460 cells in vitro and inhibited H460 tumor growth in vivo. Further studies demonstrated that the B82-induced apoptosis is mediated by activating ER stress both in vitro and in vivo. A new monocarbonyl analog of curcumin, B82, exhibited anti-tumor effects on H460 cells via an ER stress-mediated mechanism. B82 could be further explored as a potential anticancer agent for the treatment of NSCLC

  20. Synthesis and characterization of anti-bacterial and anti-fungal citrate-based mussel-inspired bioadhesives

    Science.gov (United States)

    Guo, Jinshan; Wang, Wei; Hu, Jianqing; Xie, Denghui; Gerhard, Ethan; Nisic, Merisa; Shan, Dingying; Qian, Guoying; Zheng, Siyang; Yang, Jian

    2016-01-01

    Bacterial and fungal infections in the use of surgical devices and medical implants remain a major concern. Traditional bioadhesives fail to incorporate anti-microbial properties, necessitating additional anti-microbial drug injection. Herein, by the introduction of the clinically used and inexpensive anti-fungal agent, 10-undecylenic acid (UA), into our recently developed injectable citrate-based mussel-inspired bioadhesives (iCMBAs), a new family of anti-bacterial and anti-fungal iCMBAs (AbAf iCs) was developed. AbAf iCs not only showed strong wet tissue adhesion strength, but also exhibited excellent in vitro cyto-compatibility, fast degradation, and strong initial and considerable long-term anti-bacterial and anti-fungal ability. For the first time, the biocompatibility and anti-microbial ability of sodium metaperiodate (PI), an oxidant used as a cross-linking initiator in the AbAf iCs system, was also thoroughly investigated. Our results suggest that the PI-based bioadhesives showed better anti-microbial properties compared to the unstable silver-based bioadhesive materials. In conclusion, AbAf iCs family can serve as excellent anti-bacterial and anti-fungal bioadhesive candidates for tissue/wound closure, wound dressing, and bone regeneration, especially when bacterial or fungal infections are a major concern. PMID:26874283

  1. Research on Grooved Concrete Pavement Based on the Durability of Its Anti-Skid Performance

    Directory of Open Access Journals (Sweden)

    Mulian Zheng

    2018-05-01

    Full Text Available The objectives of the present study are to investigate the anti-skid performance of concrete pavement and to attempt to enhance its durability by two different methods: using a longitudinally-transversely grooved (LT form, and using a self-developed composite curing agent containing paraffin and Na2SiO3 as the main ingredients. The friction coefficient (μ was measured by self-developed equipment to evaluate the anti-skid performance of samples with three different groove forms (LT, longitudinally grooved (L, and transversely grooved (T. Abrasion tests were then carried out to evaluate the durability of the anti-skid performance. The results indicated that anti-skid performance of LT samples was approximately 46.2% greater than that of T samples, but its durability was not as significant as that of T samples. However, the resistance to abrasion could be improved by using the aforementioned curing agent. Comparisons were carried out between samples sprayed the curing agent and control samples without any curing agent under standard conditions. It was found that the application of the curing agent increased the anti-skid durability of concrete by 35.4%~47.8%, proving it to be a useful and promising technique.

  2. High trait anxiety: a challenge for disrupting fear memory reconsolidation.

    Directory of Open Access Journals (Sweden)

    Marieke Soeter

    Full Text Available Disrupting reconsolidation may be promising in the treatment of anxiety disorders but the fear-reducing effects are thus far solely demonstrated in the average organism. A relevant question is whether disrupting fear memory reconsolidation is less effective in individuals who are vulnerable to develop an anxiety disorder. By collapsing data from six previous human fear conditioning studies we tested whether trait anxiety was related to the fear-reducing effects of a pharmacological agent targeting the process of memory reconsolidation--n = 107. Testing included different phases across three consecutive days each separated by 24 h. Fear responding was measured by the eye-blink startle reflex. Disrupting the process of fear memory reconsolidation was manipulated by administering the β-adrenergic receptor antagonist propranolol HCl either before or after memory retrieval. Trait anxiety uniquely predicted the fear-reducing effects of disrupting memory reconsolidation: the higher the trait anxiety, the less fear reduction. Vulnerable individuals with the propensity to develop anxiety disorders may need higher dosages of propranolol HCl or more retrieval trials for targeting and changing fear memory. Our finding clearly demonstrates that we cannot simply translate observations from fundamental research on fear reduction in the average organism to clinical practice.

  3. Iridoid glucosides from Vitex grandifolia displayed Anti-inflammatory ...

    African Journals Online (AJOL)

    ADOWIE PERE

    2018-03-30

    Mar 30, 2018 ... a link between low incidence of some diseases and consumption of vegetables hence advantages of these vegetables are beyond nutritional gains. ..... Bioactivities of iridoids. Anti-inflam. Anti-Allerg. Agents. Med. Chem. 6: 307–314. Croft, SL; and Yardley, V; (2002). Chemotherapy of leishmaniasis. Current ...

  4. Poly herbal formulation with anti-elastase and anti-oxidant properties for skin anti-aging.

    Science.gov (United States)

    Kalyana Sundaram, Induja; Sarangi, Deepika Deeptirekha; Sundararajan, Vignesh; George, Shinomol; Sheik Mohideen, Sahabudeen

    2018-01-29

    Skin forms an important part of human innate immune system. Wrinkles, thinning and roughening of skin are some of the symptoms that affect the skin as it ages. Reactive oxygen species induced oxidative stress plays a major role in skin aging by modulating the elastase enzyme level in the skin. Extrinsic factors that affect skin aging such as UV radiation can also cause malignant melanoma. Here we selected four medicinal plant materials, namely, leaves of Nyctanthes arbor-tristis, unripe and ripe Aegle marmelos fruit pulp and the terminal meristem of Musa paradisiaca flower and investigated their anti-aging properties and cytotoxicity in vitro individually as well as in a poly herbal formulation containing the four plant extracts in different ratios. The phytochemical contents of the plant extracts were investigated for radical scavenging activity and total reducing power. Based upon its anti-oxidant properties, a poly herbal formulation containing leaves of Nyctanthes arbor-tristis, unripe and ripe fruit pulp of Aegle marmelos, and the terminal meristem of Musa paradisiaca flower in the ratio 6:2:1:1 (Poly Herbal Formulation 1) and 1:1:1:1 (Poly Herbal Formulation 2), respectively were formulated. It has been observed that the Poly Herbal Formulation 1 was more potent than Poly Herbal Formulation 2 due to better anti-oxidant and anti-elastase activities in NIH3T3 fibroblast cells. In addition Poly Herbal formulation 1 also had better anti-cancer activity in human malignant melanoma cells. Based on these results these beneficial plant extracts were identified for its potential application as an anti-aging agent in skin creams as well as an anti-proliferation compound against cancer cells.

  5. N-acetylcysteine prevents stress-induced anxiety behavior in zebrafish.

    Science.gov (United States)

    Mocelin, Ricieri; Herrmann, Ana P; Marcon, Matheus; Rambo, Cassiano L; Rohden, Aline; Bevilaqua, Fernanda; de Abreu, Murilo Sander; Zanatta, Leila; Elisabetsky, Elaine; Barcellos, Leonardo J G; Lara, Diogo R; Piato, Angelo L

    2015-12-01

    Despite the recent advances in understanding the pathophysiology of anxiety disorders, the pharmacological treatments currently available are limited in efficacy and induce serious side effects. A possible strategy to achieve clinical benefits is drug repurposing, i.e., discovery of novel applications for old drugs, bringing new treatment options to the market and to the patients who need them. N-acetylcysteine (NAC), a commonly used mucolytic and paracetamol antidote, has emerged as a promising molecule for the treatment of several neuropsychiatric disorders. The mechanism of action of this drug is complex, and involves modulation of antioxidant, inflammatory, neurotrophic and glutamate pathways. Here we evaluated the effects of NAC on behavioral parameters relevant to anxiety in zebrafish. NAC did not alter behavioral parameters in the novel tank test, prevented the anxiety-like behaviors induced by an acute stressor (net chasing), and increased the time zebrafish spent in the lit side in the light/dark test. These data may indicate that NAC presents an anti-stress effect, with the potential to prevent stress-induced psychiatric disorders such as anxiety and depression. The considerable homology between mammalian and zebrafish genomes invests the current data with translational validity for the further clinical trials needed to substantiate the use of NAC in anxiety disorders. Copyright © 2015 Elsevier Inc. All rights reserved.

  6. On the use of pets to manage dental anxiety

    Directory of Open Access Journals (Sweden)

    Lora Manley

    2016-01-01

    Full Text Available Dental anxiety and fear can be a significant barrier to dental care, with symptoms ranging from feelings of unease to avoidance of care. The management of anxious patients is essential to improve their oral health. Triggers include sights, sounds, sensations, and smells of the equipment used in restorative procedures, and management should focus on controlling these factors. Recommendations for controlling these triggers include distraction and pharmacological interventions. In medicine, distractions include animal-assisted therapy, which proves an effective means of reducing anxiety levels. Studies have shown that interactions with live animals reduce self-reported anxiety more than distractions by either humans or magazines. The media also addresses the valuable role of emotional support by animals in boosting health and enhancing lives. In the past year, numerous news stories have reported regarding the use of certified therapy by dogs to comfort anxious patients in dental practices across the United States. Dogs serve to distract patients, drawing their focus away from dentistry, and generate a positive energy that enliven both the staff and the patients. The positive impact that therapy dogs have had on patients′ dental experiences cannot be overstated. The incorporation of pet anti-anxiety therapy is a safe, effective, and inexpensive approach to easing dental anxiety and has profound potential for improving oral health.

  7. Anti-tumor effects of an engineered “killer” transfer RNA

    International Nuclear Information System (INIS)

    Zhou, Dong-hui; Lee, Jiyoung; Frankenberger, Casey; Geslain, Renaud; Rosner, Marsha; Pan, Tao

    2012-01-01

    Highlights: ► tRNA with anti-cancer effects. ► tRNA induced protein misfolding. ► tRNA as anti-tumor agent. -- Abstract: A hallmark of cancer cells is their ability to continuously divide; and rapid proliferation requires increased protein translation. Elevating levels of misfolded proteins can elicit growth arrest due to ER stress and decreased global translation. Failure to correct prolonged ER stress eventually results in cell death via apoptosis. tRNA Ser (AAU) is an engineered human tRNA Ser with an anticodon coding for isoleucine. Here we test the possibility that tRNA Ser (AAU) can be an effective killing agent of breast cancer cells and can effectively inhibit tumor-formation in mice. We found that tRNA Ser (AAU) exert strong effects on breast cancer translation activity, cell viability, and tumor formation. Translation is strongly inhibited by tRNA Ser (AAU) in both tumorigenic and non-tumorigenic cells. tRNA Ser (AAU) significantly decreased the number of viable cells over time. A short time treatment with tRNA Ser (AAU) was sufficient to eliminate breast tumor formation in a xenograft mouse model. Our results indicate that tRNA Ser (AAU) can inhibit breast cancer metabolism, growth and tumor formation. This RNA has strong anti-cancer effects and presents an opportunity for its development into an anti-tumor agent. Because tRNA Ser (AAU) corrupts the protein synthesis mechanism that is an integral component of the cell, it would be extremely difficult for tumor cells to evolve and develop resistance against this anti-tumor agent.

  8. Soaps and Germicides as Adjunct Topical Antimycotic Agents on ...

    African Journals Online (AJOL)

    Objective: The study aims at evaluating the potentials of soaps and germicides / disinfectants as adjunct topical anti-vulvovaginal candidasis agents. Methods: In vitro inhibitory activities of the test agents, prepared according to the manufacturer's specification for toilet and midwifery purposes were determined using modified ...

  9. Antimicrobial activity of ceftaroline and other anti-infective agents against microbial pathogens recovered from the surgical intensive care patient population: a prevalence analysis.

    Science.gov (United States)

    Edmiston, Charles E; Krepel, Candace J; Leaper, David; Ledeboer, Nathan A; Mackey, Tami-Lea; Graham, Mary Beth; Lee, Cheong; Rossi, Peter J; Brown, Kellie R; Lewis, Brian D; Seabrook, Gary R

    2014-12-01

    Ceftaroline is a new parenteral cephalosporin agent with excellent activity against methicillin-sensitive (MSSA) and resistant strains of Staphylococcus aureus (MRSA). Critically ill surgical patients are susceptible to infection, often by multi-drug-resistant pathogens. The activity of ceftaroline against such pathogens has not been described. Three hundred thirty-five consecutive microbial isolates were collected from surgical wounds or abscesses, respiratory, urine, and blood cultures from patients in the surgical intensive care unit (SICU) of a major tertiary medical center. Using Clinical and Laboratory Standards Institute (CLSI) standard methodology and published breakpoints, all aerobic, facultative anaerobic isolates were tested against ceftaroline and selected comparative antimicrobial agents. All staphylococcal isolates were susceptible to ceftaroline at a breakpoint of ≤1.0 mcg/mL. In addition, ceftaroline exhibited excellent activity against all streptococcal clinical isolates and non-ESBL-producing strains of Enterobacteriaceae (93.5%) recovered from SICU patients. Ceftaroline was inactive against ESBL-producing Enterobacteriaceae, Pseudomonas aeruginosa, vancomycin-resistant enterococci, and selective gram-negative anaerobic bacteria. At present, ceftaroline is the only cephalosporin agent that is active against community and healthcare-associated MRSA. Further studies are needed to validate the benefit of this novel broad-spectrum anti-infective agent for the treatment of susceptible serious infections in the SICU patient population.

  10. Evaluating the Quality of Life of Glaucoma Patients Using the State-Trait Anxiety Inventory.

    Science.gov (United States)

    Otori, Yasumasa; Takahashi, Genichiro; Urashima, Mitsuyoshi; Kuwayama, Yasuaki

    2017-11-01

    To evaluate anxiety felt by glaucoma patients. In total, 472 glaucoma patients responded to a questionnaire on anxiety, subjective symptoms, and vision-related quality of life (VR-QOL) associated with glaucoma. Anxiety was evaluated using the State-Trait Anxiety Inventory (STAI), state anxiety (STAI-State) subscale along with our novel questionnaire, assessing visual function and subjective symptoms, specialized for glaucoma. VR-QOL was evaluated using 5 subitems from the 25-item National Eye Institute Visual Function Questionnaire (VFQ-25). Adherence to ophthalmic antiglaucoma agents was confirmed. As indexes of visual function, corrected visual acuity (measured by eye chart), mean deviation (MD) score (measured with static perimetry), and 4 thresholds at the center of vision were determined. Stages were classified according to the Aulhorn Classification. From the STAI-State scores, the prevalence of anxiety in glaucoma patients was evaluated. We analyzed the correlation between the STAI-State and VFQ-25, anxiety, subjective symptoms, adherence, and visual function indexes. In total, 78% of glaucoma patients experienced at least an intermediate level of anxiety. The STAI-State correlated significantly with anxiety and subjective symptoms as measured by our novel questionnaire, particularly for questions "current anxiety about loss of vision" and "current anxiety in life" (r=0.468 and 0.500; both Pglaucoma patients feel anxiety. The STAI-State is correlated with the VR-QOL and anxiety in glaucoma patients, making it useful for understanding the anxiety present in glaucoma patients.

  11. Golimumab and certolizumab: The two new anti-tumor necrosis factor kids on the block

    Directory of Open Access Journals (Sweden)

    Mittal Mohit

    2010-01-01

    Full Text Available Anti-tumor necrosis factor (anti-TNF agents have revolutionized treatment of psoriasis and many other inflammatory diseases of autoimmune origin. They have considerable advantages over the existing immunomodulators. Anti-TNF agents are designed to target a very specific component of the immune-mediated inflammatory cascades. Thus, they have lower risks of systemic side-effects. In a brief period of 10 years, a growing number of biological therapies are entering the clinical arena while many more biologicals remain on the horizon. With time, the long-term side-effects and efficacies of these individual agents will become clearer and help to determine which ones are the most suitable for long-term care. Golimumab (a human monoclonal anti-TNF-α antibody and Certolizumab (a PEGylated Fab fragment of humanized monoclonal TNF-α antibody are the two latest additions to the anti-TNF regimen. Here, we are providing a brief description about these two drugs and their uses.

  12. Effect of physical activity on anxiety levels in pregnant women

    Directory of Open Access Journals (Sweden)

    Inga Janik

    2017-08-01

    Full Text Available Pregnancy is a very important period in a woman's life, but it is often associated not only with positive emotions, but also with negative emotions such as anxiety, stress or depression. Women most often fear birth and various medical complications during pregnancy. Very often their unpleasant experiences at the beginning such as nausea, fatigue and strong anxiety cause them to give up their physical activity. Numerous studies show that the physical activity of pregnant women has a positive impact on mother and child health. First and foremost, it is a powerful preventive agent in cardiovascular disease, diabetes mellitus, but also has a beneficial effect on the well-being of future mothers, including lowering anxiety and lowering the incidence of postpartum depression. That is why it is so important to educate pregnant women what exercises are most beneficial for them.

  13. Early Changes of Retinal Morphology in Therapy of Neovascular Age-Related Macular Degeneration with Three Commonly Used Anti-VEGF Agents.

    Science.gov (United States)

    Enders, Philip; Sitnilska, Vasilena; Altay, Lebriz; Fauser, Sascha

    2018-01-01

    To compare changes of retinal morphology in the first weeks following injection of anti-VEGF agents for neovascular age-related macular degeneration (nAMD). In a prospective study 50 patients with active choroidal neovascularization secondary to nAMD were monitored weekly by spectral-domain optical coherence tomography for 3 weeks after treatment. Twenty-two patients received bevacizumab, 15 ranibizumab, and 13 aflibercept. Morphological parameters of retinal compartments were compared. Mean central retinal thickness (391.22 ± 123.41 µm) was reduced by -26.15 µm (p treatment. This information could be clinically helpful to evaluate early non-response. © 2017 S. Karger AG, Basel.

  14. Strategies for combating bacterial biofilms: A focus on anti-biofilm agents and their mechanisms of action

    Science.gov (United States)

    Roy, Ranita; Tiwari, Monalisa; Donelli, Gianfranco; Tiwari, Vishvanath

    2018-01-01

    ABSTRACT Biofilm refers to the complex, sessile communities of microbes found either attached to a surface or buried firmly in an extracellular matrix as aggregates. The biofilm matrix surrounding bacteria makes them tolerant to harsh conditions and resistant to antibacterial treatments. Moreover, the biofilms are responsible for causing a broad range of chronic diseases and due to the emergence of antibiotic resistance in bacteria it has really become difficult to treat them with efficacy. Furthermore, the antibiotics available till date are ineffective for treating these biofilm related infections due to their higher values of minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC), which may result in in-vivo toxicity. Hence, it is critically important to design or screen anti-biofilm molecules that can effectively minimize and eradicate biofilm related infections. In the present article, we have highlighted the mechanism of biofilm formation with reference to different models and various methods used for biofilm detection. A major focus has been put on various anti-biofilm molecules discovered or tested till date which may include herbal active compounds, chelating agents, peptide antibiotics, lantibiotics and synthetic chemical compounds along with their structures, mechanism of action and their respective MICs, MBCs, minimum biofilm inhibitory concentrations (MBICs) as well as the half maximal inhibitory concentration (IC50) values available in the literature so far. Different mode of action of anti biofilm molecules addressed here are inhibition via interference in the quorum sensing pathways, adhesion mechanism, disruption of extracellular DNA, protein, lipopolysaccharides, exopolysaccharides and secondary messengers involved in various signaling pathways. From this study, we conclude that the molecules considered here might be used to treat biofilm-associated infections after significant structural modifications, thereby

  15. Rapid and sustained symptom reduction following psilocybin treatment for anxiety and depression in patients with life-threatening cancer: a randomized controlled trial.

    Science.gov (United States)

    Ross, Stephen; Bossis, Anthony; Guss, Jeffrey; Agin-Liebes, Gabrielle; Malone, Tara; Cohen, Barry; Mennenga, Sarah E; Belser, Alexander; Kalliontzi, Krystallia; Babb, James; Su, Zhe; Corby, Patricia; Schmidt, Brian L

    2016-12-01

    Clinically significant anxiety and depression are common in patients with cancer, and are associated with poor psychiatric and medical outcomes. Historical and recent research suggests a role for psilocybin to treat cancer-related anxiety and depression. In this double-blind, placebo-controlled, crossover trial, 29 patients with cancer-related anxiety and depression were randomly assigned and received treatment with single-dose psilocybin (0.3 mg/kg) or niacin, both in conjunction with psychotherapy. The primary outcomes were anxiety and depression assessed between groups prior to the crossover at 7 weeks. Prior to the crossover, psilocybin produced immediate, substantial, and sustained improvements in anxiety and depression and led to decreases in cancer-related demoralization and hopelessness, improved spiritual wellbeing, and increased quality of life. At the 6.5-month follow-up, psilocybin was associated with enduring anxiolytic and anti-depressant effects (approximately 60-80% of participants continued with clinically significant reductions in depression or anxiety), sustained benefits in existential distress and quality of life, as well as improved attitudes towards death. The psilocybin-induced mystical experience mediated the therapeutic effect of psilocybin on anxiety and depression. In conjunction with psychotherapy, single moderate-dose psilocybin produced rapid, robust and enduring anxiolytic and anti-depressant effects in patients with cancer-related psychological distress. ClinicalTrials.gov Identifier: NCT00957359. © The Author(s) 2016.

  16. Design, Synthesis and Evaluation of Novel Phthalimide Derivatives as in Vitro Anti-Microbial, Anti-Oxidant and Anti-Inflammatory Agents

    Czech Academy of Sciences Publication Activity Database

    Lamie, P.F.; Philoppes, J.N.; El-Gendy, A.O.; Rárová, Lucie; Grúz, Jiří

    2015-01-01

    Roč. 20, č. 9 (2015), s. 16620-16642 ISSN 1420-3049 R&D Projects: GA MŠk(CZ) LO1204 Institutional support: RVO:61389030 Keywords : synthesis * phthalimides * anti-microbial Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 2.465, year: 2015

  17. Deoxypodophyllotoxin: a promising therapeutic agent from herbal medicine.

    Science.gov (United States)

    Khaled, Meyada; Jiang, Zhen-Zhou; Zhang, Lu-Yong

    2013-08-26

    Recently, biologically active compounds isolated from plants used in herbal medicine have been the center of interest. Deoxypodophyllotoxin (DPT), structurally closely related to the lignan podophyllotoxin, is a potent antitumor and anti-inflammatory agent. However, DPT has not been used clinically yet. Also, DPT from natural sources seems to be unavailable. Hence, it is important to establish alternative resources for the production of such lignan; especially that it is used as a precursor for the semi-synthesis of the cytostatic drugs etoposide phosphate and teniposide. The update paper provides an overview of DPT as an effective anticancer natural compound and a leader for cytotoxic drugs synthesis and development in order to highlight the gaps in our knowledge and explore future research needs. The present review covers the literature available from 1877 to 2012. The information was collected via electronic search using Chinese papers and the major scientific databases including PubMed, Sciencedirect, Web of Science and Google Scholar using the keywords. All abstracts and full-text articles reporting database on the history and current status of DPT were gathered and analyzed. Plants containing DPT have played an important role in traditional medicine. In light of the in vitro pharmacological investigations, DPT is a high valuable medicinal agent that has anti-tumor, anti-proliferative, anti-inflammatory and anti-allergic properties. Further, DPT is an important precursor for the cytotoxic aryltetralin lignan, podophyllotoxin, which is used to obtain semisynthetic derivatives like etoposide and teniposide used in cancer therapy. However, most studies have focused on the in vitro data. Therefore, DPT has not been used clinically yet. DPT has emerged as a potent chemical agent from herbal medicine. Therefore, in vivo studies are needed to carry out clinical trials in humans and enable the development of new anti-cancer agents. In addition, DPT from commercial

  18. Genistein alleviates anxiety-like behaviors in post-traumatic stress disorder model through enhancing serotonergic transmission in the amygdala.

    Science.gov (United States)

    Wu, Zhong-Min; Ni, Gui-Lian; Shao, Ai-Min; Cui, Rong

    2017-09-01

    Post-traumatic stress disorder (PTSD) is a chronic psychiatric disorder, characterized by intense fear, and increased arousal and avoidance of traumatic events. The current available treatments for PTSD have limited therapeutic value. Genistein, a natural isoflavone, modulates a variety of cell functions. In this study, we tested anti-anxiety activity and underlying mechanisms of genistein in a PTSD rat model. The rats were trained to associate a tone with foot shock delivery on day 0, then fear conditioning was performed on day 7, 14 and 21. Genistein (2-8mg/kg) was injected intraperitoneally daily for 7 days. The anti-anxiety effects of genistein were measured by contextual freezing behavior and elevated plus maze. By the end of the experiments, the amygdala was extracted and subject to neurochemistry analysis. Genistein alleviated contextual freezing behavior and improved performance in elevated plus maze dose-dependently in PTSD rats. Furthermore, in these rats, genistein enhanced serotonergic transmission in the amygdala, including upregulation of tryptophan hydroxylase, serotonin, and phosphorylated (p)-CaMKII and p-CREB, as well. Genistein exerts anti-anxiety effects on a PTSD model probably through enhancing serotonergic system and CaMKII/CREB signaling pathway in the amygdala. Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.

  19. Polish natural bee honeys are anti-proliferative and anti-metastatic agents in human glioblastoma multiforme U87MG cell line.

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    Justyna Moskwa

    Full Text Available Honey has been used as food and a traditional medicament since ancient times. However, recently many scientists have been concentrating on the anti-oxidant, anti-proliferative, anti-inflammatory and other properties of honey. In this study, we investigated for the first time an anticancer effect of different honeys from Poland on tumor cell line - glioblastoma multiforme U87MG. Anti-proliferative activity of honeys and its interferences with temozolomide were determined by a cytotoxicity test and DNA binding by [H3]-thymidine incorporation. A gelatin zymography was used to conduct an evaluation of metalloproteinases (MMP-2 and MMP-9 expression in U87MG treatment with honey samples. The honeys were previously tested qualitatively (diastase activity, total phenolic content, lead and cadmium content. The data demonstrated that the examined honeys have a potent anti-proliferative effect on U87MG cell line in a time- and dose-dependent manner, being effective at concentrations as low as 0.5% (multifloral light honey - viability 53% after 72 h of incubation. We observed that after 48 h, combining honey with temozolomide showed a significantly higher inhibitory effect than the samples of honey alone. We observed a strong inhibition of MMP-2 and MMP-9 for the tested honeys (from 20 to 56% and from 5 to 58% compared to control, respectively. Our results suggest that Polish honeys have an anti-proliferative and anti-metastatic effect on U87MG cell line. Therefore, natural bee honey can be considered as a promising adjuvant treatment for brain tumors.

  20. Nitrofuranyl Methyl Piperazines as New Anti-TB Agents: Identification, Validation, Medicinal Chemistry, and PK Studies

    Science.gov (United States)

    2015-01-01

    Whole-cell screening of 20,000 drug-like small molecules led to the identification of nitrofuranyl methylpiperazines as potent anti-TB agents. In the present study, validation followed by medicinal chemistry has been used to explore the structure–activity relationship. Ten compounds demonstrated potent MIC in the range of 0.17–0.0072 μM against H37Rv Mycobacterium tuberculosis (MTB) and were further investigated against nonreplicating and resistant (RifR and MDR) strains of MTB. These compounds were also tested for cytotoxicity. Among the 10 tested compounds, five showed submicromolar to nanomolar potency against nonreplicating and resistant (RifR and MDR) strains of MTB along with a good safety index. Based on their overall in vitro profiles, the solubility and pharmacokinetic properties of five potent compounds were studied, and two analogues, 14f and 16g, were found to have comparatively better solubility than others tested and acceptable pharmacokinetic properties. This study presents the rediscovery of a nitrofuranyl class of compounds with improved aqueous solubility and acceptable oral PK properties, opening a new direction for further development. PMID:26487909

  1. Generalized anxiety disorder: acute and chronic treatment.

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    Rynn, Moira A; Brawman-Mintzer, Olga

    2004-10-01

    Clinical and epidemiological data suggest that generalized anxiety disorder (GAD) is a chronic illness causing patients to suffer for many years leading to significant distress in daily life functioning. The literature suggests the several conclusions. GAD is a disorder in need of appropriate treatment and often has a chronic course with comorbid conditions, such as major depression and other anxiety disorders. Benzodiazepines, while effective anxiolytic agents acutely, when prescribed for >4 weeks cause rebound anxiety and following prolonged therapy may lead to withdrawal symptoms. Antidepressants cause significant anxiety relief compared with placebo and for psychosocial treatment cognitive-behavioral therapy is an efficacious psychosocial treatment. Many GAD patients are in need of long-term medication management. Furthermore, there is limited data for patients diagnosed with GAD the treatment outcome with the combination of medication and psychotherapy both acutely and long-term; how to best sequence these treatments; for those patients who do not meet remission criteria what is the ideal approach for augmentation; and for patients with treatment-refractory GAD the empirical evidence is lacking on medication switching and augmentation strategies. Research is needed in the area of developing treatment strategies for patients suffering from treatment-refractory GAD. There is still an urgent need to explore treatment combinations and duration strategies in the management of patients suffering with GAD.

  2. SYNTHESIS NEW POTENTIAL ANTI-INFLAMMATORY AGENT SODIUM SALT OF PENTAGAMAVUNON-0

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    Enade Perdana Istyastono

    2010-06-01

    Full Text Available Inflammation is the response of living tissues to injury. The process affects physiological changes such as erythema, edema, asthma and fever. Non-steroid Anti-inflammatory Drugs (NSAIDs have been developed since they could inhibit inflammation process because of its ability to inhibit biosynthesis of prostaglandin, one of inflammation mediators, through inhibition of cyclooxigenase (COX enzymes. Molecules, which have been reported having anti-inflammatory activity, for example, are curcumin, some curcumin derivatives and curcumin analogues. One of curcumin analogues that has been  developed is pentagamavunon-0 (PGV-0 whose IUPAC name is 2,5-bis(4'-hidroxy-3'-methoxy-benzylidenecyclo-pentanone. But PGV-0, which is like curcumin, practically insoluble in water, so it causes problems in the development. The aim of this research is to synthesize a derivative of PGV-0, a natrium salt of PGV-0 (natrium pentagamavunonate-0/Na-pentagamavunonate-0, which is hoped to have a better anti-inflammatory activity and solubility in water than PGV-0. PGV-0 was synthesized by reacting vanillin and cyclopentanone catalized by acid. Na-pentagamavunonate-0 was synthesized with PGV-0 as a starting material using an appropriate method. This research was able to synthesize new compound that was estimated as a natrium salt of PGV-0 (natrium pentagamavunonate-0/Na-pentagamavunonate-0.   Keywords: Curcumin, PGV-0, Na-pentagamavunonate-0, anti-inflammation

  3. Anti-inflammatory and anti-cancer activity of mulberry (Morus alba L.) root bark

    Science.gov (United States)

    2014-01-01

    Background Root bark of mulberry (Morus alba L.) has been used in herbal medicine as anti-phlogistic, liver protective, kidney protective, hypotensive, diuretic, anti-cough and analgesic agent. However, the anti-cancer activity and the potential anti-cancer mechanisms of mulberry root bark have not been elucidated. We performed in vitro study to investigate whether mulberry root bark extract (MRBE) shows anti-inflammatory and anti-cancer activity. Methods In anti-inflammatory activity, NO was measured using the griess method. iNOS and proteins regulating NF-κB and ERK1/2 signaling were analyzed by Western blot. In anti-cancer activity, cell growth was measured by MTT assay. Cleaved PARP, ATF3 and cyclin D1 were analyzed by Western blot. Results In anti-inflammatory effect, MRBE blocked NO production via suppressing iNOS over-expression in LPS-stimulated RAW264.7 cells. In addition, MRBE inhibited NF-κB activation through p65 nuclear translocation via blocking IκB-α degradation and ERK1/2 activation via its hyper-phosphorylation. In anti-cancer activity, MRBE deos-dependently induced cell growth arrest and apoptosis in human colorectal cancer cells, SW480. MRBE treatment to SW480 cells activated ATF3 expression and down-regulated cyclin D1 level. We also observed that MRBE-induced ATF3 expression was dependent on ROS and GSK3β. Moreover, MRBE-induced cyclin D1 down-regulation was mediated from cyclin D1 proteasomal degradation, which was dependent on ROS. Conclusions These findings suggest that mulberry root bark exerts anti-inflammatory and anti-cancer activity. PMID:24962785

  4. Medications (for IBS)

    Medline Plus

    Full Text Available ... Read more about antidiarrheal agents. Anti-anxiety medications – can be helpful for some people with IBS, mainly those with emotional distress. There are also effective medications available that relieve ...

  5. Anxiety and depression: individual entities or two sides of the same coin?

    Science.gov (United States)

    Nutt, David

    2004-01-01

    Several factors have led to suggestions that anxiety and depression are actually the same disease: very frequently, they co-exist; there is an overlap of symptoms between the two conditions; a number of similar agents can be used to treat both mental states; the same neurotransmitters are involved in both anxiety and depressive disorders; and stress can predispose both. Selective serotonin reuptake inhibitors (SSRIs) have shown efficacy in a number of neuroses: depression; obsessive-compulsive disorder (OCD) and anxiety disorders (panic disorder [PD], social anxiety disorder [SAD], generalised anxiety disorder and post-traumatic stress disorder). Furthermore, other drugs, for example, tricyclic antidepressants and monoamine oxidase inhibitors, are effective in treating both depression and some anxiety disorders. Yet some drugs are only effective in anxiety, for example, benzodiazepines, and this suggests that the two states are actually different. Despite the broad range of conditions that are treated by SSRIs, a number of differences are clear when SSRIs are used in depressive and anxious states. When used in PD and OCD, the effective dose of the SSRI is often higher than when used to treat depression. Furthermore, SSRIs often work more slowly in patients with anxiety compared with those with depression. In order to assess which serotonergic pathways and mechanisms are involved in these conditions, tryptophan depletion tests can be performed. Tryptophan is the precursor to serotonin (5-HT), so if the SSRI treatment effects are dependent on an increase in synaptic 5-HT levels, depletion will result in a relapse in symptoms. However, if the SSRI treatment works through post-receptor events, then tryptophan depletion will have little effect on the individual's symptoms. In depression, tryptophan depletion induced relapse in patients treated and controlled on SSRIs, but not in those recovered on noradrenergic agents such as desipramine. In some anxious states (PD and

  6. Anti-Infective Activities of Lactobacillus Strains in the Human Intestinal Microbiota: from Probiotics to Gastrointestinal Anti-Infectious Biotherapeutic Agents

    Science.gov (United States)

    Liévin-Le Moal, Vanessa

    2014-01-01

    SUMMARY A vast and diverse array of microbial species displaying great phylogenic, genomic, and metabolic diversity have colonized the gastrointestinal tract. Resident microbes play a beneficial role by regulating the intestinal immune system, stimulating the maturation of host tissues, and playing a variety of roles in nutrition and in host resistance to gastric and enteric bacterial pathogens. The mechanisms by which the resident microbial species combat gastrointestinal pathogens are complex and include competitive metabolic interactions and the production of antimicrobial molecules. The human intestinal microbiota is a source from which Lactobacillus probiotic strains have often been isolated. Only six probiotic Lactobacillus strains isolated from human intestinal microbiota, i.e., L. rhamnosus GG, L. casei Shirota YIT9029, L. casei DN-114 001, L. johnsonii NCC 533, L. acidophilus LB, and L. reuteri DSM 17938, have been well characterized with regard to their potential antimicrobial effects against the major gastric and enteric bacterial pathogens and rotavirus. In this review, we describe the current knowledge concerning the experimental antibacterial activities, including antibiotic-like and cell-regulating activities, and therapeutic effects demonstrated in well-conducted, placebo-controlled, randomized clinical trials of these probiotic Lactobacillus strains. What is known about the antimicrobial activities supported by the molecules secreted by such probiotic Lactobacillus strains suggests that they constitute a promising new source for the development of innovative anti-infectious agents that act luminally and intracellularly in the gastrointestinal tract. PMID:24696432

  7. Toxoplasma gondii Infection and Mixed Anxiety and Depressive Disorder: A Case-Control Seroprevalence Study in Durango, Mexico.

    Science.gov (United States)

    Alvarado-Esquivel, Cosme; Sanchez-Anguiano, Luis Francisco; Hernandez-Tinoco, Jesus; Berumen-Segovia, Luis Omar; Torres-Prieto, Yazmin Elizabeth; Estrada-Martinez, Sergio; Perez-Alamos, Alma Rosa; Ortiz-Jurado, Maria Nalleli; Molotla-de-Leon, Gabriel; Beristain Garcia, Isabel; Rabago-Sanchez, Elizabeth; Liesenfeld, Oliver

    2016-07-01

    The parasite Toxoplasma gondii (T. gondii) may invade the brain and might induce behavioral changes. We sought to determine the association of T. gondii infection and mixed anxiety and depressive disorder. Through an age- and gender-matched case-control seroprevalence study, we examined 65 patients suffering from mixed anxiety and depressive disorder (WHO ICD-10 code: F41.2) attending in a public hospital of mental health and 260 control subjects without this disorder from the general population. Sera of participants were analyzed for anti-Toxoplasma IgG and IgM antibodies using enzyme-linked immunoassays. Fifteen (23.1%) of the 65 patients and 18 (6.9%) of the 260 controls had anti-T. gondii IgG antibodies (odds ratio (OR): 4.03; 95% confidence interval (CI): 1.90 - 8.53; P 150 IU/mL) anti-T. gondii IgG levels was similar in cases and controls (OR: 0.25; 95% CI: 0.05 - 1.06; P = 0.05). Seroprevalence was similar in male cases and controls (P = 1.0); however, seroprevalence was significantly higher in female cases than in female controls (OR: 7.08; 95% CI: 2.83 - 17.67; P mixed anxiety and depressive disorder. Further research to confirm this association and to determine the seroepidemiology of T. gondii infection in patients with this disorder is needed.

  8. Irritability and Anxiety Severity Among Youth With Anxiety

    Science.gov (United States)

    Cornacchio, Danielle; Crum, Kathleen I.; Coxe, Stefany; Pincus, Donna B.; Comer, Jonathan S.

    2015-01-01

    Objective Most research on irritability and child psychopathology has focused on depressive disorders, bipolar disorder, and/or oppositional defiant disorder (ODD). Less is known about relationships between child anxiety and irritability and moderators of such associations. Method Structural equation modeling (SEM) examined associations between anxiety severity and irritability in a large sample of treatment-seeking youth with anxiety disorders (N=663, ages 7–19 years, M=12.25), after accounting for comorbid depressive disorders and ODD. Additional analyses examined whether associations were moderated by child gender, age, and generalized anxiety disorder (GAD) status. Results There was a direct link between child anxiety and irritability even after accounting for comorbid depressive disorders and ODD. Links between child anxiety and irritability were robust across child gender and age. Further, relationships between child anxiety and irritability were comparable across youth with and without GAD, suggesting that the anxiety–irritability link is relevant across child anxiety disorders and not circumscribed to youth with GAD. Conclusion Findings add to an increasing body of evidence linking child irritability to a range of internalizing and externalizing psychopathologies, and suggest that child anxiety assessment should systematically incorporate irritability evaluations. Further, youth in clinical settings displaying irritability should be assessed for the presence of anxiety. Moreover, treatments for childhood anxiety may do well to incorporate new treatment modules as needed that specifically target problems of irritability. PMID:26703910

  9. The PRECiSE 2 trial of certolizumab pegol, a new PEGylated anti-TNF agent, in the treatment of Crohn's disease - An interview with David A Schwartz, 13 June 2007

    Directory of Open Access Journals (Sweden)

    David A Schwartz

    2008-03-01

    Full Text Available David A SchwartzVanderbilt University Medical Center, Nashville, TN, USAContext: Certolizumab pegol (CDP 870 is a new anti-tumor necrosis factor (TNF therapy currently in development for the treatment of Crohn’s disease, rheumatoid arthritis, and psoriasis. Certolizumab pegol is the first PEGylated biologic anti-TNF agent and has a high binding affinity for TNF. Dr. Schwartz was an investigator of the PRECiSE (PEGylated Antibody Fragment Evaluation in Crohn’s Disease Safety and Efficacy 2 trial of certolizumab pegol in patients with Crohn’s disease.Keywords: certolizumab pegol, PRECiSE 2 trial, Crohn’s disease

  10. GC-MS analysis, evaluation of phytochemicals, anti-oxidant, thrombolytic and anti-inflammatory activities of Exacum bicolor

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    Appaji Mahesh Ashwini

    2015-12-01

    Full Text Available The aim of the present study was to investigate the GC-MS analysis, phytochemical screening, anti-oxidant, thrombolytic and anti-inflammatory activities of methanol extract of leaves of Exacum bicolor. FTIR analysis confirmed the presence of alcohol, phenols, alkanes, aromatic compounds, aldehyde and ethers. GC-MS analysis revealed the presence of eight phyto-constituents. The total phenol, flavonoid and alkaloid contents were 18.0 ± 0.2 mg/GAE/g, 13.1 ± 0.4 mg QE/g and 108.0 ± 1.2 mg AE/g respectively. The DPPH assay exhibited potent anti-oxidant abilities with IC50 8.8 µg/mL. Significant thrombolytic activity was demonstrated by clot lysis method (45.1 ± 0.8%. The methanol extract showed significant membrane stabilization on human red blood cell with IC50 value of 37.4 µg/mL. There was a significant correlation (R2>0.98 with total phenolic content versus anti-oxidant and anti-inflammatory activity. The above results confirmed that E. bicolor could be a promising anti-oxidant, thrombolytic and anti-inflammatory agent.

  11. Lichens: Unexpected anti-prion agents?

    Science.gov (United States)

    Rodriguez, Cynthia M.; Bennett, James P.; Johnson, Christopher J.

    2012-01-01

    The prion diseases sheep scrapie and cervid chronic wasting disease are transmitted, in part, via an environmental reservoir of infectivity; prions released from infected animals persist in the environment and can cause disease years later. Central to controlling disease transmission is the identification of methods capable of inactivating these agents on the landscape. We have found that certain lichens, common, ubiquitous, symbiotic organisms, possess a serine protease capable of degrading prion protein (PrP) from prion-infected animals. The protease functions against a range of prion strains from various hosts and reduces levels of abnormal PrP by at least two logs. We have now tested more than 20 lichen species from several geographical locations and from various taxa and found that approximately half of these species degrade PrP. Critical next steps include examining the effect of lichens on prion infectivity and cloning the protease responsible for PrP degradation. The impact of lichens on prions in the environment remains unknown. We speculate that lichens could have the potential to degrade prions when they are shed from infected animals onto lichens or into environments where lichens are abundant. In addition, lichens are frequently consumed by cervids and many other animals and the effect of dietary lichens on prion disease transmission should also be considered.

  12. Self-stigma by people diagnosed with schizophrenia, depression and anxiety: Cross-sectional survey design.

    Science.gov (United States)

    Hasan, Abd Al-Hadi; Musleh, Mahmoud

    2018-04-01

    This study investigated self-attitudes towards schizophrenia, depression and anxiety. A survey was conducted with 564 people with a schizophrenia, depression and anxiety who are currently being treated at a psychiatric clinic in Amman, Jordan. The research found that stigma towards schizophrenia, depression and anxiety was based around three factors: preconceived stereotypes, personal responsibility/blame and the perceived inability of a patient to recover. Schizophrenia, in particular, was linked more strongly to negative stereotypes and an inability to recover and less associated to personal responsibility/blame in comparison to depression and anxiety. Three identical stigma factors emerged for each diagnosis which reflected themes identified in previous literature. People with schizophrenia are seen as more dangerous and less likely to recover than those suffering from other mental illness. Anxiety was seen most favourably by the self; it was associated with less negative stereotypes and seen as more likely to cure. Interestingly, anxiety and depression were seen almost identically. The self-perception of mental health conditions, such as schizophrenia, depression and anxiety, have important implications for the planning of anti-stigma and awareness raising programmes. By gaining a thorough understanding of these perceptions and the rationale behind them, it may be possible to develop effective, tailor-made interventions. © 2017 Wiley Periodicals, Inc.

  13. Clinical observation on scores of anxiety, depression and quality of life for advanced gastrointestinal carcinoma patients with palliation intervention therapy

    International Nuclear Information System (INIS)

    Chen Yue; Jiang Tinghui; Jiang Yongxing; Sun Xianjun

    2007-01-01

    Objective: To evaluate the influence of palliative intervention therapy on advanced gastrointestinal carcinoma patients with depression and anxiety before and after the treatment. Methods: 56 advanced gastrointestinal carcinoma patients were selected and treated with intra-arterial perfusion chemotherapy or intra-arterial perfusion chemotherapy with embolization. Curative effects were assessed with the SDS, SAS and FACT-G before and after the treatment. In addition, all patients took self-assessment with SCL-90, comparing with the Chinese norms. Results: SCL-90 scores including the somatization agent, depression agent, and anxiety agent scores of the advanced gastrointestinal carcinoma were higher than those of Chinese norms, with significant difference (P<0.05). After palliative intervention therapy, the scores of SDS and SAS were lower than those before the palliative intervention therapy with significant difference (P< 0.05); and furthermore with an obvious improvement in the scores of FACT-G (P<0.05). Conclusion: Palliative intervention therapy for advanced gastrointestinal carcinoma patients can improve the complaints of depression anxiety and quality of life. (authors)

  14. A prospective naturalistic study of antidepressant-induced jitteriness/anxiety syndrome

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    Harada T

    2014-11-01

    Full Text Available Tsuyoto Harada, Ken Inada, Kazuo Yamada, Kaoru Sakamoto, Jun Ishigooka Department of Psychiatry, Tokyo Women’s Medical University School of Medicine, Tokyo, Japan Objective: Patients often develop neuropsychiatric symptoms such as anxiety and agitation after they have started taking an antidepressant, and this is thought to be associated with a potentially increased risk of suicide. However, the incidence of antidepressant-induced jitteriness/anxiety syndrome has not been fully investigated, and little has been reported on its predictors. The aim of this study was to survey the incidence of antidepressant-induced jitteriness/anxiety syndrome and clarify its predictors in a natural clinical setting.Materials and methods: Between January 2009 and July 2012, we prospectively surveyed 301 patients who had not taken any antidepressants for 1 month before presentation, and who were prescribed antidepressants for 1 month after their initial visit. Patients were classified as developing antidepressant-induced jitteriness/anxiety syndrome if they experienced any symptoms of anxiety, agitation, panic attacks, insomnia, irritability, hostility, aggressiveness, impulsivity, akathisia, hypomania, or mania during the first month.Results: Among the 301 patients, 21 (7.0% developed antidepressant-induced jitteriness/anxiety syndrome. Major depressive disorder and a diagnosis of mood disorder in first-degree relatives of patients were significantly associated with induction of antidepressant-induced jitteriness/anxiety syndrome (odds ratio 10.2, P=0.001; odds ratio 4.65, P=0.02; respectively. However, there was no such relationship for sex, age, class of antidepressant, combined use of benzodiazepines, or diagnosis of anxiety disorder.Conclusion: The findings of this study suggest that major depressive disorder and a diagnosis of mood disorder in first-degree relatives may be clinical predictors of antidepressant-induced jitteriness/anxiety syndrome

  15. Effects of Passion Flower Extract, as an Add-On Treatment to Sertraline, on Reaction Time in Patients ‎with Generalized Anxiety Disorder: A Double-Blind Placebo-Controlled Study.

    Science.gov (United States)

    Nojoumi, Mandana; Ghaeli, Padideh; Salimi, Samrand; Sharifi, Ali; Raisi, Firoozeh

    2016-07-01

    Objective: Because of functional impairment caused by generalized anxiety disorder and due to cognitive side ‎effects of many anti-anxiety agents, in this study we aimed to evaluate the influence of Passion ‎flower standardized extract on reaction time in patients with generalized anxiety disorder.‎ Method: Thirty patients aged 18 to 50 years of age, who were diagnosed with generalized anxiety disorder and ‎fulfilled the study criteria, entered this double-blind placebo-controlled study. Reaction time was ‎measured at baseline and after one month of treatment using computerized software. Correct ‎responses, omission and substitution errors and the mean time of correct responses (reaction time) in ‎both visual and auditory tests were collected. The analysis was performed between the two groups ‎and within each group utilizing SPSS PASW- statics, Version 18. P-value less than 0.05 was ‎considered statistically significant.‎ Results: All the participants were initiated on Sertraline 50 mg/day, and the dosage was increased to 100 ‎mg / day after two weeks. Fourteen patients received Pasipy (Passion Flower) 15 drops three times ‎daily and 16 received placebo concurrently. Inter-group comparison proved no significant difference ‎in any of the test items between assortments while a significant decline was observed in auditory ‎omission errors in passion flower group after on month of treatment using intra-group analysis.‎‎ Conclusion: This study noted that passion flower might be suitable as an add-on in the treatment of generalized ‎anxiety disorder with low side effects. Further studies with longer duration are recommended to ‎confirm the results of this study.‎.

  16. Modeling protective anti-tumor immunity via preventative cancer vaccines using a hybrid agent-based and delay differential equation approach.

    Science.gov (United States)

    Kim, Peter S; Lee, Peter P

    2012-01-01

    A next generation approach to cancer envisions developing preventative vaccinations to stimulate a person's immune cells, particularly cytotoxic T lymphocytes (CTLs), to eliminate incipient tumors before clinical detection. The purpose of our study is to quantitatively assess whether such an approach would be feasible, and if so, how many anti-cancer CTLs would have to be primed against tumor antigen to provide significant protection. To understand the relevant dynamics, we develop a two-compartment model of tumor-immune interactions at the tumor site and the draining lymph node. We model interactions at the tumor site using an agent-based model (ABM) and dynamics in the lymph node using a system of delay differential equations (DDEs). We combine the models into a hybrid ABM-DDE system and investigate dynamics over a wide range of parameters, including cell proliferation rates, tumor antigenicity, CTL recruitment times, and initial memory CTL populations. Our results indicate that an anti-cancer memory CTL pool of 3% or less can successfully eradicate a tumor population over a wide range of model parameters, implying that a vaccination approach is feasible. In addition, sensitivity analysis of our model reveals conditions that will result in rapid tumor destruction, oscillation, and polynomial rather than exponential decline in the tumor population due to tumor geometry.

  17. Anxiety and depression in people with epilepsy: The contribution of metacognitive beliefs.

    Science.gov (United States)

    Fisher, Peter L; Noble, Adam J

    2017-08-01

    Anxiety and depressive disorders frequently occur in people with epilepsy (PWE). An information processing model of psychopathology, the Self-Regulatory Executive Function (S-REF) model specifies that maladaptive metacognitive beliefs and processes play a fundamental role in the development and maintenance of anxiety and depression. This study explored whether metacognitive beliefs would explain additional variance in anxiety and depression after accounting for demographics, physical and/or psychiatric illnesses, epilepsy characteristics and medication issues. The mediational relationships between metacognitive beliefs, worry and anxiety and depression, predicted by the metacognitive model were also explored, METHODS: Three hundred and forty-nine PWE participated in an online survey and completed self-report questionnaires measuring anxiety, depression, metacognitive beliefs and worry. Participants also provided information on epilepsy characteristics, demographics, comorbid physical and/or psychiatric illnesses, number of, and perceived side effects of, anti-epileptic medication. Regression analysis showed that metacognitive beliefs were associated with symptoms of anxiety, depression, and explained additional variance in these outcomes after accounting for the control variables. Furthermore, the fundamental tenet of the metacognitive model was supported; the relationship between negative metacognitive beliefs about uncontrollability and danger of worry and anxious and depressive symptoms was partially mediated by worry. This is the first study to demonstrate that metacognitive beliefs and processes contribute to anxiety and depression beyond variables often associated with emotional distress in PWE. Further research is required to test if modification of metacognitive beliefs and processes using metacognitive therapy would effectively alleviate anxiety and depression in PWE. Copyright © 2017 British Epilepsy Association. Published by Elsevier Ltd. All rights

  18. Agomelatine, venlafaxine, and running exercise effectively prevent anxiety- and depression-like behaviors and memory impairment in restraint stressed rats.

    Directory of Open Access Journals (Sweden)

    Sarawut Lapmanee

    Full Text Available Several severe stressful situations, e.g., natural disaster, infectious disease out break, and mass casualty, are known to cause anxiety, depression and cognitive impairment, and preventive intervention for these stress complications is worth exploring. We have previously reported that the serotonin-norepinephrine-dopamine reuptake inhibitor, venlafaxine, as well as voluntary wheel running are effective in the treatment of anxiety- and depression-like behaviors in stressed rats. But whether they are able to prevent deleterious consequences of restraint stress in rats, such as anxiety/depression-like behaviors and memory impairment that occur afterward, was not known. Herein, male Wistar rats were pre-treated for 4 weeks with anti-anxiety/anti-depressive drugs, agomelatine and venlafaxine, or voluntary wheel running, followed by 4 weeks of restraint-induced stress. During the stress period, rats received neither drug nor exercise intervention. Our results showed that restraint stress induced mixed anxiety- and depression-like behaviors, and memory impairment as determined by elevated plus-maze, elevated T-maze, open field test (OFT, forced swimming test (FST, and Morris water maze (MWM. Both pharmacological pre-treatments and running successfully prevented the anxiety-like behavior, especially learned fear, in stressed rats. MWM test suggested that agomelatine, venlafaxine, and running could prevent stress-induced memory impairment, but only pharmacological treatments led to better novel object recognition behavior and positive outcome in FST. Moreover, western blot analysis demonstrated that venlafaxine and running exercise upregulated brain-derived neurotrophic factor (BDNF expression in the hippocampus. In conclusion, agomelatine, venlafaxine as well as voluntary wheel running had beneficial effects, i.e., preventing the restraint stress-induced anxiety/depression-like behaviors and memory impairment.

  19. Theory of agent-based market models with controlled levels of greed and anxiety

    International Nuclear Information System (INIS)

    Papadopoulos, P; Coolen, A C C

    2010-01-01

    We use generating functional analysis to study minority-game-type market models with generalized strategy valuation updates that control the psychology of agents' actions. The agents' choice between trend-following and contrarian trading, and their vigor in each, depends on the overall state of the market. Even in 'fake history' models, the theory now involves an effective overall bid process (coupled to the effective agent process) which can exhibit profound remanence effects and new phase transitions. For some models the bid process can be solved directly, others require Maxwell-construction-type approximations.

  20. Synthesis of Benzimidazole Derivatives: As Anti-hypertensive Agents

    Directory of Open Access Journals (Sweden)

    Jat Rakesh Kumar

    2006-01-01

    Full Text Available A new series of non peptide angiotensin(A-II receptor antagonist has been prepared. This N-(biphenyl methyl imidazoles e.g. 5-substituted (amino -2- phenyl-1-(2ʼcarboxy biphenyl-4-yl benzimidazoles differ from the previously reported and related compounds in that they produce a potent hypertensive effect upon oral administration. The earlier series were generally active only when administered intravenously. It has been found that 2’-position of biphenyl is essential. Only ortho substituted acid possess both high affinity for the AII receptor and oral anti-hypertensive potency.

  1. Engineered Mesenchymal Stem Cells as an Anti-Cancer Trojan Horse

    Science.gov (United States)

    Nowakowski, Adam; Drela, Katarzyna; Rozycka, Justyna; Janowski, Miroslaw

    2016-01-01

    Cell-based gene therapy holds a great promise for the treatment of human malignancy. Among different cells, mesenchymal stem cells (MSCs) are emerging as valuable anti-cancer agents that have the potential to be used to treat a number of different cancer types. They have inherent migratory properties, which allow them to serve as vehicles for delivering effective therapy to isolated tumors and metastases. MSCs have been engineered to express anti-proliferative, pro-apoptotic, and anti-angiogenic agents that specifically target different cancers. Another field of interest is to modify MSCs with the cytokines that activate pro-tumorigenic immunity or to use them as carriers for the traditional chemical compounds that possess the properties of anti-cancer drugs. Although there is still controversy about the exact function of MSCs in the tumor settings, the encouraging results from the preclinical studies of MSC-based gene therapy for a large number of tumors support the initiation of clinical trials. PMID:27460260

  2. The relationships between trait anxiety, place recognition memory, and learning strategy.

    Science.gov (United States)

    Hawley, Wayne R; Grissom, Elin M; Dohanich, Gary P

    2011-01-20

    Rodents learn to navigate mazes using various strategies that are governed by specific regions of the brain. The type of strategy used when learning to navigate a spatial environment is moderated by a number of factors including emotional states. Heightened anxiety states, induced by exposure to stressors or administration of anxiogenic agents, have been found to bias male rats toward the use of a striatum-based stimulus-response strategy rather than a hippocampus-based place strategy. However, no study has yet examined the relationship between natural anxiety levels, or trait anxiety, and the type of learning strategy used by rats on a dual-solution task. In the current experiment, levels of inherent anxiety were measured in an open field and compared to performance on two separate cognitive tasks, a Y-maze task that assessed place recognition memory, and a visible platform water maze task that assessed learning strategy. Results indicated that place recognition memory on the Y-maze correlated with the use of place learning strategy on the water maze. Furthermore, lower levels of trait anxiety correlated positively with better place recognition memory and with the preferred use of place learning strategy. Therefore, competency in place memory and bias in place strategy are linked to the levels of inherent anxiety in male rats. Copyright © 2010 Elsevier B.V. All rights reserved.

  3. Novel Antitumor Platinum(II) Conjugates Containing the Nonsteroidal Anti-inflammatory Agent Diclofenac: Synthesis and Dual Mechanisms of Antiproliferative Effects.

    Science.gov (United States)

    Intini, Francesco Paolo; Zajac, Juraj; Novohradsky, Vojtech; Saltarella, Teresa; Pacifico, Concetta; Brabec, Viktor; Natile, Giovanni; Kasparkova, Jana

    2017-02-06

    One concept how to improve anticancer effects of conventional metallodrugs consists in conjugation of these compounds with other biologically (antitumor) active agents, acting by a different mechanism. Here, we present synthesis, biological effects, and mechanisms of action of new Pt(II) derivatives containing one or two nonsteroidal anti-inflammatory diclofenac (DCF) ligands also known for their antitumor effects. The antiproliferative properties of these metallic conjugates show that these compounds are potent and cancer cell selective cytotoxic agents exhibiting activity in cisplatin resistant and the COX-2 positive tumor cell lines. One of these compounds, compound 3, in which DCF molecules are coordinated to Pt(II) through their carboxylic group, is more potent than parental conventional Pt(II) drug cisplatin, free DCF and the congeners of 3 in which DCF ligands are conjugated to Pt(II) via a diamine. The potency of 3 is due to several factors including enhanced internalization that correlates with enhanced DNA binding and cytotoxicity. Mechanistic studies show that 3 combines multiple effects. After its accumulation in cells, it releases Pt(II) drug capable of binding/damaging DNA and DCF ligands, which affect distribution of cells in individual phases of the cell cycle, inhibit glycolysis and lactate transport, collapse mitochondrial membrane potential, and suppress the cellular properties characteristic of metastatic progression.

  4. 2-(2-(4-Benzoylpiperazin-1-ylethylisoindoline-1,3-dione derivatives: Synthesis, docking and acetylcholinesterase inhibitory evaluation as anti-alzheimer agents

    Directory of Open Access Journals (Sweden)

    Ahmad Mohammadi-Farani

    2017-01-01

    Full Text Available Objective(s: Alzheimer’s disease (AD as progressive cognitive decline and the most common form of dementia is due to degeneration of the cholinergic neurons in the brain. Therefore, administration of the acetylcholinesterase (AChE inhibitors such as donepezil is the first choice for treatment of the AD. In the present study, we focused on the synthesis and anti-cholinesterase evaluation of new donepezil like analogs. Materials and Methods: A new series of phthalimide derivatives (compounds 4a-4j were synthesized via Gabriel protocol and subsequently amidation reaction was performed using various benzoic acid derivatives. Then, the corresponding anti-acetylcholinesterase activity of the prepared derivatives (4a-4j was assessed by utilization of the Ellman's test and obtained results were compared to donepezil. Besides, docking study was also carried out to explore the likely in silico binding interactions.  Results: According to the obtained results, electron withdrawing groups (Cl, F at position 3 and an electron donating group (methoxy at position 4 of the phenyl ring enhanced the acetylcholinesterase inhibitory activity. Compound 4e (m-Fluoro, IC50 = 7.1 nM and 4i (p-Methoxy, IC50 = 20.3 nM were the most active compounds in this series and exerted superior potency than donepezil (410 nM. Moreover, a similar binding mode was observed in silico for all ligands in superimposition state with donepezil into the active site of acetylcholinesterase. Conclusion: Studied compounds could be potential leads for discovery of novel anti-Alzheimer agents in the future.

  5. Anti-tumor effects of an engineered 'killer' transfer RNA

    Energy Technology Data Exchange (ETDEWEB)

    Zhou, Dong-hui [Department of Biochemistry and Molecular Biology, University of Chicago, Chicago, IL 60637 (United States); Lee, Jiyoung; Frankenberger, Casey [Ben May Department for Cancer Research, University of Chicago, Chicago, IL 60637 (United States); Geslain, Renaud, E-mail: rgeslain@depaul.edu [Department of Biochemistry and Molecular Biology, University of Chicago, Chicago, IL 60637 (United States); Department of Biology, DePaul University, Chicago, IL 60614 (United States); Rosner, Marsha, E-mail: m-rosner@uchicago.edu [Ben May Department for Cancer Research, University of Chicago, Chicago, IL 60637 (United States); Pan, Tao, E-mail: taopan@uchicago.edu [Department of Biochemistry and Molecular Biology, University of Chicago, Chicago, IL 60637 (United States)

    2012-10-12

    Highlights: Black-Right-Pointing-Pointer tRNA with anti-cancer effects. Black-Right-Pointing-Pointer tRNA induced protein misfolding. Black-Right-Pointing-Pointer tRNA as anti-tumor agent. -- Abstract: A hallmark of cancer cells is their ability to continuously divide; and rapid proliferation requires increased protein translation. Elevating levels of misfolded proteins can elicit growth arrest due to ER stress and decreased global translation. Failure to correct prolonged ER stress eventually results in cell death via apoptosis. tRNA{sup Ser}(AAU) is an engineered human tRNA{sup Ser} with an anticodon coding for isoleucine. Here we test the possibility that tRNA{sup Ser}(AAU) can be an effective killing agent of breast cancer cells and can effectively inhibit tumor-formation in mice. We found that tRNA{sup Ser}(AAU) exert strong effects on breast cancer translation activity, cell viability, and tumor formation. Translation is strongly inhibited by tRNA{sup Ser}(AAU) in both tumorigenic and non-tumorigenic cells. tRNA{sup Ser}(AAU) significantly decreased the number of viable cells over time. A short time treatment with tRNA{sup Ser}(AAU) was sufficient to eliminate breast tumor formation in a xenograft mouse model. Our results indicate that tRNA{sup Ser}(AAU) can inhibit breast cancer metabolism, growth and tumor formation. This RNA has strong anti-cancer effects and presents an opportunity for its development into an anti-tumor agent. Because tRNA{sup Ser}(AAU) corrupts the protein synthesis mechanism that is an integral component of the cell, it would be extremely difficult for tumor cells to evolve and develop resistance against this anti-tumor agent.

  6. Structure-Activity Relationship Study on the Ethyl p-Methoxycinnamate as an Anti-Inflammatory Agent

    Directory of Open Access Journals (Sweden)

    Ismiarni Komala

    2018-02-01

    Full Text Available Ethyl p-methoxycinnamate (EPMC (1 has been isolated as a major compound from the rhizome of Kaempferia galanga together with the other compound ethyl cinnamate (2. As reported in the literature, EPMC (1 exhibited a significant in vitro and in vivo anti-inflammatory activity. In this research, we investigated the anti-inflammatory activity of compounds 1 and 2 by using anti-denaturation of heat bovine serum albumin (BSA method. In order to analyze active sites that are responsible for the anti-inflammatory activity, therefore, it is necessary to conduct structural modification of EPMC (1. The structural modification was performed through re-esterification reaction by using conventional and assistance of the unmodified microwave oven. Evaluation of the results of the bioassay indicated that the ester and methoxy functional groups of EPMC (1 play an important role for the anti-inflammatory activity.

  7. Theory of agent-based market models with controlled levels of greed and anxiety

    Energy Technology Data Exchange (ETDEWEB)

    Papadopoulos, P; Coolen, A C C [Department of Mathematics, King' s College London, The Strand, London WC2R 2LS (United Kingdom)], E-mail: panagiotis.2.papadopoulos@kcl.ac.uk, E-mail: ton.coolen@kcl.ac.uk

    2010-01-15

    We use generating functional analysis to study minority-game-type market models with generalized strategy valuation updates that control the psychology of agents' actions. The agents' choice between trend-following and contrarian trading, and their vigor in each, depends on the overall state of the market. Even in 'fake history' models, the theory now involves an effective overall bid process (coupled to the effective agent process) which can exhibit profound remanence effects and new phase transitions. For some models the bid process can be solved directly, others require Maxwell-construction-type approximations.

  8. Ansiedade experimental humana Human experimental anxiety

    Directory of Open Access Journals (Sweden)

    Frederico Guilherme Graeff

    2007-01-01

    Full Text Available CONTEXTO: A ansiedade experimental no ser humano constitui-se em ponte entre os modelos animais e os ensaios clínicos. OBJETIVO: Este artigo focaliza métodos químicos e psicológicos utilizados para provocar ansiedade experimental em seres humanos. MÉTODOS: Realizou-se revisão seletiva da literatura. RESULTADOS: Os desafios farmacológicos têm sido usados principalmente para induzir ataques de pânico em pacientes com transtorno de pânico, os quais são mais sensíveis a eles que indivíduos normais ou pacientes portadores de outros transtornos psiquiátricos. Uma das mais importantes contribuições deste método é a de ter mostrado que os agentes panicogênicos mais seletivos, como o lactato ou a inalação de CO2, não ativam o eixo hormonal do estresse. Entre os métodos psicológicos, destacam-se o condicionamento de respostas elétricas da condutância da pele, cujo perfil farmacológico se aproxima daquele do transtorno de ansiedade generalizada, e o teste da simulação do falar em público, cuja farmacologia é semelhante à do transtorno de pânico. CONCLUSÕES: Tais resultados salientam a diferença entre a neurobiologia da ansiedade e a do pânico.BACKGROUND: Human experimental anxiety methods bridge the gap between animal models and clinical assays. OBJECTIVE: This article is focused on chemical and psychological procedures used to generate experimental anxiety in human beings. METHODS: A selective review of the literature has been carried out. RESULTS: Pharmacological challenges have been mainly used to induce panic attacks in panic disorder patients, who are more susceptible than normal individuals or patients with other psychiatric disorders. One of the most important contributions of this method is to have shown that the most selective panicogenic agents, such as lactate or CO2 inhalation, do not activate the hormonal stress axis. Among the psychological methods stand the conditioning of the electrical skin conductance

  9. Design and synthesis of some new 2,3'-bipyridine-5-carbonitriles as potential anti-inflammatory/antimicrobial agents.

    Science.gov (United States)

    Elzahhar, Perihan A; Elkazaz, Salwa; Soliman, Raafat; El-Tombary, Alaa A; Shaltout, Hossam A; El-Ashmawy, Ibrahim M; Abdel Wahab, Abeer E; El-Hawash, Soad A

    2017-08-01

    Inflammation may cause accumulation of fluid in the injured area, which may promote bacterial growth. Other reports disclosed that non-steroidal anti-inflammatory drugs may enhance progression of bacterial infection. This work describes synthesis of new series of 2,3'-bipyridine-5-carbonitriles as structural analogs of etoricoxib, linked at position-6 to variously substituted thio or oxo moieties. Biological screening results revealed that compounds 2b, 4b, 7e and 8 showed significant acute and chronic AI activities and broad spectrum of antimicrobial activity. In addition, similarity ensemble approach was applied to predict potential biological targets of the tested compounds. Then, pharmacophore modeling study was employed to determine the most important structural parameters controlling bioactivity. Moreover, title compounds showed physicochemical properties within those considered adequate for drug candidates. This study explored the potential of such series of compounds as structural leads for further modification to develop a new class of dual AI-antimicrobial agents.

  10. Preparation of fluidized catalytic cracking slurry oil-in-water emulsion as anti-collapse agent for drilling fluids

    Directory of Open Access Journals (Sweden)

    Zhengqiang Xiong

    2016-12-01

    Full Text Available Fluidized catalytic cracking slurry oil-in-water emulsion (FCCSE was prepared by using interfacial complexes generation method that was simple and versatile. The critical factors influencing the sample preparation process were optimized, for instance, the optimum value of the mixed hydrophile-lipophile balance of compound emulsifier was 11.36, the content of compound emulsifier was 4 wt%, the emulsification temperature was 75 °C, the agitation speed was 200 rpm, and the emulsification time was 30–45 min. The performance as a drilling fluid additive was also investigated with respect to rheological properties, filtration loss and inhibition of FCCSE. Experimental results showed that FCCSE was favorable to inhibiting clay expansion and dispersion and reducing fluid loss. Furthermore, it had good compatibility with other additives and did not affect the rheological properties of drilling fluids. FCCSE exhibited better performance than the available emulsified asphalt. It has a promising application as anti-collapse agent in petroleum and natural gas drilling.

  11. Povidone-iodine: an anti-oedematous agent?

    Science.gov (United States)

    Arakeri, Gururaj; Brennan, Peter A

    2011-02-01

    Polyvinylpyrrolidone-iodine (PVP-I) is a well-known antiseptic, widely used in various preparations and concentrations in all surgical fields. It is also used as an irrigant for open wounds and in some centres for irrigating sockets after tooth extraction. One of the authors (GA) incidentally discovered an anti-oedematous effect of PVP-I after using it in low concentration as an irrigant/coolant during the surgical removal of lower third molars. A prospective randomized clinical trial was subsequently performed on 50 patients (25 control, 25 treatment group) undergoing removal of impacted lower third molars. In the treatment group a 0.5% PVP-I solution at a concentration of 0.5mg/ml (we call it as "Arakeri's iodine solution") resulted in a significant reduction in postoperative swelling compared with the control group (P<0.01). This effect of PVP-I was suspected due to its inhibitory effect on leukotriene B4 and leukocyte extravasation (chemotaxis). Further evaluation of the effects of PVP-I as an irrigant in oral and maxillofacial surgery is needed. Copyright © 2010 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.

  12. Cyanobacterial pigments as natural anti-hyperglycemic agents: An in vitro study

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    Tonmoy Ghosh

    2016-08-01

    Full Text Available Traditional medicines for controlling postprandial hyperglycemia includes herbs and plant extracts as well as synthetic drugs like acarbose. Synthetic drug molecules frequently have side effects such as flatulence and diarrhea. Cyanobacterial pigments have excellent anti-oxidant and free radical scavenging properties. Thus, α-amylase and α-glucosidase inhibiting activities of purified pigments and crude extracts from three cyanobacterial species, Lyngbya, Microcoleus and Synechocystis sp., were investigated. Lyngbya extract had the highest total anti-oxidant activity (TAC before digestion (48.26 ± 0.04 µg AAE ml-1 while purified lycopene had the highest TAC after digestion (154.16 ± 0.96 µg AAE ml-1. The Microcoleus extract had the highest ABTS scavenging activity before digestion (98.23 ± 0.25 % while purified C-phycocyanin (C-PC had the highest ABTS scavenging after digestion (99.69 ±0.04 %. None of the digested or undigested extracts performed better than acarbose in inhibiting α-amylase but the digested Microcoleus extract was able to inhibit its activity by ~35 %. The purified pigments gave inhibitory activities ranging from ~ 8 – 16 %. The Lyngbya extract had the highest inhibitory activity against α-glucosidase both before and after digestion (62.22 ± 0.02 and 97.82 ± 0.03 % respectively. Purified C-phycoerythrin (C-PE, C-PC, lycopene and myxoxanthophyll could inhibit α-glucosidase in a range of ~83 – 96 %. Considering the potent inhibitory activities of purified pigments against both α-amylase and α-glucosidase, cyanobacterial pigments could be used as food additives for their dual advantage of anti-oxidant and anti-hyperglycemic activities.

  13. Anti-glycation and anti-oxidation properties of Capsicum frutescens and Curcuma longa fruits: possible role in prevention of diabetic complication.

    Science.gov (United States)

    Khan, Ibrar; Ahmad, Haroon; Ahmad, Bashir

    2014-09-01

    The accumulation of advanced glycationend products (AGE's) in the body, due to the non-enzymatic glycation of proteins is associated with several pathological conditions like aging and diabetes mellitus. Hence a plant having anti-glycation and anti-oxidation potentials may serve as therapeutic agent for diabetic complications and aging. In this study the anti-glycation and anti-oxidation properties of crude methanolic extracts of fruits of Capsicum frutescens and Curcuma longa were investigated. Among the two C. frutescens had more anti-glycation ability with a minimum inhibitory concentration (MIC50) of 90βg/mLas compared to 324βg/mL MIC50 of C. longa. Curcuma longa had the more anti-oxidation potential i.e. 35.01, 30.83 and 28.08% at 0.5mg, 0.25mg and 0.125mg respectively.

  14. New phytochemicals as potential human anti-aging compounds: Reality, promise, and challenges.

    Science.gov (United States)

    Corrêa, Rúbia C G; Peralta, Rosane M; Haminiuk, Charles W I; Maciel, Giselle Maria; Bracht, Adelar; Ferreira, Isabel C F R

    2018-04-13

    Aging is an inevitable process influenced by genetic, lifestyle, and environmental factors. Indirect evidence shows that several phytochemicals can have anti-aging capabilities, although direct evidence in this field is still limited. This report aims to provide a critical review on aspects related to the use of novel phytochemicals as anti-aging agents, to discuss the obstacles found when performing most anti-aging study protocols in humans, and to analyze future perspectives. In addition to the extensively studied resveratrol, epicatechin, quercetin, and curcumin, new phytochemicals have been reported to act as anti-aging agents, such as the amino acid L-theanine isolated from green tea, and the lignans arctigenin and matairesinol isolated from Arctium lappa seeds. Furthermore, this review discusses the application of several new extracts rich in phytochemicals with potential use in anti-aging therapies. Finally, this review also discusses the most important biomarkers to test anti-aging interventions, the necessity of conducting epidemiological studies and the need of clinical trials with adequate study protocols for humans.

  15. Palmitoylethanolamide: A Natural Body-Own Anti-Inflammatory Agent, Effective and Safe against Influenza and Common Cold

    Directory of Open Access Journals (Sweden)

    J. M. Keppel Hesselink

    2013-01-01

    Full Text Available Palmitoylethanolamide (PEA is a food component known since 1957. PEA is synthesized and metabolized in animal cells via a number of enzymes and exerts a multitude of physiological functions related to metabolic homeostasis. Research on PEA has been conducted for more than 50 years, and over 350 papers are referenced in PubMed describing the physiological properties of this endogenous modulator and its pharmacological and therapeutical profile. The major focus of PEA research, since the work of the Nobel laureate Levi-Montalcini in 1993, has been neuropathic pain states and mast cell related disorders. However, it is less known that 6 clinical trials in a total of nearly 4000 people were performed and published last century, specifically studying PEA as a therapy for influenza and the common cold. This was done before Levi-Montalcini’s clarification of PEA’s mechanism of action, analyzing the role of PEA as an anti-inflammatory agent. We will review in depth these studies, as the results support the effectiveness and safety of PEA in flu and respiratory infections.

  16. A short history of anti-rheumatic therapy - VII. Biological agents

    Directory of Open Access Journals (Sweden)

    B. Gatto

    2011-11-01

    Full Text Available The introduction of biological agents has been a major turning-point in the treatment of rheumatic diseases, particularly in rheumatoid arthritis. This review describes the principle milestones that have led, through the knowledge of the structure and functions of nucleic acids, to the development of production techniques of the three major families of biological agents: proteins, monoclonal antibodies and fusion proteins. A brief history has also been traced of the cytokines most involved in the pathogenesis of inflammatory rheumatic diseases (IL-1 and TNF and the steps which have led to the use of the main biological drugs in rheumatology: anakinra, infliximab, adalimumab, etanercept and rituximab.

  17. Statistics Anxiety, Trait Anxiety, Learning Behavior, and Academic Performance

    Science.gov (United States)

    Macher, Daniel; Paechter, Manuela; Papousek, Ilona; Ruggeri, Kai

    2012-01-01

    The present study investigated the relationship between statistics anxiety, individual characteristics (e.g., trait anxiety and learning strategies), and academic performance. Students enrolled in a statistics course in psychology (N = 147) filled in a questionnaire on statistics anxiety, trait anxiety, interest in statistics, mathematical…

  18. Severe asthma: anti-IgE or anti-IL-5?

    Directory of Open Access Journals (Sweden)

    Evgenia Papathanassiou

    2016-11-01

    Full Text Available Severe asthma is a discrete clinical entity characterised by recurrent exacerbations, reduced quality of life and poor asthma control as ordinary treatment regimens remain inadequate. Difficulty in managing severe asthma derives partly from the multiple existing phenotypes and our inability to recognise them. Though the exact pathogenetic pathway of severe allergic asthma remains unclear, it is known that numerous inflammatory cells and cytokines are involved, and eosinophils represent a key inflammatory cell mediator. Anti-IgE (omalizumab and anti-IL-5 (mepolizumab antibodies are biological agents that interfere in different steps of the Th2 inflammatory cascade and are licensed in severe asthma. Both exhibit a favourable clinical outcome as they reduce exacerbation rate and improve asthma control and quality of life, while mepolizumab also induces an oral steroid sparing effect. Nevertheless, it is still questionable which agent is more suitable in the management of severe allergic asthma since no comparable studies have been conducted. Omalizumab's established effectiveness in clinical practice over a long period is complemented by a beneficial effect on airway remodelling process mediated mainly through its impact on eosinophils and other parameters strongly related to eosinophilic inflammation. However, it is possible that mepolizumab through nearly depleting eosinophils could have a similar effect on airway remodelling. Moreover, to date, markers indicative of the patient population responding to each treatment are unavailable although baseline eosinophils and exacerbation rate in the previous year demonstrate a predictive value regarding anti-IL-5 therapy effectiveness. On the other hand, a better therapeutic response for omalizumab has been observed when low forced expiratory volume in 1 sec, high-dose inhaled corticosteroids and increased IgE concentrations are present. Consequently, conclusions are not yet safe to be drawn based on

  19. A systematic review of interventions for anxiety, depression, and PTSD in adult offenders.

    Science.gov (United States)

    Leigh-Hunt, Nicholas; Perry, Amanda

    2015-06-01

    There is a high prevalence of anxiety and depression in offender populations but with no recent systematic review of interventions to identify what is effective. This systematic review was undertaken to identify randomised controlled trials of pharmacological and non-pharmacological interventions in adult offenders in prison or community settings. A search of five databases identified 14 studies meeting inclusion criteria, which considered the impact of psychological interventions, pharmacological agents, or exercise on levels of depression and anxiety. A narrative synthesis was undertaken and Hedges g effect sizes calculated to allow comparison between studies. Effect sizes for depression interventions ranged from 0.17 to 1.41, for anxiety 0.61 to 0.71 and for posttraumatic stress disorder 0 to 1.41. Cognitive behavioural therapy interventions for the reduction of depression and anxiety in adult offenders appear effective in the short term, though a large-scale trial of sufficient duration is needed to confirm this finding. © The Author(s) 2014.

  20. Neurosteroids as neuromodulators in the treatment of anxiety disorders

    Directory of Open Access Journals (Sweden)

    Patrizia eLongone

    2011-10-01

    Full Text Available Anxiety disorders are the most common psychiatric disorders. They are frequently treated with benzodiazepines, which are fast acting highly effective anxiolytic agents. However, their long term use is impaired by tolerance development and abuse liability. In contrast, antidepressants such as selective serotonin reuptake inhibitors (SSRIs are considered as first line treatment but have a slow onset of action. Neurosteroids are powerful allosteric modulators of GABAA and glutamate receptors. However, they also modulate sigma receptors and they are modulated themselves by SSRIs. Both preclinical and clinical studies have shown that neurosteroid homeostasis is altered in depression and anxiety disorders and antidepressants may act in part through restoring neurosteroid dysbalance. Moreover, novel drugs interfering with neurosteroidogenesis such as ligands of the translocator protein (18 kDa may represent an attractive pharmacological option for novel anxiolytics which lack the unwarranted side effects of benzodiazepines. Thus, neurosteroids are important endogenous neuromodulators for the physiology and pathophysiology of anxiety and they may constitute a novel therapeutic approach in the treatment of these disorders.

