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Search Results: 1 - 10 of 119415 matches for " Jim O'Mahony "
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What's in a Name? Can Mullein Weed Beat TB Where Modern Drugs Are Failing?
Eibhlín McCarthy,Jim M. O'Mahony
Evidence-Based Complementary and Alternative Medicine , 2011, DOI: 10.1155/2011/239237
Abstract: Common mullein weed (Verbascum thapsus) has a large number of synonyms and old local “nick names” which connect the plant with mycobacteria. A strong history of medicinal use has been uncovered for the treatment of tuberculosis, tubercular skin disease, leprosy, and mycobacterial disease in animals. Here, we examine problems encountered in treating such diseases today, the historical and scientific links between mullein and pathogenic bacteria, and the possibility that this common weed could harbour the answer to beating one of the world's biggest infectious killers.
Isolation and detection of Mycobacterium avium subsp. paratuberculosis (MAP) from cattle in Ireland using both traditional culture and molecular based methods
Pierre E Douarre, William Cashman, Jim Buckley, Aidan Coffey, Jim M O'Mahony
Gut Pathogens , 2010, DOI: 10.1186/1757-4749-2-11
Abstract: M. paratuberculosis was isolated and cultured from 23 faecal samples (7.9%) on solid medium. From a molecular perspective, 105 faecal samples (36%) were PCR positive for MAP specific DNA. A complete correlation (100%) was observed between the results of both molecular targets (IS900 and ISMAP02). Sensitivity was increased by ~10% with the inclusion of a nested PCR for ISMAP02 (29 further samples were positive). When culturing and PCR were retrospectively compared, every culture positive faecal sample also yielded a PCR positive result for both targets. Alternatively, however not every PCR positive sample (n = 105, 36%) produced a corresponding culture isolate. Interestingly though when analysed collectively at the herd level, the correlation between culture and PCR results was 100% (ie every herd which recorded at least 1 early PCR +ve result later yielded culture positive samples within that herd).PCR on bovine faecal samples is a fast reliable test and should be applied routinely when screening for MAP within herds suspected of paratuberculosis. Nested PCR increases the threshold limit of detection for MAP DNA by approximately 10% but proved to be problematic in this study. Although slow and impractical, culturing is still regarded as one of the most reliable methods for detecting MAP among infected cattle.Johne's disease caused by Mycobacterium avium subsp. paratuberculosis (MAP), is one of the most widespread and economically important disease of ruminants. It is a chronic granulomatous enteritis affecting primarily ruminants and many other species [1], which is characterised by persistent diarrhoea, weight loss and a protein enteropathy, followed eventually by death [2]. Most cattle are infected early in life by the ingestion of faeces, milk or MAP contaminated water. The relatively long incubation period is characterized by the excretion of MAP in faeces for months and years before clinical symptoms develop [3]. The exposure to contaminated faeces constitutes
Modulation of pathogen-induced CCL20 secretion from HT-29 human intestinal epithelial cells by commensal bacteria
Shomik Sibartie, Ann M O'Hara, Jude Ryan, áine Fanning, Jim O'Mahony, Shaun O'Neill, Barbara Sheil, Liam O'Mahony, Fergus Shanahan
BMC Immunology , 2009, DOI: 10.1186/1471-2172-10-54
Abstract: Compared to untreated cells, S. typhimurium, C. difficile, M. paratuberculosis, and flagellin activated NF-κB and stimulated significant secretion of CCL20 and IL-8 by HT-29 cells. Conversely, B. infantis, L. salivarius or M. smegmatis did not activate NF-κB or augment CCL20 or IL-8 production. Treatment with B. infantis, but not L. salivarius, dose-dependently inhibited the baseline secretion of CCL20. In cells pre-treated with B. infantis, C. difficile-, S. typhimurium-, and flagellin-induced CCL20 were significantly attenuated. B. infantis did not limit M. Paratuberculosis-induced CCL20 secretion.This study is the first to demonstrate that a commensal strain can attenuate CCL20 secretion in HT-29 IECs. Collectively, the data indicate that M. paratuberculosis may mediate mucosal damage and that B. infantis can exert immunomodulatory effects on IECs that mediate host responses to flagellin and flagellated enteric pathogens.Intestinal epithelial cells (IECs) play a crucial role in the maintenance of mucosal homeostasis, and actively sample commensal bacteria, pathogens, and other antigens [1,2]. Under normal circumstances, the mucosal immune system exhibits a restrained response to commensal bacteria whilst retaining an ability to mount appropriate immune responses to pathogenic bacteria. IECs can trigger innate immune responses that activate pro-inflammatory signalling pathways, as well as direct the migration of various effector cells involved in adaptive immunity [2]. Bone marrow-derived dendritic cells (DCs) in the lamina propria also sample commensal and pathogenic bacteria at mucosal interfaces [3,4]. This appears to be achieved by opening tight junctions and extending dendrites between IECs [5]. Encounter with bacteria or bacterial antigens triggers the functional maturation of DCs leading to the generation of antigen-presenting cells that can activate na?ve T cells [6]. Therefore, the recruitment of DCs into the epithelium is a prerequisite for the initiatio
Bacteriophage-Derived Peptidase Eliminates and Prevents Staphylococcal Biofilms
Mark Fenton,Ruth Keary,Olivia McAuliffe,R. Paul Ross,Jim O'Mahony,Aidan Coffey
International Journal of Microbiology , 2013, DOI: 10.1155/2013/625341
Abstract: New antibacterial agents are urgently needed for the elimination of biofilm-forming bacteria that are highly resistant to traditional antimicrobial agents. Proliferation of such bacteria can lead to significant economic losses in the agri-food sector. This study demonstrates the potential of the bacteriophage-derived peptidase, , as a biocidal agent for the rapid disruption of biofilm-forming staphylococci, commonly associated with bovine mastitis. Purified applied to biofilms of Staphylococcus aureus DPC5246 completely eliminated the staphylococcal biofilms within 4?h. In addition, was able to prevent biofilm formation by this strain. The lysin also reduced S. aureus in a skin decolonization model. Our data demonstrates the potential of as a biocidal agent for prevention and treatment of biofilm-associated staphylococcal infections or as a decontaminating agent in the food and healthcare sectors. 1. Introduction Staphylococcal species commonly colonise the skin and mucosal membranes of both humans and animals. They are a significant causative agent of bovine mastitis in dairy herds [1] and are also associated with a number of diseases in humans, ranging from a variety of skin conditions to more serious infections such as septicemia [2]. Staphylococcal food poisoning is among the most common food-borne microbial diseases [3] and contamination of food industrial surfaces with staphylococcal species has been demonstrated to be a considerable risk factor [4–6]. Along with the urgent requirement for novel antibacterials to combat the prevalence of antibiotic/disinfectant resistant staphylococci in food processing, veterinary and healthcare settings, there is an increasing need for effective antimicrobial agents which can prevent and treat staphylococcal biofilm-associated infections [7–11]. Biofilms are multilayered communities of sessile cells protected by an extracellular matrix, which often adhere to food contact surfaces, damaged tissue and indwelling medical devices [12–14]. Once formed, biofilms may be up to 1,000 times more resistant to antimicrobial agents than planktonic cells alone making them particularly difficult to eliminate [15]. This can ultimately lead to increased risk of persistent infections, as is commonly the case with bovine mastitis [16]. In addition, because of their increased levels of resistance, biofilm-associated infections can result in a need for explantation of medical devices in human healthcare settings [17, 18]. Although the precise mechanisms of biofilm antibiotic resistance have yet to be fully resolved, failure to
Bacteriophages and Their Derivatives as Biotherapeutic Agents in Disease Prevention and Treatment
Mohamed Elbreki,R. Paul Ross,Colin Hill,Jim O'Mahony,Olivia McAuliffe,Aidan Coffey
Journal of Viruses , 2014, DOI: 10.1155/2014/382539
Abstract: The application of bacteriophages for the elimination of pathogenic bacteria has received significantly increased attention world-wide in the past decade. This is borne out by the increasing prevalence of bacteriophage-specific conferences highlighting significant and diverse advances in the exploitation of bacteriophages. While bacteriophage therapy has been associated with the Former Soviet Union historically, since the 1990s, it has been widely and enthusiastically adopted as a research topic in Western countries. This has been justified by the increasing prevalence of antibiotic resistance in many prominent human pathogenic bacteria. Discussion of the therapeutic aspects of bacteriophages in this review will include the uses of whole phages as antibacterials and will also describe studies on the applications of purified phage-derived peptidoglycan hydrolases, which do not have the constraint of limited bacterial host-range often observed with whole phages. 1. Bacteriophage History Bacteriophages (phages) were first characterised about 100 years ago by [1–3]. Earlier authors, such as Ernest Hankin [4], Nikolay Gamaleya [5], and Frederick Twort [6], are understood to have observed the antibacterial activity of phages without being able to recognise or identify the agents responsible. Nowadays, most recognition for the development of phage therapy goes to Felix d’Herelle who isolated these agents from the stool samples of dysentery patients, named them bacteriophages, and developed the phage assays which remain in use up to the present [7, 8]. He also initiated the first phage therapy experiments in the early 1920s. Research in phage therapy was eclipsed in the West by the advent and increasing widespread successful application of antibiotics in medical practice from the late 1940s. Phage therapy, on the other hand, was declined largely due to variable and unpredictable results, an issue related to the relatively poor understanding of phage biology at the time. Certainly, many of the illnesses that had been treated with phage preparations up to the mid-twentieth century were likely to have not had a bacterial basis. Thus, the results of phage therapy generally tended to be inferior to those observed for antibiotics, since the latter had a broader therapeutic spectrum and, generally, did not require detailed bacteriological knowledge for effective prescribing by practitioners. The use of phages to treat bacterial infections has recently gained attention in Western medicine mainly due to ever-increasing incidence of bacterial resistance to antibiotics
Enhanced expression of codon optimized Mycobacterium avium subsp. paratuberculosis antigens in Lactobacillus salivarius
Christopher D. Johnston,John P. Bannantine,Daniel Pletzer,Helge Weingart,Aidan Coffey,Jim O'Mahony,Roy D. