[Screening of anti-aging active ingredients and mechanism analysis based on molecular docking technology].

Science.gov (United States)

Du, Ran-Feng; Zhang, Xiao-Hua; Ye, Xiao-Tong; Yu, Wen-Kang; Wang, Yun

2016-07-01

Dampness evil is the source of all diseases, which is easy to cause disease and promote aging, while aging could also promote the occurence and development of diseases. In this paper, the relationship between the dampness evil and aging would be discussed, to find the anti-aging active ingredients in traditional Chinese medicine (TCM), and analyze the anti-aging mechanism of dampness eliminating drug. Molecular docking technology was used, with aging-related mammalian target of rapamycin as the docking receptors, and chemical components of Fuling, Sangzhi, Mugua, Yiyiren and Houpo as the docking molecules, to preliminarily screen the anti-aging active ingredients in dampness eliminating drug. Through the comparison with active drugs already on the market (temsirolimus and everolimus), 12 kinds of potential anti-aging active ingredients were found, but their drug gability still needs further study. The docking results showed that various components in the dampness eliminating drug can play anti-aging activities by acting on mammalian target of rapamycin. This result provides a new thought and direction for the method of delaying aging by eliminating dampness. Copyright© by the Chinese Pharmaceutical Association.

[Exploration on mechanism of anti-influenza virus activity of genus Paeonia based on network pharmacology].

Science.gov (United States)

Cai, Ya-Qi; Bao, Ya-Ting; Wang, Hong-Jin; Ren, Xiao-Dong; Huang, Lin-Fang; He, Jie; Liu, Tian-Tian; Zeng, Rui

2018-04-01

This paper aimed to investigate the anti-influenza virus activity of the genus Paeonia, screen potential anti-influenza virus compounds and predict targets of anti-influenza virus to explore the mechanism of anti-influenza virus activity. First of all, a total of 301 compounds of the genus Paeonia were summarized from the literatures in recent ten years. The candidate active ingredients from the genus Paeonia were identified by database such as PubChem and Chemical Book. The ligands were constructed by ChemDraw, Avogadro and Discovery Studio Visualizer. Secondly, 23 potential anti-influenza virus targets were developed by combining the target database and the literatures. Uniprot database was used to find the anti-influenza virus targets, and RCSB was used to identify targets associated with anti-influenza virus activity as docked receptor proteins. QuickVina 2.0 software was used for molecular docking. Finally, the Cytoscape 3.5.1 software was used to map the potential activity compounds of the genus Paeonia against influenza virus and the anti-influenza virus target network. Uniprot online database was used to analyze the target GO enrichment and KEGG metabolic pathways. The results showed that 74 compounds of the genus Paeonia had anti-influenza virus effect and 18 potential anti-influenza virus targets were screened. GO analysis concluded that the mechanism of the genus Paeonia anti-influenza virus is consistent with the mechanism of NA anti-influenza virus in order to stop the sprouting, dispersion and diffusion of virus and reduce the ability of virus to infect, so that the infection can be restricted so as to achieve the anti-influenza virus effect. Copyright© by the Chinese Pharmaceutical Association.

Recent Advances in Screening of Anti-Campylobacter Activity in Probiotics for Use in Poultry

Science.gov (United States)

Saint-Cyr, Manuel J.; Guyard-Nicodème, Muriel; Messaoudi, Soumaya; Chemaly, Marianne; Cappelier, Jean-Michel; Dousset, Xavier; Haddad, Nabila

2016-01-01

Campylobacteriosis is the most common cause of bacterial gastroenteritis worldwide. Campylobacter species involved in this infection usually include the thermotolerant species Campylobacter jejuni. The major reservoir for C. jejuni leading to human infections is commercial broiler chickens. Poultry flocks are frequently colonized by C. jejuni without any apparent symptoms. Risk assessment analyses have identified the handling and consumption of poultry meat as one of the most important sources of human campylobacteriosis, so elimination of Campylobacter in the poultry reservoir is a crucial step in the control of this foodborne infection. To date, the use of probiotics has demonstrated promising results to reduce Campylobacter colonization. This review provides recent insights into methods used for probiotic screening to reduce the prevalence and colonization of Campylobacter at the farm level. Different eukaryotic epithelial cell lines are employed to screen probiotics with an anti-Campylobacter activity and yield useful information about the inhibition mechanism involved. These in vitro virulence models involve only human intestinal or cervical cell lines whereas the use of avian cell lines could be a preliminary step to investigate mechanisms of C. jejuni colonization in poultry in the presence of probiotics. In addition, in vivo trials to evaluate the effect of probiotics on Campylobacter colonization are conducted, taking into account the complexity introduced by the host, the feed, and the microbiota. However, the heterogeneity of the protocols used and the short time duration of the experiments lead to results that are difficult to compare and draw conclusions at the slaughter-age of broilers. Nevertheless, the combined approach using complementary in vitro and in vivo tools (cell cultures and animal experiments) leads to a better characterization of probiotic strains and could be employed to assess reduced Campylobacter spp. colonization in chickens if some

Phytochemical screening and antimalarial activity of some plants traditionally used in Indonesia

Directory of Open Access Journals (Sweden)

Syamsudin Abdillah

2015-06-01

Full Text Available Objective: To evaluate ethanolic extracts of phytochemical screening, in vitro and in vivo antiplasmodial activities of 15 plants used as antimalarial in Sei Kepayang, North Sumatra. Methods: Extraction was done through maceration with 70% ethanol and screened against chemical content, in vitro test anti-plasmodium against Plasmodium falciparum 3D7 strain and in vivo test in mice infected Plasmodium berghei. Results: The results showed that the plant extract contained a group of saponins, flavonoids, alkaloids, quinone, sterols, triterpene, tannins and cumarine. However, extract of Momordica charantia, Carica papaya, Garcinia atroviridis, Alstonia scholaris, Smallanthus sonchifolia and Cassia siamea had strong anti-plasmodium activity both in vitro and in vivo. Conclusions: In vitro and in vivo antiplasmodial activities of 15 plants are used as antimalarial in Sei Kepayang, North Sumatra. All the plants have in vitro and in vivo anti-plasmodium activity except Orthosiphon stamineus and Luffa cylindrica (ED50 > 1 000 mg/kg body weight and IC50 > 100 μg/mL, respectively.

Rapid in vivo screening method for the evaluation of new anti ...

African Journals Online (AJOL)

Rapid in vivo screening method for the evaluation of new anti helicobacter ... Six to eight week-old mice pre-treated (7 days) with Amoxicillin/Metronidazole (25 ... These findings were used as a mouse model of Helicobacter pylori infection to ...

Beliefs Underlying Messages of Anti-Cancer-Screening

Science.gov (United States)

Okuhara, Tsuyoshi; Ishikawa, Hirono; Okada, Masahumi; Kato, Mio; Kiuchi, Takahiro

2018-02-26

Background: Cancer screening rates are lower in Japan than in Western countries. Meanwhile, anti-cancer-screening activists take to the internet to spread their messages that cancer screening has little or no efficacy, poses substantial health risks such as side effects from radiation exposure, and that people should forgo cancer screening. We applied a qualitative approach to explore the beliefs underlying the messages of anti-cancer-screening websites, by focusing on perceived value the beliefs provided to those who held them. Methods: We conducted online searches using Google Japan and Yahoo! Japan, targeting websites we classified as “pro,” “anti,” or “neutral” depending on their claims. We applied a dual analytic approach- inductive thematic analysis and deductive interpretative analysis- to the textual data of the anti websites. Results: Of the 88 websites analyzed, five themes that correspond to beliefs were identified: destruction of common knowledge, denial of standard cancer control, education about right cancer control, education about hidden truths, and sense of superiority that only I know the truth. Authors of anti websites ascribed two values (“safety of people” and “self-esteem”) to their beliefs. Conclusion: The beliefs of authors of anti-cancer-screening websites were supposed to be strong. It would be better to target in cancer screening promotion not outright screening refusers but screening hesitant people who are more amenable to changing their attitudes toward screening. The possible means to persuade them were discussed. Creative Commons Attribution License

In vitro thrombolytic, anthelmintic, anti-oxidant and cytotoxic activity with phytochemical screening of methanolic extract of Xanthium indicum leaves

Directory of Open Access Journals (Sweden)

Antara Ghosh

2015-12-01

Full Text Available Xanthium indicum is an important medicinal plant traditionally used in Bangladesh as a folkloric treatment. The current study was undertaken to evaluate thrombolytic, anthelmintic, anti-oxidant, cytotoxic properties with phytochemical screening of methanolic extract of X. indicum leaves. The analysis of phytochemical screening confirmed the existence of phytosetrols and diterpenes. In thrombolytic assay, a significant clot lysis was observed at four concentrations of plant extract compare to the positive control streptokinase (30,000 IU, 15,000 IU and negative control normal saline. The extract revealed potent anthelmintic activity at different concentrations. In anti-oxidant activity evaluation by two potential experiments namely total phenolic content determination and free radical scavenging assay by 2, 2-diphenylpicrylhydrazyl (DPPH, the leaves extract possess good anti-oxidant property. In the brine shrimp lethality bioassay, the crude extract showed potent (LC50 1.3 μg/mL cytotoxic activity compare to the vincristine sulfate as a positive control (LC50 0.8 μg/mL.

Anti-biofilm, anti-hemolysis, and anti-virulence activities of black pepper, cananga, myrrh oils, and nerolidol against Staphylococcus aureus.

Science.gov (United States)

Lee, Kayeon; Lee, Jin-Hyung; Kim, Soon-Il; Cho, Moo Hwan; Lee, Jintae

2014-11-01

The long-term usage of antibiotics has resulted in the evolution of multidrug-resistant bacteria. Unlike antibiotics, anti-virulence approaches target bacterial virulence without affecting cell viability, which may be less prone to develop drug resistance. Staphylococcus aureus is a major human pathogen that produces diverse virulence factors, such as α-toxin, which is hemolytic. Also, biofilm formation of S. aureus is one of the mechanisms of its drug resistance. In this study, anti-biofilm screening of 83 essential oils showed that black pepper, cananga, and myrrh oils and their common constituent cis-nerolidol at 0.01 % markedly inhibited S. aureus biofilm formation. Furthermore, the three essential oils and cis-nerolidol at below 0.005 % almost abolished the hemolytic activity of S. aureus. Transcriptional analyses showed that black pepper oil down-regulated the expressions of the α-toxin gene (hla), the nuclease genes, and the regulatory genes. In addition, black pepper, cananga, and myrrh oils and cis-nerolidol attenuated S. aureus virulence in the nematode Caenorhabditis elegans. This study is one of the most extensive on anti-virulence screening using diverse essential oils and provides comprehensive data on the subject. This finding implies other beneficial effects of essential oils and suggests that black pepper, cananga, and myrrh oils have potential use as anti-virulence strategies against persistent S. aureus infections.

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

Directory of Open Access Journals (Sweden)

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.

Identification of anti-HBV activities in Paeonia suffruticosa Andr. using GRP78 as a drug target on Herbochip®.

Science.gov (United States)

Lam, Iao-Fai; Huang, Min; Chang, Margaret Dah-Tysr; Yao, Pei-Wun; Chou, Yu-Ting; Ng, Sim-Kun; Tsai, Ying-Lin; Lin, Yu-Chang; Zhang, Yun-Feng; Yang, Xiao-Yuan; Lai, Yiu-Kay

2017-01-01

Herbochip ® technology is a high throughput drug screening platform in a reverse screening manner, in which potential chemical leads in herbal extracts are immobilized and drug target proteins can be used as probes for screening process [BMC Complementary and Alternative Medicine (2015) 15:146]. While herbal medicines represent an ideal reservoir for drug screenings, here a molecular chaperone GRP78 is demonstrated to serve as a potential target for antiviral drug discovery. We cloned and expressed a truncated but fully functional form of human GRP78 (hGRP78 1-508 ) and used it as a probe for anti-HBV drug screening on herbochips. In vitro cytotoxicity and in vitro anti-HBV activity of the herbal extracts were evaluated by MTT and ELISA assays, respectively. Finally, anti-HBV activity was confirmed by in vivo assay using DHBV DNA levels in DHBV-infected ducklings as a model. Primary screenings using GRP78 on 40 herbochips revealed 11 positives. Four of the positives, namely Dioscorea bulbifera , Lasiosphaera fenzlii , Paeonia suffruticosa and Polygonum cuspidatum were subjected to subsequent assays. None of the above extracts was cytotoxic to AML12 cells, but P. cuspidatum extract (PCE) was found to be cytotoxic to HepG2 2.2.15 cells. Both PCE and P. suffruticosa extract (PSE) suppressed secretion of HBsAg and HBeAg in HepG2 2.2.15 cells. The anti-HBV activity of PSE was further confirmed in vivo. We have demonstrated that GRP78 is a valid probe for anti-HBV drug screening on herbochips. We have also shown that PSE, while being non-cytotoxic, possesses in vitro and in vivo anti-HBV activities. Taken together, our data suggest that PSE may be a potential anti-HBV agent for therapeutic use.

IN-VITRO EVALUATION OF ANTI-TRICHOMONAL ACTIVITIES OF ...

African Journals Online (AJOL)

infective, has shown anti-malarial and antitrypanocidal 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 ...

Anti-lipolytic activity and phytochemical screening ofChelianthesalbomarginataagainst pathogenic microorganisms

Directory of Open Access Journals (Sweden)

Rini Jarial

2017-12-01

Full Text Available ABSTRACT:The aim of the present study was to evaluate the therapeutic properties of selected fern, Chelianthusalbomarginataand to identify its functional compounds. The methanolic fern-extract (MFE of these ferns was assessed for anti-bacterial activities by measuring inhibition zones against a panel of pathogenic bacterial strains using agar diffusion method. MFE at a concentration of 25 μg/ml showed marked anti-bacterial activity against all bacterial strains (6-23mm zone of inhibition and was maximum against Enterobacter sp (23 mm. In addition, the MFE of C. albomarginatahad the best MIC values of 2.25µg/ml against S. aureus and Enterobacter sp., respectively. The MFE also possessed good anti-lipolytic activity (66.5% against a porcine pancreatic lipase (PPL and cholesterol oxidase inhibition (79%. This result showed that MFE of C. albomarginataunder optimal concentrationis not only a potent source of natural anti-oxidants and anti-bacterial activity but also possesses efficient cholesterol degradation and anti-lipolytic activities, that is to be beneficial in the body weight management.

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

Science.gov (United States)

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

Screening for chlamydial infection.

Science.gov (United States)

Nelson, H D; Helfand, M

2001-04-01

To examine data on the effectiveness of screening for chlamydial infection by a physician or other health care professional. Specifically, we examine the evidence that early treatment of chlamydial infection improves health outcomes, as well as evidence of the effectiveness of screening strategies in nonpregnant women, pregnant women, and men, and the accuracy of tests used for screening. This review updates the literature since the last recommendation of the U.S. Preventive Services Task Force published in 1996. We searched the topic of chlamydia in the MEDLINE, HealthSTAR, and Cochrane Library databases from January 1994 to July 2000, supplemented by reference lists of relevant articles and from experts in the field. Articles published prior to 1994 and research abstracts were cited if particularly important to the key questions or to the interpretation of included articles. A single reader reviewed all English abstracts. Articles were selected for full review if they were about Chlamydia trachomatis genitourinary infections in nonpregnant women, pregnant women, or men and were relevant to key questions in the analytic framework. Investigators read the full-text version of the retrieved articles and applied additional eligibility criteria. For all topics, we excluded articles if they did not provide sufficient information to determine the methods for selecting subjects and for analyzing data. We systematically reviewed three types of studies about screening in nonpregnant women that relate to three key questions: (1) studies about the effectiveness of screening programs in reducing prevalence rates of infection, (2) studies about risk factors for chlamydial infection in women, and (3) studies about chlamydial screening tests in women. Our search found too few studies on pregnant women to systematically review, although pertinent studies are described. We systematically reviewed two types of studies about screening in men: (1) studies about prevalence rates and

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.

A Clinical Drug Library Screen Identifies Tosufloxacin as Being Highly Active against Staphylococcus aureus Persisters

Directory of Open Access Journals (Sweden)

Hongxia Niu

2015-07-01

Full Text Available To identify effective compounds that are active against Staphylococcus aureus (S. aureus persisters, we screened a clinical drug library consisting of 1524 compounds and identified six drug candidates that had anti-persister activity: tosufloxacin, clinafloxacin, sarafloxacin, doxycycline, thiostrepton, and chlorosalicylanilide. Among them, tosufloxacin had the highest anti-persister activity, which could completely eradicate S. aureus persisters within 2 days in vitro. Clinafloxacin ranked the second with very few persisters surviving the drug exposure. Interestingly, we found that both tosufloxacin and trovafloxacin that had high activity against persisters contained at the N-1 position the 2,4-difluorophenyl group, which is absent in other less active quinolones and may be associated with the high anti-persister activity. Further studies are needed to evaluate tosufloxacin in animal models and to explain its unique activity against bacterial persisters. Our findings may have implications for improved treatment of persistent bacterial infections.

Cell based assays for anti-Plasmodium activity evaluation.

Science.gov (United States)

Mokgethi-Morule, Thabang; N'Da, David D

2016-03-10

Malaria remains one of the most common and deadly infectious diseases worldwide. The severity of this global public health challenge is reflected by the approximately 198 million people, who were reportedly infected in 2013 and by the more than 584,000 related deaths in that same year. The rising emergence of drug resistance towards the once effective artemisinin combination therapies (ACTs) has become a serious concern and warrants more robust drug development strategies, with the objective of eradicating malaria infections. The intricate biology and life cycle of Plasmodium parasites complicate the understanding of the disease in such a way that would enhance the development of more effective chemotherapies that would achieve radical clinical cure and that would prevent disease relapse. Phenotypic cell based assays have for long been a valuable approach and involve the screening and analysis of diverse compounds with regards to their activities towards whole Plasmodium parasites in vitro. To achieve the Millennium Development Goal (MDG) of malaria eradication by 2020, new generation drugs that are active against all parasite stages (erythrocytic (blood), exo-erythrocytic (liver stages and gametocytes)) are needed. Significant advances are being made in assay development to overcome some of the practical challenges of assessing drug efficacy, particularly in the liver and transmission stage Plasmodium models. This review discusses primary screening models and the fundamental progress being made in whole cell based efficacy screens of anti-malarial activity. Ongoing challenges and some opportunities for improvements in assay development that would assist in the discovery of effective, safe and affordable drugs for malaria treatments are also discussed. Copyright © 2016 Elsevier B.V. All rights reserved.

High Throughput Screen for Novel Antimicrobials using a Whole Animal Infection Model

Science.gov (United States)

Moy, Terence I.; Conery, Annie L.; Larkins-Ford, Jonah; Wu, Gang; Mazitschek, Ralph; Casadei, Gabriele; Lewis, Kim; Carpenter, Anne E.; Ausubel, Frederick M.

2009-01-01

The nematode Caenorhabditis elegans is a unique whole animal model system for identifying small molecules with in vivo anti-infective properties. C. elegans can be infected with a broad range of human pathogens, including Enterococcus faecalis, an important human nosocomial pathogen with a mortality rate of up to 37% that is increasingly acquiring resistance to antibiotics. Here, we describe an automated, high throughput screen of 37,200 compounds and natural product extracts for those that enhance survival of C. elegans infected with E. faecalis. The screen uses a robot to accurately dispense live, infected animals into 384-well plates, and automated microscopy and image analysis to generate quantitative, high content data. We identified 28 compounds and extracts that were not previously reported to have antimicrobial properties, including 6 structural classes that cure infected C. elegans animals but do not affect the growth of the pathogen in vitro, thus acting by a mechanism of action distinct from antibiotics currently in clinical use. Our versatile and robust screening system can be easily adapted for other whole animal assays to probe a broad range of biological processes. PMID:19572548

Latent tuberculosis infection screening prior to biological treatment in Tunisian patients.

Science.gov (United States)

Slouma, Marwa; Mahmoud, Ines; Saidane, Olfa; Bouden, Selma; Abdelmoula, Leila

2017-10-01

The screening of latent tuberculosis infection (LTBI) is necessary to prevent infection in patients with chronic inflammatory disease (CID) undergoing biological treatment. We aimed to assess the efficacy of LTBI screening prior to biological treatment in Tunisia, considered as a high-incidence area of active TB disease. We conducted a retrospective study over a period of 8 years [2007-2014] including patients with chronic inflammatory rheumatism receiving biologic agents since at least 6 months. The screening of LTBI was performed according to national Tunisian guidelines. There were 35 men and 78 women. The mean age was 47.67±13.50 years. Rheumatoid arthritis (70.8%) was the most common cause of CID. The diagnosis of LTBI was established in 23 cases. Among these 23 patients, 12 patients had negative tuberculin skin test (TST) associated with positive QuantiFERON-TB Gold (QFT-G), 10 had TST more than 10mm, one patient had a TST between 5 and 10mm associated with positive QFT-G and one patient had a history of tuberculosis inadequately treated. Preventive anti-tuberculous therapy was prescribed before biological therapy initiation in cases of LTBI. During the follow-up period (3.91 years), no case of tuberculosis reactivation has been reported among patients diagnosed with LTBI. However, 2 cases of active pulmonary tuberculosis were reported in patients with initially negative TST and QFT-G. Our study showed that the Tunisian recommendations allowed detecting a LTBI in 20% of biologic therapy candidates. Preventive measures including screening of LTBI and eventually a prophylactic treatment improve the safety of biological treatments. Copyright © 2017 Société française de pharmacologie et de thérapeutique. Published by Elsevier Masson SAS. All rights reserved.

Screening of Bauhinia purpurea Linn. for analgesic and anti-inflammatory activities

Science.gov (United States)

Shreedhara, C.S.; Vaidya, V.P.; Vagdevi, H.M.; Latha, K.P.; Muralikrishna, K.S.; Krupanidhi, A.M.

2009-01-01

Objectives: Ethanol extract of the stem of Bauhinia purpurea Linn. was subjected to analgesic and anti-inflammatory activities in animal models. Materials and Methods: Albino Wistar rats and mice were the experimental animals respectively. Different CNS depressant paradigms like analgesic activity (determined by Eddy's hot plate method and acetic acid writhing method) and anti-inflammatory activity determined by carrageenan induced paw edema using plethysmometer in albino rats) were carried out, following the intra-peritoneal administration of ethanol extract of Bauhinia purpurea Linn. (BP) at the dose level of 50 mg/kg and 100 mg/kg. Results: The analgesic and anti-inflammatory activities of ethanol extracts of BP were significant (P Bauhinia purpurea has shown significant analgesic and anti-inflammatory activities at the dose of 100 mg/kg and was comparable with corresponding standard drugs. The activity was attributed to the presence of phytoconstituents in the tested extract. PMID:20336222

Bioactivity screening of microalgae for antioxidant, anti-inflammatory, anticancer, anti-diabetes and antibacterial activities

Directory of Open Access Journals (Sweden)

Chiara eLauritano

2016-05-01

Full Text Available Marine microalgae are considered a potentially new and valuable source of biologically active molecules for applications in the food industry as well as in the pharmaceutical, nutraceutical and cosmetic sectors. They can be easily cultured, have short generation times and enable an environmentally-friendly approach to drug discovery by overcoming problems associated with the over-utilization of marine resources and the use of destructive collection practices. In this study, 21 diatoms, 7 dinoflagellates and 4 flagellate species were grown in three different culturing conditions and the corresponding extracts were tested for possible antioxidant, anti-inflammatory, anticancer, anti-diabetes, antibacterial and anti-biofilm activities. In addition, for two diatoms we also tested two different clones to disclose diversity in clone bioactivity. Six diatom species displayed specific anti-inflammatory, anticancer (blocking human melanoma cell proliferation and anti-biofilm (against the bacteria Staphylococcus epidermidis activities whereas, none of the other microalgae were bioactive against the conditions tested for. Furthermore, none of the 6 diatom species tested were toxic on normal human cells. Culturing conditions (i.e. nutrient starvation conditions greatly influenced bioactivity of the majority of the clones/species tested. This study denotes the potential of diatoms as sources of promising bioactives for the treatment of human pathologies.

Screening for Anti-lipase Properties of 37 Traditional Chinese Medicinal Herbs

Directory of Open Access Journals (Sweden)

Cheng-Dong Zheng

2010-06-01

Conclusion: The results support the view that herbs represent a rich source of anti-lipase compounds. The screening of the methanolic extracts of 37 Chinese medicinal plants in vitro led to the identification of several extracts with potential activity against PPL, in particular, P. vulgaris and R. palmatum. We also found that several monomeric chemicals in these herbs exhibited good or moderate activity against PPL. To the best of our knowledge, these traditional Chinese herbal medicines or phytochemicals have not been previously screened for their lipase inhibitory activity.

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

Directory of Open Access Journals (Sweden)

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

Asian Organization for Crohn's and Colitis and Asia Pacific Association of Gastroenterology consensus on tuberculosis infection in patients with inflammatory bowel disease receiving anti-tumor necrosis factor treatment. Part 1: risk assessment

Directory of Open Access Journals (Sweden)

Dong Il Park

2018-01-01

Full Text Available Because anti-tumor necrosis factor (anti-TNF therapy has become increasingly popular in many Asian countries, the risk of developing active tuberculosis (TB among anti-TNF users may raise serious health problems in this region. Thus, the Asian Organization for Crohn's and Colitis and the Asia Pacific Association of Gastroenterology have developed a set of consensus statements about risk assessment, detection and prevention of latent TB infection, and management of active TB infection in patients with inflammatory bowel disease (IBD receiving anti-TNF treatment. Twenty-three consensus statements were initially drafted and then discussed by the committee members. The quality of evidence and the strength of recommendations were assessed by using the Grading of Recommendations Assessment, Development, and Evaluation methodology. Web-based consensus voting was performed by 211 IBD specialists from 9 Asian countries concerning each statement. A consensus statement was accepted if at least 75% of the participants agreed. Part 1 of the statements comprised 2 parts: risk of TB infection Recommendaduring anti-TNF therapy, and screening for TB infection prior to commencing anti-TNF therapy. These consensus statements will help clinicians optimize patient outcomes by reducing the morbidity and mortality related to TB infections in patients with IBD receiving anti-TNF treatment.

Anti-pulmonary fibrotic activity of salvianolic acid B was screened by a novel method based on the cyto-biophysical properties

International Nuclear Information System (INIS)

Liu, Miao; Zheng, Mingjing; Xu, Hanying; Liu, Lianqing; Li, Yanchun; Xiao, Wei; Li, Jianchun; Ma, Enlong

2015-01-01

Various methods have been used to evaluate anti-fibrotic activity of drugs. However, most of them are complicated, labor-intensive and lack of efficiency. This study was intended to develop a rapid method for anti-fibrotic drugs screening based on biophysical properties. A549 cells in vitro were stimulated with transforming growth factor-β1 (TGF-β1), and fibrogenesis was confirmed by conventional immunological assays. Meanwhile, the alterations of cyto-biophysical properties including morphology, roughness and stiffness were measured utilizing atomic force microscopy (AFM). It was found that fibrogenesis was accompanied with changes of cellular biophysical properties. TGF-β1-stimulated A549 cells became remarkably longer, rougher and stiffer than the control. Then, the effect of N-acetyl-L-cysteine (NAC) as a positive drug on ameliorating fibrogenesis in TGF-β1-stimulated A549 cells was verified respectively by immunological and biophysical markers. The result of Principal Component Analysis showed that stiffness was a leading index among all biophysical markers during fibrogenesis. Salvianolic acid B (SalB), a natural anti-oxidant, was detected by AFM to protect TGF-β1-stimulated A549 cells against stiffening. Then, SalB treatment was provided in preventive mode on a rat model of bleomycin (BLM) -induced pulmonary fibrosis. The results showed that SalB treatment significantly ameliorated BLM-induced histological alterations, blocked collagen accumulations and reduced α-SMA expression in lung tissues. All these results revealed the anti-pulmonary fibrotic activity of SalB. Detection of cyto-biophysical properties were therefore recommended as a rapid method for anti-pulmonary fibrotic drugs screening. - Highlights: • Fibrogenesis was accompanied with the changes of cyto-biophysical properties. • Cyto-biophysical properties could be markers for anti-fibrotic drugs screening. • Stiffness is a leading index among all biophysical markers. • SalB was

Anti-pulmonary fibrotic activity of salvianolic acid B was screened by a novel method based on the cyto-biophysical properties

Energy Technology Data Exchange (ETDEWEB)

Liu, Miao; Zheng, Mingjing; Xu, Hanying [Department of Pharmacology, Shenyang Pharmaceutical University, Shenyang, 110016 (China); Liu, Lianqing [Shenyang Institute of Automation China Academy of Sciences, Shenyang, 110016 (China); Li, Yanchun [Department of Pharmacology, Shenyang Pharmaceutical University, Shenyang, 110016 (China); Xiao, Wei [Jiangsu Kanion Pharmaceutical Co., Ltd., Nanjing, 222001 (China); Li, Jianchun, E-mail: lijianchun0317@sina.com.cn [Department of Pharmacology, Shenyang Pharmaceutical University, Shenyang, 110016 (China); Ma, Enlong, E-mail: enlong_ma2014@hotmail.com [Department of Pharmacology, Shenyang Pharmaceutical University, Shenyang, 110016 (China); Jiangsu Kanion Pharmaceutical Co., Ltd., Nanjing, 222001 (China)

2015-12-04

Various methods have been used to evaluate anti-fibrotic activity of drugs. However, most of them are complicated, labor-intensive and lack of efficiency. This study was intended to develop a rapid method for anti-fibrotic drugs screening based on biophysical properties. A549 cells in vitro were stimulated with transforming growth factor-β1 (TGF-β1), and fibrogenesis was confirmed by conventional immunological assays. Meanwhile, the alterations of cyto-biophysical properties including morphology, roughness and stiffness were measured utilizing atomic force microscopy (AFM). It was found that fibrogenesis was accompanied with changes of cellular biophysical properties. TGF-β1-stimulated A549 cells became remarkably longer, rougher and stiffer than the control. Then, the effect of N-acetyl-L-cysteine (NAC) as a positive drug on ameliorating fibrogenesis in TGF-β1-stimulated A549 cells was verified respectively by immunological and biophysical markers. The result of Principal Component Analysis showed that stiffness was a leading index among all biophysical markers during fibrogenesis. Salvianolic acid B (SalB), a natural anti-oxidant, was detected by AFM to protect TGF-β1-stimulated A549 cells against stiffening. Then, SalB treatment was provided in preventive mode on a rat model of bleomycin (BLM) -induced pulmonary fibrosis. The results showed that SalB treatment significantly ameliorated BLM-induced histological alterations, blocked collagen accumulations and reduced α-SMA expression in lung tissues. All these results revealed the anti-pulmonary fibrotic activity of SalB. Detection of cyto-biophysical properties were therefore recommended as a rapid method for anti-pulmonary fibrotic drugs screening. - Highlights: • Fibrogenesis was accompanied with the changes of cyto-biophysical properties. • Cyto-biophysical properties could be markers for anti-fibrotic drugs screening. • Stiffness is a leading index among all biophysical markers. • SalB was

Cancer screening in patients infected with HIV.

Science.gov (United States)

Sigel, Keith; Dubrow, Robert; Silverberg, Michael; Crothers, Kristina; Braithwaite, Scott; Justice, Amy

2011-09-01

Non-AIDS-defining cancers are a rising health concern among HIV-infected patients. Cancer screening is now an important component of health maintenance in HIV clinical practice. The decision to screen an HIV-infected patient for cancer should include an assessment of individualized risk for the particular cancer, life expectancy, and the harms and benefits associated with the screening test and its potential outcome. HIV-infected patients are at enhanced risk of several cancers compared to the general population; anal cancer, hepatocellular carcinoma, Hodgkin's lymphoma, and lung cancer all have good evidence demonstrating an enhanced risk in HIV-infected persons. A number of cancer screening interventions have shown benefit for specific cancers in the general population, but data on the application of these tests to HIV-infected persons are limited. Here we review the epidemiology and background literature relating to cancer screening interventions in HIV-infected persons. We then use these data to inform a conceptual model for evaluating HIV-infected patients for cancer screening.

Genotoxicity of topoisomerase II inhibitors: An anti-infective perspective

International Nuclear Information System (INIS)

Smart, Daniel J.

2008-01-01

At present, an inevitable consequence of a chemical's inhibitory activity on key regulators of DNA topology in bacteria, the type II topoisomerases, is a less pronounced effect on their eukaryotic counterparts. In the context of anti-infectives drug development, this may pose a risk to patient safety as inhibition of eukaryotic type II topoisomerases (TOPO II) can result in the generation of DNA double-strand breaks (DSBs), which have the potential to manifest as mutations, chromosome breakage or cell death. The biological effects of several TOPO II inhibitors in mammalian cells are described herein; their modulation of DSB damage response parameters is examined and evidence for the existence of a threshold concept for genotoxicity and its relevance in safety assessment is discussed. The potential utility of γH2AX, a promising and highly sensitive molecular marker for DSBs, in a novel genotoxicity 'pre-screen' to conventional assays is also highlighted

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

Directory of Open Access Journals (Sweden)

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.

Conjugation of Inulin Improves Anti-Biofilm Activity of Chitosan.

Science.gov (United States)

Zhang, Guiqiang; Liu, Jing; Li, Ruilian; Jiao, Siming; Feng, Cui; Wang, Zhuo A; Du, Yuguang

2018-05-04

Bacteria biofilm helps bacteria prevent phagocytosis during infection and increase resistance to antibiotics. Staphylococcus aureus is a Gram-positive pathogenic bacterium and is tightly associated with biofilm-related infections, which have led to great threat to human health. Chitosan, the only cationic polysaccharide in nature, has been demonstrated to have antimicrobial and anti-biofilm activities, which, however, require a relative high dosage of chitosan. Moreover, poor water solubility further restricts its applications on anti-infection therapy. Inulins are a group of polysaccharides produced by many types of plants, and are widely used in processed foods. Compared to chitosan, inulin is very soluble in water and possesses a mild antibacterial activity against certain pathogenic bacteria. In order to develop an effective strategy to treat biofilm-related infections, we introduce a method by covalent conjugation of inulin to chitosan. The physicochemical characterization of the inulin⁻chitosan conjugate was assayed, and the anti-biofilm activity was evaluated against S. aureus biofilm. The results indicated that, as compared to chitosan, this novel polysaccharide⁻polysaccharide conjugate significantly enhanced activities against S. aureus either in a biofilm or planktonic state. Of note, the conjugate also showed a broad spectrum anti-biofilm activity on different bacteria strains and low cellular toxicity to mammalian cells. These results suggested that chitosan conjugation of inulin was a viable strategy for treatment against biofilm-related infections. This finding may further spread the application of natural polysaccharides on treatments of infectious disease.

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.

[Ideas and methods of two-dimensional zebrafish model combined with chromatographic techniques in high-throughput screening of active anti-osteoporosis components of traditional Chinese medicines].

Science.gov (United States)

Wei, Ying-Jie; Jing, Li-Jun; Zhan, Yang; Sun, E; Jia, Xiao-Bin

2014-05-01

To break through the restrictions of the evaluation model and the quantity of compounds by using the two-dimensional zebrafish model combined with chromatographic techniques, and establish a new method for the high-throughput screening of active anti-osteoporosis components. According to the research group-related studies and relevant foreign literatures, on the basis of the fact that the zebrafish osteoporosis model could efficiently evaluate the activity, the zebrafish metabolism model could efficiently enrich metabolites and the chromatographic techniques could efficiently separate and analyze components of traditional Chinese medicines, we proposed that the inherent combination of the three methods is expected to efficiently decode in vivo and in vitro efficacious anti-osteoporosis materials of traditional Chinese medicines. The method makes it simple and efficient in the enrichment, separation and analysis on components of traditional Chinese medicines, particularly micro-components and metabolites and the screening anti-osteoporosis activity, fully reflects that efficacious materials of traditional Chinese medicines contain original components and metabolites, with characteristic of "multi-components, multi-targets and integral effect", which provides new ideas and methods for the early and rapid discovery of active anti-osteoporosis components of traditional Chinese medicines.

Should we be screening for anti-Js(a)?

Science.gov (United States)

Nikolis, Nancy M; Boctor, Fouad; Heaton, William Andrew; Martone, James

2011-01-01

We analyzed our historic patient database at North Shore University Hospital and determined both the overall frequency of anti-Js(a) and the frequency at which it was detected in combination with other alloantibodies to red blood cell (RBC) antigens. Screening cells used currently are negative for Js(a). Our data suggest that anti-Js(a) would not be detected in 30 to 40 percent of patients in which it is the sole antibody present. Since 1996 the antibody was only detected when other antibodies were found in the screening process. We are exposing 1.7 percent of our patients (90 patients/year) to Js(a). The clinical significance of anti-Js(a) is apparent with previous literature, and our conclusion is that additional studies should be performed to determine whether Js(a) should be included in current antibody screening cells.

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

New findings on the d(TGGGAG) sequence: Surprising anti-HIV-1 activity.

Science.gov (United States)

Romanucci, Valeria; Zarrelli, Armando; Liekens, Sandra; Noppen, Sam; Pannecouque, Christophe; Di Fabio, Giovanni

2018-02-10

The biological relevance of tetramolecular G-quadruplexes especially as anti-HIV agents has been extensively reported in the literature over the last years. In the light of our recent results regarding the slow G-quadruplex folding kinetics of ODNs based on d(TGGGAG) sequence, here we report a systematic anti-HIV screening to investigate the impact of the G-quadruplex folding on their anti-HIV activity. In particular, varying the single stranded concentrations of ODNs, it has been tested a pool of ODN sample solutions with different G-quadruplex concentrations. The anti-HIV assays have been designed favouring the limited kinetics involved in the tetramolecular G4-association based on the d(TGGGAG) sequence. Aiming to determine the stoichiometry of G-quadruplex structures in the same experimental conditions of the anti-HIV assays, a native gel electrophoresis was performed. The gel confirmed the G-quadruplex formation for almost all sample solutions while showing the formation of high order G4 structures for the more concentrated ODNs solutions. The most significant result is the discovery of a potent anti-HIV activity of the G-quadruplex formed by the natural d(TGGGAG) sequence (IC 50  = 14 nM) that, until now, has been reported to be completely inactive against HIV infection. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Anti-mycobacterial screening of five Indian medicinal plants and partial purification of active extracts of Cassia sophera and Urtica dioica

Institute of Scientific and Technical Information of China (English)

Rambir Singh; Shariq Hussain; Rajesh Verma; Poonam Sharma

2013-01-01

Objective: To find out the anti-mycobacterial potential of Cassia sophera (C. sophera), Urticadioica (U. dioica), Momordica dioica, Tribulus terrestris and Coccinia indica plants against multi-drug resistant (MDR) strain of Mycobacterium tuberculosis (M. tuberculosis). Methods: Plant materials were extracted successively with solvents of increasing polarity. Solvent extracts were screened for anti-mycobacterial activity against fast growing, non-pathogenic mycobacterium strain, Mycobacterium semegmatis, by disk diffusion method. The active extracts were tested against MDR and clinical isolates of M. tuberculosis by absolute concentration and proportion methods. The active extracts were subjected to bio-autoassay on TLC followed by silica column chromatography for isolation of potential drug leads. Results: Hexane extract of U. dioica (HEUD) and methanol extract of C. sophera (MECS) produced inhibition zone of 20 mm in disc diffusion assay and MIC of 250 and 125 μg/mL respectively in broth dilution assay against Mycobacteriumsemegmatis. Semipurified fraction F2 from MECS produced 86% inhibition against clinical isolate and 60% inhibition against MDR strain of M. tuberculosis. F18 from HEUD produced 81% inhibition against clinical isolate and 60% inhibition against MDR strain of M. tuberculosis. Phytochemical analysis indicated that anti-mycobacterial activity of MECS may be due to presence of alkaloids or flavonoids and that of HEUD due to terpenoids. Conclusions: C. sophera and U. dioica plant extracts exhibited promising anti-mycobacterial activity against MDR strain of M. tuberculosis. This is the first report of anti-mycobacterial activity form C. sophera. This study showed possibility of purifying novel anti-mycobacterial compound(s) from C. sophera and U. dioica.

High-throughput screen for novel antimicrobials using a whole animal infection model.

Science.gov (United States)

Moy, Terence I; Conery, Annie L; Larkins-Ford, Jonah; Wu, Gang; Mazitschek, Ralph; Casadei, Gabriele; Lewis, Kim; Carpenter, Anne E; Ausubel, Frederick M

2009-07-17

The nematode Caenorhabditis elegans is a unique whole animal model system for identifying small molecules with in vivo anti-infective properties. C. elegans can be infected with a broad range of human pathogens, including Enterococcus faecalis, an important human nosocomial pathogen. Here, we describe an automated, high-throughput screen of 37,200 compounds and natural product extracts for those that enhance survival of C. elegans infected with E. faecalis. Using a robot to dispense live, infected animals into 384-well plates and automated microscopy and image analysis, we identified 28 compounds and extracts not previously reported to have antimicrobial properties, including six structural classes that cure infected C. elegans animals but do not affect the growth of the pathogen in vitro, thus acting by a mechanism of action distinct from antibiotics currently in clinical use.

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.

Anti-pulmonary fibrotic activity of salvianolic acid B was screened by a novel method based on the cyto-biophysical properties.

Science.gov (United States)

Liu, Miao; Zheng, Mingjing; Xu, Hanying; Liu, Lianqing; Li, Yanchun; Xiao, Wei; Li, Jianchun; Ma, Enlong

Various methods have been used to evaluate anti-fibrotic activity of drugs. However, most of them are complicated, labor-intensive and lack of efficiency. This study was intended to develop a rapid method for anti-fibrotic drugs screening based on biophysical properties. A549 cells in vitro were stimulated with transforming growth factor-β1 (TGF-β1), and fibrogenesis was confirmed by conventional immunological assays. Meanwhile, the alterations of cyto-biophysical properties including morphology, roughness and stiffness were measured utilizing atomic force microscopy (AFM). It was found that fibrogenesis was accompanied with changes of cellular biophysical properties. TGF-β1-stimulated A549 cells became remarkably longer, rougher and stiffer than the control. Then, the effect of N-acetyl-L-cysteine (NAC) as a positive drug on ameliorating fibrogenesis in TGF-β1-stimulated A549 cells was verified respectively by immunological and biophysical markers. The result of Principal Component Analysis showed that stiffness was a leading index among all biophysical markers during fibrogenesis. Salvianolic acid B (SalB), a natural anti-oxidant, was detected by AFM to protect TGF-β1-stimulated A549 cells against stiffening. Then, SalB treatment was provided in preventive mode on a rat model of bleomycin (BLM) -induced pulmonary fibrosis. The results showed that SalB treatment significantly ameliorated BLM-induced histological alterations, blocked collagen accumulations and reduced α-SMA expression in lung tissues. All these results revealed the anti-pulmonary fibrotic activity of SalB. Detection of cyto-biophysical properties were therefore recommended as a rapid method for anti-pulmonary fibrotic drugs screening. Copyright © 2015 Elsevier Inc. All rights reserved.

Hepatitis C virus liver disease in women infected with contaminated anti-D immunoglobulin.

LENUS (Irish Health Repository)

Sheehan, M M

2012-02-03

Screening for hepatitis C virus (HCV) infection is carried out by detection of antibodies to the virus (enzyme-linked immunosorbent assay (ELISA) and recombinant immunoblot assay (RIBA)) with confirmation by identification of HCV RNA genome in serum (polymerase chain reaction (PCR)). We describe the histological features on liver biopsy in 88 women with chronic HCV infection (serum positive on ELISA, RIBA and PCR) acquired from virus contaminated anti-D immunoglobulin. For the majority of these patients the time interval from virus infection to presentation was between 17 and 18 years. We separately assessed necroinflammatory disease activity and architectural features on liver biopsy and applied a scoring system which permitted semi-quantitative documentation of abnormal features. Only three women showed liver biopsies within normal limits (+\\/-focal steatosis). The remaining 85 cases showed a predominantly mild or moderate degree of disease activity with interface hepatitis (56.8% of cases), spotty necrosis, apoptosis and focal inflammation (88.6% of cases) and portal inflammation (90.9% of cases). Confluent necrosis was an uncommon finding (2.3% of cases). Assessment of architectural features showed normal appearance in 35.2% of biopsies. The predominant architectural abnormality noted was portal tract fibrosis. Ten per cent of cases, however, showed significant fibrous band and\\/or nodule formation.

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

Directory of Open Access Journals (Sweden)

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.

Assessment of Anti-inflammatory Activity of Taxus Baccata Linn. Bark Extract.

Science.gov (United States)

Dutta, Satyajit; Mariappan, G; Sarkar, Dipankar; Sarkar, Piyali

2010-01-01

Taxus baccata (L) known as Sthauneyaka in Sanskrit(1) has wide range of biological activities including analgesic, anti-malarial, anti-rheumatic, sedative, anti-spasmodic, aphrodisiac and anti-asthmatic. In the present study, the dried and powdered bark of Taxus baccata (L) was extracted with 95% ethanol and ether at room temperature and screened for their anti--inflammatory activity by Carrageenan-induced paw edema method in rat. 95% ethanol extract exhibits potent anti-inflammatory activity at 200mg/kg four hours after administration in comparison with ether extract, as well reference standard, Aspirin. The observed pharmacological activities provide a scientific basis for the folklore use of the plant in treating acute inflammation.