  1. Elementary Pre-Service Teachers' Mathematics Anxiety and Mathematics Teaching Anxiety

    Science.gov (United States)

    Haciomeroglu, Guney

    2014-01-01

    The present study examined the structure of elementary pre-service teachers' mathematics anxiety and mathematics teaching anxiety by asking whether the two systems of anxiety are related. The Turkish Mathematics Anxiety Rating Scale Short Version and the Mathematics Teaching Anxiety Scale were administered to 260 elementary pre-service teachers.…

  2. Statistics anxiety, state anxiety during an examination, and academic achievement.

    Science.gov (United States)

    Macher, Daniel; Paechter, Manuela; Papousek, Ilona; Ruggeri, Kai; Freudenthaler, H Harald; Arendasy, Martin

    2013-12-01

    A large proportion of students identify statistics courses as the most anxiety-inducing courses in their curriculum. Many students feel impaired by feelings of state anxiety in the examination and therefore probably show lower achievements. The study investigates how statistics anxiety, attitudes (e.g., interest, mathematical self-concept) and trait anxiety, as a general disposition to anxiety, influence experiences of anxiety as well as achievement in an examination. Participants were 284 undergraduate psychology students, 225 females and 59 males. Two weeks prior to the examination, participants completed a demographic questionnaire and measures of the STARS, the STAI, self-concept in mathematics, and interest in statistics. At the beginning of the statistics examination, students assessed their present state anxiety by the KUSTA scale. After 25 min, all examination participants gave another assessment of their anxiety at that moment. Students' examination scores were recorded. Structural equation modelling techniques were used to test relationships between the variables in a multivariate context. Statistics anxiety was the only variable related to state anxiety in the examination. Via state anxiety experienced before and during the examination, statistics anxiety had a negative influence on achievement. However, statistics anxiety also had a direct positive influence on achievement. This result may be explained by students' motivational goals in the specific educational setting. The results provide insight into the relationship between students' attitudes, dispositions, experiences of anxiety in the examination, and academic achievement, and give recommendations to instructors on how to support students prior to and in the examination. © 2012 The British Psychological Society.

  3. In silico identification of anti-cancer compounds and plants from traditional Chinese medicine database

    Science.gov (United States)

    Dai, Shao-Xing; Li, Wen-Xing; Han, Fei-Fei; Guo, Yi-Cheng; Zheng, Jun-Juan; Liu, Jia-Qian; Wang, Qian; Gao, Yue-Dong; Li, Gong-Hua; Huang, Jing-Fei

    2016-05-01

    There is a constant demand to develop new, effective, and affordable anti-cancer drugs. The traditional Chinese medicine (TCM) is a valuable and alternative resource for identifying novel anti-cancer agents. In this study, we aim to identify the anti-cancer compounds and plants from the TCM database by using cheminformatics. We first predicted 5278 anti-cancer compounds from TCM database. The top 346 compounds were highly potent active in the 60 cell lines test. Similarity analysis revealed that 75% of the 5278 compounds are highly similar to the approved anti-cancer drugs. Based on the predicted anti-cancer compounds, we identified 57 anti-cancer plants by activity enrichment. The identified plants are widely distributed in 46 genera and 28 families, which broadens the scope of the anti-cancer drug screening. Finally, we constructed a network of predicted anti-cancer plants and approved drugs based on the above results. The network highlighted the supportive role of the predicted plant in the development of anti-cancer drug and suggested different molecular anti-cancer mechanisms of the plants. Our study suggests that the predicted compounds and plants from TCM database offer an attractive starting point and a broader scope to mine for potential anti-cancer agents.

  4. Hypertension induced by chemotherapeutic and immunosuppresive agents: a new challenge.

    Science.gov (United States)

    Abi Aad, Simon; Pierce, Matthew; Barmaimon, Guido; Farhat, Fadi S; Benjo, Alexandre; Mouhayar, Elie

    2015-01-01

    Hypertension is a common adverse effect of certain anti neoplastic therapy. The incidence and severity of hypertension are dependent mainly on the type and the dose of the drug. We reviewed the literature for studies that reported the effect of anti neoplastic agents on blood pressure in patients with malignancies. The medical databases of PubMed, MEDLINE and EMBASE were searched for articles published in English between 1955 and June 2012. The effects of specific agents on blood pressure were analyzed. Hypertension is a prevalent adverse effect of many of the new chemotherapy agents such as VEGF inhibitors. Approximately 30% of patients treated for cancer will have concomitant hypertension, and crucial chemotherapy can sometimes be stopped due to new onset or worsening severe hypertension. The importance of a timely diagnosis and optimal management of HTN in this group of patients is related to the facts that HTN is a well established risk factor for chemotherapy-induced cardiotoxicity and if left untreated, can alter cancer management and result in dose reductions or termination of anti-cancer treatments as well as life-threatening end organ damage. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  5. Anxiety and Death Anxiety in Egyptian and Spanish Nursing Students

    Science.gov (United States)

    Abdel-Khalek, Ahmed M.; Tomas-Sabado, Joaquin

    2005-01-01

    Two samples of female nursing undergraduates from Egypt (n=132) and Spain (n=126) responded to the Arabic Scale of Death Anxiety, the Spanish Death Anxiety Inventory, the Templer's Death Anxiety Scale, the Kuwait University Anxiety Scale, and the State-Trait Anxiety Inventory-Trait Subscale. Each sample answered the scales in their native…

  6. Anti-tumor promoting potential of selected spice ingredients with antioxidative and anti-inflammatory activities: a short review.

    Science.gov (United States)

    Surh, Young-Joon

    2002-08-01

    A wide variety of phenolic substances derived from spice possess potent antimutagenic and anticarcinogenic activities. Examples are curcumin, a yellow colouring agent, contained in turmeric (Curcuma longa L., Zingiberaceae), [6]-gingerol, a pungent ingredient present in ginger (Zingiber officinale Roscoe, Zingiberaceae) and capsaicin, a principal pungent principle of hot chili pepper (Capsicum annuum L, Solanaceae). The chemopreventive effects exerted by these phytochemicals are often associated with their antioxidative and anti-inflammatory activities. Cyclo-oxygenase-2 (COX-2) has been recognized as a molecular target of many chemopreventive as well as anti-inflammatory agents. Recent studies have shown that COX-2 is regulated by the eukaryotic transcription factor NF-kappaB. This short review summarizes the molecular mechanisms underlying chemopreventive effects of the aforementioned spice ingredients in terms of their effects on intracellular signaling cascades, particularly those involving NF-kappaB and mitogen-activated protein kinases.

  7. Assessment of the anti-angiogenic, anti-inflammatory and antinociceptive properties of ethyl vanillin.

    Science.gov (United States)

    Jung, Hyun-Joo; Song, Yun Seon; Kim, Kyunghoon; Lim, Chang-Jin; Park, Eun-Hee

    2010-02-01

    The present work aimed to assess novel pharmacological properties of ethyl vanillin (EVA) which is used as a flavoring agent for cakes, dessert, confectionary, etc. EVA exhibited an inhibitory activity in the chorioallantoic membrane angiogenesis. Anti-inflammatory activity of EVA was convinced using the two in vivo models, such as vascular permeability and air pouch models in mice. Antinociceptive activity of EVA was assessed using acetic acid-induced writhing model in mice. EVA suppressed production of nitric oxide and induction of inducible nitric oxide synthase in the lipopolysaccharide (LPS)-activated RAW264.7 macrophage cells. However, EVA could not suppress induction of cyclooxygenase-2 in the LPS-activated macrophages. EVA diminished reactive oxygen species level in the LPS-activated macrophages. EVA also suppressed enhanced matrix metalloproteinase-9 gelatinolytic activity in the LPSactivated RAW264.7 macrophage cells. EVA at the used concentrations couldn't diminish viability of the macrophage cells. Taken together, the anti-angiogenic, anti-inflammatory and anti-nociceptive properties of EVA are based on its suppressive effect on the production of nitric oxide possibly via decreasing the reactive oxygen species level.

  8. Anti-tumor and anti-angiogenic ergosterols from Ganoderma lucidum

    Science.gov (United States)

    Chen, Shaodan; Yong, Tianqiao; Zhang, Yifang; Su, Jiyan; Jiao, Chunwei; Xie, Yizhen

    2017-10-01

    This study was carried out to isolate chemical constituents from the lipid enriched fraction of Ganoderma lucidum extract and to evaluate their anti-proliferative effect on cancer cell lines and human umbilical vein endothelial cells. Ergosterol derivatives (1-14) were isolated from the lipid enriched fraction of G. lucidum. Their structures were established on the basis of spectroscopic analyses or by comparison of mass and NMR spectral data with those reported previously. Amongst, compound 1 was isolated and identified as a new compound. All the compounds were evaluated for their inhibitory effect on tumor cells and human umbilical vein endothelial cells in vitro. Compounds 9-13 displayed inhibitory activity against two tumor cell lines and human umbilical vein endothelial cells, which indicated that these four compounds had both anti-tumor and anti-angiogenesis activities. Compound 2 had significant selective inhibition against two tumor cell lines, while 3 exhibited selective inhibition against human umbilical vein endothelial cells. The structure–activity relationships for inhibiting human HepG2 cells were revealed by 3D-QASR. Ergosterol content in different parts of the raw material and products of G. lucidum was quantified. This study provides a basis for further development and utilization of ergosterol derivatives as natural nutraceuticals and functional food ingredients, or as source of new potential antitumor or anti-angiogenesis chemotherapy agent.

  9. A novel visual facial anxiety scale for assessing preoperative anxiety.

    Directory of Open Access Journals (Sweden)

    Xuezhao Cao

    Full Text Available There is currently no widely accepted instrument for measuring preoperative anxiety. The objective of this study was to develop a simple visual facial anxiety scale (VFAS for assessing acute preoperative anxiety.The initial VFAS was comprised of 11 similarly styled stick-figure reflecting different types of facial expressions (Fig 1. After obtaining IRB approval, a total of 265 participant-healthcare providers (e.g., anesthesiologists, anesthesiology residents, and perioperative nurses were recruited to participate in this study. The participants were asked to: (1 rank the 11 faces from 0-10 (0 = no anxiety, while 10 = highest anxiety and then to (2 match one of the 11 facial expression with a numeric verbal rating scale (NVRS (0 = no anxiety and 10 = highest level of anxiety and a specific categorical level of anxiety, namely no anxiety, mild, mild-moderate, moderate, moderate-high or highest anxiety. Based on these data, the Spearman correlation and frequencies of the 11 faces in relation to the 11-point numerical anxiety scale and 6 categorical anxiety levels were calculated. The highest frequency of a face assigned to a level of the numerical anxiety scale resulted in a finalized order of faces corresponding to the 11-point numeric rating scale.The highest frequency for each of the NVRS anxiety scores were as follow: A0, A1, A2, A3, A4, A5, A7, A6, A8, A9 and A10 (Fig 2. For the six categorical anxiety levels, a total of 260 (98.1% participants chose the face A0 as representing 'no' anxiety, 250 (94.3% participants chose the face A10 as representing 'highest' anxiety and 147 (55.5% participants chose the face A8 as representing 'moderate-high' anxiety. Spearman analysis showed a significant correlation between the faces A3 and A5 assigned to the mild-moderate anxiety category (r = 0.58, but A5 was ultimately chosen due to its higher frequency compared to the frequency of A3 (30.6% vs 24.9%(Fig 3. Similarly, the correlation of the faces A7

  10. Paediatric Anxiety Disorders

    Directory of Open Access Journals (Sweden)

    Beena Johnson

    2017-07-01

    Full Text Available Anxiety disorders are highly prevalent among children and are associated with serious morbidity. Lifetime prevalence of paediatric anxiety disorders is about fifteen percent. Social phobia, generalized anxiety disorder and separation anxiety disorder are included in the triad of paediatric anxiety disorders. Specific phobia, obsessive compulsive disorder and post-traumatic stress disorder are also commonly seen in children. Overprotection by parents, parental death or separation, female sex, low educational status, family history of anxiety disorder, financial stress in family and adverse childhood experiences are risk factors for the development of anxiety disorders. If not diagnosed and managed at the earliest, paediatric anxiety disorders can cause life threatening problems in the future. Hence early and scientific management of anxiety disorders is essential. Cognitive behavioural therapy is the effective evidence based treatment for paediatric anxiety disorders.

  11. [Biological agents].

    Science.gov (United States)

    Amano, Koichi

    2009-03-01

    There are two types of biological agents for the treatment of rheumatoid arthritis (RA); monoclonal antibodies and recombinant proteins. Among the latter, etanercept, a recombinant fusion protein of soluble TNF receptor and IgG was approved in 2005 in Japan. The post-marketing surveillance of 13,894 RA patients revealed the efficacy and safety profiles of etanercept in the Japanese population, as well as overseas studies. Abatacept, a recombinant fusion protein of CTLA4 and IgG, is another biological agent for RA. Two clinical trials disclosed the efficacy of abatacept for difficult-to-treat patients: the AIM for MTX-resistant cases and the ATTAIN for patients who are resistant to anti-TNF. The ATTEST trial suggested abatacept might have more acceptable safety profile than infliximab. These biologics are also promising for the treatment of RA for not only relieving clinical symptoms and signs but retarding structural damage.

  12. Melatonin as an Anti-Inflammatory Agent Modulating Inflammasome Activation

    Directory of Open Access Journals (Sweden)

    Gaia Favero

    2017-01-01

    Full Text Available Inflammation may be defined as the innate response to harmful stimuli such as pathogens, injury, and metabolic stress; its ultimate function is to restore the physiological homeostatic state. The exact aetiology leading to the development of inflammation is not known, but a combination of genetic, epigenetic, and environmental factors seems to play an important role in the pathogenesis of many inflammation-related clinical conditions. Recent studies suggest that the pathogenesis of different inflammatory diseases also involves the inflammasomes, intracellular multiprotein complexes that mediate activation of inflammatory caspases thereby inducing the secretion of proinflammatory cytokines. Melatonin, an endogenous indoleamine, is considered an important multitasking molecule with fundamental clinical applications. It is involved in mood modulation, sexual behavior, vasomotor control, and immunomodulation and influences energy metabolism; moreover, it acts as an oncostatic and antiaging molecule. Melatonin is an important antioxidant and also a widespread anti-inflammatory molecule, modulating both pro- and anti-inflammatory cytokines in different pathophysiological conditions. This review, first, gives an overview concerning the growing importance of melatonin in the inflammatory-mediated pathological conditions and, then, focuses on its roles and its protective effects against the activation of the inflammasomes and, in particular, of the NLRP3 inflammasome.

  13. Toxic effects of non-steroidal anti-inflammatory agents in rats ...

    African Journals Online (AJOL)

    The toxicosis of some non-steroidal anti-inflammatory drugs, piroxicam, indomethacin, phenylbutazone, and aspirin, which occasionally are locally used in Nigeria as rodenticides have been evaluated in rats using changes in the serum biochemical and haematological parameters as indices of toxicity. In the study, no ...

  14. Therapeutic management of inflammatory bowel disease in real-life practice in the current era of anti-TNF agents: analysis of the French administrative health databases 2009-2014.

    Science.gov (United States)

    Kirchgesner, J; Lemaitre, M; Rudnichi, A; Racine, A; Zureik, M; Carbonnel, F; Dray-Spira, R

    2017-01-01

    Management of inflammatory bowel disease (IBD) has evolved in the last decade. To assess IBD therapeutic management, including treatment withdrawal and early treatment use in the current era of anti-TNF agents (anti-TNFs). All patients affiliated to the French national health insurance diagnosed with IBD were included from 2009 to 2013 and followed up until 31 December 2014. Medication uses, treatment sequences after introduction of thiopurine or anti-TNF monotherapies or both (combination therapy), surgical procedures and hospitalisations were assessed. A total of 210 001 patients were diagnosed with IBD [Crohn's disease (CD), 100 112; ulcerative colitis (UC), 109 889]. Five years after diagnosis, cumulative probabilities of anti-TNF monotherapy and combination therapy exposures were 33.8% and 18.3% in CD patients and 12.9% and 7.4% in UC patients, respectively. Among incident patients who received thiopurines or anti-TNFs, the first treatment was thiopurine in 69.1% of CD and 78.2% of UC patients. Among patients treated with anti-TNFs, 45.2% and 54.5% of CD patients and 38.2% and 39.9% of UC patients started monotherapy and combination therapy within 3 months after diagnosis, respectively; 31.3% of CD and 27.1% of UC incident patients withdrew from thiopurine or anti-TNFs for more than 3 months after their first course of treatment. Five years after diagnosis, the cumulative risks of first intestinal resection in CD patients and colectomy in UC patients were 11.9% and 5.7%, respectively. Step-up approach remains the predominant strategy, while exposure to anti-TNFs is high. Surgery rates are low. Treatment withdrawal in IBD is more common than expected. © 2016 John Wiley & Sons Ltd.

  15. Basic analytical methods for identification of erythropoiesis-stimulating agents in doping control

    International Nuclear Information System (INIS)

    Postnikov, P V; Krotov, G I; Rodchenkov, G M; Efimova, Yu A

    2016-01-01

    The design of new erythropoiesis-stimulating agents for clinical use necessitates constant development of methods for detecting the abuse of these substances, which are prohibited under the World Anti-Doping Code and are included in the World Anti-Doping Agency (WADA) prohibited list. This review integrates and describes systematically the published data on the key methods currently used by WADA-accredited anti-doping laboratories around the world to detect the abuse of erythropoiesis-stimulating agents, including direct methods (various polyacrylamide gel electrophoresis techniques, enzyme-linked immunosorbent assay, membrane enzyme immunoassay and mass spectrometry) and indirect methods (athlete biological passport). Particular attention is given to promising approaches and investigations that can be used to control prohibited erythropoietins in the near future. The bibliography includes 122 references

  16. Recent developments in antiviral agents against enterovirus 71 infection.

    Science.gov (United States)

    Tan, Chee Wah; Lai, Jeffrey Kam Fatt; Sam, I-Ching; Chan, Yoke Fun

    2014-02-12

    Enterovirus 71 (EV-71) is the main etiological agent of hand, foot and mouth disease (HFMD). Recent EV-71 outbreaks in Asia-Pacific were not limited to mild HFMD, but were associated with severe neurological complications such as aseptic meningitis and brainstem encephalitis, which may lead to cardiopulmonary failure and death. The absence of licensed therapeutics for clinical use has intensified research into anti-EV-71 development. This review highlights the potential antiviral agents targeting EV-71 attachment, entry, uncoating, translation, polyprotein processing, virus-induced formation of membranous RNA replication complexes, and RNA-dependent RNA polymerase. The strategies for antiviral development include target-based synthetic compounds, anti-rhinovirus and poliovirus libraries screening, and natural compound libraries screening. Growing knowledge of the EV-71 life cycle will lead to successful development of antivirals. The continued effort to develop antiviral agents for treatment is crucial in the absence of a vaccine. The coupling of antivirals with an effective vaccine will accelerate eradication of the disease.

  17. Cultural Aspects in Social Anxiety and Social Anxiety Disorder

    Science.gov (United States)

    Hofmann, Stefan G.; Asnaani, Anu; Hinton, Devon E.

    2010-01-01

    To examine cultural aspects in social anxiety and social anxiety disorder (SAD), we reviewed the literature on the prevalence rates, expressions, and treatments of social anxiety/SAD as they relate to culture, race, and ethnicity. We further reviewed factors that contribute to the differences in social anxiety/SAD between different cultures, including individualism/collectivism, perception of social norms, self-construal, gender roles, and gender role identification. Our review suggests that the prevalence and expression of social anxiety/SAD depends on the particular culture. Asian cultures typically show the lowest rates, whereas Russian and US samples show the highest rates, of SAD. Taijin kyofusho is discussed as a possible culture-specific expression of social anxiety, although the empirical evidence concerning the validity of this syndrome has been mixed. It is concluded that the individual's social concerns need to be examined in the context of the person's cultural, racial, and ethnic background in order to adequately assess the degree and expression of social anxiety and social anxiety disorder. This has direct relevance for the upcoming DSM-V. PMID:21132847

  18. N-arylmethylideneaminophthalimide: Design, synthesis and evaluation as analgesic and anti-inflammatory agents.

    Science.gov (United States)

    Banarouei, Nasimossadat; Davood, Asghar; Shafaroodi, Hamed; Saeedi, Ghazaleh; Shafiee, Abbas

    2018-04-23

    N-aryl derivatives of phthalimide and 4-nitro phthalimide have demonstrated cyclooxygenase inhibitory activity. Also they possess an excellent analgesic and anti-inflammatory activity. In this work, a new series of N-arylmethylideneamino derivatives of phthalimide and 4-nitro phthalimide were designed and synthesized. The designed compounds were synthesized by condensation of the appropriate aldehyde and N-aminophthalimide in ethanol at room temperature at PH around 3. Their analgesic and anti-inflammatory activity were evaluated by acetic acid-induced pain test and carrageenan-induced paw edema test in mice and rats, respectively. The details of the synthesis and chemical characterization of the analogs are described. In vivo screening showed compounds 3a, 3b, 3f and 3h were the most potent analgesic compounds. In addition compounds 3a, 3c, 3d, 3e and 3j indicated comparable anti-inflammatory activity to indomethacin as reference drug. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  19. Application of a widely-used tropical anti-worm agent, mebendazole ...

    African Journals Online (AJOL)

    well-known anti-parasitic drug widely used in the tropical areas, inhibits cancer cell growth. Preclinical .... Bcl-2 and related proteins, encoded by the Bcl-2 oncogene ... homodimer that acts as an apoptosis inducer, while the ... Figure 1: Schematic presentation of proposed mebendazole anticancer mechanisms of action in.

  20. Application of a widely-used tropical anti-worm agent, mebendazole ...

    African Journals Online (AJOL)

    Although clinical trials have not been completed, it has already been confirmed that mebendazole, a well-known anti-parasitic drug widely used in the tropical areas, inhibits cancer cell growth. Preclinical studies show that mebendazole notably impedes the growth of malignant and metastatic tumors such as osteosarcoma ...

  1. Immunological effects of hypomethylating agents.

    Science.gov (United States)

    Lindblad, Katherine E; Goswami, Meghali; Hourigan, Christopher S; Oetjen, Karolyn A

    2017-08-01

    Epigenetic changes resulting from aberrant methylation patterns are a recurrent observation in hematologic malignancies. Hypomethylating agents have a well-established role in the management of patients with high-risk myelodysplastic syndrome or acute myeloid leukemia. In addition to the direct effects of hypomethylating agents on cancer cells, there are several lines of evidence indicating a role for immune-mediated anti-tumor benefits from hypomethylating therapy. Areas covered: We reviewed the clinical and basic science literature for the effects of hypomethylating agents, including the most commonly utilized therapeutics azacitidine and decitabine, on immune cell subsets. We summarized the effects of hypomethylating agents on the frequency and function of natural killer cells, T cells, and dendritic cells. In particular, we highlight the effects of hypomethylating agents on expression of immune checkpoint inhibitors, leukemia-associated antigens, and endogenous retroviral elements. Expert commentary: In vitro and ex vivo studies indicate mixed effects on the function of natural killer, dendritic cells and T cells following treatment with hypomethylating agents. Clinical correlates of immune function have suggested that hypomethylating agents have immunomodulatory functions with the potential to synergize with immune checkpoint therapy for the treatment of hematologic malignancy, and has become an active area of clinical research.

  2. Anti-inflammatory activity of Ambrosia artemisiaefolia and Rhoeo spathacea.

    Science.gov (United States)

    Pérez G, R M

    1996-09-01

    Alcoholic extracts of the leaves of Ambrosia artemisiaefolia and Rhoeo spathacea have been investigated for anti-inflammatory activity using various experimental models of inflammation (croton oil ear oedema, carrageenan-induced edema, cotton pellet granuloma and formaldehyde induced arthritis) and the results compared with phenylbutazone and bethamethasone, standard anti-inflammatory drugs. These extracts at doses of 50, 100 and 150mg/kg of A. artemisiaefolia and R. spathacea, showed significant inhibition of acute oedema in rats and mice induced by the phlogistic agents, carrageenan and croton oil, in a dose-dependant manner. The ethanol extracts reduced cotton pellet granuloma and caused a statistically significant inhibitory effect on edema in the chronic model of formaldehyde arthritis in rats. Since Ambrosia artemisiaefolia and Rhoeo spathacea were found to be effective in both acute and chronic phases of inflammation they can be considered as general anti-inflammatory agents. Copyright © 1996 Gustav Fischer Verlag · Stuttgart · Jena · New York. Published by Elsevier GmbH.. All rights reserved.

  3. Fifty years with the Hamilton scales for anxiety and depression. A tribute to Max Hamilton

    DEFF Research Database (Denmark)

    Bech, P; Bech, P

    2009-01-01

    as the method for the evaluation of the clinical effects of psychotropic drugs. Inspired by Eysenck, Hamilton took the long route around factor analysis in order to qualify his scales for anxiety (HAM-A) and depression (HAM-D) as scientific tools. From the moment when, 50 years ago, Hamilton published his first...... placebo-controlled trial with an experimental anti-anxiety drug, he realized the dialectic problem in using the total score on HAM-A as a sufficient statistic for the measurement of outcome. This dialectic problem has been investigated for more than 50 years with different types of factor analyses without...

  4. Childhood separation anxiety and the pathogenesis and treatment of adult anxiety.

    Science.gov (United States)

    Milrod, Barbara; Markowitz, John C; Gerber, Andrew J; Cyranowski, Jill; Altemus, Margaret; Shapiro, Theodore; Hofer, Myron; Glatt, Charles

    2014-01-01

    Clinically significant separation anxiety disorder in childhood leads to adult panic disorder and other anxiety disorders. The prevailing pathophysiological model of anxiety disorders, which emphasizes extinction deficits of fear-conditioned responses, does not fully consider the role of separation anxiety. Pathological early childhood attachments have far-reaching consequences for the later adult ability to experience and internalize positive relationships in order to develop mental capacities for self-soothing, anxiety tolerance, affect modulation, and individuation. Initially identified in attachment research, the phenomenon of separation anxiety is supported by animal model, neuroimaging, and genetic studies. A role of oxytocin is postulated. Adults, inured to their anxiety, often do not identify separation anxiety as problematic, but those who develop anxiety and mood disorders respond more poorly to both pharmacological and psychotherapeutic interventions. This poorer response may reflect patients' difficulty in forming and maintaining attachments, including therapeutic relationships. Psychotherapies that focus on relationships and separation anxiety may benefit patients with separation anxiety by using the dyadic therapist-patient relationship to recapture and better understand important elements of earlier pathological parent-child relationships.

  5. Spatial control of bone formation using a porous polymer scaffold co-delivering anabolic rhBMP-2 and anti-resorptive agents

    Directory of Open Access Journals (Sweden)

    NYC Yu

    2014-01-01

    Full Text Available Current clinical delivery of recombinant human bone morphogenetic proteins (rhBMPs utilises freeze-dried collagen. Despite effective new bone generation, rhBMP via collagen can be limited by significant complications due to inflammation and uncontrolled bone formation. This study aimed to produce an alternative rhBMP local delivery system to permit more controllable and superior rhBMP-induced bone formation. Cylindrical porous poly(lactic-co-glycolic acid (PLGA scaffolds were manufactured by thermally-induced phase separation. Scaffolds were encapsulated with anabolic rhBMP-2 (20 µg ± anti-resorptive agents: zoledronic acid (5 µg ZA, ZA pre-adsorbed onto hydroxyapatite microparticles, (5 µg ZA/2 % HA or IkappaB kinase (IKK inhibitor (10 µg PS-1145. Scaffolds were inserted in a 6-mm critical-sized femoral defect in Wistar rats, and compared against rhBMP-2 via collagen. The regenerate region was examined at 6 weeks by 3D microCT and descriptive histology. MicroCT and histology revealed rhBMP-induced bone was more restricted in the PLGA scaffolds than collagen scaffolds (-92.3 % TV, p < 0.01. The regenerate formed by PLGA + rhBMP-2/ZA/HA showed comparable bone volume to rhBMP-2 via collagen, and bone mineral density was +9.1 % higher (p < 0.01. Local adjunct ZA/HA or PS-1145 significantly enhanced PLGA + rhBMP-induced bone formation by +78.2 % and +52.0 %, respectively (p ≤ 0.01. Mechanistically, MG-63 human osteoblast-like cells showed cellular invasion and proliferation within PLGA scaffolds. In conclusion, PLGA scaffolds enabled superior spatial control of rhBMP-induced bone formation over clinically-used collagen. The PLGA scaffold has the potential to avoid uncontrollable bone formation-related safety issues and to customise bone shape by scaffold design. Moreover, local treatment with anti-resorptive agents incorporated within the scaffold further augmented rhBMP-induced bone formation.

  6. Synthesis, in vitro anti-inflammatory activity and molecular docking ...

    Indian Academy of Sciences (India)

    alkyl and heterocyclic alkyl moieties were synthesized, characterized and subsequently evaluated for ... Docking studies with these compounds against cyclooxygenase-2 receptor ...... thiadiazole derivatives as possible anti-tubercular agents.

  7. Introducción a los antisépticos

    Directory of Open Access Journals (Sweden)

    Laura López González

    2014-05-01

    Full Text Available Los antisépticos son agentes antiinfecciosos de uso local sobre piel o mucosas, lo cual los distingue de los desinfectantes, que se usan sobre superficies inanimadas, debido normalmente a su toxicidad. En este capítulo explicamos las diferencias entre los múltiples posibles antisépticos, prestando especial atención a los más comunes como el alcohol, la clorhexidina, la povidona yodada y el agua oxigenada. Finalmente hacemos hincapié en las diferentes formulaciones de los antisépticos, que los hacen más útiles para indicaciones determinadas.

  8. Environmental Conservation Consciousness and Anxiety From the Persective of Personal Anxiety and Social Anxiety

    OpenAIRE

    保坂, 稔

    2014-01-01

    The system of lifetime employment tends to collapse recently, the rise of anxiety reduces some kinds of aspirations. This paper analyzes the relation between environmental conservation consciousness and anxiety by using the data of 260 university students in Nagasaki. Then I find that the affirmative side which anxiety brings to environmental protection.

  9. Friedelane-type triterpenoids as selective anti-inflammatory agents by regulation of differential signaling pathways in LPS-stimulated macrophages

    Energy Technology Data Exchange (ETDEWEB)

    Villar-Lorenzo, Andrea, E-mail: avillar@iib.uam.es [Instituto de Investigaciones Biomédicas Alberto Sols (IIBm) (CSIC/UAM), C/ Arturo Duperier 4, 28029 Madrid (Spain); Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERdem), ISCIII, 28029 Madrid (Spain); Ardiles, Alejandro E., E-mail: ale_csic@gmail.com [Instituto Universitario de Bio-Orgánica Antonio González, Departamento de Química Orgánica, Universidad de La Laguna, Avenida Astrofísico Francisco Sánchez 2, 38206 La Laguna, Tenerife (Spain); Facultad de Ciencias de la Salud, Universidad Arturo Prat, Casilla 121, Iquique 1110939 (Chile); Arroba, Ana I., E-mail: aarroba@iib.uam.es [Instituto de Investigaciones Biomédicas Alberto Sols (IIBm) (CSIC/UAM), C/ Arturo Duperier 4, 28029 Madrid (Spain); Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERdem), ISCIII, 28029 Madrid (Spain); Hernández-Jiménez, Enrique, E-mail: enheji@gmail.com [Tumor Immunology Laboratory (IdiPAZ), 28029 Madrid (Spain); Centro de Investigación Biomédica en Red de Enfermedades Respiratorias (CIBERres), ISCIII, 28029 Madrid (Spain); and others

    2016-12-15

    A series of 31 pentacyclic triterpenoids isolated from the root barks of Celastrus vulcanicola and Maytenus jelskii were tested for cytotoxicity and inhibitory activity against lipopolysaccharide (LPS)-induced nitric oxide (NO) production in RAW 264.7 macrophages. Compounds 18 (C18) and 25 (C25) exhibited significant inhibition of LPS-induced NO release at 50 and 25 μM concentrations, respectively, and decreased mRNAs of pro-inflammatory cytokines. At the molecular level, C18 neither inhibited LPS-mediated phosphorylation of mitogen activated protein kinases (MAPKs) nor nuclear translocation of nuclear factor kappa beta (NFκB). Instead, C18 enhanced and prolonged nuclear translocation of nuclear factor-erythroid 2-related factor 2 (Nrf2) and increased the expression of its target genes including hemeoxigenase 1 (HO1). C25 efficiently inhibited LPS-mediated phosphorylation of JNK, p38 and ERK, without affecting NFκB or Nrf2 signaling pathways. Both compounds reduced LPS-mediated processing of caspase-1 and the cleavage of interleukin 1β (IL1β) proform, reflecting their ability to target the inflammasome. C25 also counteracted LPS effects on iNOS expression and pro-inflammatory cytokines mRNA levels in Bv-2 microglial cells. The anti-inflammatory effect of both compounds was also assessed in human macrophages. Our results suggest that triterpenoids C18 and C25 possess anti-inflammatory effects, which may be therapeutically relevant for diseases linked to inflammation. - Highlights: • Compounds 18 (C18) and 25 (C25) exert anti-inflammatory effects in macrophages. • C18 enhanced nuclear translocation of Nrf2 and increased HO1 expression. • C25 inhibited the phosphorylation of JNK, p38 and ERK, members of the MAPKs family. • C25 reduced LPS-mediated processing of caspase-1 and the cleavage of interleukin 1β. • C18 and C25 may be therapeutic agents for diseases linked to inflammation.

  10. Friedelane-type triterpenoids as selective anti-inflammatory agents by regulation of differential signaling pathways in LPS-stimulated macrophages

    International Nuclear Information System (INIS)

    Villar-Lorenzo, Andrea; Ardiles, Alejandro E.; Arroba, Ana I.; Hernández-Jiménez, Enrique

    2016-01-01

    A series of 31 pentacyclic triterpenoids isolated from the root barks of Celastrus vulcanicola and Maytenus jelskii were tested for cytotoxicity and inhibitory activity against lipopolysaccharide (LPS)-induced nitric oxide (NO) production in RAW 264.7 macrophages. Compounds 18 (C18) and 25 (C25) exhibited significant inhibition of LPS-induced NO release at 50 and 25 μM concentrations, respectively, and decreased mRNAs of pro-inflammatory cytokines. At the molecular level, C18 neither inhibited LPS-mediated phosphorylation of mitogen activated protein kinases (MAPKs) nor nuclear translocation of nuclear factor kappa beta (NFκB). Instead, C18 enhanced and prolonged nuclear translocation of nuclear factor-erythroid 2-related factor 2 (Nrf2) and increased the expression of its target genes including hemeoxigenase 1 (HO1). C25 efficiently inhibited LPS-mediated phosphorylation of JNK, p38 and ERK, without affecting NFκB or Nrf2 signaling pathways. Both compounds reduced LPS-mediated processing of caspase-1 and the cleavage of interleukin 1β (IL1β) proform, reflecting their ability to target the inflammasome. C25 also counteracted LPS effects on iNOS expression and pro-inflammatory cytokines mRNA levels in Bv-2 microglial cells. The anti-inflammatory effect of both compounds was also assessed in human macrophages. Our results suggest that triterpenoids C18 and C25 possess anti-inflammatory effects, which may be therapeutically relevant for diseases linked to inflammation. - Highlights: • Compounds 18 (C18) and 25 (C25) exert anti-inflammatory effects in macrophages. • C18 enhanced nuclear translocation of Nrf2 and increased HO1 expression. • C25 inhibited the phosphorylation of JNK, p38 and ERK, members of the MAPKs family. • C25 reduced LPS-mediated processing of caspase-1 and the cleavage of interleukin 1β. • C18 and C25 may be therapeutic agents for diseases linked to inflammation.

  11. Secoisolariciresinol diglucoside is a blood-brain barrier protective and anti-inflammatory agent: implications for neuroinflammation.

    Science.gov (United States)

    Rom, Slava; Zuluaga-Ramirez, Viviana; Reichenbach, Nancy L; Erickson, Michelle A; Winfield, Malika; Gajghate, Sachin; Christofidou-Solomidou, Melpo; Jordan-Sciutto, Kelly L; Persidsky, Yuri

    2018-01-27

    -functional response reducing oxidative stress, inflammation, and BBB permeability makes it an exciting potential therapeutic for neuroinflammatory diseases. SDG can serve as an anti-inflammatory and barrier-protective agent in neuroinflammation.

  12. Anxiety and anxiety disorders. Toward a conceptual reorientation.

    Science.gov (United States)

    Curtis, G C

    1985-03-01

    Traditionally, it has been assumed that there is only one type of anxiety; recent pharmacologic evidence suggests that there may be several. The psychoanalytic concept of "neurotic" symptoms as depressurizing mechanisms is out of keeping with most evidence now available. Spontaneous or "free-floating" anxiety may be partly biologic and genetic in origin. Anxiety symptoms evoked by specific stimuli behave in part like conditioned responses. Where conditioning theory has failed to propose a plausible unconditioned stimulus for pathologic anxiety, biology, ethology, and psychoanalysis may have been more successful.

  13. Autonomic arousal in childhood anxiety disorders: Associations with state anxiety and social anxiety disorder

    Science.gov (United States)

    Alkozei, Anna; Creswell, Cathy; Cooper, Peter J.; Allen, John J.B.

    2015-01-01

    Background Psychophysiological theories suggest that individuals with anxiety disorders may evidence inflexibility in their autonomic activity at rest and when responding to stressors. In addition, theories of social anxiety disorder, in particular, highlight the importance of physical symptoms. Research on autonomic activity in childhood (social) anxiety disorders, however, is scarce and has produced inconsistent findings, possibly because of methodological limitations. Method The present study aimed to account for limitations of previous studies and measured respiratory sinus arrhythmia (RSA) and heart rate (HR) using Actiheart heart rate monitors and software (Version 4) during rest and in response to a social and a non-social stressor in 60 anxious (30 socially anxious and 30 ‘other’ anxious), and 30 nonanxious sex-and age-matched 7–12 year olds. In addition, the effect of state anxiety during the tasks was explored. Results No group differences at rest or in response to stress were found. Importantly, however, with increases in state anxiety, all children, regardless of their anxiety diagnoses showed less autonomic responding (i.e., less change in HR and RSA from baseline in response to task) and took longer to recover once the stressor had passed. Limitations This study focused primarily on parasympathetic arousal and lacked measures of sympathetic arousal. Conclusion The findings suggest that childhood anxiety disorders may not be characterized by inflexible autonomic responding, and that previous findings to the contrary may have been the result of differences in subjective anxiety between anxious and nonanxious groups during the tasks, rather than a function of chronic autonomic dysregulation. PMID:25590763

  14. Teachers' Knowledge of Anxiety and Identification of Excessive Anxiety in

    Science.gov (United States)

    Headley, Clea; Campbell, Marilyn A.

    2013-01-01

    This study examined primary school teachers' knowledge of anxiety and excessive anxiety symptoms in children. Three hundred and fifteen primary school teachers completed a questionnaire exploring their definitions of anxiety and the indications they associated with excessive anxiety in primary school children. Results showed that teachers had an…

  15. Can smartphone mental health interventions reduce symptoms of anxiety? A meta-analysis of randomized controlled trials.

    Science.gov (United States)

    Firth, Joseph; Torous, John; Nicholas, Jennifer; Carney, Rebekah; Rosenbaum, Simon; Sarris, Jerome

    2017-08-15

    Various psychological interventions are effective for reducing symptoms of anxiety when used alone, or as an adjunct to anti-anxiety medications. Recent studies have further indicated that smartphone-supported psychological interventions may also reduce anxiety, although the role of mobile devices in the treatment and management of anxiety disorders has yet to be established. We conducted a systematic review and meta-analysis of all randomized clinical trials (RCTs) reporting the effects of psychological interventions delivered via smartphone on symptoms of anxiety (sub-clinical or diagnosed anxiety disorders). A systematic search of major electronic databases conducted in November 2016 identified 9 eligible RCTs, with 1837 participants. Random-effects meta-analyses were used to calculate the standardized mean difference (as Hedges' g) between smartphone interventions and control conditions. Significantly greater reductions in total anxiety scores were observed from smartphone interventions than control conditions (g=0.325, 95% C.I.=0.17-0.48, psmartphone interventions were significantly greater when compared to waitlist/inactive controls (g=0.45, 95% C.I.=0.30-0.61, psmartphone interventions can match (or exceed) the efficacy of recognised treatments for anxiety has yet to established. This meta-analysis shows that psychological interventions delivered via smartphone devices can reduce anxiety. Future research should aim to develop pragmatic methods for implementing smartphone-based support for people with anxiety, while also comparing the efficacy of these interventions to standard face-to-face psychological care. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

  16. Increased Anti-Phospholipid Antibodies in Autism Spectrum Disorders

    Directory of Open Access Journals (Sweden)

    Milo Careaga

    2013-01-01

    Full Text Available Autism spectrum disorders (ASD are characterized by impairments in communication, social interactions, and repetitive behaviors. While the etiology of ASD is complex and likely involves the interplay of genetic and environmental factors, growing evidence suggests that immune dysfunction and the presence of autoimmune responses including autoantibodies may play a role in ASD. Anti-phospholipid antibodies are believed to occur from both genetic and environmental factors and have been linked to a number of neuropsychiatric symptoms such as cognitive impairments, anxiety, and repetitive behaviors. In the current study, we investigated whether there were elevated levels of anti-phospholipid antibodies in a cross-sectional analysis of plasma of young children with ASD compared to age-matched typically developing (TD controls and children with developmental delays (DD other than ASD. We found that levels of anti-cardiolipin, β2-glycoprotein 1, and anti-phosphoserine antibodies were elevated in children with ASD compared with age-matched TD and DD controls. Further, the increase in antibody levels was associated with more impaired behaviors reported by parents. This study provides the first evidence for elevated production of anti-phospholipid antibodies in young children with ASD and provides a unique avenue for future research into determining possible pathogenic mechanisms that may underlie some cases of ASD.

  17. Comparison of Anxiety Management Training and Desensitization in Reducing Test and Other Anxieties.

    Science.gov (United States)

    Deffenbacher, Jerry L.; Shelton, John L.

    1978-01-01

    Effects of systematic desensitization and anxiety management training in reducing test anxiety and generalizing to other anxieties were compared. Both desensitization and anxiety management training produced significant reduction of text anxiety, but by follow-up, anxiety management training produced significantly more test-anxiety reduction on…

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

    Science.gov (United States)

    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.

  19. The EMO-Model: An Agent-Based Model of Primate Social Behavior Regulated by Two Emotional Dimensions, Anxiety-FEAR and Satisfaction-LIKE

    Science.gov (United States)

    Evers, Ellen; de Vries, Han; Spruijt, Berry M.; Sterck, Elisabeth H. M.

    2014-01-01

    Agent-based models provide a promising tool to investigate the relationship between individuals’ behavior and emerging group-level patterns. An individual’s behavior may be regulated by its emotional state and its interaction history with specific individuals. Emotional bookkeeping is a candidate mechanism to keep track of received benefits from specific individuals without requiring high cognitive abilities. However, how this mechanism may work is difficult to study in real animals, due to the complexity of primate social life. To explore this theoretically, we introduce an agent-based model, dubbed EMO-model, in which we implemented emotional bookkeeping. In this model the social behaviors of primate-like individuals are regulated by emotional processes along two dimensions. An individual’s emotional state is described by an aversive and a pleasant dimension (anxiety and satisfaction) and by its activating quality (arousal). Social behaviors affect the individuals’ emotional state. To implement emotional bookkeeping, the receiver of grooming assigns an accumulated affiliative attitude (LIKE) to the groomer. Fixed partner-specific agonistic attitudes (FEAR) reflect the stable dominance relations between group members. While the emotional state affects an individual’s general probability of executing certain behaviors, LIKE and FEAR affect the individual’s partner-specific behavioral probabilities. In this way, emotional processes regulate both spontaneous behaviors and appropriate responses to received behaviors, while emotional bookkeeping via LIKE attitudes regulates the development and maintenance of affiliative relations. Using an array of empirical data, the model processes were substantiated and the emerging model patterns were partially validated. The EMO-model offers a framework to investigate the emotional bookkeeping hypothesis theoretically and pinpoints gaps that need to be investigated empirically. PMID:24504194

  20. Effectiveness, tolerability and practical application of the newer generation anti-obesity medications

    Directory of Open Access Journals (Sweden)

    Jeffrey S MacDaniels

    2016-03-01

    Full Text Available Objective: Comparison of the efficacy and tolerability of five newer anti-obesity medications to guide clinical decision making, examining bupropion–naltrexone combination, liraglutide, lorcaserin, orlistat, and phentermine–topiramate combination. Methods: A brief literature review and internet search for high-powered, randomized and placebo-controlled drug trials was conducted. Drug trial information was established for five currently approved anti-obesity medications. Secondarily, a statistical comparison of medications through Number Needed to Treat (NNT and Number Needed to Harm (NNH analyses were attempted as a way to provide a clinical analysis across these varied medications. Finally, a commentary about clinical application is issued for each agent accounting for typical side-effects, serious side-effects, mechanism of action and ease of use. Results: All five agents are currently approved oral medications to lower weight. The NNT range was 3–12, and NNH range was 4–17. The agent with the best NNT is phentermine–topiramate combination (NNT=3 and the agent with the best NNH is bupropion–naltrexone combination (NNH=17. Conclusion: When considering each patient’s clinical presentation, knowledge of each drug’s mechanism of action, side-effect profile, efficacy, and NNT and NNH values can help in selecting an anti-obesity medication to augment his or her weight loss efforts.

  1. Marine Microalgae with Anti-Cancer Properties.

    Science.gov (United States)

    Martínez Andrade, Kevin A; Lauritano, Chiara; Romano, Giovanna; Ianora, Adrianna

    2018-05-15

    Cancer is the leading cause of death globally and finding new therapeutic agents for cancer treatment remains a major challenge in the pursuit for a cure. This paper presents an overview on microalgae with anti-cancer activities. Microalgae are eukaryotic unicellular plants that contribute up to 40% of global primary productivity. They are excellent sources of pigments, lipids, carotenoids, omega-3 fatty acids, polysaccharides, vitamins and other fine chemicals, and there is an increasing demand for their use as nutraceuticals and food supplements. Some microalgae are also reported as having anti-cancer activity. In this review, we report the microalgal species that have shown anti-cancer properties, the cancer cell lines affected by algae and the concentrations of compounds/extracts tested to induce arrest of cell growth. We also report the mediums used for growing microalgae that showed anti-cancer activity and compare the bioactivity of these microalgae with marine anticancer drugs already on the market and in phase III clinical trials. Finally, we discuss why some microalgae can be promising sources of anti-cancer compounds for future development.

  2. A blunted anxiolytic like effect of curcumin against acute lead induced anxiety in rat: involvement of serotonin.

    Science.gov (United States)

    Benammi, Hind; El Hiba, Omar; Romane, Abderrahmane; Gamrani, Halima

    2014-06-01

    Anxiety is one of the most common mental disorders sharing extreme or pathological anxiety states as the primary disturbance in mood or emotional tone, with increased fear and exaggerated acute stress responses. Medicinal plants are very variable, but some of them are used as a spice such as curcumin (Curcuma longa). Curcumin shows a wide range of pharmacological potentialities, however, little is known about its anxiolytic properties. The aim of our study was to assess the anti-anxiety potential of curcumin extract against experimental lead induced-anxiety in rats. Experiments were carried out on male Wistar rats intoxicated acutely with an intraperitoneal injection of Pb (25mg/kg B.W.) and/or concomitantly with administration of curcumin (30 mg/kg B.W.) for 3 days. Using immunohistochemistry and anxiety assessment tests (dark light box and elevated plus maze), we evaluated, respectively, the expression of serotonin (5HT) in the dorsal raphe nucleus (DRN) and the anxiety state in our animals. Our results showed, for the first time, a noticeable anxiolytic effect of curcumin against lead induced anxiety in rats and this may possibly result from modulation of central neuronal monoaminergic neurotransmission, especially serotonin, which has shown a significant reduction of the immunoreactivity within the DRN. Copyright © 2014 Elsevier GmbH. All rights reserved.

  3. Efficacy of intra-meibomian gland injection of the anti-VEGF agent bevacizumab for the treatment of meibomian gland dysfunction with lid-margin vascularity

    Directory of Open Access Journals (Sweden)

    Jiang X

    2018-05-01

    Full Text Available Xiaodan Jiang,* Yuexin Wang,* Huibin Lv, Yan Liu, Mingzhou Zhang, Xuemin Li Department of Ophthalmology, Peking University Third Hospital, Beijing, China *These authors contributed equally to this work Purpose: To investigate the efficacy of a novel treatment – intra-meibomian gland (MG injection of the anti-VEGF agent bevacizumab – for MG dysfunction (MGD with eyelid-margin vascularity. Methods: A total of 26 eyes from 13 patients diagnosed with MGD and eyelid-margin vascularity were included in our study. Patients received intra-meibomian gland injections of bevacizumab (150 µL, 2.5 mg/0.1 mL at multiple sites with a 29 G needle where telangiectasia was severe. The Ocular Surface Disease Index (OSDI, tear film, tear-breakup time (TBUT, eyelid-margin features, MG features, conjunctiva, and corneal staining were assessed at 1 day before injection and 1 week, 1 month, and 3 months after injection. Blood pressure, best-corrected visual acuity, intraocular pressure, and slit lamp examinations were performed to assure the safety of patients at 1 day before and 1 day, 1 week, 1 month, and 3 months after injection. Results: Lid-margin vascularity, conjunctival injection, expressed secretion quality, expressivity of the MG, TBUT, corneal staining, and OSDI were significantly improved 1 week, 1 month, and 3 months after injection compared to baseline values. Lid-margin vascularity, conjunctival injection, meibomian gland expressivity, TBUT, and OSDI continued to improve; the greatest improvements were observed at 1 month and sustained for 3 months. Spearman’s correlation analysis indicated that age and sex significantly influenced TBUT improvement. Females and older patients tended to have shorter baseline TBUT that followed a different trend from that of males and younger patients during postinjection visits, revealed by subgroup analysis. No local or systemic side effects were observed at follow-up visits. Conclusion: This study is the first to

  4. Anti-tumor activity of metformin: from metabolic and epigenetic perspectives

    Science.gov (United States)

    Zhai, Yansheng; Tong, Chong; Liu, Min; Ma, Lixin; Yu, Xiaolan; Li, Shanshan

    2017-01-01

    Metformin has been used to treat type 2 diabetes for over 50 years. Epidemiological, preclinical and clinical studies suggest that metformin treatment reduces cancer incidence in diabetes patients. Due to its potential as an anti-cancer agent and its low cost, metformin has gained intense research interest. Its traditional anti-cancer mechanisms involve both indirect and direct insulin-dependent pathways. Here, we discussed the anti-tumor mechanism of metformin from the aspects of cell metabolism and epigenetic modifications. The effects of metformin on anti-cancer immunity and apoptosis were also described. Understanding these mechanisms will shed lights on application of metformin in clinical trials and development of anti-cancer therapy. PMID:27902459

  5. Biological anti-TNF drugs

    DEFF Research Database (Denmark)

    Prado, Mônica Simon; Bendtzen, Klaus; Andrade, Luis Eduardo Coelho

    2017-01-01

    practice shows a significant percentage of individuals who do not exhibit the desired response. Loss of therapeutic benefit after initial successful response is designated secondary failure. Immune-biological agents are not self-antigens and are therefore potentially immunogenic. Secondary failure...... is frequently caused by antibodies against immune-biologicals, known as anti-drug antibodies (ADA). ADA that neutralize circulating immune-biologicals and/or promote their clearance can reduce treatment efficacy. Furthermore, ADA can induce adverse events by diverse immunological mechanisms. This review...... provides a comprehensive overview of ADA in rheumatoid arthritis patients treated with anti-TNF immune-biologicals, and explores the concept of therapeutic drug monitoring (TDM) as an effective strategy to improve therapeutic management. Expert opinion: Monitoring circulating ADA and therapeutic immune-biological...

  6. Cynaropicrin: a comprehensive research review and therapeutic potential as an anti- hepatitis C virus agent

    Directory of Open Access Journals (Sweden)

    Mahmoud Fahmi Elsebai

    2016-12-01

    Full Text Available The different pharmacologic properties of plants-containing cynaropicrin, especially artichokes, have been known for many centuries. More recently, cynaropicrin exhibited a potential activity against all genotypes of hepatitis C virus (HCV. Cynaropicrin has also shown a wide range of other pharmacologic properties such as anti-hyperlipidemic, anti-trypanosomal, anti-malarial, antifeedant, antispasmodic, anti-photoaging, and anti-tumor action, as well as activation of bitter sensory receptors, and anti-inflammatory properties (e.g., associated with the suppression of the key pro-inflammatory NF-κB pathway. These pharmacological effects are very supportive factors to its outstanding activity against HCV. Structurally, cynaropicrin might be considered as a potential drug candidate, since it has no violations for the rule of five and its water-solubility could allow formulation as therapeutic injections. Moreover, cynaropicrin is a small molecule that can be easily synthesized and as the major constituent of the edible plant artichoke, which has a history of safe dietary use. In summary, cynaropicrin is a promising bioactive natural product that, with minor hit-to-lead optimization, might be developed as a drug for HCV.

  7. Anti-inflammatory and Analgesic Activities of Amorphophallus bulbifer

    African Journals Online (AJOL)

    HP

    time of the animals treated with either standard or extract. Pentazocin ... standard. Results: The extract showed significant anti-inflammatory and analgesic activities at the two test dose ..... effectiveness of analgesic agents in the tail- flick pain ...

  8. Amides of non-steroidal anti-inflammatory drugs with thiomorpholine can yield hypolipidemic agents with improved anti-inflammatory activity.

    Science.gov (United States)

    Theodosis-Nobelos, Panagiotis; Kourti, Malamati; Gavalas, Antonios; Rekka, Eleni A

    2016-02-01

    Novel amides of non steroidal anti-inflammatory drugs (NSAIDs), α-lipoic acid and indole-3-acetic acid with thiomorpholine were synthesised by a simple method and at high yields (60-92%). All the NSAID derivatives highly decreased lipidemic indices in the plasma of Triton treated hyperlipidemic rats. The most potent compound was the indomethacin derivative, which decreased total cholesterol, triglycerides and LDL cholesterol by 73%, 80% and 83%, respectively. They reduced acute inflammation equally or more than most parent acids. Hence, it could be concluded that amides of common NSAIDs with thiomorpholine acquire considerable hypolipidemic potency, while they preserve or augment their anti-inflammatory activity, thus addressing significant risk factors for atherogenesis. Copyright © 2015 Elsevier Ltd. All rights reserved.

  9. Current Status of Doping in Japan Based on Japan Anti-Doping Disciplinary Panels of the Japan Anti-Doping Agency (JADA): A Suggestion on Anti-Doping Activities by Pharmacists in Japan.

    Science.gov (United States)

    Imanishi, Takashi; Kawabata, Takayoshi; Takayama, Akira

    2017-01-01

    In 2009, the Japan Anti-Doping Agency (JADA) established the "Sports Pharmacist Accreditation Program" to prevent doping in sports. Since then, anti-doping activities in Japan have been attracting attention. In this study, we investigated research about the current status of doping from 2007 to 2014 in Japan to make anti-doping activities more concrete, and we also discussed future anti-doping activities by pharmacists. In Japan, bodybuilding was the sporting event with the highest number and rate of doping from 2007 to 2014. Many of the positive doping cases were detected for class S1 (anabolic agents), S5 (diuretics and masking agents), and S6 (stimulants). Within class S1, supplements were the main cause of positive doping. Within class S5, medicines prescribed by medical doctors were the main cause of positive doping. Within class S6, non-prescription medicines (e.g., OTC) were the main cause of positive doping. When we looked at the global statistics on doping, many of the positive doping cases were detected for class S1. On comparing the Japanese statistics with the global statistics, the rate of positive doping caused by class S1 was significantly lower, but that caused by classes S5 and S6 was significantly higher in Japan than in the world. In conclusion, pharmacists in Japan should pay attention to class S1, S5, and S6 prohibited substances and to the sport events of bodybuilding. Based on this study, sports pharmacists as well as common pharmacists should suggest new anti-doping activities to prevent doping in the future.

  10. Fibrous guided tissue regeneration membrane loaded with anti-inflammatory agent prepared by coaxial electrospinning for the purpose of controlled release

    Energy Technology Data Exchange (ETDEWEB)

    He, Min; Xue, Jiajia [Beijing Laboratory of Biomedical Materials, Beijing University of Chemical Technology, Beijing 100029 (China); Geng, Huan; Gu, Hao [State Key Laboratory of Organic–Inorganic Composites, Beijing University of Chemical Technology, Beijing 100029 (China); Chen, Dafu [Laboratory of Bone Tissue Engineering of Beijing Research Institute of Traumatology and Orthopaedics, Beijing 100035 (China); Shi, Rui, E-mail: sharell@126.com [Laboratory of Bone Tissue Engineering of Beijing Research Institute of Traumatology and Orthopaedics, Beijing 100035 (China); Zhang, Liqun, E-mail: zhanglq@mail.buct.edu.cn [Beijing Laboratory of Biomedical Materials, Beijing University of Chemical Technology, Beijing 100029 (China); State Key Laboratory of Organic–Inorganic Composites, Beijing University of Chemical Technology, Beijing 100029 (China)

    2015-04-30

    Graphical abstract: The metronidazole released from PCL/gelatin core/sheath nanofiber membranes can effectively inhibit the colonization of anerobic bacteria. - Highlights: • Core/sheath PCL/gelatin nanofiber membrane loaded with metronidazole in a wide range of drug loading (5–35 wt.%) were successfully fabricated in good quality. • The encapsulation of gelatin can effectively alleviate the initial burst release of drugs. • The membrane can inhibit the growth of bacteria as the drug content reaches 10% (w/w), and the bacterial inhibition ability can effectively last at least 4 weeks. • The encapsulation of gelatin can overcome the disadvantage of PCL's hydrophobicity, which can effectively promote the adhesion and proliferation of cells. - Abstract: Here, with the aim of inhibiting inflammation during guided tissue regeneration membrane (GTRM) implant surgery, coaxial electrospinning was used to fabricate drug-loaded core/sheath nanofiber GTRMs capable of controlled drug release. Various amounts of the anti-inflammatory agent metronidazole (MNA) were encapsulated into the core/sheath nanofibers (where PCL was the core, gelatin the sheath, and the gelatin shell was crosslinked with genipin) in order to establish the minimal drug content necessary to achieve the appropriate anti-inflammatory effect. By using TEM and SEM, the core/sheath structure was confirmed. In vitro drug disolution results showed that the core/sheath nanofibers exhibited sustained release profiles that were superior to those nanofibers produced by blending electrospinning. Additionally, the membrane significantly inhibited the colonization of anaerobic bacteria. Furthermore, with gelatin as a shell, the core/shell nanofiber membranes showed improved hydrophilicity, which resulted in better cell adhesion and proliferation without cytotoxicity. Therefore, in this study, a simple and effective coaxial electrospinning approach was demonstrated for the fabrication of anti

  11. Anti-TNFα agents and methotrexate in spondyloarthritis related uveitis in a Chinese population.

    Science.gov (United States)

    Lian, Fan; Zhou, Jun; Wei, Cui; Wang, Yu; Xu, Hanshi; Liang, Liuqin; Yang, Xiuyan

    2015-11-01

    This study seeks to evaluate the clinical characteristics of spondyloarthritis (SpA)-related uveitis in a cohort from South China and to assess the efficacy and safety of therapies based on TNF blockers. SpA patients with uveitis admitted to a south China hospital were enrolled. Demographic information, clinical characteristics, laboratory findings, intraocular inflammation, visual acuity, macular thickness, and treatments were documented. Of the 1,036 SpA patients reviewed, 182 had uveitis. Ankylosing spondylitis (AS) was the most common subtype. Unilateral uveitis was found in 51 cases (51/182, 28.0%), and unilateral alternating uveitis was found in 75 cases (75/182, 41.2%). Half of the cases were recurrent uveitis (52.2%), and acute onset was common (76.4%). The most serious complication was vision loss (0.5%). No significant difference in disease activity was found between the SpA patients with or without uveitis. Predominant improvements were found in cases treated with all three anti-TNFs (infliximab, adalimumab, and etanercept) and anti-TNFs plus methotrexate (MTX). Monotherapy of methotrexate was not adequate for inducing remission. Monotherapy of etanercept was not as effective as adalimumab and infliximab, mainly in the prevention of recurrence. No significant difference in effectiveness was found among the three anti-TNFs if MTX was added. Etanercept plus MTX were well tolerated. Infliximab and adalimumab were associated with more tuberculosis and/or hepatitis flares. Uveitis is common in SpA patients. Severe complications may develop in prolonged and intractable cases. Treatments based on anti-TNFs had good clinical response, and better safety documentation were observed in etanercept plus MTX compared to the other two anti-TNF monoclonal antibodies plus MTX.

  12. A “Mini-Epidemic” of anti-glomerular basement membrane disease: Clinical and epidemiological study

    Directory of Open Access Journals (Sweden)

    Umesh Lingaraj

    2017-01-01

    Full Text Available Acute glomerulonephritis due to anti-glomerular basement membrane (anti-GBM antibody disease is rare, estimated to occur in fewer than one case per million population and accounts for less than 20% of rapidly progressive glomerulonephritis. The prevalence among patients evaluated for potential glomerular disease is lower. It accounts for fewer than 3% of all kidney biopsies done with crescentic glomerulonephritis. Cases of anti-GBM disease occurring in a cluster have rarely been reported. All biopsy proven anti-GBM disease cases were collected from January 2015 to March 2015 at our Institute. All cases were analyzed for demographic and clinical profile, pathological findings, treatment received and for any common environmental antigenic source. A total of 11 new biopsy proven anti-GBM cases were seen within a span of three months. Age group varied from 17–80 years. Seven were males and four were females. All were dialysis dependent at presentation. Seven had active cellular crescents, and four had fibrocellular. Only one patient was a smoker and none had a history of exposure to any forms of hydrocarbons. The peak seen from January 2015 to March 2015 does not correlate with any of seasonal occurrence of infections in southern India. Although there was clustering of cases to southern territories of Karnataka state, no common etiological agents could be identified. No patient had any previous urological surgeries. All patients received methylprednisolone with plasmapheresis 5–7 sessions and cyclophosphamide. All 11 patients were dialysis dependent at the end of three months. We conclude anti-GBM disease cannot be regarded as a rare cause of renal failure and lung hemorrhage. The occurrence of such epidemic within a short period suggests a possible unidentified environmental factor like infection or occupational agents as inciting agents. Identification of such inciting agents could help us in instituting appropriate preventing measures.

  13. Neurobiology of anxiety disorders and implications for treatment.

    Science.gov (United States)

    Garakani, Amir; Mathew, Sanjay J; Charney, Dennis S

    2006-11-01

    The neurobiology of the anxiety disorders, which include panic disorder, post-traumatic stress disorder (PTSD), and specific phobias, among others, has been clarified by advances in the field of classical or Pavlovian conditioning, and in our understanding of basic mechanisms of memory and learning. Fear conditioning occurs when a neutral conditioned stimulus (such as a tone) is paired with an aversive, or unconditioned stimulus (such as a footshock), and then in the absence of the unconditioned stimulus, causes a conditioned fear response. Preclinical studies have shown that the amygdala plays a key role in fear circuitry, and that abnormalities in amygdala pathways can affect the acquisition and expression of fear conditioning. Drugs such as glutamate N-methyl-D-aspartate (NMDA) antagonists, and blockers of voltage-gated calcium channels, in the amygdala, may block these effects. There is also preliminary evidence for the use of centrally acting beta-adrenergic antagonists, like propranolol, to inhibit consolidation of traumatic memories in PTSD. Finally, fear extinction, which entails new learning of fear inhibition, is central to the mechanism of effective anti-anxiety treatments. Several pharmacological manipulations, such as D-cycloserine, a partial NMDA agonist, have been found to facilitate extinction. Combining these medication approaches with psychotherapies that promote extinction, such as cognitive behavioral therapy (CBT), may offer patients with anxiety disorders a rapid and robust treatment with good durability of effect.

  14. Pathogen- and host-directed anti-inflammatory activities of macrolide antibiotics.

    Science.gov (United States)

    Steel, Helen C; Theron, Annette J; Cockeran, Riana; Anderson, Ronald; Feldman, Charles

    2012-01-01

    Macrolide antibiotics possess several, beneficial, secondary properties which complement their primary antimicrobial activity. In addition to high levels of tissue penetration, which may counteract seemingly macrolide-resistant bacterial pathogens, these agents also possess anti-inflammatory properties, unrelated to their primary antimicrobial activity. Macrolides target cells of both the innate and adaptive immune systems, as well as structural cells, and are beneficial in controlling harmful inflammatory responses during acute and chronic bacterial infection. These secondary anti-inflammatory activities of macrolides appear to be particularly effective in attenuating neutrophil-mediated inflammation. This, in turn, may contribute to the usefulness of these agents in the treatment of acute and chronic inflammatory disorders of both microbial and nonmicrobial origin, predominantly of the airways. This paper is focused on the various mechanisms of macrolide-mediated anti-inflammatory activity which target both microbial pathogens and the cells of the innate and adaptive immune systems, with emphasis on their clinical relevance.

  15. Developmental trajectories of anxiety symptoms in early adolescence: the influence of anxiety sensitivity.

    Science.gov (United States)

    Allan, Nicholas P; Capron, Daniel W; Lejuez, Carl W; Reynolds, Elizabeth K; MacPherson, Laura; Schmidt, Norman B

    2014-05-01

    Children and adolescents seem to suffer from anxiety disorders at rates similar to adults. Interestingly, anxiety symptoms appear to generally decline over time within children as evidenced by lower rates in early and middle adolescence. There is some evidence that there may be heterogeneous subpopulations of adolescent children with different trajectories of anxiety symptoms, including a class of adolescents with elevated levels of anxiety that do not dissipate over time. Anxiety sensitivity has been identified as an important risk factor in the development of anxiety psychopathology. This study prospectively examined the development of anxiety symptoms in a sample of 277 adolescents (M age = 11.52; 44 % female, 56 % male) over a 3 year period including the influence of anxiety sensitivity on this development. Further, this study investigated whether there were distinct classes of adolescents based on their anxiety symptom trajectories and including anxiety sensitivity as a predictor. Consistent with other reports, findings indicated an overall decline in anxiety symptoms over time in the sample. However, three classes of adolescents were found with distinct anxiety symptom trajectories and anxiety sensitivity was an important predictor of class membership. Adolescents with elevated anxiety sensitivity scores were more likely to be classified as having high and increasing anxiety symptoms over time versus having moderate to low and decreasing anxiety symptoms over time. There are important implications for identification of adolescents and children who are at risk for the development of an anxiety disorder.

  16. The use of intravitreal anti-vascular endothelial growth factor injection and its complications in Chiang Mai University Hospital.

    Science.gov (United States)

    Kunavisarut, Paradee; Saenpen, Nithiracht; Ittipunkul, Nimitr; Patikulsila, Direk; Choovuthayakorn, Janejit; Watanachai, Nawat; Pathanapitoon, Kessara

    2013-11-01

    To report the use of intravitreal (IVT) injections of anti-vascular endothelial growth factor agents (anti-VEGF) and its complications. The authors performed a retrospective review of consecutive patients treated with IVT injection of anti-VEGF between May 2006 and December 2010 at Chiang Mai University Hospital. Demographic data and complications were registered. The present study included 1,006 eyes of 878 patients. Mean age was 60 years (range 1 month to 91 years). Mean follow-up time was 12 months (range 1 month to 54 months). Total injections were 2,077 given as 47, 210, 399, 575, and 846 injection per year between 2006 and 2010, respectively. Anti-VEGF agents were bevacizumab (1,878; 90.42%), ranibizumab (190; 9.15%), and pegaptanib (9; 0.43%). Indications for injection based on primary diagnosis were neovascular macular degeneration (38.5%), diabetic retinopathy (38%), and retinal vein occlusion (15.9%). The incidence of endophthalmitis was 0.048% (1/2,077) for all injections and 0.053% (1/1878)for bevacizumab. The use of IVT injections of anti-VEGF is increasing, especially the use of bevacizumab. Incidence of ocular and systemic complications after IVT injection of anti- VEGF was low with no significant difference among the three anti-VEGFs agents.

  17. Effects of psychotropic agents on extinction of lever-press avoidance in a rat model of anxiety vulnerability

    Directory of Open Access Journals (Sweden)

    Xilu eJiao

    2014-09-01

    Full Text Available Avoidance and its perseveration represent key features of anxiety disorders. Both pharmacological and behavioral approaches (i.e. anxiolytics and extinction therapy have been utilized to modulate avoidance behavior in patients. However, the outcome has not always been desirable. Part of the reason is attributed to the diverse neuropathology of anxiety disorders. Here, we investigated the effect of psychotropic drugs that target various monoamine systems on extinction of avoidance behavior using lever-press avoidance task. Here we used the Wistar-Kyoto (WKY rat, a unique rat model that exhibits facilitated avoidance and extinction resistance along with malfunction of the dopamine (DA system. Sprague Dawley (SD and WKY rats were trained to acquire lever-press avoidance. WKY rats acquired avoidance faster and to a higher level compared to SD rats. During pharmacological treatment, bupropion, and desipramine significantly reduced avoidance response selectively in WKY rats. However, after the discontinuation of drug treatment, only those WKY rats that were previously treated with desipramine exhibited lower avoidance response compared to the control group. In contrast, none of the psychotropic drugs facilitated avoidance extinction in SD rats. Instead, desipramine impaired avoidance extinction and increased non-reinforced response in SD rats. Interestingly, paroxetine, a widely used antidepressant and anxiolytic, exhibited the weakest effect in WKY rats and no effects at all in SD rats. Thus, our data suggest that malfunctions in brain catecholamine system could be one of the underlying etiologies of anxiety-like behavior, particularly avoidance perseveration. Pharmacological manipulation targeting DA and norepinephrine is more effective to facilitate extinction learning in this strain. The data from the present study may shed light on new pharmacological approaches to treat patients with anxiety disorders who are not responding to serotonin re

  18. Detecting the severity of perinatal anxiety with the Perinatal Anxiety Screening Scale (PASS).

    Science.gov (United States)

    Somerville, Susanne; Byrne, Shannon L; Dedman, Kellie; Hagan, Rosemary; Coo, Soledad; Oxnam, Elizabeth; Doherty, Dorota; Cunningham, Nadia; Page, Andrew C

    2015-11-01

    The Perinatal Anxiety Screening Scale (PASS; Somerville et al., 2014) reliably identifies perinatal women at risk of problematic anxiety when a clinical cut-off score of 26 is used. This study aimed to identify a severity continuum of anxiety symptoms with the PASS to enhance screening, treatment and research for perinatal anxiety. Antenatal and postnatal women (n=410) recruited from the antenatal clinics and mental health services at an obstetric hospital completed the Edinburgh Postnatal Depression Scale (EPDS), the Depression, Anxiety and Stress Scale (DASS-21), the Spielberg State-Trait Anxiety Inventory (STAI), the Beck Depression Inventory II (BDI), and the PASS. The women referred to mental health services were assessed to determine anxiety diagnoses via a diagnostic interview conducted by an experienced mental health professional from the Department of Psychological Medicine - King Edward Memorial Hospital. Three normative groups for the PASS, namely minimal anxiety, mild-moderate anxiety, and severe anxiety, were identified based on the severity of anxiety indicated on the standardised scales and anxiety diagnoses. Two cut-off points for the normative groups were calculated using the Jacobson-Truax method (Jacobson and Truax, 1991) resulting in three severity ranges: 'minimal anxiety'; 'mild-moderate anxiety'; and 'severe anxiety'. The most frequent diagnoses in the study sample were adjustment disorder, mixed anxiety and depression, generalised anxiety, and post-traumatic stress disorder. This may limit the generalisability of the severity range results to other anxiety diagnoses including obsessive compulsive disorder and specific phobia. Severity ranges for the PASS add value to having a clinically validated cut-off score in the detection and monitoring of problematic perinatal anxiety. The PASS can now be used to identify risk of an anxiety disorder and the severity ranges can indicate developing risk for early referrals for further assessments

  19. Laboratory evaluation of anti-biofilm agents for use in dental unit waterlines.

    Science.gov (United States)

    Meiller, T F; Kelley, J I; Baqui, A A; DePaola, L G

    2001-01-01

    Dental unit waterline biofilm has been recognized as a potential point of contamination and a risk to patients with any level of immunocompromise. Biofilm in dental unit waterlines, once established, has proven formidable to efforts in disinfection/disruption. This project compared standardized evaluation techniques by assessing the efficacy of a variety of agents that have been reported or suggested as useful in surface disinfection and/or antiseptic protocols. The zones of inhibition, minimum inhibitory/bactericidal concentrations and use-dilution with stainless steel carrier replicates tests assessed the disinfection of planktonic organisms using standardized microbial testing procedures. The disruption and/or disinfection of planktonic and biofilm organisms within naturally occurring dental unit waterlines were evaluated by culture and scanning electron microscopy. The six commercially available antimicrobial agents used to assess the techniques were bleach (sodium hypochlorite), Cavicide, glutaraldehyde, Listerine Antiseptic, Peridex and Sterilex Ultra. Comparisons between the results for each technique evaluated were determined for each product. All six agents demonstrated antimicrobial efficacy at the working concentrations designated by the manufacturers. Biofilm matrix elimination evaluated by scanning electron microscopy found virtually 0% elimination by glutaraldehyde to an estimated 90% elimination by Sterilex Ultra and bleach after one treatment. Treatment with Cavicide, Listerine Antiseptic and Peridex resulted in negligible elimination of the biofilm matrix. For comparability, the use of standardized testing techniques to evaluate a disinfection agent's efficacy against dental unit waterline contamination is essential. This project demonstrates a model system for evaluating disinfection agents potentially useful in the management of dental unit waterline biofilm, and should assist in educating the dental clinician in the appraisal of existing and

  20. Logical design of anti-prion agents using NAGARA

    Energy Technology Data Exchange (ETDEWEB)

    Ma, Biao; Yamaguchi, Keiichi; Fukuoka, Mayuko [United Graduate School of Drug Discovery and Medical Information Sciences, Gifu University, 1-1 Yanagido, Gifu 501-1193 (Japan); Kuwata, Kazuo, E-mail: kuwata@gifu-u.ac.jp [United Graduate School of Drug Discovery and Medical Information Sciences, Gifu University, 1-1 Yanagido, Gifu 501-1193 (Japan); Department of Gene and Development, Graduate School of Medicine, Gifu University, 1-1 Yanagido, Gifu 501-1193 (Japan)

    2016-01-22

    To accelerate the logical drug design procedure, we created the program “NAGARA,” a plugin for PyMOL, and applied it to the discovery of small compounds called medical chaperones (MCs) that stabilize the cellular form of a prion protein (PrP{sup C}). In NAGARA, we constructed a single platform to unify the docking simulation (DS), free energy calculation by molecular dynamics (MD) simulation, and interfragment interaction energy (IFIE) calculation by quantum chemistry (QC) calculation. NAGARA also enables large-scale parallel computing via a convenient graphical user interface. Here, we demonstrated its performance and its broad applicability from drug discovery to lead optimization with full compatibility with various experimental methods including Western blotting (WB) analysis, surface plasmon resonance (SPR), and nuclear magnetic resonance (NMR) measurements. Combining DS and WB, we discovered anti-prion activities for two compounds and tegobuvir (TGV), a non-nucleoside non-structural protein NS5B polymerase inhibitor showing activity against hepatitis C virus genotype 1. Binding profiles predicted by MD and QC are consistent with those obtained by SPR and NMR. Free energy analyses showed that these compounds stabilize the PrP{sup C} conformation by decreasing the conformational fluctuation of the PrP{sup C}. Because TGV has been already approved as a medicine, its extension to prion diseases is straightforward. Finally, we evaluated the affinities of the fragmented regions of TGV using QC and found a clue for its further optimization. By repeating WB, MD, and QC recursively, we were able to obtain the optimum lead structure. - Highlights: • NAGARA integrates docking simulation, molecular dynamics, and quantum chemistry. • We found many compounds, e.g., tegobuvir (TGV), that exhibit anti-prion activities. • We obtained insights into the action mechanism of TGV as a medical chaperone. • Using QC, we obtained useful information for optimization of the

  1. Anti-Candida albicans biofilm effect of novel heterocyclic compounds.

    Science.gov (United States)

    Kagan, Sarah; Jabbour, Adel; Sionov, Edward; Alquntar, Abed A; Steinberg, Doron; Srebnik, Morris; Nir-Paz, Ran; Weiss, Aryeh; Polacheck, Itzhack

    2014-02-01

    The aims of this study were to develop new anti-biofilm drugs, examine their activity against Candida albicans biofilm and investigate their structure-activity relationship and mechanism of action. A series of thiazolidinedione and succinimide derivatives were synthesized and their ability to inhibit C. albicans biofilm formation and destroy pre-formed biofilm was tested. The biofilms' structure, metabolic activity and viability were determined by XTT assay and propidium iodide and SYTO 9 live/dead stains combined with confocal microscopic analysis. The effect of the most active compounds on cell morphology, sterol distribution and cell wall morphology and composition was then determined by specific fluorescent stains and transmission electron microscopy. Most of the compounds were active at sub-MICs. Elongation of the aliphatic side chain resulted in reduced anti-biofilm activity and the sulphur atom contributed to biofilm killing, indicating a structure-activity relationship. The compounds differed in their effects on biofilm viability, yeast-to-hyphal form transition, hyphal morphology, cell wall morphology and composition, and sterol distribution. The most effective anti-biofilm compounds were the thiazolidinedione S8H and the succinimide NA8. We developed novel anti-biofilm agents that both inhibited and destroyed C. albicans biofilm. With some further development, these agents might be suitable for therapeutic purposes.

  2. Anxiety and depressive symptoms and medical illness among adults with anxiety disorders.

    Science.gov (United States)

    Niles, Andrea N; Dour, Halina J; Stanton, Annette L; Roy-Byrne, Peter P; Stein, Murray B; Sullivan, Greer; Sherbourne, Cathy D; Rose, Raphael D; Craske, Michelle G

    2015-02-01

    Anxiety is linked to a number of medical conditions, yet few studies have examined how symptom severity relates to medical comorbidity. The current study assessed associations between severity of anxiety and depression and the presence of medical conditions in adults diagnosed with anxiety disorders. Nine-hundred eighty-nine patients diagnosed with panic, generalized anxiety, social anxiety, and posttraumatic stress disorders reported on the severity of anxiety and depressive symptoms and on diagnoses of 11 medical conditions. Severity of anxiety and depressive symptoms was strongly associated with having more medical conditions over and above control variables, and the association was as strong as that between BMI and disease. Odds of having asthma, heart disease, back problems, ulcer, migraine headache and eyesight difficulties also increased as anxiety and depressive symptom severity increased. Anxiety symptoms were independently associated with ulcer, whereas depressive symptoms were independently associated with heart disease, migraine, and eyesight difficulties. These findings add to a growing body of research linking anxiety disorders with physical health problems and indicate that anxiety and depressive symptoms deserve greater attention in their association with disease. Copyright © 2014 Elsevier Inc. All rights reserved.

  3. Arzanol, a Potent mPGES-1 Inhibitor: Novel Anti-Inflammatory Agent

    Directory of Open Access Journals (Sweden)

    Pankaj S. Kothavade

    2013-01-01

    Full Text Available Arzanol is a novel phloroglucinol α-pyrone, isolated from a Mediterranean plant Helichrysum italicum (Roth Don ssp. microphyllum which belongs to the family Asteraceae. Arzanol has been reported to possess a variety of pharmacological activities. However, anti-inflammatory, anti-HIV, and antioxidant activities have been studied in some detail. Arzanol has been reported to inhibit inflammatory transcription factor NFκB activation, HIV replication in T cells, releases of IL-1β, IL-6, IL-8, and TNF-α, and biosynthesis of PGE2 by potentially inhibiting mPGES-1 enzyme. Diversity of mechanisms of actions of arzanol may be useful in treatment of disease involving these inflammatory mediators such as autoimmune diseases and cancer. This review presents comprehensive information on the chemistry, structure-activity relationship, and pharmacological activities of arzanol. In addition this review discusses recent developments and the scope for future research in these aspects.

