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.

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

Novel agents for anti-platelet therapy

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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.

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...

Agent-based model of fecal microbial transplant effect on bile acid metabolism on suppressing Clostridium difficile infection: an example of agent-based modeling of intestinal bacterial infection.

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Peer, Xavier; An, Gary

2014-10-01

Agent-based modeling is a computational modeling method that represents system-level behavior as arising from multiple interactions between the multiple components that make up a system. Biological systems are thus readily described using agent-based models (ABMs), as multi-cellular organisms can be viewed as populations of interacting cells, and microbial systems manifest as colonies of individual microbes. Intersections between these two domains underlie an increasing number of pathophysiological processes, and the intestinal tract represents one of the most significant locations for these inter-domain interactions, so much so that it can be considered an internal ecology of varying robustness and function. Intestinal infections represent significant disturbances of this internal ecology, and one of the most clinically relevant intestinal infections is Clostridium difficile infection (CDI). CDI is precipitated by the use of broad-spectrum antibiotics, involves the depletion of commensal microbiota, and alterations in bile acid composition in the intestinal lumen. We present an example ABM of CDI (the C. difficile Infection ABM, or CDIABM) to examine fundamental dynamics of the pathogenesis of CDI and its response to treatment with anti-CDI antibiotics and a newer treatment therapy, fecal microbial transplant. The CDIABM focuses on one specific mechanism of potential CDI suppression: commensal modulation of bile acid composition. Even given its abstraction, the CDIABM reproduces essential dynamics of CDI and its response to therapy, and identifies a paradoxical zone of behavior that provides insight into the role of intestinal nutritional status and the efficacy of anti-CDI therapies. It is hoped that this use case example of the CDIABM can demonstrate the usefulness of both agent-based modeling and the application of abstract functional representation as the biomedical community seeks to address the challenges of increasingly complex diseases with the goal of

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

An update on the use of C. elegans for preclinical drug discovery: screening and identifying anti-infective drugs.

Science.gov (United States)

Kim, Wooseong; Hendricks, Gabriel Lambert; Lee, Kiho; Mylonakis, Eleftherios

2017-06-01

The emergence of antibiotic-resistant and -tolerant bacteria is a major threat to human health. Although efforts for drug discovery are ongoing, conventional bacteria-centered screening strategies have thus far failed to yield new classes of effective antibiotics. Therefore, new paradigms for discovering novel antibiotics are of critical importance. Caenorhabditis elegans, a model organism used for in vivo, offers a promising solution for identification of anti-infective compounds. Areas covered: This review examines the advantages of C. elegans-based high-throughput screening over conventional, bacteria-centered in vitro screens. It discusses major anti-infective compounds identified from large-scale C. elegans-based screens and presents the first clinically-approved drugs, then known bioactive compounds, and finally novel small molecules. Expert opinion: There are clear advantages of using a C. elegans-infection based screening method. A C. elegans-based screen produces an enriched pool of non-toxic, efficacious, potential anti-infectives, covering: conventional antimicrobial agents, immunomodulators, and anti-virulence agents. Although C. elegans-based screens do not denote the mode of action of hit compounds, this can be elucidated in secondary studies by comparing the results to target-based screens, or conducting subsequent target-based screens, including the genetic knock-down of host or bacterial genes.

Anti-N-methyl-D-aspartate receptor encephalitis associated with acute Toxoplasma gondii infection: A case report.

Science.gov (United States)

Cai, Xiaotang; Zhou, Hui; Xie, Yongmei; Yu, Dan; Wang, Zhiling; Ren, Haitao

2018-02-01

Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis has been recognized as the most frequent autoimmune encephalitis in children. Several infectious agents have been implicated in anti-NMDA encephalitis. A previously healthy immunocompetent 9-year-old girl first presented with seizures, headaches and vomiting. Cerebrospinal fluid and brain magnetic resonance imaging were normal. After one week onset, the patient gradually developed unexplained personality and behavior changes, accompanied by fever and seizures again. Repeated CSF analysis revealed a slightly lymphocytic predominant pleocytosis and positive anti-NMDAR antibody. A variety of pathogenic examinations were negative, except for positive toxoplasma IgM and IgG. The patient was diagnoses for anti-NMDA encephalitis associated with acute acquired toxoplasma gondii infection. The patient received 10 days azithromycin for treatment of acquired toxoplasma infection. The parents refuse immunotherapy because substantial recovery from clinical symptoms. The patient was substantially recovered with residual mild agitation after therapy for acquired toxoplasma gondii infection. Two months later, the patient was completely devoid of symptoms, and the levels of serum IgM and IgG of toxoplasma gondii were decreased. Acquired toxoplasma gondii infection may trigger anti-NMDAR encephalitis in children, which has not been reported previously. Clinicians should assess the possibility of toxoplasma gondii infection when evaluating a patient with anti-NMDA encephalitis.

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

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...

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

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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.

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

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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.

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.

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.

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

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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.

Pharmacological interactions of anti-microbial agents in odontology.

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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.

Oligopeptide Targeting Sortase A as Potential Anti-infective Therapy for Staphylococcus aureus

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Jianfeng Wang

2018-02-01

Full Text Available Sortase A (SrtA-catalyzed anchorage of surface proteins in most Gram-positive bacteria is indispensable for their virulence, suggesting that this transpeptidase is a promising target for antivirulence therapy. Here, an oligopeptide, LPRDA, was identified as an effective inhibitor of SrtA via virtual screening based on the LPXTG substrate sequence, and it was found to inhibit SrtA activity in vitro and in vivo (IC50 = 10.61 μM by competitively occupying the active site of SrtA. Further, the oligopeptide treatment had no anti-Staphylococcus aureus activity, but it provided protection against S. aureus-induced mastitis in a mouse model. These findings indicate that the oligopeptide could be used as an effective anti-infective agent for the treatment of infection caused by S. aureus or other Gram-positive bacteria via the targeting of SrtA.

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

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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.

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

Screening of Anti-Obesity Agent from Herbal Mixtures

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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.

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.

Marine Algae as a Potential Source for Anti-Obesity Agents

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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.

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.

The quest for anti-inflammatory and anti-infective biomaterials in clinical translation

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May Griffith

2016-09-01

Full Text Available Biomaterials are now being used or evaluated clinically as implants to supplement the severe shortage of available human donor organs. To date however, such implants have mainly been developed as scaffolds to promote the regeneration of failing organs due to old age or congenital malformations. In the real world, however, infection or immunological issues often compromise patients. For example, bacterial and viral infections can result in uncontrolled immunopathological damage and lead to organ failure. Hence, there is a need for biomaterials and implants that not only promote regeneration but also address issues that are specific to compromised patients such as infection and inflammation. Different strategies are needed to address the regeneration of organs that have been damaged by infection or inflammation for successful clinical translation. Therefore, the real quest is for multi-functional biomaterials with combined properties that can combat infections, modulate inflammation and promote regeneration at the same time. These strategies will necessitate the inclusion of methodologies for management of the cellular and signaling components elicited within the local microenvironment. In the development of such biomaterials, strategies range from the inclusion of materials that have intrinsic anti-inflammatory properties, such as the synthetic lipid polymer, 2-methacryloyloxyethyl phosphorylcholine (MPC, to silver nanoparticles that have anti-bacterial properties, to inclusion of nano- and micro-particles in biomaterials composites that deliver active drugs. In this present review, we present examples of both kinds of materials in each group along with their pros and cons. Thus, as a promising next generation strategy to aid or replace tissue/organ transplantation, an integrated smart programmable platform is needed for regenerative medicine applications to create and/or restore normal function at the cell and tissue levels. Therefore, now it is

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.

[The features in preventing recurrent lower urinary tract infection].

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Gadzhieva, Z K; Kazilov, Yu B

2016-08-01

This review outlines characteristics of medications most commonly used for preventing recurrent lower urinary tract infection (UTI). It shows that the treatment and prophylaxis of UTI should be comprehensive and include the restoration of the normal urogenital tract anatomy and use in addition to antibacterial and anti-inflammatory drugs, agents, normalizing the function of the lower urinary tract, as well as drugs for local and systemic immunoprophylaxis, protection of the urothelium from recurrent infection, local hormone replacement therapy in menopause, and dietary supplements to acidify the urine.

Novel anti-inflammatory agents in COPD

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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...

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

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

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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.

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.

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...

Anti-soluble liver antigen (SLA) antibodies in chronic HCV infection.

Science.gov (United States)

Vitozzi, Susana; Lapierre, Pascal; Djilali-Saiah, Idriss; Marceau, Gabriel; Beland, Kathie; Alvarez, Fernando

2004-05-01

Hepatitis C infection is associated with autoimmune disorders, such as the production of autoantibodies. Anti-LKM1 and anti-LC1, immunomarkers of type 2 autoimmune hepatitis, have been previously associated with a HCV infection. Anti-Soluble-Liver-Antigen autoantibodies (SLA) are specifically associated with type 1 and type 2 autoimmune hepatitis and more closely related to patients who relapse after steroid therapy. The recent molecular cloning of the soluble liver antigen provides the opportunity to develop more specific tests for the detection of antibodies against it. The aim of this work is to characterize anti-soluble-liver autoantibodies in sera from patients chronically infected by HCV. A recombinant cDNA from activated Jurkat cells coding for the full length tRNP(Ser)Sec/SLA antigen was obtained. ELISA, Western Blot and immunoprecipitation tests were developed and used to search for linear and conformational epitopes recognized by anti-SLA antibodies in sera from patients chronically infected by HCV. Anti-soluble liver antigen antibodies were found in sera from 10.4% of HCV-infected patients. The prevalence was significantly increased to 27% when anti-LKM1 was also present. Most anti-SLA reactivity was directed against conformational epitopes on the antigen. The means titers by ELISA were lower than those obtained in type 2 AIH. The result of autoantibody isotyping showed a subclass restriction to IgG1 and also IgG4. This study shows the presence of anti-SLA antibodies in approximately 10% of HCV infected patients. The prevalence of SLA autoantibodies in HCV infected patients increases when LKM1 autoantibodies are also present. The relationship between the prevalence of this characteristic autoimmune hepatitis autoantibody and the implication of an autoimmune phenomenon in the liver injury of patients chronically infected by HCV needs further investigation.

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.)

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.)

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.

A review of the clinical implications of anti-infective biomaterials and infection-resistant surfaces.

Science.gov (United States)

Campoccia, Davide; Montanaro, Lucio; Arciola, Carla Renata

2013-11-01

Infection is currently regarded as the most severe and devastating complication associated to the use of biomaterials. The important social, clinical and economic impacts of implant-related infections are promoting the efforts to obviate these severe diseases. In this context, the development of anti-infective biomaterials and of infection-resistant surfaces is being regarded as the main strategy to prevent the establishment of implant colonisation and biofilm formation by bacteria. In this review, the attention is focused on the biomaterial-associated infections, from which the need for anti-infective biomaterials originates. Biomaterial-associated infections differ markedly for epidemiology, aetiology and severity, depending mainly on the anatomic site, on the time of biomaterial application, and on the depth of the tissues harbouring the prosthesis. Here, the diversity and complexity of the different scenarios where medical devices are currently utilised are explored, providing an overview of the emblematic applicative fields and of the requirements for anti-infective biomaterials. © 2013 Elsevier Ltd. All rights reserved.

Anti-infection treatment of iatrogenic acute radiation sickness

International Nuclear Information System (INIS)

Zhang Shulan; Ke Xiaoyan; Jia Tengzhen

2006-01-01

Objective: To occumulatle experience of anti-infection treatment in acute radiation sickness (ARS) induced by medical treatment in order to provide beneficial help for victims of accidental of acute radiation sickness. Methods: The changes of peripheral blood indices, body temperature and clinical symptoms of 17 cases who were clinically irradiated with 6.0-7.2 Gy X-rays were observed both before peripheral blood stem cell transplantation(PBSCT) and after anti-infection treatment. Results: WBC count began to decrease to below 1 x 10 9 /L from the 8th to 10th days after irradiation and maintained at row level for 4 days or for 13.3 days if the patients had not received rhG-CSF treatment. In 29.4% of patients the body temperature was higher than 38.5 degree C. After comprehensive enviromental protection and anti-infection treatment, all patients could successfully tide over the period of bone marrow depression without appearance of the typical critical phase of ARS. Conclusion: PBSCT and rhG-CSF treatment can reduce the time span for reconstruction of bone marrow. Comprehensive enviromental protection and combined anti-infection treatment are key points fm successful treatment. (authors)

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.

Gammaherpesvirus Co-infection with Malaria Suppresses Anti-parasitic Humoral Immunity.

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Caline G Matar

2015-05-01

Full Text Available Immunity to non-cerebral severe malaria is estimated to occur within 1-2 infections in areas of endemic transmission for Plasmodium falciparum. Yet, nearly 20% of infected children die annually as a result of severe malaria. Multiple risk factors are postulated to exacerbate malarial disease, one being co-infections with other pathogens. Children living in Sub-Saharan Africa are seropositive for Epstein Barr Virus (EBV by the age of 6 months. This timing overlaps with the waning of protective maternal antibodies and susceptibility to primary Plasmodium infection. However, the impact of acute EBV infection on the generation of anti-malarial immunity is unknown. Using well established mouse models of infection, we show here that acute, but not latent murine gammaherpesvirus 68 (MHV68 infection suppresses the anti-malarial humoral response to a secondary malaria infection. Importantly, this resulted in the transformation of a non-lethal P. yoelii XNL infection into a lethal one; an outcome that is correlated with a defect in the maintenance of germinal center B cells and T follicular helper (Tfh cells in the spleen. Furthermore, we have identified the MHV68 M2 protein as an important virus encoded protein that can: (i suppress anti-MHV68 humoral responses during acute MHV68 infection; and (ii plays a critical role in the observed suppression of anti-malarial humoral responses in the setting of co-infection. Notably, co-infection with an M2-null mutant MHV68 eliminates lethality of P. yoelii XNL. Collectively, our data demonstrates that an acute gammaherpesvirus infection can negatively impact the development of an anti-malarial immune response. This suggests that acute infection with EBV should be investigated as a risk factor for non-cerebral severe malaria in young children living in areas endemic for Plasmodium transmission.

Delivery of gentamicin from resorbable polymeric carriers as anti-infective strategy for implant-associated osteomyelitis

NARCIS (Netherlands)

ter Boo, G.A.

2016-01-01

This thesis describes the development of gentamicin loaded resorbable polymeric carriers as anti-infective strategy for implant-associated osteomyelitis and their in vitro and in vivo evaluation. Local delivery of antibiotics has several advantages in the case of trauma to the bone and surrounding

Intrapleural agents for pleural infection: fibrinolytics and beyond.

Science.gov (United States)

Rahman, Najib M

2012-07-01

Pleural infection is a common, increasing clinical problem with a high morbidity and mortality. Medical management of pleural infection often fails, requiring invasive thoracic surgery to drain infected pleural collections, and for many years intrapleural agents have been assessed to reduce the need for surgical drainage and improve clinical outcomes. Randomized trials assessing intrapleural fibrinolytic agents have given conflicting results, and recent evidence provides important information on the role of intrapleural agents in the treatment of pleural infection, and the possible biology associated with infection progression in these patients. Pleural infection is increasing in both the adult and paediatric populations. The combined previous evidence assessing intrapleural fibrinolytics alone in pleural infection suggests lack of efficacy for clinically important outcomes. The Multi-Centre Intrapleural Sepsis Trial 2 (MIST2) study provides the first evidence of a novel treatment combination [intrapleural tissue plasminogen activator (tPA) combined with intrapleural deoxyribonuclease (DNase)], which significantly improves the chest radiograph compared with either agent alone or placebo, and has potentially important benefits to important clinical outcomes (need for surgery and hospital stay). The precise mechanism of action of combination fibrinolytic and DNase in pleural infection is speculative. Fibrinolytic therapy alone has not been proven to be of use in the treatment of pleural infection. The MIST2 study provides clear-cut evidence demonstrating improved chest radiographs, and highly suggestive secondary outcomes suggesting improved clinically important outcomes, using a combination of intrapleural tPA and DNase. This novel treatment combination may represent an important step in our understanding and treatment of pleural infection; however, larger clinical studies specifically addressing important clinical outcomes and further laboratory research describing

Biological agents and respiratory infections: Causative mechanisms and practice management.

Science.gov (United States)

Takayanagi, Noboru

2015-09-01

Biological agents are increasingly being used to treat patients with immune-mediated inflammatory disease. In Japan, currently approved biological agents for patients with rheumatoid arthritis (RA) include tumor necrosis factor inhibitors, interleukin-6 receptor-blocking monoclonal antibody, and T-cell costimulation inhibitor. Rheumatologists have recognized that safety issues are critical aspects of treatment decisions in RA. Therefore, a wealth of safety data has been gathered from a number of sources, including randomized clinical trials and postmarketing data from large national registries. These data revealed that the most serious adverse events from these drugs are respiratory infections, especially pneumonia, tuberculosis, nontuberculous mycobacteriosis, and Pneumocystis jirovecii pneumonia, and that the most common risk factors associated with these respiratory infections are older age, concomitant corticosteroid use, and underlying respiratory comorbidities. Because of this background, in 2014, the Japanese Respiratory Society published their consensus statement of biological agents and respiratory disorders. This review summarizes this statement and adds recent evidence, especially concerning respiratory infections in RA patients, biological agents and respiratory infections, and practice management of respiratory infections in patients treated with biological agents. To decrease the incidence of infections and reduce mortality, we should know the epidemiology, risk factors, management, and methods of prevention of respiratory infections in patients receiving biological agents. Copyright © 2015 The Japanese Respiratory Society. Published by Elsevier B.V. All rights reserved.

Out of the net: An agent-based model to study human movements influence on local-scale malaria transmission.

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Francesco Pizzitutti

Full Text Available Though malaria control initiatives have markedly reduced malaria prevalence in recent decades, global eradication is far from actuality. Recent studies show that environmental and social heterogeneities in low-transmission settings have an increased weight in shaping malaria micro-epidemiology. New integrated and more localized control strategies should be developed and tested. Here we present a set of agent-based models designed to study the influence of local scale human movements on local scale malaria transmission in a typical Amazon environment, where malaria is transmission is low and strongly connected with seasonal riverine flooding. The agent-based simulations show that the overall malaria incidence is essentially not influenced by local scale human movements. In contrast, the locations of malaria high risk spatial hotspots heavily depend on human movements because simulated malaria hotspots are mainly centered on farms, were laborers work during the day. The agent-based models are then used to test the effectiveness of two different malaria control strategies both designed to reduce local scale malaria incidence by targeting hotspots. The first control scenario consists in treat against mosquito bites people that, during the simulation, enter at least once inside hotspots revealed considering the actual sites where human individuals were infected. The second scenario involves the treatment of people entering in hotspots calculated assuming that the infection sites of every infected individual is located in the household where the individual lives. Simulations show that both considered scenarios perform better in controlling malaria than a randomized treatment, although targeting household hotspots shows slightly better performance.

Out of the net: An agent-based model to study human movements influence on local-scale malaria transmission.

Science.gov (United States)

Pizzitutti, Francesco; Pan, William; Feingold, Beth; Zaitchik, Ben; Álvarez, Carlos A; Mena, Carlos F

2018-01-01

Though malaria control initiatives have markedly reduced malaria prevalence in recent decades, global eradication is far from actuality. Recent studies show that environmental and social heterogeneities in low-transmission settings have an increased weight in shaping malaria micro-epidemiology. New integrated and more localized control strategies should be developed and tested. Here we present a set of agent-based models designed to study the influence of local scale human movements on local scale malaria transmission in a typical Amazon environment, where malaria is transmission is low and strongly connected with seasonal riverine flooding. The agent-based simulations show that the overall malaria incidence is essentially not influenced by local scale human movements. In contrast, the locations of malaria high risk spatial hotspots heavily depend on human movements because simulated malaria hotspots are mainly centered on farms, were laborers work during the day. The agent-based models are then used to test the effectiveness of two different malaria control strategies both designed to reduce local scale malaria incidence by targeting hotspots. The first control scenario consists in treat against mosquito bites people that, during the simulation, enter at least once inside hotspots revealed considering the actual sites where human individuals were infected. The second scenario involves the treatment of people entering in hotspots calculated assuming that the infection sites of every infected individual is located in the household where the individual lives. Simulations show that both considered scenarios perform better in controlling malaria than a randomized treatment, although targeting household hotspots shows slightly better performance.

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

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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.

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....

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.

Anti-NMDA receptor encephalitis and nonencephalitic HSV-1 infection.

Science.gov (United States)

Salovin, Amy; Glanzman, Jason; Roslin, Kylie; Armangue, Thais; Lynch, David R; Panzer, Jessica A

2018-07-01

To determine whether there is an association between nonencephalitic herpes simplex virus 1 (HSV-1) infection and anti-NMDA receptor encephalitis (anti-NMDARE). Antibody testing was performed using samples from 2 cohorts in a case-control observational study. The cohort "Philadelphia" included 16 serum samples of pediatric anti-NMDARE cases and 42 age-matched controls with other neuroinflammatory disorders studied at the Children's Hospital of Philadelphia and University of Pennsylvania. The cohort "Barcelona" contained 23 anti-NMDARE patient samples and 26 age-matched participants with other neuroinflammatory disorders studied at IDIBAPS-Hospital Clinic, University of Barcelona. The presence of HSV-1 IgG antibodies was examined by ELISA. As an additional control, IgG antibodies to cytomegalovirus (CMV) and Epstein-Barr virus viral capsid antigen (EBV-VCA) were determined. In each cohort, more participants with anti-NMDARE than controls had anti-HSV-1 IgG antibodies. In the Philadelphia cohort (58 participants), 44% of anti-NMDARE cases had antibodies to HSV-1 compared with 14% controls (OR 4.67, 95% CI 1.3-17.3, p = 0.031). In the Barcelona cohort (49 participants), 52% of participants with anti-NMDARE had antibodies to HSV-1 compared with 31% of controls (OR 2.45, 95% CI 0.7-7.9, p = 0.155). Overall, 49% of anti-NMDARE cases have antibodies to HSV-1 in these 2 combined cohorts compared with 21% of controls (Mantel-Haenszel OR 3.21, 95% CI 1.3-7.7, p = 0.007). Past HSV-1 infection was found in significantly more anti-NMDARE cases than controls. This suggests a meaningful association between nonencephalitic HSV-1 infection and development of anti-NMDARE.

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

Anti-Eimeria activity of berberine and identification of associated gene expression changes in the mouse jejunum infected with Eimeria papillata.

Science.gov (United States)

Dkhil, Mohamed A; Metwaly, Mahmoud S; Al-Quraishy, Saleh; Sherif, Nour E; Delic, Denis; Al Omar, Suliman Y; Wunderlich, Frank

2015-04-01

Plant-based natural products are promising sources for identifying novel agents with potential anti-Eimeria activity. This study explores possible effects of berberine on Eimeria papillata infections in the jejunum of male Swiss albino mice. Berberine chloride, when daily administered to mice during infection, impairs intracellular development and multiplication of E. papillata, evidenced as 60% reduction of maximal fecal output of oocysts on day 5 p.i. Concomitantly, berberine attenuates the inflammatory response, evidenced as decreased messenger RNA (mRNA) expression of IL-1β, IL-6, TNFα, IFNγ, and iNOS, as well as the oxidative stress response, evidenced as impaired increase in malondialdehyde, nitrate, and H2O2 and as prevented decrease in glutathione and catalase activity. Berberine also alters gene expression in the infected jejunum. On day 5 p.i., mRNA expression of 29 genes with annotated functions is more than 10-fold upregulated and that of 14 genes downregulated. Berberine downregulates the genes Xaf1, Itgb3bp, and Faim3 involved in apoptotic processes and upregulates genes involved in innate immune responses, as e.g., Colec11, Saa2, Klra8, Clec1b, and Crtam, especially the genes Cpa3, Fcer1a, and Mcpt1, Mcpt2, and Mcpt4 involved in mast cell activity. Additionally, 18 noncoding lincRNA species are differentially expressed more than 10-fold under berberine. Our data suggest that berberine induces hosts to exert anti-Eimeria activity by attenuating the inflammatory and oxidative stress response, by impairing apoptotic processes, and by activating local innate immune responses and epigenetic mechanisms in the host jejunum. Berberine has the potential as an anti-Eimeria food additive in animal farming.

[Systemic therapy with anti-infective agents. Principles of rational use of systemic antibiotics in dermatology].

Science.gov (United States)

Sunderkötter, C; Brehler, R; Becker, K

2014-02-01

Antibiotics are frequently prescribed and extremely valuable drugs, because they are curative. However, their often incorrect use is the main reason for the increase of multiresistant pathogens. Inappropriate prescription of broad spectrum antibiotics for skin and soft tissue infections favors the selection and spread of multiresistant bacteria not only in the skin, but also in remote visceral organs (e.g. in the intestines), due to their systemic distribution and effects in the body (so-called collateral damage). For this reason basic knowledge and special prudence when using antibiotics are just as desirable as an awareness of responsibility for the public welfare. This article intends to convey basic knowledge on the indications and selection of suitable antibiotics as well as on the development of bacterial resistance and it gives recommendations for allergological procedures when patients report alleged drug reactions to antibiotics. Systemic antibiotics for soft tissue infections are indicated when the infection spreads within the tissue so that it is no longer accessible for local antiseptics. In addition to the clinical symptoms, important parameters are high blood sedimentation rates (BSR) and high levels of C-reactive protein (CRP), leukocytosis with neutrophilia and fever (not always present in elderly or immunosuppressed patients). Certain constellations, such as the presence of severe underlying diseases, perfusion disorders or a particular localization (e.g. infection of the face) may necessitate early or parenteral administration. There is no need for systemic administration of antibiotics for uncomplicated wounds without soft tissue infections. Due to their curative effects, the decisive criterion for the use of antibiotics is their sufficient antimicrobial efficacy at the site of infection. An inappropriate administration increases both the selection pressure and costs of treatment and can have fatal consequences in serious situations. In

Anti-LC1 autoantibodies in patients with chronic hepatitis C virus infection.

Science.gov (United States)

Béland, Kathie; Lapierre, Pascal; Marceau, Gabriel; Alvarez, Fernando

2004-03-01

Various autoantibodies have been reported in patients chronically infected by hepatitis C virus. 2% to 10% of theses patients have anti-liver-kidney microsome type 1 (anti-LKM1) autoantibodies. In type 2 autoimmune hepatitis, anti-LKM1 autoantibodies are frequently associated with anti-liver-cytosol type 1 (anti-LC1) autoantibodies. To determine the prevalence of anti-LC1 autoantibodies in a hepatitis C-positive population and characterize their reactivity. 146 patients suffering from liver diseases, of which 99 were chronically infected by hepatitis C virus, were tested by Western blotting and immunoprecipitation to detect and characterize anti-LC1 autoantibodies. 12% of this hepatitis C population had anti-LC1 autoantibodies. LC1 positivity by Western blotting was 30% of LC1+ sera. Epitopes were found throughout the protein but linear epitopes were situated in the 395-541 amino acid region of formiminotransferase cyclodeaminase. Three putative conformational epitopes were identified by phage display. Anti-LC1 autoantibodies are as prevalent as anti-LKM1 autoantibodies in patients infected with hepatitis C virus and their production is not dependent of anti-LKM1 autoantibodies formation. Autoantibody reactivity against the anti-LC1 antigen is different in hepatitis C than in type 2 autoimmune hepatitis. Anti-LC1 autoantibodies can now be regarded as a serological marker of autoimmunity in chronic hepatitis C infection.

Anti-GBM disease and ANCA during dengue infection.

Science.gov (United States)

Lizarraga, Karlo J; Florindez, Jorge A; Daftarian, Pirouz; Andrews, David M; Ortega, Luis M; Mendoza, Jair Munoz; Contreras, Gabriel N; Nayer, Ali

2015-02-01

Anti-glomerular basement membrane (GBM) disease is a severe inflammatory renal disorder due to pathogenic autoantibodies directed mainly against the α3 chain of type IV collagen. In ~1/4 of patients with anti-GBM disease, antineutrophil cytoplasmic antibodies (ANCA) predominantly with myeloperoxidase (MPO) specificity can be detected. Although the inciting stimuli leading to the development of an immune response against the type IV collagen and neutrophils are unknown, evidence indicates that both genetic and environmental factors play a role. Of note, molecular mimicry between self-antigens and nonself-antigens such as antigenic determinants of microorganisms has been implicated in the pathogenesis of anti-GBM disease and ANCA-associated vasculitis. A mosquito-borne viral illness highly prevalent in the tropics and subtropics, dengue can be complicated by acute renal failure, proteinuria, hematuria and glomerulonephritis. We present a 66-year-old woman who was diagnosed with dengue infection and rapidly progressive glomerulonephritis during an outbreak of dengue in Honduras in the summer of 2013. Renal biopsy revealed severe crescentic glomerulonephritis. Immunofluorescence examination demonstrated strong linear IgG deposition along glomerular capillary walls. Serologic tests demonstrated antibodies against GBM, MPO and platelet glycoproteins. The patient was diagnosed with anti-GBM disease associated with p-ANCA with MPO specificity. Despite heavy immunosuppression and plasmapheresis, IgG titers against dengue virus continued to rise confirming the diagnosis of acute dengue infection. We present the first reported case of anti-GBM disease associated with p-ANCA with MPO specificity during dengue infection. This report calls for a heightened awareness of autoimmunity leading to crescentic glomerulonephritis in patients with dengue infection.

[Using the polymerase chain reaction to Borrelia burgdorferi infection in localized scleroderma injure (morphea), in Venezuelan patients].

Science.gov (United States)

Espinoza-León, Fabiola; Arocha, Francisco; Hassanhi, Manzur; Arévalo, Julio

2010-09-01

Borrelia burgdorferi is the causative agent of Lyme Borreliosis, an infectious multisystemic disease transmitted to humans by the Ixodes ticks bite. A possible association of Borrelia burgdorferi with localized scleroderma has been postulated. However, published data do not provide unequivocal results. Previous serologic analysis of patients with localized scleroderma in South American countries (including Venezuela), have been reported as yielding some reactivity. The present study looked for evidence of Borrelia burgdorferi infection in venezuelan patients with localized scleroderma, using the polymerase chain reaction to analyze 21 skin samples of patients with this skin condition. The results were negative in all the samples studied. Our data do not support an association of Borrelia burgdorferi infection and the sclerotic lesions of localized scleroderma; but do not rule out the possibility of a relationship between localized scleroderma and an unknown geno-specie of Borrelia burgdorferi sensu lato complex, a different Borrelia specie or a different spirochetal organism, as the etiological agents of the skin lesions in this area.

Isolation, Phylogenetic Analysis and Anti-infective Activity Screening of Marine Sponge-Associated Actinomycetes

Directory of Open Access Journals (Sweden)

Safwat Ahmed

2010-02-01

Full Text Available Terrestrial actinomycetes are noteworthy producers of a multitude of antibiotics, however the marine representatives are much less studied in this regard. In this study, 90 actinomycetes were isolated from 11 different species of marine sponges that had been collected from offshore Ras Mohamed (Egypt and from Rovinj (Croatia. Phylogenetic characterization of the isolates based on 16S rRNA gene sequencing supported their assignment to 18 different actinomycete genera representing seven different suborders. Fourteen putatively novel species were identified based on sequence similarity values below 98.2% to other strains in the NCBI database. A putative new genus related to Rubrobacter was isolated on M1 agar that had been amended with sponge extract, thus highlighting the need for innovative cultivation protocols. Testing for anti-infective activities was performed against clinically relevant, Gram-positive (Enterococcus faecalis, Staphylococcus aureus and Gram-negative (Escherichia coli, Pseudomonas aeruginosa bacteria, fungi (Candida albicans and human parasites (Leishmania major, Trypanosoma brucei. Bioactivities against these pathogens were documented for 10 actinomycete isolates. These results show a high diversity of actinomycetes associated with marine sponges as well as highlight their potential to produce anti-infective agents.

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

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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.

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.

Development of an instant 99mTc labelled HIG kit for localization of infection/inflammation

International Nuclear Information System (INIS)

Chen Fang; Zhang Yumin; Zhou Qian

1995-01-01

99m Tc labelled polyclonal human immunoglobulin G(HIG) is a novel agent for detecting infection and inflammation. We report the preparation, quality control, pharmacology and preliminary clinical evaluation of this imaging agent. After modification of HIG and purification, the HIG kit was formulated and lyofilized. Labelling yield and radiochemical purity were determined by TLC-SG, PC and Sephadex G-50 column chromatography. Animal models for pharmacologic experiments were mice, rats and rabbits. The labelling yield was 99% immediately after mixing HIG with 99m Tc and more than 90% of radioactivity was retained after keeping the labelled product at room temperature 24 hours post labelling. There were good accumulation and high T/B ratio in animal models (rats and rabbits bearing turpentine and Staphylococcus aureus induced inflammatory or infections foci). The results showed that this new agent is nearly ideal for localization of infections/inflammatory lesions

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

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.

Hepatitis B Virus Infection and Anti-HBc (Total Positivity in CKD Patients before Dialysis

Directory of Open Access Journals (Sweden)

Fareha Jesmin Rabbi

2016-09-01

Full Text Available Background: CKD patients are associated with HBV infection both as a cause and complication of treatment. CKD patients before starting dialysis therapy are considered as a high risk group because of impaired immune response compared with healthy individuals and also other risk factors related with treatment and management. Only HBsAg marker does not always follow the presence or absence of HBV infection. Anti-HBc (total alone positivity indicates previous exposure to HBV infection, window period and even after reactivation of resolved HBV infection. In some cases only anti-HBc positivity is interpreted as possible chronic low dose HBV infection (chronic carriage. Predialytic CKD patients were tested with three serological markers [HBsAg, anti-HBc (total and anti-HBs] for screening HBV infection. Proper diagnosis before dialysis and knowing the infection status would help both the patient and doctor to choose proper treatment approach. Objective: This cross-sectional study was done in the CKD patients before starting dialysis therapy to find out the HBV infection and to evaluate the infection by minimal serological markers as for screening. Materials and Methods: A total of 211 patients with chronic kidney disease stage five (CKD-V before starting dialysis therapy were included as subjects of this cross-sectional study. Among the CKD patients HBsAg was tested to see the prevalence. Other serological markers, i.e., anti-HBc (total and anti-HBs were tested in combination with HBsAg in 89 randomly selected patients among the subjects. The patients were also tested for anti-HCV to assess co-infection. After collecting all the data of different test results analyses were done by SPSS version 15.0. Results: Among total study population 10 (4.7% patients were found HBsAg positive. No patient was found positive for both HBsAg and anti-HCV. Among the 89 CKD patients only 2 (2.2% patients were HBsAg positive, and only one patient (0.9% was found positive

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

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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.

Local antimicrobial administration for prophylaxis of surgical site infections.

Science.gov (United States)

Huiras, Paul; Logan, Jill K; Papadopoulos, Stella; Whitney, Dana

2012-11-01

Despite a lack of consensus guidelines, local antibiotic administration for prophylaxis of surgical site infections is used during many surgical procedures. The rationale behind this practice is to provide high antibiotic concentrations at the site of surgery while minimizing systemic exposure and adverse effects. Local antibiotic administration for surgical site prophylaxis has inherent limitations in that antibiotics are applied after the incision is made, rather than the current standard for surgical site prophylaxis that recommends providing adequate antibiotic concentrations at the site before the incision. The efficacy and safety of local application of antibiotics for surgical site prophylaxis have been assessed in different types of surgery with a variety of antibiotic agents and methods of application. We identified 22 prospective, randomized, controlled trials that evaluated local application of antibiotics for surgical site prophylaxis. These trials were subsequently divided and analyzed based on the type of surgical procedure: dermatologic, orthopedic, abdominal, colorectal, and cardiothoracic. Methods of local application analyzed included irrigations, powders, ointments, pastes, beads, sponges, and fleeces. Overall, there is a significant lack of level I evidence supporting this practice for any of the surgical genres evaluated. In addition, the literature spans several decades, and changes in surgical procedures, systemic antibiotic prophylaxis, and microbial flora make conclusions difficult to determine. Based on available data, the efficacy of local antibiotic administration for the prophylaxis of surgical site infections remains uncertain, and recommendations supporting this practice for surgical site prophylaxis cannot be made. © 2012 Pharmacotherapy Publications, Inc.

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....

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.

Detection of experimental infections with 99mTc-labeled monoclonal antibodies against TNF-α and interleukin-8

International Nuclear Information System (INIS)

Welling, Mick; Feitsma, Hans I.J.; Calame, Wim; Pauwels, Ernest K.J.

1997-01-01

This study was designed to assess monoclonal antibodies (MAbs) directed against tumor necrosis factor-α (TNF-α) (anti-TNF) or interleukin-8 (anti-IL-8) as radioactive agents for the detection of Staphylococcus aureus- or Klebsiella pneumoniae-infected thighs in mice. At 5 min (acute infection) or 20 h (established) post-infection, 20 μg of the 99m Tc-labeled MAbs were injected. At various time intervals, the accumulation of the radiotracer in the infected thighs was assessed and expressed as a target-to-nontarget (T/NT) ratio. The binding of 99m Tc-labeled MAbs to circulating mononuclear cells and granulocytes was quantitated 20 h after injection. The pharmacokinetics of the MAbs, in relation to the control agents 99m Tc-labeled polyclonal human immunoglobulin (IgG) and a 99m Tc-labeled nonspecific IgG1 MAb, were also studied. In acute infections, 99m Tc-anti-TNF accumulated to a higher extent (p 99m Tc-IgG and was higher at 0.25 h in K. pneumoniae-infected mice (p 99m Tc-IgG. In established S. aureus and K. pneumoniae infections, 99m Tc-anti-IL-8 detected the infection more intensely than 99m Tc-IgG until 1 h after injection. In both S. aureus and K. pneumoniae infections, localization of sites of infection correlates (p 99m Tc-labeled MAbs to granulocytes and mononuclear cells in both acute and established infections. It was concluded that 99m Tc-labeled MAbs, directed against TNF-α and IL-8, accumulate in bacterial infections in mice to a higher extent than does 99m Tc-IgG after infection and is related to the binding of the antibodies to blood leukocytes. With these 99m Tc-labeled MAbs, information might be gained about the development of an infection

Extended release formulations for local anaesthetic agents.

Science.gov (United States)

Weiniger, C F; Golovanevski, L; Domb, A J; Ickowicz, D

2012-08-01

Systemic toxicity through overdose of local anaesthetic agents is a real concern. By encapsulating local anaesthetics in biodegradable carriers to produce a system for prolonged release, their duration of action can be extended. This encapsulation should also improve the safety profile of the local anaesthetic as it is released at a slower rate. Work with naturally occurring local anaestheticss has also shown promise in the area of reducing systemic and neurotoxicity. Extended duration local anaesthetic formulations in current development or clinical use include liposomes, hydrophobic based polymer particles such as Poly(lactic-co-glycolic acid) microspheres, pasty injectable and solid polymers like Poly(sebacic-co-ricinoleic acid) P(SA:RA) and their combination with synthetic and natural local anaesthetic. Their duration of action, rationale and limitations are reviewed. Direct comparison of the different agents is limited by their chemical properties, the drug doses encapsulated and the details of in vivo models described. Anaesthesia © 2012 The Association of Anaesthetists of Great Britain and Ireland.

Novel Treatment of Staphylococcus aureus Device-Related Infections Using Fibrinolytic Agents.

Science.gov (United States)

Hogan, S; O'Gara, J P; O'Neill, E

2018-02-01

Staphylococcal infections involving biofilms represent a significant challenge in the treatment of patients with device-related infections. Staphylococcus aureus biofilms have been shown to be SaeRS regulated and dependent on the coagulase-catalyzed conversion of fibrinogen into fibrin on surfaces coated with human plasma. Here we investigated the treatment of staphylococcal biofilm device-related infections by digesting the fibrin biofilm matrix with and without existing antimicrobials. The fibrinolytic agents plasmin, streptokinase, and nattokinase, and TrypLE, a recombinant trypsin-like protease, were used to digest and treat S. aureus biofilms grown in vitro using in vivo -like static biofilm assays with and without antimicrobials. Cytotoxicity, the potential to induce a cytokine response in whole human blood, and the risk of induction of tolerance to fibrinolytic agents were investigated. A rat model of intravascular catheter infection was established to investigate the efficacy of selected fibrinolytic agents in vivo Under biomimetic conditions, the fibrinolytic agents effectively dispersed established S. aureus biofilms and, in combination with common antistaphylococcal antimicrobials, effectively killed bacterial cells being released from the biofilm. These fibrinolytic agents were not cytotoxic and did not affect the host immune response. The rat model of infection successfully demonstrated the activity of the selected fibrinolytic agents alone and in combination with antimicrobials on established biofilms in vivo TrypLE and nattokinase most successfully removed adherent cells from plasma-coated surfaces and significantly improved the efficacy of existing antimicrobials against S. aureus biofilms in vitro and in vivo These biofilm dispersal agents represent a viable future treatment option for S. aureus device-related infections. Copyright © 2018 American Society for Microbiology.

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 ...

On the local applications of antibiotics and antibiotic-based agents in endodontics and dental traumatology.

Science.gov (United States)

Mohammadi, Z; Abbott, P V

2009-07-01

Antibiotics are a valuable adjunctive to the armamentarium available to health professionals for the management of bacterial infections. During endodontic treatment and when managing trauma to the teeth, antibiotics may be applied systemically (orally and/or parenterally) or locally (i.e. intra-dentally via irrigants and medicaments). Due to the potential risk of adverse effects following systemic application, and the ineffectiveness of systemic antibiotics in necrotic pulpless teeth and the periradicular tissues, the local application of antibiotics may be a more effective mode for delivery in endodontics. The aim of this article was to review the history, rationale and applications of antibiotic-containing irrigants and medicaments in endodontics and dental traumatology. The search was performed from 1981 to 2008 and was limited to English-language papers. The keywords searched on Medline were 'Antibiotics AND endodontics', 'Antibiotics AND root canal irrigation', 'Antibiotics AND intra-canal medicament', 'Antibiotics AND Dental trauma' and 'Antibiotics AND root resorption'. The reference section of each article was manually searched to find other suitable sources of information. It seems that local routes of antibiotic administration are a more effective mode than systemic applications. Various antibiotics have been tested in numerous studies and each has some advantages. Tetracyclines are a group of bacteriostatic antibiotics with antibacterial substantivity for up to 12 weeks. They are typically used in conjunction with corticosteroids and these combinations have anti-inflammatory, anti-bacterial and anti-resorptive properties, all of which help to reduce the periapical inflammatory reaction including clastic-cell mediated resorption. Tetracyclines have also been used as part of irrigating solutions but the substantivity is only for 4 weeks. Clindamycin and a combination of three antibiotics (metronidazole, ciprofloxacin and minocycline) have also been

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

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.

Labeling of antibiotics for infection diagnosis

International Nuclear Information System (INIS)

Benitez, A.; Roca, M.; Martin-Comin, J.

2006-01-01

The high impact of infection on daily clinical practice has promoted research into better and more accurate diagnostic and therapeutic methods. Localizing inflammation/infection with nuclear medicine techniques began over 40 years ago. Today, 6 7G a-scintigraphy, 9 9mT c-nanocolloid, 1 11I n and 9 9mT c in vitro labeled leukocytes, and monoclonal anti granulocyte antibodies are widely available for this purpose. While these methods are useful for localizing inflammation, they cannot always differentiate septic from aseptic processes. The ideal properties of an agent for diagnosing infection include: high specificity, early diagnosis, rapid blood clearance, ease of preparation, low toxicity, biodistribution appropriate for the disease under study, absence of immunologic response and low cost. A novel approach to infection diagnosis is the use of radiolabelled antibiotics. Antibiotics localize in the infectious focus, where they are frequently taken up and metabolized by microorganisms. The majority of the various antibiotics studied so far are those of the quinolones group (ciprofloxacin, sparfloxacin, enrofloxacin, levofloxacin, norfloxacin and ofloxacin). More recently, the labeling of ceftizoxime, a semisynthetic third generation cephalosporin, has been reported. The relevant features of labeled antibiotics in research and/or clinical infection diagnosis are the focus of this article

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.

Anti-infective efficacy of the lactoferrin-derived antimicrobial peptide HLR1r.

Science.gov (United States)

Björn, Camilla; Mahlapuu, Margit; Mattsby-Baltzer, Inger; Håkansson, Joakim

2016-07-01

Antimicrobial peptides (AMPs) have emerged as a new class of drug candidates for the treatment of infectious diseases. Here we describe a novel AMP, HLR1r, which is structurally derived from the human milk protein lactoferrin and demonstrates a broad spectrum microbicidal action in vitro. The minimum concentration of HLR1r needed for killing ≥99% of microorganisms in vitro, was in the range of 3-50μg/ml for common Gram-negative and Gram-positive bacteria, including methicillin-resistant Staphylococcus aureus (MRSA), and for the yeast Candida albicans, when assessed in diluted brain-heart infusion medium. We found that HLR1r also possesses anti-inflammatory properties as evidenced by inhibition of tumor necrosis factor alpha (TNF-α) secretion from human monocyte-derived macrophages and by repression of interleukin-6 (IL-6) and plasminogen activator inhibitor-1 (PAI-1) secretion from human mesothelial cells, without any cytotoxic effect observed at the concentration range tested (up to 400μg/ml). HLR1r demonstrated pronounced anti-infectious effect in in vivo experimental models of cutaneous candidiasis in mice and of excision wounds infected with MRSA in rats as well as in an ex vivo model of pig skin infected with S. aureus. In conclusion, HLR1r may constitute a new therapeutic alternative for local treatment of skin infections. Copyright © 2016 Elsevier Inc. All rights reserved.

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.

Local Th17/IgA immunity correlate with protection against intranasal infection with Streptococcus pyogenes.

Directory of Open Access Journals (Sweden)

Rasmus Mortensen

Full Text Available Streptococcus pyogenes (group A streptococcus, GAS is responsible for a wide array of infections. Respiratory transmission via droplets is the most common mode of transmission but it may also infect the host via other routes such as lesions in the skin. To advance the development of a future vaccine against GAS, it is therefore important to investigate how protective immunity is related to the route of vaccine administration. To explore this, we examined whether a parenterally administered anti-GAS vaccine could protect against an intranasal GAS infection or if this would require locally primed immunity. We foundd that a parenteral CAF01 adjuvanted GAS vaccine offered no protection against intranasal infection despite inducing strong systemic Th1/Th17/IgG immunity that efficiently protected against an intraperitoneal GAS infection. However, the same vaccine administered via the intranasal route was able to induce protection against repeated intranasal GAS infections in a murine challenge model. The lack of intranasal protection induced by the parenteral vaccine correlated with a reduced mucosal recall response at the site of infection. Taken together, our results demonstrate that locally primed immunity is important for the defense against intranasal infection with Streptococcus pyogenes.

Xylitol, an anticaries agent, exhibits potent inhibition of inflammatory responses in human THP-1-derived macrophages infected with Porphyromonas gingivalis.

Science.gov (United States)

Park, Eunjoo; Na, Hee Sam; Kim, Sheon Min; Wallet, Shannon; Cha, Seunghee; Chung, Jin

2014-06-01

Xylitol is a well-known anticaries agent and has been used for the prevention and treatment of dental caries. In this study, the anti-inflammatory effects of xylitol are evaluated for possible use in the prevention and treatment of periodontal infections. Cytokine expression was stimulated in THP-1 (human monocyte cell line)-derived macrophages by live Porphyromonas gingivalis, and enzyme-linked immunosorbent assay and a commercial multiplex assay kit were used to determine the effects of xylitol on live P. gingivalis-induced production of cytokine. The effects of xylitol on phagocytosis and the production of nitric oxide were determined using phagocytosis assay, viable cell count, and Griess reagent. The effects of xylitol on P. gingivalis adhesion were determined by immunostaining, and costimulatory molecule expression was examined by flow cytometry. Live P. gingivalis infection increased the production of representative proinflammatory cytokines, such as tumor necrosis factor-α and interleukin (IL)-1β, in a multiplicity of infection- and time-dependent manner. Live P. gingivalis also enhanced the release of cytokines and chemokines, such as IL-12 p40, eotaxin, interferon γ-induced protein 10, monocyte chemotactic protein-1, and macrophage inflammatory protein-1. The pretreatment of xylitol significantly inhibited the P. gingivalis-induced cytokines production and nitric oxide production. In addition, xylitol inhibited the attachment of live P. gingivalis on THP-1-derived macrophages. Furthermore, xylitol exerted antiphagocytic activity against both Escherichia coli and P. gingivalis. These findings suggest that xylitol acts as an anti-inflammatory agent in THP-1-derived macrophages infected with live P. gingivalis, which supports its use in periodontitis.

Agent Collaborative Target Localization and Classification in Wireless Sensor Networks

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Sheng Wang

2007-07-01

Full Text Available Wireless sensor networks (WSNs are autonomous networks that have beenfrequently deployed to collaboratively perform target localization and classification tasks.Their autonomous and collaborative features resemble the characteristics of agents. Suchsimilarities inspire the development of heterogeneous agent architecture for WSN in thispaper. The proposed agent architecture views WSN as multi-agent systems and mobileagents are employed to reduce in-network communication. According to the architecture,an energy based acoustic localization algorithm is proposed. In localization, estimate oftarget location is obtained by steepest descent search. The search algorithm adapts tomeasurement environments by dynamically adjusting its termination condition. With theagent architecture, target classification is accomplished by distributed support vectormachine (SVM. Mobile agents are employed for feature extraction and distributed SVMlearning to reduce communication load. Desirable learning performance is guaranteed bycombining support vectors and convex hull vectors. Fusion algorithms are designed tomerge SVM classification decisions made from various modalities. Real world experimentswith MICAz sensor nodes are conducted for vehicle localization and classification.Experimental results show the proposed agent architecture remarkably facilitates WSNdesigns and algorithm implementation. The localization and classification algorithms alsoprove to be accurate and energy efficient.

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.

[Study on the anti-NTHi infection of Hap recombinant protein in vivo].

Science.gov (United States)

Li, Wan-yi; Wang, Bao-ning; Zuo, Feng-qiong; Zeng, Wei; Feng, Feng; Kuang, Yu; Jiang, Zhong-hua; Li, Ming-yuan

2010-07-01

To observe the immune effect of Hap recombinant protein on murine model of bronchopneumonia infected with NTHi, and explore the mechanism about the anti-NTHi infection. The C57BL/6 mice intranasally immunized with purified Hap recombinant protein and CT-B were challenged by NTHi encased in agar beads. The immunifaction of anti-infection was observed through encocyte counting of BALF, bacteria detection of lung and the pathologyical change of lung tissue. In the challenge with NTHi experiment, the inflammatory exudation of the infected murine and pathological change of lung tissue was relieved by combined immunization of Hap recombinant protein and CT-B, and quantity of NTHi in lung of the infected murine was reduced obviously. The Hap recombinant protein also had good ability of anti-NTHi infection in the murine model of NTHi bronchopneumonia. This study could offer the oretical and experimental basis for development of new vaccine against NTHi.

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.

Bioactive activities of natural products against herpesvirus infection.

Science.gov (United States)

Son, Myoungki; Lee, Minjung; Sung, Gi-Ho; Lee, Taeho; Shin, Yu Su; Cho, Hyosun; Lieberman, Paul M; Kang, Hyojeung

2013-10-01

More than 90% of adults have been infected with at least one human herpesvirus, which establish long-term latent infection for the life of the host. While anti-viral drugs exist that limit herpesvirus replication, many of these are ineffective against latent infection. Moreover, drug-resistant strains of herpesvirus emerge following chemotherapeutic treatment. For example, resistance to acyclovir and related nucleoside analogues can occur when mutations arise in either HSV thymidine kinase or DNA polymerases. Thus, there exists an unmet medical need to develop new anti-herpesvirus agents with different mechanisms of action. In this Review, we discuss the promise of anti-herpetic substances derived from natural products including extracts and pure compounds from potential herbal medicines. One example is Glycyrrhizic acid isolated from licorice that shows promising antiviral activity towards human gammaherpesviruses. Secondly, we discuss anti-herpetic mechanisms utilized by several natural products in molecular level. While nucleoside analogues inhibit replicating herpesviruses in lytic replication, some natural products can disrupt the herpesvirus latent infection in the host cell. In addition, natural products can stimulate immune responses against herpesviral infection. These findings suggest that natural products could be one of the best choices for development of new treatments for latent herpesvirus infection, and may provide synergistic anti-viral activity when supplemented with nucleoside analogues. Therefore, it is important to identify which natural products are more efficacious anti-herpetic agents, and to understand the molecular mechanism in detail for further advance in the anti-viral therapies.

HBV vaccination of HCV-infected patients with occult HBV infection and anti-HBc-positive blood donors

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J.S.F. Pereira

2006-04-01

Full Text Available Anti-HBc positivity is a frequent cause of donation rejection at blood banks. Hepatitis B virus (HBV infection may also occur in HBsAg-negative patients, a situation denoted occult infection. Similarly, very low levels of HBV-DNA have also been found in the sera of patients with chronic hepatitis C virus (HCV infection, even in the absence of serum HBsAg. Initially we searched for HBV-DNA in serum of 100 blood donors and 50 HCV-infected patients who were HBsAg negative/anti-HBc positive by nested-PCR and by an HBV monitor commercial test for HBV-DNA. Anti-HBs seroconversion rates were measured in 100 blood donors and in 22 patients with chronic HCV infection after HBV vaccination to determine if the HBV vaccination could eliminate an occult HBV infection in these individuals. Occult HBV infection was detected in proportionally fewer blood donors (6/100 = 6% than chronic hepatitis C patients (12/50 = 24% (P 0.05. All subjects who were HBV-DNA(+ before the first dose of HBV vaccine (D1, became HBV-DNA(- after D1, D2, and D3. Among 22 HCV-positive patients, 10 HBV-DNA(+ and 12 HBV-DNA(-, seroconversion was observed in 9/10 (90% HBV-DNA(+ and in 9/12 (75% HBV-DNA(- subjects (P > 0.05. The disappearance of HBV-DNA in the majority of vaccinated patients suggests that residual HBV can be eliminated in patients with occult infection.

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

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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.

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.

Anti-aging pharmacology in cutaneous wound healing: effects of metformin, resveratrol, and rapamycin by local application.

Science.gov (United States)

Zhao, Pan; Sui, Bing-Dong; Liu, Nu; Lv, Ya-Jie; Zheng, Chen-Xi; Lu, Yong-Bo; Huang, Wen-Tao; Zhou, Cui-Hong; Chen, Ji; Pang, Dan-Lin; Fei, Dong-Dong; Xuan, Kun; Hu, Cheng-Hu; Jin, Yan

2017-10-01

Cutaneous wounds are among the most common soft tissue injuries and are particularly hard to heal in aging. Caloric restriction (CR) is well documented to extend longevity; pharmacologically, profound rejuvenative effects of CR mimetics have been uncovered, especially metformin (MET), resveratrol (RSV), and rapamycin (RAPA). However, locally applied impacts and functional differences of these agents on wound healing remain to be established. Here, we discovered that chronic topical administration of MET and RSV, but not RAPA, accelerated wound healing with improved epidermis, hair follicles, and collagen deposition in young rodents, and MET exerted more profound effects. Furthermore, locally applied MET and RSV improved vascularization of the wound beds, which were attributed to stimulation of adenosine monophosphate-activated protein kinase (AMPK) pathway, the key mediator of wound healing. Notably, in aged skin, AMPK pathway was inhibited, correlated with impaired vasculature and reduced healing ability. As therapeutic approaches, local treatments of MET and RSV prevented age-related AMPK suppression and angiogenic inhibition in wound beds. Moreover, in aged rats, rejuvenative effects of topically applied MET and RSV on cell viability of wound beds were confirmed, of which MET showed more prominent anti-aging effects. We further verified that only MET promoted wound healing and cutaneous integrity in aged skin. These findings clarified differential effects of CR-based anti-aging pharmacology in wound healing, identified critical angiogenic and rejuvenative mechanisms through AMPK pathway in both young and aged skin, and unraveled chronic local application of MET as the optimal and promising regenerative agent in treating cutaneous wound defects. © 2017 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.

Pyrene conjugation and spectroscopic analysis of hydroxypropyl methylcellulose compounds successfully demonstrated a local dielectric difference associated with in vivo anti-prion activity.

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Kenta Teruya

Full Text Available Our previous study on prion-infected rodents revealed that hydroxypropyl methylcellulose compounds (HPMCs with different molecular weights but similar composition and degree of substitution have different levels of long-lasting anti-prion activity. In this study, we searched these HPMCs for a parameter specifically associated with in vivo anti-prion activity by analyzing in vitro chemical properties and in vivo tissue distributions. Infrared spectroscopic and thermal analyses revealed no differences among HPMCs, whereas pyrene conjugation and spectroscopic analysis revealed that the fluorescence intensity ratio of peak III/peak I correlated with anti-prion activity. This correlation was more clearly demonstrated in the anti-prion activity of the 1-year pre-infection treatment than that of the immediate post-infection treatment. In addition, the intensity ratio of peak III/peak I negatively correlated with the macrophage uptake level of HPMCs in our previous study. However, the in vivo distribution pattern was apparently not associated with anti-prion activity and was different in the representative tissues. These findings suggest that pyrene conjugation and spectroscopic analysis are powerful methods to successfully demonstrate local dielectric differences in HPMCs and provide a feasible parameter denoting the long-lasting anti-prion activity of HPMCs in vivo.

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

Population, Environmental, and Community Effects on Local Bank Vole (Myodes glareolus) Puumala Virus Infection in an Area with Low Human Incidence

DEFF Research Database (Denmark)

Tersago, K; Schreurs, A; Linard, C

2008-01-01

In this study, the distribution of Puumala hantavirus (PUUV) infection in local bank vole Myodes glareolus populations in an area with low human PUUV infection (nephropathia epidemica [NE]) incidence in northern Belgium was monitored for 2 consecutive years. Bank voles were trapped in preferred h...... activity patterns, local environmental conditions and rodent community structure are also likely to play a role in determining PUUV infection risk for humans....... habitat and tested for anti-PUUV IgG. Infection data were related to individual bank vole features, population demography, and environmental variables. Rare occurrence of PUUV infection was found and PUUV prevalence was low compared with data from the high NE incidence area in southern Belgium. Small...

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

Agentes globais e esfera local: o pólo automobilístico de Gravataí Global agents and the local level: the Gravataí automotive complex

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Sandro Ruduit Garcia

2010-04-01

Full Text Available O artigo tenta discutir aspectos das relações global-local, focalizando o processo de formação e desenvolvimento do pólo automobilístico de Gravataí e suas implicações sociais no âmbito das relações de trabalho e emprego em empresas locais. Ao reconhecer a recente formação do sistema global, supõe-se que a presença de agentes globais em contextos locais tenderia a criar novas dinâmicas sociais que dependeriam de articulações específicas entre conjunturas econômico-institucionais, níveis e tipos de recursos econômicos e sociais disponíveis, e estratégias mobilizadas pelos agentes sociais. Os agentes globais imporiam novas referências competitivas e tecnológicas aos agentes locais, que se achariam, com frequência, despreparados para acompanhar tais exigências. Por outro lado, poderiam ser criadas, com diferentes configurações, chances de acesso a capitais, mercados, tecnologias e conhecimentos, estimulando mudanças nas relações de trabalho e emprego na esfera local. A assimetria nas relações de poder econômico não impediria a reação dos agentes locais, nas possibilidades de seus recursos e nos horizontes de seus valores, às novas regras e condições do sistema internacional. A relação global-local teria, portanto, implicações distintas entre os agentes sociais.This article discusses aspects of the global-local relations, focusing on the process of formation and development of the Gravataí automotive complex and its social implications as related to the labor relations and employment in local companies. In accordance with the recent formation of the global system, it is assumed that the presence of global agents in local contexts creates new social dynamics that depend on specific arrangements between economic and institutional circumstances, levels and types of available social and economic resources, and strategies mobilized by social agents. The global agents would impose new competitive and

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

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

[Hepatitis B infection transmission by anti-HBc-positive grafts].

Science.gov (United States)

Bárcena, Rafael

2014-07-01

In Spain, the rate of anti-HBc positive, HBsAg-negative carriers is approximately 10% of adults between the ages of 26 and 65 years. It is therefore impossible to exclude these donors without increasing the mortality of recipients on waiting lists. The incidence of de novo hepatitis B infection in HBsAg-negative recipients of anti-HBc-positive donors is high without prophylaxis and is related to the serological state of the recipient against HBV. Anti-HBc and anti-HBs-positive recipients have low risk, with or without prophylaxis. This patient group therefore does not require prophylaxis but rather periodic posttransplantation checkups. For the other recipient groups (naïve, anti-Hbc and anti-HBs isolates), prophylaxis with IgG HB, lamivudine or combined therapy decreases the incidence of infection. These patients should be treated with prophylaxis immediately after transplantation. Depending on the risk, cost and benefit, patients should currently be treated with lamivudine 100mg/d indefinitely or for longer periods (>10 years). Periodic checkups of HBsAg should be conducted, and if there is graft dysfunction then HBV DNA should be checked. IF HBV DNA is discovered in the donor and found to be positive in serum or in the biopsy, the prophylaxis should be an analogue with a high barrier to resistance from the start. Grafts from anti-HBc-positive donors are not considered at-risk grafts and are used according to donor severity, without being determined by the recipient's serological profile. Copyright © 2014 Elsevier España, S.L. All rights reserved.

Global occurrence of anti-infectives in contaminated surface waters: Impact of income inequality between countries.

Science.gov (United States)

Segura, Pedro A; Takada, Hideshige; Correa, José A; El Saadi, Karim; Koike, Tatsuya; Onwona-Agyeman, Siaw; Ofosu-Anim, John; Sabi, Edward Benjamin; Wasonga, Oliver V; Mghalu, Joseph M; dos Santos Junior, Antonio Manuel; Newman, Brent; Weerts, Steven; Yargeau, Viviane

2015-07-01

The presence anti-infectives in environmental waters is of interest because of their potential role in the dissemination of anti-infective resistance in bacteria and other harmful effects on non-target species such as algae and shellfish. Since no information on global trends regarding the contamination caused by these bioactive substances is yet available, we decided to investigate the impact of income inequality between countries on the occurrence of anti-infectives in surface waters. In order to perform such study, we gathered concentration values reported in the peer-reviewed literature between 1998 and 2014 and built a database. To fill the gap of knowledge on occurrence of anti-infectives in African countries, we also collected 61 surface water samples from Ghana, Kenya, Mozambique and South Africa, and measured concentrations of 19 anti-infectives. A mixed one-way analysis of covariance (ANCOVA) model, followed by Turkey-Kramer post hoc tests was used to identify potential differences in anti-infective occurrence between countries grouped by income level (high, upper-middle and lower-middle and low income) according to the classification by the World Bank. Comparison of occurrence of anti-infectives according to income level revealed that concentrations of these substances in contaminated surface waters were significantly higher in low and lower-middle income countries (p=0.0001) but not in upper-middle income countries (p=0.0515) compared to high-income countries. We explained these results as the consequence of the absence of or limited sewage treatment performed in lower income countries. Furthermore, comparison of concentrations of low cost anti-infectives (sulfonamides and trimethoprim) and the more expensive macrolides between income groups suggest that the cost of these substances may have an impact on their environmental occurrence in lower income countries. Since wastewaters are the most important source of contamination of anti-infectives and other

Anti-gluten immune response following Toxoplasma gondii infection in mice.

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Emily G Severance

Full Text Available Gluten sensitivity may affect disease pathogenesis in a subset of individuals who have schizophrenia, bipolar disorder or autism. Exposure to Toxoplasma gondii is a known risk factor for the development of schizophrenia, presumably through a direct pathological effect of the parasite on brain and behavior. A co-association of antibodies to wheat gluten and to T. gondii in individuals with schizophrenia was recently uncovered, suggesting a coordinated gastrointestinal means by which T. gondii and dietary gluten might generate an immune response. Here, we evaluated the connection between these infectious- and food-based antigens in mouse models. BALB/c mice receiving a standard wheat-based rodent chow were infected with T. gondii via intraperitoneal, peroral and prenatal exposure methods. Significant increases in the levels of anti-gluten IgG were documented in all infected mice and in offspring from chronically infected dams compared to uninfected controls (repetitive measures ANOVAs, two-tailed t-tests, all p≤0.00001. Activation of the complement system accompanied this immune response (p≤0.002-0.00001. Perorally-infected females showed higher levels of anti-gluten IgG than males (p≤0.009 indicating that T. gondii-generated gastrointestinal infection led to a significant anti-gluten immune response in a sex-dependent manner. These findings support a gastrointestinal basis by which two risk factors for schizophrenia, T. gondii infection and sensitivity to dietary gluten, might be connected to produce the immune activation that is becoming an increasingly recognized pathology of psychiatric disorders.

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.

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.

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

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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.

Local Th17/IgA immunity correlate with protection against intranasal infection with Streptococcus pyogenes

DEFF Research Database (Denmark)

Mortensen, Rasmus; Christensen, Dennis; Hansen, Lasse Bøllehuus

2017-01-01

Streptococcus pyogenes (group A streptococcus, GAS) is responsible for a wide array of infections. Respiratory transmission via droplets is the most common mode of transmission but it may also infect the host via other routes such as lesions in the skin. To advance the development of a future...... vaccine against GAS, it is therefore important to investigate how protective immunity is related to the route of vaccine administration. To explore this, we examined whether a parenterally administered anti-GAS vaccine could protect against an intranasal GAS infection or if this would require locally...... primed immunity. We foundd that a parenteral CAF01 adjuvanted GAS vaccine offered no protection against intranasal infection despite inducing strong systemic Th1/Th17/IgG immunity that efficiently protected against an intraperitoneal GAS infection. However, the same vaccine administered via...

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

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.

99m Tc-tazobactam, a novel infection imaging agent: Radiosynthesis, quality control, biodistribution, and infection imaging studies.

Science.gov (United States)

Rasheed, Rashid; Naqvi, Syed Ali Raza; Gillani, Syed Jawad Hussain; Zahoor, Ameer Fawad; Jielani, Asif; Saeed, Nidda

2017-05-15

The radiolabeled drug 99m Tc-tazobactam ( 99m Tc-TZB) was developed and assessed as an infection imaging agent in Pseudomonas aeruginosa and Salmonella enterica infection-induced animal models by comparing with inflammation induced animal models. Radiosynthesis of 99m Tc-TZB was assessed while changing ligand concentration, reducing agent concentration, pH, and reaction time while keeping radioactivity constant (~370 MBq). Percent labeling of the resulting complex was measured using paper chromatography and instant thin layer chromatography. The analysis of the 99m Tc-TZB complex indicated >95% labeling yield and electrophoresis revealed complex is neutral in nature. The biodistribution study also showed predominantly renal excretion; however liver, stomach, and intestine also showed slight tracer agent uptake. The agent significantly accumulated in Pseudomonas aeruginosa and Salmonella enterica infection induced tissues 3.58 ± 0.26% and 2.43 ± 0.42% respectively at 1 hour postinjection. The inflamed tissue failed to uptake noticeable activity at 1 hour time point. The scintigraphic study results were found in accordance with biodistribution pattern. On the basis of our preliminary results, the newly developed 99m Tc-TZB can be used to diagnose bacterial infection and to discriminate between infected and inflamed tissues. Copyright © 2017 John Wiley & Sons, Ltd.

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 ...

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

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

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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.

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...

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

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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.

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

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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.

Seropositivity of agents causing abortion in local goat breeds in Eastern and South-eastern Anatolia, Turkey

OpenAIRE

BABÜR, Cahit; Tan, Tolga; ATASEVEN, Lale; ATASEVEN, Veysel Soydal; OĞUZOĞLU, Tuba Çiğdem

2006-01-01

The epidemiological information has not been available on the seroprevalenceof agents causing abortion and genital tract infection in indigenousgoats of Eastern and South-eastern regions of Turkey, yet. In these regions,the goats have importance for local economy and their production of meat,milk and mohair. There are also differences of the husbandry and climateconditions between two regions. The objective of this study was to describethe seroprevalence and distribution of antibodies to agen...

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

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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.

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

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.

Fatal infections in older patients with inflammatory bowel disease on anti-tumor necrosis factor therapy

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Way-Seah Lee

2017-10-01

Full Text Available Anti-tumor necrosis factor (anti-TNF is highly effective in inflammatory bowel disease (IBD; however, it is associated with an increased risk of infections, particularly in older adults. We reviewed 349 patients with IBD, who were observed over a 12-month period, 74 of whom had received anti-TNF therapy (71 patients were aged <60 years and 3 were aged ≥60 years. All the 3 older patients developed serious infectious complications after receiving anti-TNFs, although all of them were also on concomitant immunosuppressive therapy. One patient developed disseminated tuberculosis, another patient developed cholera diarrhea followed by nosocomial pneumonia, while the third patient developed multiple opportunistic infections (Pneumocystis pneumonia, cryptococcal septicemia and meningitis, Klebsiella septicemia. All 3 patients died within 1 year from the onset of the infection(s. We recommend that anti-TNF, especially when combined with other immunosuppressive therapy, should be used with extreme caution in older adult patients with IBD.

Local production of donkey anti-sheep serum and its use as a separation system in radioimmunoassay

International Nuclear Information System (INIS)

Ali, Nagi Ibrahim

2000-01-01

In this experiment two local donkeys were immunized with sheep IgG in order to produce donkey anti-sheep serum. Blood was collected from the two donkeys, tested for the presence of antibodies. The serum of the two donkeys was pooled together in one pool. The produced donkey anti-sheep serum (DASS) has been successfully used as a second antibody separation agent in radioimmunoassay for the determination of thyroid hormones (Thyroxine and triiodothyronine) and progesterone. The titer was found to be 1/40, which was reasonably good, and consequently the six litres extracted from the two donkeys would be sufficient for more than ten years. In addition to this the locally produced antibody secures the continuous supply of the same quality of antibody for a long period of time. Speaking in financial terms, local production of antibodies reduces the cost of the immunoassay kit to one tenth of its original value if imported from outside. In addition to this it would save a lot of the limited foreign currency which other wise would be spend in order to obtain the antibody from abroad. Results of patient samples and quality control (Biorad) obtained by locally produced antibody when compared with those gained by commercial kits showed very good comparability with a correlation coefficient of 0.94 and P<0.05. (Author)

The future of infection imaging

International Nuclear Information System (INIS)

Buscombe, J.R.

2006-01-01

Over the past 10 years, there has been an unprecedented explosion in new agents suggested for imaging infection. These agents have been based on our understanding of the processes involved in invasive infection of the body by microorganisms and the body's response to them. Work with antibodies has traditionally yielded the most likely candidates, 3 of which have entered clinical use in Europe and the USA. However, the expense and limitations of producing antibodies have resulted in investigations into the use of cytokine and anti-microbial radiolabelled peptides. This work is very promising in that these types of tracers may be more specific for infection than labelled leukocytes. There remains a big question mark, however, as to whether or not these will progress from phase 1./2. trials to phase 3. trials and, ultimately, to clinical use. Finally, the investigation of radiolabelled anti-microbial continues and may prove to be most useful with anti-fungal especially in the immuno-suppressed host. We live in exciting times in the evolution of infection imaging; time and commercial constraints will determine which, if any of these tracers make it to the market and will they do so before PET rules all nuclear medicine?

Anti-infective bovine colostrum oligosaccharides: Campylobacter jejuni as a case study.

Science.gov (United States)

Lane, Jonathan A; Mariño, Karina; Naughton, Julie; Kavanaugh, Devon; Clyne, Marguerite; Carrington, Stephen D; Hickey, Rita M

2012-07-02

Campylobacter jejuni is the leading cause of acute bacterial infectious diarrhea in humans. Unlike in humans, C. jejuni is a commensal within the avian host. Heavily colonized chickens often fail to display intestinal disease, and no cellular attachment or invasion has been demonstrated in-vivo. Recently, researchers have shown that the reason for the attenuation of C. jejuni virulence may be attributed to the presence of chicken intestinal mucus and more specifically chicken mucin. Since mucins are heavily glycosylated molecules this observation would suggest that glycan-based compounds may act as anti-infectives against C. jejuni. Considering this, we have investigated naturally sourced foods for potential anti-infective glycans. Bovine colostrum rich in neutral and acidic oligosaccharides has been identified as a potential source of anti-infective glycans. In this study, we tested oligosaccharides isolated and purified from the colostrum of Holstein Friesian cows for anti-infective activity against a highly invasive strain of C. jejuni. During our initial studies we structurally defined 37 bovine colostrum oligosaccharides (BCO) by HILIC-HPLC coupled with exoglycosidase digests and off-line mass spectroscopy, and demonstrated the ability of C. jejuni to bind to some of these structures, in-vitro. We also examined the effect of BCO on C. jejuni adhesion to, invasion of and translocation of HT-29 cells. BCO dramatically reduced the cellular invasion and translocation of C. jejuni, in a concentration dependent manner. Periodate treatment of the BCO prior to inhibition studies resulted in a loss of the anti-infective activity of the glycans suggesting a direct oligosaccharide-bacterial interaction. This was confirmed when the BCO completely prevented C. jejuni binding to chicken intestinal mucin, in-vitro. This study builds a strong case for the inclusion of oligosaccharides sourced from cow's milk in functional foods. However, it is only through further

MEDICAL PROTECTION FOR THE EXPEDITIONARY FORCE IN THE EVENT OF USING BIOLOGICAL AGENTS

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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.

Treatment of Oral Multispecies Biofilms by an Anti-Biofilm Peptide.

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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.

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.

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

Nuclear techniques in the study of parasitic infections

International Nuclear Information System (INIS)

1982-01-01

Out of 57 papers published, 47 fall within the INIS subject scope. Seven main topics were covered: resistance to infections with protozoan parasites; resistance to infections with African trypanosomes and helminths of ruminant animals; resistance to infections with filarial parasites and schistosomes; pathology of parasitic infections; epidemiology and diagnosis of parasitic infections; physiology and biochemistry of parasitic organisms; pharmacodynamics of anti-parasitic agents

Nematode Peptides with host-directed anti-inflammatory activity rescue Caenorhabditis elegans from a Burkholderia pseudomallei infection

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Mei-Perng Lim

2016-09-01

Full Text Available Burkholderia pseudomallei, the causative agent of melioidosis, is among a growing number of bacterial pathogens that are increasingly antibiotic resistant. Antimicrobial peptides (AMPs have been investigated as an alternative approach to treat microbial infections, as generally, there is a lower likelihood that a pathogen will develop resistance to AMPs. In this study, 36 candidate Caenorhabditis elegans genes that encode secreted peptides of <150 amino acids and previously shown to be overexpressed during infection by B. pseudomallei were identified from the expression profile of infected nematodes. RNA interference (RNAi-based knockdown of 12/34 peptide-encoding genes resulted in enhanced nematode susceptibility to B. pseudomallei without affecting worm fitness. A microdilution test demonstrated that two peptides, NLP-31 and Y43C5A.3, exhibited anti-B. pseudomallei activity in a dose dependent manner on different pathogens. Time kill analysis proposed that these peptides were bacteriostatic against B. pseudomallei at concentrations up to 8× MIC90. The SYTOX green assay demonstrated that NLP-31 and Y43C5A.3 did not disrupt the B. pseudomallei membrane. Instead, gel retardation assays revealed that both peptides were able to bind to DNA and interfere with bacterial viability. In parallel, microscopic examination showed induction of cellular filamentation, a hallmark of DNA synthesis inhibition, of NLP-31 and Y43C5A.3 treated cells. In addition, the peptides also regulated the expression of inflammatory cytokines in B. pseudomallei infected macrophage cells. Collectively, these findings demonstrate the potential of NLP-31 and Y43C5A.3 as anti-B. pseudomallei peptides based on their function as immune modulators.

Anti-N-methyl-D-aspartate receptor encephalitis associated with intracranial Angiostrongylus cantonensis infection: a case report.

Science.gov (United States)

Peng, Yu; Liu, Xiaojia; Pan, Suyue; Xie, Zuoshan; Wang, Honghao

2017-04-01

Anti-N-methyl-D-aspartate (NMDA) receptor encephalitis is a recently described paraneoplastic syndrome with prominent neuropsychiatric symptoms. Many of these cases are associated with neoplasma especially teratoma. In addition, a few of cases with anti-NMDAR antibodies triggered by viral infection have been reported, but never by parasitic infection. Here, we report a novel case of NMDA receptor encephalitis in a 51-year-old male related to the development of anti-NMDAR antibodies triggered by Angiostrongylus cantonensis infection.

Treating infected diabetic wounds with superoxidized water as anti-septic agent: a preliminary experience

International Nuclear Information System (INIS)

Hadi, S.F.; Khaliq, T.; Zubair, M.; Saaiq, M.; Sikandar, I.

2007-01-01

To evaluate the effectiveness of superoxidized water (MicrocynTM) in diabetic patients with different wounds. One hundred known diabetic patients were enrolled. Half were randomized to the intervention group (those whose wounds were managed with superoxidized water) and half to the control group (whose wounds were treated with normal saline) using a table of random numbers. The two groups were matched for age, gender, duration of diabetes and category of wound. All patients received appropriate surgical treatment for their wounds as required. Local wound treatment was carried out daily using superoxidized water soaked gauzes on twice daily basis in the intervention group and normal saline in the control group. The treatment was continued until wound healing. The main outcome measures were duration of hospital stay, downgrading of the wound category, wound healing time and need for interventions such as amputation. Statistically significant differences were found in favour of the superoxidized water group with respect to duration of hospital stay, downgrading of the wound category and wound healing time. Although the initial results of employing superoxidized water for the management of infected diabetic wounds are encouraging, further multicentre clinical trials are warranted before this antiseptic is recommended for general use. It may offer an economical alternative to other expensive antiseptics with positive impact on the prevailing infection rates, patient outcomes and patient satisfaction. (author)

[Antibibiotic resistance by nosocomial infections' causal agents].

Science.gov (United States)

Salazar-Holguín, Héctor Daniel; Cisneros-Robledo, María Elena

2016-01-01

The antibibiotic resistance by nosocomial infections (NI) causal agents constitutes a seriously global problematic that involves the Mexican Institute of Social Security's Regional General Hospital 1 in Chihuahua, Mexico; although with special features that required to be specified and evaluated, in order to concrete an effective therapy. Observational, descriptive and prospective study; by means of active vigilance all along 2014 in order to detect the nosocomial infections, for epidemiologic study, culture and antibiogram to identify its causal agents and antibiotics resistance and sensitivity. Among 13527 hospital discharges, 1079 displayed NI (8 %), standed out: the related on vascular lines, of surgical site, pneumonia and urinal track; they added up two thirds of the total. We carried out culture and antibiogram about 300 of them (27.8 %); identifying 31 bacterian species, mainly seven of those (77.9 %): Escherichia coli, Staphylococcus aureus and epidermidis, Pseudomonas aeruginosa, Acinetobacter baumannii, Klebsiella pneumoniae and Enterobacter cloacae; showing multiresistance to 34 tested antibiotics, except in seven with low or without resistance at all: vancomycin, teicoplanin, linezolid, quinupristin-dalfopristin, piperacilin-tazobactam, amikacin and carbapenems. When we contrasted those results with the recommendations in the clinical practice guides, it aroused several contradictions; so they must be taken with reserves and has to be tested in each hospital, by means of cultures and antibiograms in practically every case of nosocomial infection.

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.

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

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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.

Tweaking Innate Immunity: The Promise of Innate Immunologicals as Anti-Infectives

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Kenneth L Rosenthal

2006-01-01

Full Text Available New and exciting insights into the importance of the innate immune system are revolutionizing our understanding of immune defense against infections, pathogenesis, and the treatment and prevention of infectious diseases. The innate immune system uses multiple families of germline-encoded pattern recognition receptors (PRRs to detect infection and trigger a variety of antimicrobial defense mechanisms. PRRs are evolutionarily highly conserved and serve to detect infection by recognizing pathogen-associated molecular patterns that are unique to microorganisms and essential for their survival. Toll-like receptors (TLRs are transmembrane signalling receptors that activate gene expression programs that result in the production of proinflammatory cytokines and chemokines, type I interferons and antimicrobial factors. Furthermore, TLR activation facilitates and guides activation of adaptive immune responses through the activation of dendritic cells. TLRs are localized on the cell surface and in endosomal/lysosomal compartments, where they detect bacterial and viral infections. In contrast, nucleotide-binding oligomerization domain proteins and RNA helicases are located in the cell cytoplasm, where they serve as intracellular PRRs to detect cytoplasmic infections, particularly viruses. Due to their ability to enhance innate immune responses, novel strategies to use ligands, synthetic agonists or antagonists of PRRs (also known as 'innate immunologicals' can be used as stand-alone agents to provide immediate protection or treatment against bacterial, viral or parasitic infections. Furthermore, the newly appreciated importance of innate immunity in initiating and shaping adaptive immune responses is contributing to our understanding of vaccine adjuvants and promises to lead to improved next-generation vaccines.

Antimycobacterial drug discovery using Mycobacteria-infected amoebae identifies anti-infectives and new molecular targets.

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Trofimov, Valentin; Kicka, Sébastien; Mucaria, Sabrina; Hanna, Nabil; Ramon-Olayo, Fernando; Del Peral, Laura Vela-Gonzalez; Lelièvre, Joël; Ballell, Lluís; Scapozza, Leonardo; Besra, Gurdyal S; Cox, Jonathan A G; Soldati, Thierry

2018-03-02

Tuberculosis remains a serious threat to human health world-wide, and improved efficiency of medical treatment requires a better understanding of the pathogenesis and the discovery of new drugs. In the present study, we performed a whole-cell based screen in order to complete the characterization of 168 compounds from the GlaxoSmithKline TB-set. We have established and utilized novel previously unexplored host-model systems to characterize the GSK compounds, i.e. the amoeboid organisms D. discoideum and A. castellanii, as well as a microglial phagocytic cell line, BV2. We infected these host cells with Mycobacterium marinum to monitor and characterize the anti-infective activity of the compounds with quantitative fluorescence measurements and high-content microscopy. In summary, 88.1% of the compounds were confirmed as antibiotics against M. marinum, 11.3% and 4.8% displayed strong anti-infective activity in, respectively, the mammalian and protozoan infection models. Additionally, in the two systems, 13-14% of the compounds displayed pro-infective activity. Our studies underline the relevance of using evolutionarily distant pathogen and host models in order to reveal conserved mechanisms of virulence and defence, respectively, which are potential "universal" targets for intervention. Subsequent mechanism of action studies based on generation of over-expresser M. bovis BCG strains, generation of spontaneous resistant mutants and whole genome sequencing revealed four new molecular targets, including FbpA, MurC, MmpL3 and GlpK.

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

Use of locally delivered dequalinium chloride in the treatment of vaginal infections: a review.

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Mendling, Werner; Weissenbacher, Ernst Rainer; Gerber, Stefan; Prasauskas, Valdas; Grob, Philipp

2016-03-01

Vaginal infections are responsible for a large proportion of gynaecological outpatient visits. Those are bacterial vaginosis (BV), vulvovaginal candidosis (VVC), aerobic vaginitis (AV) associated with aerobic bacteria, and mixed infections. Usual treatments show similar acceptable short-term efficacy, but frequent recurrences and increasing microbial resistance are unsolved issues. Furthermore, vaginal infections are associated with a variety of serious adverse outcomes in pregnancy and generally have a major impact on quality of life. Identifying the correct therapy can be challenging for the clinician, particularly in mixed infections. Dequalinium chloride (DQC) is an anti-microbial antiseptic agent with a broad bactericidal and fungicidal activity. Systemic absorption after vaginal application of DQC is very low and systemic effects negligible. Vaginal DQC (Fluomizin vaginal tablets) has been shown to have equal clinical efficacy as clindamycin in the treatment of BV. Its broad antimicrobial activity makes it appropriate for the treatment of mixed vaginal infections and in case of uncertain diagnosis. Moreover, resistance of pathogens is unlikely due to its multiple mode of action, and vaginal DQC provides also a reduced risk for post-treatment vaginal infections. Vaginal DQC (10 mg) as 6-day therapy offers a safe and effective option for empiric therapy of different vaginal infections in daily practice. This review summarizes the available and relevant pharmacological and clinical data for the therapy of vaginal infections with vaginal DQC and provides the rationale for its use in daily gynaecologic practice.

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

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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.

Peri-Prosthetic Knee Infection Management: Spacers Loaded with Two or Three Antibiotic Agents.

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Ortola, David Joaquin; Fenga, Domenico; Marcellino, Sandra; Rosi, Massimiliano; Centofanti, Francesco; Rosa, Michele Attilio

2017-07-01

The purpose of this work was to compare pre-made antibiotic-loaded spacers with two commercially available antibiotic agents and custom-made cements with three antibiotic agents added. We evaluated: (a) the validity of our procedures, (b) the control of the rate of infection in the long term, (c) complications, and (d) quality of life and patient satisfaction. A retrospective cohort study was performed on 112 consecutively treated patients between January 2010 and December 2013; 56 patients were treated with a pre-formed cement spacer (clindamycin + gentamicin), and 56 patients were treated with a spacer loaded with three antibiotic agents (clindamycin + gentamicin + vancomycin). Demographic data were collected: Classification of infection according to criteria of Cierny-Mader; microbiologic results; number of previous operations; and years of disease. Infection control or relapse after at least 18 months of follow-up was evaluated. Complications were recorded. Every patient completed the SF-36 test and Oxford Knee Score. With a follow-up of 32.87 months (standard deviation 12.04), at the end of treatment, amputation occurred in three of 112 patients because of recurrence of infection, and one patient died from other causes not related to the infection. The study population presented a rate of recurrence of infection of 2.70%. Our results suggest that a two stage re-implant with three antibiotic agents added to the spacer should be considered to avoid rescue procedures, especially in patients with multi-resistant micro-organism infections.

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

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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.

Clinical course and core variability in HBV infected patients without detectable anti-HBc antibodies.

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Anastasiou, Olympia E; Widera, Marek; Verheyen, Jens; Korth, Johannes; Gerken, Guido; Helfritz, Fabian A; Canbay, Ali; Wedemeyer, Heiner; Ciesek, Sandra

2017-08-01

The presence of anti-HBc antibodies indicates direct encounter of the immune system with hepatitis B virus (HBV). Aim of our study was to seek for anti-HBc negative but HBV replicating patients and analyze their clinical course and preconditions. From 1568 HBV-DNA positive patients, 29 patients (1.85%) tested negative for anti-HBc. The absence of anti-HBc could be confirmed in 19 patients using an alternative assay. In 16 of 19 cases, a partial or full HBV genome analysis was performed with NGS sequencing to evaluate if specific mutations were associated with anti-HBc absence. As a control group samples from 32 matched HBV infected patients with detectable anti-HBc were sequenced. Patients with detectable HBV-DNA and sequenced HBV core region in the confirmed absence of anti-HBc were diagnosed with acute HBV infection (n=3), HBV reactivation (n=9) and chronic hepatitis B (n=4). Most patients (12/16) were immunosuppressed: 3/16 patients had an HIV coinfection, 7/16 patients suffered from a malignant disease and 4/16 patients underwent solid organ transplantation (from which 2/4 had a malignant disease). Compared to the control cohort, HBV variants from anti-HBc negative patients showed less variability in the core region. In the absence of anti-HBc, HBV-DNA was most often found in immunocompromised hosts. Distinct mutations or deletions in the core region did not explain anti-HBc negativity. It would be advisable not to rely only on a single result of anti-HBc negativity to exclude HBV infection in immunocompromised hosts, but to measure anti-HBc repeatedly or with different methods. Copyright © 2017 Elsevier B.V. All rights reserved.

A review of tags anti-collision and localization protocols in RFID networks.

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Ullah, S; Alsalih, W; Alsehaim, A; Alsadhan, N

2012-12-01

Radio Frequency IDentification (RFID) has allowed the realization of ubiquitous tracking and monitoring of physical objects wirelessly with minimum human interactions. It plays a key role in a wide range of applications including asset tracking, contactless payment, access control, transportation and logistics, and other industrial applications. On the other side, RFID systems face several technical challenges that need to be overcome in order to achieve their potential benefits; tags collisions and localization of tagged objects are two important challenges. Numerous anti-collision and localization protocols have been proposed to address these challenges. This paper reviews the state-of-art tags' anti-collision and localization protocols, and provides a deep insight into technical issues of these protocols. The probabilistic and deterministic anti-collision protocols are critically studied and compared in terms of different parameters. We further review distance estimation, scene analysis, and proximity localization schemes and provide useful suggestions. We also introduce a new hybrid direction that utilizes power control to spatially partition the interrogation range of a reader for more efficient anti-collision and localization. Finally, we present the applications of RFID systems in healthcare sectors.

Anti-Bacterial Properties of Herbs against Helicobacter Pylori Infection: A Review

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Hedieh Yousef-Nezhad

2017-09-01

Full Text Available Helicobacter pylori is a gram-negative bacterium that lives in human stomach. This bacterium is the most important cause of chronic gastritis, peptic and duodenal ulcers and gastric cancer. The therapies include the use of antibiotics and a proton pump inhibitor, but unfortunately, these therapeutic methods are not always responsive due to resistance to antibiotics. In recent years, use of alternative treatment, including medicinal herbs was shown to have anti-H. Pylori properties. So, in this review, anti-H. Pylori features of herbals were investigated including ginger, garlic, cranberry, curcumin, green tea and broccoli sprouts derived through the search in Google Scholar search engine, and PubMed scientific database using English keywords such as Helicobacter pylori, anti-H. pylori, ginger, garlic, cranberry, curcumin, broccoli and green tea, between 1984 -2016. Results showed that ginger, garlic, cranberry, curcumin, broccoli and green tea have antibacterial, antioxidant and anti-inflammatory potential properties, and because of their role in protecting the stomach against H. pylori infection, it seems, they can be an appropriate treatment option for patients with this infection.

Frequency of class I anti-HLA alloantibodies in patients infected by HIV-1

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Elza Regina Manzolli Leite

2010-02-01

Full Text Available The aim of this study was to evaluate the presence of class I anti-HLA alloantibodies in patients infected by HIV-1 and relate it with the different clinical courses of the disease. Blood samples were collected in EDTA tubes from 145 individuals. HIV-1 infection was confirmed by ELISA test. The presence of class I anti-HLA alloantibodies and HLA allele's were determined. Clinical evolution was set as fast (3 years. Class I anti-HLA alloantibodies presence was lower in healthy individuals than in those infected by HIV-1 (4.2% against 32.4%. However, an equal distribution of these alloantibodies was found among the individuals infected, independent on the clinical evolution. Thus, class I anti-HLA alloantibodies was not a determinant factor for patient worsening.O objetivo deste estudo foi avaliar a presença de aloanticorpos anti-HLA classe I em pacientes infectados pelo HIV-1 e relacioná-la aos diferentes cursos clínicos da doença. Amostras de sangue de 145 indivíduos HIV positivo foram coletadas em tubos com EDTA. A infecção pelo HIV-1 foi confirmada por teste ELISA e a presença de aloanticorpos anti-HLA classe I determinada em seguida. A evolução clínica foi definida como rápida (3 anos. A presença de aloanticorpos anti-HLA classe I foi menor em indivíduos saudáveis em relação aos infectados pelo HIV-1 (4,2% contra 32,4%. Porém, a distribuição destes aloanticorpos entre os indivíduos infectados foi igual, independente da evolução clínica. Deste modo, a presença de aloanticorpos anti-HLA classe I não é um fator determinante na piora clínica do paciente.

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

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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.

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

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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

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.

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)

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.

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

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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.

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)....

Novel Ehrlichia and Hepatozoon agents infecting the crab-eating fox (Cerdocyon thous) in southeastern Brazil.

Science.gov (United States)

Almeida, Aliny P; Souza, Tayse D; Marcili, Arlei; Labruna, Marcelo B

2013-05-01

This study evaluated infection by vector-borne agents in 58 crab-eating fox (Cerdocyon thous L.) that were road-killed in an Atlantic rainforest reserve in the state of Espírito Santo, southeastern Brazil. Spleen, lung, or blood samples collected from the foxes were tested in the laboratory by a battery of polymerase chain reaction (PCR) assays targeting bacteria of the genera Rickettsia, Borrelia, Coxiella, Anaplasma, and Ehrlichia; and protozoa of the genera Babesia, Hepatozoon, and Leishmania. Of the targeted organisms, evidence of infection in the foxes was detected for Ehrlichia and Hepatozoon organisms only. Overall, six (10.3%) foxes were infected by an ehrlichial agent closely related to an ehrlichial agent recently detected in free-ranging Jaguars [(Panthera onca (L.)] in central-western Brazil, and to Ehrlichia ruminantium. For Hepatozoon, 28 (48.3%) foxes were infected by an agent closely related to Hepatozoon sp. Curupira 2 and H. americanum; and one (1.7%) fox was infected by an organism closely related to reptile-associated Hepatozoon agents. Finally, 11 (19.0%) foxes were found infested by Amblyomma cajennense (F.) nymphs, which were all PCR negative for the range of vector-borne agents cited above. Because the haplotypes found in free-ranging foxes are genetically closely related to pathogens of great veterinary importance, namely E. ruminantium and H. americanum, it is highly desirable to know if these novel organisms have any important role as agents of diseases in domestic animals and wildlife in Brazil.

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

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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

Infection diagnosis in nuclear medicine

International Nuclear Information System (INIS)

Martin-Comin, J.

1997-01-01

Full text. The clinical applicability of agents like 67 Ga and 111 In-labelled leukocytes began the era of infection imaging diagnosis in Nuclear Medicine, more than two decades ago. In this period other agents have appeared in the field. 99 m Tc-HMPAQ-leukocytes and 99 m Tc-anti granulocyte monoclonal antibodies (able to label white blood cells) and 111 In and 99 mTc-polyclonal immuno globulins (in cold kit presentation). These agents had widespread the use of Nuclear Medicine procedures in clinical practice. Nevertheless, there is not, up to now, an specific agent to diagnose infection and is some cases a second or third agent (i.e.: 99 mTc-colloid) is used to obtain an accurate diagnosis. Actually, research is orientated to the development of agents with low antigenic power (peptides or fragments of monoclonal antibodies), or other non immunogenic agents involved in the inflammation process (selectin, antibiotic). Some experiences have also been done with PET agents. The clinical usefulness of commercially available agents and the future possibilities of the new ones will be presented

Innovative Approaches to Improve Anti-Infective Vaccine Efficacy.

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Yeaman, Michael R; Hennessey, John P

2017-01-06

Safe and efficacious vaccines are arguably the most successful medical interventions of all time. Yet the ongoing discovery of new pathogens, along with emergence of antibiotic-resistant pathogens and a burgeoning population at risk of such infections, imposes unprecedented public health challenges. To meet these challenges, innovative strategies to discover and develop new or improved anti-infective vaccines are necessary. These approaches must intersect the most meaningful insights into protective immunity and advanced technologies with capabilities to deliver immunogens for optimal immune protection. This goal is considered through several recent advances in host-pathogen relationships, conceptual strides in vaccinology, and emerging technologies. Given a clear and growing risk of pandemic disease should the threat of infection go unmet, developing vaccines that optimize protective immunity against high-priority and antibiotic-resistant pathogens represents an urgent and unifying imperative.

Local sustained-release delivery systems of the antibiofilm agent thiazolidinedione-8 for prevention of catheter-associated urinary tract infections.

Science.gov (United States)

Shenderovich, Julia; Feldman, Mark; Kirmayer, David; Al-Quntar, Abed; Steinberg, Doron; Lavy, Eran; Friedman, Michael

2015-05-15

Thiazolidinedione-8 (TZD-8) is an anti-quorum-sensing molecule that has the potential to effectively prevent catheter-associated urinary tract infections, a major healthcare challenge. Sustained-release drug-delivery systems can enhance drugs' therapeutic potential, by maintaining their therapeutic level and reducing their side effects. Varnishes for sustained release of TZD-8 based on ethylcellulose or ammonio methacrylate copolymer type A (Eudragit(®) RL) were developed. The main factors affecting release rate were found to be film thickness and presence of a hydrophilic or swellable polymer in the matrix. The release mechanism of ethylcellulose-based systems matched the Higuchi model. Selected varnishes were retained on catheters for at least 8 days. Sustained-release delivery systems of TZD-8 were active against Candida albicans biofilms. The present study demonstrates promising results en route to developing applications for the prevention of catheter-associated infections. Copyright © 2015 Elsevier B.V. All rights reserved.

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)

99mTc-Alafosfalin: an antibiotic peptide infection imaging agent

International Nuclear Information System (INIS)

Tsopelas, C.; Penglis, S.; Ruszkiewicz, A.; Bartholomeusz, F.D.L.

2003-01-01

The radiolabeled antibiotic peptide 99m Tc-alafosfalin was assessed as an infection imaging agent in a rat model by comparison with 99m Tc-DTPA and 99m Tc-leukocytes. 99m Tc-alafosfalin was prepared via an instant cold kit and 99m Tc-leukocytes were prepared using 99m Tc-stannous fluoride colloid in an ex vivo labeling procedure of whole blood. In separate experiments, the three radiotracers were administered to rats infected with staphylococcus aureus. Quantitative biodistribution studies were performed as well as scintigraphic images and histopathology. 99m Tc-alafosfalin is a stable product, obtained in high radiochemical purity (>95%). This agent was mainly renally excreted, with low liver, spleen and bone uptake, and resulted in a mean ratio of infected/non-infected thighs of 4.3/1.0 at 4 hr post radiotracer injection. 99m Tc-DTPA gave a corresponding ratio of 1.9/1.0 and 99m Tc-leukocytes gave 20.0/1.0 at the same time point. An in vitro assay found the level of 99m Tc-alafosfalin binding to staphylococcus aureas higher than 99m Tc-DTPA (10% versus 1% respectively). 99m Tc-alafosfalin accumulates at sites of infection in a rat model better than the perfusion molecule 99m Tc-DTPA, yet less than 99m Tc-leukocytes. The distribution characteristics of this 99m Tc-antibiotic peptide would be an advantage in imaging abdominal and soft tissue infection

Non-oncogenic Acute Viral Infections Disrupt Anti-cancer Responses and Lead to Accelerated Cancer-Specific Host Death

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Frederick J. Kohlhapp

2016-10-01

Full Text Available In light of increased cancer prevalence and cancer-specific deaths in patients with infections, we investigated whether infections alter anti-tumor immune responses. We report that acute influenza infection of the lung promotes distal melanoma growth in the dermis and leads to accelerated cancer-specific host death. Furthermore, we show that during influenza infection, anti-melanoma CD8+ T cells are shunted from the tumor to the infection site, where they express high levels of the inhibitory receptor programmed cell death protein 1 (PD-1. Immunotherapy to block PD-1 reverses this loss of anti-tumor CD8+ T cells from the tumor and decreases infection-induced tumor growth. Our findings show that acute non-oncogenic infection can promote cancer growth, raising concerns regarding acute viral illness sequelae. They also suggest an unexpected role for PD-1 blockade in cancer immunotherapy and provide insight into the immune response when faced with concomitant challenges.

[Requirement of standardizing anti-HBs assay methods in Japan for HBV infection-preventing strategy--discrepancy of anti-HBs measurements among three different kits widely used in Japan].

Science.gov (United States)

Ogata, Norio

2006-09-01

The strategy to eliminate hepatitis B virus (HBV) infection by administrating an HB vaccine is changing worldwide; however, this is not the case in Japan. An important concern about the HBV infection-preventing strategy in Japan may be that the assay methods for the antibody to hepatitis B surface antigen (anti-HBs) are not standardized. The minimum protective anti-HBs titer against HBV infection has been established as 10 mIU/ml by World Health Organization (WHO) -standardized assay methods worldwide, but that is still determined as a "positive" test result by the passive hemagglutination (PHA) method in Japan. We compared anti-HBs measurements in given samples among PHA(Mycell II, Institute of Immunology), chemiluminescent enzyme immunoassay (CLEIA) (Lumipulse, Fujirebio), and chemiluminescent immunoassay (CLIA) (Architect, Abbott), all of which are currently in wide use in Japan. First, anti-HBs measurements in serum from individuals who received a yeast-derived recombinant HB vaccine composed of the major surface protein of either subtype adr or subtype ayw were compared. The results clearly showed that in subtype adr-vaccinees CLIA underestimated the anti-HBs amount compared with CLEIA and PHA, but in ayw-vaccinees, the discordance in the measurements among the three kits was not prominent. Second, anti-HBs measurements in standard or calibration solutions of each assay kit were compared. Surprisingly, CLEIA showed higher measurements in all three kit-associated standard or calibration solutions than CLIA. Thus, the anti-HBs titer of 10 mIU/ml is difficult to introduce in Japan as the minimum protective level against HBV infection. Efforts to standardize anti-HBs assay methods are expected to share international evidence about the HBV infection-preventing strategy.

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 ...

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

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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

Maternal hepatitis C (HCV) infection and Anti-D immunoglobulin therapy: study testing antibodies, RNA and Genotype of HCV in Baghdad.

Science.gov (United States)

Al-Kubaisy, Waqar; Daud, Suzanna; Al-Kubaisi, Mustafa Waseem; Al-Kubaisi, Omar Waseem; Abdullah, Nik Nairan

2018-04-30

Hepatitis C virus (HCV) infection is a serious health problem. It is a major contributor to end-stage liver disease. Worldwide, 1-8% of all pregnant women were infected. Women with viral hepatitis may be at an increased risk of pregnancy complications. There are several obstetrics intervention acts as risk factors, which are specific to women pertaining the HCV infection; anti-D immunoglobulin (Ig) therapy may be one of them. Our objectives were to estimate the prevalence of HCV antibodies (anti-HCV), RNA, and genotype distribution among women with anti-D Ig therapy. A cross sectional study was conducted. A sample of 154 Rhesus negative (Rh - ve) pregnant women regardless of the anti-D Ig therapy was collected. Anti-HCV were tested using third generation enzyme immunoassay (EIA-3) and immunoblot assay (Lia Tek-111), subsequently. In addition, 89 serum samples were subjected to molecular analysis using RT-PCR and DNA enzyme immunoassay (DEIA) method for the detection of HCV-RNA and genotypes. Anti-HCV, and HCV-RNA seroprevalence were significantly higher (17.1, 35.5%) among women with anti-D Ig than their counter group (6.4, 13.16%), p = .038, .018, respectively. Significant direct positive dose response correlation (r = 0.78, p = .005) had been seen between number of anti-D Ig therapy and anti-HCV seropositive rate. Anti-D Ig therapy act as a risk factor (odds ratio (OR) = 3.01, 95%CI: 1.01-8.9) especially from the third dose onward. Women with anti-D Ig therapy were at higher risk (3.6 times more) of positive HCV-RNA (OR =3.6, 95%CI =1.19-10.837). Genotype HCV-1b showed higher prevalent (52.9%) among the recipients of anti-D Ig therapy while genotype HCV-3a (6.6%) was the lowest. Our study showed that Anti-D immunoglobulin therapy acts as a risk factor for acquiring HCV infection. Screening for HCV should be recommended for all recipients of anti-D Ig. Not only HCV antibodies but HCV-RNA detection being recommended for the diagnosis of HCV

MODERN MANAGEMENT OF ACUTE RESPIRATORY INFECTIONS IN CHILDREN. RECOURSES OF SYSTEM ANTI INFLAMMATORY TREATMENT

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O.V. Zaitseva

2008-01-01

Full Text Available A problem of etiology and pathogenesis of acute respiratory infections in children are observed in this article. Modern approach to management of its treatment in pediatric patients, including often ailing children, is described. Authors give characteristics to main directions of treatment of obstructive syndrome. An experience of anti-inflammatory therapy with fenspiride (eurespal in children of different age is summa ized in this article.Key words: often ailing children, acute respiratory infections, bronchoobstructive syndrome, anti-inflammatory treatment, fenspiride.

Infection imaging with radiopharmaceuticals in the 21st century

Energy Technology Data Exchange (ETDEWEB)

Das, Satya S.; Wareham, David W. [St. Bartholomew' s Hospital, London (United Kingdom). Dept. of Medical Microbiology; Britton, Keith E. [St. Bartholomew' s Hospital, London (United Kingdom). Dept. of Nuclear Medicine; Hall, Anne V. [Harefield Hospital, Middlesex (United Kingdom). Microbiology Dept.

2002-09-01

Infection continues to be a major cause of morbidity and mortality worldwide. Nuclear medicine has an important role in aiding the diagnosis of particularly deep-seated infections such as abscesses, osteomyelitis, septic arthritis, endocarditis, and infections of prosthetic devices. Established techniques such as radiolabelled leucocytes are sensitive and specific for inflammation but do not distinguish between infective and non-infective inflammation. The challenge for Nuclear Medicine in infection imaging in the 21st century is to build on the recent trend towards the development of more infection specific radiopharmaceuticals, such as radiolabelled anti-infectives (e.g. 99 m Tc ciprofloxacin). In addition to aiding early diagnosis of infection, through serial imaging these agents might prove very useful in monitoring the response to and determining the optimum duration of anti-infective therapy. This article reviews the current approach to infection imaging with radiopharmaceuticals nd the future direction it might take. (author)

Infection imaging with radiopharmaceuticals in the 21st century

International Nuclear Information System (INIS)

Das, Satya S.; Wareham, David W.; Britton, Keith E.; Hall, Anne V.

2002-01-01

Infection continues to be a major cause of morbidity and mortality worldwide. Nuclear medicine has an important role in aiding the diagnosis of particularly deep-seated infections such as abscesses, osteomyelitis, septic arthritis, endocarditis, and infections of prosthetic devices. Established techniques such as radiolabelled leucocytes are sensitive and specific for inflammation but do not distinguish between infective and non-infective inflammation. The challenge for Nuclear Medicine in infection imaging in the 21st century is to build on the recent trend towards the development of more infection specific radiopharmaceuticals, such as radiolabelled anti-infectives (e.g. 99 m Tc ciprofloxacin). In addition to aiding early diagnosis of infection, through serial imaging these agents might prove very useful in monitoring the response to and determining the optimum duration of anti-infective therapy. This article reviews the current approach to infection imaging with radiopharmaceuticals nd the future direction it might take. (author)

Higher serum levels of rheumatoid factor and anti-nuclear antibodies in helicobacter pylori-infected peptic ulcer patients.

Science.gov (United States)

Jafarzadeh, Abdollah; Nemati, Maryam; Rezayati, Mohammad Taghi; Nabizadeh, Mansooreh; Ebrahimi, Medhi

2013-07-01

H. pylori infection has been associated with some autoimmune disorders. The aim of this study was to evaluate the serum concentrations of rheumatoid factor and anti-nuclear antibodies in H. pylori-infected peptic ulcer patients, H. pylori-infected asymptomatic carriers and a healthy control group. A Total of 100 H. pylori-infected peptic ulcer patients, 65 asymptomatic carriers and 30 healthy H. pylori-negative subjects (as a control group) were enrolled into study. Serum samples of participants tested for the levels of rheumatoid factor and anti-nuclear antibodies by use of ELISA. The mean serum levels of rheumatoid factor and anti-nuclear antibodies in peptic ulcer group was significantly higher in comparison to the control group (ppeptic ulcer patients and asymptomatic carriers groups regarding the mean serum levels of rheumatoid factor and anti-nuclear antibodies. The mean serum levels of rheumatoid factor in men with peptic ulcer was significantly higher compared to the group of healthy men (ppeptic ulcer patients or asymptomatic carriers groups, the mean serum levels of rheumatoid factor was higher than that in healthy women, but the differences were not statistically significant. Also, no significant differences were observed between men and women with peptic ulcer, asymptomatic carriers control groups based on the serum levels of anti-nuclear antibodies. The results showed higher serum levels of rheumatoid factor and anti-nuclear antibodies in H. pylori-infected patients with peptic ulcer disease which represent the H. pylori-related immune disturbance in these patients. Additional follow-up studies are necessary to clarify the clinical significance of these autoantibodies in patients with H. pylori infection.

Anti-MOG antibody-positive ADEM following infectious mononucleosis due to a primary EBV infection: a case report.

Science.gov (United States)

Nakamura, Yoshitsugu; Nakajima, Hideto; Tani, Hiroki; Hosokawa, Takafumi; Ishida, Shimon; Kimura, Fumiharu; Kaneko, Kimihiko; Takahashi, Toshiyuki; Nakashima, Ichiro

2017-04-19

Anti-Myelin oligodendrocyte glycoprotein (MOG) antibodies are detected in various demyelinating diseases, such as pediatric acute disseminated encephalomyelitis (ADEM), recurrent optic neuritis, and aquaporin-4 antibody-seronegative neuromyelitis optica spectrum disorder. We present a patient who developed anti-MOG antibody-positive ADEM following infectious mononucleosis (IM) due to Epstein-Barr virus (EBV) infection. A 36-year-old healthy man developed paresthesia of bilateral lower extremities and urinary retention 8 days after the onset of IM due to primary EBV infection. The MRI revealed the lesions in the cervical spinal cord, the conus medullaris, and the internal capsule. An examination of the cerebrospinal fluid revealed pleocytosis. Cell-based immunoassays revealed positivity for anti-MOG antibody with a titer of 1:1024 and negativity for anti-aquaporin-4 antibody. His symptoms quickly improved after steroid pulse therapy followed by oral betamethasone. Anti-MOG antibody titer at the 6-month follow-up was negative. This case suggests that primary EBV infection would trigger anti-MOG antibody-positive ADEM. Adult ADEM patients can be positive for anti-MOG antibody, the titers of which correlate well with the neurological symptoms.

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.

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

Local Antibiotic Delivery Systems: Current and Future Applications for Diabetic Foot Infections.

Science.gov (United States)

Markakis, Konstantinos; Faris, Alan Robert; Sharaf, Hamed; Faris, Barzo; Rees, Sharon; Bowling, Frank L

2018-03-01

Foot infections are common among diabetic patients with peripheral neuropathy and/or peripheral arterial disease, and it can be the pivotal event leading to a minor or major amputation of the lower extremity. Treatment of diabetic foot infections, especially deep-seated ones, remains challenging, in part because impaired blood perfusion and the presence of biofilms can impair the effectiveness of systemic antibiotics. The local application of antibiotics is an emerging field in the treatment of diabetic foot infections, with demonstrable advantages. These include delivery of high concentrations of antibiotics in the affected area, limited systemic absorption, and thus negligible side effects. Biodegradable vehicles, such as calcium sulfate beads, are the prototypical system, providing a good elution profile and the ability to be impregnated with a variety of antibiotics. These have largely superseded the nonbiodegradable vehicles, but the strongest evidence available is for calcium bead implantation for osteomyelitis management. Natural polymers, such as collagen sponge, are an emerging class of delivery systems, although thus far, data on diabetic foot infections are limited. There is recent interest in the novel antimicrobial peptide pexiganan in the form of cream, which is active against most of the microorganisms isolated in diabetic foot infections. These are promising developments, but randomized trials are required to ascertain the efficacy of these systems and to define the indications for their use. Currently, the role of topical antibiotic agents in treating diabetic foot infections is limited and outside of routine practice.

Tc-99m labeled Sparfloxacin: A specific infection imaging agent

International Nuclear Information System (INIS)

Singh, A.K.; Verma, J.; Bhatnagar, A.; Ali, A.

2003-01-01

Radiolabeled antibiotics are being used for the specific diagnosis of infection by exploiting their specific binding properties to the bacterial component, thereby making it possible to differentiate infection from sterile lesions. A new radiopharmaceutical, Tc-99m Sparfloxacin has been developed for infection imaging. Sparfloxacin is a quinolone based broad-spectrum antibiotic, which is more potent than Ciprofloxacin. Radiolabeling of Sparfloxacin with Tc-99m was standardized using direct labeling protocol. Labeling efficiency, in-vitro and in-vivo stability, blood kinetics and organ distribution studies (in balb/c mice and New Zealand White Rabbits at different time interval up to 24hrs) were carried out. Biological activity of Sparfloxacin after its labeling with Tc-99m was evaluated with S.aureus using Peptone water (DIFCO) as media. Turpentine oil (100 μl) in left thigh and S.aureus (100μl of 3x10 7 cells) in right thigh were injected intramuscularly to create sterile and infective inflammation respectively in six New Zealand white rabbits. The localization kinetics of the radiolabeled complex were studied in the animal model by injecting 70-75MBq of Tc-99m Sparfloxacin intravenously in the ear of rabbit and the images were taken with a Gamma-camera (ECIL) at different post-injection time intervals. Standardized protocol produced >95% labeled complex. About 8% of tracer leached out at 24 hrs when incubated in serum at 37 0 C, confirming high stability of the complex. Blood clearance in rabbit revealed biphasic pattern and 50% of the complex clears from the blood within 5 min. Biodistribution studies in balb/c mice showed hepatobiliary route of excretion. Presence of insignificant amount of tracer at 24 hrs in the stomach confirmed high in vivo stability of the complex. Imaging in rabbits showed significant concentration of tracer in lesions with infection. Typical imaging patterns revealed initial accumulation of radiotracer in both sterile inflammatory

A “Mini-Epidemic” of anti-glomerular basement membrane disease: Clinical and epidemiological study

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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.

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

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

Anti-bacterial susceptibility patterns of blood culture isolates at a ...

African Journals Online (AJOL)

Background: Hospital treatment guidelines are often guided by scientific evidence of efficacy of the anti-microbial agents. In developing countries, most of the treatment guidelines are adopted from the World Health Organisation (WHO). However, local data is often needed to confirm or adjust these guidelines to suit a local ...

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.

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.

Ways of Civil Society Institutes Interaction with Local Governments in the Sphere of Anti-Corruption

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Kristina V. Кondrashova

2016-06-01

Full Text Available In this article author analyzes ways of civil society institutes interaction with local government bodies in the sphere of anti-corruption, legal regulation in the sphere of anti-corruption is analyzed (including the Federal law of December 25, 2008 No. 273-FZ "About anti-corruption", opinions of scientists-jurists are researched. In the conclusion the author reviews 4 examples mutually beneficial cooperation of institutes of civil society and local government bodies.

Anti-leech activity of Scutellaria baicalensis and Morinda citrifolia extracts against Piscicola geometra

Science.gov (United States)

Rizky, P. N.; Cheng, T. C.; Nursyam, H.

2018-04-01

Piscicola geometra leeches are naturally infecting cobia juvenile. The leeches attach to cobia by sucking and biting its surface and provide the gate of second infection. Water extracts of Scutellaria baicalensis root and Morinda citrifolia leaves were used to be tested through In Vitro method to look for the anti-leeches activity against Piscicola geometra. In this study, a total number of 800 leeches from infected cobia were prepared. The anti-leech activity from water extract of S. baicalensis root and M. citrifolia leaves were compared in different dilutions of plant extracts for 96 hours. Significant anti-leech activity was observed with M. citrifolia leaves with 80% mortality of leeches. S. baicalensis root showed higher anti-leech activity with 100% mortality of leeches. The average time was needed for S.baicalensis root to paralyzing and kill the leeches were 8h, 40h, 48h, 72h, and 96h in various dilutions of S. baicalensis root. This study indicated that S. baicalensis water extract had a potent for new anti-leeches agent.

Both anti-TNF and CTLA4 Ig treatments attenuate the disease severity of staphylococcal dermatitis in mice.

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Manli Na

Full Text Available RA patients being treated with biologics are known to have an increased risk of infections. We recently demonstrated that both CTLA4 Ig and anti-TNF treatment aggravate systemic Staphylococcus aureus (S. aureus infection in mice, but with distinct clinical manifestations. However, the effects of CTLA4 Ig and anti-TNF treatments on a local S. aureus infection (e.g., skin infection might differ from their effects on a systemic infection.The aim of this study was to examine the differential effects of anti-TNF versus CTLA4 Ig treatment on S. aureus skin infections in mice.Abatacept (CTLA4 Ig, etanercept (anti-TNF treatment or PBS was given to NMRI mice subcutaneously inoculated with S. aureus strain SH1000. The clinical signs of dermatitis, along with histopathological changes due to skin infection, were compared between the groups.Both CTLA4 Ig and anti-TNF treatment resulted in less severe skin infections and smaller post-infectious hyperpigmentation compared with controls. Consistent with the clinical signs of dermatitis, smaller lesion size, more epithelial hyperplasia and more granulation were found in skin biopsies from mice receiving anti-TNF compared with PBS controls. However, both CTLA4 Ig and anti-TNF therapy tended to prolong the healing time, although this finding was not statistically significant. Serum MCP-1 levels were elevated in the anti-TNF group relative to the CTLA4 Ig and PBS groups, whereas IL-6 levels were higher in PBS controls than in the other two groups. Both anti-TNF and CTLA4 Ig treatments tended to down-regulate the necrosis/apoptosis ratio in the locally infected skin tissue. Importantly, no tangible difference was found in the bacterial burden among groups.Both CTLA4 Ig and anti-TNF therapies attenuate disease severity but may prolong the healing time required for S. aureus skin infections. Neither treatment has an impact on bacterial clearance in skin tissues.

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

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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.

Use of Anti-HIV Immunotoxins as Probes of the Biology of HIV-Infected Cells

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SETH H Pincus

1994-01-01

Full Text Available OBJECTIVE: Anti-human immunodeficiency virus (HIV immunotoxins are potential treatments for HIV infection. but they may also be used as probes to study the relationship between HIV and the cell it infects. Data from the present study indicate the complexity of this relationship.

Regulation of NKT Cell Localization in Homeostasis and Infection

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Slauenwhite, Drew; Johnston, Brent

2015-01-01

Natural killer T (NKT) cells are a specialized subset of T lymphocytes that regulate immune responses in the context of autoimmunity, cancer, and microbial infection. Lipid antigens derived from bacteria, parasites, and fungi can be presented by CD1d molecules and recognized by the canonical T cell receptors on NKT cells. Alternatively, NKT cells can be activated through recognition of self-lipids and/or pro-inflammatory cytokines generated during infection. Unlike conventional T cells, only a small subset of NKT cells traffic through the lymph nodes under homeostatic conditions, with the largest NKT cell populations localizing to the liver, lungs, spleen, and bone marrow. This is thought to be mediated by differences in chemokine receptor expression profiles. However, the impact of infection on the tissue localization and function of NKT remains largely unstudied. This review focuses on the mechanisms mediating the establishment of peripheral NKT cell populations during homeostasis and how tissue localization of NKT cells is affected during infection. PMID:26074921

Regulation of NKT Cell Localization in Homeostasis and Infection.

Science.gov (United States)

Slauenwhite, Drew; Johnston, Brent

2015-01-01

Natural killer T (NKT) cells are a specialized subset of T lymphocytes that regulate immune responses in the context of autoimmunity, cancer, and microbial infection. Lipid antigens derived from bacteria, parasites, and fungi can be presented by CD1d molecules and recognized by the canonical T cell receptors on NKT cells. Alternatively, NKT cells can be activated through recognition of self-lipids and/or pro-inflammatory cytokines generated during infection. Unlike conventional T cells, only a small subset of NKT cells traffic through the lymph nodes under homeostatic conditions, with the largest NKT cell populations localizing to the liver, lungs, spleen, and bone marrow. This is thought to be mediated by differences in chemokine receptor expression profiles. However, the impact of infection on the tissue localization and function of NKT remains largely unstudied. This review focuses on the mechanisms mediating the establishment of peripheral NKT cell populations during homeostasis and how tissue localization of NKT cells is affected during infection.

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...

Macrolide Hybrid Compounds: Drug Discovery Opportunities in Anti- Infective and Anti-inflammatory Area.

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Paljetak, Hana Cipcic; Tomaskovic, Linda; Matijasic, Mario; Bukvic, Mirjana; Fajdetic, Andrea; Verbanac, Donatella; Peric, Mihaela

2017-01-01

Macrolides, polyketide natural products, and their 15-membered semi-synthetic derivatives are composed of substituted macrocyclic lactone ring and used primarily as potent antibiotics. Recently their usefulness was extended to antimalarial and anti-inflammatory area. Hybrid macrolides presented in this article are the next generation semi-synthetic compounds that combine pharmacophores from antibacterial, antimalarial and anti-inflammatory area with 14- and 15-membered azalide scaffolds. Antibacterial azalide hybrids with sulphonamides showed improved activity against resistant streptococci while quinolone conjugates demonstrated full coverage of respiratory pathogens including macrolide resistant strains and their efficacy was confirmed in mouse pneumonia model. Antimalarial macrolide hybrids, mainly involving (chloro)quinoline pharmacophores, showed outstanding activity against chloroquine resistant strains, favourable pharmacokinetics, promising in vivo efficacy as well as encouraging developmental potential. Anti-inflammatory hybrids were obtained by combining macrolides with corticosteroid and non-steroidal anti-inflammatory drugs. They were found active in in vivo animal models of locally induced inflammation, asthma, inflammatory bowel disease and rheumatoid arthritis and demonstrated improved safety over parent steroid drugs. Overall, macrolide hybrids possess significant potential to be developed as potent novel medicines in therapeutic areas of utmost pharmaceutical interest. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

[Localized purpura revealing vascular prosthetic graft infection].

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Boureau, A S; Lescalie, F; Cassagnau, E; Clairand, R; Connault, J

2013-07-01

Prosthetic graft infection after vascular reconstruction is a rare but serious complication. We report a case of infection occurring late after implantation of an iliofemoral prosthetic vascular graft. The Staphylococcus aureus infection was revealed by vascular purpura localized on the right leg 7 years after implantation of a vascular prosthesis. This case illustrates an uncommonly late clinical manifestation presenting as an acute infection 7 years after the primary operation. In this situation, the presentation differs from early infection, which generally occurs within the first four postoperative months. Diagnosis and treatment remain a difficult challenge because prosthetic graft infection is a potentially life-threatening complication. Morbidity and mortality rates are high. Here we detail specific aspects of the clinical and radiological presentation. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

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

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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.

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.

Biocompatible Silver Nanoparticle-Modified Natural Diatomite with Anti-Infective Property

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Haolin Sun

2018-01-01

Full Text Available Nanosilver as an alternative antibacterial agent of antibiotics has been researched for possible applications in various orthopedic implants. However, it is imperative to achieve controllable release of Ag+ to reduce its cytotoxic effect on normal tissue. Here, a nanosilver release system that has potential to be used in anti-infective bone cement was reported. Nanosilver modified diatomite was developed through the reaction of Tollens’ reagent to improve the antibacterial effect and natural diatomite was used as the carrier of Ag+ ions for controlled release. Cytotoxicity and the antibacterial activities of the nanosilver release system were characterized. After 3 days, the NIH3T3 cells cultured in the extract of nanosilver modified diatomite with an initial concentration of 0.5 mg/ml showed better cell viability than cells cultured in α-MEM. The density of MC3T3-E1 cells cultured in the extract of nanosilver modified diatomite at the same concentration did not differ significantly from the density of cells cultured in α-MEM. The nanosilver modified diatomite exhibited antibacterial effect against E. coli and S. aureus when the concentration was higher than 0.5 mg/ml. With appropriate selection of Ag+ concentration, the nanosilver modified diatomite is promising for improving the antibacterial effect while not affecting the biocompatibility of reinforced calcium phosphate bone cement.