Anti-biofilm and anti-adherence activities of sub fraction 18 of Melastoma malabathricum towards Streptococcus mutans

Science.gov (United States)

Rohazila M., H.; Nazlina, I.; Yaacob W., A.

2014-09-01

A study was carried out to isolate and identify the active compounds from Melastoma malabathricum stem bark that exhibit anti-biofilm and anti-adherence activities against Streptococcus mutans. Purification of the active compounds from the stem bark extract was performed via silica gel chromatography to produce 12 fractions. Further fractionation of fraction 9 by high performance liquid chromatography (HPLC) produced 21 sub fractions. All the sub fractions were subjected to thin layer chromatography (TLC) bioautography as preliminary screening to determine anti bacterial activity. TLC-bioautography showed that sub fraction 18 (SF18) demonstrated large inhibited zone against S. mutans. Gas chromatography mass spectrometry (GCMS) was used to identify the active compounds in SF18. Fraction SF18 revealed 27 compounds such as hexanoic acid, 8-methyl-1-undecene, propanenitrile, and 1-decene. Anti-biofilm and anti-adherence activities were determined using crystal violet and glass surface assays respectively. The concentrations that produced 50% reduction in anti-biofilm and anti-adherence activities were 1.88 mg/ml and 3.75 mg/ml respectively.

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.

Anti-mycobacterial screening of five Indian medicinal plants and partial purification of active extracts of Cassia sophera and Urtica dioica.

Science.gov (United States)

Singh, Rambir; Hussain, Shariq; Verma, Rajesh; Sharma, Poonam

2013-05-13

To find out the anti-mycobacterial potential of Cassia sophera (C. sophera), Urtica dioica (U. dioica), Momordica dioica, Tribulus terrestris and Coccinia indica plants against multi-drug resistant (MDR) strain of Mycobacterium tuberculosis (M. tuberculosis). Plant materials were extracted successively with solvents of increasing polarity. Solvent extracts were screened for anti-mycobacterial activity against fast growing, non-pathogenic mycobacterium strain, Mycobacterium semegmatis, by disk diffusion method. The active extracts were tested against MDR and clinical isolates of M. tuberculosis by absolute concentration and proportion methods. The active extracts were subjected to bio-autoassay on TLC followed by silica column chromatography for isolation of potential drug leads. Hexane extract of U. dioica (HEUD) and methanol extract of C. sophera (MECS) produced inhibition zone of 20 mm in disc diffusion assay and MIC of 250 and 125 μ g/mL respectively in broth dilution assay against Mycobacterium semegmatis. Semipurified fraction F2 from MECS produced 86% inhibition against clinical isolate and 60% inhibition against MDR strain of M. tuberculosis. F18 from HEUD produced 81% inhibition against clinical isolate and 60% inhibition against MDR strain of M. tuberculosis. Phytochemical analysis indicated that anti-mycobacterial activity of MECS may be due to presence of alkaloids or flavonoids and that of HEUD due to terpenoids. C. sophera and U. dioica plant extracts exhibited promising anti-mycobacterial activity against MDR strain of M. tuberculosis. This is the first report of anti-mycobacterial activity form C. sophera. This study showed possibility of purifying novel anti-mycobacterial compound(s) from C. sophera and U. dioica. Copyright © 2013 Hainan Medical College. Published by Elsevier B.V. All rights reserved.

ANTI-MICROBIAL AND ANTI-AMOEBIC ACTIVITY SOME AZOMETHINES - POTENTIAL TEXTILE DYESTUFFS

Directory of Open Access Journals (Sweden)

DJORDJEVIC Dragan

2016-05-01

Full Text Available In this paper, new synthesized three azomethine derivatives applied in dyeing textiles checking the anti-microbial properties of active components, at the same time [1-3]. The emphasis is thrown on the verification of anti-microbial properties that are important for obtaining textile with significantly improved performance. All compounds were characterized and evaluated for their anti-microbial activity against 7 pathogenic bacteria, 1 parasitic protozoan and 1 fungus. It estimated anti-bacterial activity in vitro against the following microorganisms Staphylococcus aureus, Bacillus anthracis, Streptococcus faecalis, Enterobacter sp., Escherichia coli, Pseudomonas aeruginosa, Proteus mirabilis, and Candida albicans. The anti-amoebic activity in vitro was evaluated against the HM1: IMSS strain of Entamoeba histolytica and the results were compared with the standard drug, metronidazole. The synthesized azomethines, showed very good substantivity for wool fibers, gave fine coloring, with good degree of exhaustion after dyeing. The combination of extended synthetic analogues of natural molecules leads to discovery of chemical entities which might be excellent anti-microbial and anti-amoebic compounds as depicted in our results. Being highly the effects this compound can be explored in future as an option for decreasing pathogenic potential of infecting from different sources. Azomethines containing hydrazone (dyestuff 1 and phenylhydrazone (dyestuff 2 as moiety show average yield and moderate inhibition activity while azomethines containing thiosemicarbazone (dyestuff 3 as moiety show higher yield and greater inhibition activity towards gram-negative and gram-positive bacteria as well as a fungus.

Pharmacological screening of plants recommended by folk medicine as anti-snake venom: I. Analgesic and anti-inflammatory activities

Directory of Open Access Journals (Sweden)

Bettina M. Ruppelt

1991-01-01

Full Text Available We have observed that several plants used popularly as anti-snake venom show anti-inflammatory activity. From the list prepared by Rizzini, Mors and Pereira some species have been selected and tested for analgesic activity (number of contortions and anti-inflammatory activity (Evans blue dye diffusion - 1% solution according to Whittle's technique (intraperitoneal administration of 0.1 N-acetic acid 0.1 ml/10 g in mice. Previous oral administration of a 10% infusion (dry plant or 20% (fresh plant corresponding to 1 or 2 g/Kg of Apuleia leiocarpa, Casearia sylvestris, Brunfelsia uniflora, Chiococca brachiata, Cynara scolymus, Dorstenia brasiliensis, Elephantopus scaber, Marsypianthes chamaedrys, Mikania glomerata and Trianosperma tayuya demonstrated analgesic and/or anti-inflammatory activities of varied intensity

Antibacterial, anti-swarming and anti-biofilm formation activities of Chamaemelum nobile against Pseudomonas aeruginosa.

Science.gov (United States)

Kazemian, Hossein; Ghafourian, Sobhan; Heidari, Hamid; Amiri, Pouya; Yamchi, Jalil Kardan; Shavalipour, Aref; Houri, Hamidreza; Maleki, Abbas; Sadeghifard, Nourkhoda

2015-01-01

Chamomile (Chamaemelum nobile) is widely used throughout the world, and has anti-inflammatory, deodorant, bacteriostatic, antimicrobial, carminative, sedative, antiseptic, anti-catarrhal, and spasmolytic properties. Because of the increasing incidence of drug-resistant bacteria, the development of natural antibacterial sources such as medical herbs for the treatment of infectious diseases is necessary. Extracts from different plant parts such as the leaves, flowers, fruit, and bark of Combretum albiflorum, Laurus nobilis , and Sonchus oleraceus were found to possess anti-quorum sensing (QS) activities. In this study, we evaluated the effect of C. nobile against Pseudomonas aeruginosa biofilm formation. The P. aeruginosa samples were isolated from patients with different types of infection, including wound infection, septicemia, and urinary tract infection. The flowers of C. nobile were dried and the extract was removed using a rotary device and then dissolved in dimethyl sulfoxide at pH 7.4. The microdilution method was used to evaluate the minimum inhibitory concentration (MIC) of this extract on P. aeruginosa , and biofilm inhibition was assayed. Eighty percent of the isolated samples (16/20) could form a biofilm, and most of these were isolated from wound infections. The biofilm inhibitory concentration of the C. nobile extract was 6.25-25mg/ml, whereas the MIC was 12.5-50mg/ml. The anti-QS property of C. nobile may play an important role in its antibacterial activity, thus offering an additional strategy in the fight against bacterial infections. However, molecular investigation is required to explore the exact mechanisms of the antibacterial action and functions of this phytocompound.

Antinociceptive and anti-inflammatory activities of the methanol ...

African Journals Online (AJOL)

This study was aimed at screening the methanol tuber extract of Chlorophytum alismifolium for antinociceptive and anti-inflammatory activities using experimental animal models. The antinociceptive activity was tested using acetic acid-induced writhing response in Swiss albino mice and formalininduced pain in Wistar rats, ...

Comparative analysis of disease activity in patients of chronic hepatitis B virus, with and without super infection with hepatitis D virus; an experience at tertiary care centre

International Nuclear Information System (INIS)

Hassan, K.D.; Mahmood, T.; Farooq, M.U.

2008-01-01

The hepatitis D virus super-infection contributes significantly to the morbidity and mortality of hepatitis B virus infection. The objectives were to describe the incidence of Hepatitis D virus and comparative analysis of disease activity in patients of chronic hepatitis B virus, with and without super-infection of hepatitis D virus. This Cross-sectional comparative study was conducted at Department of Medicine and Gastroenterology Clinic Jinnah Postgraduate Medical Centre, Karachi, Pakistan from February 2007 to July 2007. HBsAg positive patients who attended our Gastroenterology clinic were selected for the study. After screening for Anti-HDV these patients were segregated in to Anti-HDV positive and negative groups. Data was analyzed on SPSS 12. Eighty-four patients were selected. Seventy-three patients who fulfilled the inclusion criteria were enrolled in to the study. Anti-HDV was positive in 23 (31.5%) patients. Among these 23 anti-HDV positive, HDV-RNA was detected in 15 (75%) patients. The differences of age, gender, marital status and area of residence whether rural or urban were not significant between the two groups. HBV-DNA was significantly suppressed in majority of anti- HDV positive patients (p=0.019). Mean serum ALT levels were significantly higher in patients who had HDV infection (p=0.014). HDV infection was common in this series of patients with a frequency of 31.5%. All patients of chronic HBV should be screened for HDV whether they are asymptomatic HBV carriers or have chronic active hepatitis particularly when they have raised serum ALT. (author)

anti-inflammatory activity of selected nigerian medicinal plants

African Journals Online (AJOL)

Extracts of nineteen plant species from an inventory of Nigerian medicinal plants were screened for activity in two in vitro anti-inflammatory model test systems, inhibition of prostaglandin biosynthesis and PAF-induced elastase release from neutrophilis. Anacardium occidentale and Acalipha hispida were active in both test ...

Antibacterial, anti-swarming and anti-biofilm formation activities of Chamaemelum nobile against Pseudomonas aeruginosa

Directory of Open Access Journals (Sweden)

Hossein Kazemian

2015-08-01

Full Text Available AbstractINTRODUCTION:Chamomile ( Chamaemelum nobile is widely used throughout the world, and has anti-inflammatory, deodorant, bacteriostatic, antimicrobial, carminative, sedative, antiseptic, anti-catarrhal, and spasmolytic properties. Because of the increasing incidence of drug-resistant bacteria, the development of natural antibacterial sources such as medical herbs for the treatment of infectious diseases is necessary. Extracts from different plant parts such as the leaves, flowers, fruit, and bark of Combretum albiflorum, Laurus nobilis , and Sonchus oleraceus were found to possess anti-quorum sensing (QS activities. In this study, we evaluated the effect of C. nobile against Pseudomonas aeruginosa biofilm formationMETHODS:The P. aeruginosa samples were isolated from patients with different types of infection, including wound infection, septicemia, and urinary tract infection. The flowers of C. nobile were dried and the extract was removed using a rotary device and then dissolved in dimethyl sulfoxide at pH 7.4. The microdilution method was used to evaluate the minimum inhibitory concentration (MIC of this extract on P. aeruginosa , and biofilm inhibition was assayed.RESULTS:Eighty percent of the isolated samples (16/20 could form a biofilm, and most of these were isolated from wound infections. The biofilm inhibitory concentration of the C. nobile extract was 6.25-25mg/ml, whereas the MIC was 12.5-50mg/ml.CONCLUSIONS:The anti-QS property of C. nobile may play an important role in its antibacterial activity, thus offering an additional strategy in the fight against bacterial infections. However, molecular investigation is required to explore the exact mechanisms of the antibacterial action and functions of this phytocompound.

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

Directory of Open Access Journals (Sweden)

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.

Screening of Ficus religiosa leaves fractions for analgesic and anti-inflammatory activities

OpenAIRE

Gulecha, Vishal; Sivakumar, T; Upaganlawar, Aman; Mahajan, Manoj; Upasani, Chandrashekhar

2011-01-01

Objective : To evaluate the different fractions of dried leaves of Ficus religiosa Linn for analgesic and anti-inflammatory activity using different models of pain and inflammation Materials and Methods : The analgesic activity of F. religiosa carried out using acetic acid-induced writhing in mice and tail flick test in rats. The anti-inflammatory activity was evaluated using carrageenan-induced rat paw edema and cotton pellet-granuloma formation in rats. Five different fractions (FRI, FR...

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.

Clinical outcomes after hepatitis C infection from contaminated anti-D immune globulin. Irish Hepatology Research Group.

LENUS (Irish Health Repository)

Kenny-Walsh, E

2012-02-03

BACKGROUND AND METHODS: In February 1994, batches of anti-D immune globulin used in Ireland during 1977 and 1978 to prevent Rh isoimmunization were found to be contaminated with hepatitis C virus (HCV) from a single infected donor. In March 1994, a national screening program was initiated for all women who had received anti-D immune globulin between 1970 and 1994. Of the 62,667 women who had been screened when this study began, 704 (1.1 percent) had evidence of past or current HCV infection, and 390 of those 704 (55 percent) had positive tests for serum HCV RNA on reverse-transcription-polymerase-chain-reaction analysis. All 390 were offered a referral for clinical assessment and therapy. We evaluated 376 of these 390 women (96 percent); the other 14 were not seen at one of the designated treatment centers. RESULTS: The mean (+\\/-SD) age of the 376 women was 45+\\/-6 years at the time of screening. They had been infected with hepatitis C for about 17 years. A total of 304 women (81 percent) reported symptoms, most commonly fatigue (248 [66 percent]). Serum alanine aminotransferase concentrations were slightly elevated (40 to 99 U per liter) in 176 of 371 women (47 percent), and the concentrations were 100 U per liter or higher in 31 (8 percent). Liver biopsies showed inflammation in 356 of 363 women (98 percent); in most cases the inflammation was slight (41 percent) or moderate (52 percent). Although the biopsy samples from 186 of the 363 women (51 percent) showed evidence of fibrosis, only 7 women (2 percent) had probable or definite cirrhosis. Two of the seven reported excessive alcohol consumption. CONCLUSIONS: Most of the women with HCV infection 17 years after receiving HCV-contaminated anti-D immune globulin had evidence of slight or moderate hepatic inflammation on liver biopsy, about half had fibrosis, and 2 percent had probable or definite cirrhosis.

Screening of Anti-Obesity Agent from Herbal Mixtures

Directory of Open Access Journals (Sweden)

Sung-Kee Jo

2012-03-01

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

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.

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

Phytochemical Screening and In Vitro Antitrypanosomal Activity of ...

African Journals Online (AJOL)

Phytochemical Screening and In Vitro Antitrypanosomal Activity of the Aerial Parts of Artemisia abyssinica Against Trypanosoma congolense Field Isolate. ... of infected blood and extracts at concentrations of 4, 2 and 0.4 mg/ml coupled with infectivity test in which a mixture of infected blood was inoculated to healthy mice.

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.

Role of signal-to-cut-off ratios of anti-hepatitis C virus antibody by enzyme immunoassays along with ID-NAT for screening of whole blood donors in India

Directory of Open Access Journals (Sweden)

Satyam Arora

2016-01-01

Full Text Available Background: The use of elevated signal-to-cut off ratios (S/CO as an alternate to further supplemental testing (i.e., RIBA has been included in the guidelines provided by the Centres for Disease Control and Prevention for HCV diagnostic purposes since 2003. With availability of screening by NAT and non availability of RIBA, further confirmation of HCV infection has been possible at the molecular level (RNA. Aims: To study the role of S/CO ratios of anti hepatitis C virus antibody detection by enzyme immunoassays (EIA along with ID-NAT for screening of whole blood donors. Methods: In this study we reviewed the donor screening status for anti HCV from January 2013 to May 2014. All the donations were screened for anti HCV with fourth generation ELISA (BioRad Monolisa Ag-Ab Ultra as well as with ID NAT (Procleix Ultrio. The S/CO ratio of all the anti-HCV reactive samples were analysed for their presence of HCV RNA. Results: On screening 21,115 donors for HCV, 83 donors (0.39% were found reactive on pilot tube and repeat plasma bag testing (S/Co ratio ≥1 by ELISA. 41 donors were HCV RNA reactive with ID-NAT. 4 samples out of 41 were NAT yields and 37 were concordant reactive with ELISA. The S/Co ratio of anti-HCV reactive samples ranged from 0.9-11.1 [mean = 5.1; SD ΁ 2.9] whereas S/Co ratio of anti HCV and NAT reactive samples (concordant positives ranged from 4.1-11.1 [mean 7.3]. In our analysis we found that S/CO ratio of 4 showed positive predictive value (PPV and sensitivity of 100%. Summary/Conclusions: Our study showed that S/CO of 4 for anti HCV on ELISA would have maximum positive predictive value of having donor with HCV RNA. S/CO ratio of 4 is very close to 3.8 which was the CDC guideline. The presence of anti-HCV does not distinguish between current or past infections but a confirmed anti-HCV-positive result indicates the need for counseling and medical evaluation for HCV infection.

Synthesis and Anti-Bacterial Activities of Some Novel Schiff Bases Derived from Aminophenazone

Directory of Open Access Journals (Sweden)

Salman A Khan

2010-10-01

Full Text Available A series of 1,5-dimethyl-2-phenyl-1,2-dihydro-3H-pyrazol-3-one-containing Schiff bases were synthesized, characterized and screened for their antibacterial activities. The structures of the synthesized compounds were established by spectroscopic (FT-IR, 1H-NMR, 13C-NMR, MS and elemental analyses. The anti-bacterial activities (with MIC values of compounds were evaluated. The anti-bacterial screening results reveal that among the six compounds screened, four compounds showed moderate to good anti-bacterial activity. Among the tested compounds, the most effective compounds against four bacterial strains, viz. Escherichia coli, Staphylococcus aureus, Salmonella typhimurium and Streptococcus pyogenes, are [(2-Chlorobenzylideneamino]-1,5-dimethyl-2-phenyl-1,2-dihydropyrazol-3-one (4 and [(1,5-Dimethyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazol-4-yliminomethyl]benzonitrile (5 with MIC values of 6.25 μg/mL.

Temporal activation of anti- and pro-apoptotic factors in human gingival fibroblasts infected with the periodontal pathogen, Porphyromonas gingivalis: potential role of bacterial proteases in host signalling

Directory of Open Access Journals (Sweden)

Takehara Tadamichi

2006-03-01

Full Text Available Abstract Background Porphyromonas gingivalis is the foremost oral pathogen of adult periodontitis in humans. However, the mechanisms of bacterial invasion and the resultant destruction of the gingival tissue remain largely undefined. Results We report host-P. gingivalis interactions in primary human gingival fibroblast (HGF cells. Quantitative immunostaining revealed the need for a high multiplicity of infection for optimal infection. Early in infection (2–12 h, P. gingivalis activated the proinflammatory transcription factor NF-kappa B, partly via the PI3 kinase/AKT pathway. This was accompanied by the induction of cellular anti-apoptotic genes, including Bfl-1, Boo, Bcl-XL, Bcl2, Mcl-1, Bcl-w and Survivin. Late in infection (24–36 h the anti-apoptotic genes largely shut down and the pro-apoptotic genes, including Nip3, Hrk, Bak, Bik, Bok, Bax, Bad, Bim and Moap-1, were activated. Apoptosis was characterized by nuclear DNA degradation and activation of caspases-3, -6, -7 and -9 via the intrinsic mitochondrial pathway. Use of inhibitors revealed an anti-apoptotic function of NF-kappa B and PI3 kinase in P. gingivalis-infected HGF cells. Use of a triple protease mutant P. gingivalis lacking three major gingipains (rgpA rgpB kgp suggested a role of some or all these proteases in myriad aspects of bacteria-gingival interaction. Conclusion The pathology of the gingival fibroblast in P. gingivalis infection is affected by a temporal shift from cellular survival response to apoptosis, regulated by a number of anti- and pro-apoptotic molecules. The gingipain group of proteases affects bacteria-host interactions and may directly promote apoptosis by intracellular proteolytic activation of caspase-3.

Genome Mining for antibiotics biosynthesis pathways with antiSMASH 3

DEFF Research Database (Denmark)

Weber, Tilmann; Kim, Hyun Uk; Blin, Kai

2014-01-01

Microorganisms are the most important source of natural products with antimicrobial or antitumor activity. These natural products are the main source for anti-­‐infectives; 80% of antibiotics currently in medical use are derived from this class of compounds. In the past, functional screenings...

Screening of Pregnant Women for Anti-Toxoplasma Antibodies and their Newborn for Vertical Transmission

Directory of Open Access Journals (Sweden)

Aysha Yasmeen

2017-10-01

the pregnant women in Kolar region, possess anti-Toxoplasma IgG antibodies and are immune to toxoplasmosis. The rest, constituting a large proportion, are susceptible and run the risk of infection during pregnancy. Routine screening of women for Toxoplasma infections during pregnancy and screening of newborns for congenital toxoplasmosis are recommended.

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.

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

Directory of Open Access Journals (Sweden)

Appaji Mahesh Ashwini

2015-12-01

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

Novel approaches in anti-arenaviral drug development

International Nuclear Information System (INIS)

Lee, Andrew M.; Pasquato, Antonella; Kunz, Stefan

2011-01-01

Hemorrhagic fevers caused by arenaviruses are among the most devastating emerging human diseases. Considering the number of individuals affected, the current lack of a licensed vaccine, and the limited therapeutic options, arenaviruses are arguably among the most neglected tropical pathogens and the development of efficacious anti-arenaviral drugs is of high priority. Over the past years significant efforts have been undertaken to identify novel potent inhibitors of arenavirus infection. High throughput screening of small molecule libraries employing pseudotype platforms led to the discovery of several potent and broadly active inhibitors of arenavirus cell entry that are effective against the major hemorrhagic arenaviruses. Mechanistic studies revealed that these novel entry inhibitors block arenavirus membrane fusion and provided novel insights into the unusual mechanism of this process. The success of these approaches highlights the power of small molecule screens in antiviral drug discovery and establishes arenavirus membrane fusion as a robust drug target. These broad screenings have been complemented by strategies targeting cellular factors involved in productive arenavirus infection. Approaches targeting the cellular protease implicated in maturation of the fusion-active viral envelope glycoprotein identified the proteolytic processing of the arenavirus glycoprotein precursor as a novel and promising target for anti-arenaviral strategies.

[Ideas and methods on efficient screening of traditional medicines for anti-osteoporosis activity based on M-Act/Tox integrated evaluation using zebrafish].

Science.gov (United States)

Wang, Mo; Ling, Jie; Chen, Ying; Song, Jie; Sun, E; Shi, Zi-Qi; Feng, Liang; Jia, Xiao-Bin; Wei, Ying-Jie

2017-11-01

The increasingly apparent liver injury problems of bone strengthening Chinese medicines have brought challenges for clinical application, and it is necessary to consider both effectiveness and safety in screening anti-osteoporosis Chinese medicines. Metabolic transformation is closely related to drug efficacy and toxicity, so it is significant to comprehensively consider metabolism-action/toxicity(M-Act/Tox) for screening anti-osteoporosis Chinese medicines. The current evaluation models and the number of compounds(including metabolites) severely restrict efficient screening in vivo. By referring to previous relevant research and domestic and abroad literature, zebrafish M-Act/Tox integrative method was put forward for efficiently screening anti-osteoporosis herb medicines, which has organically integrated zebrafish metabolism model, osteoporosis model and toxicity evaluation method. This method can break through the bottleneck and blind spots that trace compositions can't achieve efficient and integrated in vivo evaluation, and realize both efficient and comprehensive screening on anti-osteoporosis traditional medicines based on in vivo process taking both safety and effectiveness into account, which is significant to accelerate discovery of effective and safe innovative traditional Chinese medicines for osteoporosis. Copyright© by the Chinese Pharmaceutical Association.

In ova angiogenesis analgesic and anti inflammatory potency of Aerva monsoniae (Amaranthaceae

Directory of Open Access Journals (Sweden)

Sandhya S

2012-10-01

Full Text Available Objective: To evaluate the wound healing potency of aqueous extract of Aerva monsoniae (A. monsoniae by in vitro method using fertilized eggs, in vivo analgesic and anti inflammatory activity in rodents and the anti bacterial activity on the bacterial strains that infect the wound. Methods: The whole plant of A. monsoniae was extracted with water and then subjected to preliminary chemical screening. It was then evaluated for in ova angiogenesis on fertilized white leg horn eggs using the concentrations of 200-600 毺 g/mL. The analgesic activity was evaluated in mice using the dose 100 and 250 mg/kg. The anti inflammatory activity was evaluated in rats using the dose 250 mg/kg and 500 mg/kg. In both the parameters water was used as the control and diclofenac was used the standard. The anti bacterial activity on Staphylococcus aureus and Pseudomonas aerugenosa was performed. Results: The phytochemical screening revealed the presence of tannins, flavonoids and saponins. The in ova angiogenesis revealed a dose dependent activity which proves the wound healing claim of the plant as more number of blood capillaries were formed at the site of the drug. The plant proved to be a potent analgesic and anti inflammatory agent at doses 1 00 mg/kg and 250 mg/kg. The anti bacterial activity was present but at higher doses. Conclusions: The parameters studied in the present investigation proved that the plant is a potent wound healer. Further in vivo wound healing studies on animal model is desired. As the extract showed potent analgesic, anti inflammatory and anti bacterial properties, it can be considered that when formulated into suitable formulation, and it can reduce the pain, inflammation and infections related to wound very well.

Synthesis, Analgesic, Anti-inflammatory and Antimicrobial Activities ...

African Journals Online (AJOL)

Purpose: Microbial infections often produce pain and inflammation. Chemotherapeutic, analgesic and anti-inflammatory drugs are prescribed simultaneously in normal practice. The compound possessing all three activities is not common.The purpose of the present study was to examine whether molecular modification ...

Screening of Ficus religiosa leaves fractions for analgesic and anti-inflammatory activities.

Science.gov (United States)

Gulecha, Vishal; Sivakumar, T; Upaganlawar, Aman; Mahajan, Manoj; Upasani, Chandrashekhar

2011-11-01

To evaluate the different fractions of dried leaves of Ficus religiosa Linn for analgesic and anti-inflammatory activity using different models of pain and inflammation The analgesic activity of F. religiosa carried out using acetic acid-induced writhing in mice and tail flick test in rats. The anti-inflammatory activity was evaluated using carrageenan-induced rat paw edema and cotton pellet-granuloma formation in rats. Five different fractions (FRI, FRII, FRIII, FRIV and FRV) of F. religiosa at the dose level of 20 and 40 mg/kg, p.o were tested. The fraction FRI (40 mg/kg, p.o.) and FRIII (40 mg/kg, p.o) were found to be more effective (Pacetic acid induced writhing compared to the other fractions. FRI (20 mg/kg, p.o.) and FRIII (20 mg/kg, p.o.) were also found to be more effective in increasing latency period in tail flick method. Out of five different fractions of F. religiosa leaves tested, FRI and FRIII possess potent analgesic and anti-inflammatory activities against different models of inflammation and pain.

Anti-HIV-1 activities of the extracts from the medicinal plant Linum grandiflorum Desf

DEFF Research Database (Denmark)

Mohammed, Magdy M. D.; Christensen, Lars Porskjær; Ibrahim, Nabaweya A.

2009-01-01

As part of our screening of anti-AIDS agents from natural sources e.g. Ixora undulata, Paulownia tomentosa, Fortunella margarita, Aegle marmelos and Erythrina abyssinica, the different organic and aqueous extracts of Linum grandiflorum leaves and seeds were evaluated in vitro by the microculture...... tetrazolium (MTT) assay. The activity of the tested extracts against multiplication of HIV-1 wild type IIIB, N119, A17, and EFVR in acutely infected cells was based on inhibition of virus-induced cytopathicity in MT-4 cells. Results revealed that both the MeOH and the CHCl3 extracts of L. grandiflorum have...... significant inhibitory effects against HIV-1 induced infection with MT-4 cells. The MeOH extract of the leaves is more potent than other extracts against MT-4 cell cultures infected with the wild type HIV-1, strain IIIB with an ED50 of 46 ± 6 µM, while the CHCl3 extract of the seeds is more potent than other...

Discovery of Anti-Hypertensive Oligopeptides from Adlay Based on In Silico Proteolysis and Virtual Screening

Directory of Open Access Journals (Sweden)

Liansheng Qiao

2016-12-01

Full Text Available Adlay (Coix larchryma-jobi L. was the commonly used Traditional Chinese Medicine (TCM with high content of seed storage protein. The hydrolyzed bioactive oligopeptides of adlay have been proven to be anti-hypertensive effective components. However, the structures and anti-hypertensive mechanism of bioactive oligopeptides from adlay were not clear. To discover the definite anti-hypertensive oligopeptides from adlay, in silico proteolysis and virtual screening were implemented to obtain potential oligopeptides, which were further identified by biochemistry assay and molecular dynamics simulation. In this paper, ten sequences of adlay prolamins were collected and in silico hydrolyzed to construct the oligopeptide library with 134 oligopeptides. This library was reverse screened by anti-hypertensive pharmacophore database, which was constructed by our research team and contained ten anti-hypertensive targets. Angiotensin-I converting enzyme (ACE was identified as the main potential target for the anti-hypertensive activity of adlay oligopeptides. Three crystal structures of ACE were utilized for docking studies and 19 oligopeptides were finally identified with potential ACE inhibitory activity. According to mapping features and evaluation indexes of pharmacophore and docking, three oligopeptides were selected for biochemistry assay. An oligopeptide sequence, NPATY (IC50 = 61.88 ± 2.77 µM, was identified as the ACE inhibitor by reverse-phase high performance liquid chromatography (RP-HPLC assay. Molecular dynamics simulation of NPATY was further utilized to analyze interactive bonds and key residues. ALA354 was identified as a key residue of ACE inhibitors. Hydrophobic effect of VAL518 and electrostatic effects of HIS383, HIS387, HIS513 and Zn2+ were also regarded as playing a key role in inhibiting ACE activities. This study provides a research strategy to explore the pharmacological mechanism of Traditional Chinese Medicine (TCM proteins based on

Anti-trypanosomal activity of pentacyclic triterpenes isolated from Austroplenckia populnea (Celastraceae).

Science.gov (United States)

Duarte, Lucienir Pains; Vieira Filho, Sidney Augusto; Silva, Grácia Divina de Fátima; de Sousa, José Rego; Pinto, Artur da Silveira

2002-01-01

Four pentacyclic triterpenes isolated from Austroplenckia populnea and four compounds of known anti T. cruzi or anti-malarial activity were tested. Of those triterpenes tested 20alpha-hydroxy-tingenone showed high activity, epikatonic acid was less active, while populnilic and populninic acids were inactive against the trypanosome of the subgenus Schizotrypanum tested. Benzonidazole, nifurtimox, ketoconazole and primaquine presented a remarkable dose-dependent inhibitory effect reaching practically to a total growth inhibition of the parasite at the end of incubation time. The trypanosome tested appear to be a suitable model for preliminary screen for anti T. (S.) cruzi compounds.

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)

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

Directory of Open Access Journals (Sweden)

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.

Activity of andrographolide against chikungunya virus infection.

Science.gov (United States)

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.

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

Directory of Open Access Journals (Sweden)

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.

Tuberculosis Screening and Active Tuberculosis among HIV-Infected Persons in a Canadian Tertiary Care Centre

Directory of Open Access Journals (Sweden)

Paul Brassard

2009-01-01

Full Text Available RATIONALE: HIV infection increases the risk of reactivation of latent tuberculosis (TB. The present study evaluates how latent TB is detected and treated to determine the effectiveness of screening in HIV-infected patients with diverse risk profiles.

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

Directory of Open Access Journals (Sweden)

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

Phytochemical screening and study of antioxidant, antimicrobial, antidiabetic, anti-inflammatory and analgesic activities of extracts from stem wood of Pterocarpus marsupium Roxburgh.

Science.gov (United States)

Pant, Dipak Raj; Pant, Narayan Dutt; Saru, Dil Bahadur; Yadav, Uday Narayan; Khanal, Dharma Prasad

2017-01-01

The main aims of the study were to evaluate the phytochemical constituents and to study the antioxidant, antimicrobial, antidiabetic, anti-inflammatory, and analgesic activities of extracts from stem wood of Pterocarpus marsupium . Ethanol, acetone and isopropyl alcohol (IPA) (1:1) extracts of stem wood of P. marsupium were subjected to phytochemical screening and analysis of biological activities from August 2015 to January 2016. The antioxidant assay was carried out using 2, 2-diphenyl-1-picrylhydrazyl scavenging method, antimicrobial activity testing by cup diffusion method, antidiabetic test evaluation by oral glucose tolerance test in mice, anti-inflammatory effect was evaluated by hind paw edema method in mice and analgesic test evaluation by a chemical writhing method in mice. The results of the study revealed that P. marsupium is a source of various phytoconstituents such as alkaloids, glycosides, saponins, tannins, proteins, carbohydrates, cardiac glycosides, flavonoids, and terpenoids. Both the acetone and IPA extract as well as the ethanol extract of stem wood of P. marsupium exhibited a dose-dependent antioxidant activity. Acetone and IPA extract showed antibacterial activity against Gram-positive bacteria, while the ethanolic extract was found to possess antidiabetic activity. The antidiabetic activity of the extract was found to be time and dose-dependent. Similarly, the acetone and IPA extract was found to have anti-inflammatory activity, which was also time and dose-dependent. Furthermore, the ethanolic extract showed analgesic activity, which was dose-dependent. The ethanolic extract was found to be nontoxic. Thus, this study laid sufficient background for the further research on extracts from stem wood of P. marsupium for identification, subsequent purification and isolation of compounds having antibacterial, antidiabetic, anti-inflammatory, and analgesic activities.

Readability Comparison of Pro- and Anti-Cancer Screening Online Messages in Japan

Science.gov (United States)

Okuhara, Tsuyoshi; Ishikawa, Hirono; Okada, Masahumi; Kato, Mio; Kiuchi, Takahiro

2016-01-01

Background: Cancer screening rates are lower in Japan than those in western countries. Health professionals publish pro-cancer screening messages on the internet to encourage audiences to undergo cancer screening. However, the information provided is often difficult to read for lay persons. Further, anti-cancer screening activists warn against cancer screening with messages on the Internet. We aimed to assess and compare the readability of pro- and anti-cancer screening online messages in Japan using a measure of readability. Methods: We conducted web searches at the beginning of September 2016 using two major Japanese search engines (Google.jp and Yahoo!.jp). The included websites were classified as “anti”, “pro”, or “neutral” depending on the claims, and “health professional” or “non-health professional” depending on the writers. Readability was determined using a validated measure of Japanese readability. Statistical analysis was conducted using two-way ANOVA. Results: In the total 159 websites analyzed, anti-cancer screening online messages were generally easier to read than pro-cancer screening online messages, Messages written by health professionals were more difficult to read than those written by non-health professionals. Claim × writer interaction was not significant. Conclusion: When health professionals prepare pro-cancer screening materials for publication online, we recommend they check for readability using readability assessment tools and improve text for easy comprehension when necessary. PMID:28125867

Screening of Active Lyssavirus Infection in Wild Bat Populations by Viral RNA Detection on Oropharyngeal Swabs

Science.gov (United States)

Echevarría, Juan E.; Avellón, Ana; Juste, Javier; Vera, Manuel; Ibáñez, Carlos

2001-01-01

Brain analysis cannot be used for the investigation of active lyssavirus infection in healthy bats because most bat species are protected by conservation directives. Consequently, serology remains the only tool for performing virological studies on natural bat populations; however, the presence of antibodies merely reflects past exposure to the virus and is not a valid marker of active infection. This work describes a new nested reverse transcription (RT)-PCR technique specifically designed for the detection of the European bat virus 1 on oropharyngeal swabs obtained from bats but also able to amplify RNA from the remaining rabies-related lyssaviruses in brain samples. The technique was successfully used for surveillance of a serotine bat (Eptesicus serotinus) colony involved in a case of human exposure, in which 15 out of 71 oropharyngeal swabs were positive. Lyssavirus infection was detected on 13 oropharyngeal swabs but in only 5 brains out of the 34 animals from which simultaneous brain and oropharyngeal samples had been taken. The lyssavirus involved could be rapidly identified by automatic sequencing of the RT-PCR products obtained from 14 brains and three bat oropharyngeal swabs. In conclusion, RT-PCR using oropharyngeal swabs will permit screening of wild bat populations for active lyssavirus infection, for research or epidemiological purposes, in line not only with conservation policies but also in a more efficient manner than classical detection techniques used on the brain. PMID:11574590

Anti-plasmodial activity of Dicoma tomentosa (Asteraceae) and identification of urospermal A-15-O-acetate as the main active compound

Science.gov (United States)

2012-01-01

Background Natural products could play an important role in the challenge to discover new anti-malarial drugs. In a previous study, Dicoma tomentosa (Asteraceae) was selected for its promising anti-plasmodial activity after a preliminary screening of several plants traditionally used in Burkina Faso to treat malaria. The aim of the present study was to further investigate the anti-plasmodial properties of this plant and to isolate the active anti-plasmodial compounds. Methods Eight crude extracts obtained from D. tomentosa whole plant were tested in vitro against two Plasmodium falciparum strains (3D7 and W2) using the p-LDH assay (colorimetric method). The Peters’ four-days suppressive test model (Plasmodium berghei-infected mice) was used to evaluate the in vivo anti-plasmodial activity. An in vitro bioguided fractionation was undertaken on a dichloromethane extract, using preparative HPLC and TLC techniques. The identity of the pure compound was assessed using UV, MS and NMR spectroscopic analysis. In vitro cytotoxicity against WI38 human fibroblasts (WST-1 assay) and haemolytic activity were also evaluated for extracts and pure compounds in order to check selectivity. Results The best in vitro anti-plasmodial results were obtained with the dichloromethane, diethylether, ethylacetate and methanol extracts, which exhibited a high activity (IC50 ≤ 5 μg/ml). Hot water and hydroethanolic extracts also showed a good activity (IC50 ≤ 15 μg/ml), which confirmed the traditional use and the promising anti-malarial potential of the plant. The activity was also confirmed in vivo for all tested extracts. However, most of the active extracts also exhibited cytotoxic activity, but no extract was found to display any haemolytic activity. The bioguided fractionation process allowed to isolate and identify a sesquiterpene lactone (urospermal A-15-O-acetate) as the major anti-plasmodial compound of the plant (IC50 < 1 μg/ml against both 3D7 and W2 strains). This was also

Pyrazole compound BPR1P0034 with potent and selective anti-influenza virus activity

Directory of Open Access Journals (Sweden)

Yeh Jiann-Yih

2010-02-01

Full Text Available Abstract Background Influenza viruses are a major cause of morbidity and mortality around the world. More recently, a swine-origin influenza A (H1N1 virus that is spreading via human-to-human transmission has become a serious public concern. Although vaccination is the primary strategy for preventing infections, influenza antiviral drugs play an important role in a comprehensive approach to controlling illness and transmission. In addition, a search for influenza-inhibiting drugs is particularly important in the face of high rate of emergence of influenza strains resistant to several existing influenza antivirals. Methods We searched for novel anti-influenza inhibitors using a cell-based neutralization (inhibition of virus-induced cytopathic effect assay. After screening 20,800 randomly selected compounds from a library from ChemDiv, Inc., we found that BPR1P0034 has sub-micromolar antiviral activity. The compound was resynthesized in five steps by conventional chemical techniques. Lead optimization and a structure-activity analysis were used to improve potency. Time-of-addition assay was performed to target an event in the virus life cycle. Results The 50% effective inhibitory concentration (IC50 of BPR1P0034 was 0.42 ± 0.11 μM, when measured with a plaque reduction assay. Viral protein and RNA synthesis of A/WSN/33 (H1N1 was inhibited by BPR1P0034 and the virus-induced cytopathic effects were thus significantly reduced. BPR1P0034 exhibited broad inhibition spectrum for influenza viruses but showed no antiviral effect for enteroviruses and echovirus 9. In a time-of-addition assay, in which the compound was added at different stages along the viral replication cycle (such as at adsorption or after adsorption, its antiviral activity was more efficient in cells treated with the test compound between 0 and 2 h, right after viral infection, implying that an early step of viral replication might be the target of the compound. These results suggest

Discovery of a novel compound with anti-venezuelan equine encephalitis virus activity that targets the nonstructural protein 2.

Directory of Open Access Journals (Sweden)

Dong-Hoon Chung

2014-06-01

Full Text Available Alphaviruses present serious health threats as emerging and re-emerging viruses. Venezuelan equine encephalitis virus (VEEV, a New World alphavirus, can cause encephalitis in humans and horses, but there are no therapeutics for treatment. To date, compounds reported as anti-VEEV or anti-alphavirus inhibitors have shown moderate activity. To discover new classes of anti-VEEV inhibitors with novel viral targets, we used a high-throughput screen based on the measurement of cell protection from live VEEV TC-83-induced cytopathic effect to screen a 340,000 compound library. Of those, we identified five novel anti-VEEV compounds and chose a quinazolinone compound, CID15997213 (IC50 = 0.84 µM, for further characterization. The antiviral effect of CID15997213 was alphavirus-specific, inhibiting VEEV and Western equine encephalitis virus, but not Eastern equine encephalitis virus. In vitro assays confirmed inhibition of viral RNA, protein, and progeny synthesis. No antiviral activity was detected against a select group of RNA viruses. We found mutations conferring the resistance to the compound in the N-terminal domain of nsP2 and confirmed the target residues using a reverse genetic approach. Time of addition studies showed that the compound inhibits the middle stage of replication when viral genome replication is most active. In mice, the compound showed complete protection from lethal VEEV disease at 50 mg/kg/day. Collectively, these results reveal a potent anti-VEEV compound that uniquely targets the viral nsP2 N-terminal domain. While the function of nsP2 has yet to be characterized, our studies suggest that the protein might play a critical role in viral replication, and further, may represent an innovative opportunity to develop therapeutic interventions for alphavirus infection.

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

Science.gov (United States)

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.

Screening for Hepatitis C Infections in Adults

Science.gov (United States)

Understanding Task Force Recommendations Screening for Hepatitis C Virus Infection in Adults The U.S. Preventive Services Task Force (Task Force) has issued a final recommendation statement on Screening for Hepatitis C Virus ...

analgesic and anti-inflammatory activities of ethanolic extract of ...

African Journals Online (AJOL)

2015-04-30

Apr 30, 2015 ... The analgesic and anti-inflammatory activities of the ethanolic extract of Rheumatic Tea Formula ... Salix alba were studied in mice and rats using acetic acid induced writhing, hot plate method, ... albino mice, while the phytochemical screening showed the presence of alkaloids, tannins and glycosides.

Lymphocytes Negatively Regulate NK Cell Activity via Qa-1b following Viral Infection

Directory of Open Access Journals (Sweden)

Haifeng C. Xu

2017-11-01

Full Text Available NK cells can reduce anti-viral T cell immunity during chronic viral infections, including infection with the lymphocytic choriomeningitis virus (LCMV. However, regulating factors that maintain the equilibrium between productive T cell and NK cell immunity are poorly understood. Here, we show that a large viral load resulted in inhibition of NK cell activation, which correlated with increased expression of Qa-1b, a ligand for inhibitory NK cell receptors. Qa-1b was predominantly upregulated on B cells following LCMV infection, and this upregulation was dependent on type I interferons. Absence of Qa-1b resulted in increased NK cell-mediated regulation of anti-viral T cells following viral infection. Consequently, anti-viral T cell immunity was reduced in Qa-1b- and NKG2A-deficient mice, resulting in increased viral replication and immunopathology. NK cell depletion restored anti-viral immunity and virus control in the absence of Qa-1b. Taken together, our findings indicate that lymphocytes limit NK cell activity during viral infection in order to promote anti-viral T cell immunity.

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.

Congenital cytomegalovirus infection: disease burden and screening tools : towards newborn screening

OpenAIRE

Vries, Jutte Jacoba Catharina de

2012-01-01

Cytomegalovirus (CMV) infection is the most common congenital viral infection worldwide. The symptom of congenital CMV infection encountered most frequently is sensorineural hearing loss, which will affect approximately one out of five congenitally infected newborns. Because of the late-onset nature of the hearing loss, up to half of the children with congenital CMV-related hearing loss may not be detected in the newborn hearing screening. This thesis addresses several aspects of congenital CM...

Current State of and Needs for Hepatitis B Screening: Results of a Large Screening Study in a Low-Prevalent, Metropolitan Region

Science.gov (United States)

Bottero, Julie; Boyd, Anders; Lemoine, Maud; Carrat, Fabrice; Gozlan, Joel; Collignon, Anne; Boo, Nicolas; Dhotte, Philippe; Varsat, Brigitte; Muller, Gerard; Cha, Olivier; Valin, Nadia; Nau, Jean; Campa, Pauline; Silbermann, Benjamin; Bary, Marc; Girard, Pierre-Marie; Lacombe, Karine

2014-01-01

Background In low hepatitis B virus (HBV)-prevalent countries, most HBV-infected persons are unaware of their status. We aimed to evaluate whether (i) previous HBV-testing, (ii) physicians decision to screen, and (iii) CDC's recommendations identified infected individuals and which risk-factor groups needing testing. Methods During a mass, multi-center HBV-screening study from September 2010-August 2011, 3929 participants were screened for hepatitis B surface antigen (HBsAg), anti-HBs and anti-Hepatitis B core antibodies (anti-HBcAb). Questions on HBV risk-factors and testing practices were asked to participants, while participants' eligibility for HBV-testing was asked to study medical professionals. Results 85 (2.2%) participants were HBsAg-positive, while 659 (16.8%) had either resolved HBV infection or isolated anti-HBcAb. When comparing practices, HBV-testing was more likely to occur in HBV-infected participants if Centers for Disease Control and Prevention (CDC) recommendations were used (Sensitivity = 100%, 95%CI: 95.8–100) than physicians' discretion (Sensitivity = 87.1%, 95%CI: 78.0–93.4) or previous HBV-test (Sensitivity = 36.5%, 95%CI: 26.3–47.6) (p<0.0001). Nevertheless, many non-infected individuals would still have been screened using CDC-recommendations (Specificity = 31.1%, 95%CI: 29.6–32.6). Using multivariable logistic regression, HBsAg-positive status was significantly associated with the following: males, originating from high HBV-endemic region, contact with HBV-infected individual, without national healthcare, and intravenous-drug user (IDU). Of these risk-factors, physician's discretion for testing HBV was not significantly associated with participants' geographical origin or IDU. Conclusions Missed opportunities of HBV-screening are largely due to underestimating country of origin as a risk-factor. Applying CDC-recommendations could improve HBV-screening, but with the disadvantage of many tests. Further development of

Selective intrapartum anti-bioprophylaxy of group B streptococci infection of neonates: a prospective study in 2454 subsequent deliveries.

Science.gov (United States)

Poulain, P; Betremieux, P; Donnio, P Y; Proudhon, J F; Karege, G; Giraud, J R

1997-04-01

To investigate the efficacy of a selective intrapartum prophylaxy of group B streptococci (GBS) infection of the neonates. A prospective protocol of universal antepartum screening of GBS and selective intrapartum treatment from the 1st February 1994 to the 31st December 1995, on 2454 subsequent deliveries was designed. Our policy included: (1) antepartum screening as soon as possible after 28 weeks by a single vaginal and perianal sample for culture; (2) intrapartum recognition of one condition of high risk of fetal contamination during labor (these conditions included: a temperature of 38 degrees C during labor, rupture of membranes for more than 12 h or prolonged labor for more than 12 h with rupture of membranes, prematurity, twins, maternal diabetes, previous pregnancy with GBS infection of the neonate); and (3) intrapartum anti-bioprophylaxy (amoxicillin) for women with positive screening during pregnancy and one condition of high risk of fetal contamination during labor. We studied the outcome of neonates during this period to look for immediate GBS severe infection of the neonates in the form of bacteraemia or meningitis and compared the results with the rate of neonatal infection before this protocol (4.5/1000 live births in 1993). We noted that 11% of pregnant women were carriers, 25% of which led to antibiotic chemoprophylaxis during the labor. We noticed four cases of neonatal bacteraemia of GBS. One case arose from the group of carriers (but no condition of risk of fetal contamination during the labor and no chemoprophylaxy). The three other cases were from women with a negative antepartum screening. There was no case of meningitis and all four babies were in good health at day 10 of life. Comparing with results prior to the study, we noticed that the rate of neonatal bacteraemia dropped from 4.5 to 1.6 per 1000 livebirths (P < 0.0001). This protocol of intrapartum anti-bioprophylaxy significantly decreases the rate of GBS neonatal sepsis. We propose to

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.

Targeted screening strategies to detect Trypanosoma cruzi infection in children.

Directory of Open Access Journals (Sweden)

Michael Z Levy

2007-12-01

Full Text Available Millions of people are infected with Trypanosoma cruzi, the causative agent of Chagas disease in Latin America. Anti-trypanosomal drug therapy can cure infected individuals, but treatment efficacy is highest early in infection. Vector control campaigns disrupt transmission of T. cruzi, but without timely diagnosis, children infected prior to vector control often miss the window of opportunity for effective chemotherapy.We performed a serological survey in children 2-18 years old living in a peri-urban community of Arequipa, Peru, and linked the results to entomologic, spatial and census data gathered during a vector control campaign. 23 of 433 (5.3% [95% CI 3.4-7.9] children were confirmed seropositive for T. cruzi infection by two methods. Spatial analysis revealed that households with infected children were very tightly clustered within looser clusters of households with parasite-infected vectors. Bayesian hierarchical mixed models, which controlled for clustering of infection, showed that a child's risk of being seropositive increased by 20% per year of age and 4% per vector captured within the child's house. Receiver operator characteristic (ROC plots of best-fit models suggest that more than 83% of infected children could be identified while testing only 22% of eligible children.We found evidence of spatially-focal vector-borne T. cruzi transmission in peri-urban Arequipa. Ongoing vector control campaigns, in addition to preventing further parasite transmission, facilitate the collection of data essential to identifying children at high risk of T. cruzi infection. Targeted screening strategies could make integration of diagnosis and treatment of children into Chagas disease control programs feasible in lower-resource settings.

Screening of Baccaurea ramiflora (Lour.) extracts for cytotoxic, analgesic, anti-inflammatory, neuropharmacological and antidiarrheal activities.

Science.gov (United States)

Nesa, Mst Luthfun; Karim, S M Sajedul; Api, Khairunasa; Sarker, Md Moklesur Rahman; Islam, Md Monirul; Kabir, Asma; Sarker, Mithun Kumar; Nahar, Kamrun; Asadujjaman, Mohammad; Munir, Mohammad Sirajum

2018-01-30

It has been observed that the various part of Baccaurea ramiflora plant is used in rheumatoid arthritis, cellulitis, abscesses, constipation and injuries. This plant also has anticholinergic, hypolipidemic, hypoglycemic, antiviral, antioxidant, diuretic and cytotoxic activities. The present studyaimed to assess the cytotoxic, analgesic, anti-inflammatory, CNS depressant and antidiarrheal activities of methanol extract of Baccaurea ramiflora pulp and seeds in mice model. The cytotoxic activity was determined by brine shrimp lethality bioassay; anti-nociceptive activity was determined by acetic acid-induced writhing, formalin- induced licking and biting, and tail immersion methods. The anti-inflammatory, CNS depressant and anti-diarrheal activities were assessed by carrageenan-induced hind paw edema, the open field and hole cross tests, and castor oil-induced diarrheal methods, respectively. The data were analyzed by one way ANOVA (analysis of variance) followed by Dunnett's test. In brine shrimp lethality bioassay, the LC 50 values of the methanol extracts of Baccaurea ramiflora pulp and seed were 40 μg/mL and 10 μg/mL, respectively. Our investigation showed that Baccaurea ramiflora pulp and seed extracts (200 mg/kg) inhibited acetic acid induced pain 67.51 and 66.08%, respectively (p analgesic, anti-inflammatory, CNS depressant and antidiarrheal activities of methanol extract of Baccaurea ramiflora pulp and seeds (200 mg/kg).

A natural component from Euphorbia humifusa Willd displays novel, broad-spectrum anti-influenza activity by blocking nuclear export of viral ribonucleoprotein

Energy Technology Data Exchange (ETDEWEB)

Chang, So Young; Park, Ji Hoon [Respiratory Viruses Research Laboratory, Discovery Biology Department, Institut Pasteur Korea, 16, Daewangpangyo-ro 712 Beon-gil, Bundang-gu, Seongnam-si, Gyeonggi-do, 463-400 (Korea, Republic of); Kim, Young Ho; Kang, Jong Seong [College of Pharmacy, Chungnam National University, Daejeon, 305-764 (Korea, Republic of); Min, Ji-Young, E-mail: jiyoung.min@ip-korea.org [Respiratory Viruses Research Laboratory, Discovery Biology Department, Institut Pasteur Korea, 16, Daewangpangyo-ro 712 Beon-gil, Bundang-gu, Seongnam-si, Gyeonggi-do, 463-400 (Korea, Republic of)

2016-03-04

The need to develop anti-influenza drugs with novel antiviral mechanisms is urgent because of the rapid rate of antigenic mutation and the emergence of drug-resistant viruses. We identified a novel anti-influenza molecule by screening 861 plant-derived natural components using a high-throughput image-based assay that measures inhibition of the influenza virus infection. 1,3,4,6-tetra-O-galloyl-β-D-glucopyranoside (TGBG) from Euphorbia humifusa Willd showed broad-spectrum anti-influenza activity against two seasonal influenza A strains, A/California/07/2009 (H1N1) and A/Perth/16/2009 (H3N2), and seasonal influenza B strain B/Florida/04/2006. We investigated the mode of action of TGBG using neuraminidase activity inhibition and time-of-addition assays, which evaluate the viral release and entry steps, respectively. We found that TGBG exhibits a novel antiviral mechanism that differs from the FDA-approved anti-influenza drugs oseltamivir which inhibits viral release, and amantadine which inhibits viral entry. Immunofluorescence assay demonstrated that TGBG significantly inhibits nuclear export of influenza nucleoproteins (NP) during the early stages of infection causing NP to accumulate in the nucleus. In addition, influenza-induced activation of the Akt signaling pathway was suppressed by TGBG in a dose-dependent manner. These data suggest that a putative mode of action of TGBG involves inhibition of viral ribonucleoprotein (vRNP) export from the nucleus to the cytoplasm consequently disrupting the assembly of progeny virions. In summary, TGBG has potential as novel anti-influenza therapeutic with a novel mechanism of action. - Highlights: • The plant-derived natural product TGBG has broad-spectrum antiviral activity against seasonal influenza A and B viruses. • TGBG has a novel anti-viral mechanism of action that from differs from the currently available anti-influenza drugs. • TGBG hinders nuclear export of the influenza virus ribonucleoprotein (v

A natural component from Euphorbia humifusa Willd displays novel, broad-spectrum anti-influenza activity by blocking nuclear export of viral ribonucleoprotein

International Nuclear Information System (INIS)

Chang, So Young; Park, Ji Hoon; Kim, Young Ho; Kang, Jong Seong; Min, Ji-Young

2016-01-01

The need to develop anti-influenza drugs with novel antiviral mechanisms is urgent because of the rapid rate of antigenic mutation and the emergence of drug-resistant viruses. We identified a novel anti-influenza molecule by screening 861 plant-derived natural components using a high-throughput image-based assay that measures inhibition of the influenza virus infection. 1,3,4,6-tetra-O-galloyl-β-D-glucopyranoside (TGBG) from Euphorbia humifusa Willd showed broad-spectrum anti-influenza activity against two seasonal influenza A strains, A/California/07/2009 (H1N1) and A/Perth/16/2009 (H3N2), and seasonal influenza B strain B/Florida/04/2006. We investigated the mode of action of TGBG using neuraminidase activity inhibition and time-of-addition assays, which evaluate the viral release and entry steps, respectively. We found that TGBG exhibits a novel antiviral mechanism that differs from the FDA-approved anti-influenza drugs oseltamivir which inhibits viral release, and amantadine which inhibits viral entry. Immunofluorescence assay demonstrated that TGBG significantly inhibits nuclear export of influenza nucleoproteins (NP) during the early stages of infection causing NP to accumulate in the nucleus. In addition, influenza-induced activation of the Akt signaling pathway was suppressed by TGBG in a dose-dependent manner. These data suggest that a putative mode of action of TGBG involves inhibition of viral ribonucleoprotein (vRNP) export from the nucleus to the cytoplasm consequently disrupting the assembly of progeny virions. In summary, TGBG has potential as novel anti-influenza therapeutic with a novel mechanism of action. - Highlights: • The plant-derived natural product TGBG has broad-spectrum antiviral activity against seasonal influenza A and B viruses. • TGBG has a novel anti-viral mechanism of action that from differs from the currently available anti-influenza drugs. • TGBG hinders nuclear export of the influenza virus ribonucleoprotein (v

Anti-cancer activities of diospyrin, its derivatives and analogues

KAUST Repository

Sagar, Sunil; Kaur, Mandeep; Minneman, Kenneth P.; Bajic, Vladimir B.

2010-01-01

Natural products have played a vital role in drug discovery and development process for cancer. Diospyrin, a plant based bisnaphthoquinonoid, has been used as a lead molecule in an effort to develop anti-cancer drugs. Several derivatives/analogues have been synthesized and screened for their pro-apoptotic/anti-cancer activities so far. Our review is focused on the pro-apoptotic/anti-cancer activities of diospyrin, its derivatives/analogues and the different mechanisms potentially involved in the bioactivity of these compounds. Particular focus has been placed on the different mechanisms (both chemical and molecular) thought to underlie the bioactivity of these compounds. A brief bioinformatics analysis at the end of the article provides novel insights into the new potential mechanisms and pathways by which these compounds might exert their effects and lead to a better realization of the full therapeutic potential of these compounds as anti-cancer drugs. © 2010 Elsevier Masson SAS. All rights reserved.

Anti-cancer activities of diospyrin, its derivatives and analogues

KAUST Repository

Sagar, Sunil

2010-09-01

Natural products have played a vital role in drug discovery and development process for cancer. Diospyrin, a plant based bisnaphthoquinonoid, has been used as a lead molecule in an effort to develop anti-cancer drugs. Several derivatives/analogues have been synthesized and screened for their pro-apoptotic/anti-cancer activities so far. Our review is focused on the pro-apoptotic/anti-cancer activities of diospyrin, its derivatives/analogues and the different mechanisms potentially involved in the bioactivity of these compounds. Particular focus has been placed on the different mechanisms (both chemical and molecular) thought to underlie the bioactivity of these compounds. A brief bioinformatics analysis at the end of the article provides novel insights into the new potential mechanisms and pathways by which these compounds might exert their effects and lead to a better realization of the full therapeutic potential of these compounds as anti-cancer drugs. © 2010 Elsevier Masson SAS. All rights reserved.

Predictive models for anti-tubercular molecules using machine learning on high-throughput biological screening datasets.

Science.gov (United States)

Periwal, Vinita; Rajappan, Jinuraj K; Jaleel, Abdul Uc; Scaria, Vinod

2011-11-18

Tuberculosis is a contagious disease caused by Mycobacterium tuberculosis (Mtb), affecting more than two billion people around the globe and is one of the major causes of morbidity and mortality in the developing world. Recent reports suggest that Mtb has been developing resistance to the widely used anti-tubercular drugs resulting in the emergence and spread of multi drug-resistant (MDR) and extensively drug-resistant (XDR) strains throughout the world. In view of this global epidemic, there is an urgent need to facilitate fast and efficient lead identification methodologies. Target based screening of large compound libraries has been widely used as a fast and efficient approach for lead identification, but is restricted by the knowledge about the target structure. Whole organism screens on the other hand are target-agnostic and have been now widely employed as an alternative for lead identification but they are limited by the time and cost involved in running the screens for large compound libraries. This could be possibly be circumvented by using computational approaches to prioritize molecules for screening programmes. We utilized physicochemical properties of compounds to train four supervised classifiers (Naïve Bayes, Random Forest, J48 and SMO) on three publicly available bioassay screens of Mtb inhibitors and validated the robustness of the predictive models using various statistical measures. This study is a comprehensive analysis of high-throughput bioassay data for anti-tubercular activity and the application of machine learning approaches to create target-agnostic predictive models for anti-tubercular agents.

Predictive models for anti-tubercular molecules using machine learning on high-throughput biological screening datasets

Directory of Open Access Journals (Sweden)

Periwal Vinita

2011-11-01

Full Text Available Abstract Background Tuberculosis is a contagious disease caused by Mycobacterium tuberculosis (Mtb, affecting more than two billion people around the globe and is one of the major causes of morbidity and mortality in the developing world. Recent reports suggest that Mtb has been developing resistance to the widely used anti-tubercular drugs resulting in the emergence and spread of multi drug-resistant (MDR and extensively drug-resistant (XDR strains throughout the world. In view of this global epidemic, there is an urgent need to facilitate fast and efficient lead identification methodologies. Target based screening of large compound libraries has been widely used as a fast and efficient approach for lead identification, but is restricted by the knowledge about the target structure. Whole organism screens on the other hand are target-agnostic and have been now widely employed as an alternative for lead identification but they are limited by the time and cost involved in running the screens for large compound libraries. This could be possibly be circumvented by using computational approaches to prioritize molecules for screening programmes. Results We utilized physicochemical properties of compounds to train four supervised classifiers (Naïve Bayes, Random Forest, J48 and SMO on three publicly available bioassay screens of Mtb inhibitors and validated the robustness of the predictive models using various statistical measures. Conclusions This study is a comprehensive analysis of high-throughput bioassay data for anti-tubercular activity and the application of machine learning approaches to create target-agnostic predictive models for anti-tubercular agents.

Evaluation of anti-pyretic and analgesic activity of Emblica officinalis Gaertn.

Science.gov (United States)

Perianayagam, James B; Sharma, S K; Joseph, Aney; Christina, A J M

2004-11-01

The present study was designed to investigate the anti-pyretic and analgesic activity of ethanol (EEO) and aqueous (AEO) extracts of Emblica officinalis fruits in several experimental models. A single oral dose of EEO and AEO (500 mg/kg, i.p.) showed significant reduction in brewer's yeast induced hyperthermia in rats. EEO and AEO also elicited pronounced inhibitory effect on acetic acid-induced writhing response in mice in the analgesic test. Both, EEO and AEO did not show any significant analgesic activity in the tail-immersion test. These findings suggest that extracts of Emblica officinalis fruits possessed potent anti-pyretic and analgesic activity. Preliminary phytochemical screening of the extracts showed the presence of alkaloids, tannins, phenolic compounds, carbohydrates and amino acids, which may be responsible for anti-pyretic and analgesic activities.

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

Directory of Open Access Journals (Sweden)

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.

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

Directory of Open Access Journals (Sweden)

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.

Synthesis and structure-activity relationships of novel cationic lipids with anti-inflammatory and antimicrobial activities.

Science.gov (United States)

Myint, Melissa; Bucki, Robert; Janmey, Paul A; Diamond, Scott L

2015-07-15

Certain membrane-active cationic steroids are known to also possess both anti-inflammatory and antimicrobial properties. This combined functionality is particularly relevant for potential therapies of infections associated with elevated tissue damage, for example, cystic fibrosis airway disease, a condition characterized by chronic bacterial infections and ongoing inflammation. In this study, six novel cationic glucocorticoids were synthesized using beclomethasone, budesonide, and flumethasone. Products were either monosubstituted or disubstituted, containing one or two steroidal groups, respectively. In vitro evaluation of biological activities demonstrated dual anti-inflammatory and antimicrobial properties with limited cytotoxicity for all synthesized compounds. Budesonide-derived compounds showed the highest degree of both glucocorticoid and antimicrobial properties within their respective mono- and disubstituted categories. Structure-activity analyses revealed that activity was generally related to the potency of the parent glucocorticoid. Taken together, these data indicate that these types of dual acting cationic lipids can be synthesized with the appropriate starting steroid to tailor activities as desired. Copyright © 2015 Elsevier Ltd. All rights reserved.

Anti-malarial activity of 6-(8'Z-pentadecenyl-salicylic acid from Viola websteri in mice

Directory of Open Access Journals (Sweden)

Park Won-Hwan

2009-07-01

Full Text Available Abstract Background Petroleum ether extracts of Viola websteri Hemsl (Violaceae were reported to have anti-plasmodial activity against Plasmodium falciparum in vitro, with this activity being largely attributable to 6-(8'Z-pentadecenyl-salicylic acid (6-SA. Methods The schizontocidal activity of 6-SA on early Plasmodium berghei infections was evaluated in a four-day test. The possible 'repository' activity of 6-SA was assessed using the method described by Peters. The median lethal dose (LD50 of 6-SA, when given intraperitoneally, was also determined using uninfected ICR mice and the method of Lorke. Results In the present study, 6-SA was found to have anti-malarial activity in vivo, when tested against P. berghei in mice. 6-SA at 5, 10 and 25 mg/kg·day exhibited a significant blood schizontocidal activity in four-day early infections, repository evaluations and established infections with a significant mean survival time comparable to that of the standard drug, chloroquine (5 mg/kg·day. Conclusion 6-SA possesses a moderate anti-malarial activity that could be exploited for malaria therapy.

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

DEFF Research Database (Denmark)

Köhler, Ole; Petersen, Liselotte; Mors, O

2017-01-01

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

Conjugation of Inulin Improves Anti-Biofilm Activity of Chitosan

OpenAIRE

Guiqiang Zhang; Jing Liu; Ruilian Li; Siming Jiao; Cui Feng; Zhuo A. Wang; Yuguang Du

2018-01-01

Bacteria biofilm helps bacteria prevent phagocytosis during infection and increase resistance to antibiotics. Staphylococcus aureus is a Gram-positive pathogenic bacterium and is tightly associated with biofilm-related infections, which have led to great threat to human health. Chitosan, the only cationic polysaccharide in nature, has been demonstrated to have antimicrobial and anti-biofilm activities, which, however, require a relative high dosage of chitosan. Moreover, poor water solubility...

Anti-inflammatory activity of Shirishavaleha: An Ayurvedic compound formulation.

Science.gov (United States)

Yadav, Shyamlal Singh; Galib; Ravishankar, B; Prajapati, P K; Ashok, B K; Varun, B

2010-10-01

The purpose of the present study was to evaluate the anti-inflammatory activity of Shirishavaleha prepared from two different parts of Shirisha (Albizia lebbeck Benth.), viz. the bark (Twak) and the heartwood (Sara). The activity was screened in the carrageenan-induced rat paw edema model in albino rats. The raw materials were collected and authenticated in the university and the trial formulations were prepared by following standard classical guidelines. Randomly selected animals were divided into four groups of six animals each. The test drugs were administered orally at a dose of 1.8 g/kg for 5 days. Phenylbutazone was used as the standard anti-inflammatory drug for comparison. Between the two different test samples studied, the formulation made from heartwood showed a weak anti-inflammatory activity in this model while that made from the bark produced a considerable suppression of edema after 6 h. It appears that the bark sample would be preferable for clinical use.

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

OpenAIRE

Appaji Mahesh Ashwini; Latha Puttarudrappa; Belagumba Vijaykumar Ravi; Mala Majumdar

2015-01-01

The aim of the present study was to investigate the GC-MS analysis, phytochemical screening, anti-oxidant, thrombolytic and anti-inflammatory activities of methanol extract of leaves of Exacum bicolor. FTIR analysis confirmed the presence of alcohol, phenols, alkanes, aromatic compounds, aldehyde and ethers. GC-MS analysis revealed the presence of eight phyto-constituents. The total phenol, flavonoid and alkaloid contents were 18.0 ± 0.2 mg/GAE/g, 13.1 ± 0.4 mg QE/g and 108.0 ± 1.2 mg AE/g re...

PURIFICATION AND FRACTIONAL ANALYSIS OF METHANOLIC EXTRACT OF WEDELIA TRILOBATA POSSESSING APOPTOTIC AND ANTI-LEUKEMIC ACTIVITY

Science.gov (United States)

Venkatesh, Uday; Javarasetty, Chethan; Murari, Satish Kumar

2017-01-01

Background: Wedelia trilobata (L.) Hitch (WT), commonly known as yellow dots or creeping daisy, is a shrub possessing potent biological activities, and is traditionally used a medicinal plant in Ayurveda, Siddha and Unani systems of medicines, and it has also been tried against leukemia cell line MEG- 01. In the present study, purification and screening of the plant was done for bioactive compounds in methanolic extract of WT for apoptotic and anti-leukemia activity. Materials and methods: The methanolic extract of WT was initially purified through thin layer chromatography (TLC) and screened for the apoptotic and anti-leukemia activities. The positive band of TLC was subjected to silica gel column chromatography for further purification and the fractions obtained from it were screened again for anti-leukemia activity through thymidine uptake assay and apoptotic activity by DNA fragmentation, nuclear staining and flow cytometry assays. The fraction with positive result was subjected to HPLC for analysis of bioactive components. Results: Out of many combinations of solvents, the methanol and dichloromethane combination in the ratio 6:4 has revealed two bands in TLC, among which the second band showed positive results for apoptotic and anti-leukemic activities. Further purification of second band through silica gel chromatography gave five fractions in which the 3rd fraction gave positive results and it shows single peak during compositional analysis through HPLC. Conclusion: The single peak revealed through HPLC indicates the presence of pure compound with apoptotic and anti-leukemia activities encouraging for further structural analysis. PMID:28480428

Screening of HBsAg and anti HCV from tertiary care, private and public sector hospitals

International Nuclear Information System (INIS)

Khan, R.A.W.; Ahmed, W.; Alam, S.E.; Arif, A

2011-01-01

Objectives: To find out the frequency of hepatitis B surface antigen and hepatitis C antibodies in patients referred from a tertiary care public sector hospital, other public sector and private hospitals of Karachi. Settings and duration: Pakistan Medical Research Council's Specialized Research Centre for Gastroenterology and Hepatology, at Jinnah Postgraduate Medical Centre Karachi from January to December 2009. Patients and Methods: A cross sectional study was conducted where patients were referred from different departments of Jinnah Postgraduate Medical Centre (tertiary care public sector hospital), other public sector hospitals, private hospitals and clinics for the screening of hepatitis B and C virus infection. Three ml blood was collected from each patient, serum separated and tested for HBsAg and Anti HCV using Abbott Murex fourth Generation ELISA kits. Results: A total of 2965 cases were referred in a year. Overall sero prevalence of HBsAg and Anti-HCV was 5.9% and 12.8% respectively. HBsAg positivity in patient referred from public sector hospitals was 5.8%, those from private hospitals/clinics were 7.2%, and self-referred patients was 5.6%. Anti HCV positivity rates amongst these cases were 12.5%, 16.7% and 8.5% respectively. Co-infection of hepatitis B virus and hepatitis C virus was seen in 0.9, 2.5 and 1.4% cases respectively. Breakdown of viral positivity within different departments of Jinnah Postgraduate Medical Centre Karachi showed HBsAg positivity of 7.1% in Medical department, 5.2% in Surgical department, 5.0% in Gynaecology department, 6.6% in other departments of Jinnah Postgraduate Medical Centre while, only 1.7% were positive from Pakistan Railway, hospital Anti HCV positivity was maximally (20.3%) seen in medical department followed by 14% in other departments, 10.9% in surgical department, 7.9% in gynaecology and 5.1% in railway hospital. Co-infection of HBV and HCV was seen in 2% cases referred from medical department, while rest of the

Screening for Sexually Transmitted Infection Pathogens in Semen Samples

Directory of Open Access Journals (Sweden)

RW Peeling

2005-01-01

Full Text Available The transmission of sexually transmitted infection (STI pathogens from an infected donor to the recipient of a semen donation in assisted conception may result not only in acute infection but also in long-term reproductive complications or adverse outcomes of pregnancy, including infection of the offspring. Screening for bacterial STI pathogens, Chlamydia trachomatis and Neisseria gonorrhoeae is strongly recommended because these pathogens can cause serious reproductive complications in the recipients of semen donations and infection in their offspring. Screening for these pathogens should be performed using the most sensitive methods, such as nucleic acid amplified tests. False-negative results due to inhibitory substances in the semen sample should be monitored using amplification controls. Where specimen transport is not a problem and culture facilities are available, N gonorrhoeae can also be detected by culture. Laboratories performing screening should subscribe to proficiency programs and have strict quality controls. Although Trichomonas vaginalis, group B streptococcus and genital mycoplasmas have been associated with adverse outcomes of pregnancy, the frequent finding of these organisms in healthy individuals brings into question the validity of mandatory inclusion of these organisms in the screening panel. Although viral STI pathogens and Treponema pallidum -- the causative agent of syphilis -- may be detected in semen, their presence may be more sensitively detected through antibody testing of the donor. Screening donors for HIV, hepatitis B and syphilis by serology is uniformly recommended in all of the guidelines, but the value of screening either donors or semen samples for cytomegalovirus, herpes simplex viruses and human papilloma viruses is less clear.

Efficacy of selective antenatal screening for hepatitis B among pregnant women in Denmark: is selective screening still an acceptable strategy in a low-endemicity country?

DEFF Research Database (Denmark)

Jensen, Lise; Heilmann, Carsten; Smith, Else

2003-01-01

The prevalence of hepatitis B virus (HBV) carriage in Denmark is unknown, but expected to be low (0.1%). This study aimed to evaluate the efficacy of selective antenatal screening for HBV infection and the epidemiology of HBV and hepatitis C virus (HCV) among pregnant women. 4098 women were...... included in the study. Blood tests were examined for hepatitis B surface antigen (HBsAg), anti-hepatitis B core antigen (HBc) and anti-HCV. Case records were studied to evaluate whether patients at risk for HBV infection had been tested. Among the 4098 women, 18 10.4%, 95% confidence interval (95% CI) 0.......3-0.71 were HBsAg positive. All had a risk factor for HBV infection. Only 13 (72%) were identified as HBsAg positive in the selective screening programme. 115 women (2.8%, 95% CI 2.3-3.4) were anti-HBc positive only. 95 (83%) were at risk for HBV. Only 72 of these (63%) were tested for HBsAg. The screening...

Anti-nociceptive and anti-hyperprolactinemia activities of Fructus Viticis and its effective fractions and chemical constituents.

Science.gov (United States)

Hu, Y; Xin, H-L; Zhang, Q-Y; Zheng, H-C; Rahman, K; Qin, L-P

2007-10-01

Vitex rotundifolia L. is widely distributed along the sea coast of China. The aim of this study was to investigate the anti-nociceptive and anti-hyperprolactinemia activities of substances isolated from Fructus Viticis (the fruit of Vitex rotundifolia), which may be effective in the treatment of pre-menstrual symptoms, using acetic-acid-induced writhing and metoclopramide-dihydrochloride-induced hyperprolactinemia in mice. The fractions effective in terms of anti-nociceptive and anti-hyperprolactinemia activities were obtained from Fructus Viticis by elution through macro-porous resin, and polyamide and silica gel column chromatography. The standardization of the fractions obtained from the separation procedures was carried out by means of high-performance liquid chromatography (HPLC)-fingerprint. In this study, the flavone-enriched fraction (Fraction 6) showed a higher inhibitory rate than indomethacin (69.4% vs. 56.4%) at a dose of 50 mg/kg body wt., and significantly reduced the prolactin level as compared to HPRL-treated mice (8.2 ng/ml vs. 25.5 ng/ml). Furthermore, this fraction showed anti-nociceptive activity in a dose-dependent manner (10-50 mg/kg body wt., i.g.). On further purification with silica gel, Casticin was isolated from this fraction and it decreased abnormal serum levels of prolactin by approximately 50% (p screening methods, our results indicate that the presence of flavonoids such as Casticin in this plant may be responsible for the activity effects. Casticin has potent analgesic and anti-hyperprolactinaemia properties, is likely to be one of the active components of Fructus Viticis, and may have a role in treating PMS (premenstrual syndrom).

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.

Redeployment-based drug screening identifies the anti-helminthic niclosamide as anti-myeloma therapy that also reduces free light chain production

International Nuclear Information System (INIS)

Khanim, F L; Merrick, B A M E; Giles, H V; Jankute, M; Jackson, J B; Giles, L J; Birtwistle, J; Bunce, C M; Drayson, M T

2011-01-01

Despite recent therapeutic advancements, multiple myeloma (MM) remains incurable and new therapies are needed, especially for the treatment of elderly and relapsed/refractory patients. We have screened a panel of 100 off-patent licensed oral drugs for anti-myeloma activity and identified niclosamide, an anti-helminthic. Niclosamide, at clinically achievable non-toxic concentrations, killed MM cell lines and primary MM cells as efficiently as or better than standard chemotherapy and existing anti-myeloma drugs individually or in combinations, with little impact on normal donor cells. Cell death was associated with markers of both apoptosis and autophagy. Importantly, niclosamide rapidly reduced free light chain (FLC) production by MM cell lines and primary MM. FLCs are a major cause of renal impairment in MM patients and light chain amyloid and FLC reduction is associated with reversal of tissue damage. Our data indicate that niclosamides anti-MM activity was mediated through the mitochondria with rapid loss of mitochondrial membrane potential, uncoupling of oxidative phosphorylation and production of mitochondrial superoxide. Niclosamide also modulated the nuclear factor-κB and STAT3 pathways in MM cells. In conclusion, our data indicate that MM cells can be selectively targeted using niclosamide while also reducing FLC secretion. Importantly, niclosamide is widely used at these concentrations with minimal toxicity

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

Science.gov (United States)

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

2012-09-01

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

Bioactivity-guided fractionation and analysis of compounds with anti-influenza virus activity from Gardenia jasminoides Ellis.

Science.gov (United States)

Yang, Quanjun; Wu, Bin; Shi, Yujing; Du, Xiaowei; Fan, Mingsong; Sun, Zhaolin; Cui, Xiaolan; Huang, Chenggang

2012-01-01

Bioassay-guided fractionation of extracts from Fructus Gardeniae led to analysis of its bioactive natural products. After infection by influenza virus strain A/FM/1/47-MA in vivo, antiviral activity of the extracts were investigated. The target fraction was orally administered to rats and blood was collected. High-performance liquid chromatography coupled with photo diode array detector and electrospray ion trap multiple-stage tandem mass spectrometry was applied to screen the compounds absorbed into the blood. A structural characterization based on the retention time, ultraviolet spectra, parent ions and fragmentation ions was performed. Thirteen compounds were confirmed or tentatively identified. This provides an accurate profile of the composition of bioactive compounds responsible for the anti-influenza properties.

From screen to target: insights and approaches into the development of anti-virulence compounds

Directory of Open Access Journals (Sweden)

Katherine SH Beckham

2014-09-01

Full Text Available The detailed understanding of host-pathogen interactions provides exciting opportunities to interfere with the infection process. Anti-virulence compounds aim to modulate or pacify pathogenesis by reducing expression of critical virulence determinants. In particular, prevention of attachment by inhibiting adhesion mechanisms has been the subject of intense research. Whilst it has proven relatively straightforward to develop robust screens for potential antivirulence compounds, understanding their precise mode of action has proven much more challenging. In this review we illustrate this challenge from our own experiences working with the salicylidene acylhydrazide group of compounds. We aim to provide a useful perspective to guide researchers interested in this field and to avoid some of the obvious pitfalls.

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

Results of a Targeted Screening Program for Congenital Cytomegalovirus Infection in Infants Who Fail Newborn Hearing Screening.

Science.gov (United States)

Vancor, Emily; Shapiro, Eugene D; Loyal, Jaspreet

2018-01-24

Congenital cytomegalovirus (CMV) infection is a major cause of sensorineural hearing loss. By law, newborns in Connecticut who fail newborn hearing screening are tested for infection with CMV. This targeted screening is controversial, because most children with congenital CMV infection are asymptomatic, and CMV-related hearing loss can have a delayed onset. Our hospital uses a saliva polymerase chain reaction (PCR) assay (confirmed by a urine PCR assay) to detect CMV. Here, we report the results of the first year of our screening program. We reviewed the medical records of newborns in the Yale New Haven Health System who failed the newborn hearing screening test between January 1 and December 31, 2016. Of 10964 newborns, 171 failed newborn hearing screening, and 3 of these newborns had positive saliva CMV PCR test results. Of these 3 newborns, 2 had positive results on the confirmatory test (for 1 of them the confirmatory test was not performed until the infant was 10 weeks old), and 1 had a negative result on the confirmatory test. Three additional newborns with congenital CMV infection were tested because of clinical indications (1 for ventriculomegaly on prenatal ultrasound and 2 for CMV infection of the mother). Results of audiology follow-up were available for 149 (87.1%) of the 171 newborns who failed newborn hearing screening; 127 (85.2%) had normal results. Our targeted screening program for congenital CMV infection had a low yield. Consideration should be given to other strategies for identifying children at risk of hearing loss as a result of congenital CMV infection. © The Author(s) 2018. Published by Oxford University Press on behalf of The Journal of the Pediatric Infectious Diseases Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Humoral markers of active Epstein-Barr virus infection associate with anti-extractable nuclear antigen autoantibodies and plasma galectin-3 binding protein in systemic lupus erythematosus.

Science.gov (United States)

Rasmussen, N S; Nielsen, C T; Houen, G; Jacobsen, S

2016-12-01

We investigated if signs of active Epstein-Barr virus and cytomegalovirus infections associate with certain autoantibodies and a marker of type I interferon activity in patients with systemic lupus erythematosus. IgM and IgG plasma levels against Epstein-Barr virus early antigen diffuse and cytomegalovirus pp52 were applied as humoral markers of ongoing/recently active Epstein-Barr virus and cytomegalovirus infections, respectively. Plasma galectin-3 binding protein served as a surrogate marker of type I interferon activity. The measurements were conducted in 57 systemic lupus erythematosus patients and 29 healthy controls using ELISAs. Regression analyses and univariate comparisons were performed for associative evaluation between virus serology, plasma galectin-3 binding protein and autoantibodies, along with other clinical and demographic parameters. Plasma galectin-3 binding protein concentrations were significantly higher in systemic lupus erythematosus patients (P = 0.009) and associated positively with Epstein-Barr virus early antigen diffuse-directed antibodies and the presence of autoantibodies against extractable nuclear antigens in adjusted linear regressions (B = 2.02 and 2.02, P = 0.02 and P = 0.002, respectively). Furthermore, systemic lupus erythematosus patients with anti-extractable nuclear antigens had significantly higher antibody levels against Epstein-Barr virus early antigen diffuse (P = 0.02). Our study supports a link between active Epstein-Barr virus infections, positivity for anti-extractable nuclear antigens and increased plasma galectin-3 binding protein concentrations/type I interferon activity in systemic lupus erythematosus patients. © The Author(s) 2016.

Indexing Natural Products for Their Potential Anti-Diabetic Activity: Filtering and Mapping Discriminative Physicochemical Properties.

Science.gov (United States)

Zeidan, Mouhammad; Rayan, Mahmoud; Zeidan, Nuha; Falah, Mizied; Rayan, Anwar

2017-09-17

Diabetes mellitus (DM) poses a major health problem, for which there is an unmet need to develop novel drugs. The application of in silico techniques and optimization algorithms is instrumental to achieving this goal. A set of 97 approved anti-diabetic drugs, representing the active domain, and a set of 2892 natural products, representing the inactive domain, were used to construct predictive models and to index anti-diabetic bioactivity. Our recently-developed approach of 'iterative stochastic elimination' was utilized. This article describes a highly discriminative and robust model, with an area under the curve above 0.96. Using the indexing model and a mix ratio of 1:1000 (active/inactive), 65% of the anti-diabetic drugs in the sample were captured in the top 1% of the screened compounds, compared to 1% in the random model. Some of the natural products that scored highly as potential anti-diabetic drug candidates are disclosed. One of those natural products is caffeine, which is noted in the scientific literature as having the capability to decrease blood glucose levels. The other nine phytochemicals await evaluation in a wet lab for their anti-diabetic activity. The indexing model proposed herein is useful for the virtual screening of large chemical databases and for the construction of anti-diabetes focused libraries.

Utilisation of hepatocellular carcinoma screening in Australians at risk of hepatitis B virus-related carcinoma and prescribed anti-viral therapy.

Science.gov (United States)

Sheppard-Law, Suzanne; Zablotska-Manos, Iryna; Kermeen, Melissa; Holdaway, Susan; Lee, Alice; George, Jacob; Zekry, Amany; Maher, Lisa

2018-07-01

To investigate hepatocellular carcinoma screening utilisation and factors associated with utilisation among patients prescribed hepatitis B virus anti-viral therapy and at risk of hepatocellular carcinoma. The incidence of hepatocellular carcinoma has increased in Australia over the past three decades with chronic hepatitis B virus infection a major contributor. hepatocellular carcinoma surveillance programs aim to detect cancers early enabling curative treatment options, longer survival and longer times to recurrence. Multi-site cross-sectional survey. An online study questionnaire was administered to eligible participants attending three Sydney tertiary hospitals. Data were grouped into six mutually exclusive hepatocellular carcinoma risk factor categories as per American Association for the Study of Liver Diseases guidelines. All analyses were undertaken in STATA. Logistic regression was used to assess the associations between covariates and screening utilisation. Multivariate models described were assessed using the Hosmer-Lemeshow goodness of fit. Of the 177 participants, 137 (77.4%) self-reported that US had been performed in the last six months. Awareness that screening should be performed and knowing the correct frequency of US screening were independently associated with screening utilisation. Participants who knew that screening should be undertaken were three times more likely to have had pretreatment education or were prescribed hepatitis B virus anti-viral treatment for >4 years. Participants reporting a family history of hepatocellular carcinoma were less likely to know that screening should be undertaken every 6 months. While utilisation of hepatocellular carcinoma surveillance programs was higher in this study than in previous reports, strategies to further improve surveillance remain necessary. Findings from this research form the basis for proposing strategies to improve utilisation of hepatocellular carcinoma screening, inform hepatitis B virus

Anti- Sporothrix spp. activity of medicinal plants

Directory of Open Access Journals (Sweden)

Stefanie Bressan Waller

Full Text Available ABSTRACT Cases of sporotrichosis in humans and animals without satisfactory clinical response have increased, a warning sign of strains resistant to conventional antifungal agents. The urgent search for alternative therapies was an incentive for research on medicinal plants with anti-Sporothrix spp. properties. A bibliographic survey was performed based on scientific papers about in vitro and in vivo antifungal activity of essential oils and extracts of plants in differents solvents against the fungal of the Sporothrix schenckii complex. The study methodology consisted of a literature review in Google Scholar, Science Direct, Pubmed, Bireme and Springer link with papers from 1986 to 2015. We found 141 species of plants that were investigated, of which 100 species were concentrated in 39 botanical families that had confirmed anti-Sporothrix activity. Combretaceae, Asteraceae and Lamiaceae represented the botanical families with the greatest number of plants species with antifungal potential, using different methodologies. However, there are few studies with medicinal plants in experimental infection in animals that prove their activity in the treatment of sporotrichosis. It reinforces the need for further research related to standardization of in vitro methodologies and in vivo studies related to safety and to toxicity potential of these plants with anti-Sporothrix spp. activity.

A novel application of furazolidone: anti-leukemic activity in acute myeloid leukemia.

Directory of Open Access Journals (Sweden)

Xueqing Jiang

Full Text Available Acute myeloid leukemia (AML is the most common malignant myeloid disorder of progenitor cells in myeloid hematopoiesis and exemplifies a genetically heterogeneous disease. The patients with AML also show a heterogeneous response to therapy. Although all-trans retinoic acid (ATRA has been successfully introduced to treat acute promyelocytic leukemia (APL, it is rather ineffective in non-APL AML. In our present study, 1200 off-patent marketed drugs and natural compounds that have been approved by the Food and Drug Administration (FDA were screened for anti-leukemia activity using the retrovirus transduction/transformation assay (RTTA. Furazolidone (FZD was shown to inhibit bone marrow transformation mediated by several leukemia fusion proteins, including AML1-ETO. Furazolidone has been used in the treatment of certain bacterial and protozoan infections in human and animals for more than sixty years. We investigated the anti-leukemic activity of FZD in a series of AML cells. FZD displayed potent antiproliferative properties at submicromolar concentrations and induced apoptosis in AML cell lines. Importantly, FZD treatment of certain AML cells induced myeloid cell differentiation by morphology and flow cytometry for CD11b expression. Furthermore, FZD treatment resulted in increased stability of tumor suppressor p53 protein in AML cells. Our in vitro results suggest furazolidone as a novel therapeutic strategy in AML patients.

Unusual anti-leukemia activity of nanoformulated naproxen and other non-steroidal anti-inflammatory drugs

Energy Technology Data Exchange (ETDEWEB)

Kumar, Raj [School of Basic Sciences, Indian Institute of Technology Mandi, Mandi, Himachal Pradesh 175005 (India); Advanced Material Research Centre, Indian Institute of Technology Mandi, Mandi, Himachal Pradesh 175005 (India); Siril, Prem Felix, E-mail: prem@iitmandi.ac.in [School of Basic Sciences, Indian Institute of Technology Mandi, Mandi, Himachal Pradesh 175005 (India); Advanced Material Research Centre, Indian Institute of Technology Mandi, Mandi, Himachal Pradesh 175005 (India); Javid, Farideh [School of Applied Science, University of Huddersfield, Queensgate, Huddersfield HD1 3DH (United Kingdom)

2016-12-01

The non-steroidal anti-inflammatory drugs (NSAIDs) are the most widely used pharmaceuticals worldwide. Interestingly, many of them have significant anticancer properties too. However, the poor water solubility of certain NSAIDs limits their application for cancer treatment. Nanosizing of such drugs can help to improve the solubility and this may result in enhanced anticancer activities too. Moreover, over dosages and the accompanying side effects of NSAIDs can be minimized by improving their solubility and bioavailability. Successful nanoformulation of three NSAIDs: ibuprofen (IBP), ketoprufen (KP) and naproxen (NAP) using a novel evaporation assisted solvent-antisolvent interaction (EASAI) method is reported here. Three water soluble and biocompatible polymers: polyvinylpyrrolidone (PVP), polyvinyl alcohol (PVA) and hydroxypropyl methylcellulose (HPMC) were used to stabilize the drug nanoparticles. Particles having spherical morphology with average size below 30 nm were thoroughly characterized using dynamic light scattering and field emission scanning electron microscopy (FESEM) imaging. The nanoformulation resulted in ten to fifteen fold improvements in the solubility and significant enhancement in the in-vitro drug release profiles of the NSAIDs. Anticancer screening of the nanoformulated NSAIDs against five different cancer cell lines such as MCF-7 (Human breast cancer cell line), (Human pancreatic cancer cell line) MIA-PA-CA-2, (Human colon cancer cell line) HT-29, (Human leukemia cell line) Jurkat and (human ovarian carcinoma cell line) A2780 was performed. All the nanoformulated samples showed improved anticancer activity against the Leukemia cancer cell line, out of which NAP-PVP showed the highest anti-cancer activity. The anti-Leukemia activity of NAP-PVP was more than twice that of doxorubicin which is a standard anticancer drug. - Highlights: • Nanoparticles of three non-steroidal anti-inflammatory drugs were prepared. • Particle sizes were

Unusual anti-leukemia activity of nanoformulated naproxen and other non-steroidal anti-inflammatory drugs

International Nuclear Information System (INIS)

Kumar, Raj; Siril, Prem Felix; Javid, Farideh

2016-01-01

The non-steroidal anti-inflammatory drugs (NSAIDs) are the most widely used pharmaceuticals worldwide. Interestingly, many of them have significant anticancer properties too. However, the poor water solubility of certain NSAIDs limits their application for cancer treatment. Nanosizing of such drugs can help to improve the solubility and this may result in enhanced anticancer activities too. Moreover, over dosages and the accompanying side effects of NSAIDs can be minimized by improving their solubility and bioavailability. Successful nanoformulation of three NSAIDs: ibuprofen (IBP), ketoprufen (KP) and naproxen (NAP) using a novel evaporation assisted solvent-antisolvent interaction (EASAI) method is reported here. Three water soluble and biocompatible polymers: polyvinylpyrrolidone (PVP), polyvinyl alcohol (PVA) and hydroxypropyl methylcellulose (HPMC) were used to stabilize the drug nanoparticles. Particles having spherical morphology with average size below 30 nm were thoroughly characterized using dynamic light scattering and field emission scanning electron microscopy (FESEM) imaging. The nanoformulation resulted in ten to fifteen fold improvements in the solubility and significant enhancement in the in-vitro drug release profiles of the NSAIDs. Anticancer screening of the nanoformulated NSAIDs against five different cancer cell lines such as MCF-7 (Human breast cancer cell line), (Human pancreatic cancer cell line) MIA-PA-CA-2, (Human colon cancer cell line) HT-29, (Human leukemia cell line) Jurkat and (human ovarian carcinoma cell line) A2780 was performed. All the nanoformulated samples showed improved anticancer activity against the Leukemia cancer cell line, out of which NAP-PVP showed the highest anti-cancer activity. The anti-Leukemia activity of NAP-PVP was more than twice that of doxorubicin which is a standard anticancer drug. - Highlights: • Nanoparticles of three non-steroidal anti-inflammatory drugs were prepared. • Particle sizes were

Activity of andrographolide against chikungunya virus infection

OpenAIRE

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

2015-01-01

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 stud...

Preliminary Phytochemical Screening and Biological Activities of Bulbine abyssinica Used in the Folk Medicine in the Eastern Cape Province, South Africa.

Science.gov (United States)

Kibiti, Cromwell Mwiti; Afolayan, Anthony Jide

2015-01-01

Bulbine abyssinica A. Rich. is used in traditional medicine to treat rheumatism, dysentery, bilharzia, cracked lips, back pain, infertility, diabetes mellitus, and gastrointestinal, vaginal, and bladder infections. Therefore, preliminary phytochemical screening, antioxidant, anti-inflammatory, and antibacterial properties of the whole plant (acetone and aqueous extracts) were determined using standard procedures. The in vitro antioxidant model assays revealed that the plant possesses free radical scavenging potential varying with free radical species. The species showed significant protein denaturation inhibitory activity with good protection against erythrocyte membrane lysis indicating anti-inflammatory potential. The results also showed that the species was active against the growth of all the selected eight diabetic status opportunistic bacteria except one. Moreover, the species is characterized by appreciable amounts of total phenols, flavonoids, flavanols, proanthocyanidins, and alkaloids. Traces amounts of saponins and tannins were also observed. Amongst the identified phytochemicals present, empirical searches identified them being antioxidant, anti-inflammatory, and antimicrobial agents. The identification of these phytochemical constituents with their known pharmacological properties indicates that this plant is a good source of the free radical scavenging, anti-inflammatory, and antimicrobial agents. These findings also account for the multipharmacological use of B. abyssinica in fork medicine.

Anti-inflammatory therapy for urinary tract infection in children

Directory of Open Access Journals (Sweden)

A. A. Vyalkova

2015-01-01

Full Text Available Objective: to substantiate the importance of an etiological approach to diagnosing urinary tract infection in children in terms of the species and biological properties of an infectious agent and to evaluate the efficiency of anti-inflammatory therapy. The study included 116 patients aged 3-15 years with chronic pyelonephritis (Group 1 and isolated bacteriuria (Group 2. After 10-14-day antibiotic therapy, Group 1 patients were allocated to two subgroups: Subgroup la («=30 took furamag 5 mg/kg/day; Subgroup lb («=30 received furamag at the same dose in combination with canephron. The treatment cycle lasted 10-14 days. Subgroup 2a («=26 children had furamag 5 mgДg/day and Subgroup 2b (« =30 took furamag in combination with canephron. The duration of treatment was 14 days. The investigators established the high efficiency of therapy with furamag for renal infection in the children with the active and decrement phases and that of the drug of choice for its monotherapy of isolated highly virulent bacteriuria. Therapeutic efficiency was proven to be related to the species and biological characteristics of an infectious agent. Anti-inflammatory therapy for pyelonephritis in terms of the species of pathogenic bacteria was ascertained to improve the efficiency of treatment. A rationale was provided for the individual choice of antibiotics, followed by the use of furamag, eubiotics, and drugs aimed at inhibiting virulence factors and persistence of the pathogen to sanitize the primary focus of infection.

Association between discordant immunological response to highly active anti-retroviral therapy, regulatory T cell percentage, immune cell activation and very low-level viraemia in HIV-infected patients.

Science.gov (United States)

Saison, J; Ferry, T; Demaret, J; Maucort Boulch, D; Venet, F; Perpoint, T; Ader, F; Icard, V; Chidiac, C; Monneret, G

2014-06-01

The mechanisms sustaining the absence of complete immune recovery in HIV-infected patients upon long-term effective highly active anti-retroviral therapy (HAART) remain elusive. Immune activation, regulatory T cells (T(regs)) or very low-level viraemia (VLLV) have been alternatively suspected, but rarely investigated simultaneously. We performed a cross-sectional study in HIV-infected aviraemic subjects (mean duration of HAART: 12 years) to concomitantly assess parameters associated independently with inadequate immunological response. Patients were classified as complete immunological responders (cIR, n = 48) and inadequate immunological responders (iIR, n = 39), depending on the CD4(+) T cell count (> or response to long-term HAART, activation of CD4(+) and CD8(+) T cells, T(reg) percentages and very low-level viraemia. Causative interactions between T(regs) and CD4(+) T cells should now be explored prospectively in a large patients cohort. © 2014 British Society for Immunology.

Structure/activity of Pt{sup II}/N,N-disubstituted-N'-acylthiourea complexes: Anti-tumor and anti-mycobacterium tuberculosis activities

Energy Technology Data Exchange (ETDEWEB)

Plutín, Ana M.; Alvarez, Anislay; Mocelo, Raúl; Ramos, Raúl; Sánchez, Osmar C. [Laboratorio de Síntesis Orgánica, Facultad de Química, Universidad de La Habana (Cuba); Castellano, Euardo E. [Universidade de São Paulo (USP), São Carlos, SP (Brazil); Silva, Monize M. da; Villarreal, Wilmer; Colina-Vegas, Legna; Batista, Alzir A. [Universidade Federal de São Carlos (UFSCar), SP (Brazil); Pavan, Fernando R., E-mail: anap@fq.uh.cu, E-mail: daab@ufscar.br [Universidade Estadual Paulista Julio de Mesquita Filho (UNESP), Araraquara, SP (Brazil). Faculdade de Ciências Farmacêuticas

2018-05-01

The syntheses, characterization, cytotoxicity against tumor cells and anti-Mycobacterium tuberculosis activity assays of Pt{sup II}/PPh{sub 3}/N,N-disubstituted-N'-acylthioureas complexes with general formulae [Pt(PPh{sub 3}){sub 2}(L)]PF{sub 6}, PPh{sub 3} = triphenylphosphine; L = N,N-disubstituted-N'-acylthiourea, are here reported. The complexes were characterized by elemental analysis, molar conductivity, infrared (IR), nuclear magnetic resonance (NMR) ({sup 1} H, {sup 13}C{1 H} and {sup 31}P{"1 H}) spectroscopy. The {sup 31}P{"1 H} NMR data are consistent with the presence of two PPh{sup 3} ligands cis to each other position, and one N,N-disubstituted-N'-acylthiourea coordinated to the metal through O and S, in a chelate form. The structures of the complexes were determined by X-ray crystallography, forming distorted square-planar structures. The complexes were tested in human cell lines carcinomas and also screened with respect to their anti-Mycobacterium tuberculosis activity (H37RvATCC 27294). It was found that complexes with N,N-disubstituted-N'-acylthiourea containing open and small chains as R2 groups show higher cytotoxic and higher anti-Mycobacterium tuberculosis activity than those containing rings in this position. (author)

Viral hepatitis and rapid diagnostic test based screening for HBsAg in HIV-infected patients in rural Tanzania.

Directory of Open Access Journals (Sweden)

Fabian C Franzeck

Full Text Available BACKGROUND: Co-infection with hepatitis B virus (HBV is highly prevalent in people living with HIV in Sub-Saharan Africa. Screening for HBV surface antigen (HBsAg before initiation of combination antiretroviral therapy (cART is recommended. However, it is not part of diagnostic routines in HIV programs in many resource-limited countries although patients could benefit from optimized antiretroviral therapy covering both infections. Screening could be facilitated by rapid diagnostic tests for HBsAg. Operating experience with these point of care devices in HIV-positive patients in Sub-Saharan Africa is largely lacking. We determined the prevalence of HBV and Hepatitis C virus (HCV infection as well as the diagnostic accuracy of the rapid test device Determine HBsAg in an HIV cohort in rural Tanzania. METHODS: Prospectively collected blood samples from adult, HIV-1 positive and antiretroviral treatment-naïve patients in the Kilombero and Ulanga antiretroviral cohort (KIULARCO in rural Tanzania were analyzed at the point of care with Determine HBsAg, a reference HBsAg EIA and an anti-HCV EIA. RESULTS: Samples of 272 patients were included. Median age was 38 years (interquartile range [IQR] 32-47, 169/272 (63% subjects were females and median CD4+ count was 250 cells/µL (IQR 97-439. HBsAg was detected in 25/272 (9.2%, 95% confidence interval [CI] 6.2-13.0% subjects. Of these, 7/25 (28% were positive for HBeAg. Sensitivity of Determine HBsAg was rated at 96% (95% CI 82.8-99.6% and specificity at 100% (95% CI, 98.9-100%. Antibodies to HCV (anti-HCV were found in 10/272 (3.7%, 95% CI 2.0-6.4% of patients. CONCLUSION: This study reports a high prevalence of HBV in HIV-positive patients in a rural Tanzanian setting. The rapid diagnostic test Determine HBsAg is an accurate assay for screening for HBsAg in HIV-1 infected patients at the point of care and may further help to guide cART in Sub-Saharan Africa.

[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.

PREVALENCE OF ANTI-HBC IN SLOVENIAN BLOOD DONORS AND THE IMPACTON BLOOD SCREENING

Directory of Open Access Journals (Sweden)

Snežana Levičnik Stezinar

2008-04-01

Among screened donors, the anti-HBc incidence rate was 179/5959 (3.00 %. Therewere 55 samples that were anti-HBc positive only (69.83 % of anti-HBc pos, 0.90 % of alldonations. The number of units positive for both antibodies was 124 (2.10 % of all testeddonations. No significant difference was noted in the prevalence between male (3.00 %and female (2.99 %. As expected, there was a raise in frequency from 0.78 % in a group of18–29 years to 5.82 % in a group 50–65 years. In the study group there was one donorwho was HBsAg carrier.Conclusion According to the results of this study, Slovenia is ranged among the countries with mediumanti-HBc prevalence rate. Screening of donors would additionally contribute to the higherblood safety. The higher cost due to testing and destroying units is not acceptable, especiallyafter the implementation of screening for HBV DNA and excluding the units that are reallyinfectious

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

Science.gov (United States)

Steel, Helen C; Theron, Annette J; Cockeran, Riana; Anderson, Ronald; Feldman, Charles

2012-01-01

Macrolide antibiotics possess several, beneficial, secondary properties which complement their primary antimicrobial activity. In addition to high levels of tissue penetration, which may counteract seemingly macrolide-resistant bacterial pathogens, these agents also possess anti-inflammatory properties, unrelated to their primary antimicrobial activity. Macrolides target cells of both the innate and adaptive immune systems, as well as structural cells, and are beneficial in controlling harmful inflammatory responses during acute and chronic bacterial infection. These secondary anti-inflammatory activities of macrolides appear to be particularly effective in attenuating neutrophil-mediated inflammation. This, in turn, may contribute to the usefulness of these agents in the treatment of acute and chronic inflammatory disorders of both microbial and nonmicrobial origin, predominantly of the airways. This paper is focused on the various mechanisms of macrolide-mediated anti-inflammatory activity which target both microbial pathogens and the cells of the innate and adaptive immune systems, with emphasis on their clinical relevance.

Topical anti-infective sinonasal irrigations: update and literature review.

Science.gov (United States)

Lee, Jivianne T; Chiu, Alexander G

2014-01-01

Sinonasal anti-infective irrigations have emerged as a promising therapeutic modality in the comprehensive management of chronic rhinosinusitis (CRS), particularly in the context of recalcitrant disease. The purpose of this article was to delineate the current spectrum of topical anti-infective therapies available and evaluate their role in the treatment of CRS. A systematic literature review was performed on all studies investigating the use of topical antimicrobial solutions in the medical therapy of CRS. Anti-infective irrigations were stratified into topical antibacterial, antifungal, and additive preparations according to their composition and respective microbicidal properties. The use of topical antibiotic irrigations has been supported by low-level studies in the treatment of refractory CRS, with optimal results achieved in patients who have undergone prior functional endoscopic sinus surgery and received culture-directed therapy. Multiple evidence-based reviews have not established any clinical benefit with the administration of topical antifungals, and their use is not currently recommended in the management of routine CRS. Topical additives including surfactants may be beneficial as adjunctive treatment for recalcitrant CRS, but additional research is needed to investigate their efficacy in comparison with other agents and establish safety profiles. Topical anti-infective solutions are not recommended as first-line therapy for routine CRS but may be considered as a potential option for patients with refractory CRS who have failed traditional medical and surgical intervention. Additional research is necessary to determine which patient populations would derive the most benefit from each respective irrigation regimen and identify potential toxicities associated with prolonged use.

Indexing Natural Products for Their Potential Anti-Diabetic Activity: Filtering and Mapping Discriminative Physicochemical Properties

Directory of Open Access Journals (Sweden)

Mouhammad Zeidan

2017-09-01

Full Text Available Diabetes mellitus (DM poses a major health problem, for which there is an unmet need to develop novel drugs. The application of in silico techniques and optimization algorithms is instrumental to achieving this goal. A set of 97 approved anti-diabetic drugs, representing the active domain, and a set of 2892 natural products, representing the inactive domain, were used to construct predictive models and to index anti-diabetic bioactivity. Our recently-developed approach of ‘iterative stochastic elimination’ was utilized. This article describes a highly discriminative and robust model, with an area under the curve above 0.96. Using the indexing model and a mix ratio of 1:1000 (active/inactive, 65% of the anti-diabetic drugs in the sample were captured in the top 1% of the screened compounds, compared to 1% in the random model. Some of the natural products that scored highly as potential anti-diabetic drug candidates are disclosed. One of those natural products is caffeine, which is noted in the scientific literature as having the capability to decrease blood glucose levels. The other nine phytochemicals await evaluation in a wet lab for their anti-diabetic activity. The indexing model proposed herein is useful for the virtual screening of large chemical databases and for the construction of anti-diabetes focused libraries.

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

Directory of Open Access Journals (Sweden)

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.

Cidofovir Activity against Poxvirus Infections

Directory of Open Access Journals (Sweden)

Robert Snoeck

2010-12-01

Full Text Available Cidofovir [(S-1-(3-hydroxy-2-phosphonylmethoxypropylcytosine, HPMPC] is an acyclic nucleoside analog approved since 1996 for clinical use in the treatment of cytomegalovirus (CMV retinitis in AIDS patients. Cidofovir (CDV has broad-spectrum activity against DNA viruses, including herpes-, adeno-, polyoma-, papilloma- and poxviruses. Among poxviruses, cidofovir has shown in vitro activity against orthopox [vaccinia, variola (smallpox, cowpox, monkeypox, camelpox, ectromelia], molluscipox [molluscum contagiosum] and parapox [orf] viruses. The anti-poxvirus activity of cidofovir in vivo has been shown in different models of infection when the compound was administered either intraperitoneal, intranasal (aerosolized or topically. In humans, cidofovir has been successfully used for the treatment of recalcitrant molluscum contagiosum virus and orf virus in immunocompromised patients. CDV remains a reference compound against poxviruses and holds potential for the therapy and short-term prophylaxis of not only orthopox- but also parapox- and molluscipoxvirus infections.

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

Science.gov (United States)

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.

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.

Anti-allergic and anti-microbial activities of some Thai crops

Directory of Open Access Journals (Sweden)

Supinya Tewtrakul

2008-07-01

Full Text Available Thirteen Thai crops including banana, okra, jackfruit, germinated rice, rambutan, durian, jampadah, huasa potato,tamarind, coconut, mango, fan palm fruit and dioscorea tuber were tested for anti-allergic effect using RBL-2H3 cells andanti-microbial activity. These 13 crops, some of which included different parts, e.g. skin, flesh, and seed, were extracted withfour solvents separately [(95% ethanol (EtOH, 50% EtOH, water (W and hot water (HW], respectively, to obtain 112extracts. Among these extracts, mango seed in 50% EtOH possessed the highest anti-allergic activity against antigen-inducedb-hexosaminidase release as a marker of degranulation in RBL-2H3 cells with an IC50 value of 7.5±0.8 mg/ml, followed bybanana (W, IC50 = 13.5±2.4 mg/ml, okra (W, IC50 = 13.6±3.1 mg/ml, jampadah skin (HW, IC50 = 13.8±3.9 mg/ml, tamarindseed coat (HW, IC50 = 14.2±3.1 mg/ml, jampadah flesh (W, IC50 = 14.6±3.1 mg/ml; whereas other crops possessed IC50values from 21.5->100 mg/ml. Moreover, the plants showing high anti-allergic effects were also possessed marked antibacterialactivity. Rambutan peel, mango peel, mango seed and tamarind seed coat exhibited appropriate anti-bacterialactivity against Staphylococcus aureus, Bacillus subtilis and Pseudomonas aeruginosa with MIC values ranging from 250-2,000 mg/ml, but did not show any effect towards Escherichia coli and Candida albicans. This study indicates that these Thaicrops may have potential as functional foods and neutraceuticals for treatment of allergy, allergy-related diseases and somebacterial infections.

Overview of a workshop on screening methods for detecting potential (anti-) estrogenic/androgenic chemicals in wildlife

Science.gov (United States)

Ankley, Gerald T.; Mihaich, Ellen; Stahl, Ralph G.; Tillitt, Donald E.; Colborn, Theo; McMaster, Suzzanne; Miller, Ron; Bantle, John; Campbell, Pamela; Denslow, Nancy; Dickerson, Richard L.; Folmar, Leroy C.; Fry, Michael; Giesy, John P.; Gray, L. Earl; Guiney, Patrick; Hutchinson, Thomas; Kennedy, Sean W.; Kramer, Vincent; LeBlanc, Gerald A.; Mayes, Monte; Nimrod, Alison; Patino, Reynaldo; Peterson, Richard; Purdy, Richard; Ringer, Robert; Thomas, Peter C.; Touart, Les; Van Der Kraak, Glen; Zacharewski, Tim

1998-01-01

The U.S. Congress has passed legislation requiring the U.S. Environmental Protection Agency (U.S. EPA) to develop, validate, and implement screening tests for identifying potential endocrine-disrupting chemicals within 3 years. To aid in the identification of methods suitable for this purpose, the U.S. EPA, the Chemical Manufacturers Association, and the World Wildlife Fund sponsored several workshops, including the present one, which dealt with wildlife species. This workshop was convened with 30 international scientists representing multiple disciplines in March 1997 in Kansas City, Missouri, USA. Participants at the meeting identified methods in terms of their ability to indicate (anti-) estrogenic/androgenic effects, particularly in the context of developmental and reproductive processes. Data derived from structure-activity relationship models and in vitro test systems, although useful in certain contexts, cannot at present replace in vivo tests as the sole basis for screening. A consensus was reached that existing mammalian test methods (e.g., with rats or mice) generally are suitable as screens for assessing potential (anti-) estrogenic/ androgenic effects in mammalian wildlife. However, due to factors such as among-class variation in receptor structure and endocrine function, it is uncertain if these mammalian assays would be of broad utility as screens for other classes of vertebrate wildlife. Existing full and partial life-cycle tests with some avian and fish species could successfully identify chemicals causing endocrine disruption; however, these long-term tests are not suitable for routine screening. However, a number of short-term tests with species from these two classes exist that could serve as effective screening tools for chemicals inducing (anti-) estrogenic/androgenic effects. Existing methods suitable for identifying chemicals with these mechanisms of action in reptiles and amphibians are limited, but in the future, tests with species from

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

Science.gov (United States)

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

Nature is the best source of anti-inflammatory drugs: indexing natural products for their anti-inflammatory bioactivity.

Science.gov (United States)

Aswad, Miran; Rayan, Mahmoud; Abu-Lafi, Saleh; Falah, Mizied; Raiyn, Jamal; Abdallah, Ziyad; Rayan, Anwar

2018-01-01

The aim was to index natural products for less expensive preventive or curative anti-inflammatory therapeutic drugs. A set of 441 anti-inflammatory drugs representing the active domain and 2892 natural products representing the inactive domain was used to construct a predictive model for bioactivity-indexing purposes. The model for indexing the natural products for potential anti-inflammatory activity was constructed using the iterative stochastic elimination algorithm (ISE). ISE is capable of differentiating between active and inactive anti-inflammatory molecules. By applying the prediction model to a mix set of (active/inactive) substances, we managed to capture 38% of the anti-inflammatory drugs in the top 1% of the screened set of chemicals, yielding enrichment factor of 38. Ten natural products that scored highly as potential anti-inflammatory drug candidates are disclosed. Searching the PubMed revealed that only three molecules (Moupinamide, Capsaicin, and Hypaphorine) out of the ten were tested and reported as anti-inflammatory. The other seven phytochemicals await evaluation for their anti-inflammatory activity in wet lab. The proposed anti-inflammatory model can be utilized for the virtual screening of large chemical databases and for indexing natural products for potential anti-inflammatory activity.

Screen-printed nanoparticles as anti-counterfeiting tags

Science.gov (United States)

Campos-Cuerva, Carlos; Zieba, Maciej; Sebastian, Victor; Martínez, Gema; Sese, Javier; Irusta, Silvia; Contamina, Vicente; Arruebo, Manuel; Santamaria, Jesus

2016-03-01

Metallic nanoparticles with different physical properties have been screen printed as authentication tags on different types of paper. Gold and silver nanoparticles show unique optical signatures, including sharp emission bandwidths and long lifetimes of the printed label, even under accelerated weathering conditions. Magnetic nanoparticles show distinct physical signals that depend on the size of the nanoparticle itself. They were also screen printed on different substrates and their magnetic signals read out using a magnetic pattern recognition sensor and a vibrating sample magnetometer. The novelty of our work lies in the demonstration that the combination of nanomaterials with optical and magnetic properties on the same printed support is possible, and the resulting combined signals can be used to obtain a user-configurable label, providing a high degree of security in anti-counterfeiting applications using simple commercially-available sensors.

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

Science.gov (United States)

Sprague, Denise A; Ensom, Mary H H

2009-09-01

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

Performance study of the automated immunoassay test anti-hepatitis C virus VIDAS® for the qualitative detection of antibodies anti-hepatitis C virus

Directory of Open Access Journals (Sweden)

Sara Salvetti

2016-03-01

Full Text Available Background and aims: Hepatitis C virus (HCV represents a major worldwide public health problem requiring global action for the diagnosis, treatment and prevention of this infection. HCV is the leading cause of chronic liver disease, including chronic hepatitis, fibrosis, cirrhosis, and hepatocellular carcinoma and it is responsible for about 350,000 deaths yearly. Anti-HCV assays remain the first choice for screening HCV infection in most clinical laboratories. The anti-HCV VIDAS® (bioMérieux, Marcy L’Etoile, France test has been recently launched and we aimed to evaluate its performance compared with other widely used methods. Materials and methods: Routine anti-HCV screening of clinical samples was carried out on the ARCHITECT® i2000SR platform (Abbot Laboratories, Abbott Park, IL, USA; out of 8876 samples tested from October 2012 to May 2013, 70 sera with low positive anti-HCV results (1≤S/CO<8 were collected. These samples were tested for the presence of anti-HCV antibodies using anti-HCV VIDAS® and INNO-LIATM HCV score assays (Innogenetics NV, Ghent, Belgium. Results and conclusions: Positive anti-HCV results were obtained in 61.4% and 41.4% of sera tested with VIDAS® and INNO-LIATM, respectively. Concordance between methods was 63.2% for ARCHITECT® and VIDAS®, 42.6% for ARCHITECT® and INNO-LIATM, and 79.4% for VIDAS® and INNO-LIATM. Anti-HCV VIDAS® demonstrated superior specificity compared to the anti-HCV test ARCHITECT®; therefore, this assay has been introduced in our routine analysis as a second level screening test to select samples to be subjected to confirmatory anti- HCV immunoblot.

A forward-genetic screen and dynamic analysis of lambda phage host-dependencies reveals an extensive interaction network and a new anti-viral strategy.

Directory of Open Access Journals (Sweden)

Nathaniel D Maynard

2010-07-01

Full Text Available Latently infecting viruses are an important class of virus that plays a key role in viral evolution and human health. Here we report a genome-scale forward-genetics screen for host-dependencies of the latently-infecting bacteriophage lambda. This screen identified 57 Escherichia coli (E. coli genes--over half of which have not been previously associated with infection--that when knocked out inhibited lambda phage's ability to replicate. Our results demonstrate a highly integrated network between lambda and its host, in striking contrast to the results from a similar screen using the lytic-only infecting T7 virus. We then measured the growth of E. coli under normal and infected conditions, using wild-type and knockout strains deficient in one of the identified host genes, and found that genes from the same pathway often exhibited similar growth dynamics. This observation, combined with further computational and experimental analysis, led us to identify a previously unannotated gene, yneJ, as a novel regulator of lamB gene expression. A surprising result of this work was the identification of two highly conserved pathways involved in tRNA thiolation-one pathway is required for efficient lambda replication, while the other has anti-viral properties inhibiting lambda replication. Based on our data, it appears that 2-thiouridine modification of tRNAGlu, tRNAGln, and tRNALys is particularly important for the efficient production of infectious lambda phage particles.

An in vivo C. elegans model system for screening EGFR-inhibiting anti-cancer drugs.

Directory of Open Access Journals (Sweden)

Young-Ki Bae

Full Text Available The epidermal growth factor receptor (EGFR is a well-established target for cancer treatment. EGFR tyrosine kinase (TK inhibitors, such as gefinitib and erlotinib, have been developed as anti-cancer drugs. Although non-small cell lung carcinoma with an activating EGFR mutation, L858R, responds well to gefinitib and erlotinib, tumors with a doubly mutated EGFR, T790M-L858R, acquire resistance to these drugs. The C. elegans EGFR homolog LET-23 and its downstream signaling pathway have been studied extensively to provide insight into regulatory mechanisms conserved from C. elegans to humans. To develop an in vivo screening system for potential cancer drugs targeting specific EGFR mutants, we expressed three LET-23 chimeras in which the TK domain was replaced with either the human wild-type TK domain (LET-23::hEGFR-TK, a TK domain with the L858R mutation (LET-23::hEGFR-TK[L858R], or a TK domain with the T790M-L858R mutations (LET-23::hEGFR-TK[T790M-L858R] in C. elegans vulval cells using the let-23 promoter. The wild-type hEGFR-TK chimeric protein rescued the let-23 mutant phenotype, and the activating mutant hEGFR-TK chimeras induced a multivulva (Muv phenotype in a wild-type C. elegans background. The anti-cancer drugs gefitinib and erlotinib suppressed the Muv phenotype in LET-23::hEGFR-TK[L858R]-expressing transgenic animals, but not in LET-23::hEGFR-TK[T790M-L858R] transgenic animals. As a pilot screen, 8,960 small chemicals were tested for Muv suppression, and AG1478 (an EGFR-TK inhibitor and U0126 (a MEK inhibitor were identified as potential inhibitors of EGFR-mediated biological function. In conclusion, transgenic C. elegans expressing chimeric LET-23::hEGFR-TK proteins are a model system that can be used in mutation-specific screens for new anti-cancer drugs.

Pharmacist-led screening in sexually transmitted infections: current perspectives

Directory of Open Access Journals (Sweden)

Wood H

2018-06-01

Full Text Available Helen Wood, Sajni Gudka School of Allied Health, Faculty of Health and Medical Sciences, The University of Western Australia, Perth, WA, Australia Introduction: Sexually transmitted infection (STI screening is a crucial initiative that aims to reduce the increasing global prevalence of many common STIs such as chlamydia, gonorrhea, and herpes simplex virus (HSV. Many STIs are either asymptomatic or show mild symptoms that are often attributed to other infections; hence, screening is the only way to identify – and by extension, treat – them. In this way, the spread of STIs can be reduced, and the health implications of an untreated STI are minimized. Community pharmacies could provide an avenue to convenient, confidential STI screening by using noninvasive or minimally invasive sample collection techniques that are used by the consumer or pharmacist. We identified the most common STIs found globally and investigated the current and potential role of pharmacists in provision of STI screening interventions.Discussion: There is sufficient evidence for pharmacy-based chlamydia screening, with many consumers and pharmacists finding it an acceptable and highly valued service. Some evidence was found for pharmacy-based gonorrhea, hepatitis B virus (HBV, and human immunodeficiency virus (HIV screening. Appropriate sample collection for gonorrhea screening needs to be further examined in a pharmacy setting. HBV screening presented an increased risk of personal injury to pharmacists through the collection of whole blood specimens, which could be reduced through consumer self-sampling. Pharmacist-collected specimens for HIV is less risky as an oral swab can be used, nullifying the risk of transmission; but pre- and post-screen consultations can be time-intensive; hence, pharmacists would require remuneration to provide an ongoing HIV screening service. Not enough evidence was found for syphilis screening through community pharmacies; more studies are

Latent tuberculous infection screening using recombinant tuberculous allergen

Directory of Open Access Journals (Sweden)

N. A. Barmina

2016-01-01

Full Text Available In recent years the significant deterioration of health has been observed in schoolchildren. As per official data only 20% of children graduating from school are considered to be completely healthy, and 60% suffer from chronic diseases, i.e. belong to health groups III, IV and V, among which there are many children belonging to tuberculosis risk groups and suffering from undetected latent tuberculous infection. The efficiency of the new technique aimed to detect active tuberculous infection in children and adolescents of health groups III, IV and V has been evaluated. Screening proved the reduction in the number of patients in need of TB doctor advising by 8.4 fold compared to traditional mass diagnostics with tuberculin. Hyperergic reactions to diaskintest are 6 fold less common compared to Mantoux test. And 99.2% of children referred to TB doctor were registered to the dispensary follow-up versus 23.4% of children referred to TB doctor as per mass tuberculin testing results. (p < 0.001. Thus the validity of referral to TB doctor increased 4.2 fold. The detection rate of active forms of tuberculosis made 0.4 per 1000 examinations versus 0.1 in case of mass screening with tuberculin testing.

The Synthesis and Evaluation of Novel Hydroxyl Substituted Chalcone Analogs with in Vitro Anti-Free Radicals Pharmacological Activity and in Vivo Anti-Oxidation Activity in a Free Radical-Injury Alzheimer’s Model

Directory of Open Access Journals (Sweden)

Ying Pan

2013-01-01

Full Text Available Alzheimer’s disease (AD pathogenesis involves an imbalance between free radical formation and destruction. In order to obtain a novel preclinical anti-AD drug candidate, we synthesized a series of novel hydroxyl chalcone analogs which possessed anti-free radical activity, and screened their effects on scavenging 2,2-diphenyl-1-picrylhydrazyl (DPPH and OH free radicals in vitro. Compound C7, 4,2'-dihydroxy-3,5-dimethoxychalcone was found to have potent activity in these anti-free radical activity tests. Further research revealed that C7 could elevate glutathione peroxidase (GSH-PX and super oxide dismutase (SOD levels and lower malonaldehyde (MDA level in vivo in the Alzheimer’s model. The indication of C7’s effect on AD needs further study.

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

Serologic Screening for Genital Herpes Infection: US Preventive Services Task Force Recommendation Statement.

Science.gov (United States)

Bibbins-Domingo, Kirsten; Grossman, David C; Curry, Susan J; Davidson, Karina W; Epling, John W; García, Francisco A R; Kemper, Alex R; Krist, Alex H; Kurth, Ann E; Landefeld, C Seth; Mangione, Carol M; Phillips, William R; Phipps, Maureen G; Pignone, Michael P; Silverstein, Michael; Tseng, Chien-Wen

2016-12-20

Genital herpes is a prevalent sexually transmitted infection in the United States, occurring in almost 1 in 6 persons aged 14 to 49 years. Infection is caused by 2 subtypes of the herpes simplex virus (HSV), HSV-1 and HSV-2. Antiviral medications may provide symptomatic relief from outbreaks but do not cure HSV infection. Neonatal herpes infection, while uncommon, can result in substantial morbidity and mortality. To update the 2005 US Preventive Services Task Force (USPSTF) recommendation on screening for genital herpes. The USPSTF reviewed the evidence on the accuracy, benefits, and harms of serologic screening for HSV-2 infection in asymptomatic persons, including those who are pregnant, as well as the effectiveness and harms of preventive medications and behavioral counseling interventions to reduce future symptomatic episodes and transmission to others. Based on the natural history of HSV infection, its epidemiology, and the available evidence on the accuracy of serologic screening tests, the USPSTF concluded that the harms outweigh the benefits of serologic screening for genital HSV infection in asymptomatic adolescents and adults, including those who are pregnant. The USPSTF recommends against routine serologic screening for genital HSV infection in asymptomatic adolescents and adults, including those who are pregnant. (D recommendation).

ANTI-DIABETIC EFFICACY AND PHYTOCHEMICAL SCREENING OF METHANOLIC LEAF EXTRACT OF PAWPAW (Carica papaya GROWN IN NORTH CENTRAL NIGERIA.

Directory of Open Access Journals (Sweden)

Ayorinde Victor Ogundele

2016-10-01

Full Text Available Carica papaya leaves samples (Green were freshly harvested from Islamic village in Ilorin, Ilorin west local Government, Kwara State Nigeria. The leaves were extracted with methanol; the resulting extracts were screened for the phytochemical constituents using standard procedure. Phytochemical screening revealed the presence of bioactive compounds such as tannins, saponins, terpenoids, glycosides and alkaloids. The in-vitro anti-diabetic potential of the plant was also determined so as to justify the traditional usage of the plant in treating diabetes. The result of the present study confirmed that the methanolic extract of C.papaya leaves possess significant anti-diabetic activity in-vitro, this shows that the leaves has the potential for the development of drugs in combating diabetes.

Thiazoline peptides and a tris-phenethyl urea from Didemnum molle with anti-HIV activity.

Science.gov (United States)

Lu, Zhenyu; Harper, Mary Kay; Pond, Christopher D; Barrows, Louis R; Ireland, Chris M; Van Wagoner, Ryan M

2012-08-24

As part of our screening for anti-HIV agents from marine invertebrates, the MeOH extract of Didemnum molle was tested and showed moderate in vitro anti-HIV activity. Bioassay-guided fractionation of a large-scale extract allowed the identification of two new cyclopeptides, mollamides E and F (1 and 2), and one new tris-phenethyl urea, molleurea A (3). The absolute configurations were established using the advanced Marfey's method. The three compounds were evaluated for anti-HIV activity in both an HIV integrase inhibition assay and a cytoprotective cell-based assay. Compound 2 was active in both assays with IC(50) values of 39 and 78 μM, respectively. Compound 3 was active only in the cytoprotective cell-based assay, with an IC(50) value of 60 μM.

Antifungal and Anti-Biofilm Activities of Acetone Lichen Extracts against Candida albicans

Directory of Open Access Journals (Sweden)

Marion Millot

2017-04-01

Full Text Available Candida albicans is a commensal coloniser of the human gastrointestinal tract and an opportunistic pathogen, especially thanks to its capacity to form biofilms. This lifestyle is frequently involved in infections and increases the yeast resistance to antimicrobials and immune defenses. In this context, 38 lichen acetone extracts have been prepared and evaluated for their activity against C. albicans planktonic and sessile cells. Minimum inhibitory concentrations of extracts (MICs were determined using the broth microdilution method. Anti-biofilm activity was evaluated using tetrazolium salt (XTT assay as the ability to inhibit the maturation phase (anti-maturation or to eradicate a preformed 24 h old biofilm (anti-biofilm. While none of the extracts were active against planktonic cells, biofilm maturation was limited by 11 of the tested extracts. Seven extracts displayed both anti-maturation and anti-biofilm activities (half maximal inhibitory concentrations IC50_mat and IC50_biof ≤ 100 µg/mL; Evernia prunastri and Ramalina fastigiata were the most promising lichens (IC50_mat < 4 µg/mL and IC50_biof < 10 µg/mL. Chemical profiles of the active extracts performed by thin layer chromatography (TLC and high performance liquid chromatography (HPLC have been analyzed. Depsides, which were present in large amounts in the most active extracts, could be involved in anti-biofilm activities. This work confirmed that lichens represent a reservoir of compounds with anti-biofilm potential.

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

Directory of Open Access Journals (Sweden)

Yunierkis Perez-Castillo

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

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.

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

Directory of Open Access Journals (Sweden)

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.

[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.

Hepatitis C virus infection among pregnant women in Slovenia: study on 31,849 samples obtained in four screening rounds during 1999, 2003, 2009 and 2013.

Science.gov (United States)

Kopilović, B; Poljak, M; Seme, K; Klavs, I

2015-06-04

The majority of people infected with hepatitis C virus (HCV) are unaware of their infection. Assessment of the prevalence of HCV infection in the general population and in key populations at increased risk is needed for evidence-based testing policies. Our objectives were to estimate the prevalence of antibodies to HCV (anti-HCV), the prevalence of HCV viraemia (HCV RNA), and to describe HCV genotype distribution among pregnant women in Slovenia. Unlinked anonymous testing was performed on residual sera obtained from 31,849 pregnant women for routine syphilis screening during 1999, 2003, 2009, and 2013. Anti-HCV reactive specimens were tested for HCV RNA and HCV genotypes were determined. Annual prevalence of anti-HCV ranged between 0.09% (95% confidence interval (CI): 0.03–0.18) in 2009 and 0.21% (95% CI: 0.12–0.34) in 2003 and HCV RNA positivity between 0.06% (95% CI: 0.02–0.14) in 2009 and 0.14% (95% CI: 0.07–0.25) in 2003. We observed no statistically significant differences in anti-HCV or HCV RNA prevalence between age groups (Slovenia could not be recommended.

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

Symptom-based screening tool in ruling out active tuberculosis among HIV-infected patients eligible for isoniazid preventive therapy in Tanzania.

Science.gov (United States)

Shayo, Grace A; Minja, Lilian T; Egwaga, Said; Bakari, Muhammad; Mugusi, Ferdinand M

2014-06-01

We assessed the usefulness of the National TB and Leprosy Control Program (NTLP) symptom-based tuberculosis (TB) screening tool in identifying HIV-infected patients eligible for isoniazid preventive therapy in Muhimbili National Hospital, Dar es Salaam Tanzania. Descriptive cross-sectional study. Data collected included socio-demographic and clinical data. Chest X-ray, sputum for acid-fast bacilli (AFB) microscopy, mycobacterial culture, CD4 + count and complete blood count were performed. Patients were considered not having active TB if they presented with no symptom in the screening tool, which comprised these symptoms: cough, fever and excessive night sweats for ≥2 weeks; weight loss of ≥3 kg in 4 weeks and haemoptysis of any duration. The reference standard was a negative culture for Mycobacterium tuberculosis. We enroled 373 patients, of whom 72.1% were females. Active pulmonary TB was found in 4.1% (14/338) of the participants as defined by a positive culture. The sensitivity and specificity of the NTLP screening tool were 71.4% (10/14) and 75.9% (246/324), respectively. False-negative rate was 28.6% (4/10). Cough, fever for ≥2 weeks and weight loss were independent predictors of NTLP-defined TB. Cough ≥2 weeks predicted TB when a positive culture was used to define TB. The screening tool had fairly good sensitivity and specificity for TB screening; however, there is a possibility that about 29% of the screened population will be given IPT while they are supposed to receive a full course of TB treatment. © 2014 John Wiley & Sons Ltd.

The utility of screening for parasitic infections in HIV-1-infected Africans with eosinophilia in London.

Science.gov (United States)

Sarner, Liat; Fakoya, Ade O; Tawana, Cheryl; Allen, Elizabeth; Copas, Andrew J; Chiodini, Peter L; Fenton, Kevin A

2007-09-01

The presence of asymptomatic eosinophilia in HIV patients has been demonstrated to have a wide variety of causes. Untreated parasitic infections in immunocompromised individuals can have potentially serious consequences. The utility of screening for parasitic infections in immigrant HIV-positive Africans with eosinophilia was investigated in a UK-based HIV clinic. HIV-positive African patients with eosinophilia were matched with HIV-positive African controls without eosinophilia. More than half of African HIV patients with eosinophilia had positive parasitic serology, and were significantly more likely to have positive serology compared with African HIV patients without eosinophilia. This study shows that asymptomatic eosinophilia in HIV-1-infected Africans is strongly suggestive of underlying parasitic infection. Individuals with eosinophilia should thus be screened for parasitic infections according to the infections prevalent in the countries they have lived in or visited for substantial periods of time.

Anti-inflammatory, antioxidant, and antimicrobial activities of Cocos nucifera var. typica.

Science.gov (United States)

Silva, Rafaela Ribeiro; Oliveira e Silva, Davi; Fontes, Humberto Rollemberg; Alviano, Celuta Sales; Fernandes, Patricia Dias; Alviano, Daniela Sales

2013-05-16

Teas from the husk fiber of Cocos nucifera are used in the folk medicine to treat arthritis and other inflammatory processes. Some works show that some varieties have biological activities. However, one of the main variety of the species, C. nucifera var. typica, known in Brazil as "gigante", was not studied yet. Thus, this study evaluates if this variety has the anti-inflammatory and antimicrobial activities already reported in other varieties. C. nucifera aqueous crude extract (10, 50, and 100 mg/kg) and the reference drugs morphine (1 mg/kg) and acetylsalicylic acid (100 mg/kg) were evaluated in models of inflammation (formalin-induced licking and subcutaneous air pouch). The antioxidant activity was evaluated by 2,2-diphenyl-1-picryl-hydrazyl-hydrate (DPPH) photometric assay and compared with those of the standards (quercetin, rutin, and ascorbic acid). The extract was also screened against Candida albicans, Escherichia coli, Staphylococcus aureus, and methicillin-resistant Staphylococcus aureus (MRSA), in the agar diffusion method. The minimal inhibitory concentration (MIC) and minimal bactericidal concentration (MBC) were determined by the broth micro-dilution assay. Activities of combinations of the extract and antibiotics (methicillin or vancomycin) against MRSA were evaluated using checkerboard assays. The extract significantly inhibited the time that the animals spent licking the formalin-injected paws (second phase). The extract also inhibited the inflammatory process induced by subcutaneous carrageenan injection by reducing cell migration, protein extravasation, and TNF-α production. Additionally, the extract showed an antioxidant potential in vitro as good as standards in their antioxidant activity. The extract was active only against S. aureus and MRSA. MIC and the bactericidal concentrations were identical (1,024 μg/ml). The extract and methicillin acted synergistically against the clinical MRSA isolate, whereas an indifferent effect was detected

Anti-tumor Activity of Toll-Like Receptor 7 Agonists

Directory of Open Access Journals (Sweden)

Huju Chi

2017-05-01

Full Text Available Toll-like receptors (TLRs are a class of pattern recognition receptors that play a bridging role in innate immunity and adaptive immunity. The activated TLRs not only induce inflammatory responses, but also elicit the development of antigen specific immunity. TLR7, a member of TLR family, is an intracellular receptor expressed on the membrane of endosomes. TLR7 can be triggered not only by ssRNA during viral infections, but also by immune modifiers that share a similar structure to nucleosides. Its powerful immune stimulatory action can be potentially used in the anti-tumor therapy. This article reviewed the anti-tumor activity and mechanism of TLR7 agonists that are frequently applied in preclinical and clinical investigations, and mainly focused on small synthetic molecules, including imiquimod, resiquimod, gardiquimod, and 852A, etc.

Seropositivity of HBsAg, anti-HCV and anti-HIV in preoperative patients

Directory of Open Access Journals (Sweden)

Berrin Karaayak Uzun

2014-12-01

Full Text Available Objective: The infections caused by human immunodeficiency virus (HIV, hepatitis B (HBV and C (HCV viruses pose a serious occupational risk for the healthcare workers especially those in emergency services, laboratories and surgery wards. Vaccination and establishment of the strict biosafety procedures are the main principles to prevent blood-borne infections in healthcare workers. Additionally, serological screening of the preoperative patients could decrease the risk for exposure. In this study, we aimed to determine the seroprevalence of HBsAg, anti-HCV, anti-HIV 1/2 in preoperative patients. Methods: Hospital automation records were evaluated retrospectively for 4.367 patients who were scheduled for surgery and scanned for anti-HIV 1/2, HBsAg and anti-HCV as preoperative procedures in the preparation period of operation between January 2012 and December 2012. Results: HBsAg positivity rate was found in 7.7% (n=336, anti-HCV positivity rate was found in 2.3% (n=101. A two (0.05% of five patients were positive for anti-HIV 1/2 was found positive verification test and the other three samples were accepted as false positive test results. Conclusion: All healthcare workers must be trained about occupational diseases and vaccinated against Hepatitis B. Universal precautions must be strictly followed particularly in the operating room. In addition, all patients should be considered as potential carriers regarded as a carrier of the potential for infection. J Clin Exp Invest 2013; 4 (4: 449-452

Hepatitis C infection in risk groups

Directory of Open Access Journals (Sweden)

Sead Ahmetagić

2006-11-01

Full Text Available Hepatitis C infection is important global health problem with wide spectrum of health, social and economic consequences. The goal of this research was to estimate prevalence of hepatitis C virus infection in risk groups, and to determine association hepatitis C virus (HCV infection and risk factors. Research included 4627 subjects divided in two groups. Test group included 2627 subjects divided in 4 subgroups with risk for HCV infection: those who received blood transfusion without screening on HCV (it was introduced in 1995 (700; intravenous drug users (60; patients on hemodialysis (168 and health care workers (1699. Control group included 2000 healthy volunteer blood donors. In all subjects anti-HCV antibodies were tested with third generation ELISA test. Positive serum samples were tested for presence of HCVRNA, using reaction of reverse transcription and polymerase chain reaction. In all anti-HCV positive subjects further epidemiological and clinical workup was performed. Prevalence of HCV infection in risk groups was: 4.6% in subjects who have received blood transfusions without HCV blood screening, 35% in intravenous drug users, 58.9% in patients on chronic dialysis, and 0.4% in health care workers. In control group prevalence was low (0.2%. In the group of 158 anti-HCV positive subjects, 73.4% had HCVRNA. The largest number of subjects with HCV infection was in the age group of 30-49 years (45.8%. This study showed that multiple blood transfusions before introducing the blood screening for HCV, longer duration of intravenous drug abuse, longer duration of hemodialysis treatment, larger number of accidental injuries in health care workers are independent and statistically significant risk factors for those groups examined. Results of this study confirm that general screening for HCV infection is recommended in risk groups for HCV infection in order to identify to prevent and to treat it.

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

Directory of Open Access Journals (Sweden)

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.

Profound activity of the anti-cancer drug bortezomib against Echinococcus multilocularis metacestodes identifies the proteasome as a novel drug target for cestodes.

Directory of Open Access Journals (Sweden)

Britta Stadelmann

2014-12-01

Full Text Available A library of 426 FDA-approved drugs was screened for in vitro activity against E. multilocularis metacestodes employing the phosphoglucose isomerase (PGI assay. Initial screening at 20 µM revealed that 7 drugs induced considerable metacestode damage, and further dose-response studies revealed that bortezomib (BTZ, a proteasome inhibitor developed for the chemotherapy of myeloma, displayed high anti-metacestodal activity with an EC50 of 0.6 µM. BTZ treatment of E. multilocularis metacestodes led to an accumulation of ubiquinated proteins and unequivocally parasite death. In-gel zymography assays using E. multilocularis extracts demonstrated BTZ-mediated inhibition of protease activity in a band of approximately 23 kDa, the same size at which the proteasome subunit beta 5 of E. multilocularis could be detected by Western blot. Balb/c mice experimentally infected with E. multilocularis metacestodes were used to assess BTZ treatment, starting at 6 weeks post-infection by intraperitoneal injection of BTZ. This treatment led to reduced parasite weight, but to a degree that was not statistically significant, and it induced adverse effects such as diarrhea and neurological symptoms. In conclusion, the proteasome was identified as a drug target in E. multilocularis metacestodes that can be efficiently inhibited by BTZ in vitro. However, translation of these findings into in vivo efficacy requires further adjustments of treatment regimens using BTZ, or possibly other proteasome inhibitors.

Prevalence of CMV infection among staff in a metropolitan children’s hospital – occupational health screening findings

Directory of Open Access Journals (Sweden)

Stranzinger, Johanna

2016-09-01

Full Text Available Background: Staff in children’s hospitals may run an increased risk of cytomegalovirus (CMV contact infection leading to a congenital CMV fetopathy during pregnancy. The main risk factor is close contact with inapparent carriers of CMV among infants (<3 years. We therefore examined CMV seroprevalence (SP and possible risk factors for CMV infection among staff at a children’s hospital.Method: In 2014, staff at a metropolitan children’s hospital were offered a CMV antibody test in the context of occupational health screening. Besides of anti-CMV immunoglobulin G (anti-CMV IgG gender, age, profession, number of children and migration background were assessed and used as independent variables in multiple logistic regression. Women without a migration background (MIG were considered as a separate group.Results: The study included 219 employees. Women showed a significant higher risk than men of being CMV-positive (adjusted odds ratio [aOR] 3.0; 95% CI 1.1–7.8. The risk among age groups of 30 and over was double that of the under-30s (aOR 2.0; 95% CI 1.0–3.9; among those aged 40-plus it was aOR 2.3 (95% CI 1.1–4.7. Staff with an MIG tested more often positive than those without an MIG (95.5% versus 45.7%. CMV SP was 47.7% among women without an MIG. In this subgroup the probability of CMV infection increased with age (p=0.08 as well. Conclusion: In the staff group as a whole there was a significant correlation between CMV SP, country of origin and age. We found no significant differences between occupational groups; perhaps our random sample was too small. Given the low CMV SP particularly in those without MIG, women who want to have children in particular must be protected from CMV infection. Follow-up studies should be undertaken to test whether good workplace hygiene offers sufficient protection for pregnant women and could be an alternative to prohibiting certain activities.

Anti-herpes simplex virus activity of extracts from the culinary herbs ...

African Journals Online (AJOL)

This study demonstrates anti-herpes simplex virus activity of dichloromethane and methanol extracts of Ocimum sanctum L., Ocimum basilicum L. and Ocimum americanum L. Green monkey kidney cells were protected from HSV-2 infection by the dichloromethane extract of O. americanum L. and the methanol extract of O.

In vitro and in vivo assessment of the anti-malarial activity of Caesalpinia pluviosa

Directory of Open Access Journals (Sweden)

Eberlin Marcos N

2011-05-01

Full Text Available Abstract Background To overcome the problem of increasing drug resistance, traditional medicines are an important source for potential new anti-malarials. Caesalpinia pluviosa, commonly named "sibipiruna", originates from Brazil and possess multiple therapeutic properties, including anti-malarial activity. Methods Crude extract (CE was obtained from stem bark by purification using different solvents, resulting in seven fractions. An MTT assay was performed to evaluate cytotoxicity in MCF-7 cells. The CE and its fractions were tested in vitro against chloroquine-sensitive (3D7 and -resistant (S20 strains of Plasmodium falciparum and in vivo in Plasmodium chabaudi-infected mice. In vitro interaction with artesunate and the active C. pluviosa fractions was assessed, and mass spectrometry analyses were conducted. Results At non-toxic concentrations, the 100% ethanolic (F4 and 50% methanolic (F5 fractions possessed significant anti-malarial activity against both 3D7 and S20 strains. Drug interaction assays with artesunate showed a synergistic interaction with the F4. Four days of treatment with this fraction significantly inhibited parasitaemia in mice in a dose-dependent manner. Mass spectrometry analyses revealed the presence of an ion corresponding to m/z 303.0450, suggesting the presence of quercetin. However, a second set of analyses, with a quercetin standard, showed distinct ions of m/z 137 and 153. Conclusions The findings show that the F4 fraction of C. pluviosa exhibits anti-malarial activity in vitro at non-toxic concentrations, which was potentiated in the presence of artesunate. Moreover, this anti-malarial activity was also sustained in vivo after treatment of infected mice. Finally, mass spectrometry analyses suggest that a new compound, most likely an isomer of quercetin, is responsible for the anti-malarial activity of the F4.

Autophagy is involved in anti-viral activity of pentagalloylglucose (PGG) against Herpes simplex virus type 1 infection in vitro

International Nuclear Information System (INIS)

Pei, Ying; Chen, Zhen-Ping; Ju, Huai-Qiang; Komatsu, Masaaki; Ji, Yu-hua; Liu, Ge; Guo, Chao-wan; Zhang, Ying-Jun; Yang, Chong-Ren; Wang, Yi-Fei; Kitazato, Kaio

2011-01-01

Research highlights: → We showed PGG has anti-viral activity against Herpes simplex virus type 1 (HSV-1) and can induce autophgy. → Autophagy may be a novel and important mechanism mediating PGG anti-viral activities. → Inhibition of mTOR pathway is an important mechanism of induction of autophagy by PGG. -- Abstract: Pentagalloylglucose (PGG) is a natural polyphenolic compound with broad-spectrum anti-viral activity, however, the mechanisms underlying anti-viral activity remain undefined. In this study, we investigated the effects of PGG on anti-viral activity against Herpes simplex virus type 1 (HSV-1) associated with autophagy. We found that the PGG anti-HSV-1 activity was impaired significantly in MEF-atg7 -/- cells (autophagy-defective cells) derived from an atg7 -/- knockout mouse. Transmission electron microscopy revealed that PGG-induced autophagosomes engulfed HSV-1 virions. The mTOR signaling pathway, an essential pathway for the regulation of autophagy, was found to be suppressed following PGG treatment. Data presented in this report demonstrated for the first time that autophagy induced following PGG treatment contributed to its anti-HSV activity in vitro.

The anti-canine distemper virus activities of ex vivo-expanded canine natural killer cells.

Science.gov (United States)

Park, Ji-Yun; Shin, Dong-Jun; Lee, Soo-Hyeon; Lee, Je-Jung; Suh, Guk-Hyun; Cho, Duck; Kim, Sang-Ki

2015-04-17

Natural killer (NK) cells play critical roles in induction of antiviral effects against various viruses of humans and animals. However, few data on NK cell activities during canine distemper virus (CDV) infections are available. Recently, we established a culture system allowing activation and expansion of canine non-B, non-T, large granular NK lymphocytes from PBMCs of normal dogs. In the present study, we explored the ability of such expanded NK cells to inhibit CDV infection in vitro. Cultured CD3-CD5-CD21- NK cells produced large amounts of IFN-γ, exhibited highly upregulated expression of mRNAs encoding NK-cell-associated receptors, and demonstrated strong natural killing activity against canine tumor cells. Although the expanded NK cells were dose-dependently cytotoxic to both normal and CDV-infected Vero cells, CDV infection rendered Vero cells more susceptible to NK cells. Pretreatment with anti-CDV serum from hyperimmunized dogs enhanced the antibody-dependent cellular cytotoxicity (ADCC) of NK cells against CDV-infected Vero cells. The culture supernatants of NK cells, added before or after infection, dose-dependently inhibited both CDV replication and development of CDV-induced cytopathic effects (CPEs) in Vero cells. Anti-IFN-γ antibody neutralized the inhibitory effects of NK cell culture supernatants on CDV replication and CPE induction in Vero cells. Such results emphasize the potential significance of NK cells in controlling CDV infection, and indicate that NK cells may play roles both during CDV infection and in combating such infections, under certain conditions. Copyright © 2015 Elsevier B.V. All rights reserved.

Prevalence of anti HCV infection in patients with beta-thalassemia in Isfahan-Iran

Directory of Open Access Journals (Sweden)

Behrooz Ataei

2012-01-01

Conclusions: Our findings revealed that blood transfusion was the main risk factors for HCV infection among beta-thalassemic patients. Therefore, more blood donor screening programs and effective screening techniques are needed to prevent transmission of HCV infection among beta-thalassemic patients.

Significance of the “isolated EBNA-1 IgG” pattern in past EBV infection

Directory of Open Access Journals (Sweden)

Massimo De Paschale

2009-03-01

Full Text Available The ELISA screening detection of anti-EBNA-1 IgG in the absence of VCA IgG and IgM is rare but may lead to doubts in interpretation.We used immunoblotting to characterise 23 serum samples with “isolated EBNA-1 IgG” upon ELISA screening, and found that all showed VCA anti-p23 and 13 (56.6% also showed VCA anti-p18 antibodies. It therefore seems impossible for a sample to show anti-EBNA-1 IgG without anti-VCA IgG antibodies. Furthermore, although anti-p18 antibodies are thought to develop later and therefore considered to be markers of past infection, about 1% of all previously infected EBNA-1 IgG-positive patients do not have them.

Piracetam Facilitates the Anti-Amnesic but not Anti-Diabetic Activity of Metformin in Experimentally Induced Type-2 Diabetic Encephalopathic Rats.

Science.gov (United States)

Pandey, Shruti; Garabadu, Debapriya

2017-07-01

Piracetam exhibits anti-amnesic activity in several animal models of dementia. However, its anti-amnesic potential has yet to be evaluated in type-2 diabetes mellitus (T2DM)-induced encephalopathy. Therefore, in the present study, piracetam (25, 50 and 100 mg/kg) was screened for anti-amnesic and anti-diabetic activity in T2DM-induced encephalopathic male rats. Subsequently, anti-amnesic and anti-diabetic activities were evaluated for piracetam, metformin and their combination in T2DM-induced encephalopathic animals. Rats received streptozotocin (45 mg/kg) and nicotinamide (110 mg/kg) injections on day-1 (D-1) of the experimental schedule and were kept undisturbed for 35 days to exhibit T2DM-induced encephalopathy. All drug treatments were continued from D-7 to D-35 in both experiments. Piracetam (100 mg/kg) attenuated loss in learning and memory in terms of increase in escape latency on D-4 (D-34) and decrease in time spent in the target quadrant on D-5 (D-35) of Morris water maze test protocol, and spatial memory in terms of reduced spontaneous alternation behavior in Y-maze test of encephalopathic rats. Additionally, piracetam attenuated altered levels of fasting plasma glucose and insulin, HOMA-IR and HOMA-B in encephalopathic animals, comparatively lesser than metformin. In the next experiment, combination of piracetam and metformin exhibited better anti-amnesic but not anti-diabetic activity than respective monotherapies in encephalopathic rats. Further, the combination attenuated reduced acetylcholine level and increased acetylcholinesterase activity, increased glycogen synthase kinase-3β level and decreased brain-derived neurotropic factor level in hippocampus and pre-frontal cortex of encephalopathic animals. Thus, piracetam could be used as an adjuvant to metformin in the management of dementia in T2DM-induced encephalopathy.

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

Science.gov (United States)

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

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

Science.gov (United States)

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

2014-12-01

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

Treating Gulf War Illness with Novel Anti-Inflammatories: A Screening of Botantical Microglia Modulators

Science.gov (United States)

2016-10-01

AWARD NUMBER: W81XWH-14-1-0623 TITLE: Treating Gulf War Illness with Novel Anti-Inflammatories: A Screening of Botantical Microglia Modulators...Report 3. DATES COVERED 30 Sep 2015 - 29 Sep 2016 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER Treating Gulf War Illness with Novel Anti...SUBJECT TERMS Gulf War Illness, botanical, anti-inflammatory, biomarker, microglia, improvement, treatment 16. SECURITY CLASSIFICATION OF: 17

Hepatitis C virus infection can mimic type 1 (antinuclear antibody positive) autoimmune chronic active hepatitis.

Science.gov (United States)

Pawlotsky, J M; Deforges, L; Bretagne, S; André, C; Métreau, J M; Thiers, V; Zafrani, E S; Goossens, M; Duval, J; Mavier, J P

1993-01-01

Hepatitis C virus (HCV) has been shown to induce anti-liver-kidney microsomal-1 (LKM1) antibody positive chronic active hepatitis, simulating type 2 autoimmune chronic active hepatitis. The cases of five patients presenting with features of type 1 (antinuclear antibody positive) autoimmune chronic active hepatitis and extrahepatic autoimmune manifestations, in whom immunosuppressive treatment had no effect on liver disease are presented. In these patients, HCV infection could be shown by the presence in serum of anti-HCV antibodies and HCV-RNA detected by polymerase chain reaction. These cases suggest the following: (a) chronic HCV infection can mimic type 1, as well as type 2, autoimmune chronic active hepatitis; (b) HCV infection might be systematically sought in patients presenting with features of type 1 autoimmune chronic active hepatitis, with special care in patients who are unresponsive to immunosuppressive treatment. Images Figure PMID:7686122

Prevalence of hepatitis C Virus infection among hemophiliacs in Central Brazil

Directory of Open Access Journals (Sweden)

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.

Autophagy is involved in anti-viral activity of pentagalloylglucose (PGG) against Herpes simplex virus type 1 infection in vitro

Energy Technology Data Exchange (ETDEWEB)

Pei, Ying, E-mail: peiying-19802@163.com [Biomedicine Research and Development Center of Jinan University, Guangzhou, Guangdong 510632 (China); Chen, Zhen-Ping, E-mail: 530670663@qq.com [Biomedicine Research and Development Center of Jinan University, Guangzhou, Guangdong 510632 (China); Ju, Huai-Qiang, E-mail: 344464448@qq.com [Biomedicine Research and Development Center of Jinan University, Guangzhou, Guangdong 510632 (China); Komatsu, Masaaki, E-mail: komatsu-ms@igakuken.or.jp [Laboratory of Frontier Science, Tokyo Metropolitan Institute of Medical Science, Bunkyo-ku, Tokyo 113-8613 (Japan); Ji, Yu-hua, E-mail: tjyh@jnu.edu.cn [Institute of Tissue Transplantation and Immunology, College of Life Science and Technology, Jinan University, Guangzhou 510632 (China); Liu, Ge, E-mail: lggege_15@hotmail.com [Division of Molecular Pharmacology of Infectious agents, Department of Molecular Microbiology and Immunology, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki 852-8521 (Japan); Guo, Chao-wan, E-mail: chaovan_kwok@hotmail.com [Division of Molecular Pharmacology of Infectious agents, Department of Molecular Microbiology and Immunology, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki 852-8521 (Japan); Zhang, Ying-Jun, E-mail: zhangyj@mail.kib.ac.cn [Kunming Institute of Botany, the Chinese Academy of Sciences, Yunnan, Kunming 650204 (China); Yang, Chong-Ren, E-mail: cryang@mail.kib.ac.cn [Kunming Institute of Botany, the Chinese Academy of Sciences, Yunnan, Kunming 650204 (China); Wang, Yi-Fei, E-mail: twang-yf@163.com [Biomedicine Research and Development Center of Jinan University, Guangzhou, Guangdong 510632 (China); Kitazato, Kaio, E-mail: kkholi@msn.com [Division of Molecular Pharmacology of Infectious agents, Department of Molecular Microbiology and Immunology, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki 852-8521 (Japan)

2011-02-11

Research highlights: {yields} We showed PGG has anti-viral activity against Herpes simplex virus type 1 (HSV-1) and can induce autophgy. {yields} Autophagy may be a novel and important mechanism mediating PGG anti-viral activities. {yields} Inhibition of mTOR pathway is an important mechanism of induction of autophagy by PGG. -- Abstract: Pentagalloylglucose (PGG) is a natural polyphenolic compound with broad-spectrum anti-viral activity, however, the mechanisms underlying anti-viral activity remain undefined. In this study, we investigated the effects of PGG on anti-viral activity against Herpes simplex virus type 1 (HSV-1) associated with autophagy. We found that the PGG anti-HSV-1 activity was impaired significantly in MEF-atg7{sup -/-} cells (autophagy-defective cells) derived from an atg7{sup -/-} knockout mouse. Transmission electron microscopy revealed that PGG-induced autophagosomes engulfed HSV-1 virions. The mTOR signaling pathway, an essential pathway for the regulation of autophagy, was found to be suppressed following PGG treatment. Data presented in this report demonstrated for the first time that autophagy induced following PGG treatment contributed to its anti-HSV activity in vitro.

Natural product HTP screening for antibacterial (E.coli 0157:H7) and anti-inflammatory agents in (LPS from E. coli O111:B4) activated macrophages and microglial cells; focus on sepsis.

Science.gov (United States)

Mazzio, Elizabeth A; Li, Nan; Bauer, David; Mendonca, Patricia; Taka, Equar; Darb, Mohammed; Thomas, Leeshawn; Williams, Henry; Soliman, Karam F A

2016-11-15

Acute systemic inflammatory response syndrome arising from infection can lead to multiple organ failure and death, with greater susceptibility occurring in immunocompromised individuals. Moreover, sub-acute chronic inflammation is a contributor to the pathology of diverse degenerative diseases (Parkinson's disease, Alzheimer's disease and arthritis). Given the known limitations in Western medicine to treat a broad range of inflammatory related illness as well as the emergence of antibiotic resistance, there is a renewed interest in complementary and alternative medicines (CAMs) to achieve these means. A high throughput (HTP) screening of >1400 commonly sold natural products (bulk herbs, cooking spices, teas, leaves, supplement components, nutraceutical food components, fruit and vegetables, rinds, seeds, polyphenolics etc.) was conducted to elucidate anti-inflammatory substances in lipopolysaccharide (LPS) (E. coli serotype O111:B4) monocytes: RAW 264.7 macrophages [peripheral], BV-2 microglia [brain]) relative to hydrocortisone, dexamethasone and L-N6-(1Iminoethyl)lysine (L-NIL). HTP evaluation was also carried out for lethal kill curves against E.coli 0157:H7 1x10 6 CFU/mL relative to penicillin. Validation studies were performed to assess cytokine profiling using antibody arrays. Findings were corroborated by independent ELISAs and NO2-/iNOS expression quantified using the Griess Reagent and immunocytochemistry, respectively. For robust screening, we developed an in-vitro efficacy paradigm to ensure anti-inflammatory parameters were observed independent of cytotoxicity. This caution was taken given that many plants exert tumoricidal and anti-inflammatory effects at close range through similar signaling pathways, which could lead to false positives. The data show that activated BV-2 microglia cells (+ LPS 1μg/ml) release >10-fold greater IL-6, MIP1/2, RANTES and nitric oxide (NO2-), where RAW 264.7 macrophages (+ LPS 1μg/ml) produced > 10-fold rise in sTNFR2

Incidence and Risk of Cytomegalovirus Infection during Pregnancy in an Urban Area of Northern Italy

Directory of Open Access Journals (Sweden)

Massimo De Paschale

2009-01-01

Full Text Available The fetal consequences of CMV infection make it one of the most serious infections contracted during pregnancy, but the scientific community is divided over the proposed implementation of preventive screening for anti-CMV antibodies. The aim of this study was to assess the incidence and risk of infection during pregnancy in 2817 women who underwent anti-CMV IgG and IgM antibody screening during the period 2005–2007. The prevalence of anti-CMV IgG antibodies was 68.3% (95% CI: 66.6–70.0; the seroconversion rate in the 892 seronegative women was 0.32%; the results of IgG avidity testing revealed an cumulative incidence of 1.4% (95% CI: 0.97–1.83, density incidence of 0.8% (as cases/pregnant woman-trimester (95% CI: 0.47–1.13, and a risk of infection of 0.5% (95% CI: 0.24–0.76. The screening identified 13 cases of primary infection (84.6% of which occurred in the first trimester of pregnancy. The possibility to identify these cases and consequently to plan appropriate interventions, supports the use of screening during pregnancy, especially in the first trimester when the risk of infection is greater.

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

Directory of Open Access Journals (Sweden)

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.

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

Science.gov (United States)

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

2017-04-01

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

Anti-coccidial activity of the ethanol extract of Tribulus terrestris fruits on Eimeria tenella

Science.gov (United States)

Hong, Sunhwa; Moon, Mi-Na; Im, Eun-Kyung; Won, Jum-Soon; Yoo, Ji-Hyun

2018-01-01

Anti-coccidial effects of the fruits of Tribulus terrestris (Tribuli fructus) ethanol extract (TTE) were studied with animal experiment following per oral administration with Eimeria (E.) tenella. This experiment was performed on the 3-day-old chicks (n=30). The animals were divided with 3 groups; TFE 15mg per animal+infected (n=10), TTE untreated+infected (n=10) and non-infected control (n=10). Animals were administrated with or without TTE during 1 week, and then inoculated with E. tenella. The anti-coccidial activity were evaluated with oocysts shedding numbers in stools, body weights changes and food intake changes. The TTE-inoclated animals revealed significantly decreased stool oocysts numbers (P<0.05) when compared to the TTE untreated animals. Also, TTE-treated animals showed more increased body weight gains (P<0.05) than the TTE untreated animals. These results demonstrate that TTE produce anticoccidial activities against E. tenella. TTE could be a promising treatment for the coccidiosis. PMID:29628976

Anti-coccidial activity of the ethanol extract of Tribulus terrestris fruits on Eimeria tenella.

Science.gov (United States)

Hong, Sunhwa; Moon, Mi-Na; Im, Eun-Kyung; Won, Jum-Soon; Yoo, Ji-Hyun; Kim, Okjin

2018-03-01

Anti-coccidial effects of the fruits of Tribulus terrestris (Tribuli fructus) ethanol extract (TTE) were studied with animal experiment following per oral administration with Eimeria ( E .) tenella . This experiment was performed on the 3-day-old chicks (n=30). The animals were divided with 3 groups; TFE 15mg per animal+infected (n=10), TTE untreated+infected (n=10) and non-infected control (n=10). Animals were administrated with or without TTE during 1 week, and then inoculated with E. tenella . The anti-coccidial activity were evaluated with oocysts shedding numbers in stools, body weights changes and food intake changes. The TTE-inoclated animals revealed significantly decreased stool oocysts numbers ( P <0.05) when compared to the TTE untreated animals. Also, TTE-treated animals showed more increased body weight gains ( P <0.05) than the TTE untreated animals. These results demonstrate that TTE produce anticoccidial activities against E. tenella . TTE could be a promising treatment for the coccidiosis.

Identification of candidate agents active against N. ceranae infection in honey bees: establishment of a medium throughput screening assay based on N. ceranae infected cultured cells.

Science.gov (United States)

Gisder, Sebastian; Genersch, Elke

2015-01-01

Many flowering plants in both natural ecosytems and agriculture are dependent on insect pollination for fruit set and seed production. Managed honey bees (Apis mellifera) and wild bees are key pollinators providing this indispensable eco- and agrosystem service. Like all other organisms, bees are attacked by numerous pathogens and parasites. Nosema apis is a honey bee pathogenic microsporidium which is widely distributed in honey bee populations without causing much harm. Its congener Nosema ceranae was originally described as pathogen of the Eastern honey bee (Apis cerana) but jumped host from A. cerana to A. mellifera about 20 years ago and spilled over from A. mellifera to Bombus spp. quite recently. N. ceranae is now considered a deadly emerging parasite of both Western honey bees and bumblebees. Hence, novel and sustainable treatment strategies against N. ceranae are urgently needed to protect honey and wild bees. We here present the development of an in vitro medium throughput screening assay for the identification of candidate agents active against N. ceranae infections. This novel assay is based on our recently developed cell culture model for N. ceranae and coupled with an RT-PCR-ELISA protocol for quantification of N. ceranae in infected cells. The assay has been adapted to the 96-well microplate format to allow automated analysis. Several substances with known (fumagillin) or presumed (surfactin) or no (paromomycin) activity against N. ceranae were tested as well as substances for which no data concerning N. ceranae inhibition existed. While fumagillin and two nitroimidazoles (metronidazole, tinidazole) totally inhibited N. ceranae proliferation, all other test substances were inactive. In summary, the assay proved suitable for substance screening and demonstrated the activity of two synthetic antibiotics against N. ceranae.

Identification of candidate agents active against N. ceranae infection in honey bees: establishment of a medium throughput screening assay based on N. ceranae infected cultured cells.

Directory of Open Access Journals (Sweden)

Sebastian Gisder

Full Text Available Many flowering plants in both natural ecosytems and agriculture are dependent on insect pollination for fruit set and seed production. Managed honey bees (Apis mellifera and wild bees are key pollinators providing this indispensable eco- and agrosystem service. Like all other organisms, bees are attacked by numerous pathogens and parasites. Nosema apis is a honey bee pathogenic microsporidium which is widely distributed in honey bee populations without causing much harm. Its congener Nosema ceranae was originally described as pathogen of the Eastern honey bee (Apis cerana but jumped host from A. cerana to A. mellifera about 20 years ago and spilled over from A. mellifera to Bombus spp. quite recently. N. ceranae is now considered a deadly emerging parasite of both Western honey bees and bumblebees. Hence, novel and sustainable treatment strategies against N. ceranae are urgently needed to protect honey and wild bees. We here present the development of an in vitro medium throughput screening assay for the identification of candidate agents active against N. ceranae infections. This novel assay is based on our recently developed cell culture model for N. ceranae and coupled with an RT-PCR-ELISA protocol for quantification of N. ceranae in infected cells. The assay has been adapted to the 96-well microplate format to allow automated analysis. Several substances with known (fumagillin or presumed (surfactin or no (paromomycin activity against N. ceranae were tested as well as substances for which no data concerning N. ceranae inhibition existed. While fumagillin and two nitroimidazoles (metronidazole, tinidazole totally inhibited N. ceranae proliferation, all other test substances were inactive. In summary, the assay proved suitable for substance screening and demonstrated the activity of two synthetic antibiotics against N. ceranae.

ELISA with double antigen sandwich for screening specific serum anti-TP antibody in blood donors

International Nuclear Information System (INIS)

Wang Yiqing; Shi Zhixu

2002-01-01

Objective: To select a sensitive and specific laboratory examination suitable for screening serum anti-TP antibody in blood donors. Methods: The serum anti-TP antibody in 11271 blood donors were detected using ELISA with double antigen sandwich and the outcomes were compared with those using RPR assay. The conflicting specimen were confirmed by repeating the test with TPHA assay. Results: The positive rates of serum anti-TP antibody by ELISA with double antigen sandwich and RPR was 0.36% (41/11271) and 0.26% (29/11271), respectively. The coincidence of the detecting outcomes by ELISA with double antigen sandwich and RPR with TPHA was 97.5% (40/41) and 63.41%(26/41) respectively. Conclusion: Compared with RPR assay, ELISA with double antigen sandwich has higher sensibility and specificity for screening serum anti-TP antibody in blood donors

Antioxidant and Anti-Inflammatory Activity Determination of One Hundred Kinds of Pure Chemical Compounds Using Offline and Online Screening HPLC Assay

Directory of Open Access Journals (Sweden)

Kwang Jin Lee

2015-01-01

Full Text Available This study investigated the antioxidant activity of one hundred kinds of pure chemical compounds found within a number of natural substances and oriental medicinal herbs (OMH. Three different methods were used to evaluate the antioxidant activity of DPPH radical-scavenging activity, ABTS radical-scavenging activity, and online screening HPLC-ABTS assays. The results indicated that 17 compounds exhibited better inhibitory activity against ABTS radical than DPPH radical. The IC50 rate of a more practical substance is determined, and the ABTS assay IC50 values of gallic acid hydrate, (+-catechin hydrate, caffeic acid, rutin hydrate, hyperoside, quercetin, and kaempferol compounds were 1.03 ± 0.25, 3.12 ± 0.51, 1.59 ± 0.06, 4.68 ± 1.24, 3.54 ± 0.39, 1.89 ± 0.33, and 3.70 ± 0.15 μg/mL, respectively. The ABTS assay is more sensitive to identifying the antioxidant activity since it has faster reaction kinetics and a heightened response to antioxidants. In addition, there was a very small margin of error between the results of the offline-ABTS assay and those of the online screening HPLC-ABTS assay. We also evaluated the effects of 17 compounds on the NO secretion in LPS-stimulated RAW 264.7 cells and also investigated the cytotoxicity of 17 compounds using a cell counting kit (CCK in order to determine the optimal concentration that would provide an effective anti-inflammatory action with minimum toxicity. These results will be compiled into a database, and this method can be a powerful preselection tool for compounds intended to be studied for their potential bioactivity and antioxidant activity related to their radical-scavenging capacity.

[Anti-Candida activity of aroma candy and its protective activity against murine oral candidiasis].

Science.gov (United States)

Hayama, Kazumi; Takahashi, Miki; Suzuki, Motofumi; Ezawa, Kunio; Yamazaki, Masatoshi; Matsukawa, Taiji; Kishi, Akinobu; Sato, Nobuya; Abe, Shigeru

2015-01-01

A daily eatable candy that has possible protective activity against oral candidiasis was experimentally produced. The candy was made from reduced-maltose as main constituent and from several natural products, such as oligonol (depolymerized polyphenols derived from lychee), cinnamon (cassia), citral, and capric acid, which are known to have anti-Candida activity in vitro and in vivo. The candy effectively inhibited the mycelial growth of C. albicans, even when it was diluted 1,000 times with culture media. We assessed the protective activity of the candy against murine candidiasis. When 50μl of candy dissolved and diluted 4 times with water was administered 3 times into the oral cavity of Candida infected mice, the score of lesions on the Candida-infected tongues improved on day 2. These findings suggest that this candy has potential as food that provides protective activity against oral candidiasis.

Highly Efficient F, Cu doped TiO2 anti-bacterial visible light active photocatalytic coatings to combat hospital-acquired infections

Science.gov (United States)

Leyland, Nigel S.; Podporska-Carroll, Joanna; Browne, John; Hinder, Steven J.; Quilty, Brid; Pillai, Suresh C.

2016-04-01

Bacterial infections are a major threat to the health of patients in healthcare facilities including hospitals. One of the major causes of patient morbidity is infection with Staphylococcus aureus. One of the the most dominant nosocomial bacteria, Methicillin Resistant Staphylococcus aureus (MRSA) have been reported to survive on hospital surfaces (e.g. privacy window glasses) for up to 5 months. None of the current anti-bacterial technology is efficient in eliminating Staphylococcus aureus. A novel transparent, immobilised and superhydrophilic coating of titanium dioxide, co-doped with fluorine and copper has been prepared on float glass substrates. Antibacterial activity has demonstrated (by using Staphylococcus aureus), resulting from a combination of visible light activated (VLA) photocatalysis and copper ion toxicity. Co-doping with copper and fluorine has been shown to improve the performance of the coating, relative to a purely fluorine-doped VLA photocatalyst. Reductions in bacterial population of log10 = 4.2 under visible light irradiation and log10 = 1.8 in darkness have been achieved, compared with log10 = 1.8 under visible light irradiation and no activity, for a purely fluorine-doped titania. Generation of reactive oxygen species from the photocatalytic coatings is the major factor that significantly reduces the bacterial growth on the glass surfaces.

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

Directory of Open Access Journals (Sweden)

Azam Mohammad

2003-01-01

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

Anti-inflammatory activity of Vismia guianensis (Aubl.) Pers. extracts and antifungal activity against Sporothrix schenckii.

Science.gov (United States)

Oliveira, A H; de Oliveira, G G; Carnevale Neto, F; Portuondo, D F; Batista-Duharte, A; Carlos, I Z

2017-01-04

Vismia guianensis (Aubl.) Pers. is traditionally used in North and Northeast of Brazil for the treatment of dermatomycoses. Since the strategy associating immunomodulators with antifungal drugs seems to be promissory to improve the treatment efficacy in fungal infections, we aimed to investigate the antifungal activity of V. guianensis ethanolic extract of leaves (VGL) and bark (VGB) against Sporothrix schenckii ATCC 16345 and their antinflammatory activities. The extracts were analyzed by HPLC-DAD-IT MS/MS for in situ identification of major compounds. Antifungal activity was evaluated in vitro (microdilution test) and in vivo using a murine model of S. schenckii infection. The production of TNF-α, IFN-γ, IL-4, IL-10 and IL-12 by measured by ELISA, as well as measured the production and inhibition of the NO after treatment with the plant extracts or itraconazole (ITR). Two O-glucosyl-flavonoids and 16 prenylated benzophenone derivatives already described for Vismia were detected. Both VGL and VGB showed significant antifungal activity either in in vitro assay of microdilution (MIC=3.9µg/mL) and in vivo model of infection with reduction of S. schenckii load in spleen. It was also observed a predominance of reduction in the production of NO and the proinflammatory cytokines evaluated except TNFα, but with stimulation of IL-10, as evidence of a potential anti-inflammatory effect associated. The results showed that both VGL and VGB have a significant antifungal against S. schenckii and an anti-inflammatory activity. These results can support the use of these extracts for alternative treatment of sporotrichosis. Copyright © 2016 Elsevier B.V. All rights reserved.

Study on screening of anti-predator rhizosphere bacterium against Caenorhabditis elegans and its anti predation mechanism

Directory of Open Access Journals (Sweden)

HE Qingling

2016-08-01

Full Text Available Althoughmicrobial fertilizer is multi-effect,environmental friendly and long-term efficient,its practical application effect is but decreased for being prey by the other creators living in soil frequently.Many bacterium have developed their mechanisms that expel or kill worms to defend themselves from predators.Screening of anti-predator rhizosphere bacterium helps us to find out competitive plant growth promoting rhizobacteria(PGPR.Using Caenorhabditis elegans as sample,this study roughly observed two strains of biocontrol:Pseudomonas aurantiaca JD37 and Pseudomonas fluorescens P13.Using Escherichia coli OP50 as control group,we find the preference order of worms,from highest to lowest,is P13,OP50 and JD37.In slow killing assay,the death rate of worms for JD37 and P13 are 26.12% and 18.66% respectively.The activity and reproduction rate of C.elegans decrease when it is fed on JD37.The results of chemical and micro-biological study show that JD37 cannot produce any currently studied second metabolites which kill worms,while P13 can produce Hydrogen cyanide (HCN.All these results show that JD37 has the ability of anti-predator,and is more competitive under predation pressure,which suggests its broad application prospect as microbial fertilizer.

Asian Organization for Crohn's and Colitis and Asia Pacific Association of Gastroenterology consensus on tuberculosis infection in patients with inflammatory bowel disease receiving anti-tumor necrosis factor treatment. Part 2: management

Directory of Open Access Journals (Sweden)

Dong Il Park

2018-01-01

Full Text Available Because anti-tumor necrosis factor (anti-TNF therapy has become increasingly popular in many Asian countries, the risk of developing active tuberculosis (TB among anti-TNF users may raise serious health problems in this region. Thus, the Asian Organization for Crohn's and Colitis and the Asia Pacific Association of Gastroenterology have developed a set of consensus statements about risk assessment, detection and prevention of latent TB infection, and management of active TB infection in patients with inflammatory bowel disease (IBD receiving anti-TNF treatment. Twenty-three consensus statements were initially drafted and then discussed by the committee members. The quality of evidence and the strength of recommendations were assessed by using the Grading of Recommendations Assessment, Development, and Evaluation methodology. Web-based consensus voting was performed by 211 IBD specialists from 9 Asian countries concerning each statement. A consensus statement was accepted if at least 75% of the participants agreed. Part 2 of the statements comprised 3 parts: management of latent TB in preparation for anti-TNF therapy, monitoring during anti-TNF therapy, and management of an active TB infection after anti-TNF therapy. These consensus statements will help clinicians optimize patient outcomes by reducing the morbidity and mortality related to TB infections in patients with IBD receiving anti-TNF treatment.

Evaluation of the HISCL Anti-Treponema pallidum Assay as a Screening Test for Syphilis.

Science.gov (United States)

An, Jingna; Chen, Qixia; Liu, Qianqian; Rao, Chenli; Li, Dongdong; Wang, Tingting; Tao, Chuanmin; Wang, Lanlan

2015-07-01

The resurgence of syphilis in recent years has become a serious threat to public health worldwide, and the serological detection of specific antibodies against Treponema pallidum remains the most reliable method for laboratory diagnosis of syphilis. This study examined the performance of the recently launched HISCL anti-Treponema pallidum (anti-TP) assay as a screening test for syphilis in a high-volume laboratory. The HISCL anti-TP assay was tested in 300 preselected syphilis-positive samples, 704 fresh syphilis-negative samples, 48 preselected potentially interfering samples, and 30 "borderline" samples and was compared head to head with the commercially available Lumipulse G TP-N. In this study, the HISCL anti-TP assay was in perfect agreement with the applied testing algorithms with an overall agreement of 100%, comparable to that of Lumipulse G TP-N (99.63%). The sensitivity and specificity of the HISCL anti-TP assay were 100% (95% confidence interval [CI], 98.42% to 100%) and 100% (95% CI, 99.37% to 100%), respectively. Considering the excellent ease of use and automation, high throughput, and its favorable sensitivity and specificity, the HISCL anti-TP assay may represent a new choice for syphilis screening in high-volume laboratories. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

In vivo screening antifungal activity of methanolic extract of Protoparmeliopsis muralis against Aspergillus flavus

Directory of Open Access Journals (Sweden)

Somaye Rashki

2017-06-01

Full Text Available Background & Objective: Lichens are the result of the symbiosis of fungi and algae or a cyanobacterium. Various biological activities of some lichen and their components such as: antifungal, anti-bacterial, anti-tumor, anti-inflammatory, antiprotozoal substances are known. In the present study, antifungal activity of methanolic extract of Protoparmeliopsis muralis against Aspergillus flavus is investigated on rats. Materials & Methods: 500 g of Protoparmeliopsis muralis was collected from KaneGonbad mountains in Ilam province, the methanol extract was prepared by soxhle. In order to determine the antifungal activity in in vivo conditions, a wound was created and infected with Aspergillus flavus. Having infected the wound, the researchers divided the rats into 4 subgroups: negative control group, treated with Kotrimoksazol, %5 ointment extract methanolic P. muralis, and with %10 ointment extract methanolic P. muralis. Treatment continued until complete healing of the wound. Finally, the percentage of wound healing was calculated. Results: The result of the present study demonstrated that methanolic extract of P. muralis decreased the area of wound in the treatment group compared to the control group. Conclusion: The antifungal and antioxidant activity of the extract of Protoparmeliopsis muralis accelerated the wound healing process.

Anti-infective Discorhabdins from a Deep-Water Alaskan Sponge of the Genus Latrunculia†

Science.gov (United States)

Na, MinKyun; Ding, Yuanqing; Wang, Bin; Tekwani, Babu L.; Schinazi, Raymond F.; Franzblau, Scott; Kelly, Michelle; Stone, Robert; Li, Xing-Cong; Ferreira, Daneel; Hamann, Mark T.

2016-01-01

Bioassay- and LC-MS-guided fractionation of a methanol extract from a new deep-water Alaskan sponge species of the genus Latrunculia resulted in the isolation of two new brominated pyrroloiminoquinones, dihydrodiscorhabdin B (1) and discorhabdin Y (2), along with six known pyrroloiminoquinone alkaloids, discorhabdins A (3), C (4), E (5), and L (6), dihydrodiscorhabdin C (7), and the benzene derivative 8. Compounds 3, 4, and 7 exhibited anti-HCV activity, antimalarial activity, and selective antimicrobial activity. Although compounds 3 and 7 displayed potent and selective in vitro antiprotozoal activity, Plasmodium berghei-infected mice did not respond to these metabolites due to their toxicity in vivo. PMID:20337497

Anti-infective discorhabdins from a deep-water alaskan sponge of the genus Latrunculia.

Science.gov (United States)

Na, Minkyun; Ding, Yuanqing; Wang, Bin; Tekwani, Babu L; Schinazi, Raymond F; Franzblau, Scott; Kelly, Michelle; Stone, Robert; Li, Xing-Cong; Ferreira, Daneel; Hamann, Mark T

2010-03-26

Bioassay- and LC-MS-guided fractionation of a methanol extract from a new deep-water Alaskan sponge species of the genus Latrunculia resulted in the isolation of two new brominated pyrroloiminoquinones, dihydrodiscorhabdin B and discorhabdin Y (2), along with six known pyrroloiminoquinone alkaloids, discorhabdins A (3), C (4), E (5), and L (6), dihydrodiscorhabdin C (7), and the benzene derivative 8. Compounds 3, 4, and 7 exhibited anti-HCV activity, antimalarial activity, and selective antimicrobial activity. Although compounds 3 and 7 displayed potent and selective in vitro antiprotozoal activity, Plasmodium berghei-infected mice did not respond to these metabolites due to their toxicity in vivo.

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 ...

Screening for Antiviral Activities of Isolated Compounds from Essential Oils

Directory of Open Access Journals (Sweden)

Akram Astani

2011-01-01

Full Text Available Essential oil of star anise as well as phenylpropanoids and sesquiterpenes, for example, trans-anethole, eugenol, β-eudesmol, farnesol, β-caryophyllene and β-caryophyllene oxide, which are present in many essential oils, were examined for their antiviral activity against herpes simplex virus type 1 (HSV-1 in vitro. Antiviral activity was analyzed by plaque reduction assays and mode of antiviral action was determined by addition of the drugs to uninfected cells, to the virus prior to infection or to herpesvirus-infected cells. Star anise oil reduced viral infectivity by >99%, phenylpropanoids inhibited HSV infectivity by about 60–80% and sesquiterpenes suppressed herpes virus infection by 40–98%. Both, star anise essential oil and all isolated compounds exhibited anti-HSV-1 activity by direct inactivation of free virus particles in viral suspension assays. All tested drugs interacted in a dose-dependent manner with herpesvirus particles, thereby inactivating viral infectivity. Star anise oil, rich in trans-anethole, revealed a high selectivity index of 160 against HSV, whereas among the isolated compounds only β-caryophyllene displayed a high selectivity index of 140. The presence of β-caryophyllene in many essential oils might contribute strongly to their antiviral ability. These results indicate that phenylpropanoids and sesquiterpenes present in essential oils contribute to their antiviral activity against HSV.

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.

Dried blood spots, valid screening for viral hepatitis and human immunodeficiency virus in real-life

DEFF Research Database (Denmark)

Mössner, Belinda K; Staugaard, Benjamin; Jensen, Janne

2016-01-01

AIM: To detect chronic hepatitis B (CHB), chronic hepatitis C (CHC) and human immunodeficiency virus (HIV) infections in dried blood spot (DBS) and compare these samples to venous blood sampling in real-life. METHODS: We included prospective patients with known viral infections from drug treatment......, but correctly classified 95% of the anti-HCV-positive patients with chronic and past infections. Anti-HBc and anti-HBS showed low sensitivity in DBS (68% and 42%). CONCLUSION: DBS sampling, combined with an automated analysis system, is a feasible screening method to diagnose chronic viral hepatitis and HIV...

An integrative review of guidelines for anal cancer screening in HIV-infected persons.

Science.gov (United States)

Wells, Jessica S; Holstad, Marcia M; Thomas, Tami; Bruner, Deborah Watkins

2014-07-01

HIV-infected individuals are 28 times more likely than the general population to be diagnosed with anal cancer. An integrative review of recommendations and guidelines for anal cancer screening was performed to provide a succinct guide to inform healthcare clinicians. The review excluded studies that were of non-HIV populations, redundant articles or publications, non-English manuscripts, or nonclinical trials. The review found no formal national or international guidelines exist for routine screening of anal cancer for HIV-infected individuals. To date, no randomized control trial provides strong evidence supporting efficaciousness and effectiveness of an anal cancer screening program. The screening recommendations from seven international-, national-, and state-based reports were reviewed and synthesized in this review. These guidelines suggest anal cancer screening, albeit unproven, may be beneficial at decreasing the incidence of anal cancer. This review highlights the paucity of screening-related research and is an area of need to provide clear direction and to define standard of care for anal cancer screening in HIV-infected persons.

In vitro and in vivo antivirus activity of an anti-programmed death-ligand 1 (PD-L1 rat-bovine chimeric antibody against bovine leukemia virus infection.

Directory of Open Access Journals (Sweden)

Asami Nishimori

Full Text Available Programmed death-1 (PD-1, an immunoinhibitory receptor on T cells, is known to be involved in immune evasion through its binding to PD-ligand 1 (PD-L1 in many chronic diseases. We previously found that PD-L1 expression was upregulated in cattle infected with bovine leukemia virus (BLV and that an antibody that blocked the PD-1/PD-L1 interaction reactivated T-cell function in vitro. Therefore, this study assessed its antivirus activities in vivo. First, we inoculated the anti-bovine PD-L1 rat monoclonal antibody 4G12 into a BLV-infected cow. However, this did not induce T-cell proliferation or reduction of BLV provirus loads during the test period, and only bound to circulating IgM+ B cells until one week post-inoculation. We hypothesized that this lack of in vivo effects was due to its lower stability in cattle and so established an anti-PD-L1 rat-bovine chimeric antibody (Boch4G12. Boch4G12 was able to bind specifically with bovine PD-L1, interrupt the PD-1/PD-L1 interaction, and activate the immune response in both healthy and BLV-infected cattle in vitro. Therefore, we experimentally infected a healthy calf with BLV and inoculated it intravenously with 1 mg/kg of Boch4G12 once it reached the aleukemic (AL stage. Cultivation of peripheral blood mononuclear cells (PBMCs isolated from the tested calf indicated that the proliferation of CD4+ T cells was increased by Boch4G12 inoculation, while BLV provirus loads were significantly reduced, clearly demonstrating that this treatment induced antivirus activities. Therefore, further studies using a large number of animals are required to support its efficacy for clinical application.

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.

Bioassay guided isolation and identification of anti-inflammatory and ...

African Journals Online (AJOL)

The present study describes the anti-inflammatory, anti-microbial activity and lipophilic profile with acute toxicological studies of Urtica dioica. Successive extraction of the leaves with organic solvents of increasing polarity and their screening for anti-inflammatory and anti-microbial activity was assessed. Hexane extract ...

IgA deficiency evidence after anti-TNF-α treatment in a psoriatic arthritis patient: case report

Directory of Open Access Journals (Sweden)

R. Scarpa

2012-03-01

Full Text Available It is known that the use of anti-TNF-α drugs is related to an increased incidence of infective diseases. This therapy can not be administered to patients having active infections and it has to be considered with caution in case of acquired or congenital immunodeficiency diseases. We report the case of a 28-years-old man affected by psoriatic arthritis; he developed some infections during treatment with TNF-α blockers. The infections were caused by a selective IgA deficiency, that was not evident before the anti-TNF-α blockers administration and disappeared after withdrawing the biological therapy. This case-report draws our attention to the possibility of cases of subclinical immunodeficiency, unknown by the patients, but important in the prognosis and in the therapeutic approach to these diseases. Therefore, it is important to evaluate carefully the immunologic status of patients during the pre-therapeutic screening for TNF-α blocking therapy.

Evidence-based screening for low bone mineral density in HIV-infected men.

Science.gov (United States)

Albright, Patsi; Du, Ping; Haas, Richard E; Pugh, Linda C

2014-01-01

Low bone mineral density, which leads to osteoporosis and fracture risk, is an emerging clinical problem in HIV-infected patients. Our evidence-based practice project screened a convenience sample of 225 HIV-infected men for low bone mineral density using the Osteoporosis Self-Assessment Tool, and of those men, 173 were also screened by quantitative ultrasound of the calcaneus. One hundred twelve men had low bone mineral density by either or both screening methods. Seventy-one of these 112 men were tested by dual-energy x-ray absorptiometry and 73% had low bone mineral density. The positive protective value of the Osteoporosis Self-Assessment Tool was 73% and for quantitative ultrasound was 88%. These results suggest that routine low bone mineral density screening should be included as standard practice for all HIV-infected patients. Copyright © 2014 Association of Nurses in AIDS Care. Published by Elsevier Inc. All rights reserved.

Low prevalence of hepatitis B and C among tuberculosis patients in Duhok Province, Kurdistan: Are HBsAg and anti-HCV prerequisite screening parameters in tuberculosis control program?

Science.gov (United States)

Merza, Muayad A; Haji, Safer M; Alsharafani, Abid Mohialdeen Hasan; Muhammed, Shivan U

2016-09-01

Viral hepatitis, particularly hepatitis B virus (HBV) and hepatitis C virus (HCV), infections and tuberculosis (TB) are a global public health concern. Co-infection with HBV or HCV among TB patients may potentiate the risk of hepatotoxicity induced by anti-TB drugs. Hence, the aim of this study was to identify the prevalence of HBV and HCV among TB patients included in the Duhok National Tuberculosis Program (NTP). The Duhok NTP Center is a specialized institution in Duhok City, Iraq, concerned with management and follow-up of TB patients. A cross-sectional study was conducted at the center between June 2015 and May 2016. All documented TB patients were analyzed on the basis of socio-demographic and other characteristics. Thereafter, all patients underwent screening for hepatitis B surface antigen (HBsAg), anti-HCV, and anti-HIV using enzyme-linked immunosorbent assay (ELISA). The results obtained were analyzed by entering the data in binary format into a Microsoft Excel spreadsheet. A p value of Kurdistan, the negative history of injection drug use, and adherence to universal infection-control measures, including vaccination for HBV. Both history of dental intervention and belonging to a Syrian population were independent risk factors for HBV/TB co-infection. Copyright © 2016 Asian-African Society for Mycobacteriology. Published by Elsevier Ltd. All rights reserved.

Bioassay-guided evaluation of anti-inflammatory and antinociceptive activities of pistachio, Pistacia vera L.

Science.gov (United States)

Orhan, I; Küpeli, E; Aslan, M; Kartal, M; Yesilada, E

2006-04-21

The ethanolic and aqueous extracts prepared from different parts of Pistacia vera L. (Anacardiaceae) as well as its oleoresin were evaluated for their in vivo anti-inflammatory and antinociceptive activities. Among the extracts screened, only the oleoresin was shown to possess a marked anti-inflammatory activity against carrageenan-induced hind paw edema model in mice without inducing any gastric damage at both 250 and 500 mg/kg doses whereas the rest of the extracts were totally inactive. While the oleoresin was found to display significant antinociceptive activity at 500 mg/kg dose, the ethanolic and aqueous extracts belonging to fruit, leaf, branch and peduncle of Pistacia vera did not exhibit any noticeable antinociception in p-benzoquinone-induced abdominal contractions in mice. Fractionation of the oleoresin indicated the n-hexane fraction to be active, which further led to recognition of some monoterpenes, mainly alpha-pinene (77.5%) by capillary gas chromatography-mass spectrometry (GC-MS) as well as the oleoresin itself. alpha-Pinene was also assessed for its antinociceptive and anti-inflammatory activities in the same manner and exerted a moderate anti-inflammatory effect at 500 mg/kg dose.

Screening for latent tuberculous infection in people living with HIV infection in Auckland, New Zealand.

Science.gov (United States)

Gow, N; Briggs, S; Nisbet, M

2017-09-01

New Zealand, which has a low incidence of tuberculosis (TB), has historically taken a risk-based approach to screening for latent tuberculous infection (LTBI) in adult people living with the human immunodeficiency virus infection (PLHIV). To evaluate LTBI screening, treatment and outcomes in an adult PLHIV population. This was a retrospective clinical record review of an initial cohort of adult PLHIV attending the Auckland City Hospital HIV clinic in 2011, and a second cohort of adult PLHIV newly attending the clinic in 2014. We analysed high-risk (born in or acquiring HIV in a high TB incidence country) and low-risk patients using descriptive statistical methods. Of the 752 patients from the initial cohort, 416 (55%) had documentation of LTBI screening, which was positive in 74 (10%): 19/461 (4%) low-risk and 55/291 (19%) high-risk patients. LTBI treatment was received in 13 low-risk and 44 high-risk patients. Of 73 patients in the second cohort, 68 (93%) were screened. LTBI screening was incomplete in our clinic, but improved between 2011 and 2014. A significant number of patients with LTBI did not originate from a high TB incidence country.

Evaluation of the HISCL Anti-Treponema pallidum Assay as a Screening Test for Syphilis

OpenAIRE

An, Jingna; Chen, Qixia; Liu, Qianqian; Rao, Chenli; Li, Dongdong; Wang, Tingting; Tao, Chuanmin; Wang, Lanlan

2015-01-01

The resurgence of syphilis in recent years has become a serious threat to public health worldwide, and the serological detection of specific antibodies against Treponema pallidum remains the most reliable method for laboratory diagnosis of syphilis. This study examined the performance of the recently launched HISCL anti-Treponema pallidum (anti-TP) assay as a screening test for syphilis in a high-volume laboratory. The HISCL anti-TP assay was tested in 300 preselected syphilis-positive sample...

In silico structure-based drug screening of novel antimycobacterial pharmacophores by DOCK-GOLD tandem screening

Directory of Open Access Journals (Sweden)

Junichi Taira

2017-01-01

Full Text Available Background: Enzymes responsible for cell wall development in Mycobacterium tuberculosis are considered as potential targets of anti-tuberculosis (TB agents. Mycobacterial cyclopropane mycolic acid synthase 1 (CmaA1 is essential for mycobacterial survival because of its critical role in synthesizing mycolic acids. Materials and Methods: We screened compounds that were capable of interacting with the mycobacterial CmaA1 active site using a virtual compound library with an in silico structure-based drug screening (SBDS. Following the selection of such compounds, their antimycobacterial activity was examined. Results: With the in silico SBDS, for which we also used DOCK-GOLD programs and screening methods that utilized the structural similarity between the selected active compounds, we identified two compounds with potent inhibitory effects on mycobacterial growth. The antimycobacterial effect of the compounds was comparable to that of isoniazid, which is used as a first-line anti-TB drug. Conclusion: The compounds identified through SBDS were expected to be a novel class of anti-TB pharmacophores.

Parallel screening of wild-type and drug-resistant targets for anti-resistance neuraminidase inhibitors.

Directory of Open Access Journals (Sweden)

Kai-Cheng Hsu

Full Text Available Infection with influenza virus is a major public health problem, causing serious illness and death each year. Emergence of drug-resistant influenza virus strains limits the effectiveness of drug treatment. Importantly, a dual H275Y/I223R mutation detected in the pandemic influenza A 2009 virus strain results in multidrug resistance to current neuraminidase (NA drugs. Therefore, discovery of new agents for treating multiple drug-resistant (MDR influenza virus infections is important. Here, we propose a parallel screening strategy that simultaneously screens wild-type (WT and MDR NAs, and identifies inhibitors matching the subsite characteristics of both NA-binding sites. These may maintain their potency when drug-resistant mutations arise. Initially, we analyzed the subsite of the dual H275Y/I223R NA mutant. Analysis of the site-moiety maps of NA protein structures show that the mutant subsite has a relatively small volume and is highly polar compared with the WT subsite. Moreover, the mutant subsite has a high preference for forming hydrogen-bonding interactions with polar moieties. These changes may drive multidrug resistance. Using this strategy, we identified a new inhibitor, Remazol Brilliant Blue R (RB19, an anthraquinone dye, which inhibited WT NA and MDR NA with IC(50 values of 3.4 and 4.5 µM, respectively. RB19 comprises a rigid core scaffold and a flexible chain with a large polar moiety. The former interacts with highly conserved residues, decreasing the probability of resistance. The latter forms van der Waals contacts with the WT subsite and yields hydrogen bonds with the mutant subsite by switching the orientation of its flexible side chain. Both scaffolds of RB19 are good starting points for lead optimization. The results reveal a parallel screening strategy for identifying resistance mechanisms and discovering anti-resistance neuraminidase inhibitors. We believe that this strategy may be applied to other diseases with high

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

Science.gov (United States)

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.

Anti-trypanosomal activity of cationic N-heterocyclic carbene gold(I) complexes.

Science.gov (United States)

Winter, Isabel; Lockhauserbäumer, Julia; Lallinger-Kube, Gertrud; Schobert, Rainer; Ersfeld, Klaus; Biersack, Bernhard

2017-06-01

Two gold(I) N-heterocyclic carbene complexes 1a and 1b were tested for their anti-trypanosomal activity against Trypanosoma brucei parasites. Both gold compounds exhibited excellent anti-trypanosomal activity (IC 50 =0.9-3.0nM). The effects of the gold complexes 1a and 1b on the T. b. brucei cytoskeleton were evaluated. Rapid detachment of the flagellum from the cell body occurred after treatment with the gold complexes. In addition, a quick and complete degeneration of the parasitic cytoskeleton was induced by the gold complexes, only the microtubules of the detached flagellum remained intact. Both gold compounds 1a and 1b feature selective anti-trypanosomal agents and were distinctly more active against T. b. brucei cells than against human HeLa cells. Thus, the gold complexes 1a and 1b feature promising drug candidates for the treatment of trypanosome infections such as sleeping sickness (human African Trypanosomiasis caused by Trypanosoma brucei parasites). Copyright © 2017 Elsevier B.V. All rights reserved.

Role of seminal plasma in the anti-HIV-1 activity of candidate microbicides

Directory of Open Access Journals (Sweden)

Li Yun-Yao

2006-10-01

Full Text Available Abstract Background Evaluation of microbicides for prevention of HIV-1 infection in macaque models for vaginal infection has indicated that the concentrations of active compounds needed for protection by far exceed levels sufficient for complete inhibition of infection in vitro. These experiments were done in the absence of seminal plasma (SP, a vehicle for sexual transmission of the virus. To gain insight into the possible effect of SP on the performance of selected microbicides, their anti-HIV-1 activity in the presence, and absence of SP, was determined. Methods The inhibitory activity of compounds against the X4 virus, HIV-1 IIIB, and the R5 virus, HIV-1 BaL was determined using TZM-bl indicator cells and quantitated by measuring β-galactosidase induced by infection. The virucidal properties of cellulose acetate 1,2-benzene-dicarboxylate (CAP, the only microbicide provided in water insoluble, micronized form, in the presence of SP was measured. Results The HIV-1 inhibitory activity of the polymeric microbicides, poly(naphthalene sulfonate, cellulose sulfate, carrageenan, CAP (in soluble form and polystyrene sulfonate, respectively, was considerably (range ≈ 4 to ≈ 73-fold diminished in the presence of SP (33.3%. Formulations of micronized CAP, providing an acidic buffering system even in the presence of an SP volume excess, effectively inactivated HIV-1 infectivity. Conclusion The data presented here suggest that the in vivo efficacy of polymeric microbicides, acting as HIV-1 entry inhibitors, might become at least partly compromised by the inevitable presence of SP. These possible disadvantages could be overcome by combining the respective polymers with acidic pH buffering systems (built-in for formulations of micronized CAP or with other anti-HIV-1 compounds, the activity of which is not affected by SP, e.g. reverse transcriptase and zinc finger inhibitors.

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.

Antenatal screening for hepatitis B virus in HIV-infected and ...

African Journals Online (AJOL)

Background. Despite enormous strides in preventing hepatitis B virus (HBV) infection, perinatal transmission still contributes significantly to HBV epidemiology worldwide; this could account for approximately 50% of chronically infected individuals. Objective. To assess the need for HBV screening in antenatal clinics in the ...

Filaricidal activities on Onchocerca ochengi and Loa loa, toxicity and phytochemical screening of extracts of Tragia benthami and Piper umbellatum.

Science.gov (United States)

Cho-Ngwa, Fidelis; Monya, Elvis; Azantsa, Boris K; Manfo, Faustin Pascal T; Babiaka, Smith B; Mbah, James A; Samje, Moses

2016-08-30

Onchocerciasis is the world's second leading infectious cause of blindness. Its control is currently hampered by the lack of a macrofilaricidal drug and by severe adverse events observed when the lone recommended microfilaricide, ivermectin is administered to individuals co-infected with Loa loa. Therefore, there is the need for a safe and effective macrofilaricidal drug that will be able to cure the infection and break transmission cycles, or at least, an alternative microfilaricide that does not kill L. loa microfilariae (mf). Fourteen extracts from two medicinal plants, Tragia benthami and Piper umbellatum were screened in vitro against Onchocerca ochengi parasite and L. loa mf. Activities of extracts on male worms and microfilariae were assessed by motility reduction, while MTT/Formazan assay was used to assess biochemically the death of female worms. Cytotoxicity and acute toxicity of active extracts were tested on monkey kidney cells and Balb/c mice, respectively. At 500 μg/mL, all extracts showed 100 % activity on Onchocerca ochengi males and microfilariae, while 9 showed 100 % activity on female worms. The methylene chloride extract of Piper umbellatum leaves was the most active on adult male and female worms (IC50s: 16.63 μg/mL and 35.65 μg/mL, respectively). The three most active extracts on Onchocerca ochengi females were also highly active on Loa loa microfilariae, with IC50s of 35.12 - 13.9 μg/mL. Active extracts were generally more toxic to the worms than to cells and showed no acute toxicity to Balb/c mice. Phytochemical screening revealed the presence of saponins, steroids, tannins and flavanoids in the promising extracts. These results unfold potential sources of novel anti-Onchocerca lead compounds and validate the traditional use of the plants in onchocerciasis treatment.

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

Science.gov (United States)

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.

Effect of screening for red cell antibodies, other than anti-D, to detect hemolytic disease of the fetus and newborn: a population study in the Netherlands.

Science.gov (United States)

Koelewijn, J M; Vrijkotte, T G M; van der Schoot, C E; Bonsel, G J; de Haas, M

2008-05-01

Hemolytic disease of the fetus and newborn (HDFN) is a severe disease, resulting from maternal red cell (RBC) alloantibodies directed against fetal RBCs. The effect of a first-trimester antibody screening program on the timely detection of HDFN caused by antibodies other than anti-D was evaluated. Nationwide, all women (1,002 in 305,000 consecutive pregnancies during 18 months) with alloantibodies other than anti-D, detected by a first-trimester antibody screen, were included in a prospective index-cohort study. In a parallel-coverage validation study, patients with HDFN caused by antibodies other than anti-D, that were missed by the screening program, were retrospectively identified. The prevalence of positive antibody screens at first-trimester screening was 1,232 in 100,000; the prevalence of alloantibodies other than anti-D was 328 in 100,000, of which 191 of 100,000 implied a risk for occurrence of HDFN because the father carried the antigen. Overall, severe HDFN, requiring intrauterine or postnatal (exchange) transfusions, occurred in 3.7 percent of fetuses at risk: for anti-K in 11.6 percent; anti-c in 8.5 percent; anti-E in 1.1 percent; Rh antibodies other than anti-c, anti-D, or anti-E in 3.8 percent; and for antibodies other than Rh antibodies or anti-K, in none of the fetuses at risk. All affected children, where antibodies were detected, were promptly treated and healthy at the age of 1 year. The coverage validation study showed a sensitivity of the screening program of 75 percent. Five of 8 missed cases were caused by anti-c, with delay-induced permanent damage in at least 1. First-trimester screening enables timely treatment of HDFN caused by antibodies other than anti-D, however, with a sensitivity of only 75 percent. A second screening at Week 30 of c- women will enhance the screening program. Severe HDFN, caused by antibodies other than anti-D, is associated with anti-K, anti-c, and to a lesser extent with other Rh-alloantibodies.

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

Directory of Open Access Journals (Sweden)

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.

Hemolytic disease of the fetus and newborn caused by anti-D and anti-S alloantibodies: a case report

Directory of Open Access Journals (Sweden)

Yousuf Rabeya

2012-02-01

Full Text Available Abstract Introduction Hemolytic disease of the fetus and newborn is most commonly caused by anti-D alloantibody. It is usually seen in Rhesus D (RhD-negative mothers that have been previously sensitized. We report here a case of hemolytic disease of the fetus and newborn in a newborn baby caused by anti-D and anti-S alloantibodies, born to a mother who was RhD negative, but with no previous serological evidence of RhD alloimmunization. Case presentation A one-day-old Chinese baby boy was born to a mother who was group A RhD negative. The baby was jaundiced with hyperbilirubinemia, but with no evidence of infection. His blood group was group A RhD positive, his direct Coombs' test result was positive and red cell elution studies demonstrated the presence of anti-D and anti-S alloantibodies. Investigations performed on the maternal blood during the 22 weeks of gestation showed the presence of anti-S antibodies only. Repeat investigations performed post-natally showed the presence of similar antibodies as in the newborn and an anti-D titer of 1:32 (0.25 IU/mL, which was significant. A diagnosis of hemolytic disease of the fetus and newborn secondary to anti-D and anti-S was made. The baby was treated with phototherapy and close monitoring. He was discharged well after five days of phototherapy. Conclusions This case illustrates the possibility of an anamnestic response of allo-anti-D from previous sensitization in a RhD-negative mother, or the development of anti-D in mid-trimester. Thus, it highlights the importance of thorough antenatal ABO, RhD blood grouping and antibody screening, and if necessary, antibody identification and regular monitoring of antibody screening and antibody levels for prevention or early detection of hemolytic disease of the fetus and newborn, especially in cases of mothers with clinically significant red cell alloantibody.

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

Directory of Open Access Journals (Sweden)

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

A study of anti-inflammatory and analgesic activity of new 2,4,6-trisubstituted pyrimidines.

Science.gov (United States)

Yejella, Rajendra Prasad; Atla, Srinivasa Rao

2011-01-01

Chalcone derivatives (3a-m) were prepared by condensing 4-aminoacetophenone with various substituted aromatic and hetero aromatic aldehydes according to Claisen-Schmidt condensation. These chalcones, on reaction with guanidine hydrochloride under basic alcoholic conditions gave 2,4,6-trisubstituted pyrimidines (5a-m) in quantitative yields. All the newly synthesized pyrimidines were characterized by means of IR, ¹H- and ¹³C-NMR, Electron Ionization (EI)-mass and elemental analyses and screened for anti-inflammatory and analgesic activities by in vivo. 2-amino-4-(4-aminophenyl)-6-(2,4-dichlorophenyl)pyrimidine (5b) and 2-amino-4-(4-aminophenyl)-6-(3-bromophenyl) pyrimidine (5d) were found to be the most potent anti-inflammatory and analgesic activity compared with ibuprofen, reference standard. And also it was found that compound 5b identified as lead structure among all in both the activities. Pyrimidines which showed good anti-inflammatory activity also displayed better analgesic activity.

CRISPR genetic screens to discover host-virus interactions.

Science.gov (United States)

McDougall, William M; Perreira, Jill M; Reynolds, Erin C; Brass, Abraham L

2018-04-01

Viruses impose an immense burden on human health. With the goal of treating and preventing viral infections, researchers have carried out genetic screens to improve our understanding of viral dependencies and identify potential anti-viral strategies. The emergence of CRISPR genetic screening tools has facilitated this effort by enabling host-virus screens to be undertaken in a more versatile and fidelitous manner than previously possible. Here we review the growing number of CRISPR screens which continue to increase our understanding of host-virus interactions. Copyright © 2018 Elsevier B.V. All rights reserved.

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

Directory of Open Access Journals (Sweden)

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.

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

Science.gov (United States)

2014-01-01

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

Mycobacterium tuberculosis: Active disease and latent infection in a renal transplant cohort.

Science.gov (United States)

Rafiei, Nastaran; Williams, Jackie; Mulley, William R; Trauer, James M; Jenkin, Grant A; Rogers, Benjamin A

2018-04-16

Tuberculosis (TB) is a serious opportunistic infection in renal transplant recipients associated with high mortality. Screening and treatment of latent Mycobacterium tuberculosis infection (LTBI) offers an opportunity to prevent subsequent active disease. We retrospectively reviewed the records of all adult patients who underwent renal transplantation at our centre from 2005 to 2014 to assess current screening practices, the risks for and burden of active TB. A total of 660 individuals underwent renal transplantation during this period, totalling 3647 person years of follow up. Three patients were diagnosed with active TB after renal transplant, resulting in an incidence of 82 per 100,000 person-years. Of 656 transplant recipients, 102 (15.5%) were born in high TB incidence countries and 89 (13.5%) had an interferon gamma release assay (IGRA) at any point. Individuals born in high TB risk countries had a much higher incidence of active TB (530 per 100,000 person-years). Ten individuals had positive IGRA tests, of whom two were treated for active TB, two received chemoprophylaxis and six were not treated. In the absence of formal guidelines, IGRA-based screening for LTBI was infrequently performed. Our data suggests that screening and treatment of renal transplant recipients born in high incidence countries is an important preventive measure. This article is protected by copyright. All rights reserved.

Management of Chlamydia trachomatis genital tract infection: screening and treatment challenges

Directory of Open Access Journals (Sweden)

Brandie D Taylor

2011-01-01

Full Text Available Brandie D Taylor, Catherine L HaggertyUniversity of Pittsburgh, Department of Epidemiology, Pittsburgh, PA, USAAbstract: Chlamydia trachomatis is a prevalent sexually transmitted infection that can lead to serious reproductive morbidity. Management and control of C. trachomatis is a challenge, largely due to its asymptomatic nature and our incomplete understanding of its natural history. Although chlamydia screening programs have been implemented worldwide, several countries have observed increasing rates of reported chlamydia cases. We reviewed the literature relating to the long-term complications of C. trachomatis, as well as screening strategies, treatment, and prevention strategies for reducing chlamydia in the population. Articles from 1950–2010 were identified through a Medline search using the keyword “Chlamydia trachomatis” combined with “screening”, “pelvic inflammatory disease”, “endometritis”, “salpingitis”, “infertility”, "ectopic pregnancy”, “urethritis”, “epididymitis”, “proctitis”, “prostatitis”, “reinfection”, “cost-effectiveness”, “treatment”, “vaccines”, or “prevention”. Progression of C. trachomatis varies, and recurrent infections are common. Currently, there is limited evidence on the effectiveness of chlamydia screening. Higher quality studies are needed to determine the efficacy of more frequent screening, on a broader range of sequelae, including infertility and ectopic pregnancy, in addition to pelvic inflammatory disease. Studies should focus on delineating the natural history of recurrent infections, paying particular attention to treatment failures. Furthermore, alternatives to screening, such as vaccines, should continue to be explored.Keywords: Chlamydia trachomatis, sexually transmitted disease, chlamydia screening, chlamydia treatment

Vitual screening and binding mode elucidation of curcumin analogues on Cyclooxygenase-2 using AYO_COX2_V1.1 protocol

Science.gov (United States)

Mulatsari, E.; Mumpuni, E.; Herfian, A.

2017-05-01

Curcumin is yellow colored phenolic compounds contained in Curcuma longa. Curcumin is known to have biological activities as anti-inflammatory, antiviral, antioxidant, and anti-infective agent [1]. Synthesis of curcumin analogue compounds has been done and some of them had biological activity like curcumin. In this research, the virtual screening of curcumin analogue compounds has been conducted. The purpose of this research was to determine the activity of these compounds as selective Cyclooxygenase-2inhibitors in in-silico. Binding mode elucidation was made by active and inactive representative compounds to see the interaction of the amino acids in the binding site of the compounds. This research used AYO_COX2_V.1.1, a structure-based virtual screening protocol (SBVS) that has been validated by Mumpuni E et al, 2014 [2]. AYO_COX2_V.1.1 protocol using a variety of integrated applications such as SPORES, PLANTS, BKchem, OpenBabel and PyMOL. The results of virtual screening conducted on 49 curcumin analogue compounds obtained 8 compounds with 4 active amino acid residues (GLY340, ILE503, PHE343, and PHE367) that were considered active as COX-2 inhibitor.

Screening of Lactic Acid Bacteria for Anti-Fusarium Activity and Optimization of Incubation Conditions.

Science.gov (United States)

Zhao, Hui; Vegi, Anuradha; Wolf-Hall, Charlene

2017-10-01

Anti-Fusarium activities of lactic acid bacteria (LAB) Lactobacillus plantarum 299V, L. plantarum NRRL-4496, and Lactobacillus rhamnosus VT1 were determined by a microdilution assay developed in this study against Fusarium graminearum 08/RG/BF/51. A cell-free Lactobacillus culture supernatant (CFLCS) of L. rhamnosus VT1 had the highest anti-Fusarium activity. Response surface methodology was used to optimize the incubation conditions for production of CFLCS. A Box-Behnken factorial design was used to investigate the effects of incubation time, shaking speed, and incubation temperature on the inhibition rate of CFLCS. A model equation was generated to predict the inhibition rate of CFLCS under various incubation conditions. A low probability value (0.0012) and associated F value of 25.10 suggested that the model was highly significant. A high R 2 value (0.978) indicated a very satisfactory model performance. Response surface methodology analysis suggested that an incubation temperature at 34°C, a shaking speed at 170 rpm, and an incubation time of 55 h were the best combination for production of CFLCS from L. rhamnosus VT1. Under these incubation conditions, a 10% L. rhamnosus VT1 CFLCS solution was predicted to inhibit the growth of F. graminearum by 75.6% in vitro and inhibited 83.7% of the growth in the validation experiment. Thus, the CFLCS of L. rhamnosus VT1 was an effective anti-Fusarium mixture.

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.

Highly Efficient F, Cu doped TiO2 anti-bacterial visible light active photocatalytic coatings to combat hospital-acquired infections

OpenAIRE

Nigel S. Leyland; Joanna Podporska-Carroll; John Browne; Steven J. Hinder; Brid Quilty; Suresh C. Pillai

2016-01-01

Bacterial infections are a major threat to the health of patients in healthcare facilities including hospitals. One of the major causes of patient morbidity is infection with Staphylococcus aureus. One of the the most dominant nosocomial bacteria, Methicillin Resistant Staphylococcus aureus (MRSA) have been reported to survive on hospital surfaces (e.g. privacy window glasses) for up to 5 months. None of the current anti-bacterial technology is efficient in eliminating Staphylococcus aureus. ...

Prospective use of soluble urokinase plasminogen activator receptor to screen TB co-infected with HIV patient among TB patient

Directory of Open Access Journals (Sweden)

Tri Yudani Mardining Raras

2017-10-01

Conclusion: Plasma suPAR level of TB patients co-infected with HIV showed significantly difference from that of TB-AFB(+ patients suggested its potential to screen the TB/HIV among pulmonary TB-AFB(+ patients.

Screening colonoscopy for the detection of neoplastic lesions in asymptomatic HIV-infected subjects.

Science.gov (United States)

Bini, E J; Green, B; Poles, M A

2009-08-01

Although non-AIDS defining malignancies are rapidly increasing as HIV-infected subjects live longer, little is know about the results of screening for colonic neoplasms (adenomatous polyps and adenocarcinomas) in this population. We conducted a screening colonoscopy study to determine the prevalence of colonic neoplasms in 136 asymptomatic HIV-infected subjects >or=50 years of age and 272 asymptomatic uninfected control subjects matched for age, sex, and family history of colorectal cancer. Advanced neoplasms were defined as adenomas >or=10 mm or any adenoma, regardless of size, with villous histology, high-grade dysplasia, or adenocarcinoma. The prevalence of neoplastic lesions was significantly higher in HIV-infected subjects than in control subjects (62.5% vs 41.2%, pscreening colonoscopy should be offered to HIV-infected subjects, but the age of initiation and the optimal frequency of screening require further study.

Attitudes toward newborn screening for cytomegalovirus infection.

Science.gov (United States)

Din, Erica S; Brown, Cedric J; Grosse, Scott D; Wang, Chengbin; Bialek, Stephanie R; Ross, Danielle S; Cannon, Michael J

2011-12-01

Newborns are not routinely screened for cytomegalovirus (CMV), the leading infectious cause of developmental disability. Congenital CMV satisfies a number of criteria for inclusion in newborn screening, and screening potentially offers benefits. Screening could also introduce harms such as anxiety and unnecessary costs for the families of the substantial proportion of CMV-infected children who never develop CMV-related disabilities. Our objective was to assess attitudes toward newborn screening for CMV. We analyzed responses to 5 statements about CMV and newborn screening from 3922 participants in the 2009 HealthStyles survey, a national mail survey designed to include a group similar to the US population with respect to gender, age, race/ethnicity, income, and household size. Two-step cluster analysis was performed to identify clusters of parental attitudes. The majority of respondents strongly or somewhat agreed that they would want to have their newborn tested for CMV even if it was not performed routinely (84%), they had to pay $20 (87%), or CMV-related problems never developed (84%). Nearly half (47%) of them "would worry that the CMV test would lead to unneeded doctor visits and expenses," and 32% "think CMV problems are too rare to worry about." Three clusters of parent respondents were identified on the basis of their attitudes toward CMV screening: "strongly in favor" (31%), "moderately in favor" (49%), and "weakly opposed" (20%). Among most parents, costs, worry, and anxiety associated with newborn screening for CMV would be acceptable. Although attitudes were generally favorable, a minority of the parents were weakly opposed to newborn screening for CMV.

Anti-fibrinolytic and anti-microbial activities of a serine protease inhibitor from honeybee (Apis cerana) venom.

Science.gov (United States)

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

2017-10-01

Bee venom contains a variety of peptide constituents, including low-molecular-weight protease inhibitors. While the putative low-molecular-weight serine protease inhibitor Api m 6 containing a trypsin inhibitor-like cysteine-rich domain was identified from honeybee (Apis mellifera) venom, no anti-fibrinolytic or anti-microbial roles for this inhibitor have been elucidated. In this study, we identified an Asiatic honeybee (A. cerana) venom serine protease inhibitor (AcVSPI) that was shown to act as a microbial serine protease inhibitor and plasmin inhibitor. AcVSPI was found to consist of a trypsin inhibitor-like domain that displays ten cysteine residues. Interestingly, the AcVSPI peptide sequence exhibited high similarity to the putative low-molecular-weight serine protease inhibitor Api m 6, which suggests that AcVSPI is an allergen Api m 6-like peptide. Recombinant AcVSPI was expressed in baculovirus-infected insect cells, and it demonstrated inhibitory activity against trypsin, but not chymotrypsin. Additionally, AcVSPI has inhibitory effects against plasmin and microbial serine proteases; however, it does not have any detectable inhibitory effects on thrombin or elastase. Consistent with these inhibitory effects, AcVSPI inhibited the plasmin-mediated degradation of fibrin to fibrin degradation products. AcVSPI also bound to bacterial and fungal surfaces and exhibited anti-microbial activity against fungi as well as gram-positive and gram-negative bacteria. These findings demonstrate the anti-fibrinolytic and anti-microbial roles of AcVSPI as a serine protease inhibitor. Copyright © 2017 Elsevier Inc. All rights reserved.

Autoantibodies and human immunodeficiency viruses infection: a case-control study.

Science.gov (United States)

Chretien, P; Monier, J C; Oksman, F; San Marco, M; Escande, A; Goetz, J; Cohen, J; Baquey, A; Humbel, R L; Sibilia, J

2003-01-01

To determine the prevalence of organ-specific and non-specific autoantibodies in HIV-infected patients. A multicentric collaborative case-control study including 105 HIV patients and 100 sex- and age-matched HIV-negative healthy volunteers. Antinuclear, anti-ds DNA, anti-histone, anti-Sm, rheumatoid factor(IgM), anti-beta 2 glycoprotein 1, antineutrophil cytoplasmic, anti-LKM1, anti-LCA1, anti-gastric parietal cell, antiplatelet, anti-intermediate filament, anti-mitotic spindle apparatus, anti-Golgi, anti-ribosome and anti-thyroid autoantibodies were screened in six European laboratories. Only IgG and IgM anticardiolipin, IgG antiplatelet, anti-smooth muscle and anti-thyroglobulin antibodies were statistically more frequent in HIV patients. There was no correlation with the numbers of CD4+ cells except in the case of anti-smooth muscle antibodies. We were unable to find specific autoantibodies such as anti-ds DNA, anti-Sm, AMA, anti-LKM1, anti-LCA1 or anti-beta 2 GP1 antibodies in these patients. Our results indicate that the autoantibody profile of HIV infections is comparable to those of other chronic viral infections. HIV does not seem to be more autoimmunogenic than other viruses.

Anemia as a complication of parvovirus b19 infection in renal transplant recipients.

Science.gov (United States)

Čapenko, Svetlana; Kozireva, Svetlana; Folkmane, Inese; Bernarde, Kristīna; Rozentāls, Rafails; Murovska, Modra

2012-01-01

The frequency of B19 infection in renal transplant donors and recipients was studied to determine the significance of active viral infection in the development of anemia. Serum, plasma, and peripheral blood leukocyte samples of 47 renal transplant donors, 38 recipients with anemia (Group 1), and 25 without anemia (Group 2) after renal transplantation were evaluated for the presence of anti-B19 specific antibodies (ELISA) and B19 DNA (nPCR). Active persistent B19 infection after renal transplantation was detected in 12 of the 38 in the Group 1 (10 had reactivation and 2 primary infection), and none of the recipients in the Group 2 had it. Of the 12 recipients in the Group 1, 10 were seropositive and 2 seronegative before renal transplantation; 10 received the transplants from the seropositive and 2 from seronegative donors. rHuEPO therapy-resistant severe anemia was detected only in the recipients with active B19 infection after renal transplantation in the Group 1 (7/12). The logistic regression analysis revealed a significant relationship between active B19 infection and severe anemia (OR, 0.039; 95% CI, 0.006-0.257; P=0.001). Active B19 infection was documented only in the anemic recipients and could be associated with the development of severe anemia after renal transplantation. This allows us to recommend concurrent screening for viral DNA in plasma and detection of anti-B19 IgM class antibodies. To find the association between B19 infection and the development of anemia, further investigations are necessary.

No association of oral lichen planus and hepatitis C virus infection in central Germany.

Science.gov (United States)

Remmerbach, Torsten W; Liese, Jan; Krause, Sarah; Schiefke, Ingolf; Schiefke, Franziska; Maier, Melanie; Liebert, Uwe G

2016-01-01

Co-occurrence of oral lichen planus (OLP) and chronic hepatitis C virus (HCV) infection suggests a strong association, but the relation between mucocutaneus, autoimmune lichen planus and HCV infection remains unclear. In areas with higher prevalence of HCV infection in general population, like Japan and southern Europe, 20 to 40 % of patients with OLP test positive for anti-HCV antibodies, whereas in German populations, a co-occurrence of 4.2 to 16 % was reported. We screened 143 patients with histopathologically proven OLP for prevalence of anti-HCV antibodies. Additionally, we examined 51 anti-HCV-positive subjects with current or past HCV infection for clinical symptoms of OLP. In all patients, confirmatory diagnosis was made by the detection of HCV RNA via reverse transcription-polymerase chain reaction (RT-PCR). A randomized control group comprised 109 blood sera samples of patients without any characteristics of OLP. The results of all patients showed no co-occurrence in either cohort. In conclusion, no association between oral lichen planus and chronic HCV infection in our study population was found. Anti-HCV antibody screening in patients with confirmed oral lichen planus is not indicated routinely in central Germany.

Identification of KX2-391 as an inhibitor of HBV transcription by a recombinant HBV-based screening assay.

Science.gov (United States)

Harada, Keisuke; Nishitsuji, Hironori; Ujino, Saneyuki; Shimotohno, Kunitada

2017-08-01

Antiviral therapies for chronic hepatitis B virus (HBV) infection that are currently applicable for clinical use are limited to nucleos(t)ide analogs targeting HBV polymerase activity and pegylated interferon alpha (PEG-IFN). Towards establishing an effective therapy for HBV related diseases, it is important to develop a new anti-HBV agent that suppresses and eradicates HBV. This study used recombinant HBV encoding NanoLuc to screen anti-HBV compounds from 1827 US Food and Drug Administration approved compounds and identified several compounds that suppressed HBV infection. Among them, KX2-391, a non-ATP-competitive inhibitor of SRC kinase and tubulin polymerization, was identified as a lead candidate for an anti-HBV drug. Treatment of sodium taurocholate cotransporting polypeptide (NTCP) transduced-HepG2 (HepG2-NTCP) or primary human hepatocytes with KX2-391 suppressed HBV replication in a dose-dependent manner. The anti-HBV activity of KX2-391 appeared not to depend on SRC kinase activity because siRNA for SRC mRNA did not impair the HBV infection/replication. The anti-HBV activity of KX2-391 depended on the inhibitory effect of tubulin polymerization similar to other tubulin polymerization inhibitors, some of which were shown to inhibit HBV replication. KX2-391 inhibited HBV transcription driven by a HBV precore promoter in an HBV X protein-independent manner but did not inhibit the activity of HBV-S1, -S2, -X or cytomegalovirus promoters. Treatment with KX2-391 reduced the expression of several various factors including hepatocyte nuclear factor-4a. Copyright © 2017 Elsevier B.V. All rights reserved.

Does erythrocyte sedimentation rate reflect and discriminate flare from infection in systemic lupus erythematosus? Correlation with clinical and laboratory parameters of disease activity.

Science.gov (United States)

Schäfer, Valentin Sebastian; Weiß, Katharina; Krause, Andreas; Schmidt, Wolfgang Andreas

2018-07-01

To examine disease activity parameters in patients with systemic lupus erythematosus (SLE) experiencing flare, infection, both, or neither condition, focusing on erythrocyte sedimentation rate (ESR). This study is a retrospective analysis of 371 consecutive inpatient SLE cases from 2006 to 2015. Cases were classified as flare (n = 147), infection (n = 48), both (n = 23), or neither (n = 135). ESR levels were correlated to C-reactive protein (CRP), ferritin, anti-dsDNA antibodies, complement C3 reduction, serositis, and erythrocyturia with proteinuria (Pearson's correlation). ESR levels were related to an age- and gender-adapted cut-off value (ESRp). We analyzed mean values of age, ESR, ESRp, CRP, ferritin and distribution of anti-dsDNA antibodies, C3 reduction, serositis, and erythrocyturia with proteinuria. Sensitivity and specificity were calculated via receiver operating characteristic or two-by-two table. Association of parameters with disease activity and infection was tested via two-sided chi square test. ESR correlated moderately with CRP in cases with flare and/or infection (r = 0.505-0.586). While ESR and CRP were normal in remission, mean values overlapped in cases with flare, infection, or both. ESRp was higher in flare than in infection (p = 0.048). ESR lost association to activity in infected cases, CRP to infection in flaring cases. ESRp, serositis, and anti-dsDNA antibodies were related to disease activity regardless of infections. Anti-dsDNA antibodies were most sensitive for detecting flares (74%), while serositis, proteinuria with erythrocyturia, anti-dsDNA antibodies, C3 reduction, and ESRp values ≥ 2 were most specific. ESR levels were raised by flares, infections, and age; adapting them to age and gender increased their diagnostic value. Obtaining several parameters remains necessary to differentiate flare from infection.

Screening of six Ayurvedic medicinal plants for anti-obesity potential: An investigation on bioactive constituents from Oroxylum indicum (L.) Kurz bark.

Science.gov (United States)

Mangal, Priyanka; Khare, Pragyanshu; Jagtap, Sneha; Bishnoi, Mahendra; Kondepudi, Kanthi Kiran; Bhutani, Kamlesh Kumar

2017-02-02

As an effort to identify newer anti-obesity lead(s) we have selected 13 plant materials from the six plant species which have been reported in Indian Ayurvedic medicine as remedy against complications affecting glucose and lipid homeostasis. In vitro screening of six Indian Ayurvedic medicinal plants on anti-adipogenic and pancreatic lipase (PL) inhibition potential followed by bioactivity guided isolation from most active plant material. In vitro anti-adipogenic assay using 3T3-L1 preadipocytes and pancreatic lipase (PL) inhibition assay were performed for hexanes, dichloromethane, ethyl acetate and methanolic extracts of all the plant materials. Bioactivity guided isolation approach was used to identify active constituent for anti-adipogenesis and PL inhibition assay. Inhibition of lipid accumulation and adipogenic transcription factor was measured by oil Red 'O' staining and quantitative real-time PCR method respectively. Ethyl acetate extract of Oroxylum indicum bark was found to be most active in screening of anti-adipogenesis (59.12±1.66% lipid accumulation as compared to control at 50μg/mL dose) and PL inhibition (89.12±6.87% PL inhibition at 250μg/mL dose) assays. Further, three bioactive flavonoids were isolated and identified as oroxylin A, chrysin and baicalein from O. indicum bark. Oroxylin A, chrysin, and baicalein were inhibited lipid accumulation in 3T3-L1 preadipocytes (75.00±5.76%, 70.21±4.23% and 77.21±5.49% lipid accumulation respectively in comparison to control at 50μM dose) and PL enzyme (69.86±2.96%, 52.08±2.14% and 45.06±2.42% PL inhibition respectively at 250μg/mL dose). In addition, oroxylin A and chrysin also inhibited PPARγ and C/EBPα, major adipogenic transcription factors, in 3T3L-1 preadipocytes during adipogenesis process at 50μM dose. The present study augurs the anti-obesity potential of well practiced Ayurvedic herb O. indicum and its flavonoids. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Altertoxins with potent anti-HIV activity from Alternaria tenuissima QUE1Se, a fungal endophyte of Quercus emoryi

OpenAIRE

Bashyal, Bharat P.; Wellensiek, Brian P.; Ramakrishnan, Rajesh; Faeth, Stanley H.; Ahmad, Nafees; Leslie Gunatilaka, A. A.

2014-01-01

Screening of a small library of natural product extracts derived from endophytic fungi of the Sonoran desert plants in a cell-based anti-HIV assay involving T-cells infected with the HIV-1 virus identified the EtOAc extract of a fermentation broth of Alternaria tenuissima QUE1Se inhabiting the stem tissue of Quercus emoryi as a promising candidate for further investigation. Bioactivity-guided fractionation of this extract led to the isolation and identification of two new metabolites, alterto...

Anti-trypanosomal activity of pentacyclic triterpenes isolated from Austroplenckia populnea (Celastraceae Atividade anti-tripanosomicida de triterpenes pentacíclicos isolados de Austroplenckia populnea (Celastraceae

Directory of Open Access Journals (Sweden)

Lucienir Pains DUARTE

2002-04-01

Full Text Available Four pentacyclic triterpenes isolated from Austroplenckia populnea and four compounds of known anti T. cruzi or anti-malarial activity were tested. Of those triterpenes tested 20alpha-hydroxy-tingenone showed high activity, epikatonic acid was less active, while populnilic and populninic acids were inactive against the trypanosome of the subgenus Schizotrypanum tested. Benzonidazole, nifurtimox, ketoconazole and primaquine presented a remarkable dose-dependent inhibitory effect reaching practically to a total growth inhibition of the parasite at the end of incubation time. The trypanosome tested appear to be a suitable model for preliminary screen for anti T. (S. cruzi compounds.Foram testados quatro triterpenos pentacíclicos isolados de Austroplenckia populnea e quatro compostos de conhecida atividade anti-T. cruzi ou anti-malárica. Dos triterpenos testados 20alfa-hidroxi-tingenona mostrou atividade elevada, ácido epicatônico foi menos ativo, enquanto ácido populnílico e populnínico foram inativos contra o tripanossoma do subgênero Schizotrypanum testado. Benzonidazole, nifurtimox, cetoconazole e primaquina apresentaram efeito inibitório dose-dependente atingindo praticamente a inibição total do crescimento do parasita no final do tempo de incubação. O tripanossoma testado mostrou ser um modelo adequado para uma seleção preliminar de compostos anti. T. (S. cruzi.

Search for Anti-EA(D Antibodies in Subjects with an “Isolated VCA IgG” Pattern

Directory of Open Access Journals (Sweden)

Massimo De Paschale

2010-01-01

Full Text Available The presence of an “isolated viral capsid antigen (VCA IgG” pattern in serum is not easy to interpret without the aid of further tests, such as specific immunoblotting or a virus genome search, that often give rise to organisational and economic problems. However, one alternative is to use an enzyme-linked immunosorbent assay (ELISA to detect anti-early antigen (EA antibodies, which can be found in about 85% of subjects with acute Epstein-Barr virus (EBV infections. The purpose of this work was to search for anti-EA(D antibodies in 130 samples with an isolated VCA IgG pattern at ELISA screening and classified as being indicative of past (102 cases or acute (28 cases infection on the basis of the immunoblotting results. Thirty-seven samples (28.5% were positive for anti-EA(D, of which 25 (89.3% had been classified by immunoblotting as indicating acute and 12 (11.8% past EBV infection. This difference was statistically significant (<.01. The results of our search for anti-EA(D antibodies correctly identified nearly 90% of acute (presence or past EBV infections (absence. When other tests are not available, the search for anti-EA antibodies may therefore be helpful in diagnosing patients with an isolated VCA IgG pattern at screening tests.

Phytochemical Analysis and Antimicrobial, Antinociceptive, and Anti-Inflammatory Activities of Two Chemotypes of Pimenta pseudocaryophyllus (Myrtaceae

Directory of Open Access Journals (Sweden)

Joelma Abadia Marciano de Paula

2012-01-01

Full Text Available Preparations from Pimenta pseudocaryophyllus (Gomes L.R. Landrum (Myrtaceae have been widely used in Brazilian folk medicine. This study aims to evaluate the antimicrobial activity of the crude ethanol extracts, fractions, semipurified substances, and essential oils obtained from leaves of two chemotypes of P. pseudocaryophyllus and to perform the antinociceptive and anti-inflammatory screening. The ethanol extracts were purified by column chromatography and main compounds were spectrally characterised (1D and 2D 1H and 13C NMR. The essential oils constituents were identified by GC/MS. The broth microdilution method was used for testing the antimicrobial activity. The abdominal contortions induced by acetic acid and the ear oedema induced by croton oil were used for screening of antinociceptive and anti-inflammatory activities, respectively. The phytochemical analysis resulted in the isolation of pentacyclic triterpenes, flavonoids, and phenol acids. The oleanolic acid showed the best profile of antibacterial activity for Gram-positive bacteria (31.2–125 μg mL−1, followed by the essential oil of the citral chemotype (62.5–250 μg mL−1. Among the semipurified substances, Ppm5, which contained gallic acid, was the most active for Candida spp. (31.2 μg mL−1 and Cryptococcus spp. (3.9–15.6 μg mL−1. The crude ethanol extract and fractions from citral chemotype showed antinociceptive and anti-inflammatory effects.

Transfusion Related Hepatitis C Virus (HCV) Infection in Sickle Cell ...

African Journals Online (AJOL)

Rev Olaleye

ABSTRACT: This study aimed to determine retrospectively, the prevalence of hepatitis C virus infection in relation to a background history of blood transfusion; through anti HCV antibody screening test, amongst adult sickle cell disease patients. Anti HCV antibody was tested for in the serum of 92 consecutively selected ...

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.

Porritoxins, metabolites of Alternaria porri, as anti-tumor-promoting active compounds.

Science.gov (United States)

Horiuchi, Masayuki; Tokuda, Harukuni; Ohnishi, Keiichiro; Yamashita, Masakazu; Nishino, Hoyoku; Maoka, Takashi

2006-02-01

To search for possible cancer chemopreventive agents from natural sources, we performed primary screening of metabolites of Alternaria porri by examining their possible inhibitory effects on Epstein-Barr virus early antigen (EBV-EA) activation induced by 12-O-tetradecanoylphorbol-13-acetate (TPA) in Raji cells. The ethyl acetate extract of A. porri showed the inhibitory effect on EBV-EA activation. Three porritoxins (1-3) were obtained as inhibitory active compounds for EBV-EA from ethyl acetate extract. 6-(3',3'-Dimethylallyloxy)-4-methoxy-5-methylphthalide (2) showed the strongest activity among them. Inhibitory effect of porritoxin (1) and (2) was superior to that of beta-carotene, a well-known anti-tumor promoter. Furthermore, the structure-activity correlation of porritoxins and their related compounds were discussed.

Innovative Approaches to Improve Anti-Infective Vaccine Efficacy.

Science.gov (United States)

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.

Viral load in children with congenital cytomegalovirus infection identified on newborn hearing screening.

Science.gov (United States)

Kawada, Jun-ichi; Torii, Yuka; Kawano, Yoshihiko; Suzuki, Michio; Kamiya, Yasuko; Kotani, Tomomi; Kikkawa, Fumitaka; Kimura, Hiroshi; Ito, Yoshinori

2015-04-01

Congenital cytomegalovirus (CMV) infection is the most common non-genetic cause of sensorineural hearing loss (SNHL) in children. However, congenital SNHL without other clinical abnormalities is rarely diagnosed as CMV-related in early infancy. The aim of this study was to identify and treat patients with congenital CMV-related SNHL or CMV-related clinical abnormalities other than SNHL. The association between CMV load and SNHL was also evaluated. Newborns who had abnormal hearing screening results or other clinical abnormalities were screened for congenital CMV infection by PCR of saliva or urine specimens, and identified infected patients were treated with valganciclovir (VGCV) for 6 weeks. The CMV load of patients with or without SNHL was compared at regular intervals during as well as after VGCV treatment. Of 127 infants with abnormal hearing screening results, and 31 infants with other clinical abnormalities, CMV infection was identified in 6 and 3 infants, respectively. After VGCV treatment, 1 case had improved hearing but the other 5 SNHL cases had little or no improvement. Among these 9 patients with or without SNHL at 1 year of age, there was no significant difference in CMV blood or urine load at diagnosis, but both were significantly higher in patients with SNHL during VGCV treatment. Selective CMV screening of newborns having an abnormal hearing screening result would be a reasonable strategy for identification of symptomatic congenital CMV infection. Prolonged detection of CMV in blood could be a risk factor for SNHL. Copyright © 2015 Elsevier B.V. All rights reserved.

High-throughput screen of drug repurposing library identifies inhibitors of Sarcocystis neurona growth

Directory of Open Access Journals (Sweden)

Gregory D. Bowden

2018-04-01

Full Text Available The apicomplexan parasite Sarcocystis neurona is the primary etiologic agent of equine protozoal myeloencephalitis (EPM, a serious neurologic disease of horses. Many horses in the U.S. are at risk of developing EPM; approximately 50% of all horses in the U.S. have been exposed to S. neurona and treatments for EPM are 60–70% effective. Advancement of treatment requires new technology to identify new drugs for EPM. To address this critical need, we developed, validated, and implemented a high-throughput screen to test 725 FDA-approved compounds from the NIH clinical collections library for anti-S. neurona activity. Our screen identified 18 compounds with confirmed inhibitory activity against S. neurona growth, including compounds active in the nM concentration range. Many identified inhibitory compounds have well-defined mechanisms of action, making them useful tools to study parasite biology in addition to being potential therapeutic agents. In comparing the activity of inhibitory compounds identified by our screen to that of other screens against other apicomplexan parasites, we found that most compounds (15/18; 83% have activity against one or more related apicomplexans. Interestingly, nearly half (44%; 8/18 of the inhibitory compounds have reported activity against dopamine receptors. We also found that dantrolene, a compound already formulated for horses with a peak plasma concentration of 37.8 ± 12.8 ng/ml after 500 mg dose, inhibits S. neurona parasites at low concentrations (0.065 μM [0.036–0.12; 95% CI] or 21.9 ng/ml [12.1–40.3; 95% CI]. These studies demonstrate the use of a new tool for discovering new chemotherapeutic agents for EPM and potentially providing new reagents to elucidate biologic pathways required for successful S. neurona infection. Keywords: Drug repurposing, High-throughput screen, Sarcocystis neurona, Equine protozoal myeloencephalitis

Medicinal plants and their isolated compounds showing anti-Trichomonas vaginalis- activity.

Science.gov (United States)

Mehriardestani, Mozhgan; Aliahmadi, Atousa; Toliat, Tayebeh; Rahimi, Roja

2017-04-01

Trichomonas vaginalis is a major of non-viral sexually-transmitted infection and an important cause of serious obstetrical and gynecological complications. Treatment options for trichomoniasis are limited to nitroimidazole compounds. The increasing resistance and allergic reactions to nitroimidazole and recurrent trichomoniasis make it essential to identify and develop new drugs against trichomoniasis. Medicinal plants are an important source for discovery of new medications. This review discusses the anti-trichomonas effects of medicinal plants and their chemical constituents to find better options against this pathogenic protozoon. Electronic databases were searched to collect all data from the year 2000 through September 2015 for in vitro, in vivo and clinical studies on the effect of medicinal plants on T. vaginalis. A total of 95 in vitro and clinical studies were identified. Only four human studies were found in this review. The Asteracea, Lamiaceae and Myrtaceae families contained the greatest number of plants with anti-trichomonas activity. Persea americana, Ocimum basilicum and Verbascum thapsus were the most efficacious against T. vaginalis. Plant metabolites containing alkaloids, isoflavonoid glucosides, essential oils, lipids, saponins and sesquiterpene lactones were found to possess anti-trichomonas properties. Assessing the structure-activity of highly-potent anti-trichomonas phytochemicals is suggested for finding natural, semisynthetic and synthetic anti-trichomonas compounds. Further clinical studies are necessary for confirmation of natural anti-trichomonas substances and completion of their safety profiles. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

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.

Assessment of Anti HSV-1 Activity of Aloe Vera Gel Extract: an In Vitro Study

Science.gov (United States)

Rezazadeh, Fahimeh; Moshaverinia, Maryam; Motamedifar, Mohammad; Alyaseri, Montazer

2016-01-01

Statement of the Problem Herpes simplex virus (HSV) infection is one of the most common and debilitating oral diseases; yet, there is no standard topical treatment to control it. The extract of Aloe vera leaves has been previously reported to have anti-inflammatory, antibacterial, and also antiviral effects. There is no data on anti-Herpes simplex virus type 1 (HSV-1) activity of Aloe vera gel. Purpose This study aimed to evaluate the anti-HSV-1 activity of Aloe vera gel in Vero cell line. Materials and Method In this study, gel extraction and cytotoxicity of various increasing concentrations of Aloe vera gel (0.2, 0.5, 1, 2, and 5%) was evaluated in Dulbecco’s Modified Eagle Medium (DMEM) containing 2% fetal bovine serum (FBS). Having been washed with phosphate buffered saline, 50 plaque-forming units (PFU) of HSV-1 was added to each well. After 1 hour of incubation at 37°C, cell monolayers in 24 well plates were exposed to different increasing concentrations of Aloe vera gel. The anti-HSV-1 activity of Aloe vera gel in different concentrations was assessed by plaque reduction assays. Data were analyzed by using One-way ANOVA. Results The cytotoxicity assay showed that Aloe vera in prearranged concentrations was cell-compatible. The inhibitory effect of various concentrations of Aloe vera was observed one hour after the Vero cell was infected with HSV-1. However, there was no significant difference between two serial concentrations (p> 0.05). One-way ANOVA also revealed no significant difference between the groups. The findings indicated a dose-dependent antiviral effect of Aloe vera. Conclusion The findings showed significant inhibitory effect of 0.2-5% Aloe vera gel on HSV-1 growth in Vero cell line. Therefore, this gel could be a useful topical treatment for oral HSV-1 infections without any significant toxicity. PMID:26966709

Cost effectiveness of screening strategies for early identification of HIV and HCV infection in injection drug users.

Directory of Open Access Journals (Sweden)

Lauren E Cipriano

Full Text Available To estimate the cost, effectiveness, and cost effectiveness of HIV and HCV screening of injection drug users (IDUs in opioid replacement therapy (ORT.Dynamic compartmental model of HIV and HCV in a population of IDUs and non-IDUs for a representative U.S. urban center with 2.5 million adults (age 15-59.We considered strategies of screening individuals in ORT for HIV, HCV, or both infections by antibody or antibody and viral RNA testing. We evaluated one-time and repeat screening at intervals from annually to once every 3 months. We calculated the number of HIV and HCV infections, quality-adjusted life years (QALYs, costs, and incremental cost-effectiveness ratios (ICERs.Adding HIV and HCV viral RNA testing to antibody testing averts 14.8-30.3 HIV and 3.7-7.7 HCV infections in a screened population of 26,100 IDUs entering ORT over 20 years, depending on screening frequency. Screening for HIV antibodies every 6 months costs $30,700/QALY gained. Screening for HIV antibodies and viral RNA every 6 months has an ICER of $65,900/QALY gained. Strategies including HCV testing have ICERs exceeding $100,000/QALY gained unless awareness of HCV-infection status results in a substantial reduction in needle-sharing behavior.Although annual screening for antibodies to HIV and HCV is modestly cost effective compared to no screening, more frequent screening for HIV provides additional benefit at less cost. Screening individuals in ORT every 3-6 months for HIV infection using both antibody and viral RNA technologies and initiating ART for acute HIV infection appears cost effective.

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

Directory of Open Access Journals (Sweden)

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.

Anti-inflammatory and anti-oxidant activities of Secamone afzelii ...

African Journals Online (AJOL)

. This study re-ports the anti-inflammatory and antioxidant properties of S. afzelii. The anti-inflammatory activity was determined by the carrageenan-induced paw oedema method in 7 day old chicks and antioxi-dant property by the 2 ...

Anti-acetylcholinesterase activity and antioxidant properties of extracts and fractions of Carpolobia lutea.

Science.gov (United States)

Nwidu, Lucky Legbosi; Elmorsy, Ekramy; Thornton, Jack; Wijamunige, Buddhika; Wijesekara, Anusha; Tarbox, Rebecca; Warren, Averil; Carter, Wayne Grant

2017-12-01

There is an unmet need to discover new treatments for Alzheimer's disease. This study determined the anti-acetylcholinesterase (AChE) activity, DPPH free radical scavenging and antioxidant properties of Carpolobia lutea G. Don (Polygalaceae). The objective of this study is to quantify C. lutea anti-AChE, DPPH free radical scavenging, and antioxidant activities and cell cytotoxicity. Plant stem, leaves and roots were subjected to sequential solvent extractions, and screened for anti-AChE activity across a concentration range of 0.02-200 μg/mL. Plant DPPH radical scavenging activity, reducing power, and total phenolic and flavonoid contents were determined, and cytotoxicity evaluated using human hepatocytes. Carpolobia lutea exhibited concentration-dependent anti-AChE activity. The most potent inhibitory activity for the stem was the crude ethanol extract and hexane stem fraction oil (IC 50  = 140 μg/mL); for the leaves, the chloroform leaf fraction (IC 50  = 60 μg/mL); and for roots, the methanol, ethyl acetate and aqueous root fractions (IC 50  = 0.3-3 μg/mL). Dose-dependent free radical scavenging activity and reducing power were observed with increasing stem, leaf or root concentration. Total phenolic contents were the highest in the stem: ∼632 mg gallic acid equivalents/g for a hexane stem fraction oil. Total flavonoid content was the highest in the leaves: ∼297 mg quercetin equivalents/g for a chloroform leaf fraction. At 1 μg/mL, only the crude ethanol extract oil was significantly cytotoxic to hepatocytes. Carpolobia lutea possesses anti-AChE activity and beneficial antioxidant capacity indicative of its potential development as a treatment of Alzheimer's and other diseases characterized by a cholinergic deficit.

In vivo neutralization of hepatitis B virus infection by an anti-preS1 humanized antibody in chimpanzees

International Nuclear Information System (INIS)

Hong, Hyo Jeong; Ryu, Chun Jeih; Hur, Hyangsuk; Kim, Seho; Oh, Han Kyu; Oh, Mee Sook; Park, Song Yong

2004-01-01

Previously, we generated a murine monoclonal antibody (mAb), KR127, that recognizes amino acids (aa) 37-45 of the preS1 of hepatitis B virus (HBV). In this study, we have constructed a humanized version of KR127 and evaluated its HBV-neutralizing activity in chimpanzees. A study chimpanzee was given a single intravenous dose of the humanized antibody, followed by intravenous challenge with adr subtype of wild type HBV, while a control chimpanzee was only challenged with the virus. The result showed that the study chimpanzee did not develop HBV infection during 1 year, while the control chimpanzee was infected, indicating that the humanized antibody exhibited in vivo virus-neutralizing activity and thus protected the chimpanzee from HBV infection. In addition, the humanized antibody bound to the preS1 of all subtypes of HBV. We first demonstrate that an anti-preS1 mAb can neutralize HBV infection in vivo. This humanized antibody will be useful for the immunoprophylaxis of HBV infection

In-silico screening for anti-Zika virus phytochemicals.

Science.gov (United States)

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.

[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.

Novel curcumin analogue 14p protects against myocardial ischemia reperfusion injury through Nrf2-activating anti-oxidative activity

Energy Technology Data Exchange (ETDEWEB)

Li, Weixin [Department of Cardiology, The 5th Affiliated Hospital of Wenzhou Medical University, Lishui, Zhejiang (China); Chemical Biology Research Center, School of Pharmaceutical Science, Wenzhou Medical University, Wenzhou, Zhejiang (China); Wu, Mingchai [Department of Pharmacy, The Third Affiliated Hospital of Wenzhou Medical University, Wenzou, Zhejiang (China); Tang, Longguang; Pan, Yong; Liu, Zhiguo [Chemical Biology Research Center, School of Pharmaceutical Science, Wenzhou Medical University, Wenzhou, Zhejiang (China); Zeng, Chunlai [Department of Cardiology, The 5th Affiliated Hospital of Wenzhou Medical University, Lishui, Zhejiang (China); Wang, Jingying [Chemical Biology Research Center, School of Pharmaceutical Science, Wenzhou Medical University, Wenzhou, Zhejiang (China); Wei, Tiemin, E-mail: lswtm@sina.com [Department of Cardiology, The 5th Affiliated Hospital of Wenzhou Medical University, Lishui, Zhejiang (China); Liang, Guang, E-mail: wzmcliangguang@163.com [Chemical Biology Research Center, School of Pharmaceutical Science, Wenzhou Medical University, Wenzhou, Zhejiang (China)

2015-01-15

Background: Alleviating the oxidant stress associated with myocardial ischemia reperfusion has been demonstrated as a potential therapeutic approach to limit ischemia reperfusion (I/R)-induced cardiac damage. Curcumin, a natural compound with anti-oxidative activity, exerts beneficial effect against cardiac I/R injury, but poor chemical and metabolic stability. Previously, we have designed and synthesized a series of mono-carbonyl analogues of curcumin (MACs) with high stability. This study aims to find new anti-oxidant MACs and to demonstrate their effects and mechanisms against I/R-induced heart injury. Methods: H9c2 cells challenged with H{sub 2}O{sub 2} or TBHP were used for in vitro bio-screening and mechanistic studies. The MDA, H{sub 2}O{sub 2} and SOD levels in H9C2 cells were determined, and the cell viability was assessed by MTT assay. Myocardial I/R mouse models administrated with or without the compound were used for in vivo studies. Results: The in vitro cell-based screening showed that curcumin analogues 8d and 14p exhibited strong anti-oxidative effects. Pre-treatment of H9c2 cells with 14p activated Nrf2 signaling pathway, attenuated H{sub 2}O{sub 2}-increased MDA and SOD level, followed by the inhibition of TBHP-induced cell death and Bax/Bcl-2–caspase-3 pathway activation. Silencing Nrf2 significantly reversed the protective effects of 14p. In in vivo animal model of myocardial I/R, administration of low dose 14p (10 mg/kg) reduced infarct size and myocardial apoptosis to the same extent as the high dose curcumin (100 mg/kg). Conclusion: These data support the novel curcumin analogue 14p as a promising antioxidant to decrease oxidative stress and limit myocardial ischemia reperfusion injury via activating Nrf2. - Highlights: • Mono-carbonyl analogue of curcumin, 14p, exhibited better chemical stability. • Compound 14p inhibited TBHP-induced apoptosis through activating Nrf2 in vitro. • Compound 14p limited myocardial ischemia

Structural and sociocultural factors associated with cervical cancer screening among HIV-infected African American women in Alabama.

Science.gov (United States)

Williams, Michelle; Moneyham, Linda; Kempf, Mirjam-Colette; Chamot, Eric; Scarinci, Isabel

2015-01-01

African American women have disproportionately high prevalence rates of HIV and cervical cancer. HIV-infected women are significantly less likely to obtain recommended cervical cancer screenings than HIV-uninfected women. The purpose of this study was to examine sociocultural and structural factors associated with cervical cancer screening among HIV-infected African American in Alabama. The PEN-3 Model and the Health Belief Model were used as theoretical frameworks. In-depth interviews were conducted with twenty HIV-infected African American women to identify perceptions, enablers, and nurturers, perceived susceptibility, perceived severity, and perceived benefits related to cervical cancer and screening. The most common positive perceptions, enablers, and nurturers that contributed to cervical cancer screening included internal motivation and awareness of the importance of HIV-infected women getting Pap tests due to their weakened immune system. Negative perceptions, enablers, and nurturers included lack of knowledge about cervical cancer and screening, and lack of perceived susceptibility to cervical cancer. The results of this study can be used to guide the development of culturally relevant cervical cancer and screening education interventions aimed at increasing cervical cancer screening adherence among HIV-infected African American women.

[Anti-inflammatory, analgesic and anti-pyretic activities of a non-steroidal anti-inflammatory drug, etofenamate, in experimental animals].

Science.gov (United States)

Nakamura, H; Motoyoshi, S; Imazu, C; Ishii, K; Yokoyama, Y; Seto, Y; Kadokawa, T; Shimizu, M

1982-08-01

Anti-inflammatory, analgesic, and anti-pyretic activities of orally administered etofenamate, the diethylene glycol ester of flufenamic acid, were investigated in experimental animals. Against acetic acid-induced vascular permeability in mice and ultra-violet light-induced erythema in guinea pigs, etofenamate produced a dose related inhibition at doses of 40--320 mg/kg and 5--20 mg/kg, respectively. In rats, felt-pellet-induced granuloma formation and adjuvant-induced arthritis were significantly inhibited by repeated administration of etofenamate at doses of 20 mg/kg/day for 5 days and 40 mg/kg/day for 21 days, respectively. Etofenamate showed an inhibitory activity on the squeak response caused by flexing and extending the silver nitrate-induced arthritic joint in rats; and it produced a dose related anti-writhing activity at doses of 50--300 mg/kg and 10--80 mg/kg in mice and rats, respectively, in the acetic acid-induced writhing test. Etofenamate showed a significant anti-pyretic activity at doses of 0.2 mg/kg or more. These potencies of etofenamate were 0.5 to 1.6 times those of flufenamic acid. In particular, the anti-erythema, anti-arthritis, and anti-pyretic activities of etofenamate were approximately equivalent to or superior to those of flufenamic acid. From these results, it was suggested that etofenamate given orally, like other non-steroidal anti-inflammatory drugs, showed anti-inflammatory, analgesic, and anti-pyretic activities in experimental animals.

Susceptibility of pregnant women to toxoplasma infection--potential benefits for newborn screening.

LENUS (Irish Health Repository)

Ferguson, W

2008-08-20

Congenital toxoplasmosis (CT) arises as a result of new acquisition of Toxoplasma infection by a susceptible woman during pregnancy. Early detection of CT through neonatal screening programmes could optimize management and improve infant outcome. This study sought to estimate the prevalence of Toxoplasma susceptibility in pregnant women. As detection of Toxoplasma antibodies in neonatal blood reflects maternal exposure history, maternal antibody seroprevalence was determined using anonymized residual blood from newborn screening cards. A total of 20,252 cards were tested in 1 year. 4,991 (24.6%) cards tested positive for Toxoplasma antibody. Results were stratified by county. Toxoplasma antibody seroprevalence rates of 25% indicated that Toxoplasma infection is common in Ireland and that up to 75% of women remain susceptible to primary infection during pregnancy. This study aimed to a) determine the seroprevalence of Toxoplasma antibody in pregnant women, and hence b) estimate the risk for acquisition of primary toxoplasmosis in pregnancy in order to support an application to fund a pilot newborn screening programme.

Plants used in Guatemala for the treatment of protozoal infections. I. Screening of activity to bacteria, fungi and American trypanosomes of 13 native plants.

Science.gov (United States)

Cáceres, A; López, B; González, S; Berger, I; Tada, I; Maki, J

1998-10-01

Extracts were prepared from 13 native plants used for the treatment of protozoal infections. Activity against bacteria and fungi was demonstrated by dilution procedures; Trypanosoma cruzi was evaluated in vitro against epimastigote and trypomastigotes and in vivo against trypomastigotes. In active extracts, toxicity was evaluated by Artemia salina nauplii, oral acute toxicity (1-5 g/kg) and oral and intraperitoneal subacute toxicity in mice (500 mg/kg). From the plants screened, six showed activity (Neurolaena lobata and Solanum americanum; in vitro or in vivo activity was shown by Acalypha guatemalensis, Petiveria alliacea and Tridax procumbens. Toxicity studies showed that extracts from S. americanum are toxic to A. salina (aqueous, 160 ppm). None showed acute or oral toxicity to mice; S. americanum showed intraperitoneal subacute toxicity.

Anti-HIV activity in cervical-vaginal secretions from HIV-positive and -negative women correlate with innate antimicrobial levels and IgG antibodies.

Directory of Open Access Journals (Sweden)

Mimi Ghosh

2010-06-01

Full Text Available We investigated the impact of antimicrobials in cervicovaginal lavage (CVL from HIV(+ and HIV(- women on target cell infection with HIV. Since female reproductive tract (FRT secretions contain a spectrum of antimicrobials, we hypothesized that CVL from healthy HIV(+ and (- women inhibit HIV infection.CVL from 32 HIV(+ healthy women with high CD4 counts and 15 healthy HIV(- women were collected by gently washing the cervicovaginal area with 10 ml of sterile normal saline. Following centrifugation, anti-HIV activity in CVL was determined by incubating CVL with HIV prior to addition to TZM-bl cells. Antimicrobials and anti-gp160 HIV IgG antibodies were measured by ELISA. When CXCR4 and CCR5 tropic HIV-1 were incubated with CVL from HIV(+ women prior to addition to TZM-bl cells, anti-HIV activity in CVL ranged from none to 100% inhibition depending on the viral strains used. CVL from HIV(- controls showed comparable anti-HIV activity. Analysis of CH077.c (clone of an R5-tropic, mucosally-transmitted founder virus viral inhibition by CVL was comparable to laboratory strains. Measurement of CVL for antimicrobials HBD2, trappin-2/elafin, SLPI and MIP3alpha indicated that each was present in CVL from HIV(+ and HIV(- women. HBD2 and MIP3alpha correlated with anti-HIV activity as did anti-gp160 HIV IgG antibodies in CVL from HIV(+ women.These findings indicate that CVL from healthy HIV(+ and HIV(- women contain innate and adaptive defense mechanisms that inhibit HIV infection. Our data suggest that innate endogenous antimicrobials and HIV-specific IgG in the FRT can act in concert to contribute toward the anti-HIV activity of the CVL and may play a role in inhibition of HIV transmission to women.

Anti-HCV activity of the Chinese medicinal fungus Cordyceps militaris.

Science.gov (United States)

Ueda, Youki; Mori, Kyoko; Satoh, Shinya; Dansako, Hiromichi; Ikeda, Masanori; Kato, Nobuyuki

2014-05-02

Persistent hepatitis C virus (HCV) infection causes chronic liver diseases and is a global health problem. Although the sustained virologic response rate in the treatment of genotype 1 using new triple therapy (pegylated-interferon, ribavirin, and telaprevir/boceprevir) has been improved by more than 70%, several severe side effects such as skin rash/ageusia and advanced anemia have become a problem. Under these circumstances, a new type of anti-HCV oral drug with few side effects is needed. Our recently developed HCV drug assay systems, including the HuH-7 cell line-derived OR6 and AH1R, and the Li23 cell line-derived ORL8 and ORL11, allow genome-length HCV RNAs (several strains of genotype 1b) encoding renilla luciferase to replicate efficiently. Using these systems as anti-HCV candidates, we have identified numerous existing medicines that can be used against HCV with few side effects, such as statins and teprenon. To obtain additional anti-HCV candidates, we evaluated a number of oral health supplements, and found that the capsule but not the liquid form of Cordyceps militaris (CM) (Ascomycotinanorth, North Chinese caterpillar fungus), which is used as a Chinese herbal medicine, exhibited moderate anti-HCV activity. In combination with interferon-α or ribavirin, CM exhibited an additive inhibitory effect. Among the main components of CM, cordycepin, but not ergosterol, contributed to the anti-HCV activity of CM. In consideration of all these results, we suggest that CM would be useful as an oral anti-HCV agent in combination with interferon-α and/or ribavirin. Copyright © 2014 Elsevier Inc. All rights reserved.

Antimicrobial, anti-inflammatory activities and toxicology of phenylethanoid glycosides from Monochasma savatieri Franch. ex Maxim.

Science.gov (United States)

Liu, Yan-li; He, Wen-jun; Mo, Li; Shi, Meng-fan; Zhu, Ying-ying; Pan, Shu; Li, Xiao-ran; Xu, Qiong-ming; Yang, Shi-lin

2013-09-16

Monochasma savatieri Franch. ex Maxim is used for treating many diseases in Traditional Chinese Medicine. The present study was designed to evaluate antibacterial, anti-inflammatory activities and toxicity of the total phenylethanoid glycosides from Monochasma savatieri Franch. ex Maxim (TPG). The antibacterial activity of TPG was checked by MIC and MBC in vitro; survival of mice with Pseudomonas aeruginosa or Staphylococcus aureus infection-induced sepsis was investigated to evaluate antibacterial activity of TPG in vivo. Additionally, antibacterial activities of TPG were also investigated in a Pseudomonas aeruginosa infection-induced pneumonia in the mice model. Cotton pellet induced granuloma and xylene induced ear swelling in mice models were used to quantify the anti-inflammatory activity. TPG showed a significant possess bacteriostatic properties against five bacteria strains at a concentration between 0.0625 and 16 mg/ml. Moreover, TPG has bactericidal activity against Pseudomonas aeruginosa, Streptococcus pneumoniae or Escherichia coli. TPG (60, 120, and 180 mg/kg) prolonged survival rate of mice with Pseudomonas aeruginosa or Staphylococcus aureus infection-induced sepsis. In addition, TPG (180 mg/kg) could reduce the bacterial colony-forming units in lung tissue. Furthermore, TPG (60-180 mg/kg) had significantly reduced xylene-induced ear edema and granulomat formation induced by cotton pellet at a dose-dependent manner. In addition, administration of TPG (1.5 g/kg) for 15 days did not result in toxicities in liver, kidney, spleen and thymus tissue in rats. These results indicated that TPG might be useful for the development of a novel treatment for respiratory infections or pneumonia caused by Pseudomonas aeruginosa or Staphylococcus aureus. © 2013 Elsevier Ireland Ltd. All rights reserved.

The different clinical effects of anti-BLyS, anti-APRIL and anti-CD20 antibodies point at a critical pathogenic role of γ-herpesvirus infected B cells in the marmoset EAE model.

Science.gov (United States)

Anwar Jagessar, S; Fagrouch, Zahra; Heijmans, Nicole; Bauer, Jan; Laman, Jon D; Oh, Luke; Migone, Thi; Verschoor, Ernst J; 't Hart, Bert A

2013-06-01

The robust and rapid clinical effect of depleting anti-CD20 monoclonal antibodies (mAb) in multiple sclerosis (MS) demonstrates a critical pathogenic contribution of B cells. The clinical effect of anti-CD20 mAb has been replicated in a relevant preclinical MS model, experimental autoimmune encephalomyelitis (EAE) in marmoset monkeys (Callithrix jacchus). By contrast, treatment with mAbs against two essential cytokines in B cell activation growth and survival, i.e. BlyS/BAFF and APRIL, was only partially effective. All three mAbs induced depletion of CD20+ B cells from the circulation, albeit with different kinetics and based on distinct mechanisms of action. In the current study we analyzed whether the different clinical effect of anti-CD20 mAb or the anti-BLyS and anti-APRIL mAbs is due to different depletion of B cells infected with the EBV of marmosets, CalHV3. Employing a novel PCR-based assay, half of the colony of group-housed marmosets was tested positive for CalHV3 DNA in secondary lymphoid organs. The same prevalence was observed in placebo-treated monkeys. In marmosets treated with anti-CD20 mAb the load of CalHV3 DNA in lymphoid organs was substantially reduced, while this was not observed in the monkeys treated with anti-BLyS or anti-APRIL mAbs. To examine the pathogenic role of virus-transformed B cells, we infused EBV-transformed B lymphoblastic cell (BLC) lines presenting the immunodominant MOG34-56 peptide. We observed in the recipients of MOG34-56 pulsed BLC, but not in their fraternal siblings infused with non-pulsed BLC, activation of anti-MOG34-56 T cells and meningeal inflammation. Collectively, the data show that among CD20+ B cells, the herpesvirus-transformed subset has a particularly important pathogenic role in the marmoset EAE model.

Biological activities (anti-inflammatory and anti-oxidant) of fractions ...

African Journals Online (AJOL)

Biological activities (anti-inflammatory and anti-oxidant) of fractions and methanolic extract of Philonotis hastate (Duby Wijk & MargaDant). ... The fractions and methanolic extract exhibited moderate antioxidant potentials with various models. The flavonoid contents of the methanol extract and fractions ranged between 1.70 ...

Polysaccharides from Sargassum thunbergii: Monthly variations and anti-complement and anti-tumour activities.

Science.gov (United States)

Jin, Weihua; Liu, Ge; Zhong, Weihong; Sun, Chaomin; Zhang, Quanbin

2017-12-01

Monthly variations of polysaccharides from Sargassum thunbergii and their anti-complement and anti-tumour activities were investigated. It was observed that an increase in fucose and total sugar contents occurred during the growth period (from early April to mid-June), accompanied by a decrease in molar ratios of other monosaccharides to fucose. The highest yields were obtained from early July to early September, which was in accordance with the significant increase in molar ratio of glucose to fucose and decrease in molar ratio of other monosaccharides to fucose. And the above results suggested that S. Thunbergii synthesized large amount of laminaran, the storage substance of brown algae, during the senescence period. However, sulfate contents were relatively stable in the life cycle of S. thunbergii. These results suggested that S. thunbergii synthesized complex sulfated heteropolysacchairdes during inactive period, while during other periods, it synthesized more sulfated galactofucan. All polysaccharides showed anti-complement activity, suggesting that the harvesting time did not influence the anti-complement activities. In the anti-tumour assay in vitro, the polysaccharides taken during the senescence period had much lower anti-tumour activity, suggesting that fucoidan, but not laminaran, determined the anti-tumour activities. Therefore, polysaccharides from S. thunbergii might have great potential in anti-complement and anti-tumour application. Copyright © 2017 Elsevier B.V. All rights reserved.

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

Directory of Open Access Journals (Sweden)

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.

Frequency of anti-HCV antibodies in patients with lichen planus

International Nuclear Information System (INIS)

Mahboob, A.; Haroon, T.S.; Iqbal, Z.; Butt, A.K.

2003-01-01

Objective: To determine the frequency of anti-HCV antibodies, identify risk factors associated with HCV infection and to screen asymptomatic carries in patients with lichen planus. Subjects and Methods: A total of 184 clinically diagnosed cased of lichen (LP) were selected for the study. Blood samples of all the patients were tested for anti hepatitis C virus antibodies (anti-HCV-Ab). Polymerase chain reaction for hepatitis C virus was done in patients with positive anti-HCV-Ab. Trancutaneous liver biopsy was performed in 7 patients with positive HCV-RNA. The histopathological results were evaluated using validated Metavir and Knodell scoring systems. Results: Out of 184 LP patients, 43 (23.4%) were anti-HCV antibodies positive. Females were predominantly affected and male to female ratio was 1:5.1. Maximum positively for anti-HCV was observed in age group 31-40 years (39.53%) followed by 41-50 years (25.58%). Eighty-one percent patients had history of dental treatment and 63% had received multiple injections for various ailments. Forty percent patients had family history of jaundice while 26% had jaundice in the past. Ten out of 16 anti-HCV antibody positive patients, checked for HCV-RNA, had high levels of virus in blood. Transcutaneous liver biopsy done in 7 patients revealed underlying liver disease at various stages. Four patients treated with alpha-interferon and ribazole therapy for liver disease, showed marked improvement in their skin disease. Conclusion: A high prevalence of HCV infection was detected in patients with lichen planus. Patients with lichen planus should be screened for HCV carrier state. (author)

Correlation of pharmacodynamic activity, pharmacokinetics, and anti-product antibody responses to anti-IL-21R antibody therapeutics following IV administration to cynomolgus monkeys

Directory of Open Access Journals (Sweden)

Spaulding Vikki

2010-04-01

Full Text Available Abstract Background Anti-IL-21R antibodies are potential therapeutics for the treatment of autoimmune diseases. This study evaluated correlations between the pharmacodynamic (PD activity, pharmacokinetics, and anti-product antibody responses of human anti-IL-21R antibodies Ab-01 and Ab-02 following IV administration to cynomolgus monkeys. Methods The PD assay was based on the ability of recombinant human IL-21 (rhuIL-21 to induce expression of the IL-2RA gene in cynomolgus monkey whole blood samples ex vivo. Monkeys screened for responsiveness to rhuIL-21 stimulation using the PD assay, were given a single 10 mg/kg IV dosage of Ab-01, Ab-02, or a control antibody (3/group, and blood samples were evaluated for PD activity (inhibition of IL-2RA expression for up to 148 days. Anti-IL-21R antibody concentrations and anti-product antibody responses were measured in serum using immunoassays and flow cytometry. Results Following IV administration of Ab-01 and Ab-02 to cynomolgus monkeys, PD activity was observed as early as 5 minutes (first time point sampled. This PD activity had good correlation with the serum concentrations and anti-product antibody responses throughout the study. The mean terminal half-life (t1/2 was ~10.6 and 2.3 days for Ab-01 and Ab-02, respectively. PD activity was lost at ~5-13 weeks for Ab-01 and at ~2 weeks for Ab-02, when serum concentrations were relatively low. The estimated minimum concentrations needed to maintain PD activity were ~4-6 nM for Ab-01 and ~2.5 nM for Ab-02, and were consistent with the respective KD values for binding to human IL-21R. For Ab-01, there was noticeable inter-animal variability in t1/2 values (~6-14 days and the resulting PD profiles, which correlated with the onset of anti-product antibody formation. While all three Ab-01-dosed animals were positive for anti-Ab-01 antibodies, only one monkey (with the shortest t1/2 and the earliest loss of PD activity had evidence of neutralizing anti-Ab-01

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

Directory of Open Access Journals (Sweden)

Chi H.J. Kao

2013-02-01

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

A High Throughput Screening Assay for Anti-Mycobacterial Small Molecules Based on Adenylate Kinase Release as a Reporter of Cell Lysis.

Directory of Open Access Journals (Sweden)

Lauren Forbes

Full Text Available Mycobacterium tuberculosis (Mtb is well-established to be one of the most important bacterial pathogens for which new antimicrobial therapies are needed. Herein, we describe the development of a high throughput screening assay for the identification of molecules that are bactericidal against Mycobacteria. The assay utilizes the release of the intracellular enzyme adenylate kinase into the culture medium as a reporter of mycobacterial cell death. We demonstrate that the assay is selective for mycobactericidal molecules and detects anti-mycobacterial activity at concentrations below the minimum inhibitory concentration of many molecules. Thus, the AK assay is more sensitive than traditional growth assays. We have validated the AK assay in the HTS setting using the Mtb surrogate organism M. smegmatis and libraries of FDA approved drugs as well as a commercially available Diversity set. The screen of the FDA-approved library demonstrated that the AK assay is able to identify the vast majority of drugs with known mycobactericidal activity. Importantly, our screen of the Diversity set revealed that the increased sensitivity of the AK assay increases the ability of M. smegmatis-based screens to detect molecules with relatively poor activity against M. smegmatis but good to excellent activity against Mtb.

Anti-caries activity of selected Sudanese medicinal plants with emphasis on Terminalia laxiflora

Directory of Open Access Journals (Sweden)

Ebtihal Abdalla M. Mohieldin

Full Text Available Abstract In Sudan, some medicinal plants, such as Acacia seyal, Calotropis procera and Balanites aegyptiaca have been used to prevent or treat oral health problems. The stem and stem bark of Terminalia laxiflora Engl., Combretaceae, are used as antiseptics for mouthwash to prevent gingivitis and thrush in Africa. Methanol and 50% hydroethanolic extracts of 25 plants that are used in traditional Sudanese medicine for several diseases and cavity disorders were screened for anti-cavity activities. T. laxiflora methanolic wood extracts, which exhibited such activity, were investigated. The crude extracts were assayed for their antimicrobial activities against Streptococcus sobrinus in terms of minimum inhibitory concentration and glucosyltransferase inhibition. The active extract of T. laxiflora wood was subsequently fractionated by different chromatographic techniques. Isolated compounds were identified by spectroscopic methods and assessed for S. sobrinus and glucosyltransferase inhibitory effects. Methanolic extracts of Terminalia brownii (bark, T. laxiflora (wood, A. seyal (bark, Persicaria glabra (leaves and Tamarix nilotica (stem showed good activities against both S. sobrinus and glucosyltransferase (MIC ≤ 1 mg/ml, IC50 values <50 µg/ml. Over all plant extracts, T. laxiflora demonstrated the good combined activities (MIC 0.5 mg/ml, glucosyltransferase, IC50 10.3 µg/ml; therefore, its methanolic wood extracts were selected for further phytochemical studies. Four constituents were isolated by chromatographic techniques and identified by spectroscopic techniques. Pharmacological evaluation of the obtained compounds showed that flavogallonic acid dilactone had comparatively good antibacterial activity. In the glucosyltransferase inhibitory test, terchebulin displayed potent activity with an IC50 of 7.5 µM. The screening presented in this study showed that methanol extracts of T. laxiflora wood possessed promising anti-cavity effects.

Comparative screening of the anti-oxidant and antimicrobial activities of Sempervivum marmoreum L. extracts obtained by various extraction techniques

Directory of Open Access Journals (Sweden)

SASA S. STOJICEVIC

2008-06-01

Full Text Available This paper presents a comparative study of the anti-oxidant and anti-microbial activities, total phenolic compounds and total flavonoids in extracts obtained from houseleek (Sempervivum marmoreum L. leaves by the classical (maceration, ultrasonic and Soxhlet extraction (CE, UE and SE, respectively. The extract obtained by the CE contained higher amounts of phenolic and flavonoid compounds and showed a better antioxidant activity than those obtained using other two techniques. All the extracts, independent of the extraction technique applied, showed antimicrobial activities against Aspergillus niger and Candida albicans only but not against the tested bacteria.

Influence of diabetes mellitus and risk factors in activating latent tuberculosis infection: a case for targeted screening in malaysia.

Science.gov (United States)

Swarna Nantha, Y

2012-10-01

A review of the epidemiology of tuberculosis, its contributing risk factors (excluding HIV) and the role of screening latent tuberculosis infection in Malaysia was done. Despite the global and domestic decrease in prevalence rates of tuberculosis in the past decade, there is an alarming increase in the trend of non communicable diseases in the country. High prevalence rates of major risk factors leading to reactivation of tuberculosis were seen within the population, with diabetes mellitus being in the forefront. The rising numbers in the ageing population of Malaysia poses a further threat of re-emergence of tuberculosis in the years to come. Economically, screening of diabetic patients with comorbidities for latent tuberculosis infection (LTBI) using two major techniques, namely tuberculin sensitivity (TST) and Interferon gamma release assay tests (IGRA) could be a viable option. The role of future research in the detection of LTBI in the Malaysian setting might be necessary to gauge the disease reservoir before implementing prophylactic measures for high risk groups involved.

Anticoccidial activities of Chitosan on Eimeria papillata-infected mice.

Science.gov (United States)

Abdel-Latif, Mahmoud; Abdel-Haleem, Heba M; Abdel-Baki, Abdel-Azeem S

2016-07-01

Eimeria spp. multiply within the intestinal tract causing severe inflammatory responses. Chitosan (CS), meanwhile, has been shown to exhibit anti-inflammatory activities in different experimental models. Here, we investigated the effect of CS on the outcome of inflammation caused by Eimeria papillata in the mouse intestine. Investigations were undertaken into the oocyst output in feces and developmental stages and goblet cells in intestinal tissue. Assays for lipid peroxidation, nitric oxide (NO), and myeloperoxidase (MPO) were also performed. T cells in intestinal tissue were counted using immunohistochemistry while total IgA in serum or intestinal wash was assayed using ELISA. In addition, mRNA expression of tumor necrosis factor alpha (TNF-α), transforming growth factor β (TGF-β), interleukin (IL)-10, and IL-4 were detected using real-time PCR. The data indicated a reduction in both oocyst output and in the number of parasite developmental stages following CS treatment, while the goblet cell hypoplasia in infected mice was also inhibited. CS decreased lipid peroxidation, NO, and MPO but did not alter the T cell count or IgA levels in comparison to the infected group. The expression of TNF-α and TGF-β decreased but IL-10 and IL-4 increased after CS treatment in comparison to the non-treated infected group. In conclusion, CS showed anti-inflammatory and protective effects against E. papillata infection.

Analgesic, anti-inflmmatory and antipyretic activities of methanolic leaf extract of Maerua crassifolia

Directory of Open Access Journals (Sweden)

Godwin Christian Akuodor

2016-03-01

Full Text Available Objective: To investigate the the analgesic, anti-inflammatory and antipyretic activities of the methanolic leaf extract of Maerua crassifolia in mice and rats. Methods: Acetic acid-induced writhing and tail immersion methods were used to assess analgesic activity, while xylene and carrageenan-induced paw oedema methods were used to evaluate the anti-inflammatory effect of the leaf extract. Yeast and amphetamine-induced pyrexia were used to investigate the antipyretic activity. The phytochemical analysis and oral acute toxicity of the methanolic leaf extract of Maerua crassifolia were also evaluated. Results: The leaf extract (100, 200, and 400 mg/kg showed a dose dependent and significant (P < 0.05 inhibition of pain in acetic acid-induced writhing and tail immersion tests. The extract also produced significant (P < 0.05 anti-inflammatory activity in both paradigms. A significant (P < 0.05 reduction in hyperpyrexia was also observed with the leaf extract. The phytochemical screening revealed the presence of alkaloids, flavonoids, terpenoids, tannins, steroids, resins, saponins and cardiac glycosides. The oral median lethal dose of the leaf extract was estimated to be greater than 5 000 mg/kg in rats. Conclusions: The findings confirmed its ethnomedical use in the treatment of pains and feverish conditions.

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.

MAIT cells are activated in acute Dengue virus infection and after in vitro Zika virus infection.

Directory of Open Access Journals (Sweden)

Dominic Paquin-Proulx

2018-01-01

Full Text Available Dengue virus (DENV and Zika virus (ZIKV are members of the Flaviviridae and are predominantly transmitted via mosquito bites. Both viruses are responsible for a growing number of infections in tropical and subtropical regions. DENV infection can cause lethargy with severe morbidity and dengue shock syndrome leading to death in some cases. ZIKV is now linked with Guillain-Barré syndrome and fetal malformations including microcephaly and developmental disorders (congenital Zika syndrome. The protective and pathogenic roles played by the immune response in these infections is unknown. Mucosal-associated invariant T (MAIT cells are a population of innate T cells with potent anti-bacterial activity. MAIT cells have also been postulated to play a role in the immune response to viral infections. In this study, we evaluated MAIT cell frequency, phenotype, and function in samples from subjects with acute and convalescent DENV infection. We found that in acute DENV infection, MAIT cells had elevated co-expression of the activation markers CD38 and HLA-DR and had a poor IFNγ response following bacterial stimulation. Furthermore, we found that MAIT cells can produce IFNγ in response to in vitro infection with ZIKV. This MAIT cell response was independent of MR1, but dependent on IL-12 and IL-18. Our results suggest that MAIT cells may play an important role in the immune response to Flavivirus infections.

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.

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.

Directory of Open Access Journals (Sweden)

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.

High affinity anti-TIM-3 and anti-KIR monoclonal antibodies cloned from healthy human individuals.

Directory of Open Access Journals (Sweden)

Stefan Ryser

Full Text Available We report here the cloning of native high affinity anti-TIM-3 and anti-KIR IgG monoclonal antibodies (mAbs from peripheral blood mononuclear cells (PBMC of healthy human donors. The cells that express these mAbs are rare, present at a frequency of less than one per 105 memory B-cells. Using our proprietary multiplexed screening and cloning technology CellSpot™ we assessed the presence of memory B-cells reactive to foreign and endogenous disease-associated antigens within the same individual. When comparing the frequencies of antigen-specific memory B-cells analyzed in over 20 screening campaigns, we found a strong correlation of the presence of anti-TIM-3 memory B-cells with memory B-cells expressing mAbs against three disease-associated antigens: (i bacterial DNABII proteins that are a marker for Gram negative and Gram positive bacterial infections, (ii hemagglutinin (HA of influenza virus and (iii the extracellular domain of anaplastic lymphoma kinase (ALK. One of the native anti-KIR mAbs has similar characteristics as lirilumab, an anti-KIR mAb derived from immunization of humanized transgenic mice that is in ongoing clinical trials. It is interesting to speculate that these native anti-TIM-3 and anti-KIR antibodies may function as natural regulatory antibodies, analogous to the pharmacological use in cancer treatment of engineered antibodies against the same targets. Further characterization studies are needed to define the mechanisms through which these native antibodies may function in healthy and disease conditions.

Antiplasmodial activity of Xanthium strumarium against Plasmodium berghei-infected BALB/c mice.

Science.gov (United States)

Chandel, Sanjeev; Bagai, Upma; Vashishat, Nisha

2012-03-01

The present work was undertaken to evaluate the antiplasmodial activity of ethanolic leaves extract of traditional medicinal plant Xanthium strumarium in Plasmodium berghei-infected BALB/c mice along with phytochemical screening and acute toxicity test to support its traditional medicinal use as a malaria remedy. The ethanolic leaves extract of X. strumarium (ELEXS) 150, 250, 350 and 500 mg/kg/day demonstrated dose-dependent chemosuppression during early and established infection long with significant (p strumarium as malarial remedy and indicate the potential of plant for active antiplasmodial components.

Lymphogranuloma venereum in men screened for pharyngeal and rectal infection, Germany.

Science.gov (United States)

Haar, Karin; Dudareva-Vizule, Sandra; Wisplinghoff, Hilmar; Wisplinghoff, Fabian; Sailer, Andrea; Jansen, Klaus; Henrich, Birgit; Marcus, Ulrich

2013-03-01

To determine prevalence of lymphogranuloma venereum among men who have sex with men in Germany, we conducted a multicenter study during 2009-2010 and found high rates of rectal and pharyngeal infection in men positive for the causative agent, Chlamydia trachomatis. Many infections were asymptomatic. An adjusted C. trachomatis screening policy is justified in Germany.

Disappointing performance of literature-derived selective screening criteria for asymptomatic Chlamydia trachomatis infection in an inner-city population

NARCIS (Netherlands)

van Valkengoed, I G; Boeke, A J; Morré, S A; van den Brule, A J; Meijer, C J; Devillé, W; Bouter, L M

2000-01-01

BACKGROUND: In an inner-city population with a low prevalence of Chlamydia trachomatis infection, selective screening may be indicated to increase the efficiency of screening. GOAL: To evaluate the performance of sets of selective screening criteria for asymptomatic Chlamydia trachomatis infection

The role of fear in predicting sexually transmitted infection screening.

Science.gov (United States)

Shepherd, Lee; Smith, Michael A

2017-07-01

This study assessed the extent to which social-cognitive factors (attitude, subjective norm and perceived control) and the fear of a positive test result predict sexually transmitted infection (STI) screening intentions and subsequent behaviour. Study 1 (N = 85) used a longitudinal design to assess the factors that predict STI screening intention and future screening behaviour measured one month later at Time 2. Study 2 (N = 102) used an experimental design to determine whether the relationship between fear and screening varied depending on whether STI or HIV screening was being assessed both before and after controlling for social-cognitive factors. Across the studies the outcome measures were sexual health screening. In both studies, the fear of having an STI positively predicted STI screening intention. In Study 1, fear, but not the social-cognitive factors, also predicted subsequent STI screening behaviour. In Study 2, the fear of having HIV did not predict HIV screening intention, but attitude negatively and response efficacy positively predicted screening intention. This study highlights the importance of considering the nature of the health condition when assessing the role of fear on health promotion.

Benefits and harms of lung cancer screening in HIV-infected individuals with CD4+ ≥ 500: a simulation study.

Science.gov (United States)

Kong, Chung Yin; Sigel, Keith; Criss, Steven D; Sheehan, Deirdre F; Triplette, Matthew; Silverberg, Michael J; Henschke, Claudia I; Justice, Amy; Braithwaite, R Scott; Wisnivesky, Juan; Crothers, Kristina

2018-04-19

Lung cancer is the leading cause of non-AIDS-defining cancer deaths among HIV-infected individuals. Although lung cancer screening with low-dose computed tomography (LDCT) is endorsed by multiple national organizations, whether HIV-infected individuals would have similar benefit as uninfected individuals from lung cancer screening is unknown. Our objective was to determine the benefits and harms of lung cancer screening among HIV-infected individuals. We modified an existing simulation model, the Lung Cancer Policy Model, for HIV-infected patients. Veterans Aging Cohort Study, Kaiser Permanente Northern California HIV Cohort, and medical literature. Target population: HIV-infected current and former smokers. Lifetime. Population. Annual LDCT screening from ages 45, 50, or 55 until ages 72 or 77 years. Benefits assessed included lung cancer mortality reduction and life-years gained; harms assessed included numbers of LDCT examinations, false-positive results, and overdiagnosed cases. For HIV-infected patients with CD4 at least 500 and 100% antiretroviral therapy adherence, screening using the Centers for Medicare & Medicaid Services criteria (age 55-77, 30 pack-years of smoking, current smoker or quit within 15 years of screening) would reduce lung cancer mortality by 18.9%, similar to the mortality reduction of uninfected individuals. Alternative screening strategies utilizing lower screening age and/or pack-years criteria increase mortality reduction, but require more LDCT examinations. Strategies assumed 100% screening adherence. Lung cancer screening reduces mortality in HIV-infected patients with CD4 at least l500, with a number of efficient strategies for eligibility, including the current Centers for Medicare & Medicaid Services criteria.

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

Science.gov (United States)

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.

Evaluation of immunomodulatory and anti-inflammatory effects and phytochemical screening of Alternanthera tenella Colla (Amaranthaceae aqueous extracts

Directory of Open Access Journals (Sweden)

Carla de Agostino Biella

2008-09-01

Full Text Available Alternanthera tenella Colla extracts are used in Brazilian traditional folk medicine to treat a variety of infectious diseases as well as inflammation and fever. In this work, the immunomodulatory, anti-inflammatory and potential toxic effects of cold (CAE and hot (HAE aqueous extracts of A. tenella were investigated in vivo. In addition, we analyzed the phytochemical properties of both extracts. BALB/c mice were immunized in vivo with sheep red blood cells and concomitantly inoculated intraperitoneally (i.p. with each extract (50, 100 or 200 mg/kg. Specific antibody-producing cells were enumerated using plaque-forming cell assays (PFC and anti-SRBC IgG and IgM serum levels were measured via enzyme-linked immunosorbent assay. Body and lymphoid organ weights were determined after treatments in order to evaluate toxic effects. Carrageenan-induced paw edema was employed to investigate anti-inflammatory activity in mice inoculated i.p. with CAE or HAE (200 or 400 mg/kg. Phytochemical screening was performed using spectrometric and chromatographic approaches and revealed that CAE possessed higher tannin and flavonoid levels than HAE. PFC numbers were increased after treatment with CAE (100 mg/kg four days after immunization, as were the serum antibody titers after four and seven days, suggesting immunostimulatory activity through modulation of B lymphocyte functions. Body and organ weights did not show major changes, suggesting that extracts administered to mice did not induce significant toxicity. Both extracts had significant anti-inflammatory activity in the paw edema assay. These results suggested that aqueous extracts from A. tenella contained several chemical compounds that possess positive and/or negative modulator effects on the immune system, which appeared to correlate with tannin and flavonoid levels in those extracts. In summary, these studies provide important insight into the biological activities of A. tenella.

The nature of the GRE influences the screening for GR-activity enhancing modulators.

Directory of Open Access Journals (Sweden)

Karen Dendoncker

Full Text Available Glucocorticoid resistance (GCR, i.e. unresponsiveness to the beneficial anti-inflammatory activities of the glucocorticoid receptor (GR, poses a serious problem in the treatment of inflammatory diseases. One possible solution to try and overcome GCR, is to identify molecules that prevent or revert GCR by hyper-stimulating the biological activity of the GR. To this purpose, we screened for compounds that potentiate the dexamethasone (Dex-induced transcriptional activity of GR. To monitor GR transcriptional activity, the screen was performed using the lung epithelial cell line A549 in which a glucocorticoid responsive element (GRE coupled to a luciferase reporter gene construct was stably integrated. Histone deacetylase inhibitors (HDACi such as Vorinostat and Belinostat are two broad-spectrum HDACi that strongly increased the Dex-induced luciferase expression in our screening system. In sharp contrast herewith, results from a genome-wide transcriptome analysis of Dex-induced transcripts using RNAseq, revealed that Belinostat impairs the ability of GR to transactivate target genes. The stimulatory effect of Belinostat in the luciferase screen further depends on the nature of the reporter construct. In conclusion, a profound discrepancy was observed between HDACi effects on two different synthetic promoter-luciferase reporter systems. The favorable effect of HDACi on gene expression should be evaluated with care, when considering them as potential therapeutic agents. GEO accession number GSE96649.

Application of Molecular Topology for the Prediction of Reaction Yields and Anti-Inflammatory Activity of Heterocyclic Amidine Derivatives

Directory of Open Access Journals (Sweden)

Ramón García-Domenech

2011-02-01

Full Text Available Topological-mathematical models based on multiple linear regression analyses have been built to predict the reaction yields and the anti-inflammatory activity of a set of heterocylic amidine derivatives, synthesized under environmental friendly conditions, using microwave irradiation. Two models with three variables each were selected. The models were validated by cross-validation and randomization tests. The final outcome demonstrates a good agreement between the predicted and experimental results, confirming the robustness of the method. These models also enabled the screening of virtual libraries for new amidine derivatives predicted to show higher values of reaction yields and anti-inflammatory activity.

Autofluorescence: A screening test for mycotic infection in tissues

Directory of Open Access Journals (Sweden)

Rao Shalinee

2008-04-01

Full Text Available Fungal infection is a major health concern as the clinical features are not very distinctive. Lack of rapid diagnostic techniques results in delay in diagnosis, which may even culminate in a fatal outcome. The fact that many pathogenic fungal organisms autofluoresce in hematoxylin and eosin (H and E-stained sections under ultraviolet illumination led us to evaluate the role of autofluorescence as a rapid screening technique for fungal infections. The aim of the present study was to assess the value of autofluorescence as a screening method for detecting fungi on tissue sections and to compare the results of autofluorescence with conventional histochemical stains for fungi. Hematoxylin and eosin-stained slides of mycotic lesions were examined under fluorescent microscope and the findings were compared with results of Gomori′s methenamine silver and periodic acid-Schiff stains. We found fungal autofluorescence in 63 out of 64 cases studied, with a sensitivity of 97.8% and specificity of 100% in comparison with fungal stains. This was statistically significant (P < 0.05. We conclude that autofluorescence can be used as a rapid screening method for identification of fungi in tissue sections as it does not require any other specialized staining procedure

Utilization of free dental health care services provided to the perinatally infected human immunodeficiency virus children in Bangalore: Longitudinal study

OpenAIRE

Beena Javaregowda Parvathy

2014-01-01

Background: Use of Highly active anti-retroviral therapy have increased the life expectancy of human immunodeficiency virus (HIV) infected patients and hence it is imperative that all efforts have to be made by Pediatric dentists to provide a better oral health for these children. Aim: The aim of this study was to evaluate the rate of utilization of free dental treatment provided to these perinatally infected HIV positive children who were previously screened as a part of oral health survey. ...

Screening and syndromic approaches to identify gonorrhea and chlamydial infection among women.

Science.gov (United States)

Sloan, N L; Winikoff, B; Haberland, N; Coggins, C; Elias, C

2000-03-01

The standard diagnostic tools to identify sexually transmitted infections are often expensive and have laboratory and infrastructure requirements that make them unavailable to family planning and primary health-care clinics in developing countries. Therefore, inexpensive, accessible tools that rely on symptoms, signs, and/or risk factors have been developed to identify and treat reproductive tract infections without the need for laboratory diagnostics. Studies were reviewed that used standard diagnostic tests to identify gonorrhea and cervical chlamydial infection among women and that provided adequate information about the usefulness of the tools for screening. Aggregation of the studies' results suggest that risk factors, algorithms, and risk scoring for syndromic management are poor indicators of gonorrhea and chlamydial infection in samples of both low and high prevalence and, consequently, are not effective mechanisms with which to identify or manage these conditions. The development and evaluation of other approaches to identify gonorrhea and chlamydial infections, including inexpensive and simple laboratory screening tools, periodic universal treatment, and other alternatives must be given priority.

Phytochemical screening, safety evaluation, anti-inflammatory and ...

African Journals Online (AJOL)

The analgesic and anti-inflammatory activities of the leaves of Lannea welwitschii ... was investigated in this study because the plant is used in Traditional African Medicine (TAM) to treat swellings, oedema, gout and diarrhoea. ... that tannin, flavonoid and reducing sugar were present while alkaloids, cardiac glycosides, ...

The characteristics of residents with unawareness of hepatitis C virus infection in community.

Directory of Open Access Journals (Sweden)

Pin-Nan Cheng

Full Text Available Control of hepatitis C virus infection (HCV is an increasingly important issue. Enhancing screening coverage is necessary to discover more HCV infected subjects in community. However, a substantial population is unaware of HCV infection that needs more attention.The aims of this study were to evaluate the status of HCV infected residents in remote villages, to compare characteristics between already known and unaware HCV infection subjects, and to analyze the disease insights.Screening intervention for liver diseases was conducted in remote villages of Tainan City of southern Taiwan from August 2014 to July 2016. Items of screening examinations included questionnaire, blood sampling for liver tests and viral hepatitis markers (hepatitis B surface antigen and anti-HCV antibody, abdominal sonography survey, and liver stiffness measurement by transient elastography. Quantitation of HCV RNA was measured for residents with positive anti-HCV antibody.A total of 194 (13.5% out of 1439 participants showed positive for anti-HCV antibody. HCV viremia was detected in 119 (61.3% residents. Previously unaware HCV infection by questionnaire record was present in 68 (35.1% of ant-HCV positive residents. By multivariate logistic analysis, unaware HCV infected residents exhibited significantly mild liver fibrosis (OR 0.876, 95% CI 0.782~0.981, p = 0.022, more prevalent of heart diseases (OR 6.082, 95% CI 1.963~18.839, p = 0.002, and less cluster of family history of liver diseases (OR 0.291, 95% CI 0.113~0.750, p = 0.011 when comparing with already known HCV infected residents. Among the 126 already know HCV infected residents, only 59 (46.8% received antiviral treatment or regular follow-up. No concept or no willing to receive medical care was observed in 44 (34.9% residents.In HCV endemic villages of Taiwan, residents with unaware HCV infection comprised about one third of HCV infected residents and exhibited obscure characteristics to identify. Less than half

High-throughput screen of drug repurposing library identifies inhibitors of Sarcocystis neurona growth.

Science.gov (United States)

Bowden, Gregory D; Land, Kirkwood M; O'Connor, Roberta M; Fritz, Heather M

2018-04-01

The apicomplexan parasite Sarcocystis neurona is the primary etiologic agent of equine protozoal myeloencephalitis (EPM), a serious neurologic disease of horses. Many horses in the U.S. are at risk of developing EPM; approximately 50% of all horses in the U.S. have been exposed to S. neurona and treatments for EPM are 60-70% effective. Advancement of treatment requires new technology to identify new drugs for EPM. To address this critical need, we developed, validated, and implemented a high-throughput screen to test 725 FDA-approved compounds from the NIH clinical collections library for anti-S. neurona activity. Our screen identified 18 compounds with confirmed inhibitory activity against S. neurona growth, including compounds active in the nM concentration range. Many identified inhibitory compounds have well-defined mechanisms of action, making them useful tools to study parasite biology in addition to being potential therapeutic agents. In comparing the activity of inhibitory compounds identified by our screen to that of other screens against other apicomplexan parasites, we found that most compounds (15/18; 83%) have activity against one or more related apicomplexans. Interestingly, nearly half (44%; 8/18) of the inhibitory compounds have reported activity against dopamine receptors. We also found that dantrolene, a compound already formulated for horses with a peak plasma concentration of 37.8 ± 12.8 ng/ml after 500 mg dose, inhibits S. neurona parasites at low concentrations (0.065 μM [0.036-0.12; 95% CI] or 21.9 ng/ml [12.1-40.3; 95% CI]). These studies demonstrate the use of a new tool for discovering new chemotherapeutic agents for EPM and potentially providing new reagents to elucidate biologic pathways required for successful S. neurona infection. Copyright © 2018. Published by Elsevier Ltd.

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

Science.gov (United States)

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.

Predonation screening of candidate donors and prevention of window period donations.

Science.gov (United States)

Lieshout-Krikke, Ryanne W; Zaaijer, Hans L; van de Laar, Thijs J W

2015-02-01

Infectious window period donations slip through routine donor screening procedures. To explore the potential value of predonation screening of candidate donors, we compared the proportion of incident transfusion-transmissible infections in candidate donors, in first-time donors, and in repeat donors. A retrospective analysis was performed of all incident hepatitis B virus (HBV), hepatitis C virus (HCV), and human immunodeficiency virus (HIV) infections in candidate, first-time, and repeat donors in the Netherlands during the period 2009 to 2013. In total, 176,716 candidate donors, 144,226 first-time donations, and 4,143,455 repeat donations were screened for HBV, HCV, and HIV infection. Acute HBV infection was identified in the predonation sample of six candidate donors. One first-time donor, testing HIV-negative at predonation screening, tested positive for anti-HIV and HIV RNA in the first donation 29 days later. Among repeat donations we identified 15, one, and six incident HBV, HCV and HIV infections, respectively. The proportion of incident infections among candidate donors/first-time donations/repeat donations was for HBV, 3.40/0/0.36; for HCV, 0/0/0.02; and for HIV 0/0.69/0.14 per 100,000, respectively. Predonation screening of candidate donors very likely causes a loss of donations, but it might prevent undetected window period donations. Further studies are necessary to determine the value of predonation screening as an additional safety measure. © 2014 AABB.

ANTI-VIRAL ACTIVITY OF GLYCIRRHETINIC AND GLYCIRRHIZIC ACIDS

Directory of Open Access Journals (Sweden)

V. V. Zarubaev

2016-01-01

Full Text Available Influenza is a highly contagious human disease. In the course of use of antiviral drugs drug-resistant strains of the virus are formed, resulting in reduced efficiency of the chemotherapy. The review describes the biological activity of glycirrhetinic (GLA and glycirrhizic (GA acids in terms of their use as a therapeutic agent for viral infections. So, these compounds are against a broad spectrum of viruses, including herpes, corona-, alphaand flaviviruses, human immunodeficiency virus, vaccinia virus, poliovirus type I, vesicular stomatitis virus and influenza A virus. These data indicate that anti-viral effect of these compounds is due to several types of activity — direct antiviral effects, effects on cellular proand anti-viral and immunomodulating pathways, in particular by activation of innate immunity system. GA interferes with early steps of the viral reproductive cycle such as virus binding to its receptor, the absorption of the virus by endocytosis or virus decapsidation in the cytoplasm. This is due to the effect of GA-induced reduction of membrane fluidity. Thus, one mechanism for the antiviral activity of GA is that GA molecule increases the rigidity of cellular and viral membranes after incorporation in there. This results in increasing of energy threshold required for the formation of negative curvature at the fusion zones, as well as difficult lateral migration of the virus-receptor complexes. In addition, glycyrrhizin prevents interaction of viral nucleoprotein with cellular protein HMGB1, which is necessary for the viral life cycle. Glycyrrhizin also inhibits the induction of oxidative stress during influenza infection, exhibiting antioxidant properties, which leads to a reduction of virus-induced production of cytokines/chemokines, without affecting the replication of the virus. A wide spectrum of biological activity and effect on various aspects of the viral pathogenesis substantiate the effect of GA and GLA as a component

EVALUATION OF ANTI-INFLAMMATORY, ANTIBACTERIAL AND ...

African Journals Online (AJOL)

User

Anti-inflammatory activity was determined using a LOX-inhibitor screening assay kit according to the ... and the Ferric ion reducing antioxidant power (FRAP). Antimicrobial activities ..... the best of our knowledge this is the first report on the.

Development of a bioassay to screen for chemicals mimicking the anti-aging effects of calorie restriction

Energy Technology Data Exchange (ETDEWEB)

Chiba, Takuya, E-mail: takuya@nagasaki-u.ac.jp [Department of Investigative Pathology, Graduate School of Biomedical Sciences, Nagasaki University, 1-12-4 Sakamoto, Nagasaki 852-8523 (Japan); Tsuchiya, Tomoshi [Division of Surgical Oncology, Graduate School of Biomedical Sciences, Nagasaki University, 1-7-1 Sakamoto, Nagasaki 852-8501 (Japan); Komatsu, Toshimitsu; Mori, Ryoichi; Hayashi, Hiroko [Department of Investigative Pathology, Graduate School of Biomedical Sciences, Nagasaki University, 1-12-4 Sakamoto, Nagasaki 852-8523 (Japan); Shimano, Hitoshi [Department of Internal Medicine (Endocrinology and Metabolism), Graduate School of Comprehensive Human Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba Ibaraki 305-8575 (Japan); Spindler, Stephen R. [Department of Biochemistry, Room 5478, Boyce Hall, University of California - Riverside, Riverside, CA 92521 (United States); Shimokawa, Isao [Department of Investigative Pathology, Graduate School of Biomedical Sciences, Nagasaki University, 1-12-4 Sakamoto, Nagasaki 852-8523 (Japan)

2010-10-15

Research highlights: {yields} We identified four sequence motifs lying upstream of putative pro-longevity genes. {yields} One of these motifs binds to HNF-4{alpha}. {yields} HNF-4{alpha}/PGC-1{alpha} could up-regulate the transcription of a reporter gene linked to this motif. {yields} The reporter system described here could be used to screen candidate anti-aging molecules. -- Abstract: Suppression of the growth hormone/insulin-like growth factor-I pathway in Ames dwarf (DF) mice, and caloric restriction (CR) in normal mice extends lifespan and delays the onset of age-related disorders. In combination, these interventions have an additive effect on lifespan in Ames DF mice. Therefore, common signaling pathways regulated by DF and CR could have additive effects on longevity. In this study, we tried to identity the signaling mechanism and develop a system to assess pro-longevity status in cells and mice. We previously identified genes up-regulated in the liver of DF and CR mice by DNA microarray analysis. Motif analysis of the upstream sequences of those genes revealed four major consensus sequence motifs, which have been named dwarfism and calorie restriction-responsive elements (DFCR-REs). One of the synthesized sequences bound to hepatocyte nuclear factor-4{alpha} (HNF-4{alpha}), an important transcription factor involved in liver metabolism. Furthermore, using this sequence information, we developed a highly sensitive bioassay to identify chemicals mimicking the anti-aging effects of CR. When the reporter construct, containing an element upstream of a secreted alkaline phosphatase (SEAP) gene, was co-transfected with HNF-4{alpha} and its regulator peroxisome proliferator-activated receptor (PPAR) {gamma} coactivator-1{alpha} (PGC-1{alpha}), SEAP activity was increased compared with untransfected controls. Moreover, transient transgenic mice established using this construct showed increased SEAP activity in CR mice compared with ad libitum-fed mice. These data

Internet recruitment for sexually transmitted infection screening among men who have sex with men in Eastern Europe.

Science.gov (United States)

Mangine, Cara; Kukk, Aigi; Noormets, Helen; Jänes, Jaak; Rüütel, Kristi

2018-03-01

Men who have sex with men (MSM) face negative health outcomes such as sexually transmitted infections (STIs) at disproportionate rates. Nonetheless, infections may be underestimated due to limited uptake in testing. To increase testing, screening interventions have been utilized in the past; however, some have resulted in limitations such as poor recruitment. To increase recruitment for screening of MSM in Estonia, two different recruitment strategies were examined. Recruitment was separated into two promotional periods: passive and active. Passive consisted of banners on gay-related sites, while active also placed banners on websites to the general public such as Facebook linked to specific thematic pages and users self-identifying as men. More men were recruited during the active period of five weeks (n = 134) than the passive period of 46 weeks (n = 126). Active promotion was so successful in that the number of home sampling kit orders far exceeded what was projected, forcing promotion to the general public to be closed after 13 days. Recruiting MSM through a combination of general public and gay-related websites and applications has the ability to quickly recruit for testing interventions. This method can recruit a large number in a short amount of time; therefore, a budget must be planned accordingly to support testing for all that participate.

[A case with chronic active EB virus infection accompanied with pulmonary candidiasis].

Science.gov (United States)

Karino, T; Nakamura, J; Fujita, K; Kobashi, Y; Yano, T; Okimoto, N; Soejima, R

1998-12-01

A 44-year-old woman with a history of intermittent fever for several years was admitted because of burn on her leg. On admission, she had hepatosplenomegaly and fever. Antibiotic therapy was started for bacterial infection of the burn. She lost her appetite and IVH was started. During the treatment, high fever appeared and chest X-ray films showed multiple nodular infiltrates throughout both lung fields. Candida albicans was isolated from IVH catheter culture and pulmonary candidiasis was suspected. Her fever and lung involvements were successfully treated with fluconazole. During the course, serum anti-EB-VCA-IgG antibody persisted at a high titer and anti-EBNA antibody remained negative. EB virus DNA was detected in the peripheral blood and bone marrow. Thus, she was diagnosed as chronic active EB virus infection.

Prevalence of HBsAg and anti-HBs among delivering women.

Science.gov (United States)

Sabău, M; Căpîlnă; Kiss, E

1979-01-01

A survey of 2,500 delivering women revealed a 7.6% incidence of past infection with hepatitis B virus (HBV) (HBsAg or anti-HBs). Only 5.9% of the anti-HBs-positive mothers had a possible history of parenteral exposure to hepatitis B and none of the 55 HBsAg carriers had such a history. The findings suggest that HBV is endemic and that it is probably spread in part by nonparenteral means. The high rates of HBsAg and anti-HBs point to the possible preventive value of routine screenings for this system among pregnant women.

Low prevalence of hepatitis B and C among tuberculosis patients in Duhok Province, Kurdistan: Are HBsAg and anti-HCV prerequisite screening parameters in tuberculosis control program?

Directory of Open Access Journals (Sweden)

Muayad A Merza

2016-01-01

Full Text Available Objective/background: Viral hepatitis, particularly hepatitis B virus (HBV and hepatitis C virus (HCV, infections and tuberculosis (TB are a global public health concern. Co-infection with HBV or HCV among TB patients may potentiate the risk of hepatotoxicity induced by anti-TB drugs. Hence, the aim of this study was to identify the prevalence of HBV and HCV among TB patients included in the Duhok National Tuberculosis Program (NTP. Methods: The Duhok NTP Center is a specialized institution in Duhok City, Iraq, concerned with management and follow-up of TB patients. A cross-sectional study was conducted at the center between June 2015 and May 2016. All documented TB patients were analyzed on the basis of socio-demographic and other characteristics. Thereafter, all patients underwent screening for hepatitis B surface antigen (HBsAg, anti-HCV, and anti-HIV using enzyme-linked immunosorbent assay (ELISA. The results obtained were analyzed by entering the data in binary format into a Microsoft Excel spreadsheet. A p value of <.05 was considered to be statistically significant. Results: Two-hundred fourteen documented TB patients were recruited in this study, with 127 (59.3% males and 87 (40.7% females. The mean age of the patients was 40.34 years (±20.29. Of the total number of patients, four cases (1.8% were HBsAg-positive and one case (0.9% was positive for anti-HCV. The variables significantly associated with HBV were history of surgical dental procedure [odds ratio (OR, 0.04; 95% confidence interval (CI, −0.01 to 0.04; p = .03], and nationality (OR, 13.67; 95% CI, 0.46–210.85; p = .007. Conclusion: The prevalence of HBV and HCV co-infection among TB patients in this study was low. This may be explained by the low rate of blood transfusion among the patients, the very low prevalence of HIV infections in Kurdistan, the negative history of injection drug use, and adherence to universal infection-control measures, including vaccination for HBV

Hexagonal-shaped chondroitin sulfate self-assemblies have exalted anti-HSV-2 activity.

Science.gov (United States)

Galus, Aurélia; Mallet, Jean-Maurice; Lembo, David; Cagno, Valeria; Djabourov, Madeleine; Lortat-Jacob, Hugues; Bouchemal, Kawthar

2016-01-20

The initial step in mucosal infection by the herpes simplex virus type 2 (HSV-2) requires its binding to certain glycosaminoglycans naturally present on host cell membranes. We took advantage of this interaction to design biomimetic supramolecular hexagonal-shaped nanoassemblies composed of chondroitin sulfate having exalted anti-HSV-2 activity in comparison with native chondroitin sulfate. Nanoassemblies were formed by mixing hydrophobically-modified chondroitin sulfate with α-cyclodextrin in water. Optimization of alkyl chain length grafted on chondroitin sulfate and the ratio between hydrophobically-modified chondroitin sulfate and α-cyclodextrin showed that more cohesive and well-structured nanoassemblies were obtained using higher α-cyclodextrin concentration and longer alkyl chain lengths. A structure-activity relationship was found between anti-HSV-2 activity and the amphiphilic nature of hydrophobically-modified chondroitin sulfate. Also, antiviral activity of hexagonal nanoassemblies against HSV-2 was further improved in comparison with hydrophobically-modified chondroitin sulfate. This work suggests a new biomimetic formulation approach that can be extended to other heparan-sulfate-dependent viruses. Copyright © 2015 Elsevier Ltd. All rights reserved.

Anti-inflammatory and neuropharmacological activities of ...

African Journals Online (AJOL)

The crude methanolic extracts of leaves of Caesalpinia pulcherrima were evaluated for its anti-inflammatory and neuropharmacological activities. When given orally to rats at dose of 200 and 400 mg/kg, the extract showed a significant (P<0.001) anti-inflammatory activity against carrageenin induced paw edema in rats ...

Qualitative phytochemical screening and evaluation of anti-inflammatory, analgesic and antipyretic activities of Microcos paniculata barks and fruits.

Science.gov (United States)

Aziz, Md Abdullah

2015-05-01

The main objectives of this study were to qualitatively evaluate the profile of phytochemical constituents present in methanolic extract of Microcos paniculata bark (BME) and fruit (FME), as well as to evaluate their anti-inflammatory, analgesic and antipyretic activities. Phytochemical constituents of BME and FME were determined by different qualitative tests such as Molisch's test, Fehling's test, alkaloid test, frothing test, FeCl3 test, alkali test, Salkowski's test and Baljet test. The anti-inflammatory, analgesic and antipyretic activities of the extracts were evaluated through proteinase-inhibitory assay, xylene-induced ear edema test, cotton pellet-induced granuloma formation in mice, formalin test, acetic acid-induced writhing test, tail immersion test and Brewer's yeast-induced pyrexia in mice. M. paniculata extracts revealed the presence of carbohydrates, alkaloids, saponins, tannins, flavonoids and triterpenoids. All of the extracts showed significant (Panalgesic activities at 60 min in the tail immersion test. Again, the significant (Panalgesic and antipyretic activities.

Anti-oxidant and anti-inflammatory activity of leaf extracts and fractions of Mangifera indica.

Science.gov (United States)

Mohan, C G; Deepak, M; Viswanatha, G L; Savinay, G; Hanumantharaju, V; Rajendra, C E; Halemani, Praveen D

2013-04-13

To evaluate the anti-oxidant and anti-inflammatory activity of leaf extracts and fractions of Mangifera indica in in vitro conditions. In vitro DPPH radical scavenging activity and lipoxygenase (LOX) inhibition assays were used to evaluate the anti-oxidant and anti-inflammatory activities respectively. Methanolic extract (MEMI), successive water extract (SWMI) and ethyl acetate fraction (EMEMI), n-butanol fraction (BMEMI) and water soluble fraction (WMEMI) of methanolic extract were evaluated along with respective reference standards. In in vitro DPPH radical scavenging activity, the MEMI, EMEMI and BMEMI have offered significant antioxidant activity with IC(50) values of 13.37, 3.55 and 14.19 μg/mL respectively. Gallic acid, a reference standard showed significant antioxidant activity with IC(50) value of 1.88 and found to be more potent compared to all the extracts and fractions. In in vitro LOX inhibition assay, the MEMI, EMEMI and BMEMI have showed significant inhibition of LOX enzyme activity with IC(50) values of 96.71, 63.21 and 107.44 μg/mL respectively. While, reference drug Indomethacin also offered significant inhibition against LOX enzyme activity with IC(50) of 57.75. Furthermore, MEMI was found to more potent than SWMI and among the fractions EMEMI was found to possess more potent antioxidant and anti-inflammatory activity. These findings suggest that the MEMI and EMEMI possess potent anti-oxidant and anti-inflammatory activities in in vitro conditions. Copyright © 2013 Hainan Medical College. Published by Elsevier B.V. All rights reserved.

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

Science.gov (United States)

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

2014-10-01

Screening for opportunistic infections prior to starting biological therapy in patients with inflammatory bowel disease is recommended. To assess adherence to screening for opportunistic infections prior to starting biological therapy in Crohn's disease patients and its yield. A multicentre retrospective study was conducted in Crohn's disease patients in whom infliximab or adalimumab was started between 2000 and 2010. Screening included tuberculin skin test, interferon-gamma release assay or chest X-ray for tuberculosis. Extended screening included screening for tuberculosis and viral infections. Patients were followed until three months after ending treatment. Primary endpoints were opportunistic and serious infections. 611 patients were included, 91% on infliximab. 463 (76%) patients were screened for tuberculosis, of whom 113 (24%) underwent extended screening. Screening for tuberculosis and hepatitis B increased to, respectively, 90-97% and 36-49% in the last two years. During a median follow-up of two years, 64/611 (9%, 3.4/100 patient-years) opportunistic infections and 26/611 (4%, 1.6/100 patient-years) serious infections were detected. Comorbidity was significantly associated with serious infections (hazard ratio 3.94). Although screening rates for tuberculosis and hepatitis B increased, screening for hepatitis B was still suboptimal. More caution is required when prescribing biologicals in patients with comorbid conditions. Copyright © 2014 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

Identification of three classes of heteroaromatic compounds with activity against intracellular Trypanosoma cruzi by chemical library screening.

Directory of Open Access Journals (Sweden)

Esther Bettiol