  4. Arzanol, a Potent mPGES-1 Inhibitor: Novel Anti-Inflammatory Agent

    Science.gov (United States)

    Kothavade, Pankaj S.; Nagmoti, Dnyaneshwar M.; Bulani, Vipin D.; Juvekar, Archana R.

    2013-01-01

    Arzanol is a novel phloroglucinol α-pyrone, isolated from a Mediterranean plant Helichrysum italicum (Roth) Don ssp. microphyllum which belongs to the family Asteraceae. Arzanol has been reported to possess a variety of pharmacological activities. However, anti-inflammatory, anti-HIV, and antioxidant activities have been studied in some detail. Arzanol has been reported to inhibit inflammatory transcription factor NFκB activation, HIV replication in T cells, releases of IL-1β, IL-6, IL-8, and TNF-α, and biosynthesis of PGE2 by potentially inhibiting mPGES-1 enzyme. Diversity of mechanisms of actions of arzanol may be useful in treatment of disease involving these inflammatory mediators such as autoimmune diseases and cancer. This review presents comprehensive information on the chemistry, structure-activity relationship, and pharmacological activities of arzanol. In addition this review discusses recent developments and the scope for future research in these aspects. PMID:24198734

  5. Contributions of fluoride to the sensitivity of oral isolates to some anti ...

    African Journals Online (AJOL)

    Objective: Plaque formation on teeth surfaces, gingivitis and caries has been associated with the presence and activities of oral flora; and several agents have been demonstrated to exhibit anti-plaque potentials. This Study is designed to evaluate the inhibitory potentials of some agents on fluoride-exposed and ...

  6. Targeted delivery of anti-tuberculosis drugs to macrophages: targeting mannose receptors

    Science.gov (United States)

    Filatova, L. Yu; Klyachko, N. L.; Kudryashova, E. V.

    2018-04-01

    The development of systems for targeted delivery of anti-tuberculosis drugs is a challenge of modern biotechnology. Currently, these drugs are encapsulated in a variety of carriers such as liposomes, polymers, emulsions and so on. Despite successful in vitro testing of these systems, virtually no success was achieved in vivo, because of low accessibility of the foci of infection located in alveolar macrophage cells. A promising strategy for increasing the efficiency of therapeutic action of anti-tuberculosis drugs is to encapsulate the agents into mannosylated carriers targeting the mannose receptors of alveolar macrophages. The review addresses the methods for modification of drug substance carriers, such as liposomes and biodegradable polymers, with mannose residues. The use of mannosylated carriers to deliver anti-tuberculosis agents increases the drug circulation time in the blood stream and increases the drug concentration in alveolar macrophage cells. The bibliography includes 113 references.

  7. B Lymphocytes in Rheumatoid Arthritis and the Effects of Anti-TNF-α Agents on B Lymphocytes: A Review of the Literature.

    Science.gov (United States)

    Pala, Ozlem; Diaz, Alain; Blomberg, Bonnie B; Frasca, Daniela

    2018-05-22

    The aim of this article was to review published research related to B lymphocytes in rheumatoid arthritis, their role in the pathogenesis of the disease, the effects of tumor necrosis factor (TNF)-α inhibitors on B lymphocytes, the risk for infection, and responses to vaccines. A PubMed search was conducted to review recent advances related to B lymphocytes and the effects of anti-TNF-α on B lymphocytes in rheumatoid arthritis. B lymphocytes play an important role in the pathogenesis of rheumatoid arthritis. In this review, we summarize the major mechanisms by which B lymphocytes play a pathologic role in the development and propagation of the disease, as B lymphocytes are recruited to the synovial fluid, where they contribute to local inflammation through the secretion of pro-inflammatory mediators (cytokines, chemokines, micro-RNAs) and present antigens to T cells. We discuss the effects of TNF-α, either direct or indirect, on B lymphocytes expressing receptors for this cytokine. We also show that total B-cell numbers have been reported to be reduced in the blood of patients with rheumatoid arthritis versus healthy controls, but are significantly increased up to normal levels in patients undergoing anti-TNF-α therapy. As for B-cell subsets, controversial results have been reported, with studies showing decreased frequencies of total memory B cells (and memory subsets) and others showing no differences in patients versus healthy controls. Studies investigating the effects of anti-TNF-α therapy have also given controversial results, with therapy found to increase (or not) the frequency of memory B lymphocytes, in patients with rheumatoid arthritis versus healthy controls. Those highly variable results could have been due to differences in patient characteristics and limited numbers of subjects. Finally, we summarize the effects of blocking TNF-α with anti-TNF-α agents on possible infections that patients with rheumatoid arthritis may contract, as well as on

  8. Radioiodination of monoclonal antibody intact anti-CEA

    International Nuclear Information System (INIS)

    Okada, H.; Souza, I.T.T.; Silva, C.P.G.

    1990-11-01

    The purpose of this study is to examine a convenient system that can be used to iodinate monoclonal antibodies which is rapid, simple, efficient and reproducible, and which can be accomplished in radiopharmaceutical laboratories. It is important to remember that antibodies are sensitive biochemicals, subject to losses of the activity that is essential to their mode of action, namely the ability to bind specific antigen. The advent of solid phase iodination agents has greatly expanded the range of gentle iodination techniques available for iodinating sensitive biological materials. The agent most widely used is the Iodogen (1,3,4,6 tetrachloro-3a-6a diphenylglycoluril) method. Anti-CEA 4C sub(11) IgG sub(2a,k) (prepared in the Ludwig Institute-Sao Paulo-Brazil ) is used as model to evaluate the Iodogen methodology. The miniature chromatographic system, also rapid, accurate, simple, efficient was elaborated to determine the labelling efficiency incorporation of iodine into immunoglobulin, and the radiochemical purity of sup(131)I-anti-CEA. (author)

  9. Neuroprotective and Anti-Aging Potentials of Essential Oils from Aromatic and Medicinal Plants.

    Science.gov (United States)

    Ayaz, Muhammad; Sadiq, Abdul; Junaid, Muhammad; Ullah, Farhat; Subhan, Fazal; Ahmed, Jawad

    2017-01-01

    The use of essential oils (EOs) and their components is known since long in traditional medicine and aromatherapy for the management of various diseases, and is further increased in the recent times. The neuroprotective and anti-aging potentials of EOs and their possible mechanism of actions were evaluated by numerous researchers around the globe. Several clinically important EOs and their components from Nigella sativa , Acorus gramineus, Lavandula angustifolia, Eucalyptus globulus, Mentha piperita, Rosmarinus officinalis, Jasminum sambac, Piper nigrum and so many other plants are reported for neuroprotective effects. This review article was aimed to summarize the current finding on EOs tested against neurodegenerative disorders like Alzheimer disease (AD) and dementia. The effects of EOs on pathological targets of AD and dementia including amyloid deposition (Aβ), neurofibrillary tangles (NFTs), cholinergic hypofunction, oxidative stress and glutamatergic abnormalities were focused. Furthermore, effects of EOs on other neurological disorders including anxiety, depression, cognitive hypofunction epilepsy and convulsions were also evaluated in detail. In conclusion, EOs were effective on several pathological targets and have improved cognitive performance in animal models and human subjects. Thus, EOs can be developed as multi-potent agents against neurological disorders with better efficacy, safety and cost effectiveness.

  10. Treatment of obesity: an update on anti-obesity medications.

    Science.gov (United States)

    Halpern, A; Mancini, M C

    2003-02-01

    The information presented in this article provides an overview of physiological agents, therapeutics in current use, and medications that have been extensively used in the past but are no longer available, or are not classically considered as anti-obesity drugs. The authors present an extensive review on the criteria for anti-obesity management efficacy, on physiological mechanisms that regulate central and/or peripheral action energetic homeostasis (nutrients, monoamines and peptides), and on beta-phenethylamine pharmacological-derivative agents (fenfluramine, dexfenfluramine, phentermine, diethylpropion, fenproporex and sibutramine), tricyclic derivatives (mazindol), phenylpropanolamine derivatives (ephedrine, phenylpropanolamine), a phenylpropanolamine oxy-tri-fluor-phenyl derivative (fluoxetine), a naftilamine derivative (sertraline) and a lipstatine derivative (orlistat). An analysis of all clinical trials longer than 10 weeks in duration is also presented for medications used in the management of obesity.

  11. Lansoprazole-sulfide, pharmacokinetics of this promising anti-tuberculous agent.

    Science.gov (United States)

    Mdanda, Sipho; Baijnath, Sooraj; Shobo, Adeola; Singh, Sanil D; Maguire, Glenn E M; Kruger, Hendrik G; Arvidsson, Per I; Naicker, Tricia; Govender, Thavendran

    2017-12-01

    Lansoprazole (LPZ) is a commercially available proton-pump inhibitor whose primary metabolite, lansoprazole sulfide (LPZS) was recently reported to have in vitro and in vivo activity against Mycobacterium tuberculosis. It was also reported that a 300 mg kg -1 oral administration of LPZS was necessary to reach therapeutic levels in the lung, with the equivalent human dose being unrealistic. A validated liquid chromatography-tandem mass spectrometric method (LC-MS/MS) for the simultaneous quantification LPZ and LPZS in rat plasma and lung homogenates was developed. We administered 15 mg kg -1 oral doses of LPZ to a healthy rat model to determine the pharmacokinetics of its active metabolite, LPZS, in plasma and lung tissue. We found that the LPZS was present in amounts that were below the limit of quantification. This prompted us to administer the same dose of LPZS to the experimental animals intraperitoneally (i.p.). Using this approach, we found high concentrations of LPZS in plasma and lung, 7841.1 and 9761.2 ng mL -1 , respectively, which were significantly greater than the minimum inhibitory concentration (MIC) for Mycobacterium tuberculosis. While oral and i.p. administration of LPZ resulted in significant concentrations in the lung, it did not undergo sufficient cellular conversion to its anti-TB metabolite. However, when LPZS itself was administered i.p., significant amounts penetrated the tissue. These results have implications for future in vivo studies exploring the potential of LPZS as an anti-TB compound. Copyright © 2017 John Wiley & Sons, Ltd.

  12. Seagrass as a potential source of natural antioxidant and anti-inflammatory agents.

    Science.gov (United States)

    Yuvaraj, N; Kanmani, P; Satishkumar, R; Paari, A; Pattukumar, V; Arul, V

    2012-04-01

    Halophila spp. is a strong medicine against malaria and skin diseases and is found to be very effective in early stages of leprosy. Seagrasses are nutraceutical in nature and therefore of importance as food supplements. The antibacterial, antioxidant, and anti-inflammatory activities of Halophila ovalis R. Br. Hooke (Hydrocharitaceae) methanol extract were investigated and the chemical constituents of purified fractions were analyzed. Plant materials were collected from Pondicherry coastal line, and antimicrobial screening of crude extract, and purified fractions was carried out by the disc diffusion method and the minimum inhibitory concentration (MICs) of the purified fractions and reference antibiotics were determined by microdilution method. Antioxidant and anti-inflammatory activities were investigated in vitro. Chemical constituents of purified fractions V and VI were analyzed by gas chromatography-mass spectrometry (GC-MS), and the phytochemicals were quantitatively determined. Methanol extract inhibited the growth of Bacillus cereus at a minimum inhibitory concentration of 50 µg/mL and other Gram-negative pathogens at 75 µg/ml, except Vibrio vulnificus. Reducing power and total antioxidant level increased with increasing extract concentration. H. ovalis exhibited strong scavenging activity on 2,2-diphenyl-1-picrylhydrazyl (DPPH) and superoxide radicals at IC(50) of 0.13 and 0.65 mg/mL, respectively. Methanol extract of H. ovalis showed noticeable anti-inflammatory activity at IC(50) of 78.72 µg/mL. The GC-MS analysis of H. ovalis revealed the presence of triacylglycerols as major components in purified fractions. Quantitative analysis of phytochemicals revealed that phenols are rich in seagrass H. ovalis. These findings demonstrated that the methanol extract of H. ovalis exhibited appreciable antibacterial, noticeable antioxidant, and anti-inflammatory activities, and thus could be use as a potential source for natural health products.

  13. Evaluation of anti-obesity activity of duloxetine in comparison with sibutramine along with its anti-depressant activity: an experimental study in obese rats.

    Science.gov (United States)

    Chudasama, H P; Bhatt, P A

    2009-11-01

    5-HT and noradrenaline are important neurotransmitters that control increase in body mass and are involved in the pathophysiology of obesity and depression. Sibutramine, an established anti-obesity agent, and duloxetine, an anti-depressant agent, are serotonin noradrenaline reuptake inhibitors (SNRIs). The objective of the present study was to compare the anti-obesity effect of duloxetine with sibutramine along with its effect on blood pressure and depression in obese rats. The secondary objective of the study was to determine if a relationship exists between obesity and depression. Obesity was induced by high-fat diet (HFD) in healthy male Sprague-Dawley rats. After 5 weeks of feeding HFD, animals were overweight (17.57%) with high food intake (57.15%) in comparison with normal animals. These obese animals were treated with duloxetine (30 mg x kg(-1), p.o.) and sibutramine (5 mg x kg(-1), p.o.) for 4 weeks. Control animals were treated with duloxetine alone (30 mg x kg(-1), p.o.). Our results depict that duloxetine was as effective as sibutramine in reducing food intake, body mass, and relative adiposity, and increasing rectal temperature with an added advantage of decreasing blood pressure, which sibutramine failed to do. Besides reduction in body mass, unlike sibutramine, duloxetine improved depressive state as evaluated by despair swimming test, tail suspension test, and open field test, speculating its use as an anti-obesity agent in obese-depressive animals. Since obese control animals reflected decreased locomotor activity, a positive relationship can be speculated to exist between obesity and depression. Further studies on various antidepressant models are required to confirm this relationship.

  14. Anti-inflammatory agents in the treatment of bipolar depression

    DEFF Research Database (Denmark)

    Rosenblat, Joshua D; Kakar, Ron; Berk, Michael

    2016-01-01

    for qualitative review. Eight RCTs (n = 312) assessing adjunctive nonsteroidal anti-inflammatory drugs (n = 53), omega-3 polyunsaturated fatty acids (n = 140), N-acetylcysteine (n = 76), and pioglitazone (n = 44) in the treatment of BD met the inclusion criteria for quantitative analysis. The overall effect size...... sample sizes limited interpretation of the current analysis.......OBJECTIVE: Inflammation has been implicated in the risk, pathophysiology, and progression of mood disorders and, as such, has become a target of interest in the treatment of bipolar disorder (BD). Therefore, the objective of the current qualitative and quantitative review was to determine...

  15. Generalised anxiety disorder

    Directory of Open Access Journals (Sweden)

    Bojana Avguštin Avčin

    2013-10-01

    Full Text Available Generalised anxiety disorder is characterised by persistent, excessive and difficult-to-control worry, which may be accompanied by several psychic and somatic symptoms, including suicidality. Generalized anxiety disorder is the most common psychiatric disorder in the primary care, although it is often underrecognised and undertreated. Generalized anxiety disorder is typically a chronic condition with low short- and medium-term remission rates. Clinical presentations often include depression, somatic illness, pain, fatigue and problems sleeping. The evaluation of prognosis is complicated by frequent comorbidity with other anxiety disorders and depression, which worsen the long-term outcome and accompanying burden of disability. The two main treatments for generalised anxiety disorder are medications and psychotherapy. Selective serotonin reuptake inhibitors and serotonin-norepinephrine reuptake inhibitors represent first-line psychopharmacologic treatment for generalised anxiety disorder. The most extensively studied psychotherapy for anxiety is cognitive behavioural therapy which has demonstrated efficacy throughout controlled studies.

  16. Emotional reasoning and anxiety sensitivity: associations with social anxiety disorder in childhood.

    Science.gov (United States)

    Alkozei, Anna; Cooper, Peter J; Creswell, Cathy

    2014-01-01

    Two specific cognitive constructs that have been implicated in the development and maintenance of anxiety symptoms are anxiety sensitivity and emotional reasoning, both of which relate to the experience and meaning of physical symptoms of arousal or anxiety. The interpretation of physical symptoms has been particularly implicated in theories of social anxiety disorder, where internal physical symptoms are hypothesized to influence the individual's appraisals of the self as a social object. The current study compared 75 children on measures of anxiety sensitivity and emotional reasoning: 25 with social anxiety disorder, 25 with other anxiety disorders, and 25 nonanxious children (aged 7-12 years). Children with social anxiety disorder reported higher levels of anxiety sensitivity and were more likely than both other groups to view ambiguous situations as anxiety provoking, whether physical information was present or not. There were no group differences in the extent to which physical information altered children's interpretation of hypothetical scenarios. This study is the first to investigate emotional reasoning in clinically anxious children and therefore replication is needed. In addition, those in both anxious groups commonly had comorbid conditions and, consequently, specific conclusions about social anxiety disorder need to be treated with caution. The findings highlight cognitive characteristics that may be particularly pertinent in the context of social anxiety disorder in childhood and which may be potential targets for treatment. Furthermore, the findings suggest that strategies to modify these particular cognitive constructs may not be necessary in treatments of some other childhood anxiety disorders. © 2013 The Authors. Published by Elsevier B.V. All rights reserved.

  17. Emotional reasoning and anxiety sensitivity: Associations with social anxiety disorder in childhood☆

    Science.gov (United States)

    Alkozei, Anna; Cooper, Peter J.; Creswell, Cathy

    2014-01-01

    Background Two specific cognitive constructs that have been implicated in the development and maintenance of anxiety symptoms are anxiety sensitivity and emotional reasoning, both of which relate to the experience and meaning of physical symptoms of arousal or anxiety. The interpretation of physical symptoms has been particularly implicated in theories of social anxiety disorder, where internal physical symptoms are hypothesized to influence the individual's appraisals of the self as a social object. Method The current study compared 75 children on measures of anxiety sensitivity and emotional reasoning: 25 with social anxiety disorder, 25 with other anxiety disorders, and 25 nonanxious children (aged 7–12 years). Results Children with social anxiety disorder reported higher levels of anxiety sensitivity and were more likely than both other groups to view ambiguous situations as anxiety provoking, whether physical information was present or not. There were no group differences in the extent to which physical information altered children's interpretation of hypothetical scenarios. Limitations This study is the first to investigate emotional reasoning in clinically anxious children and therefore replication is needed. In addition, those in both anxious groups commonly had comorbid conditions and, consequently, specific conclusions about social anxiety disorder need to be treated with caution. Conclusion The findings highlight cognitive characteristics that may be particularly pertinent in the context of social anxiety disorder in childhood and which may be potential targets for treatment. Furthermore, the findings suggest that strategies to modify these particular cognitive constructs may not be necessary in treatments of some other childhood anxiety disorders. PMID:24120086

  18. Potencial de Formigas (Hymenoptera: Formicidae como Agentes Anti-herbívoros em Cultivo de Café (Coffea canephora Pierre e Feijão Guandu [Cajanus cajans (L. Millsp

    Directory of Open Access Journals (Sweden)

    Leandro Chevalier

    2013-07-01

    Abstract. This study analyzed the role of ants as anti-herbivore agents in Coffee (Coffea canephora Pierre and Pigeon Pea [Cajanus cajans (L. Millsp] plants in agroecosystem under organic management. In these plants we used artificial eggs and sugar solution in experiments that simulated the presence of herbivore insects. Coffee plants did not possess any natural attractive that could intensify foraging activity of ants, but pigeon pea plants were infested by treehoppers which attracted ants. Activity of ants was surveyed after sugar solution application and artificial eggs removal was measured 24 and 48 h after start of the experiments. Sugar solution sprinkled on plants foliage increased significantly the activity of ants on coffee and pigeon pea plants. The removal of artificial eggs was significantly greater in branch with ants than without ants for pigeon pea plants. The sugar solution addiction resulted in greater artificial eggs removal in pigeon pea plants, but not in coffee plants. The treatment with sugar solution and presence of treehoppers had similar effects on the activity of ants on the plants. This study showed that the application of sugar solution can be used to increase activity of ants on plants as well as the potential of ants as anti-herbivore agents can be evaluated in experiments that simulate the presence of insects on the plants.

  19. Treatment of Oral Multispecies Biofilms by an Anti-Biofilm Peptide.

    Directory of Open Access Journals (Sweden)

    Zhejun Wang

    Full Text Available Human oral biofilms are multispecies microbial communities that exhibit high resistance to antimicrobial agents. Dental plaque gives rise to highly prevalent and costly biofilm-related oral infections, which lead to caries or other types of oral infections. We investigated the ability of the recently identified anti-biofilm peptide 1018 to induce killing of bacterial cells present within oral multispecies biofilms. At 10 μg/ml (6.5 μM, peptide 1018 was able to significantly (p50% of the biofilm being killed and >35% being dispersed in only 3 minutes. Peptide 1018 may potentially be used by itself or in combination with CHX as a non-toxic and effective anti-biofilm agent for plaque disinfection in clinical dentistry.

  20. Arterite de Takayasu: tratamento com anti-TNF em uma casuística brasileira Takayasu arteritis: anti-TNF therapy in a Brazilian setting

    Directory of Open Access Journals (Sweden)

    Guilherme Nunes

    2010-06-01

    Full Text Available O objetivo deste estudo é descrever as características clínicas e as respostas às intervenções terapêuticas, incluindo a terapia antifator de necrose tumoral (TNF, em uma série de casos brasileiros de arterite de Takayasu (AT. Foi realizado um estudo observacional, retrospectivo, com base na revisão de prontuários, incluindo todos os pacientes com AT, de acordo com os critérios de classificação do American College of Rheumatology, em acompanhamento no Serviço de Reumatologia do Hospital Universitário da Universidade Federal de Santa Catarina (UFSC, Brasil. Foram incluídos 15 pacientes, sendo 14 (93,3% mulheres, com idade média ao diagnóstico de 29,6 anos. Hipertensão arterial sistêmica (60,0% e ausência de pulsos em membros superiores (53,3% foram os achados clínicos mais comuns ao diagnóstico. As artérias subclávias e carotídeas foram os vasos mais frequentemente acometidos. Doze pacientes (80,0% não obtiveram remissão sustentada em terapia isolada com corticosteroide, tendo sido empregada terapia imunossupressora, sendo metotrexato, azatioprina e ciclofosfamida as drogas utilizadas. Intervenções cirúrgicas foram necessárias em 53,3% dos casos. Três casos (20,0% foram refratários à terapia com corticoides e imunossupressores e foram tratados com agentes anti-TNF, com subsequente remissão da doença. Em conclusão, observou-se que uma parcela importante dos casos de AT é refratária à terapia tradicional e os agentes anti-TNF podem representar uma opção promissora para o controle da doença nesses casos.The aim of this study was to describe clinical features and response to different therapeutic interventions, including anti-tumor necrosis factor (TNF agents, in a case series of Takayasu arteritis (TA from Brazil. A retrospective observational chart-review study was performed including all patients meeting the American College of Rheumatology TA classification criteria followed at the rheumatology

  1. Radioiodination and bio-evaluation of some anti-inflammatory drugs

    International Nuclear Information System (INIS)

    Mohamed, H.H.

    2009-01-01

    This thesis deals with the electrophilic substitution radioiodination reaction of non-steroidal anti-inflammatory drugs namely, Piroxicam (Pirox), Meloxicam (Melox), Etodolac and Naproxen for using them as anti-inflammatory imaging agent. The factors affecting the percent of radiochemical yields such as drug concentration, ph of the reaction mixtures, different oxidizing agents, reaction time, temperature and different organic media were studied. We can divide the objective of this thesis into three parts: First part performs to compare the electrophilic substitution radioiodination reaction of Piroxicam (Pirox) and Meloxicam (Melox) with Iodine-125 where both chloramine-T (CAT) and iodogen were used as oxidizing agents. The maximum radiochemical yield of 125 I-Piroxicam ( 125 I-Pirox) was (94%) using 3.7 MBq of Na 125 I, 0.4 mM of Pirox as substrate, 3.6 mM of chloramine-T (CAT) as oxidizing agent in acetone at neutral ph=7 at 60 degree C within 20 min where the maximum radiochemical yield of ( 125 I-Melox) was (92%) using 0.7 mM of Melox as substrate, 0.62 mM of iodogen as oxidizing agent in acetone at neutral ph=7 at 25 degree C within 30 min. The radiochemical yields were determined by TLC using methylene chloride: ethyl acetate (3: 7 v/v) as a developing system and by high-pressure liquid chromatography (HPLC) using reversed phase RP-18 column and methanol: water (70: 30 v/v) as mobile phase at flow rate (1 ml/min). Tracers showed good localization in inflamed muscle either (septic or sterile). The collected data indicates that Pirox can be used as anti-inflammatory imaging agent at 24 h post injection however Melox can be used as anti-inflammatory imaging agent at 2 h due to its shorter biological half life (t 1/2 ) compared with Pirox. Second part describes a fast and efficient method for radiolabeling of etodolac with iodine-125, where both chloramine-T and iodogen were used as oxidizing agents. The labeling reaction was carried out via electrophilic

  2. The prevalence and correlates of adult separation anxiety disorder in an anxiety clinic

    Directory of Open Access Journals (Sweden)

    Wagner Renate

    2010-03-01

    Full Text Available Abstract Background Adult separation anxiety disorder (ASAD has been identified recently, but there is a paucity of data about its prevalence and associated characteristics amongst anxiety patients. This study assessed the prevalence and risk factor profile associated with ASAD in an anxiety clinic. Methods Clinical psychologists assigned 520 consecutive patients to DSM-IV adult anxiety subcategories using the SCID. We also measured demographic factors and reports of early separation anxiety (the Separation Anxiety Symptom Inventory and a retrospective diagnosis of childhood separation anxiety disorder. Other self-report measures included the Adult Separation Anxiety Symptom Questionnaire (ASA-27, the Depression, Anxiety, Stress Scales (DASS-21, personality traits measured by the NEO PI-R and the Work and Social Adjustment Scale. These measures were included in three models examining for overall differences and then by gender: Model 1 compared the conventional SCID anxiety subtypes (excluding PTSD and OCD because of insufficient numbers; Model 2 divided the sample into those with and without ASAD; Model 3 compared those with ASAD with the individual anxiety subtypes in the residual group. Results Patients with ASAD had elevated early separation anxiety scores but this association was unique in females only. Except for social phobia in relation to some comparisons, those with ASAD recorded more severe symptoms of depression, anxiety and stress, higher neuroticism scores, and greater levels of disability. Conclusions Patients with ASAD attending an anxiety clinic are highly symptomatic and disabled. The findings have implications for the classification, clinical identification and treatment of adult anxiety disorders.

  3. Anti-TNFα Treatment for HLA-B27-Positive Ankylosing Spondylitis-Related Uveitis.

    Science.gov (United States)

    Kim, Mirinae; Won, Jae-Yon; Choi, Seung Yong; Ju, Ji Hyeon; Park, Young-Hoon

    2016-10-01

    To assess the long-term efficacy of the most widely used anti-tumor necrosis factor alpha (TNFα) agents for treatment of HLA-B27-positive ankylosing spondylitis (AS)-related uveitis. Retrospective cohort study. The medical records of 143 patients with HLA-B27-positive AS who visited Seoul St. Mary's Hospital and were taking an anti-TNFα agent for at least 1 year were studied. Subjects were divided into 3 groups according to anti-TNFα treatment: Group 1 (infliximab, 66), Group 2 (adalimumab, 45), and Group 3 (etanercept, 32). Mean age was 41.0 ± 13.0 years, and 97 patients (67.8%) were male. Mean follow-up period was 70.6 ± 37.9 months. In cases of active ocular inflammation at the onset of anti-TNFα treatment, patients showed improved activity of uveitis after 24.0 ± 15.0 days (Group 1), 17.9 ± 6.0 days (Group 2), and 25.9 ± 18.0 days (Group 3). After the anti-TNFα treatment, 71 of 94 patients (32 [76.2%] in Group 1, 26 [78.8%] in Group 2, and 13 [68.4%] in Group 3) remained without uveitis relapse. A reduction in the number of systemic medications was achieved in 129 patients (90.2%). Twenty-eight cases of minor side effects were observed, and 4 cases were tuberculosis leading to discontinuation of anti-TNFα treatment. Infliximab, adalimumab, and etanercept were effective for treating and reducing the number of uveitis relapses in HLA-B27-positive AS. However, the risk of serious infections was noted, so ophthalmologists should consider the possibility that prolonged use of biologic agents may result in systemic side effects. Copyright © 2016 Elsevier Inc. All rights reserved.

  4. Analysis of anti-bacterial and anti oxidative activity of Azadirachta indica bark using various solvents extracts

    Directory of Open Access Journals (Sweden)

    Raid Al Akeel

    2017-01-01

    Full Text Available Herbal medications have been used for relief of symptoms of disease. Regardless of the great advances observed in current medicine in recent decades, plants still make a significant contribution to health care. An alarming increase in bacterial strains resistant to a number of antimicrobial agents demands that a renewed effort be made to seek antibacterial agents effective against pathogenic bacteria resistant to or less sensitive to current antibiotics. Anti-bacterial activity of Azadirachta indica stem bark was tested against pathogenic Salmonella paratyphi and Salmonella typhi using various solvent extracts. The in vitro anti-bacterial activity was performed by agar well diffusion method and the results were expressed as the average diameter of zone of inhibition of bacterial growth around the well. The ethanol and methanol extracts showed better anti-bacterial activity with zone of inhibition (20–25 mm when compared with other tested extracts and standard antibiotic Erythromycin (15 mcg with zone of inhibition (13–14 mm. Using Fisher’s exact test of significance difference was found between two Salmonella strains sensitivity patterns against tested extracts (P ⩽ 0.035. Extracts of A. indica stem bark also exhibited significant antioxidant activity, thus establishing the extracts as an antioxidant. The results obtained in this study give some scientific support to the A. indica stem bark for further investigation of compounds and in future could be used as drug.

  5. Social anxiety disorder

    Science.gov (United States)

    Phobia - social; Anxiety disorder - social; Social phobia; SAD - social anxiety disorder ... People with social anxiety disorder fear and avoid situations in which they may be judged by others. It may begin in ...

  6. "Smart tattoo" glucose biosensors and effect of coencapsulated anti-inflammatory agents.

    Science.gov (United States)

    Srivastava, Rohit; Jayant, Rahul Dev; Chaudhary, Ayesha; McShane, Michael J

    2011-01-01

    Minimally invasive glucose biosensors with increased functional longevity form one of the most promising techniques for continuous glucose monitoring. In the present study, we developed a novel nanoengineered microsphere formulation comprising alginate microsphere glucose sensors and anti-inflammatory-drug-loaded alginate microspheres. The formulation was prepared and characterized for size, shape, in vitro drug release, biocompatibility, and in vivo acceptability. Glucose oxidase (GOx)- and Apo-GOx-based glucose sensors were prepared and characterized. Sensing was performed both in distilled water and simulated interstitial body fluid. Layer-by-layer self-assembly techniques were used for preventing drug and sensing chemistry release. Finally, in vivo studies, involving histopathologic examination of subcutaneous tissue surrounding the implanted sensors using Sprague-Dawley rats, were performed to test the suppression of inflammation and fibrosis associated with glucose sensor implantation. The drug formulation showed 100% drug release with in 30 days with zero-order release kinetics. The GOx-based sensors showed good enzyme retention and enzyme activity over a period of 1 month. Apo-GOx-based visible and near-infrared sensors showed good sensitivity and analytical response range of 0-50 mM glucose, with linear range up to 12 mM glucose concentration. In vitro cell line studies proved biocompatibility of the material used. Finally, both anti-inflammatory drugs were successful in controlling the implant-tissue interface by suppressing inflammation at the implant site. The incorporation of anti-inflammatory drug with glucose biosensors shows promise in improving sensor biocompatibility, thereby suggesting potential application of alginate microspheres as "smart tattoo" glucose sensors with increased functional longevity. © 2010 Diabetes Technology Society.

  7. Anxiety

    Science.gov (United States)

    ... at your home, feeling a bit worried about getting everything done on time can help you focus and finish the job. This kind of anxiety is a normal response to stress. But too much anxiety is another thing. It’s not normal and it’s not helpful. You ...

  8. Epilepsy and anxiety

    Directory of Open Access Journals (Sweden)

    Marly de Albuquerque

    1993-09-01

    Full Text Available We have analyzed 155 subjects with STAI (State-Trait Anxiety Inventory: 75 epileptic patients and 80 normal subjects used as a control group. A higher trait-anxiety score (chronic anxiety than that of controls was found for the epileptic group. For the epileptic group higher levels of the A-trait occurred in patients with EEG abnormalities with left temporal localization. We have also observed that the shorter the epilepsy lasts (less than two years, the higher the trait-anxiety levels. Convulsions and awareness loss during epileptic seizures do not modify state and trait-anxiety scores.

  9. Alteration of serum thymus and activation-regulated chemokine level during biologic therapy for psoriasis: Possibility as a marker reflecting favorable response to anti-interleukin-17A agents.

    Science.gov (United States)

    Shibuya, Takashi; Honma, Masaru; Iinuma, Shin; Iwasaki, Takeshi; Takahashi, Hidetoshi; Ishida-Yamamoto, Akemi

    2018-06-01

    Biologics show great efficacy in treating psoriasis, a chronic inflammatory skin disease. The high cost and side-effects of biologics, dose-reduction, elongation of administration interval and suspension are possible options. However, there has been no reliable biomarker we can use when we consider these moderations in therapy. This study was conducted to test the possibility of using serum thymus and activation-regulated chemokine (TARC) level as an indicator for step down of biologic therapy. Serum TARC level was measured in 70 psoriatic patients at Asahikawa Medical University, and a correlation of TARC and severity of skin lesions was analyzed. Referring to serum TARC level, psoriatic patients can be divided into two groups. One is a population in which serum TARC level is positively correlated with severity of skin lesions, and the other is a population with low psoriatic severity and high TARC level. Serum TARC level was higher in the group that achieved PASI-clear with biologics than in the group which did not achieve PASI-clear. Among biologics, the group treated with secukinumab, an anti-interleukin (IL)-17A agent, showed significantly higher TARC level compared with the group treated with anti-tumor necrosis factor agents. In certain populations achieving PASI-clear, serum TARC level may be a potent marker reflecting better response to IL-17A inhibitors, and in this case step down of treatment for psoriasis is possible. © 2018 Japanese Dermatological Association.

  10. The Analgesic Efficacy of Nonsteroidal Anti-inflammatory Agents (NSAIDs) in Patients Undergoing Cesarean Deliveries: A Meta-Analysis.

    Science.gov (United States)

    Zeng, Angela M; Nami, Nina F; Wu, Christopher L; Murphy, Jamie D

    Postoperative pain after cesarean delivery, which accounts for approximately 1 in 3 live births in the United States, can be severe in many patients. Nonsteroidal anti-inflammatory agents (NSAIDs) are potent analgesics that are effective in the treatment of postoperative pain. In this meta-analysis, we assessed the analgesic efficacy of NSAIDs in postoperative cesarean delivery patients. An electronic literature search of the Library of Medicine's PubMed, Cochrane CENTRAL, Scopus, and EMBASE databases was conducted in May 2013 and updated in January 2015 (Appendix, Supplemental Digital Content 1, http://links.lww.com/AAP/A174). Searches were limited to randomized controlled trials. The primary outcome variable was visual analog scale or numerical rating scale pain scores. Secondary outcomes included cumulative postoperative opioid consumption and opioid-related adverse effects (drowsiness/sedation, nausea, and vomiting). Data extraction was performed independently by 2 reviewers. Extracted data were input into Review Manager. Twenty-two randomized controlled trials compared a NSAID (n = 639) to a control (n = 674). Patients in the NSAID group versus control reported lower pain scores at 12 hours (P = 0.003) and at 24 hours (P breastfeeding.

  11. Health anxiety and illness behaviour in children of mothers with severe health anxiety

    DEFF Research Database (Denmark)

    Thorgaard, Mette Viller

    2017-01-01

    costs when untreated. Growing research suggests that health anxiety may originate in childhood, and studies have demonstrated that cognitive and behavioural features similar to those described for health anxiety in adults may be present. The development of health anxiety probably has a complex nature...... perspectives also assume an association between childhood experiences and family factors and a later development of health anxiety. This dissertation is based on a systematic review and a family case-control study and aims to answer the following questions: 1) What is the empirical evidence for the influence...... of childhood and family factors for the development of health anxiety? 2) Does exposure to severe maternal health anxiety contribute to health anxiety symptoms in their children or perhaps more broadly affect the children emotionally? 3) Do mothers with severe health anxiety express more health anxiety...

  12. Fisetin, a dietary flavonoid, augments the anti-invasive and anti-metastatic potential of sorafenib in melanoma.

    Science.gov (United States)

    Pal, Harish C; Diamond, Ariana C; Strickland, Leah R; Kappes, John C; Katiyar, Santosh K; Elmets, Craig A; Athar, Mohammad; Afaq, Farrukh

    2016-01-12

    Melanoma is the most aggressive and deadly form of cutaneous neoplasm due to its propensity to metastasize. Oncogenic BRAF drives sustained activation of the BRAF/MEK/ERK (MAPK) pathway and cooperates with PI3K/AKT/mTOR (PI3K) signaling to induce epithelial to mesenchymal transition (EMT), leading to cell invasion and metastasis. Therefore, targeting these pathways is a promising preventive/therapeutic strategy. We have shown that fisetin, a flavonoid, reduces human melanoma cell invasion by inhibiting EMT. In addition, fisetin inhibited melanoma cell proliferation and tumor growth by downregulating the PI3K pathway. In this investigation, we aimed to determine whether fisetin can potentiate the anti-invasive and anti-metastatic effects of sorafenib in BRAF-mutated melanoma. We found that combination treatment (fisetin + sorafenib) more effectively reduced the migration and invasion of BRAF-mutated melanoma cells both in vitro and in raft cultures compared to individual agents. Combination treatment also effectively inhibited EMT as observed by a decrease in N-cadherin, vimentin and fibronectin and an increase in E-cadherin both in vitro and in xenograft tumors. Furthermore, combination therapy effectively inhibited Snail1, Twist1, Slug and ZEB1 protein expression compared to monotherapy. The expression of MMP-2 and MMP-9 in xenograft tumors was further reduced in combination treatment compared to individual agents. Bioluminescent imaging of athymic mice, intravenously injected with stably transfected CMV-luciferase-ires-puromycin.T2A.EGFP-tagged A375 melanoma cells, demonstrated fewer lung metastases following combination treatment versus monotherapy. Our findings demonstrate that fisetin potentiates the anti-invasive and anti-metastatic effects of sorafenib. Our data suggest that fisetin may be a worthy adjuvant chemotherapy for the management of melanoma.

  13. Cyanobacteria as a Source for Novel Anti-Leukemic Compounds.

    Science.gov (United States)

    Humisto, Anu; Herfindal, Lars; Jokela, Jouni; Karkman, Antti; Bjørnstad, Ronja; Choudhury, Romi R; Sivonen, Kaarina

    2016-01-01

    Cyanobacteria are an inspiring source of bioactive secondary metabolites. These bioactive agents are a diverse group of compounds which are varying in their bioactive targets, the mechanisms of action, and chemical structures. Cyanobacteria from various environments, especially marine benthic cyanobacteria, are found to be rich sources for the search for novel bioactive compounds. Several compounds with anticancer activities have been discovered from cyanobacteria and some of these have succeeded to enter the clinical trials. Varying anticancer agents are needed to overcome increasing challenges in cancer treatments. Different search methods are used to reveal anticancer compounds from natural products, but cell based methods are the most common. Cyanobacterial bioactive compounds as agents against acute myeloid leukemia are not well studied. Here we examined our new results combined with previous studies of anti-leukemic compounds from cyanobacteria with emphasis to reveal common features in strains producing such activity. We report that cyanobacteria harbor specific anti-leukemic compounds since several studied strains induced apoptosis against AML cells but were inactive against non-malignant cells like hepatocytes. We noted that particularly benthic strains from the Baltic Sea, such as Anabaena sp., were especially potential AML apoptosis inducers. Taken together, this review and re-analysis of data demonstrates the power of maintaining large culture collections for the search for novel bioactivities, and also how anti-AML activity in cyanobacteria can be revealed by relatively simple and low-cost assays.

  14. Statistics Anxiety, State Anxiety during an Examination, and Academic Achievement

    Science.gov (United States)

    Macher, Daniel; Paechter, Manuela; Papousek, Ilona; Ruggeri, Kai; Freudenthaler, H. Harald; Arendasy, Martin

    2013-01-01

    Background: A large proportion of students identify statistics courses as the most anxiety-inducing courses in their curriculum. Many students feel impaired by feelings of state anxiety in the examination and therefore probably show lower achievements. Aims: The study investigates how statistics anxiety, attitudes (e.g., interest, mathematical…

  15. [Drug eruptions caused by noncorticoid anti-inflammatory agents].

    Science.gov (United States)

    Roujeau, J C; Guillaume, J C; Revuz, J; Touraine, R

    1984-01-01

    Non-steroidal anti-inflammatory drugs (NSAI) may elicit various kinds of cutaneous side effects. The commonest ones are non-specific erythematous eruptions, sometimes with a phototoxic distribution, and urticaria. Vasculitis and severe bullous eruptions (Stevens-Johnson's syndrome and Toxic Epidermal Necrolysis) are rare but may have severe outcomes. The overall incidence of cutaneous reactions is about the same for all NSAI, 1 to 3 p. 100, during the clinical studies performed before marketing the drug, but this increases afterwards (up to 45 p. 100 for Benoxaprofen). Drugs with long half-lives may carry a higher risk for severe cutaneous reactions. NSAI are now the main cause of drug induced TEN. Urticarial reactions seem related to pharmacological phenomena while the pathogenic events leading to other kinds of skin reactions remain unknown. An hypersensitivity reaction is postulated. The therapeutic value of corticosteroids for the severe cutaneous side effects of drugs is still controversial.

  16. Kefir protective effects against nicotine cessation-induced anxiety and cognition impairments in rats.

    Science.gov (United States)

    Noori, Negin; Bangash, Mohammad Yasan; Motaghinejad, Majid; Hosseini, Pantea; Noudoost, Behshad

    2014-01-01

    Nicotine as one of the potent psychostimulant drugs is characterized by its parasympathomimetic activity. Upon the abrupt discontinuation of nicotine intake, a number of symptoms such as anxiety, depression and cognition impairment develop. Kefir as a food supplement is rich in tryptophan. In this study, we have evaluated the effects of Kefir on nicotine cessation-induced anxiety, depression and cognition impairment. Forty adult male rats were divided into four groups. All the groups received 6 mg/kg/day of nicotine for 17 days and then the negative control groups got 5 mg/kg/day of normal saline. The positive control groups were given 40 mg/kg/day of Sertraline HCl for 7 days. The group treated with Cow Milk Kefir (CMK) and Soy Milk Kefir (SMK) received 5 mg/kg/day for 7 days. On the 25(th) day, Elevated Plus Maze (EPM), Open Field Test (OFT) and Forced Swim Test (FST) were used to investigate anxiety and depression. In addition, Moris Water Maze was applied to evaluate learning and memory in the animals between the 20(th) and 25(th) days. The results showed that administration of CMK, SMK and Sertraline had higher anti-depression and anxiolytic effects on nicotine withdrawal-induced depression and anxiety in rats (P Kefir had a potential effect on the treatment of nicotine cessation-induced depression, anxiety and cognition impairment in the animal model. Kefir may be useful for adjunct therapy for nicotine abandonment treatment protocols.

  17. Genetic and environmental influences on relationship between anxiety sensitivity and anxiety subscales in children

    OpenAIRE

    Waszczuk, M.A.; Zavos, H.M.S.; Eley, T.C.

    2013-01-01

    Anxiety sensitivity, a belief that symptoms of anxiety are harmful, has been proposed to influence development of panic disorder. Recent research suggests it may be a vulnerability factor for many anxiety subtypes. Moderate genetic influences have been implicated for both anxiety sensitivity and anxiety, however, little is known about the aetiology of the relationship between these traits in children. Self-reports of anxiety sensitivity and anxiety symptoms were collected from approximately 3...

  18. Anxiety and Epigenetics.

    Science.gov (United States)

    Bartlett, Andrew A; Singh, Rumani; Hunter, Richard G

    2017-01-01

    Anxiety disorders are highly prevalent psychiatric disorders often comorbid with depression and substance abuse. Twin studies have shown that anxiety disorders are moderately heritable. Yet, genome-wide association studies (GWASs) have failed to identify gene(s) significantly associated with diagnosis suggesting a strong role for environmental factors and the epigenome. A number of anxiety disorder subtypes are considered "stress related." A large focus of research has been on the epigenetic and anxiety-like behavioral consequences of stress. Animal models of anxiety-related disorders have provided strong evidence for the role of stress on the epigenetic control of the hypothalamic-pituitary-adrenal (HPA) axis and of stress-responsive brain regions. Neuroepigenetics may continue to explain individual variation in susceptibility to environmental perturbations and consequently anxious behavior. Behavioral and pharmacological interventions aimed at targeting epigenetic marks associated with anxiety may prove fruitful in developing treatments.

  19. Ethnobotany and ethnopharmacy--their role for anti-cancer drug development.

    Science.gov (United States)

    Heinrich, Michael; Bremner, Paul

    2006-03-01

    Local and traditional knowledge has been the starting point for many successful drug development projects over the last decades. Here we discuss some examples of anti-cancer drugs which have had enormous impact as anti-cancer agents (camptothecan, taxol and derivatives) and a few examples of drugs currently under various stages of preclinical development. Ethnobotanists investigate the relationship between humans and plants in all its complexity, and such research is generally based on a detailed observation and study of the use a society makes of plants. The requirements of modern research on natural products as, for example, outlined in the Convention on Biological Diversity (Rio Convention) and the overall approach in ethnobotanical research are also discussed. Selected phytochemical-pharmacological studies based on traditional plant use are used to highlight the potential of ethnobotany driven anti-cancer research. The link between traditionally used plants and targets of the NF-kappaB pathway is discussed using on an EU-funded, multidisciplinary project as an example. Lastly the potential of chemopreventive agents derived from traditional food plants is briefly addressed.

  20. Treatment of adolescents with morbid obesity with bariatric procedures and anti-obesity pharmacological agents

    Directory of Open Access Journals (Sweden)

    Um SS

    2011-12-01

    Full Text Available Scott S Um1, Wendelin Slusser2, Daniel A DeUgarte11Department of Surgery, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA; 2Department of Pediatrics, David Geffen School of Medicine at UCLA, Los Angeles, CA, USAAbstract: Adolescent obesity is a growing health concern that can have immense physical and psychological impact. Treatment of morbidly obese adolescents should include a multidisciplinary team to address medical comorbidities, diet, physical activity, mental health, and behavior modification. Anti-obesity pharmacologic agents have a limited role in the treatment of adolescents because of concerns with side effects, safety, and efficacy. Orlistat (GlaxoSmithKline, Moon Township, PA is the only approved medication for weight-loss in adolescents. However, it is associated with gastrointestinal side effects and its long-term efficacy is unknown. Bariatric surgery is the most effective therapy to treat morbid obesity. However, adolescents must meet rigorous criteria and have appropriate cognitive, psychological, and social clearance before being considered for surgical intervention. Gastric bypass remains the gold standard bariatric operation. The adjustable gastric band is not FDA-approved for use in patients under 18 years of age. Sleeve gastrectomy is a promising procedure for adolescents because it avoids an intestinal bypass and the implantation of a foreign body. Prospective longitudinal assessment of bariatric surgery procedures is required to determine long-term outcomes. In this manuscript, we review the treatment options, efficacy, and impact on quality of life for morbidly obese adolescents.Keywords: bariatric surgery, morbid obesity, weight loss, adolescent

  1. Pre-clinical assessment of A-674563 as an anti-melanoma agent

    International Nuclear Information System (INIS)

    Zou, Ying; Fan, Guobiao; Wang, Xuemin

    2016-01-01

    The present study aims to investigate the anti-melanoma activity by an Akt1 specific inhibitor A-674563. We showed that A-674563 was anti-proliferative and cytotoxic when added to human melanoma cells (A375, WM-115 and SK-Mel-2 lines). A-674563 induced caspase-dependent apoptotic death of human melanoma cells, and its cytotoxicity was inhibited with pre-treatment of caspase inhibitors. Further, A-674563 treatment blocked Akt and its downstream S6 Kinase 1 (S6K1) activation in A375 melanoma cells. Significantly, restoring Akt-S6K1 activation via introduction of constitutively-active Akt1 (ca-Akt1) only partially attenuated A-674563's cytotoxicity against A375 cells. Further, A-674563 induced pro-apoptotic ceramide production in A375 cells. Significantly, sphingosine-1-phosphate (S1P) inhibited A-674563-induced ceramide production and subsequent A375 cell apoptosis. On the other hand, co-treatment with the glucosylceramide synthase (GCS) inhibitor PDMP or the cell permeable short-chain ceramide (C6) potentiated A-674563's cytotoxicity against A375 cells. In vivo, A-674563 oral gavage inhibited A375 xenograft growth in severe combined immunodeficiency (scid) mice. Akt inactivation, caspase-3 activation and ceramide production were also observed in A-674563-treated A375 xenografts. Together, these results suggest that A-674563 exerts potent anti-melanoma activity, involving Akt-dependent and Akt-independent mechanisms. - Highlights: • A-674563 inhibits human melanoma cell survival and proliferation. • A-674563 induces melanoma cell apoptotic death, inhibited by caspase inhibitors. • A-674563 inhibits melanoma cells via Akt-dependent and -independent mechanisms. • A-674563 induces ceramide production in melanoma cells, independent of Akt inhibition. • A-674563 oral administration potently inhibits A375 xenograft growth in mice.

  2. Pre-clinical assessment of A-674563 as an anti-melanoma agent

    Energy Technology Data Exchange (ETDEWEB)

    Zou, Ying; Fan, Guobiao; Wang, Xuemin, E-mail: wangxuemeidr@yeah.net

    2016-08-12

    The present study aims to investigate the anti-melanoma activity by an Akt1 specific inhibitor A-674563. We showed that A-674563 was anti-proliferative and cytotoxic when added to human melanoma cells (A375, WM-115 and SK-Mel-2 lines). A-674563 induced caspase-dependent apoptotic death of human melanoma cells, and its cytotoxicity was inhibited with pre-treatment of caspase inhibitors. Further, A-674563 treatment blocked Akt and its downstream S6 Kinase 1 (S6K1) activation in A375 melanoma cells. Significantly, restoring Akt-S6K1 activation via introduction of constitutively-active Akt1 (ca-Akt1) only partially attenuated A-674563's cytotoxicity against A375 cells. Further, A-674563 induced pro-apoptotic ceramide production in A375 cells. Significantly, sphingosine-1-phosphate (S1P) inhibited A-674563-induced ceramide production and subsequent A375 cell apoptosis. On the other hand, co-treatment with the glucosylceramide synthase (GCS) inhibitor PDMP or the cell permeable short-chain ceramide (C6) potentiated A-674563's cytotoxicity against A375 cells. In vivo, A-674563 oral gavage inhibited A375 xenograft growth in severe combined immunodeficiency (scid) mice. Akt inactivation, caspase-3 activation and ceramide production were also observed in A-674563-treated A375 xenografts. Together, these results suggest that A-674563 exerts potent anti-melanoma activity, involving Akt-dependent and Akt-independent mechanisms. - Highlights: • A-674563 inhibits human melanoma cell survival and proliferation. • A-674563 induces melanoma cell apoptotic death, inhibited by caspase inhibitors. • A-674563 inhibits melanoma cells via Akt-dependent and -independent mechanisms. • A-674563 induces ceramide production in melanoma cells, independent of Akt inhibition. • A-674563 oral administration potently inhibits A375 xenograft growth in mice.

  3. POTENTIAL USE OF MELATONIN IN PROCEDURAL ANXIETY AND PAIN IN CHILDREN UNDERGOING BLOOD WITHDRAWAL.

    Science.gov (United States)

    Marseglia, L; Manti, S; D'Angelo, G; Arrigo, T; Cuppari, C; Salpietro, C; Gitto, E

    2015-01-01

    The recognition of the value of pain, especially in the pediatric population, has increased over the last decade. It is known that pain-related anxiety can increase perceived pain intensity. There are several different approaches to the treatment of pre-procedural anxiety and procedural pain in children. Melatonin, a neurohormone with the profile of a novel hypnotic-anaesthetic agent, plays an important role in anxiolysis and analgesia. This study investigated the effects of oral melatonin premedication to reduce anxiety and pain in children having blood samples taken. The investigations were carried out on 60 children, aged 1-14 years, divided into 2 equal groups. Using a computer-generated randomization schedule, patients were given either melatonin orally (0.5 mg/kg BW, max 5 mg) or placebo 30 min before blood draw. Pre-procedural anxiety was assessed using the scale from the Children’s Anxiety and Pain Scales, while procedural pain used the Face, Legs, Activity, Cry and Consolability assessment tool for children under the age of 3 years, Faces Pain Scale-Revised for children aged 3-8 years and Numeric Rating Scale for children over the age of 8 years. Oral administration of melatonin before the blood withdrawal procedure significantly reduced both anxiety (pchildren under 3 years and pchildren over 3 years). These data support the use of melatonin for taking blood samples due to its anxiolytic and analgesic properties. Further studies are needed to support the routine use of melatonin to alleviate anxiety and pain in pediatric patients having blood samples taken.

  4. MEDICAL PROTECTION FOR THE EXPEDITIONARY FORCE IN THE EVENT OF USING BIOLOGICAL AGENTS

    Directory of Open Access Journals (Sweden)

    Viorel ORDEANUL

    2014-12-01

    Full Text Available The ADM/CBRN military or terrorist attack is most likely to be enforced on the force deployed in the theaters of operations (TO, as peace making troops, peace keeping troops, etc. For the medical protection of the expeditionary forces deployed in external theaters of operations (T.O., when using biological agents, we conducted a documentary study on the prophylaxis and specific treatment for the medical force protection, when using biological agents, by updating and improving the medical protection countermeasures against BWA, by anti-infective prophylaxis (antibacterial and antiviral pre-exposure, post-exposure and anti-infective etiology and support of the vital fuctions treatment.

  5. Anti-Inflammatory and Antioxidant Effects of an Ethanolic Extract of ...

    African Journals Online (AJOL)

    inflammatory agent dexamethasone (0.3-3 mg kg-1, i.p.) dosedependently reduced ... HLE as well as the positive controls, dexamethasone and methotrexate, showed significant anti-arthritic properties when applied to established adjuvant arthritis.

  6. Anti-inflammatory activity of Agaricus blazei Murill extract in the ...

    African Journals Online (AJOL)

    admin

    potential therapy of atherosclerosis disease. Keywords: Anti-inflammatory agent, Agaricus blazei Murill, Proinflammatory cytokine, TNF-α, IL-10. This is an ..... belong to the β2 integrin family. .... Response through Intestinal Epithelial Cells and.

  7. Anti-nociceptive, anti-hyperalgesic and anti-arthritic activity of amides and extract obtained from Piper amalago in rodents.

    Science.gov (United States)

    da Silva Arrigo, Jucicléia; Balen, Eloise; Júnior, Ubirajara Lanza; da Silva Mota, Jonas; Iwamoto, Renan Donomae; Barison, Andersson; Sugizaki, Mario Mateus; Leite Kassuya, Cândida Aparecida

    2016-02-17

    amides obtained seemed to be the active component(s) present in the EEPA because they proved to be anti-nociceptive and anti-hyperalgesic in models of acute pain. Considering that few drugs are currently available for the treatment of chronic pain, especially neuropathic pain, the present results may have clinical relevance and open new possibilities for the development of new anti-hyperalgesic and anti-arthritic agents from P. amalago. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  8. Heart-related anxieties in relation to general anxiety and severity of illness in cardiology patients.

    Science.gov (United States)

    Muschalla, Beate; Glatz, Johannes; Linden, Michael

    2014-01-01

    Absence of an adequate reason for anxiety is a criterion for pathological anxiety. However, the presence of danger or fear-provoking stimuli may even be a risk factor for anxiety and does not exclude that there is additionally pathological anxiety too. The question is, to what degree can heart-related anxiety be explained by the severity of illness or trait anxiety? Two hundred and nine patients (37.8% women) from a cardiology inpatient unit completed the Heart-Anxiety-Questionnaire, Progression-Anxiety-Questionnaire, Job-Anxiety-Scale and the State-Trait-Anxiety-Inventory. The severity of cardiac illness was rated by the treating cardiologists using the Multidimensional Severity of Morbidity Rating. Time absent from work due to sickness was assessed as an indicator for illness-related impairment. Heart anxiety was significantly related to progression anxiety and, to a lesser extent, trait anxiety and indicators of subjective symptoms of somatic illness. No association was found with medical ratings for prognosis, multimorbidity, or reduction in life expectancy. Heart-related anxiety is a symptom of an anxiety disorder. Although partially dependent on subjective suffering, it cannot be explained by the severity of medical illness. Treatment of health-related anxieties should focus on how to cope with subjective symptoms of illness.

  9. Monitoring and Targeting Anti-VEGF Induced Hypoxia within the Viable Tumor by 19F–MRI and Multispectral Analysis

    Directory of Open Access Journals (Sweden)

    Yunzhou Shi

    2017-11-01

    Full Text Available The effect of anti-angiogenic agents on tumor oxygenation has been in question for a number of years, where both increases and decreases in tumor pO2 have been observed. This dichotomy in results may be explained by the role of vessel normalization in the response of tumors to anti-angiogenic therapy, where anti-angiogenic therapies may initially improve both the structure and the function of tumor vessels, but more sustained or potent anti-angiogenic treatments will produce an anti-vascular response, producing a more hypoxic environment. The first goal of this study was to employ multispectral (MS 19F–MRI to noninvasively quantify viable tumor pO2 and evaluate the ability of a high dose of an antibody to vascular endothelial growth factor (VEGF to produce a strong and prolonged anti-vascular response that results in significant tumor hypoxia. The second goal of this study was to target the anti-VEGF induced hypoxic tumor micro-environment with an agent, tirapazamine (TPZ, which has been designed to target hypoxic regions of tumors. These goals have been successfully met, where an antibody that blocks both murine and human VEGF-A (B20.4.1.1 was found by MS 19F–MRI to produce a strong anti-vascular response and reduce viable tumor pO2 in an HM-7 xenograft model. TPZ was then employed to target the anti-VEGF-induced hypoxic region. The combination of anti-VEGF and TPZ strongly suppressed HM-7 tumor growth and was superior to control and both monotherapies. This study provides evidence that clinical trials combining anti-vascular agents with hypoxia-activated prodrugs should be considered to improved efficacy in cancer patients.

  10. Performance evaluation of nanoclay enriched anti-microbial hydrogels for biomedical applications

    Directory of Open Access Journals (Sweden)

    Sonali Karnik

    2016-02-01

    Full Text Available A major factor contributing to the failure of orthopedic and orthodontic implants is post-surgical infection. Coating metallic implant surfaces with anti-microbial agents has shown promise but does not always prevent the formation of bacterial biofilms. Furthermore, breakdown of these coatings within the human body can cause release of the anti-microbial drugs in an uncontrolled or unpredictable fashion. In this study, we used a calcium alginate and calcium phosphate cement (CPC hydrogel composite as the base material and enriched these hydrogels with the anti-microbial drug, gentamicin sulfate, loaded within a halloysite nanotubes (HNTs. Our results demonstrate a sustained and extended release of gentamicin from hydrogels enriched with the gentamicin-loaded HNTs. When tested against the gram-negative bacteria, the hydrogel/nanoclay composites showed a pronounced zone of inhibition suggesting that anti-microbial doped nanoclay enriched hydrogels can prevent the growth of bacteria. The release of gentamicin sulfate for a period of five days from the nanoclay-enriched hydrogels would supply anti-microbial agents in a sustained and controlled manner and assist in preventing microbial growth and biofilm formation on the titanium implant surface. A pilot study, using mouse osteoblasts, confirmed that the nanoclay enriched surfaces are also cell supportive as osteoblasts readily, proliferated and produced a type I collagen and proteoglycan matrix.

  11. Language Anxiety and Achievement.

    Science.gov (United States)

    Horwitz, Elaine K.

    2001-01-01

    Considers the literature on language learning anxiety in an effort to clarify the relationship between anxiety and second language learning. Suggests that anxiety is indeed a cause of poor language learning in some individuals and discusses possible sources of this anxiety. (Author/VWL)

  12. Curcumin-albumin conjugates as an effective anti-cancer agent with immunomodulatory properties.

    Science.gov (United States)

    Aravind, S R; Krishnan, Lissy K

    2016-05-01

    Curcumin (diferuloylmethane) is an active ingredient in turmeric (Curcuma longa) with anti-inflammatory, antioxidant, chemopreventive, chemosensitization, and radiosensitization properties. Conjugation of curcumin (Curc) to albumin (Alb) has been found to increase the aqueous solubility of the drug. The current study aimed to prove the safe use of the Curc-Alb conjugate in animals and to demonstrate that it retains drug action both in vitro and in vivo. Dalton's lymphoma ascites (DLA) cell viability was inhibited by the Curc-Alb conjugate in a dose dependent manner in vitro, as evidenced by the MTT assay. Administration of up to 11.4 mg of conjugated curcumin per kg body weight to healthy animals was non-toxic both in terms of lethality and weight loss. Histological analysis of vital organs (kidney, liver and spleen) also did not show toxic effects. Favorable immuno-modulatory activity was observed after continuous administration of sub-acute doses of the conjugate which caused increase in total leukocyte count, platelet count, and viable cell count in bone marrow, and enhanced proliferation of lymphocyte in vitro upon culture. In vivo studies in the DLA tumor model in mice demonstrated that conjugated drug induces tumor reduction and prevention. Significant tumor reduction was observed when the Curc-Alb conjugate was administered intraperitoneally in DLA-induced mice after 1 day (prevention therapy) and 7 days (reduction therapy) of tumor induction. There was significant reduction in both tumor volume and tumor cell numbers in the treated animals as well as a marked increase in their mean survival time and percent increase in life span. The effect was greater when the conjugate was administered soon after inducing the tumor as compared to when treatment was started after allowing tumor to grow for 7 days. Thus, the results of the present study suggest that curcumin albumin conjugate has immunomodulatory and tumor growth inhibition properties. The study postulates

  13. Hepatoprotective Effects of Chinese Medicinal Herbs: A Focus on Anti-Inflammatory and Anti-Oxidative Activities

    Directory of Open Access Journals (Sweden)

    Puiyan Lam

    2016-03-01

    Full Text Available The liver is intimately connected to inflammation, which is the innate defense system of the body for removing harmful stimuli and participates in the hepatic wound-healing response. Sustained inflammation and the corresponding regenerative wound-healing response can induce the development of fibrosis, cirrhosis and eventually hepatocellular carcinoma. Oxidative stress is associated with the activation of inflammatory pathways, while chronic inflammation is found associated with some human cancers. Inflammation and cancer may be connected by the effect of the inflammation-fibrosis-cancer (IFC axis. Chinese medicinal herbs display abilities in protecting the liver compared to conventional therapies, as many herbal medicines have been shown as effective anti-inflammatory and anti-oxidative agents. We review the relationship between oxidative stress and inflammation, the development of hepatic diseases, and the hepatoprotective effects of Chinese medicinal herbs via anti-inflammatory and anti-oxidative mechanisms. Moreover, several Chinese medicinal herbs and composite formulae, which have been commonly used for preventing and treating hepatic diseases, including Andrographis Herba, Glycyrrhizae Radix et Rhizoma, Ginseng Radix et Rhizoma, Lycii Fructus, Coptidis Rhizoma, curcumin, xiao-cha-hu-tang and shi-quan-da-bu-tang, were selected for reviewing their hepatoprotective effects with focus on their anti-oxidative and ant-inflammatory activities. This review aims to provide new insight into how Chinese medicinal herbs work in therapeutic strategies for liver diseases.

  14. Alcohol use, anxiety, and insomnia in older adults with generalized anxiety disorder

    Science.gov (United States)

    Ivan, M. Cristina; Amspoker, Amber B.; Nadorff, Michael R.; Kunik, Mark E.; Cully, Jeffrey A.; Wilson, Nancy; Calleo, Jessica; Kraus-Schuman, Cynthia; Stanley, Melinda A.

    2013-01-01

    Objectives We examined the presence and frequency of alcohol consumption among older primary care patients with generalized anxiety disorder (GAD) and their relation to demographic variables, insomnia, worry, and anxiety. We expected alcohol-use distribution to be similar to previous reports and alcohol use to be associated with higher anxiety and insomnia. A third aim was to examine the moderating role of alcohol use on the relation between anxiety and insomnia. We expected alcohol use to worsen the relation between anxiety and insomnia. Design Baseline data from a randomized controlled trial Sample 223 patients, age 60 and older, with DSM-IV GAD diagnoses Setting Patients were recruited through internal medicine, family practice, and geriatric clinics at 2 diverse healthcare settings: Michael E. DeBakey Veterans Administration Medical Center and Baylor College of Medicine. Measurements Measures addressed alcohol use (presence and frequency); insomnia (Insomnia Severity Index); self-reported worry severity (Penn State Worry Questionnaire − Abbreviated); clinician-rated worry severity (Generalized Anxiety Disorder Severity Scale); self-reported anxiety severity (State-Trait Anxiety Inventory - Trait); and clinician-rated anxiety (Structured Interview Guidelines for the Hamilton Anxiety Rating Scale). Results Most patients endorsed alcohol use in the past month, but overall weekly frequency was low. Presence and frequency of use among patients with GAD were greater than in prior reports of primary care samples. Alcohol use among patients with GAD was associated with higher education and female gender. Higher education also was associated with more drinks per week, and Caucasians reported more drinks per week than African Americans. Alcohol use was associated with less severe insomnia, lower self-reported anxiety, and less clinician-rated worry and anxiety. More drinks per week were associated with lower clinician-rated anxiety. Moderation analyses revealed lower

  15. Is cannabis treatment for anxiety, mood, and related disorders ready for prime time?

    Science.gov (United States)

    Turna, Jasmine; Patterson, Beth; Van Ameringen, Michael

    2017-11-01

    Anxiety and related disorders are the most common mental conditions affecting the North American population. Despite their established efficacy, first-line antidepressant treatments are associated with significant side effects, leading many afflicted individuals to seek alternative treatments. Cannabis is commonly viewed as a natural alternative for a variety of medical and mental health conditions. Currently, anxiety ranks among the top five medical symptoms for which North Americans report using medical marijuana. However, upon careful review of the extant treatment literature, the anxiolytic effects of cannabis in clinical populations are surprisingly not well-documented. The effects of cannabis on anxiety and mood symptoms have been examined in healthy populations and in several small studies of synthetic cannabinoid agents but there are currently no studies which have examined the effects of the cannabis plant on anxiety and related disorders. In light of the rapidly shifting landscape regarding the legalization of cannabis for medical and recreational purposes, it is important to highlight the significant disconnect between the scientific literature, public opinion, and related policies. The aim of this article is to provide a comprehensive review of the current cannabis treatment literature, and to identify the potential for cannabis to be used as a therapeutic intervention for anxiety, mood, and related disorders. Searches of five electronic databases were conducted (PubMed, MEDLINE, Web of Science, PsychINFO, and Google Scholar), with the most recent in February 2017. The effects of cannabis on healthy populations and clinical psychiatric samples will be discussed, focusing primarily on anxiety and mood disorders. © 2017 Wiley Periodicals, Inc.

  16. Examination of the Relationship among Death Anxiety, Spirituality, Religious Orientation and Existential Anxiety

    Directory of Open Access Journals (Sweden)

    Merve Halıcı Kurtulan

    2016-08-01

    Full Text Available In this study, the associations among death anxiety, spiritual tendencies, existential anxiety, and religious tendencies were examined. In addition, this study investigated whether these variables changed with respect to demographic characteristics. The study group was composed of 404 university students. Data was collected by administering the personal demographic form, Death Anxiety Scale, Existential Scale, Religious Tendency Scale, and Spirituality Scale. In line with the purpose of the study, the relational screening model and descriptive methods have been used and participants are identified as study groups. Male participants scored significantly higher than female participants. Gender was not found to have an effect on the other variables. Existential anxiety did not differ within groups with respect to having a religious education. Participants who had received a religious education had higher death anxiety and less spiritual tendencies. Motivation for religious tendencies was found to be external. According to the results, death anxiety and existential anxiety are negatively correlated; existential anxiety and spiritual tendencies are positively correlated; and religious tendencies, which have externally motivations, and spiritual tendencies are negatively correlated. Death anxiety, spiritual tendencies, and religious tendencies predict existential anxiety. As suggestions, the number of studies that examine the associations among existential anxiety, religious tendencies, and spiritual tendencies should be increased, and the quality of religious education should be discussed in detail.

  17. Parental state anxiety correlates with preoperative anxiety in Chinese preschool children.

    Science.gov (United States)

    Cui, Xulei; Zhu, Bo; Zhao, Jing; Huang, Yuguang; Luo, Ailun; Wei, Jing

    2016-06-01

    Preoperative anxiety in children is largely dependent on age and is influenced by anxiety level in parents. The current study compared the level of preoperative anxiety in preschool children versus school-aged children and its relationship with the state and trait anxiety of the parents. This study included 54 preschool children (2-5 years of age) and 48 school-age children (6-12 years) scheduled to receive ear, nose and throat, plastic or ophthalmologic surgeries. Preoperative anxiety of children was assessed in the holding area immediately prior to the surgery using a modified Yale Preoperative Anxiety Scale (m-YPAS). Compliance with anaesthesia induction was assessed using an Induction Compliance Checklist (ICC). The state and trait anxiety of the parent who accompanied the child was assessed using a State-Trait Anxiety Inventory (STAI) questionnaire. Both m-YPAS and ICC scores were higher in preschool children than in school-age children with significant correlation between the two measures. The STAI-S score of parents was higher in the preschool group than in the school-age group. No significant difference was found in STAI-T score between the two age groups. Children's m-YPAS score correlated with parental STAI-T score in both groups (rho = 0.297, P = 0.029 and rho = 0.338, P = 0.019, respectively) but only with STAI-S score in the preschool group (rho = 0.400, P = 0.003). Both preschool children and their parents are more anxious than school-age dyads prior to surgery. The anxiety level of the children correlates with state anxiety of the parents in preschool children but not in school-age children. © 2016 Paediatrics and Child Health Division (The Royal Australasian College of Physicians).

  18. Anti-ischemic effects of inotropic agents in experimental right ventricular infarction.

    NARCIS (Netherlands)

    Hein, M.; Roehl, A.B.; Baumert, J.H.; Scherer, K.; Steendijk, P.; Rossaint, R.

    2009-01-01

    BACKGROUND: Right ventricular (RV) function is an important determinant of survival after myocardial infarction. The efficacy of reperfusion therapy might be increased by the cardioprotective action of inotropic agents, which are used for symptomatic therapy in situations with compromised

  19. Secondary Leukemia Associated with the Anti-Cancer Agent, Etoposide, a Topoisomerase II Inhibitor

    OpenAIRE

    Sachiko Ezoe

    2012-01-01

    Etoposide is an anticancer agent, which is successfully and extensively used in treatments for various types of cancers in children and adults. However, due to the increases in survival and overall cure rate of cancer patients, interest has arisen on the potential risk of this agent for therapy-related secondary leukemia. Topoisomerase II inhibitors, including etoposide and teniposide, frequently cause rearrangements involving the mixed lineage leukemia (MLL<...

  20. The Moderating Effect of Attachment Styles (Anxiety And Avoidance on Consumer Intention

    Directory of Open Access Journals (Sweden)

    Valter Afonso Vieira

    2016-12-01

    Full Text Available 800x600 This paper investigates firm-focused customer attachment styles relationship, rather than general or interpersonal attachment styles. We proposed a theoretical framework and analyzed the customers’ attachment styles and their moderating effect on happiness, commitment, loyalty, satisfaction and preference for closeness. In Study 1, we survey clients from main banks in Brazil, who evaluated their relationship with banks. In Study 2, we survey clients from insurance agent broker. The results showed that the anxiety × avoidance interaction had negative association with switching intention. Second, the outcomes suggested that the anxiety × avoidance interaction attenuates the main effect of all marketing variables on repurchase intention and switching intention, creating a three-way interaction. Normal 0 21 false false false PT-BR X-NONE X-NONE MicrosoftInternetExplorer4

  1. Anxiety Disorders

    Science.gov (United States)

    ... the death of a loved one or parents' divorce) and major life transitions (like moving to a ... Ways to Deal With Anxiety Dealing With Difficult Emotions Anxiety Disorders Posttraumatic Stress Disorder Fears and Phobias ...

  2. Intergenerational Effects of Parents' Math Anxiety on Children's Math Achievement and Anxiety.

    Science.gov (United States)

    Maloney, Erin A; Ramirez, Gerardo; Gunderson, Elizabeth A; Levine, Susan C; Beilock, Sian L

    2015-09-01

    A large field study of children in first and second grade explored how parents' anxiety about math relates to their children's math achievement. The goal of the study was to better understand why some students perform worse in math than others. We tested whether parents' math anxiety predicts their children's math achievement across the school year. We found that when parents are more math anxious, their children learn significantly less math over the school year and have more math anxiety by the school year's end-but only if math-anxious parents report providing frequent help with math homework. Notably, when parents reported helping with math homework less often, children's math achievement and attitudes were not related to parents' math anxiety. Parents' math anxiety did not predict children's reading achievement, which suggests that the effects of parents' math anxiety are specific to children's math achievement. These findings provide evidence of a mechanism for intergenerational transmission of low math achievement and high math anxiety. © The Author(s) 2015.

  3. Zoledronic acid produces combinatory anti-tumor effects with cisplatin on mesothelioma by increasing p53 expression levels.

    Directory of Open Access Journals (Sweden)

    Shinya Okamoto

    Full Text Available We examined anti-tumor effects of zoledronic acid (ZOL, one of the bisphosphonates agents clinically used for preventing loss of bone mass, on human mesothelioma cells bearing the wild-type p53 gene. ZOL-treated cells showed activation of caspase-3/7, -8 and -9, and increased sub-G1 phase fractions. A combinatory use of ZOL and cisplatin (CDDP, one of the first-line anti-cancer agents for mesothelioma, synergistically or additively produced the cytotoxicity on mesothelioma cells. Moreover, the combination achieved greater anti-tumor effects on mesothelioma developed in the pleural cavity than administration of either ZOL or CDDP alone. ZOL-treated cells as well as CDDP-treated cells induced p53 phosphorylation at Ser 15, a marker of p53 activation, and up-regulated p53 protein expression levels. Down-regulation of p53 levels with siRNA however did not influence the ZOL-mediated cytotoxicity but negated the combinatory effects by ZOL and CDDP. In addition, ZOL treatments augmented cytotoxicity of adenoviruses expressing the p53 gene on mesothelioma. These data demonstrated that ZOL-mediated augmentation of p53, which was not linked with ZOL-induced cytotoxicity, played a role in the combinatory effects with a p53 up-regulating agent, and suggests a possible clinical use of ZOL to mesothelioma with anti-cancer agents.

  4. An investigation of anxiety about radiotherapy deploying the radiotherapy categorical anxiety scale

    International Nuclear Information System (INIS)

    Shimotsu, Sakie; Karasawa, Kumiko; Ito, Kana; Saito, Anneyuko I.; Izawa, Hiromi; Kawase, Eri; Horikawa, Naoshi

    2010-01-01

    Radiotherapy is one of the major methods for treating cancer, but many patients undergoing radiotherapy have deep concerns about receiving radiation treatment. This problem is not generally appreciated and has not been adequately studied. The objective of this investigation was to empirically investigate the anxieties that cancer patients feel towards radiotherapy by using questionnaires to classify and quantitatively measure their concerns. A preliminary interview to develop a questionnaire was carried out with 48 patients receiving radiotherapy to discover their anxieties about on-going treatments. Subsequently, a main study was performed using a questionnaire with 185 patients to classify their types of anxiety and to ascertain the reliability and validity of the responses. Confirmatory factor analysis was then carried out with a 17-item Radiotherapy Categorical Anxiety Scale. Three anxiety factors were abstracted by factor analysis: adverse effects of radiotherapy, environment of radiotherapy, and treatment effects of radiotherapy. Reliability, content validity, and concurrent validity were obtained. The adequacy of the three-factor model of anxiety concerning radiotherapy was confirmed. A 17-item Radiotherapy Categorical Anxiety Scale was formulated to quantitatively measure the specific types of anxiety among cancer patients receiving radiotherapy. (author)

  5. Interpretation bias and social anxiety: does interpretation bias mediate the relationship between trait social anxiety and state anxiety responses?

    Science.gov (United States)

    Chen, Junwen; Milne, Kirby; Dayman, Janet; Kemps, Eva

    2018-05-23

    Two studies aimed to examine whether high socially anxious individuals are more likely to negatively interpret ambiguous social scenarios and facial expressions compared to low socially anxious individuals. We also examined whether interpretation bias serves as a mediator of the relationship between trait social anxiety and state anxiety responses, in particular current state anxiety, bodily sensations, and perceived probability and cost of negative evaluation pertaining to a speech task. Study 1 used ambiguous social scenarios and Study 2 used ambiguous facial expressions as stimuli to objectively assess interpretation bias. Undergraduate students with high and low social anxiety completed measures of state anxiety responses at three time points: baseline, after the interpretation bias task, and after the preparation for an impromptu speech. Results showed that high socially anxious individuals were more likely to endorse threat interpretations for ambiguous social scenarios and to interpret ambiguous faces as negative than low socially anxious individuals. Furthermore, negative interpretations mediated the relationship between trait social anxiety and perceived probability of negative evaluation pertaining to the speech task in Study 1 but not Study 2. The present studies provide new insight into the role of interpretation bias in social anxiety.

  6. Developmental Trajectories of Anxiety Symptoms in Early Adolescence: The Influence of Anxiety Sensitivity

    OpenAIRE

    Allan, Nicholas P.; Capron, Daniel W.; Lejuez, Carl W.; Reynolds, Elizabeth K.; MacPherson, Laura; Schmidt, Norman B.

    2014-01-01

    Children and adolescents seem to suffer from anxiety disorders at rates similar to adults. Interestingly, anxiety symptoms appear to generally decline over time within children as evidenced by lower rates in early and middle adolescence. There is some evidence that there may be heterogeneous subpopulations of adolescent children with different trajectories of anxiety symptoms, including a class of adolescents with elevated levels of anxiety that do not dissipate over time. Anxiety sensitivity...

  7. Psoriatic arthritis: treatment strategies using biologic agents

    Directory of Open Access Journals (Sweden)

    C. Palazzi

    2012-06-01

    Full Text Available The traditional management of psoriatic arthritis (PsA includes NSAIDs, corticosteroids and DMARDs. Advancement in the knowledge of the immunopathogenesis of PsA has been associated with the development of biologic agents which have revolutionized the management of the disease. Among biologics drugs, there are the 4 currently availablee anti-TNFα blocking agents (etanercept, infliximab, adalimumab and golimumab which are more effective than traditional DMARDs on symptoms/signs of inflammation, quality of life, function, and in inhibiting the progression of the structural joint damage. Despite of the high cost, TNF inhibitors are costeffective on both the musculoskeletal and skin manifestations of psoriatic disease.

  8. Parkinson's disease and anxiety

    OpenAIRE

    Walsh, K; Bennett, G

    2001-01-01

    There has been a recent surge of interest in the subject of anxiety in patients with Parkinson's disease. Up to 40% of patients with Parkinson's disease experience clinically significant anxiety. This anxiety may be a psychological reaction to the stress of the illness or may be related to the neurochemical changes of the disease itself. Antiparkinsonian drugs may have a role in the pathogenesis of the anxiety. The anxiety disorders in Parkinson's disease patients appear to be clustered in th...

  9. Anxiety, Mood, and Substance Use Disorders in Parents of Children with Anxiety Disorders

    Science.gov (United States)

    Hughes, Alicia A.; Furr, Jami M.; Sood, Erica D.; Barmish, Andrea J.; Kendall, Philip C.

    2009-01-01

    Examined the prevalence of anxiety, mood, and substance use disorders in the parents of anxiety disordered (AD) children relative to children with no psychological disorder (NPD). The specificity of relationships between child and parent anxiety disorders was also investigated. Results revealed higher prevalence rates of anxiety disorders in…

  10. Preparation of 99''m technitium labelled erythrocytes coated with anti-rhesus-D immunoglobulin (anti-Rho-D IgG) for defective spleen diagnosis

    International Nuclear Information System (INIS)

    Nanny Kartini, H.; Karnama, S.; Ahmad Muhtadi; Karna Awangga

    1999-01-01

    Preparation of 99m technetium-red blood cells coated with anti-rhesus-D IgG has been carried out and evaluated. Some factors such as the concentration of Sn(II) and incubation time which can influence the labelling yield are discussed. A labelling efficiency of greater than 90% (93.1 ±1.4% ) was obtained. Biological studies in normal human volunteers, showed that 99m Tc-red blood cell coated with anti-rhesus-D IgG accumulated in the spleen and may become a spleen imaging agent. (author)

  11. Anxiety and Tobacco

    Directory of Open Access Journals (Sweden)

    Cristina Mae Wood

    2010-02-01

    Full Text Available Tobacco use is the first preventable cause of death. This is associated not only with physical illness and a shorter life expectancy, but also with different mental disorders such as anxiety disorders. Given the low risk perception of use, this paper reports a systematic review of the scientific literature on the relationship between anxiety and tobacco from an emotional perspective, including data on smoking prevalence, factors associated with the onset and maintenance of tobacco use, as well as those factors that hamper smoking cessation and increase relapse rates. The high rates of comorbidity between tobacco use and anxiety disorders make necessary the development of new and better tobacco cessation treatments, especially designed for those smokers with high state anxiety or anxiety sensitivity, with the aim of maximizing the efficacy.

  12. CoMFA and CoMSIA studies on C-aryl glucoside SGLT2 inhibitors as potential anti-diabetic agents.

    Science.gov (United States)

    Vyas, V K; Bhatt, H G; Patel, P K; Jalu, J; Chintha, C; Gupta, N; Ghate, M

    2013-01-01

    SGLT2 has become a target of therapeutic interest in diabetes research. CoMFA and CoMSIA studies were performed on C-aryl glucoside SGLT2 inhibitors (180 analogues) as potential anti-diabetic agents. Three different alignment strategies were used for the compounds. The best CoMFA and CoMSIA models were obtained by means of Distill rigid body alignment of training and test sets, and found statistically significant with cross-validated coefficients (q²) of 0.602 and 0.618, respectively, and conventional coefficients (r²) of 0.905 and 0.902, respectively. Both models were validated by a test set of 36 compounds giving satisfactory predicted correlation coefficients (r² pred) of 0.622 and 0.584 for CoMFA and CoMSIA models, respectively. A comparison was made with earlier 3D QSAR study on SGLT2 inhibitors, which shows that our 3D QSAR models are better than earlier models to predict good inhibitory activity. CoMFA and CoMSIA models generated in this work can provide useful information to design new compounds and helped in prediction of activity prior to synthesis.

  13. Punishment does not promote cooperation under exploration dynamics when anti-social punishment is possible.

    Science.gov (United States)

    P Hauser, Oliver; A Nowak, Martin; G Rand, David

    2014-11-07

    It has been argued that punishment promotes the evolution of cooperation when mutation rates are high (i.e. when agents engage in 'exploration dynamics'). Mutations maintain a steady supply of agents that punish free-riders, and thus free-riders are at a disadvantage. Recent experiments, however, have demonstrated that free-riders sometimes also pay to punish cooperators. Inspired by these empirical results, theoretical work has explored evolutionary dynamics where mutants are rare, and found that punishment does not promote the evolution of cooperation when this 'anti-social punishment' is allowed. Here we extend previous theory by studying the effect of anti-social punishment on the evolution of cooperation across higher mutation rates, and by studying voluntary as well as compulsory Public Goods Games. We find that for intermediate and high mutation rates, adding punishment does not promote cooperation in either compulsory or voluntary public goods games if anti-social punishment is possible. This is because mutations generate agents that punish cooperators just as frequently as agents that punish defectors, and these two effects cancel each other out. These results raise questions about the effectiveness of punishment for promoting cooperation when mutations are common, and highlight how decisions about which strategies to include in the strategy set can have profound effects on the resulting dynamics. Copyright © 2014 Elsevier Ltd. All rights reserved.

  14. Neuropeptide AF induces anxiety-like and antidepressant-like behavior in mice.

    Science.gov (United States)

    Palotai, Miklós; Telegdy, Gyula; Tanaka, Masaru; Bagosi, Zsolt; Jászberényi, Miklós

    2014-11-01

    Little is known about the action of neuropeptide AF (NPAF) on anxiety and depression. Only our previous study provides evidence that NPAF induces anxiety-like behavior in rats. Therefore, the aim of the present study was to investigate the action of NPAF on depression-like behavior and the underlying neurotransmissions in mice. In order to determine whether there are species differences between rats and mice, we have investigated the action of NPAF on anxiety-like behavior in mice as well. A modified forced swimming test (mFST) and an elevated plus maze test (EPMT) were used to investigate the depression and anxiety-related behaviors, respectively. Mice were treated with NPAF 30min prior to the tests. In the mFST, the animals were pretreated with a non-selective muscarinic acetylcholine receptor antagonist, atropine, a non-selective 5-HT2 serotonergic receptor antagonist, cyproheptadine, a mixed 5-HT1/5-HT2 serotonergic receptor antagonist, methysergide, a D2/D3/D4 dopamine receptor antagonist, haloperidol, a α1/α2β-adrenergic receptor antagonist, prazosin or a non-selective β-adrenergic receptor antagonist, propranolol 30min before the NPAF administration. In the mFST, NPAF decreased the immobility time and increased the climbing and swimming times. This action was reversed completely by methysergide and partially by atropine, whereas cyproheptadine, haloperidol, prazosin and propranolol were ineffective. In the EPMT, NPAF decreased the time spent in the arms (open/open+closed). Our results demonstrate that NPAF induces anti-depressant-like behavior in mice, which is mediated, at least in part, through 5HT2-serotonergic and muscarinic cholinergic neurotransmissions. In addition, the NPAF-induced anxiety is species-independent, since it develops also in mice. Copyright © 2014 Elsevier B.V. All rights reserved.

  15. The Effects of Histaminergic Agents in the Nucleus ccumbens of Rats in the Elevated Plus-Maze Test of Anxiety

    Directory of Open Access Journals (Sweden)

    Ameneh Rezayof

    2010-05-01

    Full Text Available "n Objective: "n The nucleus accumbens (NAc receive histaminergic neurons from tuberomammillary nuclei. There are reports indicating that central histamine systems are involved in many physiological behavioral processes, including anxiety. The aim of the present study was to assess whether the histaminergic system of the NAc is involved in anxiety-related behaviors. Methods: Rats were anesthetized with intra-peritoneal injection of ketamine hydrochloride, plus xylazine and then were placed in a stereotaxic apparatus. In addition, two stainless-steel cannuale were placed 2 mm above the nucleus accumbens shell. Seven days after recovery from surgery, the behavioral testing was started. As a model of anxiety, the elevated plus maze which is a useful test to investigate the effects of anxiogenic or anxiolytic drugs in rodents, was used in male Wistar rats.  "nResults: Intra-NAc administration of histamine (0.01, 0.1 and 1 µg/rat increased the percentage of open arm time (%OAT and open arm entries (%OAE ,but not locomotor activity, indicating an anxiolytic response. Furthermore, bilateral  microinjections of different doses of the H1 receptor  antagonist pyrilamine (0.001, 0.01, 0.1 and 1 µg/rat or the H2 receptor antagonist ranitidine (0.001, 0.01, 0.1 and 1 µg/rat into the NAc increased %OAT and %OAE , but not locomotor activity. However, both histamine and histamine receptor antagonists showed an anxiolytic-like effect ; the antagonists (1 µg/rat also decreased the histamine response. "n "n Conclusion: The results may indicate a modulatory effect for the H1 and H2 histamine receptors of nucleus accumbens in the anxiety behavior of rats.

  16. Water-soluble derivatives of 25-OCH3-PPD and their anti-proliferative activities.

    Science.gov (United States)

    Zhou, Wu-Xi; Sun, Yuan-Yuan; Yuan, Wei-Hui; Zhao, Yu-Qing

    2017-05-01

    (20R)-25-Methoxyl-dammarane-3β,12β,20-triol (25-OCH 3 -PPD, AD-1) is a dammarane-type sapogenin showing anti-tumor potential. In the search for new anti-tumor agents with higher potency than our previously identified compound 25-OCH 3 -PPD, 11 novel sulfamic acid and diacid derivatives that could improve water solubility and contribute to good drug potency and pharmacokinetic profiles were designed and synthesized. Their in vitro anti-tumor activities in MCF-7, A-549, HCT-116, and BGC-823 cell lines and one normal cell line were tested by standard MTT assay. Results showed that compared with compound 25-OCH 3 -PPD, compounds 1, 4, and 5 exhibited higher cytotoxic activity on almost all cell lines, together with lower toxicity in the normal cell. In particular, compound 1 exhibited the best anti-tumor activity in the in vitro assays. The water solubility of 25-OCH 3 -PPD and its derivatives was tested and the results showed that the solubility of 25-OCH 3 -PPD sulfamic acid and diacid derivatives were better than that of 25-OCH 3 -PPD in water, which may provide valuable data for the research and development of new anti-tumor agents. Copyright © 2017 Elsevier Inc. All rights reserved.

  17. Anti-Inflammatory Activity of Iridoids and Verbascoside Isolated from Castilleja tenuiflora

    Directory of Open Access Journals (Sweden)

    Verónica Rodríguez-López

    2013-09-01

    Full Text Available Castilleja tenuiflora (Orobanchaceae has been used in Mexican traditional medicine as a treatment for cough, dysentery, anxiety, nausea and vomiting as well as hepatic and gastrointestinal diseases. The ethanolic extract of the aerial parts of Castilleja tenuiflora was separated by silica gel column chromatography. The fractions were evaluated using the induced edema acetate 12-O-tetradecanoylphorbol (TPA anti-inflammatory activity model. The most active fraction was subjected to medium-pressure liquid chromatography (MPLC with UV detection at 206 and 240 nm. The following iridoids were isolated: geniposidic acid, aucubin, bartioside, 8-epi-loganin, mussaenoside, and the phenylpropanoid verbascoside. The most active iridoid was geniposidic acid, which was more active than the control (indomethacin, and the least active iridoid was mussaenoside. 8-epi-Loganin, and mussaenoside have not been previously reported to be anti-inflammatory compounds. The results of these investigations confirm the potential of Mexican plants for the production of bioactive compounds and validate the ethnomedical use of Castilleja tenuiflora-like anti-inflammatory plants.

  18. Use of anti-obesity drugs among college students.

    Science.gov (United States)

    Martins, Maria do Carmo de Carvalho e; Souza Filho, Manoel Dias de; Moura, Felipe Scipião; Carvalho, Juliana de Sousa Ribeiro de; Müller, Marina Costa; Neves, Rebeka Valença; Mousinho, Patrícia Coelho; Lima, Iúri Paz

    2011-01-01

    To evaluate the use of anti-obesity drugs among students attending a public university. This was a cross sectional random study of 664 college students. Drug use, socioeconomic, and anthropometric variables were observed. Body mass index (BMI) and waist circumference (WC) were classified according to World Health Organization criteria. Current or previous use of anti-obesity drugs was reported by 6.8% of students. Amphetamine and sympathomimetic amines (40.5%) were the most commonly used drugs. Among those who reported use of anti-obesity agents, 62.2% were female. Only 31.1% of medications were prescribed by doctors. Mean BMI and WC were higher among students reporting the use of such drugs, but 47% of them were classified as eutrophic by BMI, and 76.5% had normal WC measure. The use of anti-obesity drugs among college students is of concern, particularly due to the high proportion of drug use without indication or prescription.

  19. A Novel Anti-Pollution Filter for Volatile Agents During Cardiopulmonary Bypass: Preliminary Tests.

    Science.gov (United States)

    Nigro Neto, Caetano; Landoni, Giovanni; Tardelli, Maria Angela

    2017-08-01

    Concerns regarding pollution of the operating room by volatile anesthetics and effects on atmospheric ozone depletion exist. Volatile agents commonly are used during cardiopulmonary bypass to provide anesthesia independent of any supposed myocardial protective effects. The authors' aim was to create and to assess the performance of a prototype filter for volatile agents to be connected to the cardiopulmonary bypass circuit to avoid the emission of volatile agents to the operating room, and also to the environment without causing damage to the membrane oxygenator. Observational trial. University hospital. Prototype filter for volatile agents. The prototype filter was tested in a single ex vivo experiment. The main data measured during the test were pressure drop to detect interference with the performance of the oxygenator, back pressure to detect overpressure to the outlet gas jacket of the oxygenator, analysis of exhaled sevoflurane after the membrane oxygenator, and after the filter to detect any presence of sevoflurane. The prototype filter adsorbed the sevoflurane eliminated through the outlet portion of the oxygenator. During the entire test, the back pressure remained constant (4 mmHg) and pressure drop varied from 243 mmHg to 247 mmHg. The prototype filter was considered suitable to absorb the sevoflurane, and it did not cause an overpressure to the membrane oxygenator during the test. Copyright © 2017 Elsevier Inc. All rights reserved.

  20. Hypothyroidism in Cancer Patients on Immune Checkpoint Inhibitors with anti-PD1 Agents: Insights on Underlying Mechanisms.

    Science.gov (United States)

    Alhusseini, M; Samantray, J

    2017-04-01

    Background: Immune therapy using monoclonal antibodies against cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) and programmed cell death 1 receptor (PD-1) for various cancers have been reported to cause thyroid dysfunction. Little is known, however, about the underlying pathogenic mechanisms and the course of hypothyroidism that subsequently develops. In this report, we use the change in thyroglobulin and thyroid antibody levels in patients on immune therapy who develop hypothyroidism to better understand its pathogenesis as well as examine the status of hypothyroidism in the long term. Methods: We report a case series of 10 patients who developed hypothyroidism after initiation of immune therapy (either anti-PD-1 alone or in combination with anti-CTLA-4). Available thyroid antibodies including anti-thyroglobulin (anti-Tg), anti-thyroid peroxidase (anti-TPO), and thyroid stimulating immunoglobulin (TSI) were noted during the initial thyroiditis phase as well as the hypothyroid phase. Persistence or remission of hypothyroidism was noted at 6 months. Summary: During the thyroiditis phase, 50% of the patients had elevated Tg titers, 40% had elevated anti-Tg, and 40% had elevated TSI. All of these titers decreased during the hypothyroid phase. Permanent hypothyroidism was noted in 80% of the cases. Conclusion: Hypothyroidism following initiation of immune therapy has immunologic and non-immunologic mediated mechanisms and is likely to be persistent. © Georg Thieme Verlag KG Stuttgart · New York.

  1. Dental anxiety and personality: investigating the relationship between dental anxiety and self-consciousness.

    Science.gov (United States)

    Economou, George C

    2003-09-01

    This study investigated whether personality plays a role in a condition called dental anxiety. Specifically, the study examined the relationship between dental anxiety (the negative response to the stress elicited from a dental interaction) and self-consciousness (the tendency to evaluate aspects of oneself that are subject to private and public display). The purpose of this study was to identify the characteristics possessed by dentally anxious individuals who face potential health risks because of their avoidance. Sixty York University undergraduate students were recruited by convenience sampling to participate. These subjects completed Corah's Dental Anxiety Scale and the Self-Consciousness Scale. The Self-Consciousness Scale consists of three subscales, including private self-consciousness, public self-consciousness, and social anxiety. Results indicated an 0.54 significant correlation between dental anxiety and self-consciousness. The public self-consciousness and social anxiety subscales correlated the most with dental anxiety. Furthermore, the data did not indicate a significant moderating relationship for gender between the two aforementioned variables. These results contribute to the establishment of personality characteristics as one of the dimensions determining dental anxiety.

  2. Simultaneous virtual prediction of anti-Escherichia coli activities and ADMET profiles: A chemoinformatic complementary approach for high-throughput screening.

    Science.gov (United States)

    Speck-Planche, Alejandro; Cordeiro, M N D S

    2014-02-10

    Escherichia coli remains one of the principal pathogens that cause nosocomial infections, medical conditions that are increasingly common in healthcare facilities. E. coli is intrinsically resistant to many antibiotics, and multidrug-resistant strains have emerged recently. Chemoinformatics has been a great ally of experimental methodologies such as high-throughput screening, playing an important role in the discovery of effective antibacterial agents. However, there is no approach that can design safer anti-E. coli agents, because of the multifactorial nature and complexity of bacterial diseases and the lack of desirable ADMET (absorption, distribution, metabolism, elimination, and toxicity) profiles as a major cause of disapproval of drugs. In this work, we introduce the first multitasking model based on quantitative-structure biological effect relationships (mtk-QSBER) for simultaneous virtual prediction of anti-E. coli activities and ADMET properties of drugs and/or chemicals under many experimental conditions. The mtk-QSBER model was developed from a large and heterogeneous data set of more than 37800 cases, exhibiting overall accuracies of >95% in both training and prediction (validation) sets. The utility of our mtk-QSBER model was demonstrated by performing virtual prediction of properties for the investigational drug avarofloxacin (AVX) under 260 different experimental conditions. Results converged with the experimental evidence, confirming the remarkable anti-E. coli activities and safety of AVX. Predictions also showed that our mtk-QSBER model can be a promising computational tool for virtual screening of desirable anti-E. coli agents, and this chemoinformatic approach could be extended to the search for safer drugs with defined pharmacological activities.

  3. Neuroprotective and Anti-Aging Potentials of Essential Oils from Aromatic and Medicinal Plants

    Directory of Open Access Journals (Sweden)

    Muhammad Ayaz

    2017-05-01

    Full Text Available The use of essential oils (EOs and their components is known since long in traditional medicine and aromatherapy for the management of various diseases, and is further increased in the recent times. The neuroprotective and anti-aging potentials of EOs and their possible mechanism of actions were evaluated by numerous researchers around the globe. Several clinically important EOs and their components from Nigella sativa, Acorus gramineus, Lavandula angustifolia, Eucalyptus globulus, Mentha piperita, Rosmarinus officinalis, Jasminum sambac, Piper nigrum and so many other plants are reported for neuroprotective effects. This review article was aimed to summarize the current finding on EOs tested against neurodegenerative disorders like Alzheimer disease (AD and dementia. The effects of EOs on pathological targets of AD and dementia including amyloid deposition (Aβ, neurofibrillary tangles (NFTs, cholinergic hypofunction, oxidative stress and glutamatergic abnormalities were focused. Furthermore, effects of EOs on other neurological disorders including anxiety, depression, cognitive hypofunction epilepsy and convulsions were also evaluated in detail. In conclusion, EOs were effective on several pathological targets and have improved cognitive performance in animal models and human subjects. Thus, EOs can be developed as multi-potent agents against neurological disorders with better efficacy, safety and cost effectiveness.

  4. Social Exclusion Anxiety

    DEFF Research Database (Denmark)

    Søndergaard, Dorte Marie

    2017-01-01

    Social exclusion anxiety is a term which builds on a social-psychological concept of human beings as existentially dependent on social embeddedness. This entry explores the concept in relation to bullying among children, which is a widespread and serious problem in schools and institutions. Social...... exclusion anxiety and longing for belonging are both central aspects of the affects and processes that enact and challenge social groups. Social exclusion anxiety should not be confused with ‘social phobia’, which is a concept within clinical psychology that focuses on the individual and refers to a phobic...... psychological condition. Social exclusion anxiety instead points to a distributed affect which circulates and smolders in all social groups. This is the result of an ever-present risk of someone being judged unworthy to belong to, or deemed not a legitimate participant in, a social group. Such anxiety may...

  5. Anti-Angiogenics: Current Situation and Future Perspectives.

    Science.gov (United States)

    Zirlik, Katja; Duyster, Justus

    2018-01-01

    Angiogenesis, the process leading to the formation of new blood vessels, is one of the hallmarks of cancer. Extensive studies established that i) vascular endothelial growth factor (VEGF) is a key driver of sprouting angiogenesis, ii) VEGF is overexpressed in most solid cancers, and iii) inhibition of VEGF can suppress tumor growth in animal models. This has led to the development of pharmacological agents for anti-angiogenesis to disrupt the vascular supply and starve the tumor of nutrients and oxygen, primarily through the blockade of VEGF/VEGF receptor signaling. This effort has resulted in 11 anti-VEGF drugs approved for certain advanced cancers, either alone or in combination with chemotherapy and other targeted therapies. However, inhibition of VEGF signaling is not effective in all cancers, and anti-angiogenics have often only limited impact on overall survival of cancer patients. This review focuses on the current status of FDA-approved anti-angiogenic antibodies and tyrosine kinase inhibitors and summarizes the progress and future directions of VEGF-targeted therapy. © 2018 S. Karger GmbH, Freiburg.

  6. Osmium(VI) complexes as a new class of potential anti-cancer agents.

    Science.gov (United States)

    Ni, Wen-Xiu; Man, Wai-Lun; Cheung, Myra Ting-Wai; Sun, Raymond Wai-Yin; Shu, Yuan-Lan; Lam, Yun-Wah; Che, Chi-Ming; Lau, Tai-Chu

    2011-02-21

    A nitridoosmium(VI) complex [Os(VI)(N)(sap)(OH(2))Cl] (H(2)sap = N-salicylidene-2-aminophenol) displays prominent in vitro and in vivo anti-cancer properties, induces S- and G2/M-phase arrest and forms a stable adduct with dianionic 5'-guanosine monophosphate.

  7. Activity of antimicrobial peptide mimetics in the oral cavity: II. Activity against periopathogenic biofilms and anti-inflammatory activity

    Science.gov (United States)

    Hua, J; Scott, R.W.; Diamond, G

    2011-01-01

    Whereas periodontal disease is ultimately of bacterial etiology, from multispecies biofilms of gram-negative anaerobic microorganisms, much of the deleterious effects are caused by the resultant epithelial inflammatory response. Hence, development of a treatment that combines anti-biofilm antibiotic activity with anti-inflammatory activity would be of great utility. Antimicrobial peptides (AMPs) such as defensins are naturally occurring peptides that exhibit broad-spectrum activity as well as a variety of immunomodulatory activities. Furthermore, bacteria do not readily develop resistance to these agents. However, clinical studies have suggested that they do not represent optimal candidates for exogenous therapeutic agents. Small-molecule mimetics of these AMPs exhibit similar activities to the parent peptides, in addition to having low toxicity, high stability and low cost. To determine whether AMP mimetics have the potential for treatment of periodontal disease, we examined the activity of one mimetic, mPE, against biofilm cultures of Aggregatibacter actinomycetemcomitans and Porphyromonas gingivalis. Metabolic assays as well as culture and biomass measurement assays demonstrated that mPE exhibits potent activity against biofilm cultures of both species. Furthermore, as little as 2 µg ml−1 mPE was sufficient to inhibit interleukin-1β-induced secretion of interleukin-8 in both gingival epithelial cells and THP-1 cells. This anti-inflammatory activity is associated with a reduction in activation of nuclear factor-κB, suggesting that mPE can act both as an anti-biofilm agent in an anaerobic environment and as an anti-inflammatory agent in infected tissues. PMID:21040516

  8. Anti-photoaging and Photoprotective Compounds Derived from Marine Organisms

    Directory of Open Access Journals (Sweden)

    Ramjee Pallela

    2010-04-01

    Full Text Available Marine organisms form a prominent component of the oceanic population, which significantly contribute in the production of cosmeceutical and pharmaceutical molecules with biologically efficient moieties. In addition to the molecules of various biological activities like anti-bacterial, anti-cancerous, anti-inflammatory and anti-oxidative etc., these organisms also produce potential photoprotective or anti-photoaging agents, which are attracting present day researchers. Continuous exposure to UV irradiation (both UV-A and UV-B leads to the skin cancer and other photoaging complications, which are typically mediated by the reactive oxygen species (ROS, generated in the oxidative pathways. Many of the anti-oxidative and anti-photoaging compounds have been identified previously, which work efficiently against photodamage of the skin. Recently, marine originated photoprotective or anti-photoaging behavior was observed in the methanol extracts of Corallina pilulifera (CPM. These extracts were found to exert potent antioxidant activity and protective effect on UV-A-induced oxidative stress in human dermal fibroblast (HDF cells by protecting DNA and also by inhibiting matrix metalloproteinases (MMPs, a key component in photoaging of the skin due to exposure to UV-A. The present review depicts various other photoprotective compounds from algae and other marine sources for further elaborative research and their probable use in cosmeceutical and pharmaceutical industries.

  9. The tree-species-specific effect of forest bathing on perceived anxiety alleviation of young-adults in urban forests

    Directory of Open Access Journals (Sweden)

    Haoming Guan

    2017-12-01

    Full Text Available Forest bathing, i.e. spending time in a forest to walk, view and breathe in a forest, can alleviate the mental depression of visitors, but the tree-species-specific effect of this function by the urban forest is unknown. In this study, sixty-nine university students (aged 19-22, male ratio: 38% were recruited as participants to visit urban forests dominated by birch (Betula platyphylla Suk., maple (Acer triflorum Komarov and oak (Quercus mongolica Fisch. ex Ledeb trees in a park at the center of Changchun City, Northeast China. In the maple forest only the anxiety from study interest was decreased, while the anxiety from employment pressure was alleviated to the most extent in the birch forest. Participants perceived more anxiety from lesson declined in the oak forest than in the birch forest. Body parameters of weight and age were correlated with the anti-anxiety scores. In the oak forest, female participants can perceive more anxiety alleviation than male participants. For university students, forest bathing in our study can promote their study interest. Forest bathing can be more effective to alleviate the anxiety of young adults with greater weight. The birch forest was recommended to be visited by students to alleviate the pressure of employment worry, and the oak forest was recommended to be visited by girls.

  10. Anti-venom potentials of Friedelin isolated from hexane extract ...

    African Journals Online (AJOL)

    ... taenicidal, cough remedy, dysentery, cancer, diabetes mellitus, tuberculosis and snake bite remedy. In this report, an attempt has been made to evaluate the bioactive molecules in the plant that are anti-venom agents. Consequently, the stem bark was exhaustively extracted with hexane and subsequently with methanol.

  11. Anti-venom Potentials of Friedelin Isolated from Hexane Extract

    African Journals Online (AJOL)

    USER

    474. Selvanayagam et al.,1995). Quite a good record of plant anti-venom agents used among the various ethnic groups and regions of Nigeria has been established through ethnobanical and ethnomedical records. Notably ...... Guidelines for the Management of snake-bites. WHO Library Cataloguing-in-. Publication data ...

  12. Baby Shampoo versus Commercial Anti-fogging Solution to Prevent Fogging during Nasal Endoscopy: A Randomized Double-Blinded, Matched-Pair, Equivalent Trial.

    Science.gov (United States)

    Chainansamit, Seksun; Piromchai, Patorn; Anantpinijwatna, Intira; Kasemsiri, Pornthep; Thanaviratananich, Sanguansak

    2015-08-01

    To compare the minimization of the fog condensation during nasal endoscopy between a commercial anti-fogging agent and baby shampoo. This randomized double-blinded matched pair study was conducted at the Department of Otorhinolaryngology, Faculty of Medicine, Khon Kaen University during February 4, 2013 to March 14, 2013. The commercial anti-fogging solution (Ultrastop®) and baby shampoo solution (Johnson's® no more tear®) were compared. A computer generated randomization was performed to select the solution applying on the lens for nasal endoscopy of the right nasal cavity. The other solution was then used for the left one. Three passes of endoscopy were performed to examine the floor of the nose, the sphenoethmoidal recess and the middle meatus area which spent about 30 seconds for each time of endoscopy. The time to become foggy on the lens and the preferred solution assessed by the endoscopists were recorded. There were 71 eligible patients recruited in the study, 37 males (52.1%) and 34 females (47.9%). There was no fogging during a 30-second nasal endoscopy either by baby shampoo or commercial anti-fogging solution. However, 9.86% (95% C12.75-16.97) of endoscopists preferred commercial anti-fogging agent, 7.04% (95% CI 0.94-13.14) preferred baby shampoo and 83.10% (95% CI 74.16-92.03) had equal satisfaction. Both agents had no statistically significant difference for preventing foggy on the lens. Baby shampoo is an effective agent to prevent fogging during nasal endoscopy and comparable with the commercial anti-fogging agent.

  13. The feasibility of a targeted ultrasound contrast agent carrying genes and cell-penetrating peptides to hypoxic HUVEC

    International Nuclear Information System (INIS)

    Tian Ju; Wang Zhigang; Ren Jianli; Zhang Qingfeng; Liu Li

    2012-01-01

    Objective: To prepare an anti-P-selectin targeted ultrasound contrast agent carrying genes and cell-penetrating peptides (CPP) and to investigate its feasibility of delivery to hypoxic human umbilical vein endothelial cells (HUVEC). Methods: Anti-P-selectin targeted ultrasound contrast agent carrying a green fluorescent protein gene (pEGFP-N1) and CPP was prepared by mechanical vibration and carbodiimide techniques. The appearance, distribution, concentration and diameter of the ultrasound contrast agent were measured. The gene and CPP distribution on the agent was investigated using confocal laser scanning microscopy (CLSM). The efficiency of the ultrasound contrast agent to carry the gene and CPP was investigated by fluorospectrophotometry. HUVEC were cultured in vitro and hypoxic HUVEC were prepared using hydrogen peroxide (H 2 O 2 ). Hypoxic HUVEC were randomly assigned targeted ultrasound contrast agents and non-targeted ultrasound contrast agents for transfection. The transfection effect of green fluorescent protein in the two groups was observed using fluorescence microscopy and flow cytometry. T-test and linear correlation analysis were used for statistical analysis. Results: The average diameter of anti-P-selectin targeted ultrasound contrast agents carrying gene and CPP was (2.15 ±0.36) μm and the concentration was (1.58 ± 0.23) × 10 7 /ml.The results of CLSM showed that gene and CPP were distributed on the shell of the agent. The gene encapsulation efficiency was 28% (y=0.932x-0.09, r=0.993, P<0.05), and the CPP encapsulation efficiency was 25% (y=5.875x-0.81, r=0.987, P<0.05). EGFP expression was observed using fluorescence microscopy in targeted ultrasound contrast agents and non-targeted ultrasound contrast agents. The average transfection efficiencies of targeted ultrasound contrast agents and non-targeted ultrasound contrast agents were (18.74 ± 0.47) % and (15.34 ± 0.22) % after 24 h (t=10.923, P<0.001). Conclusions: The in vitro studies

  14. Competitive anxiety in young athletes: differentiating somatic anxiety, worry, and concentration disruption.

    Science.gov (United States)

    Grossbard, Joel R; Smith, Ronald E; Smoll, Frank L; Cumming, Sean P

    2009-03-01

    The age-appropriate Sport Anxiety Scale-2 (SAS-2; Smith, Smoll, Cumming, & Grossbard, 2006) was used to assess levels of cognitive and somatic anxiety among male and female youth sport participants. Confirmatory factor analyses with a sample of 9-14 year old athletes (N=1038) supported the viability of a three-factor model of anxiety involving somatic anxiety, worry, and concentration disruption previously demonstrated in high school and college samples. Tests for factorial invariance revealed that the three-factor model was an equally good fit for 9-11 year olds and 12-14 year olds, and for both males and females. Gender and age were modestly related to anxiety scores. Worry about performing poorly was highest in girls and in older athletes, whereas boys reported higher levels of concentration disruption in competitive sport situations. Implications for emotional perception and for the study of competitive anxiety in young athletes are discussed.

  15. Plasma exchanges for severe acute neurological deterioration in patients with IgM anti-myelin-associated glycoprotein (anti-MAG) neuropathy.

    Science.gov (United States)

    Baron, M; Lozeron, P; Harel, S; Bengoufa, D; Vignon, M; Asli, B; Malphettes, M; Parquet, N; Brignier, A; Fermand, J P; Kubis, N; Arnulf, Bertrand

    2017-06-01

    Monoclonal IgM anti-myelin-associated glycoprotein (MAG) antibody-related peripheral neuropathy (anti-MAG neuropathy) is predominantly a demyelinating sensory neuropathy with ataxia and distal paresthesia. The clinical course of anti-MAG neuropathy is usually slowly progressive making difficult the identification of clear criteria to start a specific treatment. Although no consensus treatment is yet available, a rituximab-based regimen targeting the B-cell clone producing the monoclonal IgM may be proposed, alone or in combination with alkylating agents or purine analogs. However, in some rare cases, an acute and severe neurological deterioration can occur in few days leading to a rapid loss of autonomy. In these cases, a treatment rapidly removing the monoclonal IgM from the circulation might be useful before initiating a specific therapy. We report successful treatment with plasma exchanges (PE) in four patients presenting with acute neurological deterioration. PE allowed a dramatic and rapid neurological improvement in all patients. PE are safe and may be useful at the initial management of these cases of anti-MAG neuropathy.

  16. Marine Peptides and Their Anti-Infective Activities

    OpenAIRE

    Kang, Hee Kyoung; Seo, Chang Ho; Park, Yoonkyung

    2015-01-01

    Marine bioresources are a valuable source of bioactive compounds with industrial and nutraceutical potential. Numerous clinical trials evaluating novel chemotherapeutic agents derived from marine sources have revealed novel mechanisms of action. Recently, marine-derived bioactive peptides have attracted attention owing to their numerous beneficial effects. Moreover, several studies have reported that marine peptides exhibit various anti-infective activities, such as antimicrobial, antifungal,...

  17. Socioeconomic and therapy factor influence on self-reported fatigue, anxiety and depression in rheumatoid arthritis patients

    Directory of Open Access Journals (Sweden)

    Mirjana Lapčević

    Full Text Available Abstract Introduction: Fatigue, anxiety and depression are very frequent symptoms in patients with rheumatoid arthritis (RA. Goals: In this study we evaluated the influence of socioeconomic characteristics, therapy and comorbidities on the self-reported high fatigue, anxiety and depression in patients with RA. Method: Multicenter cross-sectional study was performed in 22 health institutions in Serbia during the period from April-August 2014 in population of older RA patients. Self-reported patients health status was measured by: Fatigue Assessment Scale, Patient Health Questionnaire-9 and Generalized Anxiety Disorder-7. Treatment modalities were defined as: (1 non-steroidal anti-inflammatory drugs (NSAIDs and/or analgesics and/or corticosteroids; (2 synthetic disease-modifying antirheumatic drugs (DMARDs alone or in combination with corticosteroids and/or NSAIDs and (3 any RA treatment which includes biologic DMARDs. Results: There were significant predictors of high depression: synthetic DMARDs therapy in combination with corticosteroids and/or NSAIDs, physiotherapist self-payment, frequent taxi use, alternative treatment and employment status. The need for another person's assistance, supplemental calcium therapy and professional qualifications were the predictors of a high fatigue, whereas the age above 65 years had the protective effect on it. Anxiety was an independent high fatigue predictor. The predictors of a high anxiety were: gastroprotection with proton-pump inhibitors and patient occupation. Conclusion Socioeconomic predictors of self-reported high depression, anxiety or fatigue are different for each of the mentioned outcomes, while accompanied with the basic RA treatment they exclusively explain a high depression. The anxiety, jointed with the socioeconomic variables and supplemental therapy, is a significant fatigue predictor in RA patients.

  18. Generalised anxiety disorder

    OpenAIRE

    Gale, Christopher K; Millichamp, Jane

    2011-01-01

    Generalised anxiety disorder is characterised by persistent, excessive and difficult-to-control worry, which may be accompanied by several psychic and somatic symptoms, including suicidality. Generalized anxiety disorder is the most common psychiatric disorder in the primary care, although it is often underrecognised and undertreated. Generalized anxiety disorder is typically a chronic condition with low short- and medium-term remission rates. Clinical presentations often include depression, ...

  19. Gallium a unique anti-resorptive agent in bone: Preclinical studies on its mechanisms of action

    International Nuclear Information System (INIS)

    Bockman, R.; Adelman, R.; Donnelly, R.; Brody, L.; Warrell, R.; Jones, K.W.

    1990-01-01

    The discovery of gallium as a new and unique agent for the treatment of metabolic bone disorders was in part fortuitous. Gallium is an exciting new therapeutic agent for the treatment of pathologic states characterized by accelerated bone resorption. Compared to other therapeutic metal compounds containing platinum or germanium, gallium affects its antiresorptive action without any evidence of a cytotoxic effect on bone cells. Gallium is unique amongst all therapeutically available antiresorptive agents in that it favors bone formation. 18 refs., 1 fig

  20. Molecularly characterized solvent extracts and saponins from Polygonum hydropiper L show high anti-angiogenic, anti-tumor, brine shrimp and fibroblast NIH/3T3 cell line cytotoxicity

    Directory of Open Access Journals (Sweden)

    Muhammad eAyaz

    2016-03-01

    Full Text Available Polygonum hydropiper is used as anti-cancer and anti-rheumatic agent in folk medicine. This study was designed to investigate the anti-angiogenic, anti-tumor and cytotoxic potentials of different solvent extracts and isolated saponins. Samples were analyzed using GC, GC-MS to identify major and bioactive compounds. Quantitation of antiangiogenesis for the plant's samples including methanolic extract (Ph.Cr, its subsequent fractions; n-hexane (Ph.Hex, chloroform (Ph.Chf, ethyl acetate (Ph.EtAc, n-Butanol (Ph.Bt, aqueous (Ph.Aq, saponins (Ph.Sp were performed using the chick embryo chorioallantoic membrane (CAM assay. Potato disc anti-tumor assay was performed on Agrobacterium tumefaciens containing tumor inducing plasmid. Cytotoxicity was performed on Artemia salina and mouse embryonic fibroblast NIH/3T3 cell line using brine shrimps and MTT cells viability assays. The GC-MS analysis of Ph.Cr, Ph.Hex, Ph.Chf, Ph.Bt and Ph.EtAc identified 126, 124, 153, 131 and 164 compounds respectively. In anti-angiogenic assay, Ph.Chf, Ph.Sp, Ph.EtAc and Ph.Cr exhibited highest activity with IC50 of 28.65, 19.21, 88.75 and 461.53 µg/ml respectively. In anti-tumor assay, Ph.Sp, Ph.Chf, Ph.EtAc and Ph.Cr were most potent with IC50 of 18.39, 73.81, 217.19 and 342.53 µg/ml respectively. In MTT cells viability assay, Ph.Chf, Ph.EtAc, Ph.Sp were most active causing 79.00, 72.50 and 71.50% cytotoxicity respectively at 1000 µg/ml with the LD50 of 140, 160 and 175 µg/ml respectively. In overall study, Ph.Chf and Ph.Sp have shown overwhelming results which signifies their potentials as sources of therapeutic agents against cancer.

  1. Interaction of Induced Anxiety and Verbal Working Memory: Influence of Trait Anxiety

    Science.gov (United States)

    Patel, Nilam; Stoodley, Catherine; Pine, Daniel S.; Grillon, Christian; Ernst, Monique

    2017-01-01

    This study examines the influence of trait anxiety on working memory (WM) in safety and threat. Interactions between experimentally induced anxiety and WM performance (on different cognitive loads) have been reported in healthy, nonanxious subjects. Differences in trait anxiety may moderate these interactions. Accordingly, these interactions may…

  2. In silico and in vivo anti-malarial studies of 18β glycyrrhetinic acid from Glycyrrhiza glabra.

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    Komal Kalani

    Full Text Available Malaria is one of the most prevailing fatal diseases causing between 1.2 and 2.7 million deaths all over the world each year. Further, development of resistance against the frontline anti-malarial drugs has created an alarming situation, which requires intensive drug discovery to develop new, more effective, affordable and accessible anti-malarial agents possessing novel modes of action. Over the past few years triterpenoids from higher plants have shown a wide range of anti-malarial activities. As a part of our drug discovery program for anti-malarial agents from Indian medicinal plants, roots of Glycyrrhizaglabra were chemically investigated, which resulted in the isolation and characterization of 18β-glycyrrhetinic acid (GA as a major constituent. The in vitro studies against P. falciparum showed significant (IC50 1.69 µg/ml anti-malarial potential for GA. Similarly, the molecular docking studies showed adequate docking (LibDock score of 71.18 for GA and 131.15 for standard anti-malarial drug chloroquine. Further, in silico pharmacokinetic and drug-likeness studies showed that GA possesses drug-like properties. Finally, in vivo evaluation showed a dose dependent anti-malarial activity ranging from 68-100% at doses of 62.5-250 mg/kg on day 8. To the best of our knowledge this is the first ever report on the anti-malarial potential of GA. Further work on optimization of the anti-malarial lead is under progress.

  3. Sleep and anxiety disorders

    OpenAIRE

    Staner, Luc

    2003-01-01

    Sleep disturbances-particularly insomnia - are highly prevalent in anxiety disorders and complaints such as insomnia or nightmares have even been incorporated in some anxiety disorder definitions, such as generalized anxiety disorder and posttraumatic stress disorder. In the first part of this review, the relationship between sleep and anxiety is discussed in terms of adaptive response to stress. Recent studies suggested that the corticotropin-releasing hormone system and the locus ceruleus-a...

  4. Treatment of anxiety disorders

    OpenAIRE

    Bandelow, Borwin; Michaelis, Sophie; Wedekind, Dirk

    2017-01-01

    Anxiety disorders (generalized anxiety disorder, panic disorder/agoraphobia, social anxiety disorder, and others) are the most prevalent psychiatric disorders, and are associated with a high burden of illness. Anxiety disorders are often underrecognized and undertreated in primary care. Treatment is indicated when a patient shows marked distress or suffers from complications resulting from the disorder. The treatment recommendations given in this article are based on guidelines, meta-analyses...

  5. Specificity of dysfunctional thinking in children with symptoms of social anxiety, separation anxiety and generalised anxiety

    NARCIS (Netherlands)

    Bogels, S.M.; Snieder, N.; Kindt, M.

    2003-01-01

    The present study investigated whether children with high symptom levels of either social phobia (SP), separation anxiety disorder (SAD), or generalised anxiety disorder (GAD) are characterised by a specific set of dysfunctional interpretations that are consistent with the cognitive model of their

  6. A novel screening method based on menadione mediated rapid reduction of tetrazolium salt for testing of anti-mycobacterial agents.

    Science.gov (United States)

    Singh, Upasana; Akhtar, Shamim; Mishra, Abhishek; Sarkar, Dhiman

    2011-02-01

    A microplate-based rapid, inexpensive and robust technique is developed by using tetrazolium salt 2,3-bis[2-methyloxy-4-nitro-5-sulfophenyl]-2H-tetrazolium-5-carboxanilide (XTT) and menadione to determine the viability of Mycobacterium tuberculosis, Mycobacterium bovis BCG and Mycobacterium smegmatis bacilli in microplate format. In general, XTT reduction is an extremely slow process which takes almost 24 h to produce a detectable signal. Menadione could drastically induce this reduction to an almost equal extent within a few minutes in a dose dependent manner. The reduction of XTT is directly proportional to the cell concentration in the presence of menadione. The standardized protocol used 200 μM of XTT and 60 μM of menadione in 250 μl of cell suspension grown either in aerobic or anaerobic conditions. The cell suspension of M. bovis BCG and M. tuberculosis were incubated for 40 min before reading the optical density at 470 nm whereas M. smegmatis was incubated for 20 min. Calculated Signal/Noise (S/N) ratios obtained by applying this protocol were 5.4, 6.4 and 9.4 using M. bovis BCG, M. tuberculosis and M. smegmatis respectively. The calculated Z' factors were >0.8 for all mycobacterium bacilli indicating the robustness of the XTT Reduction Menadione Assay (XRMA) for rapid screening of inhibitors. The assay protocol was validated by applying 10 standard anti-tubercular agents on M. tuberculosis, M. bovis BCG and M. smegmatis. The Minimum Inhibitory Concentration (MIC) values were found to be similar to reported values from Colony Forming Unit (CFU) and REMA (resazurin microplate assay) assays. Altogether, XRMA is providing a novel anti-tubercular screening protocol which could be useful in high throughput screening programs against different physiological stages of the bacilli. Copyright © 2010 Elsevier B.V. All rights reserved.

  7. Separation Anxiety (For Parents)

    Science.gov (United States)

    ... Safe Videos for Educators Search English Español Separation Anxiety KidsHealth / For Parents / Separation Anxiety What's in this ... both of you get through it. About Separation Anxiety Babies adapt pretty well to other caregivers. Parents ...

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

    Science.gov (United States)

    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

  9. Cystic Fibrosis Transmembrane Regulator Modulators: Implications for the Management of Depression and Anxiety in Cystic Fibrosis.

    Science.gov (United States)

    Talwalkar, Jaideep S; Koff, Jonathan L; Lee, Hochang B; Britto, Clemente J; Mulenos, Arielle M; Georgiopoulos, Anna M

    Individuals with cystic fibrosis (CF) are at high risk for depression and anxiety, which are associated with worse medical outcomes. Novel therapies for CF hold great promise for improving physical health, but the effects of these therapies on mental health remain poorly understood. This review aims to familiarize psychiatrists with the potential effect of novel CF therapies on depression and anxiety. We discuss novel therapies that directly target the mutant CF protein, the CF transmembrane regulator (CFTR), which are called CFTR modulators. We summarize depression and anxiety screening and treatment guidelines under implementation in accredited CF centers. Case vignettes highlight the complexities of caring for individuals with CF with comorbid depression and anxiety, including patients experiencing worsening depression and anxiety proximate to initiation of CFTR modulator therapy, and management of drug-drug interactions. Although CFTR modulator therapies provide hope for improving clinical outcomes, worsening depression and anxiety occurs in some patients when starting these novel agents. This phenomenon may be multifactorial, with hypothesized contributions from CFTR modulator-psychotropic medication interactions, direct effects of CFTR modulators on central nervous system function, the psychologic effect of starting a potentially life-altering drug, and typical triggers of depression and anxiety such as stress, pain, and inflammation. The medical and psychiatric complexity of many individuals with CF warrants more direct involvement of mental health specialists on the multidisciplinary CF team. Inclusion of mental health variables in patients with CF registries will facilitate further examination at an epidemiologic level. Copyright © 2017 The Academy of Psychosomatic Medicine. Published by Elsevier Inc. All rights reserved.

  10. ANTI-DIABETIC EFFECTS OF TURMERIC IN ALLOXAN INDUCE D DIABETIC RATS

    OpenAIRE

    Jeevangi; Manjunath; Deepak D; Prakash G; Prashant; Chetan

    2013-01-01

    ABSTRACT: OBJECTIVE AND BACKGROUND: Turmeric (Curcuma longa) is one of the common constituents of our daily food. The present study wa s undertaken to evaluate the anti-diabetic effects of ethanolic extract of Rhizomes of curcuma longa in alloxan induced diabetic rats and compared with of Pioglitazone, which is the standard anti-diabetic agent. METHODS: Alloxan monohydrate is used to induce diabetes mellitus in albino rats in the dose of 120mg/kg i.p. and ...

  11. Importancia del escrutinio para tuberculosis previo a la administración de agentes anti-TNF-α en uveítis: a propósito de un caso clínico

    Directory of Open Access Journals (Sweden)

    Enrique Leopoldo Zaldívar-Orta

    2014-10-01

    Conclusión: Es indispensable realizar pruebas de escrutinio para tuberculosis latente antes de iniciar tratamiento con agentes biológicos anti-TNF-α, particularmente con infliximab. Las pruebas que miden la producción de interferón gamma (IFN-γ in vitro en respuesta a los antígenos tuberculosos son una alternativa a la prueba cutánea clásica con tuberculina (PPD en la detección de tuberculosis, particularmente en individuos vacunados con el bacilo de Calmette-Guérin (BCG.

  12. Social Anxiety among Chinese People.

    Science.gov (United States)

    Fan, Qianqian; Chang, Weining C

    2015-01-01

    The experience of social anxiety has largely been investigated among Western populations; much less is known about social anxiety in other cultures. Unlike the Western culture, the Chinese emphasize interdependence and harmony with social others. In addition, it is unclear if Western constructed instruments adequately capture culturally conditioned conceptualizations and manifestations of social anxiety that might be specific to the Chinese. The present study employed a sequence of qualitative and quantitative approaches to examine the assessment of social anxiety among the Chinese people. Interviews and focus group discussions with Chinese participants revealed that some items containing the experience of social anxiety among the Chinese are not present in existing Western measures. Factor analysis was employed to examine the factor structure of the more comprehensive scale. This approach revealed an "other concerned anxiety" factor that appears to be specific to the Chinese. Subsequent analysis found that the new factor-other concerned anxiety-functioned the same as other social anxiety factors in their association with risk factors of social anxiety, such as attachment, parenting, behavioral inhibition/activation, and attitude toward group. The implications of these findings for a more culturally sensitive assessment tool of social anxiety among the Chinese were discussed.

  13. Inflammation in Depression and the Potential for Anti-Inflammatory Treatment

    DEFF Research Database (Denmark)

    Kohler, Ole; Krogh, Jesper; Mors, Ole

    2016-01-01

    Accumulating evidence supports an association between depression and inflammatory processes, a connection that seems to be bidirectional. Clinical trials have indicated antidepressant treatment effects for anti-inflammatory agents, both as add-on treatment and as monotherapy. In particular......, nonsteroidal anti-inflammatory drugs (NSAIDs) and cytokine-inhibitors have shown antidepressant treatment effects compared to placebo, but also statins, poly-unsaturated fatty acids, pioglitazone, minocycline, modafinil, and corticosteroids may yield antidepressant treatment effects. However, the complexity...... of the inflammatory cascade, limited clinical evidence, and the risk for side effects stress cautiousness before clinical application. Thus, despite proof-of-concept studies of anti-inflammatory treatment effects in depression, important challenges remain to be investigated. Within this paper, we review...

  14. The relation between public speaking anxiety and social anxiety: a review.

    Science.gov (United States)

    Blöte, Anke W; Kint, Marcia J W; Miers, Anne C; Westenberg, P Michiel

    2009-04-01

    This article reviewed the literature on public speaking anxiety in the context of social phobia subtyping. In total, 18 empirical studies on subtype issues related to public speaking anxiety were analyzed. Results of the reviewed studies are discussed in relation to their research method, that is, whether it focused on qualitative or quantitative aspects of subtype differences and whether it used a clinical or community sample. Evidence supported the premise that public speaking anxiety is a distinct subtype, qualitatively and quantitatively different from other subtypes of social phobia. The significance of this finding for social phobia studies using speech tasks to assess participants' state anxiety and behavioral performance is discussed.

  15. A Collaborator's Reputation Can Bias Decisions and Anxiety under Uncertainty.

    Science.gov (United States)

    Qi, Song; Footer, Owen; Camerer, Colin F; Mobbs, Dean

    2018-02-28

    Informational social influence theory posits that under conditions of uncertainty, we are inclined to look to others for advice. This leaves us remarkably vulnerable to being influenced by others' opinions or advice. Rational agents, however, do not blindly seek and act on arbitrary information, but often consider the quality of its source before committing to a course of action. Here, we ask the question of whether a collaborator's reputation can increase their social influence and, in turn, bias perception and anxiety under changing levels of uncertainty. Human male and female participants were asked to provide estimations of dot direction using the random dot motion (RDM) perceptual discrimination task and were paired with transient collaborators of high or low reputation whom provided their own estimations. The RDM varied in degrees of uncertainty and joint performance accuracy was linked to risk of an electric shock. Despite providing identical information, we show that collaborating with a high reputation compared with a low reputation partner, led to significantly more conformity during the RDM task for uncertain perceptual decisions. Consequently, high reputation partners decreased the subjects' anxiety during the anticipatory shock periods. fMRI data showed that parametric changes in conformity resulted in increased activity in the ventromedial PFC, whereas dissent was associated with increased in activity in the dorsal anterior cingulate cortex (dACC). Furthermore, the dACC and insula, regions involved in anticipatory pain, were significantly more active when collaborating with a low reputation partner. These results suggest that information about reputation can influence both cognitive and affective processes and in turn alter the neural circuits that underlie decision-making and emotion. SIGNIFICANCE STATEMENT Humans look to others for advice when making decisions under uncertainty. Rational agents, however, do not blindly seek information, but often

  16. The Study of the Relationship between Mothers' Anxiety with the Mathematical Performance and Students' Anxiety

    Directory of Open Access Journals (Sweden)

    Sepideh Moradpour

    2015-04-01

    Full Text Available Today mathematics stress have considered under interesting of many psychologists of mathematics education and cognitive psychologists too so that recognize emotion and mental stimulations of students in mathematics and to find scientific strategies for removing and controlling them. Anxiety is one of important and effective issues of 21th century. This study is done with aim of the study of relationship between mothers' anxiety with mathematics performance and anxiety of their children at first grade of high school at zone one of Tehran. Among population, 97 students and their mothers are chosen. Data of this research are collected by Cattell standard questionnaire for studying mothers' anxiety and standard questionnaire of mathematics anxiety for studying mathematics anxiety and a math exam for studying of students' performance. Research findings indicate that there is significant relationship between mothers' anxiety with mathematics anxiety and performance of students. Also it indicated that there is significant difference between students with high and low mathematics anxiety in term of mathematics performance.

  17. Relational anxiety in interracial interactions.

    Science.gov (United States)

    West, Tessa V; Shelton, J Nicole; Trail, Thomas E

    2009-03-01

    Most of the research on intergroup anxiety has examined the impact of people's own anxiety on their own outcomes. In contrast, we show that in intergroup interactions, one's partner's anxiety is just as important as one's own anxiety (if not more important). Using a diary study among college roommates, we show that partners' anxiety predicts respondents' anxiety across time on a daily basis, as well as respondents' interest in living together again the next year. We discuss the importance of taking a relational approach to understanding intergroup interactions.

  18. Anti-angiogenic Therapy in Patients with Advanced Gastric and Gastroesophageal Junction Cancer: A Systematic Review.

    Science.gov (United States)

    Chen, Li-Tzong; Oh, Do-Youn; Ryu, Min-Hee; Yeh, Kun-Huei; Yeo, Winnie; Carlesi, Roberto; Cheng, Rebecca; Kim, Jongseok; Orlando, Mauro; Kang, Yoon-Koo

    2017-10-01

    Despite advancements in therapy for advanced gastric and gastroesophageal junction cancers, their prognosis remains dismal. Tumor angiogenesis plays a key role in cancer growth and metastasis, and recent studies indicate that pharmacologic blockade of angiogenesis is a promising approach to therapy. In this systematic review, we summarize current literature on the clinical benefit of anti-angiogenic agents in advanced gastric cancer. We conducted a systematic search of PubMed and conference proceedings including the American Society of Clinical Oncology, the European Society for Medical Oncology, and the European Cancer Congress. Included studies aimed to prospectively evaluate the efficacy and safety of anti-angiogenic agents in advanced gastric or gastroesophageal junction cancer. Each trial investigated at least one of the following endpoints: overall survival, progression-free survival/time to progression, and/or objective response rate. Our search yielded 139 publications. Forty-two met the predefined inclusion criteria. Included studies reported outcomes with apatinib, axitinib, bevacizumab, orantinib, pazopanib, ramucirumab, regorafenib, sorafenib, sunitinib, telatinib, and vandetanib. Second-line therapy with ramucirumab and third-line therapy with apatinib are the only anti-angiogenic agents so far shown to significantly improve survival of patients with advanced gastric cancer. Overall, agents that specifically target the vascular endothelial growth factor ligand or receptor have better safety profile compared to multi-target tyrosine kinase inhibitors.

  19. An artemisinin derivative of praziquantel as an orally active antischistosomal agent.

    Directory of Open Access Journals (Sweden)

    Lanlan Dong

    Full Text Available Schistosomiasis is a major health problem in tropical and sub-tropical areas caused by species of trematode belonging to the genus Schistosoma. The treatment and control of this disease has been relying on the use of a single drug praziquantel. However, the drug resistance concern urged the development of new drugs against schistosoma. Here, we report our systematic biological evaluation of DW-3-15, a new lead compound developed based on our conjugation design rationale as an effective anti-schistosomal agent.The antischistosomal activity of DW-3-15 was systematically evaluated in S. japonicum infected mouse model for its stage-sensitivity and dose response. The results revealed that DW-3-15 exhibited 60-85% worm reduction rate against different development stage of worm. Scanning electron microscopy (SEM observation indicated that DW-3-15 may damage to the tegument of male schistosomes.Our results demonstrated that DW-3-15 showed potent anti-schistosomal activities in vivo. The results strongly support our conjugation design strategy of artemisinin analogs and further development of DW-3-15 as a new lead compound as anti-schistosomal agent.

  20. Does D-cycloserine enhance exposure therapy for anxiety disorders in humans? A meta-analysis.

    Directory of Open Access Journals (Sweden)

    Helga Rodrigues

    Full Text Available The treatment of anxiety is on the edge of a new era of combinations of pharmacologic and psychosocial interventions. A new wave of translational research has focused on the use of pharmacological agents as psychotherapy adjuvants using neurobiological insights into the mechanism of the action of certain psychological treatments such as exposure therapy. Recently, d-cycloserine (DCS an antibiotic used to treat tuberculosis has been applied to enhance exposure-based treatment for anxiety and has proved to be a promising, but as yet unproven intervention. The present study aimed to evaluate the efficacy of DCS in the enhancement of exposure therapy in anxiety disorders. A systematic review/meta-analysis was conducted. Electronic searches were conducted in the databases ISI-Web of Science, Pubmed and PsycINFO. We included only randomized, double-blind, placebo-controlled trials with humans, focusing on the role of DCS in enhancing the action of exposure therapy for anxiety disorders. We identified 328 references, 13 studies were included in our final sample: 4 on obsessive-compulsive disorder, 2 on panic disorder, 2 on social anxiety disorder, 2 on posttraumatic stress disorder, one on acrophobia, and 2 on snake phobia. The results of the present meta-analysis show that DCS enhances exposure therapy in the treatment of anxiety disorders (Cohen d =  -0.34; CI: -0.54 to -0.14, facilitating the specific process of extinction of fear. DCS seems to be effective when administered at a time close to the exposure therapy, at low doses and a limited number of times. DCS emerges as a potential new therapeutic approach for patients with refractory anxiety disorders that are unresponsive to the conventional treatments available. When administered correctly, DCS is a promising strategy for augmentation of CBT and could reduce health care costs, drop-out rates and bring faster relief to patients.

  1. G-Quadruplex Forming Oligonucleotides as Anti-HIV Agents.

    Science.gov (United States)

    Musumeci, Domenica; Riccardi, Claudia; Montesarchio, Daniela

    2015-09-22

    Though a variety of different non-canonical nucleic acids conformations have been recognized, G-quadruplex structures are probably the structural motifs most commonly found within known oligonucleotide-based aptamers. This could be ascribed to several factors, as their large conformational diversity, marked responsiveness of their folding/unfolding processes to external stimuli, high structural compactness and chemo-enzymatic and thermodynamic stability. A number of G-quadruplex-forming oligonucleotides having relevant in vitro anti-HIV activity have been discovered in the last two decades through either SELEX or rational design approaches. Improved aptamers have been obtained by chemical modifications of natural oligonucleotides, as terminal conjugations with large hydrophobic groups, replacement of phosphodiester linkages with phosphorothioate bonds or other surrogates, insertion of base-modified monomers, etc. In turn, detailed structural studies have elucidated the peculiar architectures adopted by many G-quadruplex-based aptamers and provided insight into their mechanism of action. An overview of the state-of-the-art knowledge of the relevance of putative G-quadruplex forming sequences within the viral genome and of the most studied G-quadruplex-forming aptamers, selectively targeting HIV proteins, is here presented.

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

    Science.gov (United States)

    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.

  3. Secondary Leukemia Associated with the Anti-Cancer Agent, Etoposide, a Topoisomerase II Inhibitor

    Directory of Open Access Journals (Sweden)

    Sachiko Ezoe

    2012-07-01

    Full Text Available Etoposide is an anticancer agent, which is successfully and extensively used in treatments for various types of cancers in children and adults. However, due to the increases in survival and overall cure rate of cancer patients, interest has arisen on the potential risk of this agent for therapy-related secondary leukemia. Topoisomerase II inhibitors, including etoposide and teniposide, frequently cause rearrangements involving the mixed lineage leukemia (MLL gene on chromosome 11q23, which is associated with secondary leukemia. The prognosis is extremely poor for leukemias associated with rearrangements in the MLL gene, including etoposide-related secondary leukemias. It is of great importance to gain precise knowledge of the clinical aspects of these diseases and the mechanism underlying the leukemogenesis induced by this agent to ensure correct assessments of current and future therapy strategies. Here, I will review current knowledge regarding the clinical aspects of etoposide-related secondary leukemia, some probable mechanisms, and strategies for treating etoposide-induced leukemia.

  4. Conditioned Subjective Responses to Socially Relevant Stimuli in Social Anxiety Disorder and Subclinical Social Anxiety.

    Science.gov (United States)

    Tinoco-González, Daniella; Fullana, Miquel Angel; Torrents-Rodas, David; Bonillo, Albert; Vervliet, Bram; Pailhez, Guillem; Farré, Magí; Andión, Oscar; Perez, Víctor; Torrubia, Rafael

    2015-01-01

    Although enhanced fear conditioning has been implicated in the origins of social anxiety disorder (SAD), laboratory evidence in support of this association is limited. Using a paradigm employing socially relevant unconditioned stimuli, we conducted two separate studies to asses fear conditioning in individuals with SAD and non-clinical individuals with high social anxiety (subclinical social anxiety [SSA]). They were compared with age-matched and gender-matched individuals with another anxiety disorder (panic disorder with agoraphobia) and healthy controls (Study 1) and with individuals with low social anxiety (Study 2). Contrary to our expectations, in both studies, self-report measures (ratings of anxiety, unpleasantness and arousal to the conditioned stimuli) of fear conditioning failed to discriminate between SAD or SSA and the other participant groups. Our results suggest that enhanced fear conditioning does not play a major role in pathological social anxiety. We used a social conditioning paradigm to study fear conditioning in clinical and subclinical social anxiety. We found no evidence of enhanced fear conditioning in social anxiety individuals. Enhanced fear conditioning may not be a hallmark of pathological social anxiety. Copyright © 2014 John Wiley & Sons, Ltd.

  5. Explicit memory in anxiety disorders

    NARCIS (Netherlands)

    Becker, E.S.; Roth, W.T.; Andrich, M.; Margraf, J.

    1999-01-01

    Two experiments were conducted to study selective memory bias favoring anxiety-relevant materials in patients with anxiety disorders. In the 1st experiment, 32 patients with generalized anxiety disorder (GAD), 30 with social phobia (speaking anxiety), and 31 control participants incidentally learned

  6. Anti-vascular endothelial growth factor therapy for the treatment of myopic choroidal neovascularization

    Directory of Open Access Journals (Sweden)

    Tan CS

    2017-09-01

    Full Text Available Colin S Tan,1,2 SriniVas R Sadda3 1National Healthcare Group Eye Institute, Tan Tock Seng Hospital, Singapore; 2Fundus Image Reading Center, National Healthcare Group Eye Institute, Singapore; 3Doheny Eye Institute, University of California Los Angeles, CA, USA Abstract: Myopic choroidal neovascularization (CNV is a sight-threatening condition which occurs in eyes with myopia, particularly in those with pathologic myopia. It is the most common cause of CNV among patients younger than 50 years. Hemorrhage and exudation from the CNV lesion may eventually result in scarring or chorioretinal atrophy. While myopic CNV was previously treated with focal laser photocoagulation or photodynamic therapy (PDT, the current treatment of choice is anti-vascular endothelial growth factor (VEGF agents. Many studies have demonstrated the efficacy of intravitreal anti-VEGF agents in the treatment of myopic CNV. The RADIANCE study reported that intravitreal ranibizumab was superior to PDT in eyes with myopic CNV (at 3 months, both groups receiving intravitreal ranibizumab gained 10.5 and 10.6 letters vs 2.2 letters among patients receiving PDT. In addition, the study demonstrated similar visual outcomes in eyes treated on the basis of visual acuity stabilization or disease activity criteria. Other clinical studies have provided evidence for the efficacy of ranibizumab and aflibercept in the treatment of myopic CNV. This review addresses the epidemiology, pathophysiology, and imaging characteristics of myopic CNV, and discusses the evidence for the efficacy of anti-VEGF agents as compared to laser photocoagulation and PDT. Keywords: myopic choroidal neovascularization, ranibizumab, anti-vascular endothelial growth factor

  7. Adult attachment style and anxiety

    DEFF Research Database (Denmark)

    Nielsen, Sara Kerstine Kaya; Lønfeldt, Nicole Nadine; Wolitzky-Taylor, Kate

    2017-01-01

    Although there is substantial evidence for the role of emotion regulation in the etiology and maintenance of anxiety disorders, knowledge about what contributes to emotion dysregulation is sparse. Attachment style is related to emotion regulation and anxiety symptoms, but these variables have rar...... knowledge to examine the mediating role of emotion regulation between attachment dimensions (avoidance and anxiety) and anxiety symptoms.......Although there is substantial evidence for the role of emotion regulation in the etiology and maintenance of anxiety disorders, knowledge about what contributes to emotion dysregulation is sparse. Attachment style is related to emotion regulation and anxiety symptoms, but these variables have...... rarely been examined together. Examining emotion dysregulation within the context of anxiety disorders through an attachment theory framework will lead to a better understanding of the etiology and maintenance of anxiety disorders. In the present study we combined theoretically and empirically derived...

  8. Fascaplysin Sensitizes Anti-Cancer Effects of Drugs Targeting AKT and AMPK

    Directory of Open Access Journals (Sweden)

    Taek-In Oh

    2017-12-01

    Full Text Available Fascaplysin, a natural product isolated from marine sponges, is a potential candidate for the development of anti-cancer drugs. However, the mechanism underlying its therapeutic effect of strengthening anti-cancer efficacy of other drugs is poorly understood. Here, we found that fascaplysin increases phosphorylation of protein kinase B (PKB, also known as AKT, and adenosine monophosphate-activated protein kinase (AMPK, which are considered therapeutic targets for cancer treatment due to their anti-apoptotic or pro-survival functions in cancer. A cell viability assay revealed that pharmacological suppression of AKT using LY294002 enhanced the anti-cancer effect of fascaplysin in various cancer cells. Similarly, fascaplysin was observed to have improved anti-cancer effects in combination with compound C, a selective AMPK inhibitor. Another challenge showed that fascaplysin increased the efficacy of methotrexate (MTX-mediated cancer therapy by suppressing genes related to folate and purine metabolism. Overall, these results suggest that fascaplysin may be useful for improving the anti-cancer efficacy of targeted anti-cancer drugs, such as inhibitors of phosphoinositide 3-kinase AKT signaling, and chemotherapeutic agents, such as MTX.

  9. Anxiety disorders: diagnosis and treatment.

    Science.gov (United States)

    Jack, R A; Mathew, R J

    1985-07-01

    Pathologic anxiety, marked by inappropriate apprehension and/or fear, causes patients to seek help. Anxiety is associated with a wide variety of physical illnesses, and these must be initially considered when making a diagnosis. Similarly, anxiety associated with a wide variety of psychiatric syndromes must also be considered. Finally, the possibility of transient situational anxiety is ever present. Once it is determined that a primary anxiety disorder exists, then the presence or absence of phobias, panic attacks, and chronic "free-floating" anxiety will fully characterize the disorder. With an accurate diagnosis in hand, a multifaceted treatment approach can be designed. Effective treatments now exist for phobic and panic disorders, and more effective treatment for chronic generalized anxiety may be forthcoming.

  10. The Influence of Parent Preprocedural Anxiety on Child Procedural Pain: Mediation by Child Procedural Anxiety

    OpenAIRE

    Bearden, Donald J.; Feinstein, Amanda; Cohen, Lindsey L.

    2012-01-01

    Objective Data suggest parents’ preprocedural anxiety is related to children's acute procedural anxiety and pain. This study examined the temporal relations among these constructs to determine whether children's anxiety mediates the relation between parents' anticipatory anxiety and children's procedural pain. Methods A total of 90 preschoolers receiving immunizations, their parents, and the nurses rated children's procedural anxiety and pain. Parents provided ratings of their own preprocedur...

  11. Possible mechanism of anti-inflammatory activity and safety profile ...

    African Journals Online (AJOL)

    Animals were grouped and treated with diclofenac, chlorpheniramine, and granisetron (reference anti-inflammatory agents), or aqueous and ethanolic extracts of Pistia stratiotes at doses of 30, 100, and 300 mg/kg orally. Control groups received distilled water. Paw thicknesses was measured at 30 or 60 min intervals for 2.5 ...

  12. Anti-bribery control and incentives as agency theory approaches

    OpenAIRE

    Fabian Teichmann

    2017-01-01

    This article takes an agency theory approach towards bribery in multinational corporations. In particular, it is advocated that incentives could help to align the interests of principals and agents and reduce information asymmetries. This could help to increase anti-bribery compliance and hence support the fight against corruption in Eastern Europe.

  13. Radiolabeling of anti-CD20 with Re0-188: liquid kit

    International Nuclear Information System (INIS)

    Dias, Carla Roberta; Osso Junior, Joao Alberto

    2007-01-01

    Radioimmunotherapy uses the targeting features of monoclonal antibody to deliver radiation from an attached radionuclide. The radionuclide 188 Re is currently produced from the father nuclide 188 W through a transportable generator system. Because of its easy availability and suitable nuclear properties (E βMAX =2.1 MeV, t 1/2 =16.9 h, E γ =155 keV), this radionuclide is considered an attractive candidate for application as therapeutic agents and could be conveniently utilized for imaging and dosimetric purposes. The objective of this work is the optimization of radiolabeling of anti-CD20 with 188 Re using a liquid formulation. Anti-CD20 was reduced by incubation with 2-ME and purified over a PD-10 column. The number of resulting free SH was assayed with Ellman's reagent. Optimization of radiolabeling was achieved by varying parameters: antibody mass, reducing agent, reaction time and 188 Re volume in the liquid kit. Radiochemical purity of 188 Re-anti-CD20 was evaluated. An average of 12 SH groups per mol in the reductions was found. The best labeling efficiency (> 93%) was achieved in the following conditions: 1 mg anti-CD20; 82.8 mg sodium tartrate; 1 mg SnCl 2 ; 0.25 mg gentisic acid, 1 mL 188 Re and reaction time of 1 hour at room temperature. (author)

  14. Lifetime anxiety disorder and current anxiety symptoms associated with hastened depressive recurrence in bipolar disorder.

    Science.gov (United States)

    Shah, Saloni; Kim, Jane P; Park, Dong Yeon; Kim, Hyun; Yuen, Laura D; Do, Dennis; Dell'Osso, Bernardo; Hooshmand, Farnaz; Miller, Shefali; Wang, Po W; Ketter, Terence A

    2017-09-01

    To assess differential relationships between lifetime anxiety disorder/current anxiety symptoms and longitudinal depressive severity in bipolar disorder (BD). Stanford BD Clinic outpatients enrolled during 2000-2011 were assessed with the Systematic Treatment Enhancement Program for BD (STEP-BD) Affective Disorders Evaluation and followed with the STEP-BD Clinical Monitoring Form while receiving naturalistic treatment for up to two years. Baseline unfavorable illness characteristics/current mood symptoms and times to depressive recurrence/recovery were compared in patients with versus without lifetime anxiety disorder/current anxiety symptoms. Among 105 currently recovered patients, lifetime anxiety disorder was significantly associated with 10/27 (37.0%) demographic/other unfavorable illness characteristics/current mood symptoms/current psychotropics, hastened depressive recurrence (driven by earlier onset age), and a significantly (> two-fold) higher Kaplan-Meier estimated depressive recurrence rate, whereas current anxiety symptoms were significantly associated with 10/27 (37.0%) demographic/other unfavorable illness characteristics/current mood symptoms/current psychotropics and hastened depressive recurrence (driven by lifetime anxiety disorder), but only a numerically higher Kaplan-Meier estimated depressive recurrence rate. In contrast, among 153 currently depressed patients, lifetime anxiety disorder/current anxiety symptoms were not significantly associated with time to depressive recovery or depressive recovery rate. American tertiary BD clinic referral sample, open naturalistic treatment. Research is needed regarding differential relationships between lifetime anxiety disorder and current anxiety symptoms and hastened/delayed depressive recurrence/recovery - specifically whether lifetime anxiety disorder versus current anxiety symptoms has marginally more robust association with hastened depressive recurrence, and whether both have marginally more robust

  15. Multiplexed evaluation of capture agent binding kinetics using arrays of silicon photonic microring resonators.

    Science.gov (United States)

    Byeon, Ji-Yeon; Bailey, Ryan C

    2011-09-07

    High affinity capture agents recognizing biomolecular targets are essential in the performance of many proteomic detection methods. Herein, we report the application of a label-free silicon photonic biomolecular analysis platform for simultaneously determining kinetic association and dissociation constants for two representative protein capture agents: a thrombin-binding DNA aptamer and an anti-thrombin monoclonal antibody. The scalability and inherent multiplexing capability of the technology make it an attractive platform for simultaneously evaluating the binding characteristics of multiple capture agents recognizing the same target antigen, and thus a tool complementary to emerging high-throughput capture agent generation strategies.

  16. Attention network functioning in children with anxiety disorders, attention-deficit/hyperactivity disorder and non-clinical anxiety.

    Science.gov (United States)

    Mogg, K; Salum, G A; Bradley, B P; Gadelha, A; Pan, P; Alvarenga, P; Rohde, L A; Pine, D S; Manfro, G G

    2015-01-01

    Research with adults suggests that anxiety is associated with poor control of executive attention. However, in children, it is unclear (a) whether anxiety disorders and non-clinical anxiety are associated with deficits in executive attention, (b) whether such deficits are specific to anxiety versus other psychiatric disorders, and (c) whether there is heterogeneity among anxiety disorders (in particular, specific phobia versus other anxiety disorders). We examined executive attention in 860 children classified into three groups: anxiety disorders (n = 67), attention-deficit/hyperactivity disorder (ADHD; n = 67) and no psychiatric disorder (n = 726). Anxiety disorders were subdivided into: anxiety disorders excluding specific phobia (n = 43) and specific phobia (n = 21). The Attention Network Task was used to assess executive attention, alerting and orienting. Findings indicated heterogeneity among anxiety disorders, as children with anxiety disorders (excluding specific phobia) showed impaired executive attention, compared with disorder-free children, whereas children with specific phobia showed no executive attention deficit. Among disorder-free children, executive attention was less efficient in those with high, relative to low, levels of anxiety. There were no anxiety-related deficits in orienting or alerting. Children with ADHD not only had poorer executive attention than disorder-free children, but also higher orienting scores, less accurate responses and more variable response times. Impaired executive attention in children (reflected by difficulty inhibiting processing of task-irrelevant information) was not fully explained by general psychopathology, but instead showed specific associations with anxiety disorders (other than specific phobia) and ADHD, as well as with high levels of anxiety symptoms in disorder-free children.

  17. Sonodynamic therapy combined with novel anti-cancer agents, sanguinarine and ginger root extract: Synergistic increase in toxicity in the presence of PANC-1 cells in vitro.

    Science.gov (United States)

    Prescott, Matthew; Mitchell, James; Totti, Stella; Lee, Judy; Velliou, Eirini; Bussemaker, Madeleine

    2018-01-01

    The presence of ultrasound-induced cavitation in sonodynamic therapy (SDT) treatments has previously enhanced the activity and delivery of certain sonosensitisers in biological systems. The purpose of this work was to investigate the potential for two novel anti-cancer agents from natural derivatives, sanguinarine and ginger root extract (GRE), as sonosensitisers in an SDT treatment with in vitro PANC-1 cells. Both anti-cancer compounds had a dose-dependent cytotoxicity in the presence of PANC-1 cells. A range of six discreet ultrasound power-frequency configurations were tested and it was found that the cell death caused directly by ultrasound was likely due to the sonomechanical effects of cavitation. Combined treatment used dosages of 100μM sanguinarine or 1mM of GRE with 15s sonication at 500kHz and 10W. The sanguinarine-SDT and GRE-SDT treatments showed a 6% and 17% synergistic increase in observed cell death, respectively. Therefore both sanguinarine and GRE were found to be effective sonosensitisers and warrant further development for SDT, with a view to maximising the magnitude of synergistic increase in toxicity. Copyright © 2017 Elsevier B.V. All rights reserved.

  18. Inflammation-Specific T1 Imaging Using Anti-Intercellular Adhesion Molecule 1 Antibody-Conjugated Gadolinium Diethylenetriaminepentaacetic Acid

    Directory of Open Access Journals (Sweden)

    Kyu-Sil Choi

    2007-03-01

    Full Text Available To examine inflammatory tissue, an initial and common symptom of various types of pathogenesis, we designed inflammation-targeted T1 contrast agents prepared by bioconjugation of gadolinium diethylenetriaminepentaacetic acid (Gd-DTPA with anti-intercellular adhesion molecule 1 (ICAM-1 antibody. The anti-ICAM-1 antibody was coupled with DTPA and was then conjugated with Gd. The specific binding of the Gd-DTPA-anti-ICAM-1 antibody complex to the ICAM-1-expressing cells was examined in the cultured endothelial cells where ICAM-1 expression was stimulated. Inflammation-specific T1 imaging was then assessed using a mouse abscess model with the 1.5-Tesla module. The Gd-DTPA-anti-ICAM-1 antibody displayed increased r1, which was two times higher than that of Gd-DTPA and showed predominant binding to cultured endothelial cells, which expressed a high level of ICAM-1. Moreover, the inflammation-specific T1 enhancement was imaged with the Gd-DTPA-anti-ICAM-1 antibody in the mouse acute inflammation model. The Gd-DTPA-anti-ICAM-1 antibody showed significantly increased vascular circulation time, which thereby offered a greater chance for its binding to the target cells. The Gd-DTPA-anti-ICAM-1 antibody displays a potential targeted T1 contrast agent specific to the inflammatory tissue that expresses ICAM-1.

  19. Marine Peptides and Their Anti-Infective Activities

    Directory of Open Access Journals (Sweden)

    Hee Kyoung Kang

    2015-01-01

    Full Text Available Marine bioresources are a valuable source of bioactive compounds with industrial and nutraceutical potential. Numerous clinical trials evaluating novel chemotherapeutic agents derived from marine sources have revealed novel mechanisms of action. Recently, marine-derived bioactive peptides have attracted attention owing to their numerous beneficial effects. Moreover, several studies have reported that marine peptides exhibit various anti-infective activities, such as antimicrobial, antifungal, antimalarial, antiprotozoal, anti-tuberculosis, and antiviral activities. In the last several decades, studies of marine plants, animals, and microbes have revealed tremendous number of structurally diverse and bioactive secondary metabolites. However, the treatments available for many infectious diseases caused by bacteria, fungi, and viruses are limited. Thus, the identification of novel antimicrobial peptides should be continued, and all possible strategies should be explored. In this review, we will present the structures and anti-infective activity of peptides isolated from marine sources (sponges, algae, bacteria, fungi and fish from 2006 to the present.

  20. Local production of donkey anti-rabbit's sera for human prolactin radioimmunoassay

    International Nuclear Information System (INIS)

    Hassan, Ammar Mohamed Elamin

    2001-11-01

    Pure Rabbit's IgG was used in this study to raise donkey anti rabbit's sera to be used as separating agent in radioimmunoassay. Two healthy donkeys have been immunized. The anti rabbit's sera have been titrated as (i) crude, (ii) purified and dialysed coupled to magnetic particles. Then this antibody was used as separating agent in a radioimmunoassay for measurement of human prolactin (PRL). Coupled Sudanese donkey and rabbit's sera (Sud-DARS) was used as 1/8 titre using chelsea RIA kit for human prolactin while 1/200 of liquid Sud-DARS was found to be the best titre using the Chinese kit. The best condition for estimation of the prolactin were optimized by determining the suitable incubation time and temperature. The assay can be done at room temperature but it should be incubated for 6 hours as recommended by the Chinese kit. Validity tests were done. The regression coefficients were 0.994 and 0.999 for linearity and recovery tests respectively. Measurement of human PRL wa found to be reproducible using Sud-DARS as separating agent since the coefficient of variation (C.V. %) was found to be less than 15% for both within batch and between assays. Comparing Sud D ARS to the Chinese kit, separating agent as reference agent, regression coefficient was found to be 0.977 which indicate that Sud-DARS can be used as separating agent. Prolactin in Sudanese subject was determined using the Chinese kit the Sud-DARS as separating agent. The ranges were 74-398 mIU/L in males and 102-414 mI/L in the preovulatory phase for the females while in the post ovulatory phase it was 114-442 mIU/L. Ovulation was confirmed by measurement of progesterone level 7 days before the next suspected mensuration. (Author)