Evaluation of localized bacterial infection using radioisotope-labeled nucleosides imaging modality

Energy Technology Data Exchange (ETDEWEB)

Jang, Su Jin; Kang, Joo Hyun; Lee, Yong Jin; Lee, Tae Sup; Kim, Kwang Il; Lee, Kyo Chul; An, Gwang II; Cheon, Gi Jeong; Lim, Sang Moo [KIRAMS, Seoul (Korea, Republic of); Lim, Sang Yong [Korea Atomic Energy Research Institute, Daejeon (Korea, Republic of)

2011-10-15

Conventional diagnostic methods for infections are difficult to distinguish localized bacterial infections from sites of sterile inflammation. For this reason, the importance of developing methods to image bacterial infections is widely recognized. In this study to acquire bacterial infection imaging with radiolabeled nucleosides, in vitro bacterial thymidine kinase (tk) activities of Salmonella typhimurium with [{sup 18}F]FLT and [{sup 125}I]IVDU were measured and localized infections model in BALB/c mice was imaged with [{sup 18}F]FLT or [{sup 125}I]FIAU

INFECTIOUS AETIOLOGY OF MARGINAL ZONE LYMPHOMA AND ROLE OF ANTI-INFECTIVE THERAPY

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Salvatore Perrone

2016-01-01

Full Text Available Marginal zone lymphomas have been associated with several infectious agents covering both viral and bacterial pathogens and in some cases a clear aetiological role has been established. Pathogenetic mechanisms are currently not completely understood, however the role of chronic stimulation of the host immune response with persistent lymphocyte activation represents the most convincing explanation for lymphoproliferation. Gastric MALT lymphoma is strictly associated with Helicobacter pylori infection and various eradicating protocols, developed due to increasing antibiotic resistance, represent the first line therapy. The response rate to eradication is good with 80% of response at 1 year; this finding is also noteworthy because recapitulates a cancer cured only by antibacterial approach and it satisfies the Koch postulates of causation, establishing a causative relationship between Hp and gastric MALT lymphoma. Patients with chronic HCV infection have 5 times higher risk to develop MZL, in particular an association with splenic and nodal MZL has been shown in several studies. Moreover, there is evidence of lymphoma regression after antiviral therapy with interferon+ribavirin, thus rising hope that new available drugs, extremely effective against HCV replication, could improve outcome also in HCV-driven lymphomas. The rare cases of MZL localized to orbital fat and eye conjunctivas have been associated with Chlamydia psittaci infection carried by birds. Efficacy of antibacterial therapy against C. psittaci are conflicting and generally poorer thain gastric MALT. Finally some case-reports will cover the relationship between primary cutaneous B-cell Lymphomas and Borrelia Burgdorferi.

Besifloxacin: a novel anti-infective for the treatment of bacterial conjunctivitis

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Timothy L Comstock

2010-03-01

Full Text Available Timothy L Comstock1, Paul M Karpecki2, Timothy W Morris3, Jin-Zhong Zhang41Global Medical Affairs, Pharmaceuticals, Bausch and Lomb, Inc., Rochester, NY, USA; 2Koffler Vision Group, Lexington, KY, USA; 3Research and Development Microbiology and Sterilization Sciences, Bausch and Lomb, Inc., Rochester, NY, USA; 4Global Preclinical Development, Bausch and Lomb, Inc., Rochester, NY, USAAbstract: Bacterial conjunctivitis, commonly known as pink eye, is demographically unbiased in its prevalence and can be caused by a variety of aerobic and anaerobic bacteria. Timely empiric treatment with a broad-spectrum anti-infective, such as a topical fluoroquinolone, is critical in preventing potentially irreversible ocular damage. However, the rise in ocular methicillin-resistant Staphylococcus aureus isolates and the patterns of fluoroquinolone resistance for patients with other ocular bacterial infections mandate the need for new agents targeted for ocular use. Besifloxacin, a novel broad-spectrum fluoroquinolone, is approved for the treatment of bacterial conjunctivitis. It has a uniquely balanced dual-targeting activity that inhibits both DNA gyrase and topoisomerase IV and is associated with a lower incidence of resistance development. Besifloxacin is not marketed in other formulations, ensuring that its exposure is limited to bacterial populations in and around the eye. This specifically precludes any bacterial exposure to besifloxacin resulting from systemic use, which further reduces the likelihood of emergence of bacterial resistance. In vitro, besifloxacin has demonstrated equivalent or superior activity compared with other commonly used topical antibiotics. In clinical trials, besifloxacin has consistently demonstrated efficacy and safety in the treatment of patients with bacterial conjunctivitis. Besifloxacin is considered safe and is well tolerated with no observed contraindications.Keywords: conjunctivitis, fluoroquinolones, besifloxacin

Bioprospecting Deep-Sea Actinobacteria for Novel Anti-infective Natural Products

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Dongbo Xu

2018-04-01

Full Text Available The global prevalence of drug resistance has created an urgent need for the discovery of novel anti-infective drugs. The major source of antibiotics in current clinical practice is terrestrial actinobacteria; the less-exploited deep-sea actinobacteria may serve as an unprecedented source of novel natural products. In this study, we evaluated 50 actinobacteria strains derived from diverse deep water sponges and environmental niches for their anti-microbial activities against a panel of pathogens including Candida albicans, Clostridium difficile, Staphylococcus aureus, and methicillin-resistant S. aureus (MRSA, and Pseudomonas aeruginosa. More than half of the tested strains (27 were identified as active in at least one assay. The rare earth salt lanthanum chloride (LaCl3 was shown to be as an effective elicitor. Among the 27 strains, the anti-microbial activity of 15 were induced or enhanced by the addition of LaCl3. This part of study focused on one strain R818, in which potent antifungal activity was induced by the addition of LaCl3. We found that the LaCl3-activated metabolites in R818 are likely antimycin-type compounds. One of them, compound 1, has been purified. Spectroscopic analyses including HR-MS and 1D NMR indicated that this compound is urauchimycin D. The antifungal activity of compound 1 was confirmed with a minimal inhibitory concentration (MIC of 25 μg/mL; the purified compound also showed a moderate activity against C. difficile. Additional notable strains are: strain N217 which showed both antifungal and antibacterial (including P. aeruginosa activities and strain M864 which showed potent activity against C. difficile with an MIC value (0.125 μg/mL lower than those of vancomycin and metronidazole. Our preliminary studies show that deep-sea actinobacteria is a promising source of anti-infective natural products.

Non-adherence to anti-TB drugs among TB/HIV co-infected patients ...

African Journals Online (AJOL)

Non-adherence to anti-TB drugs among TB/HIV co-infected patients in Mbarara Hospital ... and its associated factors have not been studied in these patients in Uganda. ... Methods: A cross-sectional study with qualitative and quantitative data ...

Anti-Idiotypic Antibodies Specific to prM Monoantibody Prevent Antibody Dependent Enhancement of Dengue Virus Infection

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Miao Wang

2017-05-01

Full Text Available Dengue virus (DENV co-circulates as four serotypes (DENV1-4. Primary infection only leads to self-limited dengue fever. But secondary infection with another serotype carries a higher risk of increased disease severity, causing life-threatening dengue hemorrhagic fever/dengue shock syndrome (DHF/DSS. Serotype cross-reactive antibodies facilitate DENV infection in Fc-receptor-bearing cells by promoting virus entry via Fcγ receptors (FcγR, a process known as antibody dependent enhancement (ADE. Most studies suggested that enhancing antibodies were mainly specific to the structural premembrane protein (prM of DENV. However, there is still no effective drugs or vaccines to prevent ADE. In this study, we firstly confirmed that both DENV-2 infected human sera (anti-DENV-2 and DENV-2 prM monoclonal antibody (prM mAb could significantly enhance DENV-1 infection in K562 cells. Then we developed anti-idiotypic antibodies (prM-AIDs specific to prM mAb by immunizing of Balb/c mice. Results showed that these polyclonal antibodies can dramatically reduce ADE phenomenon of DENV-1 infection in K562 cells. To further confirm the anti-ADE effect of prM-AIDs in vivo, interferon-α and γ receptor-deficient mice (AG6 were used as the mouse model for DENV infection. We found that administration of DENV-2 prM mAb indeed caused a higher DENV-1 titer as well as interleukin-10 (IL-10 and alaninea minotransferase (ALT in mice infected with DENV-1, similar to clinical ADE symptoms. But when we supplemented prM-AIDs to DENV-1 challenged AG6 mice, the viral titer, IL-10 and ALT were obviously decreased to the negative control level. Of note, the number of platelets in peripheral blood of prM-AIDs group were significantly increased at day 3 post infection with DENV-1 compared that of prM-mAb group. These results confirmed that our prM-AIDs could prevent ADE not only in vitro but also in vivo, suggested that anti-idiotypic antibodies might be a new choice to be considered to

Anti-Idiotypic Antibodies Specific to prM Monoantibody Prevent Antibody Dependent Enhancement of Dengue Virus Infection.

Science.gov (United States)

Wang, Miao; Yang, Fan; Huang, Dana; Huang, Yalan; Zhang, Xiaomin; Wang, Chao; Zhang, Shaohua; Zhang, Renli

2017-01-01

Dengue virus (DENV) co-circulates as four serotypes (DENV1-4). Primary infection only leads to self-limited dengue fever. But secondary infection with another serotype carries a higher risk of increased disease severity, causing life-threatening dengue hemorrhagic fever/dengue shock syndrome (DHF/DSS). Serotype cross-reactive antibodies facilitate DENV infection in Fc-receptor-bearing cells by promoting virus entry via Fcγ receptors (FcγR), a process known as antibody dependent enhancement (ADE). Most studies suggested that enhancing antibodies were mainly specific to the structural premembrane protein (prM) of DENV. However, there is still no effective drugs or vaccines to prevent ADE. In this study, we firstly confirmed that both DENV-2 infected human sera (anti-DENV-2) and DENV-2 prM monoclonal antibody (prM mAb) could significantly enhance DENV-1 infection in K562 cells. Then we developed anti-idiotypic antibodies (prM-AIDs) specific to prM mAb by immunizing of Balb/c mice. Results showed that these polyclonal antibodies can dramatically reduce ADE phenomenon of DENV-1 infection in K562 cells. To further confirm the anti-ADE effect of prM-AIDs in vivo , interferon-α and γ receptor-deficient mice (AG6) were used as the mouse model for DENV infection. We found that administration of DENV-2 prM mAb indeed caused a higher DENV-1 titer as well as interleukin-10 (IL-10) and alaninea minotransferase (ALT) in mice infected with DENV-1, similar to clinical ADE symptoms. But when we supplemented prM-AIDs to DENV-1 challenged AG6 mice, the viral titer, IL-10 and ALT were obviously decreased to the negative control level. Of note, the number of platelets in peripheral blood of prM-AIDs group were significantly increased at day 3 post infection with DENV-1 compared that of prM-mAb group. These results confirmed that our prM-AIDs could prevent ADE not only in vitro but also in vivo , suggested that anti-idiotypic antibodies might be a new choice to be considered to treat

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

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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.

The serological markers of acute infection with hepatitis A, B, C, D, E and G viruses revisited.

Science.gov (United States)

Pondé, Robério Amorim de Almeida

2017-12-01

Viral hepatitis is a liver infection caused by one of the six hepatitis viruses: hepatitis A, B, C, D, E, and G virus (HAV to HEV and HGV). These agents differ in their biological, immunological, pathological and epidemiological characteristics. They cause infections that, when symptomatic, lead to clinical manifestations and laboratory findings that are not specific to a particular virus, often making differential diagnosis difficult, especially when no knowledge is available regarding the patient's medical history or the epidemiological background. A number of acute-phase serological markers, such as anti-HAV, anti-HBc, anti-HDV and anti-HEV IgM antibodies, are able to provide a clear indication of an infection caused by HAV, HBV, HDV or HEV. Anti-HCV antibodies and HGV/RNA are used for the diagnosis of HCV and HGV infections. The importance of each of these markers will be reviewed, and different factors that can interfere with the diagnosis of acute infections caused by these viruses will be described.

Hepatitis E virus co-infection in HIV-infected patients in Foggia and Naples in southern Italy.

Science.gov (United States)

Scotto, Gaetano; Grisorio, Benvenuto; Filippini, Pietro; Ferrara, Sergio; Massa, Salvatore; Bulla, Fabio; Martini, Salvatore; Filippini, Alberico; Tartaglia, Alessandra; Lo Muzio, Lorenzo; Fazio, Vincenzina

2015-01-01

Hepatitis E virus (HEV) infection represents an emerging infection in developed countries and is thought to be a zoonotic infection. It has recently been described as a new causative agent of acute and chronic hepatitis in immunosuppressed subjects, including HIV-infected patients. The aim of this study was to assess the sero-virological prevalence of HEV in HIV patients and in the general population as control group. A prospective and observational cohort study was carried out in two hospitals in southern Italy. The seroprevalence of HEV was determined in a cohort of 959 subjects, 509 (53%) of whom were HIV-positive patients and 450 were from the general population. Serum samples were tested for anti-HEV antibodies; repeatedly positive results were confirmed by a Western blot assay. In positive patients HEV RNA and genotypes were also determined. A total of 46 (4.8%) of the 959 serum samples examined were reactive to anti-HEV Ig and confirmed by Western blotting. The prevalence of HEV antibodies (IgG and/or IgM) was 2.7% in the control group and 6.7% in HIV-infected patients. Anti-HEV IgM was found in 6/46 (13.0%) of the anti-HEV Ig-positive serum samples, in 5/34 HIV patients and in 1/12 of the general population. No HIV-infected patient presented chronic hepatitis with HEV infection alone. This study indicates a higher circulation of HEV in HIV-infected patients, whereas a low prevalence of HEV antibodies in the general Italian population was shown. Chronic hepatitis with HEV alone was absent, while it was present in subjects with HIV-HEV, co-infected with hepatitis B virus (HBV) and/or hepatitis C virus (HCV).

Introducción a los antisépticos

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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.

Anti-Bovine Programmed Death-1 Rat–Bovine Chimeric Antibody for Immunotherapy of Bovine Leukemia Virus Infection in Cattle

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Tomohiro Okagawa

2017-06-01

Full Text Available Blockade of immunoinhibitory molecules, such as programmed death-1 (PD-1/PD-ligand 1 (PD-L1, is a promising strategy for reinvigorating exhausted T cells and preventing disease progression in a variety of chronic infections. Application of this therapeutic strategy to cattle requires bovinized chimeric antibody targeting immunoinhibitory molecules. In this study, anti-bovine PD-1 rat–bovine chimeric monoclonal antibody 5D2 (Boch5D2 was constructed with mammalian expression systems, and its biochemical function and antiviral effect were characterized in vitro and in vivo using cattle infected with bovine leukemia virus (BLV. Purified Boch5D2 was capable of detecting bovine PD-1 molecules expressed on cell membranes in flow cytometric analysis. In particular, Biacore analysis determined that the binding affinity of Boch5D2 to bovine PD-1 protein was similar to that of the original anti-bovine PD-1 rat monoclonal antibody 5D2. Boch5D2 was also capable of blocking PD-1/PD-L1 binding at the same level as 5D2. The immunomodulatory and therapeutic effects of Boch5D2 were evaluated by in vivo administration of the antibody to a BLV-infected calf. Inoculated Boch5D2 was sustained in the serum for a longer period. Boch5D2 inoculation resulted in activation of the proliferation of BLV-specific CD4+ T cells and decrease in the proviral load of BLV in the peripheral blood. This study demonstrates that Boch5D2 retains an equivalent biochemical function to that of the original antibody 5D2 and is a candidate therapeutic agent for regulating antiviral immune response in vivo. Clinical efficacy of PD-1/PD-L1 blockade awaits further experimentation with a large number of animals.

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

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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.

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

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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.

New strategies for local treatment of vaginal infections.

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Palmeira-de-Oliveira, Rita; Palmeira-de-Oliveira, Ana; Martinez-de-Oliveira, José

2015-09-15

Vaginal infections are extremely prevalent, particularly among women of reproductive age. Although they do not result in high mortality rates, these infections are associated with high levels of anxiety and reduction of quality of life. In most cases, topical treatment of vaginal infections has been shown to be at least as effective as oral treatment, resulting in higher local drug concentrations, with fewer drug interactions and adverse effects. Furthermore, the emergence of microbial resistance to chemotherapeutics and the difficulties in managing infection recurrences sustain the need for more effective local treatments. However, conventional dosage forms have been associated with low retention in the vagina and discomfort. Formulation strategies such as the development of bioadhesive, thermogelling systems and microtechnological or nanotechnological approaches have been proposed to improve delivery of traditional drugs, and other treatment modalities such as new drugs, plant extracts, and probiotics are being studied. This article reviews the recent strategies studied to improve the treatment and prevention of the commonest vaginal infections-namely, vaginal bacteriosis, aerobic vaginitis, vulvovaginal candidosis, and trichomoniasis-through the intravaginal route. Copyright © 2015 Elsevier B.V. All rights reserved.

Targeted delivery of anti-tuberculosis drugs to macrophages: targeting mannose receptors

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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.

Pathogen- and host-directed anti-inflammatory activities of macrolide antibiotics.

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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.

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

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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.

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

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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.

Protection status against hepatitis B infection assessed fromanti-HBs level, history of vaccination andhistory of infection based on anti-HBc in medical students

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Annisa; Zain, LH; Loesnihari, R.

2018-03-01

Hepatitis B virus (HBV) is one of the most contagious pathogens where the risk of exposure is very high among health care workers, especially students in the clerkship. This study describes the protection status by measuring anti-HBs level, history of vaccination, and history of HBV infection in medical students.Forty-four (44) students over 18 years old were randomly selected, interviewed for their vaccination history and then had their blood serum taken for anti-HBs and anti-HBc examinations to determine the protectivity and history of infection.There were 81.8% students without a protective anti-HBs level. Before starting their clerkship, 18.2% students received thevaccination, and only one-fourth formed protective antibody level above 10mIU/mL. Seventeen (38.6%) students had been exposed to HBV(positive anti-HBc), and only six of them showed protective anti-HBs level. None of the students that received vaccine underwent a post-vaccination serological test (PVST) to determine their immune response. These results indicated the vulnerability of medical students to the risk of HBV transmission while performing medical care. With the high incidence of HBV transmission, educational institutions are encouraged to make provisions for vulnerable students to receive a booster and an adequate PVST before their clerkship.

Challenges in the local delivery of peptides and proteins for oral mucositis management.

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Campos, João C; Cunha, João D; Ferreira, Domingos C; Reis, Salette; Costa, Paulo J

2018-04-24

Oral mucositis, a common inflammatory side effect of oncological treatments, is a disorder of the oral mucosa that can cause painful ulcerations, local motor disabilities, and an increased risk of infections. Due to the discomfort it produces and the associated health risks, it can lead to cancer treatment restrains, such as the need for dose reduction, cycle delays or abandonment. Current mucositis management has low efficiency in prevention and treatment. A topical drug application for a local action can be a more effective approach than systemic routes when addressing oral cavity pathologies. Local delivery of growth factors, antibodies, and anti-inflammatory cytokines have shown promising results. However, due to the peptide and protein nature of these novel agents, and the several anatomic, physiological and environmental challenges of the oral cavity, their local action might be limited when using traditional delivering systems. This review is an awareness of the issues and strategies in the local delivery of macromolecules for the management of oral mucositis. Copyright © 2018. Published by Elsevier B.V.

Anti-Streptococcus IgM Antibodies Induce Repetitive Stereotyped Movements: Cell Activation and Co-Localization with Fcα/μ Receptors in the Striatum and Motor Cortex

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Zhang, Danhui; Patel, Ankur; Zhu, Youhua; Siegel, Allan; Zalcman, Steven S.

2012-01-01

Group A beta-hemolytic streptococcus (GABHS) infections are implicated in neuropsychiatric disorders associated with an increased expression of repetitive stereotyped movements. Anti-streptococcus IgG presumably cross-reacts with elements on basal ganglia cells, modifies their function, and triggers symptoms. IgM may play a unique role in precipitating behavioral disturbances since variations in cortico-striatal activity occur in temporal congruity with peak IgM titers during an orchestrated immune response. We discovered in Balb/c mice that single subcutaneous injections of mouse monoclonal IgM antibodies to Streptococcus Group A bacteria induce marked dose-dependent increases in repetitive stereotyped movements, including head bobbing, sniffing, and intense grooming. Effects were antibody- and antigen-specific: anti-streptococcus IgG stimulated ambulatory activity and vertical activity but not these stereotypies, while anti-KLH IgM reduced activity. We suggest that anti-streptococcus IgM and IgG play unique roles in provoking GABHS-related behavioral disturbances. Paralleling its stereotypy-inducing effects, anti-streptococcus IgM stimulated Fos-like immunoreactivity in regions linked to cortico-striatal projections involved in motor control, including subregions of the caudate, nucleus accumbens, and motor cortex. This is the first evidence that anti-streptococcus IgM antibodies induce in vivo functional changes in these structures. Moreover, there was a striking similarity in the distributions of anti-streptococcus IgM deposits and Fos-like immunoreactivity in these regions. Of further importance, Fcα/μ receptors, which bind IgM, were present- and co-localized with anti-streptococcus IgM in these structures. We suggest that anti-streptococcus IgM-induced alterations of cell activity reflect local actions of IgM that involve Fcα/μ receptors. These findings support the use of anti-streptococcus monoclonal antibody administration in Balb/c mice to model GABHS

Activity of andrographolide against chikungunya virus infection.

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Wintachai, Phitchayapak; Kaur, Parveen; Lee, Regina Ching Hua; Ramphan, Suwipa; Kuadkitkan, Atichat; Wikan, Nitwara; Ubol, Sukathida; Roytrakul, Sittiruk; Chu, Justin Jang Hann; Smith, Duncan R

2015-09-18

Chikungunya virus (CHIKV) is a re-emerging mosquito-borne alphavirus that has recently engendered large epidemics around the world. There is no specific antiviral for treatment of patients infected with CHIKV, and development of compounds with significant anti-CHIKV activity that can be further developed to a practical therapy is urgently required. Andrographolide is derived from Andrographis paniculata, a herb traditionally used to treat a number of conditions including infections. This study sought to determine the potential of andrographolide as an inhibitor of CHIKV infection. Andrographolide showed good inhibition of CHIKV infection and reduced virus production by approximately 3log10 with a 50% effective concentration (EC50) of 77 μM without cytotoxicity. Time-of-addition and RNA transfection studies showed that andrographolide affected CHIKV replication and the activity of andrographolide was shown to be cell type independent. This study suggests that andrographolide has the potential to be developed further as an anti-CHIKV therapeutic agent.

Clinical efficacy of anti-glycopeptidolipid-core IgA test for diagnosing Mycobacterium avium complex infection in lung.

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Numata, Takanori; Araya, Jun; Yoshii, Yutaka; Shimizu, Kenichiro; Hara, Hiromichi; Nakayama, Katsutoshi; Kuwano, Kazuyoshi

2015-11-01

It is difficult to verify the bacteriological diagnosis of Mycobacterium avium complex (MAC) infection. The anti-glycopeptidolipid (GPL)-core IgA antibody test was recently developed as a diagnostic method for MAC pulmonary disease. Only a few studies evaluate its clinical efficacy. We conducted retrospective evaluations of clinical characteristics of patients suspected of MAC infection to explore the usefulness of the anti-GPL-core IgA antibody test. We retrospectively evaluated 296 patients who were suspected to have MAC infection and underwent anti-GPL-core IgA antibody test between March 2013 and July 2014 in Jikei University hospital. A total of 29 patients were diagnosed with 'definite MAC' based on the American Thoracic Society (ATS) criteria with multiple identifications of MAC. On the other hand, 106 patients were diagnosed with other pulmonary diseases than MAC. The sensitivity and specificity of anti-GPL-core IgA antibody test for MAC diagnosis were 58.6% and 98.1%, respectively. The definite MAC group showed no significant differences in strains, treatment history or number of segments involved. The duration of MAC disease in the positive-antibody group was significantly longer than in the negative-antibody group (P = 0.046). A significant increase in the false-negative rate was observed in patients with malignant disease (P = 0.029). The anti-GPL-core IgA antibody test demonstrated high sensitivity and specificity for the diagnosis of MAC infection especially in patients without malignant diseases. © 2015 Asian Pacific Society of Respirology.

Prosthetic vascular graft infection and prosthetic joint infection caused by Pseudomonas stutzeri.

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Bonares, Michael J; Vaisman, Alon; Sharkawy, Abdu

2016-01-01

Pseudomonas stutzeri is infrequently isolated from clinical specimens, and if isolated, more likely represents colonization or contamination rather than infection. Despite this, there are dozens of case reports which describe clinically significant P. stutzeri infections at variable sites. A 69-year-old man had a P. stutzeri infection of a prosthetic vascular graft infection, which he received in Panama City. He was successfully treated with a single antipseudomonal agent for 6 weeks and the removal of the infected vascular graft. A 70-year-old man had a P. stutzeri infection of a prosthetic joint, which was successfully treated with a single anti-pseudomonal agent for 6 weeks. There is only one other documented case of a prosthetic vascular graft infection secondary to P. stutzeri . There are 5 documented cases of P. stutzeri prosthetic joint infections. The previous cases were treated with antibiotics and variably, source control with the removal of prosthetic material. Most cases of P. stutzeri infection are due to exposure in health care settings. Immunocompromised states such as HIV or hematological and solid tumor malignancies are risk factors for P. stutzeri infection. Infections caused by P. stutzeri are far less frequent and less fatal than those caused by P. aeruginosa. The etiology of a P. stutzeri infection could be exposure to soil and water, but also contaminated material in the health care setting or an immunocompromised state. Iatrogenic infections that are secondary to health care tourism are a potential cause of fever in the returned traveler.

Use of human immunoglobulins as an anti-infective treatment: the experience so far and their possible re-emerging role.

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Bozzo, Jordi; Jorquera, Juan I

2017-06-01

Pooled human immunoglobulins (IGs) are prepared from plasma obtained from healthy donors as a concentrated antibody-containing solution. In addition, high-titer IGs (hyperimmune) against a specific pathogen can be obtained from vaccinated or convalescing donors. Currently, IGs can be used for the treatment of a variety of infections for which no specific therapy exists or that remain difficult to treat. Moreover, the recent pathogen outbreaks for which there is no approved treatment have renewed attention to the role of convalescent plasma and IGs. Areas covered: In this review, a historical perspective of the use of sera and IGs in humans as anti-infective agents (any viral, bacterial, parasitic infection), excluding immunodeficient patients, is presented from early development to the latest clinical studies. A Medline search was conducted to examine the peer-reviewed literature, with no date limits. Expert commentary: Human pooled plasma-derived IG products benefit from the polyclonal response of every individual donor and from the interindividual variability in such response. The trend to increased availability of vaccines for infectious diseases also opens new potential applications of hyperimmune IGs for emerging or re-emerging infectious diseases (e.g.: Ebola, Zika, Dengue), for the prevention and treatment in the general population, healthcare personnel and caregivers.

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.

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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.

Spectrum of imaging appearances of intracranial cryptococcal infection in HIV/AIDS patients in the anti-retroviral therapy era

International Nuclear Information System (INIS)

Offiah, Curtis E.; Naseer, Aisha

2016-01-01

Cryptococcus neoformans infection is the most common fungal infection of the central nervous system (CNS) in advanced human immunodeficiency virus (HIV) and acquired immunodeficiency syndrome (AIDS) patients, but remains a relatively uncommon CNS infection in both the immunocompromised and immunocompetent patient population, rendering it a somewhat elusive and frequently overlooked diagnosis. The morbidity and mortality associated with CNS cryptococcal infection can be significantly reduced by early recognition of the imaging appearances by the radiologist in order to focus and expedite clinical management and treatment. The emergence and evolution of anti-retroviral therapy have also impacted significantly on the imaging appearances, morbidity, and mortality of this neuro-infection. The constellation of varied imaging appearances associated with cryptococcal CNS infection in the HIV and AIDS population in the era of highly active anti-retroviral therapy (HAART) will be presented in this review.

Multi-agent search for source localization in a turbulent medium

International Nuclear Information System (INIS)

Hajieghrary, Hadi; Hsieh, M. Ani; Schwartz, Ira B.

2016-01-01

We extend the gradient-less search strategy referred to as “infotaxis” to a distributed multi-agent system. “Infotaxis” is a search strategy that uses sporadic sensor measurements to determine the source location of materials dispersed in a turbulent medium. In this work, we leverage the spatio-temporal sensing capabilities of a mobile sensing agents to optimize the time spent finding and localizing the position of the source using a multi-agent collaborative search strategy. Our results suggest that the proposed multi-agent collaborative search strategy leverages the team's ability to obtain simultaneous measurements at different locations to speed up the search process. We present a multi-agent collaborative “infotaxis” strategy that uses the relative entropy of the system to synthesize a suitable search strategy for the team. The result is a collaborative information theoretic search strategy that results in control actions that maximize the information gained by the team, and improves estimates of the source position. - Highlights: • We extend the gradient-less infotaxis search strategy to a distributed multi-agent system. • Leveraging the spatio-temporal sensing capabilities of a team of mobile sensing agents speeds up the search process. • The resulting information theoretic search strategy maximizes the information gained and improves the estimate of the source position.

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.

The impact of changing antiseptic skin preparation agent used for cardiac implantable electronic device (CIED) procedures on the risk of infection.

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Qintar, Mohammed; Zardkoohi, Omeed; Hammadah, Muhammad; Hsu, Amy; Wazni, Oussama; Wilkoff, Bruce L; Tarakji, Khaldoun G

2015-02-01

Cardiac implantable electronic device (CIED) infection is a major complication that is associated with increased morbidity and mortality. Recent data suggested a relationship between the antiseptic agent used for skin preparation at time of CIED procedure and risk for infection. On April 30, 2011, we changed the antiseptic agent used for skin preparation at our tertiary care facility from chlorhexidine-alcohol to povidone-iodine for all CIED procedures. We retrospectively reviewed records of all patients who underwent CIED procedure 1 year before and after the change. CIED infection was defined as pocket or endovascular systemic infection that required removal within 1 year of the index procedure. We examined if the change affected the risk of CIED infection. A total of 2,792 patients underwent 2,840 CIED procedures; 1,748 (61.5%) had implantable cardioverter defibrillator procedures and 1,092 (38.4%) had permanent pacemaker procedures. Chlorhexidine-alcohol agent was used in 1,450 (51.1%) procedures, and povidone-iodine agent was used in 1,390 (48.9%). After 1 year of follow-up, 31 patients (1.09%) developed CIED infection that required system removal. The 1-year infection rate was 1.1% among both antiseptic agent groups and there were no significant differences in the infection presentations among both groups (P = 0.950). Multivariate Cox proportional hazards regression model showed that risk factors for infection within 1 year included age, diabetes, and African American race. In one large cohort of patients undergoing CIED procedures, the antiseptic agent used for skin preparation (chlorhexidine-alcohol vs povidone-iodine) was not associated with increased risk of developing CIED infection. ©2014 Wiley Periodicals, Inc.

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

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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.

Prospective of 68Ga Radionuclide Contribution to the Development of Imaging Agents for Infection and Inflammation

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2018-01-01

During the last decade, the utilization of 68Ga for the development of imaging agents has increased considerably with the leading position in the oncology. The imaging of infection and inflammation is lagging despite strong unmet medical needs. This review presents the potential routes for the development of 68Ga-based agents for the imaging and quantification of infection and inflammation in various diseases and connection of the diagnosis to the treatment for the individualized patient management. PMID:29531507

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...

Chromobacterium Csp_P reduces malaria and dengue infection in vector mosquitoes and has entomopathogenic and in vitro anti-pathogen activities.

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Ramirez, Jose Luis; Short, Sarah M; Bahia, Ana C; Saraiva, Raul G; Dong, Yuemei; Kang, Seokyoung; Tripathi, Abhai; Mlambo, Godfree; Dimopoulos, George

2014-10-01

Plasmodium and dengue virus, the causative agents of the two most devastating vector-borne diseases, malaria and dengue, are transmitted by the two most important mosquito vectors, Anopheles gambiae and Aedes aegypti, respectively. Insect-bacteria associations have been shown to influence vector competence for human pathogens through multi-faceted actions that include the elicitation of the insect immune system, pathogen sequestration by microbes, and bacteria-produced anti-pathogenic factors. These influences make the mosquito microbiota highly interesting from a disease control perspective. Here we present a bacterium of the genus Chromobacterium (Csp_P), which was isolated from the midgut of field-caught Aedes aegypti. Csp_P can effectively colonize the mosquito midgut when introduced through an artificial nectar meal, and it also inhibits the growth of other members of the midgut microbiota. Csp_P colonization of the midgut tissue activates mosquito immune responses, and Csp_P exposure dramatically reduces the survival of both the larval and adult stages. Ingestion of Csp_P by the mosquito significantly reduces its susceptibility to Plasmodium falciparum and dengue virus infection, thereby compromising the mosquito's vector competence. This bacterium also exerts in vitro anti-Plasmodium and anti-dengue activities, which appear to be mediated through Csp_P -produced stable bioactive factors with transmission-blocking and therapeutic potential. The anti-pathogen and entomopathogenic properties of Csp_P render it a potential candidate for the development of malaria and dengue control strategies.

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

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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

CNS infections in immunocompetent patients

International Nuclear Information System (INIS)

Hartmann, K.M.; Zimmer, A.; Reith, W.

2008-01-01

This article gives a review of the most frequent infective agents reasonable for CNS infections in immunocompetent patients as well as their localisation and imaging specifications. MRI scanning is the gold standard to detect inflammatory conditions in the CNS. Imaging can be normal or nonspecifically altered although the infection is culturally or bioptically proven. There are no pathognomonic, pathogen-specific imaging criteria. The localization and dimension of the inflammation depends on the infection pathway. (orig.) [de

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)

Antimicrobial peptides as potential anti-biofilm agents against multidrug-resistant bacteria.

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Chung, Pooi Yin; Khanum, Ramona

2017-08-01

Bacterial resistance to commonly used drugs has become a global health problem, causing increased infection cases and mortality rate. One of the main virulence determinants in many bacterial infections is biofilm formation, which significantly increases bacterial resistance to antibiotics and innate host defence. In the search to address the chronic infections caused by biofilms, antimicrobial peptides (AMP) have been considered as potential alternative agents to conventional antibiotics. Although AMPs are commonly considered as the primitive mechanism of immunity and has been extensively studied in insects and non-vertebrate organisms, there is now increasing evidence that AMPs also play a crucial role in human immunity. AMPs have exhibited broad-spectrum activity against many strains of Gram-positive and Gram-negative bacteria, including drug-resistant strains, and fungi. In addition, AMPs also showed synergy with classical antibiotics, neutralize toxins and are active in animal models. In this review, the important mechanisms of action and potential of AMPs in the eradication of biofilm formation in multidrug-resistant pathogen, with the goal of designing novel antimicrobial therapeutics, are discussed. Copyright © 2017. Published by Elsevier B.V.

Autecology Essential Oil Composition, Antibacterial, Anti Candidacies and Ethnopharmacological Survey of Ferula Gummosa L. As Anti Infection to Treat Of Vaginal Infections in Traditional Medicine of Razavi Khorasan Province (North East of Iran

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Mazandarani Masoumeh

2015-04-01

Full Text Available Objective: Ferula gummosa Boiss. (Apiaceae family, which has been used in traditional medicine of Iran as anti vaginal infection, anti-sinusitis, sedative, and anti-inflammation. Materials and Methods: In this research, the gums of plant root were collected from the Heidary nature reserve in Razavi Khorasan Province (Iran in August 2012. The ethnopharmacological data about traditional uses of plant were obtained from the rural healers (women 67-75 year of this region. Essential oil of the plant root gum was obtained by hydrodistillation (Clevenger apparatus and was analyzed by gas chromatography–mass spectrometry. Antibacterial activity of plant ethanolic extract was studied in vitro against Candida albicans and 9 Gram-positive and negative bacteria using well method and the minimum inhibitory concentration (MIC assay. Results: Results showed that a total of 39 components have been identified in the plant sampl oil, representing 81% of the total oil and β-pinene (19.88%, guaiol (8%, shyobunone (6.96%, delta-cadinene (4.65%, α-pinene (3.16 %, β-phellandrene (3.28% and myrtenol (2.8%, were the main essential oil composition, respectively. The results from antibacterial screening (Table 2, were showed that C. albicans (25.2 ± 1.6, Staphylococcus epidermidis (23.6 ± 0.7 mm, Staphylococcus aureus (21.3 ± 0.2 mm, Escherichia coli (16.5 ± 0.8 mm, Bacillus cereus (19.5 ± 0.1 mm, Enterococcus faecalis (17.2 ± 0.8 mm and Pseudomonas aeroginosa ( 17.8 ± 0.2 mm inhibition zone and MIC (35.4-112 μg/ml were the most sensitive pathogenes to the plant extract respectively, which followed Shigella (12.3 ± 0.3 mm and Klebsiella pneumonia (12.5 ± 0.2 mm were found to be moderate sensitive bacteria and then the Salmonella typhymorium which completely was resistant to plant root extract. Conclusion: According to these results, it can be concluded that the extract of F. gummosa L. have suitable antimicrobial and anti-Candidacies activity, which can be

Concentrations of Adalimumab and Infliximab in Mothers and Newborns, and Effects on Infection

DEFF Research Database (Denmark)

Julsgaard, Mette; Christensen, Lisbet Ambrosius; Gibson, Peter R.

2016-01-01

these correlated with drug concentrations in mothers at birth and risk of infection during the first year of life.  Methods  We performed a prospective study of 80 pregnant women with inflammatory bowel diseases at tertiary hospitals in Denmark, Australia, and New Zealand from March 2012 through November 2014: 36......) and in mothers at time of birth (adalimumab, r = -0.80; infliximab, r = -0.80; P mother drug concentration at birth was 1.21 for adalimumab (95% confidence interval [CI], 0.94–1.49) and 1.97 for infliximab (95% CI, 1.50–2.43). The mean time to drug clearance...... risk for infection was 2.7 in infants whose mothers received the combination of an anti-TNF agent and thiopurine, compared with anti-TNF monotherapy (95% CI, 1.09–6.78; P =.02).  Conclusions  In a prospective study of infants born to mothers who received anti-TNF agents during pregnancy, we detected...

Anal lymphogranuloma venereum infection screening with IgA anti-Chlamydia trachomatis-specific major outer membrane protein serology.

Science.gov (United States)

de Vries, Henry J C; Smelov, Vitaly; Ouburg, Sander; Pleijster, Jolein; Geskus, Ronald B; Speksnijder, Arjen G C L; Fennema, Johannes S A; Morré, Servaas A

2010-12-01

Anal lymphogranuloma venereum (LGV) infections, caused by Chlamydia trachomatis biovar L (Ct+/LGV+), are endemic among men who have sex with men (MSM). Anal non-LGV biovar Ct infections (Ct+/LGV-) can be eradicated with 1 week doxycycline, whereas Ct+/LGV+ infections require 3-week doxycycline. To differentiate Ct+/LGV+ from Ct+/LGV- infections, biovar-specific Nucleic Acid Amplification Test (NAAT) are standard, but also expensive and laborious. A chlamydia-specific serological assay could serve as an alternative test. MSM were screened for anal Ct+/LGV+ and Ct+/LGV- infections with a commercial nonspecific NAAT and an in house biovar L-specific NAAT. Serum samples were evaluated with chlamydia-specific anti-Major Outer Membrane Protein (MOMP) and antilipopolysaccharide assays of IgA and IgG classes. Asymptomatic patients were identified as: (1) no anal complaints or (2) no microscopic inflammation (i.e., <10 leucocytes per high power field in anal smears). The best differentiating assay was subsequently evaluated in 100 Ct+/LGV+ and 100 Ct+/LGV- MSM using different cut-off points. The anti-MOMP IgA assay was the most accurate to differentiate Ct+/LGV+ (n = 42) from Ct+/LGV- (n = 19) with 85.7% sensitivity (95% confidence interval [CI], 72.2-93.3) and 84.2% specificity (95% CI, 62.4-94.5), even among asymptomatic patients. In a population comprising 98 Ct+/LGV+ and 105 Ct+/LGV- patients, the anti-MOMP IgA assay scored most accurate when the cut-off point was set to 2.0 with 75.5% (95% CI, 65.8-83.6) sensitivity and 74.3% (95% CI, 64.8-82.3) specificity. The IgA anti-MOMP assay can identify a considerable proportion of the (asymptomatic) anal LGV infections correctly. Yet, biovar L-specific NAAT are still the preferred diagnostic tests in clinical settings.

CNS activity of Pokeweed Anti-viral Protein (PAP in mice infected with Lymphocytic Choriomeningitis Virus (LCMV

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Tibbles Heather E

2005-02-01

Full Text Available Abstract Background Others and we have previously described the potent in vivo and in vitro activity of the broad-spectrum antiviral agent PAP (Pokeweed antiviral protein against a wide range of viruses. The purpose of the present study was to further elucidate the anti-viral spectrum of PAP by examining its effects on the survival of mice challenged with lymphocytic choriomeningitis virus (LCMV. Methods We examined the therapeutic effect of PAP in CBA mice inoculated with intracerebral injections of the WE54 strain of LCMV at a 1000 PFU dose level that is lethal to 100% of mice within 7–9 days. Mice were treated either with vehicle or PAP administered intraperitoneally 24 hours prior to, 1 hour prior to and 24 hours, 48 hours 72 hours and 96 hours after virus inoculation. Results PAP exhibits significant in vivo anti- LCMV activity in mice challenged intracerebrally with an otherwise invariably fatal dose of LCMV. At non-toxic dose levels, PAP significantly prolonged survival in the absence of the majority of disease-associated symptoms. The median survival time of PAP-treated mice was >21 days as opposed to 7 days median survival for the control (p = 0.0069. Conclusion Our results presented herein provide unprecedented experimental evidence that PAP exhibits antiviral activity in the CNS of LCMV-infected mice.

Drug loaded homogeneous electrospun PCL/gelatin hybrid nanofiber structures for anti-infective tissue regeneration membranes.

Science.gov (United States)

Xue, Jiajia; He, Min; Liu, Hao; Niu, Yuzhao; Crawford, Aileen; Coates, Phil D; Chen, Dafu; Shi, Rui; Zhang, Liqun

2014-11-01

Infection is the major reason for guided tissue regeneration/guided bone regeneration (GTR/GBR) membrane failure in clinical application. In this work, we developed GTR/GBR membranes with localized drug delivery function to prevent infection by electrospinning of poly(ε-caprolactone) (PCL) and gelatin blended with metronidazole (MNA). Acetic acid (HAc) was introduced to improve the miscibility of PCL and gelatin to fabricate homogeneous hybrid nanofiber membranes. The effects of the addition of HAc and the MNA content (0, 1, 5, 10, 20, 30, and 40 wt.% of polymer) on the properties of the membranes were investigated. The membranes showed good mechanical properties, appropriate biodegradation rate and barrier function. The controlled and sustained release of MNA from the membranes significantly prevented the colonization of anaerobic bacteria. Cells could adhere to and proliferate on the membranes without cytotoxicity until the MNA content reached 30%. Subcutaneous implantation in rabbits for 8 months demonstrated that MNA-loaded membranes evoked a less severe inflammatory response depending on the dose of MNA than bare membranes. The biodegradation time of the membranes was appropriate for tissue regeneration. These results indicated the potential for using MNA-loaded PCL/gelatin electrospun membranes as anti-infective GTR/GBR membranes to optimize clinical application of GTR/GBR strategies. Copyright © 2014 Elsevier Ltd. All rights reserved.

Enhancement of retroviral infection in vitro by anti-Le(y) IgG: reversal by humanization of monoclonal mouse antibody

DEFF Research Database (Denmark)

Hansen, J E; Sørensen, A M; Arendrup, M

1993-01-01

Monoclonal mouse IgG3 antibody (ABL 364) against the carbohydrate Le(y) antigen enhanced infection in vitro with HTLV-1 and with HIV-1 when propagated in both transformed and normal lymphocytes. Enhancement was independent of complement, occurred with both lymphocytes and monocytes as target cells...... with no indication of any alternative pathway of infection, as evidenced by abrogation of enhancement by anti-CD4 MAb or soluble recombinant CD4, and also the inability of anti-Le(y) MAb to mediate HIV infection of HSB-2 cells in which HTLV-1/HIV pseudovirus infection was enhanced. While F(ab)2 fragments of ABL 364...

Topical retapamulin in the management of infected traumatic skin lesions

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Ribhi Shawar

2008-12-01

Full Text Available Ribhi Shawar1, Nicole Scangarella-Oman1, MaryBeth Dalessandro2, John Breton2, Monique Twynholm3, Gang Li4, Harmony Garges51Infectious Disease Center for Excellence in Drug Discovery, GlaxoSmithKline, Collegeville, PA, USA; 2Anti-infectives Medicine Development Center, GlaxoSmithKline, Collegeville, PA, USA; 3Infectious Diseases Medicine Development Centre Europe, GlaxoSmithKline, Greenford, Middlesex, UK; 4MDC BDS – Infectious Disease, GlaxoSmithKline, Collegeville, PA, USA; 5Anti-infectives Medicine Development Center, GlaxoSmithKline, Research Triangle Park, NC, USAAbstract: Retapamulin is a novel semisynthetic pleuromutilin antibiotic specifically designed for use as a topical agent. The unique mode of action by which retapamulin selectively inhibits bacterial protein synthesis differentiates it from other nonpleuromutilin antibacterial agents that target the ribosome or ribosomal factors, minimizing the potential for target-specific cross-resistance with other antibacterial classes in current use. In vitro studies show that retapamulin has high potency against the Gram-positive bacteria (Staphylococcus aureus, Streptococcus pyogenes, and coagulase-negative staphylococci commonly found in skin and skin-structure infections (SSSIs, including S. aureus strains with resistance to agents such as macrolides, fusidic acid, or mupirocin, and other less common organisms associated with SSSIs, anaerobes, and common respiratory tract pathogens. Clinical studies have shown that twice-daily topical retapamulin for 5 days is comparable to 10 days of oral cephalexin in the treatment of secondarily infected traumatic lesions. A 1% concentration of retapamulin ointment has been approved for clinical use as an easily applied treatment with a short, convenient dosing regimen for impetigo. Given the novel mode of action, low potential for cross-resistance with established antibacterial agents, and high in vitro potency against many bacterial pathogens

Long-Term Safety of In Utero Exposure to Anti-TNFα Drugs for the Treatment of Inflammatory Bowel Disease

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Chaparro, M; Verreth, A; Lobaton, T

2018-01-01

OBJECTIVES: The long-term safety of exposure to anti-tumor necrosis factor (anti-TNFα) drugs during pregnancy has received little attention. We aimed to compare the relative risk of severe infections in children of mothers with inflammatory bowel disease (IBD) who were exposed to anti-TNFα drugs...... in utero with that of children who were not exposed to the drugs. METHODS: Retrospective multicenter cohort study. Exposed cohort: children from mothers with IBD receiving anti-TNFα medication (with or without thiopurines) at any time during pregnancy or during the 3 months before conception. Non......-exposed cohort: children from mothers with IBD not treated with anti-TNFα agents or thiopurines at any time during pregnancy or the 3 months before conception. The cumulative incidence of severe infections after birth was estimated using Kaplan-Meier curves, which were compared using the log-rank test. Cox...

Non-local spatial frequency response of photopolymer materials containing chain transfer agents: I. Theoretical modelling

International Nuclear Information System (INIS)

Guo, Jinxin; Gleeson, Michael R; Liu, Shui; Sheridan, John T

2011-01-01

The non-local photopolymerization driven diffusion (NPDD) model predicts that a reduction in the non-local response length within a photopolymer material will improve its high spatial frequency response. The introduction of a chain transfer agent reduces the average molecular weight of polymer chains formed during free radical polymerization. Therefore a chain transfer agent (CTA) provides a practical method to reduce the non-local response length. An extended NPDD model is presented, which includes the chain transfer reaction and most major photochemical processes. The addition of a chain transfer agent into an acrylamide/polyvinyl alcohol photopolymer material is simulated and the predictions of the model are examined. The predictions of the model are experimentally examined in part II of this paper

Chlamydia trachomatis Infection and Anti-Hsp60 Immunity: The Two Sides of the Coin

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Cappello, Francesco; Conway de Macario, Everly; Di Felice, Valentina; Zummo, Giovanni; Macario, Alberto J. L.

2009-01-01

Chlamydia trachomatis (CT) infection is one of the most common causes of reproductive tract diseases and infertility. CT-Hsp60 is synthesized during infection and is released in the bloodstream. As a consequence, immune cells will produce anti-CT-Hsp60 antibodies. Hsp60, a ubiquitous and evolutionarily conserved chaperonin, is normally sequestered inside the cell, particularly into mitochondria. However, upon cell stress, as well as during carcinogenesis, the chaperonin becomes exposed on the cell surface (sf-Hsp60) and/or is secreted from cells into the extracellular space and circulation. Reports in the literature on circulating Hsp and anti-Hsp antibodies are in many cases short on details about Hsp60 concentrations, and about the specificity spectra of the antibodies, their titers, and their true, direct, pathogenetic effects. Thus, more studies are still needed to obtain a definitive picture on these matters. Nevertheless, the information already available indicates that the concurrence of persistent CT infection and appearance of sf-Hsp60 can promote an autoimmune aggression towards stressed cells and the development of diseases such as autoimmune arthritis, multiple sclerosis, atherosclerosis, vasculitis, diabetes, and thyroiditis, among others. At the same time, immunocomplexes composed of anti-CT-Hsp60 antibodies and circulating Hsp60 (both CT and human) may form deposits in several anatomical locations, e.g., at the glomerular basal membrane. The opposite side of the coin is that pre-tumor and tumor cells with sf-Hsp60 can be destroyed with participation of the anti-Hsp60 antibody, thus stopping cancer progression before it is even noticed by the patient or physician. PMID:19714222

Chlamydia trachomatis infection and anti-Hsp60 immunity: the two sides of the coin.

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Francesco Cappello

2009-08-01

Full Text Available Chlamydia trachomatis (CT infection is one of the most common causes of reproductive tract diseases and infertility. CT-Hsp60 is synthesized during infection and is released in the bloodstream. As a consequence, immune cells will produce anti-CT-Hsp60 antibodies. Hsp60, a ubiquitous and evolutionarily conserved chaperonin, is normally sequestered inside the cell, particularly into mitochondria. However, upon cell stress, as well as during carcinogenesis, the chaperonin becomes exposed on the cell surface (sf-Hsp60 and/or is secreted from cells into the extracellular space and circulation. Reports in the literature on circulating Hsp and anti-Hsp antibodies are in many cases short on details about Hsp60 concentrations, and about the specificity spectra of the antibodies, their titers, and their true, direct, pathogenetic effects. Thus, more studies are still needed to obtain a definitive picture on these matters. Nevertheless, the information already available indicates that the concurrence of persistent CT infection and appearance of sf-Hsp60 can promote an autoimmune aggression towards stressed cells and the development of diseases such as autoimmune arthritis, multiple sclerosis, atherosclerosis, vasculitis, diabetes, and thyroiditis, among others. At the same time, immunocomplexes composed of anti-CT-Hsp60 antibodies and circulating Hsp60 (both CT and human may form deposits in several anatomical locations, e.g., at the glomerular basal membrane. The opposite side of the coin is that pre-tumor and tumor cells with sf-Hsp60 can be destroyed with participation of the anti-Hsp60 antibody, thus stopping cancer progression before it is even noticed by the patient or physician.

Local immune response to primary infection and re-infection by Clonorchis sinensis in FVB mice.

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Kim, Eun-Min; Yu, Hak Sun; Jin, Yan; Choi, Min-Ho; Bae, Young Mee; Hong, Sung-Tae

2017-08-01

Although Clonorchis sinensis lives in the bile duct, few studies have investigated the local immune response in the liver and bile duct. To investigate the local immune response to C. sinensis, we investigated the activation and recruitment of various immune cells and cytokine levels in the liver and bile duct lymph nodes (BLN) in FVB mice after primary infection and re-infection. Male 4-week-old FVB mice were divided into 6 experimental groups: uninfected controls, primary infection lasting 1week (PI 1w), primary infection lasting 4weeks (PI 4w), praziquantel treatment after PI 4w (Tx), re-infection lasting 1week after Tx (RI 1w), and re-infection lasting 4weeks after Tx (RI 4w). Recovery rates were 80.0% and 73.0% in PI 1w and PI 4w mice, respectively, but significantly decreased during re-infection to 26.6% in RI 1w and 13.3% in RI 4w. This result suggested that the mice were resistant to re-infection. In the liver, Kupffer cells were augmented 70-fold in PI 1w mice (Psinensis-specific IgG1 and IgG2a strongly increased in RI 1w mice. Secretion of C. sinensis-specific IgE reached a plateau at 4weeks after primary infection, and remained elevated in all infected groups. In conclusion, during infection with C. sinensis, Kupffer cells likely act as antigen-presenting cells, stimulating the Th2 cytokine production system. Copyright © 2016. Published by Elsevier B.V.

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.

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

Combination of anti-retroviral drugs and radioimmunotherapy specifically kills infected cells from HIV infected individuals

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Dina Tsukrov

2016-09-01

Full Text Available Eliminating virally infected cells is an essential component of any HIV eradication strategy. Radioimmunotherapy (RIT, a clinically established method for killing cells using radiolabeled antibodies, was recently applied to target HIV-1 gp41 antigen expressed on the surface of infect-ed cells. Since gp41 expression by infected cells is likely down-regulated in patients on an-tiretroviral therapy (ART, we evaluated the ability of RIT to kill ART-treated infected cells us-ing both in vitro models and lymphocytes isolated from HIV-infected subjects. Human peripheral blood mononuclear cells (PBMCs were infected with HIV and cultured in the presence of two clinically relevant ART combinations. Scatchard analysis of the 2556 human monoclonal anti-body to HIV gp41 binding to the infected and ART-treated cells demonstrated sufficient residual expression of gp41 on the cell surface to warrant subsequent RIT. This is the first time the quantification of gp41 post-ART is being reported. Cells were then treated with Bismuth-213-labeled 2556 antibody. conjugated to the human monoclonal antibody 2556, which binds to HIV gp41. Cell survival was quantified by Trypan blue and residual viremia by p24 ELISA. Cell surface gp41 expression was assessed by Scatchard analysis. The experiments were repeated using PBMCs isolated from blood specimens obtained from 15 HIV-infected individuals: ten on ART and five ART-naive. We found that 213Bi-2556 killed ART-treated infected PBMCs and reduced viral production to undetectable levels. ART and RIT co-treatment was more effective at reducing viral load in vitro than either therapy alone, indicating that gp41 expression under ART was sufficient to allow 213Bi-2556 to deliver cytocidal doses of radiation to infected cells. This study provides proof of concept that 213Bi-2556 may represent an innovative and effective targeting method for killing HIV-infected cells treated with ART, and supports continued development of 213Bi

The role of spatial heterogeneity in the evolution of local and global infections of viruses.

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Koich Saeki

2018-01-01

Full Text Available Viruses have two modes spread in a host body, one is to release infectious particles from infected cells (global infection and the other is to infect directly from an infected cell to an adjacent cell (local infection. Since the mode of spread affects the evolution of life history traits, such as virulence, it is important to reveal what level of global and local infection is selected. Previous studies of the evolution of global and local infection have paid little attention to its dependency on the measures of spatial configuration. Here we show the evolutionarily stable proportion of global and local infection, and how it depends on the distribution of target cells. Using an epidemic model on a regular lattice, we consider the infection dynamics by pair approximation and check the evolutionarily stable strategy. We also conduct the Monte-Carlo simulation to observe evolutionary dynamics. We show that a higher local infection is selected as target cells become clustered. Surprisingly, the selected strategy depends not only on the degree of clustering but also the abundance of target cells per se.

Cranberry juice-- a well-characterized folk-remedy against bacterial urinary tract infection.

Science.gov (United States)

Nowack, Rainer

2007-01-01

Cranberry (Vaccinium macrocarpon) is a North-American folk remedy for treating and preventing infection. Research has identified an anti-adhesive mechanism of cranberry-proanthocyanidins that inhibit docking of bacteria on tissues "in vitro". This efficacy mechanism can be traced in the patient's urine following oral intake of cranberry juice. The efficacy of cranberry juice and extracts as a prophylactic agent against recurrent urinary infections is well documented in women. The anti-adhesion effect of cranberry-proanthocyandins can also be applied for treatment of other common diseases of bacterial pathogenesis, e.g. Helicobacter pylori-associated gastritis and dental caries/periodontal disease.

Latent tuberculosis infection in individuals with human immunodeficiency virus infection: comparison of tuberculin skin test to the anti TB-IgM antibodies

International Nuclear Information System (INIS)

Alvi, S.M.; Nadimi, M.; Shokri, S.; Zamani, G.A.

2010-01-01

To determine Latent Tuberculosis Infection (LTBI) prevalence and compare TST results to the anti TB-IgM anti bodies (ATIA) for the diagnosis of LTBI in HIV infected individuals. Sixty two randomized sampled HIV infected subjects from an addict treatment center in Ahvaz southwest Iran underwent TST, using 5 TU of purified protein derivative, and measuring ATIA. Data were analyzed in SPSS (version 16, USA). Of 62 participants, 34 (54.8%) had positive result for TST, whereas 6(9.7%) had positive ATIA. Overall concordance between TST and ATIA was 45.2% (Kappa= 0.37, P = 0.32). In subjects with positive test results by either TST or ATIA, only 4.8% had positive test results by both tests. Discordant results were found in 54.8% of subjects. Positive results for both tests in subjects categorized in two groups (above and below 200 CD4-cell/mm3) had no significant difference (P>0.05). LTBI prevalence among HIV infected individuals in studied area is higher than other parts of the world. TST is a useful test for LTBI diagnosis and prefer to ATIA. Concordance between TST and ATIA is low. (author)

Immunoglobulin GM and KM allotypes and prevalence of anti-LKM1 autoantibodies in patients with hepatitis C virus infection.

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Muratori, Paolo; Sutherland, Susan E; Muratori, Luigi; Granito, Alessandro; Guidi, Marcello; Pappas, Georges; Lenzi, Marco; Bianchi, Francesco B; Pandey, Janardan P

2006-05-01

GM and KM allotypes-genetic markers of immunoglobulin (Ig) gamma and kappa chains, respectively-are associated with humoral immunity to several infection- and autoimmunity-related epitopes. We hypothesized that GM and KM allotypes contribute to the generation of autoantibodies to liver/kidney microsomal antigen 1 (LKM1) in hepatitis C virus (HCV)-infected persons. To test this hypothesis, we characterized 129 persons with persistent HCV infection for several GM and KM markers and for anti-LKM1 antibodies. The heterozygous GM 1,3,17 23 5,13,21 phenotype was significantly associated with the prevalence of anti-LKM1 antibodies (odds ratio, 5.13; P=0.002), suggesting its involvement in this autoimmune phenomenon in HCV infection.

Host-Targeting Agents to Prevent and Cure Hepatitis C Virus Infection.

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Zeisel, Mirjam B; Crouchet, Emilie; Baumert, Thomas F; Schuster, Catherine

2015-11-02

Chronic hepatitis C virus (HCV) infection is a major cause of liver cirrhosis and hepatocellular carcinoma (HCC) which are leading indications of liver transplantation (LT). To date, there is no vaccine to prevent HCV infection and LT is invariably followed by infection of the liver graft. Within the past years, direct-acting antivirals (DAAs) have had a major impact on the management of chronic hepatitis C, which has become a curable disease in the majority of DAA-treated patients. In contrast to DAAs that target viral proteins, host-targeting agents (HTAs) interfere with cellular factors involved in the viral life cycle. By acting through a complementary mechanism of action and by exhibiting a generally higher barrier to resistance, HTAs offer a prospective option to prevent and treat viral resistance. Indeed, given their complementary mechanism of action, HTAs and DAAs can act in a synergistic manner to reduce viral loads. This review summarizes the different classes of HTAs against HCV infection that are in preclinical or clinical development and highlights their potential to prevent HCV infection, e.g., following LT, and to tailor combination treatments to cure chronic HCV infection.

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

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

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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.

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.

Investigational drugs for the treatment of infections caused by multidrug-resistant Gram-negative bacteria.

Science.gov (United States)

Avery, Lindsay M; Nicolau, David P

2018-04-01

Infections caused by multidrug-resistant Gram-negative bacteria (MDR-GNB) are associated with significant mortality and costs. New drugs in development to combat these difficult-to-treat infections primarily target carbapenem-resistant Enterobacteriaceae, MDR Pseudomonas aeruginosa, and MDR Acinetobacter baumannii. Areas covered: The authors summarize in vitro and in vivo efficacy studies, as well as available clinical trial findings, for new agents in development for treatment of infection caused by MDR-GNB. Information regarding dosage regimens utilized in clinical trials and key pharmacokinetic and pharmacodynamic considerations are provided if available. A summary of recently approved agents, delafloxacin and meropenem/vaborbactam, is also included. Expert opinion: The development of multiple novel agents to fight MDR-GNB is promising to help save the lives of patients who acquire infection, and judicious use of these agents is imperative once they come to market to prevent the development of resistance. The other component paramount to this field of research is implementation of effective infection control policies and carbapenem-resistant Enterobacteriaceae (CRE) carrier screening protocols to mitigate the worldwide spread of MDR-GNB. Further investigation of anti-infective synergistic combinations will also be important, as well as support for economic research to reveal the true cost-benefit of utilization of the new agents discussed herein.

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

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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.

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...

Control of group of mobile autonomous agents via local strategies

Institute of Scientific and Technical Information of China (English)

Lixin GAO; Daizhan CHENG; Yiguang HONG

2008-01-01

This paper considers the formation control problem of multi-agent systems in a distributed fashion.Two cases of the information propagating topologies among multiple agents,characterized by graphics model,are considered.One is fixed topology.The other is switching topology which represents the limited and less reliable information exchange.The local formation control strategies established in this paper are based on a simple modification of the existing consensus control strategies.Moreover,some existing convergence conditions ale shown to be a special case of our model even in the continuous-time consensus case.Therefore.the results of this paper extend the existing results about the consensus problem.

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

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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.

Potential use of 68Ga-apo-transferrin as a PET imaging agent for detecting Staphylococcus aureus infection

International Nuclear Information System (INIS)

Kumar, Vijay; Boddeti, Dilip K.; Evans, Scott G.; Roesch, Frank; Howman-Giles, Robert

2011-01-01

Introduction: 67 Ga citrate has been extensively used to detect infection and inflammation since 1971. However, its clinical utility is compromised due to several limitations. The present project explored whether 68 Ga-apo-transferrin ( 68 Ga-TF), when prepared in vitro, is a useful agent for positron emission tomography (PET) imaging of bacterial infection. Methods: An infection was induced in male Wistar rats by injecting 5x10 5 CFU units of Staphyococcus aureus in the right thigh muscle. 68 Ga-TF was synthesized by mixing 68 GaCl 3 with apo-transferrin (TF, 2 mg) in sodium carbonate (0.1 M, pH 7.0) and incubating at 40 o C for 1 h. Animals were injected with 10-15 MBq of 68 Ga-TF containing approximately 0.2 mg TF and imaged at different time intervals using Siemens Biograph PET-CT. Results: When 68 Ga-TF were injected in the infected rats, the infection lesion was detectable within 20 min post injection. The biodistribution showed the uptake at the lesion increased with time as shown by significantly increased standard uptake values for up to 4 h post injection. There was a considerable decrease in the background activity during the same period of study, giving higher target-to-muscle ratios. Blood pool activity at 3 h post injection was insignificant. 68 GaCl 3 (when not conjugated to TF) did not localize at the infection lesion up to 120 min post injection. Conclusion: The preliminary results suggest that 68 Ga-TF is capable of detecting S. aureus infection in the rat model, within an hour after intravenous injection.

The combination of anti-HBc and anti-HBs levels is a useful predictor of the development of chemotherapy-induced reactivation in lymphoma patients with resolved HBV infection

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Matsubara, Tokuhiro; Nishida, Tsutomu; Shimoda, Akiyoshi; Shimakoshi, Hiromi; Amano, Takahiro; Sugimoto, Aya; Takahashi, Kei; Mukai, Kaori; Yamamoto, Masashi; Hayashi, Shiro; Nakajima, Sachiko; Fukui, Koji; Inada, Masami

2017-01-01

Fatal chemotherapy-induced hepatitis B virus reactivation (HBV-R) is a well-described serious complication observed in patients with lymphoma and resolved HBV infection. The aim of the present study was to determine the predictive factors of the development of chemotherapy-induced HBV-R. A total of 77 consecutive newly diagnosed patients with lymphoma and resolved HBV infection, who received chemotherapy from 2007 through 2015 were analysed retrospectively. Significant predictive factors associated with HBV-R were identified based on the data from these patients. Ten patients developed HBV-R during and following chemotherapy, and two of these 10 patients developed HBV-associated hepatitis flares. There was a significant negative correlation between anti-hepatitis B core (HBc) titres prior to chemotherapy and time to HBV-R (P=0.016, R=−0.732). Univariate and multivariate logistic regression analyses demonstrated that anti-HBc and anti-hepatitis B surface (HBs) titres at baseline were significant predictive factors for HBV-R. In addition, patients with high anti-HBc titres at baseline (above 10 S/CO) were significantly more likely to experience HBV-R than patients with low anti-HBc and high anti-HBs titres (above 28 mIU/ml), who did not experience complete reactivation (PHBV-R than those with high anti-HBs titres (P=0.031). All HBV-R episodes among the patients with high anti-HBc titres occurred within 3 months following the initiation of chemotherapy. The combination of anti-HBc and anti-HBs titres, as opposed to either titre alone, at baseline in patients with lymphoma may serve as a surrogate marker for the occurrence of HBV-R under the influence of chemotherapy. PMID:29151907

Anti-infective properties of the melanin-glucan complex obtained from medicinal tinder bracket mushroom, Fomes fomentarius (L.: Fr.) Fr. (Aphyllophoromycetideae).

Science.gov (United States)

Seniuk, Olga F; Gorovoj, Leontiy F; Beketova, Galina V; Savichuk, Hatalia O; Rytik, Petr G; Kucherov, Igor I; Prilutskay, Alla B; Prilutsky, Alexandr I

2011-01-01

The goal of this investigation was to comparatively study the efficiency of traditionally used anti-infective drugs and biopolymer complexes originated from the medicinal mushroom Fomes fomentarius (L.:Fr.) Fr.: 1) water-soluble melanin-glucan complex (MGC; -80% melanins and -20% beta-glucans) and 2) insoluble chitin-glucan-melanin complex (ChGMC; -70% chitin, -20% beta-glucans, and -10% melanins). Infectious materials (Helicobacter pylori, Candida albicans, and Herpes vulgaris I and HIV-1(zmb) were used in pure cultures of in vitro and in vivo models on experimental animals. Comparison studies of fungal biopolymers and effective modern antifungal, antibacterial, and antiviral drugs were used in in vitro models. The comparative clinical efficiency of ChGMC and of etiotropic pharmaceuticals in models of H. pylori, C. albicans, and H. vulgaris I infection contamination were studied. Using in vitro models, it was established that MGC completely depresses growth of C. albicans. MGC had an antimicrobial effect on H. pylori identical to erythromycin in all concentrations, and had a stronger action on this bacterium than other tested antibiotics. Tested MGC possesses simultaneously weak toxicity and high anti-HIV-1 activity in comparison with zidovudine (Retrovir). The obtained results show that CLUDDT therapy in Wistar rats with the application of ChGMC is, on average, 1.35-1.43 times as effective as a traditional one. Considering the absence of MGC and ChGMC toxic properties on blood cells even in very high concentrations, these complexes may be used as a source of biopolymers for the creation of essentially new agents for wide application in infectious pathology.

High-throughput screening for novel anti-infectives using a C. elegans pathogenesis model.

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Conery, Annie L; Larkins-Ford, Jonah; Ausubel, Frederick M; Kirienko, Natalia V

2014-03-14

In recent history, the nematode Caenorhabditis elegans has provided a compelling platform for the discovery of novel antimicrobial drugs. In this protocol, we present an automated, high-throughput C. elegans pathogenesis assay, which can be used to screen for anti-infective compounds that prevent nematodes from dying due to Pseudomonas aeruginosa. New antibiotics identified from such screens would be promising candidates for treatment of human infections, and also can be used as probe compounds to identify novel targets in microbial pathogenesis or host immunity. Copyright © 2014 John Wiley & Sons, Inc.

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

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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.

Pathogenesis and treatment modalities of localized scleroderma.

Science.gov (United States)

Valančienė, Greta; Jasaitienė, Daiva; Valiukevičienė, Skaidra

2010-01-01

Localized scleroderma is a chronic inflammatory disease primarily of the dermis and subcutaneous fat that ultimately leads to a scar-like sclerosis of connective tissue. The disorder manifests as various plaques of different shape and size with signs of skin inflammation, sclerosis, and atrophy. This is a relatively rare inflammatory disease characterized by a chronic course, unknown etiology, and insufficiently clear pathogenesis. Many factors may influence its appearance: trauma, genetic factors, disorders of the immune system or hormone metabolism, viral infections, toxic substances or pharmaceutical agents, neurogenic factors, and Borrelia burgdorferi infection. Various therapeutic modalities are being used for the treatment of localized scleroderma. There is no precise treatment scheme for this disease. A majority of patients can be successfully treated with topical pharmaceutical agents and phototherapy, but some of them with progressive, disseminated, and causing disability localized scleroderma are in need of systemic treatment. The aim of this article is not only to dispute about the clinical and morphological characteristics of localized scleroderma, but also to present the newest generalized data about the possible origin, pathogenesis, and treatment modalities of this disease.

Current management of severe dengue infection.

Science.gov (United States)

Lee, Tau Hong; Lee, Linda Kay; Lye, David Chien; Leo, Yee Sin

2017-01-01

Traditionally a disease mainly affecting the pediatric population, dengue burden has increased significantly in recent decades and adults with severe disease may become more common. There is currently no effective anti-viral agent available for the treatment of dengue and supportive care is the mainstay of management. Areas covered: We present a review of current literature on dengue severity classification systems and the management of severe dengue in adults. In particular, emphasis was placed on organ impairment in dengue and management of elderly individuals with multiple medical problems. Expert commentary: There is an urgent need to search for an effective anti-viral agent to treat infected individuals. The commercial availability of a dengue vaccine in older children has provided optimism in reducing the disease burden but long term efficacy and safety are unknown. The results from phase III trials of two new candidate vaccines are eagerly awaited.

In Vivo, In Vitro, and In Silico Characterization of Peptoids as Antimicrobial Agents

DEFF Research Database (Denmark)

Czyzewski, Ann M.; Jenssen, Håvard; Fjell, Christopher D.

2016-01-01

report a new QSAR model that we developed based on 27 diverse peptoid sequences, which accurately correlates antimicrobial peptoid structure with antimicrobial activity. We have identified a number of peptoids that have potent, broad-spectrum in vitro activity against multi-drug resistant bacterial......Bacterial resistance to conventional antibiotics is a global threat that has spurred the development of antimicrobial peptides (AMPs) and their mimetics as novel anti-infective agents. While the bioavailability of AMPs is often reduced due to protease activity, the non-natural structure of AMP...... potential of peptoids as antimicrobial agents....

A peptide from human β thymosin as a platform for the development of new anti-biofilm agents for Staphylococcus spp. and Pseudomonas aeruginosa.

Science.gov (United States)

Schillaci, Domenico; Spinello, Angelo; Cusimano, Maria Grazia; Cascioferro, Stella; Barone, Giampaolo; Vitale, Maria; Arizza, Vincenzo

2016-08-01

Conventional antibiotics might fail in the treatment of biofilm-associated infections causing infection recurrence and chronicity. The search for antimicrobial peptides has been performed with the aim to discover novel anti-infective agents active on pathogens in both planktonic and biofilm associated forms. The fragment 9-19 of human thymosin β4 was studied through 1 μs MD simulation. Two main conformations of the peptide were detected, both constituted by a central hydrophobic core and by the presence of peripheral charged residues suggesting a possible mechanism of interaction with two models of biological membranes, related to eukaryotic or bacterial membrane respectively. In addition, the peptide was chemically synthesized and its antimicrobial activity was tested in vitro against planktonic and biofilm form of a group of reference strains of Staphylococcus spp. and one P. aeruginosa strain. The human thymosin β4 fragment EIEKFDKSKLK showed antibacterial activity against staphylococcal strains and Pseudomonas aeruginosa ATCC 15442 at concentrations from 12.5 to 6.2 mg/ml and inhibited biofilm formation at sub-inhibitory concentrations (3.1-0.75 mg/ml). The activity of the fragment in inhibiting biofilm formation, could be due to the conformations highlighted by the MD simulations, suggesting its interaction with the bacterial membrane. Human thymosin β4 fragment can be considered a promising lead compound to develop novel synthetic or recombinant derivatives with improved pharmaceutical potential.

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.

Modulation of Quorum Sensing in a Gram-Positive Pathogen by Linear Molecularly Imprinted Polymers with Anti-infective Properties.

Science.gov (United States)

Motib, Anfal; Guerreiro, Antonio; Al-Bayati, Firas; Piletska, Elena; Manzoor, Irfan; Shafeeq, Sulman; Kadam, Anagha; Kuipers, Oscar; Hiller, Luisa; Cowen, Todd; Piletsky, Sergey; Andrew, Peter W; Yesilkaya, Hasan

2017-12-22

We describe the development, characterization, and biological testing of a new type of linear molecularly imprinted polymer (LMIP) designed to act as an anti-infective by blocking the quorum sensing (QS) mechanism and so abrogating the virulence of the pathogen Streptococcus pneumoniae. The LMIP is prepared (polymerized) in presence of a template molecule, but unlike in traditional molecular imprinting approaches, no cross-linker is used. This results in soluble low-molecular-weight oligomers that can act as a therapeutic agent in vitro and in vivo. The LMIP was characterized by mass spectrometry to determine its monomer composition. Fragments identified were then aligned along the peptide template by computer modeling to predict the possible monomer sequence of the LMIP. These findings provide a proof of principle that LMIPs can be used to block QS, thus setting the stage for the development of LMIPs a novel drug-discovery platform and class of materials to target Gram-positive pathogens. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

In vitro anti-bacterial and anti-adherence effects of Lactobacillus delbrueckii subsp bulgaricus on Escherichia coli.

Science.gov (United States)

Abedi, D; Feizizadeh, S; Akbari, V; Jafarian-Dehkordi, A

2013-10-01

Considering the emergence of antibiotic resistance, scientists are interested in using new antimicrobial agents in the treatment of infectious diseases including infections of the enteric systems. Lactic acid bacteria have the great potential to produce antimicrobial compounds that inhibit and control pathogenic bacteria. The aim of this study was to determine the anti-bacterial and anti-adherence properties of Lactobacillus delbrueckii subsp bulgaricus against Escherichia coli. The antibacterial activity of L. delbrueckii was investigated using disc diffusion and spot on lawn methods. In vitro anti-adhesion effect of L. delbrueckii against E. coli was examined using Caco-2 cells. In anti-adhesion assay, three competition conditions including competitive inhibition, adhesion inhibition, and displacement were examined. In spot on lawn method the zone of growth inhibition of E. coli by L. delbrueckii was 21.1 mm. The cell free supernatant of L. delbrueckii showed a good antibacterial activity against E. coli which was mainly related to lactic acid produced by L. delbrueckii. When two bacteria added simultaneously (competitive inhibition) degree of inhibition of E. coli binding by L. delbrueckii was 77%. In adhesion inhibition assay, L. delbrueckii was able to exclude E. coli adherence by around 43.5%. Displacement assay showed that L. delbrueckii had strong displacement ability toward E. coli and reduction of E. coli attachment by bound L. delbrueckii was 81.3%. The results suggest that L. delbrueckii may be able to inhibit E. coli infection in the gut; however more studies including in vivo studies need to be performed.

Use of antibiotics in the management of postirradiation wound infection and sepsis

Energy Technology Data Exchange (ETDEWEB)

Brook, I.

1988-07-01

Ionizing gamma irradiation depresses the host defenses and enhances the susceptibility of the immunocompromised host to local and systemic infection due to endogenous or exogenous microorganisms. Trauma and wounding act synergistically and decrease the survival after exposure to irradiation. The current antimicrobial agents suitable for controlling serious infections and their use in post irradiation local and systemic infection with and without trauma are discussed. The experience gained in managing immunocompromised patients following chemotherapy is reviewed. Empiric single agent or combination agent therapy should be directed at the eradication of potential gram-negative as well as gram-positive pathogens. The most important organisms known to cause these infections are Pseudomonas sp. and Enterobacteriaceae. Management of intra-abdominal infections following trauma should include early surgical correlation and antimicrobials directed against the Bacteroides fragilis group and Enterobacteriaceae. Staphylococcus aureus and Streptococcus pyogenes cause most skin and soft tissue infections following trauma. Chemoprophylaxis of enteric sources of systemic infection can be achieved by antimicrobials that selectively inhibit the Enterobacteriaceae sp. and preserve the anaerobic flora. The management of infection in the injured and irradiated host includes supportive and restorative therapy. Supportive therapy includes debridement and cleansing of wounds, fluids, immunoglobulin, and antimicrobials. Restorative therapy includes definite surgery repair and replenishment of the immune system by use of immunomodulators, growth factors, and bone marrow transplantation. Further studies are needed to examine the usefulness of presently available drugs and experimental agents in the irradiated and traumatized host. 111 references.

Use of antibiotics in the management of postirradiation wound infection and sepsis

International Nuclear Information System (INIS)

Brook, I.

1988-01-01

Ionizing gamma irradiation depresses the host defenses and enhances the susceptibility of the immunocompromised host to local and systemic infection due to endogenous or exogenous microorganisms. Trauma and wounding act synergistically and decrease the survival after exposure to irradiation. The current antimicrobial agents suitable for controlling serious infections and their use in post irradiation local and systemic infection with and without trauma are discussed. The experience gained in managing immunocompromised patients following chemotherapy is reviewed. Empiric single agent or combination agent therapy should be directed at the eradication of potential gram-negative as well as gram-positive pathogens. The most important organisms known to cause these infections are Pseudomonas sp. and Enterobacteriaceae. Management of intra-abdominal infections following trauma should include early surgical correlation and antimicrobials directed against the Bacteroides fragilis group and Enterobacteriaceae. Staphylococcus aureus and Streptococcus pyogenes cause most skin and soft tissue infections following trauma. Chemoprophylaxis of enteric sources of systemic infection can be achieved by antimicrobials that selectively inhibit the Enterobacteriaceae sp. and preserve the anaerobic flora. The management of infection in the injured and irradiated host includes supportive and restorative therapy. Supportive therapy includes debridement and cleansing of wounds, fluids, immunoglobulin, and antimicrobials. Restorative therapy includes definite surgery repair and replenishment of the immune system by use of immunomodulators, growth factors, and bone marrow transplantation. Further studies are needed to examine the usefulness of presently available drugs and experimental agents in the irradiated and traumatized host. 111 references

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

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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

In-silico screening for anti-Zika virus phytochemicals.

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Byler, Kendall G; Ogungbe, Ifedayo Victor; Setzer, William N

2016-09-01

Zika virus (ZIKV) is an arbovirus that has infected hundreds of thousands of people and is a rapidly expanding epidemic across Central and South America. ZIKV infection has caused serious, albeit rare, complications including Guillain-Barré syndrome and congenital microcephaly. There are currently no vaccines or antiviral agents to treat or prevent ZIKV infection, but there are several ZIKV non-structural proteins that may serve as promising antiviral drug targets. In this work, we have carried out an in-silico search for potential anti-Zika viral agents from natural sources. We have generated ZIKV protease, methyltransferase, and RNA-dependent RNA polymerase using homology modeling techniques and we have carried out molecular docking analyses of our in-house virtual library of phytochemicals with these protein targets as well as with ZIKV helicase. Overall, 2263 plant-derived secondary metabolites have been docked. Of these, 43 compounds that have drug-like properties have exhibited remarkable docking profiles to one or more of the ZIKV protein targets, and several of these are found in relatively common herbal medicines, suggesting promise for natural and inexpensive antiviral therapy for this emerging tropical disease. Copyright © 2016 Elsevier Inc. All rights reserved.

Anti-Rhodotorula activity of mycophenolic acid enhanced in the presence of polyene antibiotic nystatin.

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Kinoshita, H; Wongsuntornpoj, S; Ihara, F; Nihira, T

2017-02-01

Rhodotorula species are opportunistic pathogens, which cause not only systemic fungaemia but also other localized infections. Despite serious side effects such as nephrotoxicity and hypokalemia, amphotericin B (a polyene antifungal) has been commonly prescribed for Rhodotorula infection because Rhodotorula species are resistant against a candin family of antifungal agents. In this study, novel active compounds against Rhodotorula species were screened from the extracts of entomopathogenic fungi based on the synergistic effect of polyene nystatin (NYS), which causes efficient targeting of compounds due to increased permeability through the fungal cell membrane. Around 37% of culture extracts from 31 entomopathogenic fungal strains showed anti-Rhodotorula activity in the synergistic bioassay system, suggesting that the coexistence assay with NYS enhanced the discovery of anti-Rhodotorula compounds. Judging from various physicochemical data, the active component from strain HF763 was identified as an immunosuppressant drug, mycophenolic acid (MPA). The minimum inhibitory concentration of MPA against three pathogenic Rhodotorula strains was determined, focusing on the synergistic effect with NYS. The results revealed that the values decreased by at least 87% in the presence of NYS, indicating that MPA showed a synergistic effect with NYS. This study aimed to screen active compounds against Rhodotorula species that are resistant to a candin family of antifungal agents, from entomopathogenic fungi. Assuming that most of the latent antifungal compounds do not exert their activity due to their inability to penetrate the membrane, we took advantage of polyene nystatin in the screening to increase permeability through the fungal cell membrane. The result of the screening revealed hidden antifungal activity of mycophenolic acid, demonstrating that the method applied in this study unlocks the potentials of bioresources, and proposes a new remedy for mycosis. © 2016 The

In vitro studies on the relationship between the anti-inflammatory activity of Physalis peruviana extracts and the phagocytic process.

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Martínez, Willington; Ospina, Luis Fernando; Granados, Diana; Delgado, Gabriela

2010-03-01

The study of plants used in traditional medicine has drawn the attention of researchers as an alternative in the development of new therapeutics agents, such as the American Solanaceae Physalis peruviana, which has significant anti-inflammatory activity. The Physalis peruviana anti-inflammatory effect of ethanol or ether calyces extracts on the phagocytic process was assessed by using an in vitro phagocytosis model (Leishmania panamensis infection to murine macrophages). The Physalis peruviana extracts do not inhibit microorganism internalization and have no parasiticide effect. Most ET and EP extracts negatively affected the parasite's invasion of macrophages (Infected cells increased.). This observation might result from a down-regulation of the macrophage's microbicide ability associated with a selective reduction of proinflammatory cytokines levels. Physalis peruviana's anti-inflammatory activity described in this model is related to an immunomodulatory effect exerted on macrophages infected, which directly or indirectly "blocks" their ability to secrete soluble proinflammatory mediators.

Differences in reactivation of tuberculosis induced from anti-TNF treatments are based on bioavailability in granulomatous tissue.

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Simeone Marino

2007-10-01

Full Text Available The immune response to Mycobacterium tuberculosis (Mtb infection is complex. Experimental evidence has revealed that tumor necrosis factor (TNF plays a major role in host defense against Mtb in both active and latent phases of infection. TNF-neutralizing drugs used to treat inflammatory disorders have been reported to increase the risk of tuberculosis (TB, in accordance with animal studies. The present study takes a computational approach toward characterizing the role of TNF in protection against the tubercle bacillus in both active and latent infection. We extend our previous mathematical models to investigate the roles and production of soluble (sTNF and transmembrane TNF (tmTNF. We analyze effects of anti-TNF therapy in virtual clinical trials (VCTs by simulating two of the most commonly used therapies, anti-TNF antibody and TNF receptor fusion, predicting mechanisms that explain observed differences in TB reactivation rates. The major findings from this study are that bioavailability of TNF following anti-TNF therapy is the primary factor for causing reactivation of latent infection and that sTNF--even at very low levels--is essential for control of infection. Using a mathematical model, it is possible to distinguish mechanisms of action of the anti-TNF treatments and gain insights into the role of TNF in TB control and pathology. Our study suggests that a TNF-modulating agent could be developed that could balance the requirement for reduction of inflammation with the necessity to maintain resistance to infection and microbial diseases. Alternatively, the dose and timing of anti-TNF therapy could be modified. Anti-TNF therapy will likely lead to numerous incidents of primary TB if used in areas where exposure is likely.

Local infection of opium poppy leaves by Peronospora somniferi sporangia can give rise to systemic infections and seed infection in resistant cultivars

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Montes-Borrego, M.; Muñoz-Ledesma, F.J.; Jiménez-Díaz, R.M.; Landa, B.B.

2017-07-01

Downy mildew (DM) of opium poppy (Papaver somniferum) caused by Peronospora somniferi is one of the most destructive diseases of this crop due to the systemic nature of infection as compared with local infections caused by Peronospora meconopsidis, the other downy mildew pathogen of this crop. We developed an inoculation method using Peronospora somniferi sporangia as inoculum and demonstrated for the first time that local infection of leaves by sporangia give rise to systemic infections in the plant as well as of seeds. Our results also showed that this inoculation protocol was very effective in reproducing disease symptoms and assessing the resistance response to DM in opium poppy genotypes under field conditions. More interestingly, results indicate that up to 100% of seed samples from some genotypes showing a complete (symptomless) resistant phenotype were infected by the pathogen when seeds were analyzed by a P. somniferi-specific nested-PCR protocol. This latter aspect deserves further attention while breeding opium poppy for resistance to P. somniferi.

Local infection of opium poppy leaves by Peronospora somniferi sporangia can give rise to systemic infections and seed infection in resistant cultivars

International Nuclear Information System (INIS)

Montes-Borrego, M.; Muñoz-Ledesma, F.J.; Jiménez-Díaz, R.M.; Landa, B.B.

2017-01-01

Downy mildew (DM) of opium poppy (Papaver somniferum) caused by Peronospora somniferi is one of the most destructive diseases of this crop due to the systemic nature of infection as compared with local infections caused by Peronospora meconopsidis, the other downy mildew pathogen of this crop. We developed an inoculation method using Peronospora somniferi sporangia as inoculum and demonstrated for the first time that local infection of leaves by sporangia give rise to systemic infections in the plant as well as of seeds. Our results also showed that this inoculation protocol was very effective in reproducing disease symptoms and assessing the resistance response to DM in opium poppy genotypes under field conditions. More interestingly, results indicate that up to 100% of seed samples from some genotypes showing a complete (symptomless) resistant phenotype were infected by the pathogen when seeds were analyzed by a P. somniferi-specific nested-PCR protocol. This latter aspect deserves further attention while breeding opium poppy for resistance to P. somniferi.

An agent-based simulation model for Clostridium difficile infection control.

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Codella, James; Safdar, Nasia; Heffernan, Rick; Alagoz, Oguzhan

2015-02-01

Control of Clostridium difficile infection (CDI) is an increasingly difficult problem for health care institutions. There are commonly recommended strategies to combat CDI transmission, such as oral vancomycin for CDI treatment, increased hand hygiene with soap and water for health care workers, daily environmental disinfection of infected patient rooms, and contact isolation of diseased patients. However, the efficacy of these strategies, particularly for endemic CDI, has not been well studied. The objective of this research is to develop a valid, agent-based simulation model (ABM) to study C. difficile transmission and control in a midsized hospital. We develop an ABM of a midsized hospital with agents such as patients, health care workers, and visitors. We model the natural progression of CDI in a patient using a Markov chain and the transmission of CDI through agent and environmental interactions. We derive input parameters from aggregate patient data from the 2007-2010 Wisconsin Hospital Association and published medical literature. We define a calibration process, which we use to estimate transition probabilities of the Markov model by comparing simulation results to benchmark values found in published literature. In a comparison of CDI control strategies implemented individually, routine bleach disinfection of CDI-positive patient rooms provides the largest reduction in nosocomial asymptomatic colonization (21.8%) and nosocomial CDIs (42.8%). Additionally, vancomycin treatment provides the largest reduction in relapse CDIs (41.9%), CDI-related mortalities (68.5%), and total patient length of stay (21.6%). We develop a generalized ABM for CDI control that can be customized and further expanded to specific institutions and/or scenarios. Additionally, we estimate transition probabilities for a Markov model of natural CDI progression in a patient through calibration. © The Author(s) 2014.

Current and Emerging Topical Antibacterials and Antiseptics: Agents, Action, and Resistance Patterns.

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Williamson, Deborah A; Carter, Glen P; Howden, Benjamin P

2017-07-01

Bacterial skin infections represent some of the most common infectious diseases globally. Prevention and treatment of skin infections can involve application of a topical antimicrobial, which may be an antibiotic (such as mupirocin or fusidic acid) or an antiseptic (such as chlorhexidine or alcohol). However, there is limited evidence to support the widespread prophylactic or therapeutic use of topical agents. Challenges involved in the use of topical antimicrobials include increasing rates of bacterial resistance, local hypersensitivity reactions (particularly to older agents, such as bacitracin), and concerns about the indiscriminate use of antiseptics potentially coselecting for antibiotic resistance. We review the evidence for the major clinical uses of topical antibiotics and antiseptics. In addition, we review the mechanisms of action of common topical agents and define the clinical and molecular epidemiology of antimicrobial resistance in these agents. Moreover, we review the potential use of newer and emerging agents, such as retapamulin and ebselen, and discuss the role of antiseptic agents in preventing bacterial skin infections. A comprehensive understanding of the clinical efficacy and drivers of resistance to topical agents will inform the optimal use of these agents to preserve their activity in the future. Copyright © 2017 American Society for Microbiology.

Predictive model of urinary tract infection after surgical treatment for women with endometrial cancer.

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Machida, Hiroko; Hom, Marianne S; Shabalova, Anastasiya; Grubbs, Brendan H; Matsuo, Koji

2017-08-01

The aim of the study was to identify risk factors associated with postoperative urinary tract infections (UTIs) following hysterectomy-based surgical staging in women with endometrial cancer. This is a retrospective study utilizing an institutional database (2008-2016) of stage I-IV endometrial cancer cases that underwent hysterectomy-based surgery. UTIs occurring within a 30-day time period after surgery were examined and correlated to patient clinico-pathological demographics. UTIs were observed in 44 (6.4%, 95% confidence interval 4.6-8.2) out of 687 cases subsequent to the diagnosis of endometrial cancer. UTI cases were significantly associated with obesity, advanced stage, prolonged operative time, hysterectomy type, pelvic lymphadenectomy, non-β-lactam antibiotics, and intraoperative urinary tract injury (all, p Urinary tract infections are common in women following surgical treatment for women with endometrial cancer with risk factors being a prolonged surgical time, radical hysterectomy, and non-guideline perioperative anti-microbial agent use. Consideration of prophylactic anti-microbial agent use in a high-risk group of postoperative urinary tract infection merits further investigation.

A review of the biomaterials technologies for infection-resistant surfaces.

Science.gov (United States)

Campoccia, Davide; Montanaro, Lucio; Arciola, Carla Renata

2013-11-01

Anti-infective biomaterials need to be tailored according to the specific clinical application. All their properties have to be tuned to achieve the best anti-infective performance together with safe biocompatibility and appropriate tissue interactions. Innovative technologies are developing new biomaterials and surfaces endowed with anti-infective properties, relying either on antifouling, or bactericidal, or antibiofilm activities. This review aims at thoroughly surveying the numerous classes of antibacterial biomaterials and the underlying strategies behind them. Bacteria repelling and antiadhesive surfaces, materials with intrinsic antibacterial properties, antibacterial coatings, nanostructured materials, and molecules interfering with bacterial biofilm are considered. Among the new strategies, the use of phages or of antisense peptide nucleic acids are discussed, as well as the possibility to modulate the local immune response by active cytokines. Overall, there is a wealth of technical solutions to contrast the establishment of an implant infection. Many of them exhibit a great potential in preclinical models. The lack of well-structured prospective multicenter clinical trials hinders the achievement of conclusive data on the efficacy and comparative performance of anti-infective biomaterials. © 2013 Elsevier Ltd. All rights reserved.

Infections and vasculitis.

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Thomas, Konstantinos; Vassilopoulos, Dimitrios

2017-01-01

To review recent evidence for infection rates in patients with systemic vasculitides, the role of specific infectious agents in the pathogenesis of vasculitis and recent breakthroughs in the treatment of virus-associated vasculitides. In well designed recent studies, infections were found to be common during the first 6-12 months in patients with anti-neutrophil cytoplasmic antibodies (ANCA)-associated vasculitides (AAV) and giant cell arteritis (GCA) and to contribute significantly to increased mortality during this period. New therapeutic schemes with lower cyclophosphamide doses and shorter corticosteroid courses were associated with decreased infectious rates in elderly patients with AAV whereas a prednisone dose greater than 10 mg/day at the end of the first year were associated with increased infectious-related mortality in patients with GCA. Recently, a potential role for varicella zoster virus in GCA pathogenesis has been proposed but more data are needed in order to establish a causal relationship. Finally, preliminary data show excellent short-term efficacy and safety of the new, interferon-free, oral antiviral agents in the treatment of hepatitis C virus-associated cryoglobulinemic vasculitis. Infections continue to be one of the main causes of mortality in patients with systemic vasculitides, emphasizing the need for safer immunosuppressive therapies and appropriate prophylaxis.

In vivo mitochondrial function in HIV-infected persons treated with contemporary anti-retroviral therapy: a magnetic resonance spectroscopy study.

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Brendan A I Payne

Full Text Available Modern anti-retroviral therapy is highly effective at suppressing viral replication and restoring immune function in HIV-infected persons. However, such individuals show reduced physiological performance and increased frailty compared with age-matched uninfected persons. Contemporary anti-retroviral therapy is thought to be largely free from neuromuscular complications, whereas several anti-retroviral drugs previously in common usage have been associated with mitochondrial toxicity. It has recently been established that patients with prior exposure to such drugs exhibit irreversible cellular and molecular mitochondrial defects. However the functional significance of such damage remains unknown. Here we use phosphorus magnetic resonance spectroscopy ((31P-MRS to measure in vivo muscle mitochondrial oxidative function, in patients treated with contemporary anti-retroviral therapy, and compare with biopsy findings (cytochrome c oxidase (COX histochemistry. We show that dynamic oxidative function (post-exertional ATP (adenosine triphosphate resynthesis was largely maintained in the face of mild to moderate COX defects (affecting up to ∼10% of fibers: τ½ ADP (half-life of adenosine diphosphate clearance, HIV-infected 22.1±9.9 s, HIV-uninfected 18.8±4.4 s, p = 0.09. In contrast, HIV-infected patients had a significant derangement of resting state ATP metabolism compared with controls: ADP/ATP ratio, HIV-infected 1.24±0.08×10(-3, HIV-uninfected 1.16±0.05×10(-3, p = 0.001. These observations are broadly reassuring in that they suggest that in vivo mitochondrial function in patients on contemporary anti-retroviral therapy is largely maintained at the whole organ level, despite histochemical (COX defects within individual cells. Basal energy requirements may nevertheless be increased.

Properties of a non-bioactive fluorescent derivative of differentiation-inducing factor-3, an anti-tumor agent found in Dictyostelium discoideum

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Yuzuru Kubohara

2014-03-01

Full Text Available Differentiation-inducing factor-3 (DIF-3, found in the cellular slime mold Dictyostelium discoideum, and its derivatives, such as butoxy-DIF-3 (Bu-DIF-3, are potent anti-tumor agents. To investigate the activity of DIF-like molecules in tumor cells, we recently synthesized a green fluorescent DIF-3 derivative, BODIPY-DIF-3G, and analyzed its bioactivity and cellular localization. In this study, we synthesized a red (orange fluorescent DIF-3 derivative, BODIPY-DIF-3R, and compared the cellular localization and bioactivities of the two BODIPY-DIF-3s in HeLa human cervical cancer cells. Both fluorescent compounds penetrated the extracellular membrane within 0.5 h and localized mainly to the mitochondria. In formalin-fixed cells, the two BODIPY-DIF-3s also localized to the mitochondria, indicating that the BODIPY-DIF-3s were incorporated into mitochondria independently of the mitochondrial membrane potential. After treatment for 3 days, BODIPY-DIF-3G, but not BODIPY-DIF-3R, induced mitochondrial swelling and suppressed cell proliferation. Interestingly, the swollen mitochondria were stainable with BODIPY-DIF-3G but not with BODIPY-DIF-3R. When added to isolated mitochondria in vitro, BODIPY-DIF-3G increased dose-dependently the rate of O2 consumption, but BODIPY-DIF-3R did not. These results suggest that the bioactive BODIPY-DIF-3G suppresses cell proliferation, at least in part, by altering mitochondrial activity, whereas the non-bioactive BODIPY-DIF-3R localizes to the mitochondria but does not affect mitochondrial activity or cell proliferation.

Potential use of rapamycin in HIV infection

DEFF Research Database (Denmark)

Donia, Marco; McCubrey, James A; Bendtzen, Klaus

2010-01-01

The strong need for the development of alternative anti-HIV agents is primarily due to the emergence of strain-resistant viruses, the need for sustained adherence to complex treatment regimens and the toxicity of currently used antiviral drugs. This review analyzes proof of concept studies......, the evidence presented in this review suggests that RAPA may be a useful drug that should be evaluated for the prevention and treatment of HIV-1 infection....... indicating that the immunomodulatory drug rapamycin (RAPA) possesses anti-HIV properties both in vitro and in vivo that qualifies it as a potential new anti-HIV drug. It represents a literature review of published studies that evaluated the in vitro and in vivo activity of RAPA in HIV. RAPA represses HIV-1...

[Cervugid ovules in cervico-vaginal infections and cervix uteri precancerous conditions treatment].

Science.gov (United States)

Zanoschi, Ch; Anton, C; Anton, E; Costăchescu, Gh; Teleman, S; Costăchescu, G; Ciupilan, I; Cărăuleanu, M; Cărăuleanu, A; Leica, V; Pânzaru, C; Grigore, M; Merticaru, I; Huianu, O; Huianu, L; Chifan, M

2004-01-01

This medicine was authorized by the National Drug Agency (ANM, Bucureşti) in 2001. To evaluate the effectiveness and the tolerance to Cervugid-ovules, a preparation that combines the polyvalent local antiinflammatory action of chloramphenicol, metronidazole and nystatin with the effect of hydrocortisone acetate, an unspecific anti-inflammatory agent; they all are embedded in a Lipex-403, semisynthetic fat. The evaluation of 500 patients ages between 15 and 85 years with genital infections, registered in the files of "Cl. II Obst. and Gynecology" of the Cuza-Vodă Hospital from Iaşi has been studied. We studied the subjective manifestations (local discomfort and pelvic pains, local burning and dryness,vulvovaginal itching and dyspareunia) and objective manifestations (vaginal and cervical secretion, the cytotest performed and colored though the Papanicolaou method and reported in the Bethesda system). Healing of the subjective symptoms in 98%, healing of the leukorrhea--as a main objective symptom--in 95%; The Bethesda system cytotest was one of the inflammatory type in the most of the cases and there wew found in 85 cases: 6 ASCUS, 41 LSIL, and 37 HSIL. The use of Cervugid had a healing response in most of the cases when used in acute and chronic cervico-vaginal inflammatory processes. Cervugid may be considered as an important agent in the treatment of the precancerous affections af the cervix uteri on the following reasons: zhe cure of the infections caused by chlamydia, involved in the etiology of cervical neoplasms, the cure of the HPV infection under episome form, classified in the Bethesda system within the ASCUS, AGUS or LSIL classes. When the cytotest was in the HSIL class, a conization in the LLETZ method was performed. Cervugid is conceived for those three main categories of pathogenic factors related to the etiology of cervico-vaginitis: microbia germs, protozoa and mycosis. In addition, it is active on chlamydia and mycoplasms, always sensitive to

Chitosan-propolis nanoparticle formulation demonstrates anti-bacterial activity against Enterococcus faecalis biofilms.

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Teik Hwa Ong

Full Text Available Propolis obtained from bee hives is a natural substance with antimicrobial properties. It is limited by its insolubility in aqueous solutions; hence ethanol and ethyl acetate extracts of Malaysian propolis were prepared. Both the extracts displayed antimicrobial and anti-biofilm properties against Enterococcus faecalis, a common bacterium associated with hospital-acquired infections. High performance liquid chromatography (HPLC analysis of propolis revealed the presence of flavonoids like kaempferol and pinocembrin. This study investigated the role of propolis developed into nanoparticles with chitosan for its antimicrobial and anti-biofilm properties against E. faecalis. Bacteria that grow in a slimy layer of biofilm are resistant to penetration by antibacterial agents. The use of nanoparticles in medicine has received attention recently due to better bioavailability, enhanced penetrative capacity and improved efficacy. A chitosan-propolis nanoformulation was chosen based on ideal physicochemical properties such as particle size, zeta potential, polydispersity index, encapsulation efficiency and the rate of release of the active ingredients. This formulation inhibited E. faecalis biofilm formation and reduced the number of bacteria in the biofilm by ~90% at 200 μg/ml concentration. When tested on pre-formed biofilms, the formulation reduced bacterial number in the biofilm by ~40% and ~75% at 200 and 300 μg/ml, respectively. The formulation not only reduced bacterial numbers, but also physically disrupted the biofilm structure as observed by scanning electron microscopy. Treatment of biofilms with chitosan-propolis nanoparticles altered the expression of biofilm-associated genes in E. faecalis. The results of this study revealed that chitosan-propolis nanoformulation can be deemed as a potential anti-biofilm agent in resisting infections involving biofilm formation like chronic wounds and surgical site infections.

Efficacy of feline anti-parvovirus antibodies in the treatment of canine parvovirus infection.

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Gerlach, M; Proksch, A L; Unterer, S; Speck, S; Truyen, U; Hartmann, K

2017-07-01

This prospective, randomised, placebo-controlled, double-blinded study aimed to evaluate efficacy of commercially available feline anti-parvovirus antibodies in dogs with canine parvovirus infection. First, cross-protection of feline panleukopenia virus antibodies against canine parvovirus was evaluated in vitro. In the subsequent prospective clinical trial, 31 dogs with clinical signs of canine parvovirus infection and a positive faecal canine parvovirus polymerase chain reaction were randomly assigned to a group receiving feline panleukopenia virus antibodies (n=15) or placebo (n=16). All dogs received additional routine treatment. Clinical signs, blood parameters, time to clinical recovery and mortality were compared between the groups. Serum antibody titres and quantitative faecal polymerase chain reaction were compared on days 0, 3, 7, and 14. In vitro, canine parvovirus was fully neutralised by feline panleukopenia virus antibodies. There were no detected significant differences in clinical signs, time to clinical recovery, blood parameters, mortality, faecal virus load, or viral shedding between groups. Dogs in the placebo group showed a significant increase of serum antibody titres and a significant decrease of faecal virus load between day 14 and day 0, which was not detectable in dogs treated with feline panleukopenia virus antibodies. No significant beneficial effect of passively transferred feline anti-parvovirus antibodies in the used dosage regimen on the treatment of canine parvovirus infection was demonstrated. © 2017 British Small Animal Veterinary Association.

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

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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.

Potential use of rapamycin in HIV infection

DEFF Research Database (Denmark)

Donia, Marco; McCubrey, James A; Bendtzen, Klaus

2010-01-01

The strong need for the development of alternative anti-HIV agents is primarily due to the emergence of strain-resistant viruses, the need for sustained adherence to complex treatment regimens and the toxicity of currently used antiviral drugs. This review analyzes proof of concept studies...... indicating that the immunomodulatory drug rapamycin (RAPA) possesses anti-HIV properties both in vitro and in vivo that qualifies it as a potential new anti-HIV drug. It represents a literature review of published studies that evaluated the in vitro and in vivo activity of RAPA in HIV. RAPA represses HIV-1...... replication in vitro through different mechanisms including, but not limited, to down regulation of CCR5. In addition RAPA synergistically enhances the anti-HIV activity of entry inhibitors such as vicriviroc, aplaviroc and enfuvirtide in vitro. RAPA also inhibits HIV-1 infection in human peripheral blood...

Anti-acne activity of Italian medicinal plants used for skin infection

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Kate Nelson

2016-11-01

Full Text Available Propionibacterium acnes is implicated in the pathogenesis of acne vulgaris, which impacts >85% of teenagers. Novel therapies are in high demand and an ethnopharmacological approach to discovering new plant sources of anti-acne therapeutics could contribute to filling this void in effective therapies. The aims of our study were two-fold: 1 To determine if species identified in ethnopharmacological field studies as having traditional uses for skin and soft tissue infection (SSTI exhibit significantly more activity against P. acnes than species with no such reported use; and 2 Chemically characterize active extracts and assess their suitability for future investigation. Extracts of Italian medicinal (for acne and other skin infection and randomly collected plants and fungi were screened for growth-inhibitory and anti-biofilm activity in P. acnes using broth microdilution methods. Bioactive extracts were chemically characterized by HPLC and examined for cytotoxicity against human keratinocytes (HaCaTs. Following evaluation of 157 extracts from 10 fungi and 58 plants, we identified crude extracts from seven species exhibiting growth inhibitory activity (MICs 64-256 µg mL-1. All active extracts were examined for cytotoxicity against HaCaTs; extracts from one fungal and one plant species were toxic (IC50 256 µg mL-1. HPLC analysis with chemical standards revealed many of these extracts contained chlorogenic acid, p-coumaric acid, ellagic acid, gallic acid and tannic acid. In conclusion, species used in traditional medicine for the skin exhibited significantly greater (p<0.05 growth inhibitory and biofilm eradication activity than random species, supporting the validity of an ethnobotanical approach to identifying new therapeutics. The anti-acne activity of three extracts is reported for the first time: Vitis vinifera leaves, Asphodelus microcarpus leaves and Vicia sativa aerial parts.

Localized cowpox infection in a 5-month-old Rottweiler.

Science.gov (United States)

von Bomhard, Wolf; Mauldin, Elizabeth A; Breuer, Wolfram; Pfleghaar, Stephan; Nitsche, Andreas

2011-02-01

Cowpox virus (CPXV) infections are a sporadic cause of localized or disseminated skin disease in domestic animals and humans in Europe. Rodents are considered the primary reservoir host for CPXV. Cats can become infected by close contact with rodents and are the most important source of human infections. Recently, public awareness has also been drawn to CPXV infections by an outbreak of rat to human infections in central Europe. In dogs, CPXV infections are rare. Here we report a case of a 5-month-old Rottweiler with a focal nodule on the muzzle. The lesion was fully excised, and recovery was uneventful. The preliminary diagnosis of a CPXV infection was established by the characteristic inclusion bodies on histopathological examination. The diagnosis was confirmed by electron microscopy and polymerase chain reaction (PCR). Sequencing of the PCR product led to a 231 bp sequence of the orthopoxvirus HA gene that was identical to a CPXV strain previously isolated from a cat. This is the third documented case of a canine CPXV infection. © 2010 The Authors. Journal compilation © 2010 ESVD and ACVD.

Performance evaluation of nanoclay enriched anti-microbial hydrogels for biomedical applications

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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.

Radiosynthesis and preclinical studies of 177Lu-labeled sulfadiazine. A possible theranostic agent for deep-seated bacterial infection

International Nuclear Information System (INIS)

Syed Ali Raza Naqvi; Rashid Rasheed; Muhammad Tauqeer Ahmed; Ameer Fawad Zahoor

2017-01-01

Sulfadiazine acts through inhibition of bacterial dihydropteroate synthetase. The radio-labeling of sulfadiazine with lutetium-177 ( 177 Lu) is expected to serve as a theranostic agent for deep-seated bacterial infections. The radiosynthesis of 177 Lu-sulfadiazine indicated a > 95% yield under optimized reaction conditions, and promising stability was found in blood serum. Biodistribution data in the absence of infection revealed minimal accumulation in key body organs. Kidneys were the main excretory organs, showed an uptake of 1.76 ± 0.09% ID/g organ at 6-h post-injection. Biodistribution, scintigraphic data, glomerular filtration rate, and cytotoxicity results encourage clinical investigation of 177 Lu-sulfadiazine as a novel theranostic agent for deep-seated bacterial infection. (author)

Effect of Winemaking on the Composition of Red Wine as a Source of Polyphenols for Anti-Infective Biomaterials

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Arianna Di Lorenzo

2016-04-01

Full Text Available Biomaterials releasing bactericides have currently become tools for thwarting medical device-associated infections. The ideal anti-infective biomaterial must counteract infection while safeguarding eukaryotic cell integrity. Red wine is a widely consumed beverage to which many biological properties are ascribed, including protective effects against oral infections and related bone (osteoarthritis, osteomyelitis, periprosthetic joint infections and cardiovascular diseases. In this study, fifteen red wine samples derived from grapes native to the Oltrepò Pavese region (Italy, obtained from the winemaking processes of “Bonarda dell’Oltrepò Pavese” red wine, were analyzed alongside three samples obtained from marc pressing. Total polyphenol and monomeric anthocyanin contents were determined and metabolite profiling was conducted by means of a chromatographic analysis. Antibacterial activity of wine samples was evaluated against Streptococcus mutans, responsible for dental caries, Streptococcus salivarius, and Streptococcus pyogenes, two oral bacterial pathogens. Results highlighted the winemaking stages in which samples exhibit the highest content of polyphenols and the greatest antibacterial activity. Considering the global need for new weapons against bacterial infections and alternatives to conventional antibiotics, as well as the favorable bioactivities of polyphenols, results point to red wine as a source of antibacterial substances for developing new anti-infective biomaterials and coatings for biomedical devices.

Frequency of viruses associated with acute respiratory infections in children younger than five years of age at a locality of Mexico City

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C Cabello

2006-02-01

Full Text Available A locality in the district of Tlalpan, Mexico City, was selected in order to identify the viral agents in children younger than 5 years of age with acute respiratory infection (ARI. A total of 300 children were randomly selected and were included in this study for a period of 13 months. During this period nasopharyngeal exudates were collected for the isolation of viral agents. Monoclonal fluorescent antibodies were used for viral identification after cell culture. Viral infection was detected in 65% of the specimens. The respiratory syncytial virus (RSV was the most common virus agent detected. Children required an average of two consultations during the study period. Two high incidence peaks were observed, one during the summer and the other during winter; the most frequent viruses during these seasons were influenza A and RSV, respectively. The largest number of viruses was isolated in the group of children between 1 and 2 years of age and in the group between 4 and 5 years of age. This study demonstrated the presence of ARI and of different viruses in a period of 13 months, as well as the most frequent viruses in children younger than 5 years of age from a community of Mexico City.

Retrospective investigation of serological finding in diagnosis of parasite agents caused mass in liver

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Safinaz Demirkaya

2014-06-01

Full Text Available Objective: Many of parasite agent cause diseases damaging the liver. The parasite infections settled the liver give rise to focal mass named as reactive hyperplasia or granulomatous reactions in this organ. Some of parasites caused focal mass in liver are cystic echinococ, Fasciola hepatica and Entamoeba histolytica. The diagnoses of these parasites which are localized to liver have been carried out with serological methods (Indirect hemagglutination (IHA, Indirect Fluorescent Antibody Technic (IFAT and ELISA (Enzyme Linked Immunosorbent Assay and radiological imaging. In this study, we was aimed to investigating of prevalence with serological methods of parasite diseases like cystic echinococcosis, fascioliasis and amebic liver abscess in patients determined preliminary diagnosis mass with radiological imaging Methods: For this study, One hundred patient’s sera were included to investigation. It were investigated E.histolytica antibody with IHA method, anti-echinococcus IgG antibody with IFAT method and anti-fasciolia hepatica IgG antibody with ELISA method in sera of patient’s determined mass preliminary diagnosis with radiological imaging. Results: It were encountered these parasite in 27% of patients who determined mass preliminary diagnosis. It was determined in 1% E.histolytica, 13% Cystic echinococcus and 13% Fasciola hepatica seropositive of patients. Conclusion: The patients detected mass preliminary in liver should be evaluated for these parasites. We believe that will not be enough only radiological imaging in identification of these parasitic infections and should definitely need to be supported with a serological test.

Anti-Enterovirus 71 Agents of Natural Products.

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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.

An artemisinin derivative of praziquantel as an orally active antischistosomal agent.

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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.

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

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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.

Anti-Inflammatory Properties of Menthol and Menthone in Schistosoma mansoni Infection

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Zaia, Mauricio G.; Cagnazzo, Túlio di Orlando; Feitosa, Karina A.; Soares, Edson G.; Faccioli, Lúcia H.; Allegretti, Silmara M.; Afonso, Ana; Anibal, Fernanda de Freitas

2016-01-01

Schistosomiasis is a parasitic disease caused by several species of trematode worms and it is believed that more than 261 million people are affected worldwide. New drug development has become essential because there is a risk of the parasite becoming resistant to Praziquantel, the only drug available for this infection. This study evaluated parasitological, immunological and histological parameters in mice infected with Schistosoma mansoni and treated with an herbal commercial medicine. This drug consists of menthol (30–55%) and menthone (14–32%). A 60 day treatment regimen with the herbal medicine decreased the number of S. mansoni eggs in the feces, liver, and intestine and reduced the number of hepatic granulomas. We observed a reduction of 84% in blood eosinophilia and a decrease in the IL-4 and IL-10 blood levels after treatment. Therefore, we propose that schistosomiasis treatment with this herbal medicine for 60 days has an immunomodulatory and anti-inflammatory action in this animal model for schistosomiasis thus contributing to the decrease in physio pathological effects caused by S. mansoni infection. PMID:27378927

Prevalence of hepatitis C Virus infection among hemophiliacs in Central Brazil

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Adriana P Barbosa

2002-07-01

Full Text Available In order to investigate the hepatitis C virus (HCV infection prevalence and risk factors in hemophiliacs in Central Brazil, 90 patients were interviewed and serum samples tested for HCV RNA and anti-HCV antibodies. An overall prevalence of 63.3% (CI 95%: 53.0-72.7 was found. Multivariate analysis of risk factors showed that number of blood transfusions was significantly associated with this infection. Most hemophiliacs received locally produced cryoprecipitate. All infected patients were transfused before the screening of blood units for anti-HCV. However, hemophiliacs who received exclusively screened cryoprecipitate were HCV negative. It confirms the expected decline in transfusion-acquired hepatitis C.

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

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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

Anti-Enterovirus 71 Agents of Natural Products

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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.

[Epidemiologic diagnostic of nosocomial suppurative-septic infections of Pseudomonas etiology based on intraspecies typing of causative agent].

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Fel'dblium, I V; Zakharova, Iu A; Nikolaeva, A M; Fedotova, O S

2013-01-01

Scientific justification of optimization of epidemiologic diagnostic of suppurative-septic infection (SSI) caused by Pseudomonas aeruginosa based on comparability of antibiotic sensitivity and beta-lactamase production. Intraspecies typing of 37 P. aeruginosa strains isolated during microbiological monitoring of 106 patients and 131 objects of clinical environment of surgical and obstetrician hospitals by using a complex ofphenotypic and molecular-biological methods including determination of sensitivity to antibiotics by serial dilutions method and PCR-diagnostics with determination of TEM, SHV, CTX, OXA, MBL, VIM genes was performed. P. aeruginosa strains combined into groups by isolation location during studies turned out to be heterogeneous by sensitivity to antibiotics and beta-lactamase production that allowed to form subgroups of strains by focality attribute. Isolates recovered from different SSI foci had significant differences in minimal inhibitory concentration (MIC) reaching 1024 times. MIC parameter within subgroups did not exceed 8 - 16 consequent dilutions. Use of a complex of phenotypic and molecular-biologic methods of causative agent typing including determination of sensitivity to antibiotics by serial dilutions method and evaluation of beta-lactamase production allowed to establish a mechanism of development of SSI epidemic process caused by P. aeruginosa, detect origins and reservoirs of infection in hospital, modes and factors of transmission and reach maximum justification of epidemiologic control and prophylaxis measures of localization of foci of nosocomial infections of pseudomonas etiology.

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.

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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

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

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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.

Seroprevalence of anti-HCV and hepatitis B surface antigen in HIV infected patients

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Tankhiwale S

2003-01-01

Full Text Available Human immunodeficiency virus (HIV is known to influence the natural history of infections with certain hepatitis viruses and interactions between HIV and hepatitis viruses may potentiate HIV replication. There is high degree of epidemiological similarity between hepatitis B virus and HIV as regard to high-risk group and route of transmission. Transmission of hepatitis C virus (HCV through blood transfusion and intravenous drug abuse is well documented. Present study deals with the study of concurrent infection of HBV and HCV with HIV infection. In the study of 110 HIV seropositive patients, 34(30.4% were positive for HBV and 8(7.27% for HCV. The difference of concomitant infection was highly significant compared to controls. (p value < 0.0001. Heterosexual high risk behaviour was observed in 89(80.91% of 110 HIV positive patients, out of which 23(25.8% and 5(5.62% were HBsAg and anti-HCV positive respectively. History of transmission was unclear in remaining patients. Concomitant infection of HIV and HBV was found to be significantly more in the symptomatic group (40.68% compared to asymptomatic group (19.6%. As HIV infection is known to affect the natural history of both HBV and HCV infection, screening of their concurrent association is necessary.

Bacterial infection identification by an anti-peptidoglycan aptamer labeled with Technetium-99m

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Andrade, Antero Silva Ribeiro; Ferreira, Iêda Mendes [Centro de Desenvolvimento da Tecnologia Nuclear (CDTN/CNEN-MG), Belo Horizonte, MG (Brazil); Barros, Andre Luis Branco de; Cardoso, Valbert Nascimento [Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, MG (Brazil)

2017-07-01

Full text: Introduction: A variety of radiopharmaceuticals is used to detect infection, but long-term clinical use has shown that the majority of them cannot distinguish between inflammation and infection. Nuclear medicine clinics are still awaiting the optimal scintigraphic imaging agents capable of discriminating between infection and inflammation, and between fungal and bacterial infections. Aptamers are oligonucleotides that display high affinity and specificity for their molecular targets and are emerging as promising molecules for radiopharmaceuticals development. Material and Methods: An aptamer for the peptidoglycan (main constituent of bacterial cell walls) termed Antibac1 was selected in a previous work. In the present study, this aptamer were labeled with {sup 99m}Tc and evaluated for bacterial infections identification by scintigraphy. All protocols were approved by the local Ethics Committee for Animal Experimentation of the Federal University of Minas Gerais (CETEA / UFMG), Protocol number 108/2014. Labeling with {sup 99m}Tc was performed by the direct method and the complex stability was evaluated in saline, plasma and presence of cysteine. The biodistribution and scintigraphic imaging studies with the {sup 99m}Tc-Antibac1 were carried out in two distinct experimental infection models: Swiss mice infected in the right thigh with Staphylococcus aureus or Candida albicans. {sup 99m}Tc radiolabeled library, consisting of oligonucleotides with random sequences, was used as a control in both experimental models. The direct radiolabeling allowed radiolabel yields above 90%. Results: A high complex stability was obtained in saline solution and plasma, but 51% of transchelation was verified after 24 h in the presence of cysteine. Scintigraphic images of S. aureus infected mice that received the {sup 99m}Tc-Antibac1 showed target to non-target ratios of 4.7 ± 0.90 and 4.6 ± 0.10 at 1.5 and 3.0 h, respectively. These values were statistically higher than

Bacterial infection identification by an anti-peptidoglycan aptamer labeled with Technetium-99m

International Nuclear Information System (INIS)

Andrade, Antero Silva Ribeiro; Ferreira, Iêda Mendes; Barros, Andre Luis Branco de; Cardoso, Valbert Nascimento

2017-01-01

Full text: Introduction: A variety of radiopharmaceuticals is used to detect infection, but long-term clinical use has shown that the majority of them cannot distinguish between inflammation and infection. Nuclear medicine clinics are still awaiting the optimal scintigraphic imaging agents capable of discriminating between infection and inflammation, and between fungal and bacterial infections. Aptamers are oligonucleotides that display high affinity and specificity for their molecular targets and are emerging as promising molecules for radiopharmaceuticals development. Material and Methods: An aptamer for the peptidoglycan (main constituent of bacterial cell walls) termed Antibac1 was selected in a previous work. In the present study, this aptamer were labeled with 99m Tc and evaluated for bacterial infections identification by scintigraphy. All protocols were approved by the local Ethics Committee for Animal Experimentation of the Federal University of Minas Gerais (CETEA / UFMG), Protocol number 108/2014. Labeling with 99m Tc was performed by the direct method and the complex stability was evaluated in saline, plasma and presence of cysteine. The biodistribution and scintigraphic imaging studies with the 99m Tc-Antibac1 were carried out in two distinct experimental infection models: Swiss mice infected in the right thigh with Staphylococcus aureus or Candida albicans. 99m Tc radiolabeled library, consisting of oligonucleotides with random sequences, was used as a control in both experimental models. The direct radiolabeling allowed radiolabel yields above 90%. Results: A high complex stability was obtained in saline solution and plasma, but 51% of transchelation was verified after 24 h in the presence of cysteine. Scintigraphic images of S. aureus infected mice that received the 99m Tc-Antibac1 showed target to non-target ratios of 4.7 ± 0.90 and 4.6 ± 0.10 at 1.5 and 3.0 h, respectively. These values were statistically higher than found for the 99m Tc

Anti-HIV-1 activity of flavonoid myricetin on HIV-1 infection in a dual-chamber in vitro model.

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Silvana Pasetto

Full Text Available HIV infection by sexual transmission remains an enormous global health concern. More than 1 million new infections among women occur annually. Microbicides represent a promising prevention strategy that women can easily control. Among emerging therapies, natural small molecules such as flavonoids are an important source of new active substances. In this study we report the in vitro cytotoxicity and anti-HIV-1 and microbicide activity of the following flavonoids: Myricetin, Quercetin and Pinocembrin. Cytotoxicity tests were conducted on TZM-bl, HeLa, PBMC, and H9 cell cultures using 0.01-100 µM concentrations. Myricetin presented the lowest toxic effect, with Quercetin and Pinocembrin relatively more toxic. The anti-HIV-1 activity was tested with TZM-bl cell plus HIV-1 BaL (R5 tropic, H9 and PBMC cells plus HIV-1 MN (X4 tropic, and the dual tropic (X4R5 HIV-1 89.6. All flavonoids showed anti-HIV activity, although Myricetin was more effective than Quercetin or Pinocembrin. In TZM-bl cells, Myricetin inhibited ≥90% of HIV-1 BaL infection. The results were confirmed by quantification of HIV-1 p24 antigen in supernatant from H9 and PBMC cells following flavonoid treatment. In H9 and PBMC cells infected by HIV-1 MN and HIV-1 89.6, Myricetin showed more than 80% anti-HIV activity. Quercetin and Pinocembrin presented modest anti-HIV activity in all experiments. Myricetin activity was tested against HIV-RT and inhibited the enzyme by 49%. Microbicide activities were evaluated using a dual-chamber female genital tract model. In the in vitro microbicide activity model, Myricetin showed promising results against different strains of HIV-1 while also showing insignificant cytotoxic effects. Further studies of Myricetin should be performed to identify its molecular targets in order to provide a solid biological foundation for translational research.

Ethnobotany and ethnopharmacy--their role for anti-cancer drug development.

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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.

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.

Antiviral effects of two Ganoderma lucidum triterpenoids against enterovirus 71 infection

International Nuclear Information System (INIS)

Zhang, Wenjing; Tao, Junyan; Yang, Xiaoping; Yang, Zhuliang; Zhang, Li; Liu, Hongsheng; Wu, Kailang; Wu, Jianguo

2014-01-01

Highlights: • Triterpenoids GLTA and GLTB display anti-EV71 activities without cytotoxicity. • The compounds prevent EV71 infection by blocking adsorption of the virus to the cells. • GLTA and GLTB bind to EV71 capsid at the hydrophobic pocket to block EV71 uncoating. • The two compounds significantly inhibit the replication of EV71 viral RNA. • GLTA and GLTB may be used as potential therapeutic agents to treat EV71 infection. - Abstract: Enterovirus 71 (EV71) is a major causative agent for hand, foot and mouth disease (HFMD), and fatal neurological and systemic complications in children. However, there is currently no clinical approved antiviral drug available for the prevention and treatment of the viral infection. Here, we evaluated the antiviral activities of two Ganoderma lucidum triterpenoids (GLTs), Lanosta-7,9(11),24-trien-3-one,15;26-dihydroxy (GLTA) and Ganoderic acid Y (GLTB), against EV71 infection. The results showed that the two natural compounds display significant anti-EV71 activities without cytotoxicity in human rhabdomyosarcoma (RD) cells as evaluated by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) cell proliferation assay. The mechanisms by which the two compounds affect EV71 infection were further elucidated by three action modes using Ribavirin, a common antiviral drug, as a positive control. The results suggested that GLTA and GLTB prevent EV71 infection through interacting with the viral particle to block the adsorption of virus to the cells. In addition, the interactions between EV71 virion and the compounds were predicated by computer molecular docking, which illustrated that GLTA and GLTB may bind to the viral capsid protein at a hydrophobic pocket (F site), and thus may block uncoating of EV71. Moreover, we demonstrated that GLTA and GLTB significantly inhibit the replication of the viral RNA (vRNA) of EV71 replication through blocking EV71 uncoating. Thus, GLTA and GLTB may represent two potential

Antiviral effects of two Ganoderma lucidum triterpenoids against enterovirus 71 infection

Energy Technology Data Exchange (ETDEWEB)

Zhang, Wenjing; Tao, Junyan; Yang, Xiaoping [State Key Laboratory of Virology and College of Life Sciences, Wuhan University, Wuhan 430072 (China); Yang, Zhuliang [Key Laboratory of Biodiversity and Biogeography, Kunming Institute of Botany, Chinese Academy of Science, Kunming 650201 (China); Zhang, Li; Liu, Hongsheng [Department of Academy of Sciences, Liaoning University, Shenyang 110036 (China); Wu, Kailang [State Key Laboratory of Virology and College of Life Sciences, Wuhan University, Wuhan 430072 (China); Wu, Jianguo, E-mail: jwu@whu.edu.cn [State Key Laboratory of Virology and College of Life Sciences, Wuhan University, Wuhan 430072 (China)

2014-07-04

Highlights: • Triterpenoids GLTA and GLTB display anti-EV71 activities without cytotoxicity. • The compounds prevent EV71 infection by blocking adsorption of the virus to the cells. • GLTA and GLTB bind to EV71 capsid at the hydrophobic pocket to block EV71 uncoating. • The two compounds significantly inhibit the replication of EV71 viral RNA. • GLTA and GLTB may be used as potential therapeutic agents to treat EV71 infection. - Abstract: Enterovirus 71 (EV71) is a major causative agent for hand, foot and mouth disease (HFMD), and fatal neurological and systemic complications in children. However, there is currently no clinical approved antiviral drug available for the prevention and treatment of the viral infection. Here, we evaluated the antiviral activities of two Ganoderma lucidum triterpenoids (GLTs), Lanosta-7,9(11),24-trien-3-one,15;26-dihydroxy (GLTA) and Ganoderic acid Y (GLTB), against EV71 infection. The results showed that the two natural compounds display significant anti-EV71 activities without cytotoxicity in human rhabdomyosarcoma (RD) cells as evaluated by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) cell proliferation assay. The mechanisms by which the two compounds affect EV71 infection were further elucidated by three action modes using Ribavirin, a common antiviral drug, as a positive control. The results suggested that GLTA and GLTB prevent EV71 infection through interacting with the viral particle to block the adsorption of virus to the cells. In addition, the interactions between EV71 virion and the compounds were predicated by computer molecular docking, which illustrated that GLTA and GLTB may bind to the viral capsid protein at a hydrophobic pocket (F site), and thus may block uncoating of EV71. Moreover, we demonstrated that GLTA and GLTB significantly inhibit the replication of the viral RNA (vRNA) of EV71 replication through blocking EV71 uncoating. Thus, GLTA and GLTB may represent two potential

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.

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

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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.

MR brain scan tissues and structures segmentation: local cooperative Markovian agents and Bayesian formulation

International Nuclear Information System (INIS)

Scherrer, B.

2008-12-01

Accurate magnetic resonance brain scan segmentation is critical in a number of clinical and neuroscience applications. This task is challenging due to artifacts, low contrast between tissues and inter-individual variability that inhibit the introduction of a priori knowledge. In this thesis, we propose a new MR brain scan segmentation approach. Unique features of this approach include (1) the coupling of tissue segmentation, structure segmentation and prior knowledge construction, and (2) the consideration of local image properties. Locality is modeled through a multi-agent framework: agents are distributed into the volume and perform a local Markovian segmentation. As an initial approach (LOCUS, Local Cooperative Unified Segmentation), intuitive cooperation and coupling mechanisms are proposed to ensure the consistency of local models. Structures are segmented via the introduction of spatial localization constraints based on fuzzy spatial relations between structures. In a second approach, (LOCUS-B, LOCUS in a Bayesian framework) we consider the introduction of a statistical atlas to describe structures. The problem is reformulated in a Bayesian framework, allowing a statistical formalization of coupling and cooperation. Tissue segmentation, local model regularization, structure segmentation and local affine atlas registration are then coupled in an EM framework and mutually improve. The evaluation on simulated and real images shows good results, and in particular, a robustness to non-uniformity and noise with low computational cost. Local distributed and cooperative MRF models then appear as a powerful and promising approach for medical image segmentation. (author)

In-vitro evaluation of anti-trichomonal activities of Eugenia uniflora leaf.

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Ibikunle, Gabriel Femi; Adebajo, Adeleke Clement; Famuyiwa, Funmilayo Gladys; Aladesanmi, Adetunji Joseph; Adewunmi, Clement Oladapo

2011-01-01

Eugenia uniflora, used ethnomedically in some tropical countries as an anti-infective, has shown anti-malarial and anti-trypanocidal activities. Therefore using bioactivity guided fractionation, anti-trichomonal activity of E. uniflora leaf was investigated. Anti-trichomonal activities of leaf methanol extract and its fractions against Trichomonas gallinae as well as their cytotoxicities using an in vitro haemaglutination assay were determined. Anti-trichomonacidal activities of the extract improved on purification up to a stage. Subfractions E(2-5) had LC(50) and LC(90) values of 4.77 - 5.28, 18.49 - 25.00 and 4.53 - 5.18, 18.32 - 19.07 µg/ml at 24 and 48 hrs, respectively that were better than those of metronidazole. Further purification of E(2-5) led to loss of activity suggesting that the active components were probably working synergistically and additively. Demonstration of low haemaglutination titre values of 0.00 - 5.33 by methanolic extract and its partition fractions suggested their low toxicity profile. The established safety of the leaf indicated that its anti-trichomonal activity was not due to non-specific cytotoxicity, hence could be used in ethnomedicine as an anti-trichomonal agent.

Guidelines for using antiretroviral agents among HIV-infected adults and adolescents.

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Dybul, Mark; Fauci, Anthony S; Bartlett, John G; Kaplan, Jonathan E; Pau, Alice K

2002-09-03

The availability of an increasing number of antiretroviral agents and the rapid evolution of new information have introduced substantial complexity into treatment regimens for persons infected with human immunodeficiency virus (HIV). In 1996, the Department of Health and Human Services and the Henry J. Kaiser Family Foundation convened the Panel on Clinical Practices for the Treatment of HIV to develop guidelines for clinical management of HIV-infected adults and adolescents (CDC. Report of the NIH Panel To Define Principles of Therapy of HIV Infection and Guidelines for the use of antiretroviral agents in HIV-infected adults and adolescents. MMWR. 1998;47[RR-5]:1-41). This report, which updates the 1998 guidelines, addresses 1) using testing for plasma HIV ribonucleic acid levels (i.e., viral load) and CD4+ T cell count; 2) using testing for antiretroviral drug resistance; 3) considerations for when to initiate therapy; 4) adherence to antiretroviral therapy; 5) considerations for therapy among patients with advanced disease; 6) therapy-related adverse events; 7) interruption of therapy; 8) considerations for changing therapy and available therapeutic options; 9) treatment for acute HIV infection; 10) considerations for antiretroviral therapy among adolescents; 11) considerations for antiretroviral therapy among pregnant women; and 12) concerns related to transmission of HIV to others. Antiretroviral regimens are complex, have serious side effects, pose difficulty with adherence, and carry serious potential consequences from the development of viral resistance because of nonadherence to the drug regimen or suboptimal levels of antiretroviral agents. Patient education and involvement in therapeutic decisions are critical. Treatment should usually be offered to all patients with symptoms ascribed to HIV infection. Recommendations for offering antiretroviral therapy among asymptomatic patients require analysis of real and potential risks and benefits. In general

Seroprevalence of Anti-Toxoplasma gondii Antibodies Among Lebanese Pregnant Women.

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Nahouli, Hasan; El Arnaout, Nour; Chalhoub, Elias; Anastadiadis, Elie; El Hajj, Hiba

2017-12-01

Toxoplasma gondii, the causative agent of toxoplasmosis, is a zoonotic obligate intracellular protozoan parasite responsible for the infection of almost one-third of the world's population. T. gondii is particularly threatening for primo-infected pregnant women and may lead, following vertical transplacental transmission, to spontaneous abortion, miscarriage, or severe manifestations in the newborn. The aim of this study was to provide an updated estimate of the seroprevalence of anti-T. gondii antibodies among a group of Lebanese pregnant women and its seroconversion rate. This is a retrospective cohort study, in which medical records of 11,000 pregnant women were screened. These women visited a private Obstetrics and Gynecology clinic located in Beirut, the capital of Lebanon, during the period of January 1994 till September 2015. Serological results of anti-T. gondii immunoglobulin G (IgG) and immunoglobulin M (IgM) results of 2456 Lebanese pregnant women who fulfilled the inclusion criteria were included in the analysis. Seropositivity and seroconversion rates for women with repeated tests were reported according to age and area of residence. The overall anti-T. gondii IgG and IgM seropositivity among 2456 Lebanese pregnant women was 82.6% and 1.8% respectively. The highest IgG seropositivity is among the age group of 35-44 years (87.81%) and at the governorate of "Mount Lebanon" (82.95%). Sixty-four seroconversions were detected and two abortions due to T. gondii infection during pregnancy were recorded. The seroprevalence of anti-T. gondii IgG among the screened pregnant women in Lebanon is the highest in the Arab region. These results highlight the importance of running a national sample survey to estimate the real potential burden of this infection and its impact on maternal and fetal health.

Phentolamine mesylate: It′s role as a reversal agent for unwarranted prolonged local analgesia

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Harpreet Singh Grover

2015-01-01

Full Text Available Administration of local anesthesia is an integral procedure prior to dental treatments to minimize the associated pain. It is learned that its effect stays more than the time required for the dental procedure to be completed. This prolonged soft tissue anesthesia (STA can be detrimental, inconvenient, and unnecessary. Phentolamine mesylate, a Food and Drug Administration-approved drug essentially serves the purpose of faster recovery from numbness at the site of local anesthesia. This article reviews the development of the drug phentolamine mesylate and its indication as a local anesthetic reversal agent. A literature search for phentolamine mesylate as a STA reversal agent was conducted in PubMed using the terms "dental local anesthesia reversal, phentolamine mesylate" up to March 2014. The search was limited to articles published in English. The search revealed 13 PubMed indexed articles stating the development and application of phentolamine mesylate. Phentolamine mesylate is an important step in the progress of developing patient care as well as an aid to the dental clinician.

Anti-TNFα Treatment for HLA-B27-Positive Ankylosing Spondylitis-Related Uveitis.

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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.

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

Survey of malaria and anti-dengue virus IgG among febrile HIV-infected patients attending a tertiary hospital in Abuja, Nigeria.

Science.gov (United States)

Mustapha, Jelili Olaide; Emeribe, Anthony Uchenna; Nasir, Idris Abdullahi

2017-01-01

Dengue and malaria are infections, of great public health concern, especially in sub-Saharan Africa where the burden of HIV infection is high. This study was conducted to determine the seroprevalence of dengue virus IgG antibodies and dengue/malaria coinfection among febrile HIV-infected patients attending the University of Abuja Teaching Hospital, Gwagwalada, Abuja. In this cross-sectional study, blood samples from 178 consenting HIV-infected patients receiving antiretroviral therapy were collected and tested for plasmodiasis and anti-Dengue virus IgG using malaria microscopy and ELISA, respectively. Interviewer-based questionnaires were used to assess subjects' sociodemographic variables and dengue risk factors. Of the 178 screened participants, 44.4% were seropositive for dengue virus IgG antibody, whereas 29.2% were positive for Plasmodium falciparum. About 44.2% were positive for both dengue virus and P. falciparum . There was a statistical association between anti-dengue IgG and occupation ( p =0.03) but not with age, residential area, educational level and patients' gender ( p >0.05). Seroprevalence of anti-dengue specific IgG was relatively higher in participants who adopted protective measures. There was a statistical association between seroprevalence of anti-dengue IgG and adoption of preventive measures ( p <0.05). The high prevalence of malaria and dengue virus IgG indicates the need to strengthen vector control and dengue surveillance programs.

Evaluation of biocontrol agents for grapevine pruning wound protection against trunk pathogen infection.

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Charl KOTZE

2011-12-01

Full Text Available Trunk diseases of grapevine are caused by numerous pathogens, including Eutypa lata, Phaeomoniella chlamydospora, and species of Botryosphaeriaceae (incl. Botryosphaeria and aggregate genera, Phomopsis and Phaeoacremonium. Since infections occur mainly through pruning wounds, that have been shown by previous research to stay susceptible for up to 16 weeks after pruning, long-term pruning wound protection is required for prevention of infection. This study evaluated several biocontrol agents against a range of trunk disease pathogens in dual plate laboratory trials to determine macroscopic and microscopic interactions. The biocontrol agents had a substantial effect on all the pathogens, with a wide range of macroscopic and microscopic interactions observed. The best performing biocontrol agents were tested in two field trials. Fresh pruning wounds were treated with benomyl, Trichoderma products (Biotricho®, Vinevax® and ECO 77® and isolates (USPP-T1 and -T2, identified as T. atroviride and Bacillus subtilis. Seven days after treatment the pruning wounds were inoculated by spraying with spore suspensions of Neofusicoccum australe, N. parvum, Diplodia seriata, Lasiodiplodia theobromae, Eutypa lata, Phaeomoniella chlamydospora or Phomopsis viticola. Eight months after inoculation, the treatments were evaluated by isolation onto potato dextrose agar. The efficacy of the biocontrol agents was in most cases similar or superior to that observed for benomyl. Isolate USPP-T1, in particular, was very effective, reducing incidence of Ph. viticola, E. lata, Pa. chlamydospora, N. australe, N. parvum, D. seriata and L. theobromae by 69, 76, 77, 78, 80, 85 and 92%, respectively. This is the first report of biological protection of grapevine pruning wounds against this group of grapevine trunk disease pathogens.

Post-exposure Treatment with Anti-rabies VHH and Vaccine Significantly Improves Protection of Mice from Lethal Rabies Infection

Science.gov (United States)

Terryn, Sanne; Francart, Aurélie; Rommelaere, Heidi; Stortelers, Catelijne; Van Gucht, Steven

2016-01-01

Post-exposure prophylaxis (PEP) against rabies infection consists of a combination of passive immunisation with plasma-derived human or equine immune globulins and active immunisation with vaccine delivered shortly after exposure. Since anti-rabies immune globulins are expensive and scarce, there is a need for cheaper alternatives that can be produced more consistently. Previously, we generated potent virus-neutralising VHH, also called Nanobodies, against the rabies glycoprotein that are effectively preventing lethal disease in an in vivo mouse model. The VHH domain is the smallest antigen-binding functional fragment of camelid heavy chain-only antibodies that can be manufactured in microbial expression systems. In the current study we evaluated the efficacy of half-life extended anti-rabies VHH in combination with vaccine for PEP in an intranasal rabies infection model in mice. The PEP combination therapy of systemic anti-rabies VHH and intramuscular vaccine significantly delayed the onset of disease compared to treatment with anti-rabies VHH alone, prolonged median survival time (35 versus 14 days) and decreased mortality (60% versus 19% survival rate), when treated 24 hours after rabies virus challenge. Vaccine alone was unable to rescue mice from lethal disease. As reported also for immune globulins, some interference of anti-rabies VHH with the antigenicity of the vaccine was observed, but this did not impede the synergistic effect. Post exposure treatment with vaccine and human anti-rabies immune globulins was unable to protect mice from lethal challenge. Anti-rabies VHH and vaccine act synergistically to protect mice after rabies virus exposure, which further validates the possible use of anti-rabies VHH for rabies PEP. PMID:27483431

Post-exposure Treatment with Anti-rabies VHH and Vaccine Significantly Improves Protection of Mice from Lethal Rabies Infection.

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Sanne Terryn

2016-08-01

Full Text Available Post-exposure prophylaxis (PEP against rabies infection consists of a combination of passive immunisation with plasma-derived human or equine immune globulins and active immunisation with vaccine delivered shortly after exposure. Since anti-rabies immune globulins are expensive and scarce, there is a need for cheaper alternatives that can be produced more consistently. Previously, we generated potent virus-neutralising VHH, also called Nanobodies, against the rabies glycoprotein that are effectively preventing lethal disease in an in vivo mouse model. The VHH domain is the smallest antigen-binding functional fragment of camelid heavy chain-only antibodies that can be manufactured in microbial expression systems. In the current study we evaluated the efficacy of half-life extended anti-rabies VHH in combination with vaccine for PEP in an intranasal rabies infection model in mice. The PEP combination therapy of systemic anti-rabies VHH and intramuscular vaccine significantly delayed the onset of disease compared to treatment with anti-rabies VHH alone, prolonged median survival time (35 versus 14 days and decreased mortality (60% versus 19% survival rate, when treated 24 hours after rabies virus challenge. Vaccine alone was unable to rescue mice from lethal disease. As reported also for immune globulins, some interference of anti-rabies VHH with the antigenicity of the vaccine was observed, but this did not impede the synergistic effect. Post exposure treatment with vaccine and human anti-rabies immune globulins was unable to protect mice from lethal challenge. Anti-rabies VHH and vaccine act synergistically to protect mice after rabies virus exposure, which further validates the possible use of anti-rabies VHH for rabies PEP.

Expression, tissue localization and serodiagnostic potential of Taenia multiceps acidic ribosomal protein P2.

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Huang, Xing; Chen, Lin; Yang, Yingdong; Gu, Xiaobin; Wang, Yu; Lai, Weimin; Peng, Xuerong; Yang, Guangyou

2015-12-01

The larval stage of Taenia multiceps, also known as coenurus, is the causative agent of coenurosis, which results in severe health problems in sheep, goats, cattle and other animals that negatively impact on animal husbandry. There is no reliable method to identify coenurus infected goats in the early period of infection. We identified a full-length cDNA that encodes acidic ribosomal protein P2 from the transcriptome of T. multiceps (TmP2). Following cloning, sequencing and structural analyses were performed using bioinformatics tools. Recombinant TmP2 (rTmP2) was prokaryotically expressed and then used to test immunoreactivity and immunogenicity in immunoblotting assays. The native proteins in adult stage and coenurus were located via immunofluorescence assays, while the potential of rTmP2 for indirect ELISA-based serodiagnostics was assessed using native goat sera. In addition, 20 goats were randomly divided into a drug treatment group and a control group. Each goat was orally given mature, viable T. multiceps eggs. The drug treatment group was given 10% praziquantel by intramuscular injection 45 days post-infection (p.i), and all goats were screened for anti-TmP2 antibodies with the indirect ELISA method established here, once a week for 17 weeks p.i. The open reading frame (366 bp) of the target gene encodes a 12.62 kDa protein, which showed high homology to that from Taenia solium (93% identity) and lacked a signal peptide. Immunofluorescence staining showed that TmP2 was highly localized to the parenchymatous zone of both the adult parasite and the coenurus; besides, it was widely distributed in cystic wall of coenurus. Building on good immunogenic properties, rTmP2-based ELISA exhibited a sensitivity of 95.0% (19/20) and a specificity of 96.3% (26/27) in detecting anti-P2 antibodies in the sera of naturally infected goats and sheep. In goats experimentally infected with T. multiceps, anti-TmP2 antibody was detectable in the control group from 3 to 10 weeks

Labelling and biodistribution of /sup 99m/Tc-ceftriaxone: a new imaging agent

International Nuclear Information System (INIS)

Khurshid, Z.; Roohi, S.; Zahoor, R.; Tariq, S.

2012-01-01

Most commonly used infection imaging agents are specific for inflammation. Some newer agents like labeled antimicrobials and peptides have shown infection seeking properties. Research is underway for synthesis of newer imaging agents specific for infections. In this quest we have labeled and bio evaluated /sup 99m/Tc-ceftriaxone. Ceftriaxone is a commonly used third generation cephalosporin antibiotic having a broad anti-bacterial spectrum but has more specificity for gram-negative bacteria. /sup 99m/Tc-ceftriaxone was prepared at ph 7 by adding 30 mg of ligand to /sup 99m/Tc in the presence of 50 mu g of SnCl/sub 2/./sup 2/H/sub 2/O. Boiling for ten minutes gave maximum labeling yield (96+1.76%). The stability at room temperature both with and without human serum was more than 90% till 24 hours. In-vitro binding revealed maximum binding of 68% and 47% with E.coli and S.aureus respectively after 4 hours incubation. Biodistribution studies in normal rats showed maximum uptake in hepatobiliary system followed by kidney. In infection and inflammation models the maximum target to non- target ratios of 12.66 +- 2.59, 2.36 +- 0.30 and 1.44 +- 0.53 were achieved with E. coli, S. aureus and oil inflammation respectively 4 hours post injection. Scintigraphic findings also correlated with biodistribution results. (Orig./A.B.)

Impact of hepatitis B virus infection on HIV response to antiretroviral therapy in a Chinese antiretroviral therapy center

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Rongrong Yang

2014-11-01

Conclusions: HBV co-infection can affect late immunological and virological responses to ART and increase the risk of hepatotoxicity. Mortality due to liver disease was high among HIV/HBV co-infected individuals in this study, despite HBV-active ART. As long as HIV/HBV co-infected persons need anti-HBV therapy, they should be recommended ART that includes agents with activity against both HIV and HBV, regardless of the CD4 cell count level.

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

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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.

HUMAN TOXOPLASMOSIS OUTBREAKS AND THE AGENT INFECTING FORM. FINDINGS FROM A SYSTEMATIC REVIEW

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Luciana Regina MEIRELES

2015-10-01

Full Text Available SUMMARY Toxoplasmosis, a worldwide highly prevalent zoonotic infection, is transmitted either by the oocysts, from water and soil, or the tissue cysts, in raw or undercooked infected meat, of Toxoplasma gondii. An ongoing debate is whether there are differences between the clinical and epidemiological characteristics of the outbreaks due to one or the other infective form of the agent. We performed a systematic review, recovering 437 reported outbreaks of which 38 were selected. They were complete reports containing ascribed Toxoplasma infecting form, and clinical and demographic data. There was no gender or age group selection in the outbreaks, which were described more often in the Americas. A large number of individuals were affected when oocysts, associated with soil and water contaminated with cat feces, were considered the transmission source. Onset of symptoms occurred early when the infection was ascribed to meat tissue cysts (11.4 ± 6.7 days with sharpened temporal distribution of cases, while a broader and prolonged appearance of new cases was observed when oocysts in water were the source of the infection (20 ± 7 days, p < 0.001. Such information may be useful in the design and implementation of control strategies.

Resistance profiles to antimicrobial agents in bacteria isolated from acute endodontic infections: systematic review and meta-analysis.

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Lang, Pauline M; Jacinto, Rogério C; Dal Pizzol, Tatiane S; Ferreira, Maria Beatriz C; Montagner, Francisco

2016-11-01

Infected root canal or acute apical abscess exudates can harbour several species, including Fusobacterium, Porphyromonas, Prevotella, Parvimonas, Streptococcus, Treponema, Olsenella and not-yet cultivable species. A systematic review and meta-analysis was performed to assess resistance rates to antimicrobial agents in clinical studies that isolated bacteria from acute endodontic infections. Electronic databases and the grey literature were searched up to May 2015. Clinical studies in humans evaluating the antimicrobial resistance of primary acute endodontic infection isolates were included. PRISMA guidelines were followed. A random-effect meta-analysis was employed. The outcome was described as the pooled resistance rates for each antimicrobial agent. Heterogeneity and sensitivity analyses were performed. Subgroup analyses were conducted based upon report or not of the use of antibiotics prior to sampling as an exclusion factor (subgroups A and B, respectively). Data from seven studies were extracted. Resistance rates for 15 different antimicrobial agents were evaluated (range, 3.5-40.0%). Lower resistance rates were observed for amoxicillin/clavulanic acid and amoxicillin; higher resistance rates were detected for tetracycline. Resistance rates varied according to previous use of an antimicrobial agent as demonstrated by the subgroup analyses. Heterogeneity was observed for the resistance profiles of penicillin G in subgroup A and for amoxicillin, clindamycin, metronidazole and tetracycline in subgroup B. Sensitivity analyses demonstrated that resistance rates changed for metronidazole, clindamycin, tetracycline and amoxicillin. These findings suggest that clinical isolates had low resistance to β-lactams. Further well-designed studies are needed to clarify whether the differences in susceptibility among the antimicrobial agents may influence clinical responses to treatment. Copyright © 2016 Elsevier B.V. and International Society of Chemotherapy. All rights

Treatment of Oral Multispecies Biofilms by an Anti-Biofilm Peptide.

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Wang, Zhejun; de la Fuente-Núñez, Cesar; Shen, Ya; Haapasalo, Markus; Hancock, Robert E W

2015-01-01

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 (pbiofilm formation over 3 days. The activity of the peptide on preformed biofilms was found to be concentration-dependent since more than 60% of the total plaque biofilm cell population was killed by 10 μg/ml of peptide 1018 in 3 days, while at 5 μg/ml 50% of cells were dead and at 1 μg/ml the peptide triggered cell death in around 30% of the total bacterial population, as revealed by confocal microscopy. The presence of saliva did not affect peptide activity, since no statistically significant difference was found in the ability of peptide 1018 to kill oral biofilms using either saliva coated and non-saliva coated hydroxyapatite surfaces. Scanning electron microscopy experiments indicated that peptide 1018 induced cell lysis in plaque biofilms. Furthermore, combined treatment using peptide 1018 and chlorhexidine (CHX) increased the anti-biofilm activity of each compound compared to when these were used alone, resulting in >50% 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.

Anti-chikungunya activity of luteolin and apigenin rich fraction from Cynodon dactylon

Institute of Scientific and Technical Information of China (English)

Krishnan Saravana Murali; Srinivasan Sivasubramanian; Savariar Vincent; Shanmugaraj Bala Murugan; Bupesh Giridaran; Sundaram Dinesh; Palani Gunasekaran; Kaveri Krishnasamy; Ramalingam Sathishkumar

2015-01-01

Objective:To obtain luteolin and apigenin rich fraction from the ethanolic extract ofCynodon dactylon (L.) (C. dactylon) Pers and evaluate the fraction’s cytotoxicity and anti-Chikungunya potential using Vero cells.Methods:The ethanolic extract ofC. dactylon was subjected to silica gel column chromatography to obtain anti-chikungunya virus (CHIKV) fraction. Reverse phase-HPLC and GC-MS studies were carried out to identify the major phytochemicals in the fraction using phytochemical standards. Cytotoxicity and the potential of the fraction against CHIKV were evaluatedin vitrousing Vero cells. Reduction in viral replication was assessed by reverse transcriptase-polymerase chain reaction (RT-PCR) after treating the viral infected Vero cells with the fraction.Results:Reverse Phase-HPLC and GC-MS studies confirmed the presence of flavonoids, luteolin and apigenin as major phytochemicals in the anti-CHIKV ethanolic fraction ofC. dactylon. The fraction was found to exhibit potent viral inhibitory activity (about 98%) at the concentration of 50 µg/mL as observed by reduction in cytopathic effect, and the cytotoxic concentration of the fraction was found to be 250 µg/mL. RT-PCR analyses indicated that the reduction in viral mRNA synthesis in fraction treated infected cells was much higher than the viral infected control cells.Conclusions:Luteolin and apigenin rich ethanolic fraction fromC. dactylon can be utilized as a potential therapeutic agent against CHIKV infection as the fraction does not show cytotoxicity while inhibiting the virus.

Anti-Quorum Sensing Potential of Potato Rhizospheric Bacteria

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Adeleh Sobhanipour

2017-01-01

Full Text Available The occurrence of antibiotic-resistant pathogenic bacteria is becoming a serious problem. The rise of multiresistance strains has forced the pharmaceutical industry to come up with new generation of more effective and potent antibiotics, therefore creating development of antivirulence compounds. Due to extensive usage of cell-to-cell bacterial communication (QS systems to monitor the production of virulence factors, disruption of QS system results in creation of a promising strategy for the control of bacterial infection. Numerous natural quorum quenching (QQ agents have been identified. In addition, many microorganisms are capable of producing smaller molecular QS inhibitors and/or macromolecular QQ enzymes. In present survey, anti QS activity of 1280 rhizosphere bacteria was assessed using the Pectobacterium carotovorum as AHL-donor and Chromobacterium violaceum CV026 as biosensor system. The results showed that 61 strains had highly AHL-degrading activity. Both Lux I and Lux R activity were affected by some isolates, suggesting that the rhizobacteria target both QS signal and receptor. These soil microorganisms with their anti-QS activity have the potential to be novel therapeutic agents for reducing virulence and pathogenicity of antibiotic resistant bacteria.

Carbon nanotubes as anti-bacterial agents.

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Mocan, Teodora; Matea, Cristian T; Pop, Teodora; Mosteanu, Ofelia; Buzoianu, Anca Dana; Suciu, Soimita; Puia, Cosmin; Zdrehus, Claudiu; Iancu, Cornel; Mocan, Lucian

2017-10-01

Multidrug-resistant bacterial infections that have evolved via natural selection have increased alarmingly at a global level. Thus, there is a strong need for the development of novel antibiotics for the treatment of these infections. Functionalized carbon nanotubes through their unique properties hold great promise in the fight against multidrug-resistant bacterial infections. This new family of nanovectors for therapeutic delivery proved to be innovative and efficient for the transport and cellular translocation of therapeutic molecules. The current review examines the latest progress in the antibacterial activity of carbon nanotubes and their composites.

Anti-influenza Hyperimmune Immunoglobulin Enhances Fc-functional Antibody Immunity during Human Influenza Infection.

Science.gov (United States)

Vanderven, Hillary A; Wragg, Kathleen; Ana-Sosa-Batiz, Fernanda; Kristensen, Anne B; Jegaskanda, Sinthujan; Wheatley, Adam K; Wentworth, Deborah; Wines, Bruce D; Hogarth, P Mark; Rockman, Steve; Kent, Stephen J

2018-05-31

New treatments for severe influenza are needed. Passive transfer of influenza-specific hyperimmune pooled immunoglobulin (Flu-IVIG) boosts neutralising antibody responses to past strains in influenza-infected subjects. The effect of Flu-IVIG on antibodies with Fc-mediated functions, which may target diverse influenza strains, is unclear. We studied the capacity of Flu-IVIG, relative to standard IVIG, to bind to Fc receptors and mediate antibody-dependent cellular cytotoxicity in vitro. The effect of Flu-IVIG infusion, compared to placebo infusion, was examined in serial plasma samples from 24 subjects with confirmed influenza infection in the INSIGHT FLU005 pilot study. Flu-IVIG contains higher concentrations of Fc-functional antibodies than IVIG against a diverse range of influenza hemagglutinins. Following infusion of Flu-IVIG into influenza-infected subjects, a transient increase in Fc-functional antibodies was present for 1-3 days against infecting and non-infecting strains of influenza. Flu-IVIG contains antibodies with Fc-mediated functions against influenza virus and passive transfer of Flu-IVIG increases anti-influenza Fc-functional antibodies in the plasma of influenza-infected subjects. Enhancement of Fc-functional antibodies to a diverse range of influenza strains suggests that Flu-IVIG infusion could prove useful in the context of novel influenza virus infections, when there may be minimal or no neutralising antibodies in the Flu-IVIG preparation.

The influence of anti-infective periodontal treatment on C-reactive protein: a systematic review and meta-analysis of randomized controlled trials.

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Ryan T Demmer

Full Text Available Periodontal infections are hypothesized to increase the risk of adverse systemic outcomes through inflammatory mechanisms. The magnitude of effect, if any, of anti-infective periodontal treatment on systemic inflammation is unknown, as are the patient populations most likely to benefit. We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs to test the hypothesis that anti-infective periodontal treatment reduces systemic c-reactive protein (CRP.MEDLINE, EMBASE, CENTRAL and CINAHL databases were searched using sensitivity-enhancing search terms. Eligible RCTs enrolled patients with periodontal infection, compared a clearly defined anti-infective periodontal intervention (experimental group to an "inactive control" (no periodontal intervention or to an "active control" (lower treatment intensity than the experimental group. Mean differences in final CRP values at the earliest post-treatment time point (typically 1-3 months between experimental and control groups were analyzed using random-effects regression. Among 2,753 possible studies 20 were selected, which included 2,561 randomized patients(median=57. Baseline CRP values were >3.0 mg/L in 40% of trials. Among studies with a control group receiving no treatment, the mean difference in CRP final values among experimental treatment vs. control groups was -0.37 mg/L [95%CI=-0.64, -0.11], (P=0.005, favoring experimental treatment. Trials for which the experimental group received antibiotics had stronger effects (P for interaction=0.03 and the mean difference in CRP final values among experimental treatment vs. control was -0.75 mg/L [95%CI=-1.17,-0.33]. No treatment effect was observed among studies using an active treatment comparator. Treatment effects were stronger for studies that included patients with co-morbidities vs. studies that included "systemically healthy" patients, although the interaction was not significant (P=0.48.Anti-infective periodontal

Hypofractionated radiotherapy as local hemostatic agent in advanced cancer

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Malik Tariq Rasool

2011-01-01

Full Text Available Purpose : Tumor bleeding continues to remain a challenge in an oncological setting, and radiotherapy has been studied as a local hemostatic agent. We studied the role of local radiotherapy in controlling bleeding at our center. Materials and Methods : We reviewed 25 treated cases (cancer urinary bladder: 12, lung cancer: 5, cervical cancer: 4, uterine cancer: 1, rectal cancer: 2, schwanoma: 1 at our center from March 2008 to December 2010. All patients had either an advanced or recurrent disease. Radiotherapy schedule was either 20 Gray in 5 fractions or 15 Gray in 5 fractions and was delivered with Cobalt 60. Results and Conclusion : Of 25 patients, 22 (88% responded, and there was complete cessation of bleeding. Both 15 Gray and 20 Gray dose schedule had equal efficacy. Treatment was well tolerated without any intermission. Radiotherapy is a safe and effective option in controlling tumor bleeding.

A Negative Feedback Loop Between Autophagy and Immune Responses in Mycobacterium leprae Infection.

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Ma, Yuelong; Zhang, Li; Lu, Jie; Shui, Tiejun; Chen, Jia; Yang, Jun; Yuan, Joanna; Liu, Yeqiang; Yang, Degang

2017-01-01

The obligate intracellular bacterium Mycobacterium leprae is the causative agent of leprosy and primarily infects macrophages, leading to irreversible nerve damage and deformities. So far, the underlying reasons allowing M. leprae to persist and propagate in macrophages, despite the presence of cellular immunity, are still a mystery. Here, we investigated the role of autophagy, a cellular process that degrades cytosolic materials and intracellular pathogens, in M. leprae infection. We found that live M. leprae infection of macrophages resulted in significantly elevated autophagy level. However, macrophages with high autophagy levels preferentially expressed lower levels of proinflammatory cytokines, including interleukin (IL)-1β, IL-6, IL-12, and tumor necrosis factor-α, and preferentially primed anti-inflammatory T cells responses, characterized by high IL-10 and low interferon-γ, granzyme B, and perforin responses. These anti-inflammatory T cells could suppress further induction of autophagy, leading to improved survival of intracellular M. leprae in infected macrophages. Therefore, these data demonstrated that although autophagy had a role in eliminating intracellular pathogens, the induction of autophagy resulted in anti-inflammatory immune responses, which suppressed autophagy in a negative feedback loop and allowed the persistence of M. leprae.

Broad, Intense Anti-Human Immunodeficiency Virus (HIV) Ex Vivo CD8+ Responses in HIV Type 1-Infected Patients: Comparison with Anti-Epstein-Barr Virus Responses and Changes during Antiretroviral Therapy

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Dalod, Marc; Dupuis, Marion; Deschemin, Jean-Christophe; Sicard, Didier; Salmon, Dominique; Delfraissy, Jean-Francois; Venet, Alain; Sinet, Martine; Guillet, Jean-Gerard

1999-01-01

The ex vivo antiviral CD8+ repertoires of 34 human immunodeficiency virus (HIV)-seropositive patients with various CD4+ T-cell counts and virus loads were analyzed by gamma interferon enzyme-linked immunospot assay, using peptides derived from HIV type 1 and Epstein-Barr virus (EBV). Most patients recognized many HIV peptides, with markedly high frequencies, in association with all the HLA class I molecules tested. We found no correlation between the intensity of anti-HIV CD8+ responses and the CD4+ counts or virus load. In contrast, the polyclonality of anti-HIV CD8+ responses was positively correlated with the CD4+ counts. The anti-EBV responses were significantly less intense than the anti-HIV responses and were positively correlated with the CD4+ counts. Longitudinal follow-up of several patients revealed the remarkable stability of the anti-HIV and anti-EBV CD8+ responses in two patients with stable CD4+ counts, while both antiviral responses decreased in two patients with obvious progression toward disease. Last, highly active antiretroviral therapy induced marked decreases in the number of anti-HIV CD8+ T cells, while the anti-EBV responses increased. These findings emphasize the magnitude of the ex vivo HIV-specific CD8+ responses at all stages of HIV infection and suggest that the CD8+ hyperlymphocytosis commonly observed in HIV infection is driven mainly by virus replication, through intense, continuous activation of HIV-specific CD8+ T cells until ultimate progression toward disease. Nevertheless, highly polyclonal anti-HIV CD8+ responses may be associated with a better clinical status. Our data also suggest that a decrease of anti-EBV CD8+ responses may occur with depletion of CD4+ T cells, but this could be restored by highly active antiretroviral treatment. PMID:10438796

Minocycline Has Anti-inflammatory Effects and Reduces Cytotoxicity in an Ex Vivo Spinal Cord Slice Culture Model of West Nile Virus Infection.

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Quick, Eamon D; Seitz, Scott; Clarke, Penny; Tyler, Kenneth L

2017-11-15

West Nile virus (WNV) is a neurotropic flavivirus that can cause significant neurological disease. Mouse models of WNV infection demonstrate that a proinflammatory environment is induced within the central nervous system (CNS) after WNV infection, leading to entry of activated peripheral immune cells. We utilized ex vivo spinal cord slice cultures (SCSC) to demonstrate that anti-inflammatory mechanisms may also play a role in WNV-induced pathology and/or recovery. Microglia are a type of macrophage that function as resident CNS immune cells. Similar to mouse models, infection of SCSC with WNV induces the upregulation of proinflammatory genes and proteins that are associated with microglial activation, including the microglial activation marker Iba1 and CC motif chemokines CCL2, CCL3, and CCL5. This suggests that microglia assume a proinflammatory phenotype in response to WNV infection similar to the proinflammatory (M1) activation that can be displayed by other macrophages. We now show that the WNV-induced expression of these and other proinflammatory genes was significantly decreased in the presence of minocycline, which has antineuroinflammatory properties, including the ability to inhibit proinflammatory microglial responses. Minocycline also caused a significant increase in the expression of anti-inflammatory genes associated with alternative anti-inflammatory (M2) macrophage activation, including interleukin 4 (IL-4), IL-13, and FIZZ1. Minocycline-dependent alterations to M1/M2 gene expression were associated with a significant increase in survival of neurons, microglia, and astrocytes in WNV-infected slices and markedly decreased levels of inducible nitric oxide synthase (iNOS). These results demonstrate that an anti-inflammatory environment induced by minocycline reduces viral cytotoxicity during WNV infection in ex vivo CNS tissue. IMPORTANCE West Nile virus (WNV) causes substantial morbidity and mortality, with no specific therapeutic treatments available

Mathematical modeling of malaria infection with innate and adaptive immunity in individuals and agent-based communities.

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Gurarie, David; Karl, Stephan; Zimmerman, Peter A; King, Charles H; St Pierre, Timothy G; Davis, Timothy M E

2012-01-01

Agent-based modeling of Plasmodium falciparum infection offers an attractive alternative to the conventional Ross-Macdonald methodology, as it allows simulation of heterogeneous communities subjected to realistic transmission (inoculation patterns). We developed a new, agent based model that accounts for the essential in-host processes: parasite replication and its regulation by innate and adaptive immunity. The model also incorporates a simplified version of antigenic variation by Plasmodium falciparum. We calibrated the model using data from malaria-therapy (MT) studies, and developed a novel calibration procedure that accounts for a deterministic and a pseudo-random component in the observed parasite density patterns. Using the parasite density patterns of 122 MT patients, we generated a large number of calibrated parameters. The resulting data set served as a basis for constructing and simulating heterogeneous agent-based (AB) communities of MT-like hosts. We conducted several numerical experiments subjecting AB communities to realistic inoculation patterns reported from previous field studies, and compared the model output to the observed malaria prevalence in the field. There was overall consistency, supporting the potential of this agent-based methodology to represent transmission in realistic communities. Our approach represents a novel, convenient and versatile method to model Plasmodium falciparum infection.

Mathematical modeling of malaria infection with innate and adaptive immunity in individuals and agent-based communities.

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David Gurarie

Full Text Available BACKGROUND: Agent-based modeling of Plasmodium falciparum infection offers an attractive alternative to the conventional Ross-Macdonald methodology, as it allows simulation of heterogeneous communities subjected to realistic transmission (inoculation patterns. METHODOLOGY/PRINCIPAL FINDINGS: We developed a new, agent based model that accounts for the essential in-host processes: parasite replication and its regulation by innate and adaptive immunity. The model also incorporates a simplified version of antigenic variation by Plasmodium falciparum. We calibrated the model using data from malaria-therapy (MT studies, and developed a novel calibration procedure that accounts for a deterministic and a pseudo-random component in the observed parasite density patterns. Using the parasite density patterns of 122 MT patients, we generated a large number of calibrated parameters. The resulting data set served as a basis for constructing and simulating heterogeneous agent-based (AB communities of MT-like hosts. We conducted several numerical experiments subjecting AB communities to realistic inoculation patterns reported from previous field studies, and compared the model output to the observed malaria prevalence in the field. There was overall consistency, supporting the potential of this agent-based methodology to represent transmission in realistic communities. CONCLUSIONS/SIGNIFICANCE: Our approach represents a novel, convenient and versatile method to model Plasmodium falciparum infection.

Interdigital foot infections: Corynebacterium minutissimum and agents of superficial mycoses

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Fatma Mutlu Sariguzel

2014-09-01

Full Text Available Interdigital foot infections are mostly caused initially by dermatophytes, yeasts and less frequently by bacteria. Erythrasma caused by Corynebacterium minutissimum can be confused with superficial mycoses. The aim of the study was to determine the prevalence of the etiologic agents of superficial mycoses and the frequency of Corynebacterium minutissimum in interdigital foot infections. All the samples obtained from the 121 patients with interdigital foot infections were examined directly with the use of 20% potassium hydroxide mounts and Gram stain under the microscope and cultured on Sabouraud's dextrose agar plates. In identification of superficial mycoses, the rate was found to be 14% with the cultural method and 14% with direct microscopic examination. Using a combination of direct microscopic examination and culture, a 33.8% ratio was achieved. In the culture of these samples, the most isolated factor was Trichophyton rubrum (33.7%. In 24 of the patients (19.8% Corynebacterium minutissimum was detected by Gram staining, in 6 of these patients Trichophyton rubrum was found, Trichophyton mentagrophytes was found in 2 and Trichosporon spp. was found in 1. The examination of interdigital foot lesions in the laboratory, the coexistence of erythrasma with dermatophytes and yeast should be considered.

Tumor Necrosis Factor-Alpha Targeting Can Protect against Arthritis with Low Sensitization to Infection

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Nadia Belmellat

2017-11-01

Full Text Available Tumor necrosis factor-alpha (TNF-α blockade is an effective treatment for rheumatoid arthritis (RA and other inflammatory diseases, but in patients, it is associated with reduced resistance to the infectious agents Mycobacterium tuberculosis and Listeria monocytogenes, among others. Our goal was to model infection and arthritis in mice and to compare etanercept, a currently used anti-TNF-α inhibitor, to an anti-TNF-α vaccine. We developed a murine surrogate of the TNF-α kinoid and produced an anti-murine TNF-α vaccine (TNFKi composed of keyhole limpet hemocyanin conjugated to TNF-α, which resulted in anti-TNF-α antibody production in mice. We also used etanercept (a soluble receptor of TNF commonly used to treat RA as a control of TNF neutralization. In a mouse model of collagen-induced arthritis, TNFKi protected against inflammation similar to etanercept. In a mouse model of acute L. monocytogenes infection, all TNFKi-treated mice showed cleared bacterial infection and survived, whereas etanercept-treated mice showed large liver granulomas and quickly died. Moreover, TNFKi mice infected with the virulent H37Rv M. tuberculosis showed resistance to infection, in contrast with etanercept-treated mice or controls. Depending on the TNF-α blockade strategy, treating arthritis with a TNF-α inhibitor could result in a different profile of infection suceptibility. Our TNFKi vaccine allowed for a better remaining host defense than did etanercept.

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.

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

DIRECT AND INDIRECT FLUORESCENT-ANTIBODY TECHNIQUES FOR THE PSITTACOSIS-LYMPHOGRANULOMA VENEREUM-TRACHOMA GROUP OF AGENTS1

Science.gov (United States)

Ross, Martin R.; Borman, Earle K.

1963-01-01

Ross, Martin R. (Connecticut State Department of Health, Hartford) and Earle K. Borman. Direct and indirect fluorescent-antibody techniques for the psittacosis-lymphogranuloma venereum-trachoma group of agents. J. Bacteriol. 85:851–858. 1963.—Direct and indirect fluorescent-antibody (FA) techniques were developed for the detection of group antigen in infected tissue cultures and the titration of group antibody in human antiserum. The growth of the agent of meningopneumonitis (MP) in mouse embryo lung cell monolayers was followed by infectivity and complement-fixing (CF) antigen titrations, and cytological examination of FA stained cultures. Although infectivity and CF antigen reached a peak at 2 days and remained constant for an additional 3 days, only cells tested 2 to 3 days after infection were suitable for FA staining with labeled anti-MP serum because of excessive artifacts in the older cultures. Fluorescein isothiocyanate-labeled rooster and guinea pig anti-MP serums and human antipsittacosis serums were titrated in direct FA and hemagglutination-inhibition (HI) tests. The rooster conjugate showed brighter staining and higher antibody titers than the guinea pig or human conjugates and was more effective in detecting minimal amounts of virus antigen. FA staining reactions with 1 and 2 units of labeled rooster serum were inhibited by unlabeled rooster serum but clear-cut inhibition with human antipsittacosis serum could not be demonstrated. The indirect FA technique was successfully used for the titration of group antibody in human serum. A comparison of the indirect FA, HI, and CF tests showed the indirect FA technique to be intermediate in sensitivity between the HI and CF tests. None of the three tests showed significant cross reactions with human serums reactive for influenza A and B; parainfluenza 1, 2, and 3; respiratory syncytial virus; Q fever; or the primary atypical pneumonia agent. PMID:14044954

Simultaneous virtual prediction of anti-Escherichia coli activities and ADMET profiles: A chemoinformatic complementary approach for high-throughput screening.

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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.

Etiologic Agents of Central Nervous System Infections among Febrile Hospitalized Patients in the Country of Georgia

OpenAIRE

Akhvlediani, Tamar; Bautista, Christian T.; Shakarishvili, Roman; Tsertsvadze, Tengiz; Imnadze, Paata; Tatishvili, Nana; Davitashvili, Tamar; Samkharadze, Tamar; Chlikadze, Rusudan; Dvali, Natia; Dzigua, Lela; Karchava, Mariam; Gatserelia, Lana; Macharashvili, Nino; Kvirkvelia, Nana

2014-01-01

OBJECTIVES: There is a large spectrum of viral, bacterial, fungal, and prion pathogens that cause central nervous system (CNS) infections. As such, identification of the etiological agent requires multiple laboratory tests and accurate diagnosis requires clinical and epidemiological information. This hospital-based study aimed to determine the main causes of acute meningitis and encephalitis and enhance laboratory capacity for CNS infection diagnosis. METHODS: Children and adults patients cli...

Skin Infections and Antibiotic Stewardship: Analysis of Emergency Department Prescribing Practices, 2007-2010

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Daniel J. Pallin

2014-05-01

Full Text Available Introduction: National guidelines suggest that most skin abscesses do not require antibiotics, and that cellulitis antibiotics should target streptococci, not community-associated MRSA (CA-MRSA. The objective of this study is to describe antimicrobial treatment of skin infections in U.S. emergency departments (EDs and analyze potential quality measures. Methods: The National Hospital Ambulatory Medical Care Survey (NHAMCS is a 4-stage probability sample of all non-federal U.S. ED visits. In 2007 NHAMCS started recording whether incision and drainage was performed at ED visits. We conducted a retrospective analysis, pooling 2007-2010 data, identified skin infections using diagnostic codes, and identified abscesses by performance of incision and drainage. We generated national estimates and 95% confidence intervals using weighted analyses; quantified frequencies and proportions; and evaluated antibiotic prescribing practices. We evaluated 4 parameters that might serve as quality measures of antibiotic stewardship, and present 2 of them as potentially robust enough for implementation. Results: Of all ED visits, 3.2% (95% confidence interval 3.1-3.4% were for skin infection, and 2.7% (2.6-2.9% were first visits for skin infection, with no increase over time (p=0.80. However, anti-CA-MRSA antibiotic use increased, from 61% (56-66% to 74% (71-78% of antibiotic regimens (p<0.001. Twenty-two percent of visits were for abscess, with a non-significant increase (p=0.06. Potential quality measures: Among discharged abscess patients, 87% were prescribed antibiotics (84-90%, overuse. Among antibiotic regimens for abscess patients, 84% included anti-CA-MRSA agents (81-89%, underuse. Conclusion: From 2007-2010, use of anti-CA-MRSA agents for skin infections increased significantly, despite stable visit frequencies. Antibiotics were over-used for discharged abscess cases, and CA-MRSA-active antibiotics were underused among regimens when antibiotics were used for

Pediatric Infective Endocarditis: Has Staphylococcus aureus Overtaken Viridans Group Streptococci as the Predominant Etiological Agent?

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Aisha Alshammary

2008-01-01

Full Text Available BACKGROUND: Viridans group streptococci (VGS have traditionally been the most common etiological agents of infective endocarditis (IE. Advances in cardiovascular surgery and the increasing use of long-term central venous catheters may have altered the epidemiology of pediatric IE.

Variable transcription of pro- and anti-inflammatory cytokines in phocine lymphocytes following canine distemper virus infection.

Science.gov (United States)

Seibel, H; Siebert, U; Rosenberger, T; Baumgärtner, W

2014-10-15

Canine distemper virus (CDV) is a highly contagious viral pathogen. Domesticated dogs are the main reservoir of CDV. Although phocine distemper virus was responsible for the recent epidemics in seals in the North and Baltic Seas, most devastating epidemics in seals were also caused by CDV. To further study the pathogenesis of CDV infection in seals, it was the aim of the present study to investigate the mechanisms of CDV induced immunosuppression in seals by analyzing the gene transcription of different pro- and anti-inflammatory cytokines in Concanavalin A (Con A) stimulated and non-stimulated phocine lymphocytes in vitro following infection with the CDV Onderstepoort (CDV-OND) strain. Phocine lymphocytes were isolated via density gradient centrifugation. The addition of 1 μg/ml Con A and virus was either performed simultaneously or lymphocytes were stimulated for 48 h with Con A prior to virus infection. Gene transcription of interleukin (IL)-6, IL-12 and tumor necrosis factor alpha (TNFα) as pro-inflammatory cytokines and IL-4, IL-10 and transforming growth factor beta (TGFβ) as anti-inflammatory cytokines were determined by using RT-qPCR. CDV-OND infection caused an initial increase of pro-inflammatory phocine cytokines mRNA 24h after infection, followed by a decrease in gene transcription after 48 h. A strong increase in the transcription of IL-4 and TGFβ was detected after 48 h when virus and mitogen were added simultaneously. An increased IL-10 production occurred only when stimulation and infection were performed simultaneously. Furthermore, an inhibition of IL-12 on IL-4 was noticed in phocine lymphocytes which were stimulated for 48 h prior to infection. In summary, the duration of the stimulation or the lymphocytes seem to have an important influence on the cytokine transcription and indicates that the outcome of CDV infection is dependent on various factors that might sensitize lymphocytes or make them more susceptible or reactive to CDV infection

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

Biological evaluation of 99mTc-Voriconazole as a potential agent for diagnosis of fungal infections by gamma scintigraphy

International Nuclear Information System (INIS)

Reyes, Laura; Martinez, Elena; Giglio, Javier; Teran, Mariella

2011-01-01

The spread of HIV has led to an increase of fungal infections such as candidiasis and invasive aspergillosis. Several types of antifungals are used to treat them and some of them can be radiolabeled with a gamma emitting agent to allow detection by scintigraphy of foci of infection. Voriconazole is a triazole agent, suitable for the synthesis of a complex linked with the precursor [ 99m Tc(H 2 O) 3 (CO) 3 ] + . The aim of his work was to label and determine the physicochemical and biological characteristics of voriconazole with 99m Tc for the early detection of fungal infections. Radiochemical purity was determined by HPLC and the complex remained stable during at least 120 min. In vivo studies in rats bearing either sterile inflammation, infection with C. Albicans or A. Niger showed differentiation of the processes not only in biodistribution but also in scintigraphic images

Impact of Anti-Helicobacter Therapy of H.pylori-Infected Parents on H.pylori Reinfection Rate in Children after Successful Eradication

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O.P. Volosovets

2012-02-01

Full Text Available The article presents the data about the rate of H.pylori reinfection during 12 months after anti-helicobacter therapy among the children after successful eradication. It was shown that H.pylori reinfection rate was lower in children after successful eradication who were living after the treatment with parents non-infectead with H.pylori than among children who were living with H.pylori-infected parents. It was demonstrated that simultaneous anti-helicobacter therapy in H.pylori-infected parents of children with with chronic gastroduodenal diseases associated with H.pylori decreased H.pylori reinfection rate in children with successful eradication.

Paradoxical Deterioration During Anti-Tuberculous Therapy in Non-HIV-Infected Patients with Pleural Tuberculosis: A Pragmatic Approach

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Luis Corral-Gudino

2016-09-01

Full Text Available We report a case of paradoxical deterioration. A male patient diagnosed with pleural tuberculosis, but who was not infected with human immunodeficiency virus (HIV, experienced clinical deterioration 3 weeks after the initiation of anti-tuberculous treatment. After other diagnoses were ruled out, a paradoxical response to treatment was established and the patient was started on systemic corticosteroids. Paradoxical response to treatment should be considered in patients with clinical deterioration after they start on anti-tuberculous treatment.

Current trends in local antibacterial therapy of periprosthetic infection and osteomyelitis

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S. A. Bozhkova

2015-01-01

Full Text Available The rational use of antibiotics in the treatment of orthopedic infection still presents a significant problem. Local antibiotic delivery systems enable to achieve effective concentrations of drugs in the focus of bone infection without the development of toxicity. It is the important accompaniment to systemic antibiotics in the treatment of periprosthetic infection and osteomyelitis. The data collected through the PubMed and eLIBRARY databases (http://www.ncbi.nlm. nih.gov/pubmed, 1995-2015; http://elibrary.ru, 2005-2015 years present the information about bone substitutes used for local antibiotic therapy in scientific investigations and in clinical practice. The information is submitted in accordance with the groups of materials: cements based on polymethylmethacrylate, bone grafts, demineralized bone matrix, bioceramics, natural and synthetic polymers, combined antibiotic delivery systems. The majority of these materials have only been studied experimentally and only a limited range of them is registered for use in clinical practice. Informing orthopedic surgeons about current methods of local antibiotic use is the key to the development of a modern integrated approach to the therapy of infectious complications after orthopedic surgery.

Effective anthelmintic therapy of residents living in endemic area of high prevalence for Hookworm and Schistosoma mansoni infections enhances the levels of allergy risk factor anti-Der p1 IgE

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Sabrina S. Campolina

2015-01-01

Full Text Available In this work were investigated the relationship between Hookworm/Schistosoma mansoni infections and allergy related risk factors in two endemic areas with distinct prevalence of infections and co-infection. The intensity of infections, eosinophilia, allergy risk factors, infections status and anti-Der p1 IgE levels before and 2 years (population 1 and 3 years (population 2 after anthelmintic treatment, were evaluated. It was observed that the population with lower prevalence and intensity of infection (population 2 had lower eosinophils counts (>600/mm3 and higher animal contact than the population with higher parasites intensity (population 1. After anthelmintic treatment the intensity of S. mansoni single infection decreased, but no changes were observed in Hookworm and co-infected individuals. The anthelmintic treatment also enhanced anti-Der p1 IgE optical density in ELISA on the subgroups that became negative for helminth infection regardless of their previous infection condition in population 1. Facing that, we evaluated the anti-Der p1 IgE reactivity index, and the ratio (after/before treatment was significantly higher in patients co-infected before treatment. On the other hand, no association between anti-Der p1 IgE reactivity index and the intensity of infections were observed. In conclusion, effective anthelmintic therapy of subjects from endemic areas with high prevalence of Hookworm and S. mansoni infections enhances anti-Der p1 IgE levels.

[Gastropathy caused by non-steroidal anti-inflammatory agents and its association with Helicobacter pylori].

Science.gov (United States)

Rodríguez-Hernández, Heriberto; Jacobo-Karam, Janett S; Jáquez-Quintana, Joel O; Avila-Romero, Hilda G; Galván-Román, Liliana; Lara-Miranda, Sandra C; Sánchez-Anguiano, Luis F

2003-01-01

Upper gastrointestinal bleeding that is related with older patients and NSAIDs use. The frequency of peptic ulcer bleeding varies of 15% to 30% of cases. To determine the gastropathy features of patients who receive nonsteroidal anti-inflammatory drug, and its relation with Helicobacter pylori (Hp). Men and women with GU or DU with or without haemorrhage, were included into two groups, NSAIDs users and non users. We determined the incidence rate of peptic ulcer and the frequencies of risk factors as tobacco use, previous peptic ulcer or haemorrhage, concomitant disease presence and its association with Hp infection. We included 434 (67.5%) patients that used NSAIDs and 209 (32.5%) non NSAIDs users control subjects. The average was 62.5 +/- 17.2 years and 49.5 +/- 19.4 years respectively. The annual incidence rate of peptic ulcer in NSAIDs users was 17.5%. Gastrointestinal bleeding was more frequent in NSAIDs users and its relations with Hp infection (23.5%) was smaller than patients without NSAIDs user (47.7%) (OR 0.39 p = 0.0000). The GU was highly frequent in the older people who using NSAIDs. The Hp infection shows lower incidence of gastrointestinal bleeding NSAIDs users.

Iota-Carrageenan is a potent inhibitor of rhinovirus infection

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Meier Christiane

2008-09-01

Full Text Available Abstract Background Human rhinoviruses (HRVs are the predominant cause of common cold. In addition, HRVs are implicated in the worsening of COPD and asthma, as well as the loss of lung transplants. Despite significant efforts, no anti-viral agent is approved for the prevention or treatment of HRV-infection. Results In this study we demonstrate that Iota-Carrageenan, a sulphated polysaccharide derived from red seaweed, is a potent anti-rhinoviral substance in-vitro. Iota-Carrageenan reduces HRV growth and inhibits the virus induced cythopathic effect of infected HeLa cells. In addition, Iota-Carrageenan effectively prevents the replication of HRV1A, HRV2, HRV8, HRV14, HRV16, HRV83 and HRV84 in primary human nasal epithelial cells in culture. The data suggest that Iota-Carrageenan acts primarily by preventing the binding or the entry of virions into the cells. Conclusion Since HRV infections predominately occur in the nasal cavity and the upper respiratory tract, a targeted treatment with a product containing Iota-Carrageenan is conceivable. Clinical trials are needed to determine whether Iota-Carrageenan-based products are effective in the treatment or prophylaxis of HRV infections.

Surface localization of the nuclear receptor CAR in influenza A virus-infected cells

International Nuclear Information System (INIS)

Takahashi, Tadanobu; Moriyama, Yusuke; Ikari, Akira; Sugatani, Junko; Suzuki, Takashi; Miwa, Masao

2008-01-01

Constitutive active/androstane receptor CAR is a member of the nuclear receptors which regulate transcription of xenobiotic metabolism enzymes. CAR is usually localized in the cytosol and nucleus. Here, we found that CAR was localized at the cell surface of influenza A virus (IAV)-infected cells. Additionally, we demonstrated that expression of a viral envelope glycoprotein, either hemagglutinin (HA) or neuraminidase (NA), but not viral nucleoprotein (NP), was responsible for this localization. This report is the first demonstration of CAR at the surface of tissue culture cells, and suggests that CAR may exert the IAV infection mechanism

Potential management of resistant microbial infections with a novel non-antibiotic

DEFF Research Database (Denmark)

Dutta, Noton Kumar; Annadurai, Subramanian; Mazumdar, Kaushiki

2007-01-01

Diclofenac sodium (Dc), an anti-inflammatory agent, has remarkable inhibitory action both against drug-sensitive and drug-resistant clinical isolates of various Gram-positive and Gram-negative bacteria. The aim of this study was to determine the ability of Dc to protect mice from a virulent...... Salmonella infection. Dc injected at 1.5 microg/g and 3.0 microg/g mouse body weight significantly protected animals from the lethality of Salmonella infection. As was the case for the in vitro interaction, Dc in combination with streptomycin was even more effective. The non-antibiotic drug Dc has potential...... for the management of problematic antibiotic-resistant bacterial infections....

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

Promising biocidal activity of thymol loaded chitosan silver nanoparticles (T-C@AgNPs) as anti-infective agents against perilous pathogens.

Science.gov (United States)

Manukumar, H M; Umesha, S; Kumar, H N Naveen

2017-09-01

The advent of biodegradable polymer-encapsulated drug nanoparticles has made an exciting area of drug delivery research. The present study investigated novel and simple route for synthesis of thymol loaded chitosan silver nanoparticles (T-C@AgNPs) using chitosan and thymol as reducing, capping agent respectively to understand the therapeutic efficacy. The UV-vis spectroscopy, DLS, FT-IR, SEM, EDS, XRD used for characterization and radical scavenging activity, anti-microbial and biocompatibility was taken to ascertain an efficacy of novel T-C@AgNPs. The T-C@AgNPs intense peak at 490nm indicates the formation of nanoparticles and had average particle size of 28.94nm with spherical shape, monodisperse state in water, also exhibited excellent biocompatibility of cubic shaped pure silver element containing T-C@AgNPs. The antibacterial activity was studied for gram positive and gram negative food-borne pathogens and effective inhibition at 100μgmL -1 to S. aureus, S. epidermidis, S. haemolyticus (10.08, 10.00, 11.23mm) and S. typhimurium, P. aeruginosa and S. flexneri (9.28, 9.33, 12.03mm) compared to antibiotic Streptomycin. This study revealed the efficacy against multiple food-borne pathogens and therapeutic efficacy of T-C@AgNPs offers a valuable contribution in the area of nanotechnology. This proved to be a first-class novel antimicrobial material for the first time in this study. Copyright © 2017 Elsevier B.V. All rights reserved.

Apolipoprotein B-associated cholesterol is a determinant of treatment outcome in patients with chronic hepatitis C virus infection receiving anti-viral agents interferon-alpha and ribavirin.

Science.gov (United States)

Sheridan, D A; Price, D A; Schmid, M L; Toms, G L; Donaldson, P; Neely, D; Bassendine, M F

2009-06-15

Hepatitis C virus (HCV) co-opts very-low-density lipoprotein (VLDL) pathways for replication, secretion and entry into hepatocytes and associates with apolipoprotein B (apoB) in plasma. Each VLDL contains apoB-100 and variable amounts of apolipoproteins E and C, cholesterol and triglycerides. To determine whether baseline lipid levels predicted treatment outcome. Retrospective analysis was performed of 250 chronic hepatitis C (CHC) patients who had received anti-viral agents interferon-alpha and ribavirin; 165 had a sustained virological response (SVR). Pre- and post-treatment nonfasting lipid profiles were measured and non-high-density lipoprotein (non-HDL) cholesterol (i.e. apoB-associated) was calculated. Binary logistic regression analysis assessed factors independently associated with treatment outcome. There was an independent association between higher apoB-associated cholesterol (non-HDL-C) and increased odds of SVR (odds ratio 2.09, P = 0.042). In multivariate analysis, non-HDL-C was significantly lower in HCV genotype 3 (g3) than genotype 1 (P = 0.007); this was reversible upon eradication of HCVg3 (pre-treatment non-HDL-C = 2.8 mmol/L, SVR = 3.6 mmol/L, P < 0.001). Higher apoB-associated cholesterol is positively associated with treatment outcome in CHC patients receiving anti-viral therapy, possibly due to competition between apoB-containing lipoproteins and infectious low-density HCV lipo-viral particles for hepatocyte entry via shared lipoprotein receptors.

Preventing Pseudomonas aeruginosa and Chromobacterium violaceum infections by anti-adhesion-active components of edible seeds

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Rachmaninov Ofra

2012-02-01

Full Text Available Abstract Background Pseudomonas aeruginosa adhesion to animal/human cells for infection establishment involves adhesive proteins, including its galactose- and fucose-binding lectins PA-IL (LecA and PA-IIL (LecB. The lectin binding to the target-cell receptors may be blocked by compatible glycans that compete with those of the receptors, functioning as anti-adhesion glycodecoys. The anti-adhesion treatment is of the utmost importance for abrogating devastating antibiotic-resistant P. aeruginosa infections in immunodeficient and cystic fibrosis (CF patients. This strategy functions in nature in protecting embryos and neonates. We have shown that PA-IL, PA-IIL, and also CV-IIL (a PA-IIL homolog produced in the related pathogen Chromobacterium violaceum are highly useful for revealing natural glycodecoys that surround embryos in diverse avian eggs and are supplied to neonates in milks and royal jelly. In the present study, these lectins were used as probes to search for seed embryo-protecting glycodecoys. Methods The lectin-blocking glycodecoy activities were shown by the hemagglutination-inhibition test. Lectin-binding glycoproteins were detected by Western blotting with peroxidase-labeled lectins. Results The present work reports the finding - by using PA-IL, PA-IIL, and CV-IIL - of rich glycodecoy activities of low ( 10 kDa compounds (including glycoproteins in extracts of cashew, cocoa, coffee, pumpkin, and tomato seeds, resembling those of avian egg whites, mammal milks, and royal jelly. Conclusions Edible seed extracts possess lectin-blocking glycodecoys that might protect their embryos from infections and also might be useful for hampering human and animal infections.

year surveillance of wound infections at a rural tertiary hospital in ...

African Journals Online (AJOL)

EB

Conclusions: Staphylococcus aureus was the most predominant etiologic agent of wound infection among in and out patients. ... methicillin – resistant Staphylococus aureus (MRSA) and ... Northeast local government area of Edo State,.

Emergence of anti-red blood cell antibodies triggers red cell phagocytosis by activated macrophages in a rabbit model of Epstein-Barr virus-associated hemophagocytic syndrome.

Science.gov (United States)

Hsieh, Wen-Chuan; Chang, Yao; Hsu, Mei-Chi; Lan, Bau-Shin; Hsiao, Guan-Chung; Chuang, Huai-Chia; Su, Ih-Jen

2007-05-01

Hemophagocytic syndrome (HPS) is a fatal complication frequently associated with viral infections. In childhood HPS, Epstein-Barr virus (EBV) is the major causative agent, and red blood cells (RBCs) are predominantly phagocytosed by macrophages. To investigate the mechanism of RBC phagocytosis triggered by EBV infection, we adopted a rabbit model of EBV-associated HPS previously established by using Herpesvirus papio (HVP). The kinetics of virus-host interaction was studied. Using flow cytometry, we detected the emergence of antibody-coated RBCs, as well as anti-platelet antibodies, at peak virus load period at weeks 3 to 4 after HVP injection, and the titers increased thereafter. The presence of anti-RBCs preceded RBC phagocytosis in tissues and predicted the full-blown development of HPS. The anti-RBC antibodies showed cross-reactivity with Paul-Bunnell heterophile antibodies. Preabsorption of the HVP-infected serum with control RBCs removed the majority of anti-RBC activities and remarkably reduced RBC phagocytosis. The RBC phagocytosis was specifically mediated via an Fc fragment of antibodies in the presence of macrophage activation. Therefore, the emergence of anti-RBC antibodies and the presence of macrophage activation are both essential in the development of HPS. Our observations in this animal model provide a potential mechanism for hemophagocytosis in EBV infection.

Progress in the Discovery of Treatments for C. difficile Infection: A Clinical and Medicinal Chemistry Review

Science.gov (United States)

Tsutsumi, Lissa S.; Owusu, Yaw B.; Hurdle, Julian G.; Sun, Dianqing

2014-01-01

Clostridium difficile is an anaerobic, Gram-positive pathogen that causes C. difficile infection, which results in significant morbidity and mortality. The incidence of C. difficile infection in developed countries has become increasingly high due to the emergence of newer epidemic strains, a growing elderly population, extensive use of broad spectrum antibiotics, and limited therapies for this diarrheal disease. Because treatment options currently available for C. difficile infection have some drawbacks, including cost, promotion of resistance, and selectivity problems, new agents are urgently needed to address these challenges. This review article focuses on two parts: the first part summarizes current clinical treatment strategies and agents under clinical development for C. difficile infection; the second part reviews newly reported anti-difficile agents that have been evaluated or reevaluated in the last five years and are in the early stages of drug discovery and development. Antibiotics are divided into natural product inspired and synthetic small molecule compounds that may have the potential to be more efficacious than currently approved treatments. This includes potency, selectivity, reduced cytotoxicity, and novel modes of action to prevent resistance. PMID:24236721

Effect of Antiviral Agents in Equine Abortion Virus-Infected Hamsters1

Science.gov (United States)

Lieberman, Melvin; Pascale, Andrea; Schafer, Thomas W.; Came, Paul E.

1972-01-01

Equine abortion virus, a member of the herpesvirus group, produces a lethal infection in hamsters. With this system, the protective effect of certain inhibitors of deoxyribonucleic acid viruses, inducers of interferon and exogenous interferon, was evaluated. Of the various agents studied, 9-β-d-arabinofuranosyladenine markedly suppressed mortality, and 5-iodo-2′-deoxyuridine, distamycin A, and N-ethylisatin β-thiosemicarbazone were inactive. Of the inducers tested, statolon, ultraviolet-irradiated Newcastle disease virus, and polyriboinosinic:polyribocytidylic acid (poly I:C) were protective, and endotoxin, polyacrylic acid, and polymethacrylic acid did not protect. Administration of exogenous interferon did not afford protection. Statolon and ultraviolet-irradiated Newcastle disease virus induced circulating interferon in hamsters, whereas poly I:C, endotoxin, and polyacrylic acid did not produce interferon. Because of the severity of the disease produced in hamsters by equine abortion virus, lack of protective activity by an agent in this system should not preclude possible efficacy against other members of the herpesvirus group. PMID:4376907

High throughput virtual screening and in silico ADMET analysis for rapid and efficient identification of potential PAP248-286 aggregation inhibitors as anti-HIV agents

Science.gov (United States)

Malik, Ruchi; Bunkar, Devendra; Choudhary, Bhanwar Singh; Srivastava, Shubham; Mehta, Pakhuri; Sharma, Manish

2016-10-01

Human semen is principal vehicle for transmission of HIV-1 and other enveloped viruses. Several endogenous peptides present in semen, including a 39-amino acid fragments of prostatic acid phosphatase (PAP248-286) assemble into amyloid fibrils named as semen-derived enhancer of viral infection (SEVI) that promote virion attachment to target cells which dramatically enhance HIV virus infection by up to 105-fold. Epigallocatechin-3-gallate (EGCG), a polyphenolic compound, is the major catechin found in green tea which disaggregates existing SEVI fibers, and inhibits the formation of SEVI fibers. The aim of this study was to screen a number of relevant polyphenols to develop a rational approach for designing PAP248-286 aggregation inhibitors as potential anti-HIV agents. The molecular docking based virtual screening results showed that polyphenolic compounds 2-6 possessed good docking score and interacted well with the active site residues of PAP248-286. Amino acid residues of binding site namely; Lys255, Ser256, Leu258 and Asn265 are involved in binding of these compounds. In silico ADMET prediction studies on these hits were also found to be promising. Polyphenolic compounds 2-6 identified as hits may act as novel leads for inhibiting aggregation of PAP248-286 into SEVI.

Immunoglobulin GM and KM Allotypes and Prevalence of Anti-LKM1 Autoantibodies in Patients with Hepatitis C Virus Infection

OpenAIRE

Muratori, Paolo; Sutherland, Susan E.; Muratori, Luigi; Granito, Alessandro; Guidi, Marcello; Pappas, Georges; Lenzi, Marco; Bianchi, Francesco B.; Pandey, Janardan P.

2006-01-01

GM and KM allotypes—genetic markers of immunoglobulin (Ig) γ and κ chains, respectively—are associated with humoral immunity to several infection- and autoimmunity-related epitopes. We hypothesized that GM and KM allotypes contribute to the generation of autoantibodies to liver/kidney microsomal antigen 1 (LKM1) in hepatitis C virus (HCV)-infected persons. To test this hypothesis, we characterized 129 persons with persistent HCV infection for several GM and KM markers and for anti-LKM1 antibo...

Assessment of acute phase proteins and oxidative stress status of Nigerians using bleaching agents

International Nuclear Information System (INIS)

Akibinu, M.O.; Arinola, O.G.; Afolabi, K.A.

2010-01-01

The disruption of primary innate immune function of the epidermal layer of the skin accounts for the susceptibility of individuals using bleaching agents to localized or systemic infections. This subverted innate immunity in these people may lead to other pathological conditions. The resultant effects of skin bleaching and phagocytes activation in response to infections have not been studied in Nigerians using bleaching agents. The present study therefore assessed the levels of C-reactive protein (CRP), albumin, total antioxidant potential (TAP), total plasma peroxides (TPP), oxidative stress index (OSI) and malonaldehyde (MDA) in the users bleaching agents. Thirty (30) people who had used bleaching agents for average of 4.9 + 1.2 years participated in this study. They were recruited from various schools and markets within the city of Ibadan, Oyo State, Nigeria. Thirty apparently healthy staffs of University College Hospital Ibadan, Ibaadan, Nigeria, who had never used bleaching agents served as controls. All the subjects used for this study had no metabolic abnormality and tested negative to both HIV and hepatitis B infections. The mean value of TAP (p 0.20) when compared with the controls. Oxidative stress and chronic inflammation are possible consequences of skin bleaching. The users of skin bleaching agents may need antioxidant therapies to avert the risks of oxidative stress. (author)

Estimating risks of importation and local transmission of Zika virus infection

Directory of Open Access Journals (Sweden)

Kyeongah Nah

2016-04-01

Full Text Available Background. An international spread of Zika virus (ZIKV infection has attracted global attention. ZIKV is conveyed by a mosquito vector, Aedes species, which also acts as the vector species of dengue and chikungunya viruses. Methods. Arrival time of ZIKV importation (i.e., the time at which the first imported case was diagnosed in each imported country was collected from publicly available data sources. Employing a survival analysis model in which the hazard is an inverse function of the effective distance as informed by the airline transportation network data, and using dengue and chikungunya virus transmission data, risks of importation and local transmission were estimated. Results. A total of 78 countries with imported case(s have been identified, with the arrival time ranging from 1 to 44 weeks since the first ZIKV was identified in Brazil, 2015. Whereas the risk of importation was well explained by the airline transportation network data, the risk of local transmission appeared to be best captured by additionally accounting for the presence of dengue and chikungunya viruses. Discussion. The risk of importation may be high given continued global travel of mildly infected travelers but, considering that the public health concerns over ZIKV infection stems from microcephaly, it is more important to focus on the risk of local and widespread transmission that could involve pregnant women. The predicted risk of local transmission was frequently seen in tropical and subtropical countries with dengue or chikungunya epidemic experience.

First reported outbreak of locally acquired hepatitis E virus infection in Australia.

Science.gov (United States)

Yapa, Chaturangi M; Furlong, Catriona; Rosewell, Alexander; Ward, Kate A; Adamson, Sheena; Shadbolt, Craig; Kok, Jen; Tracy, Samantha L; Bowden, Scott; Smedley, Elizabeth J; Ferson, Mark J; Sheppeard, Vicky; McAnulty, Jeremy M

2016-04-18

To determine the source and extent of a locally acquired hepatitis E virus (HEV) infection outbreak. A cluster of notified cases of HEV infection linked to a single restaurant (X) was identified in May 2014. People with laboratory-confirmed HEV infection in New South Wales between January 2013 and December 2014 were interviewed about potential risk factors for HEV infection. Co-diners at restaurant X and patients with suspected but unexplained viral hepatitis were retrospectively tested. Foods eaten by the infected persons were compared with those of seronegative co-diners. HEV RNA detected in sera from infected persons was sequenced and genotyped. Implicated foods were traced back to their sources. Potential sources of infection, including overseas travel and foods eaten, and origin of implicated food products. In 55 serologically confirmed cases of HEV infection, 24 people had not travelled overseas during their incubation periods. Of the 24, 17 reported having eaten at restaurant X, 15 of whom could be interviewed. All reported consuming pork liver pâté, compared with only four of seven uninfected co-diners (P restaurant X isolates. HEV RNA was isolated from pork sausages from a batch implicated in one of the locally acquired infections not linked with restaurant X. The pork livers used for pâté preparation by restaurant X were traced to a single Australian farm. This is the first reported HEV outbreak in Australia. HEV should be considered in patients presenting with a compatible illness, even without a history of overseas travel. Pork products should be thoroughly cooked before consumption.

Anti-chikungunya activity of luteolin and apigenin rich fraction from Cynodon dactylon.

Science.gov (United States)

Murali, Krishnan Saravana; Sivasubramanian, Srinivasan; Vincent, Savariar; Murugan, Shanmugaraj Bala; Giridaran, Bupesh; Dinesh, Sundaram; Gunasekaran, Palani; Krishnasamy, Kaveri; Sathishkumar, Ramalingam

2015-05-01

To obtain luteolin and apigenin rich fraction from the ethanolic extract of Cynodon dactylon (L.) (C. dactylon) Pers and evaluate the fraction's cytotoxicity and anti-Chikungunya potential using Vero cells. The ethanolic extract of C. dactylon was subjected to silica gel column chromatography to obtain anti-chikungunya virus (CHIKV) fraction. Reverse phase-HPLC and GC-MS studies were carried out to identify the major phytochemicals in the fraction using phytochemical standards. Cytotoxicity and the potential of the fraction against CHIKV were evaluated in vitro using Vero cells. Reduction in viral replication was assessed by reverse transcriptase-polymerase chain reaction (RT-PCR) after treating the viral infected Vero cells with the fraction. Reverse Phase-HPLC and GC-MS studies confirmed the presence of flavonoids, luteolin and apigenin as major phytochemicals in the anti-CHIKV ethanolic fraction of C. dactylon. The fraction was found to exhibit potent viral inhibitory activity (about 98%) at the concentration of 50 µg/mL as observed by reduction in cytopathic effect, and the cytotoxic concentration of the fraction was found to be 250 µg/mL. RT-PCR analyses indicated that the reduction in viral mRNA synthesis in fraction treated infected cells was much higher than the viral infected control cells. Luteolin and apigenin rich ethanolic fraction from C. dactylon can be utilized as a potential therapeutic agent against CHIKV infection as the fraction does not show cytotoxicity while inhibiting the virus. Copyright © 2015 Hainan Medical College. Production and hosting by Elsevier B.V. All rights reserved.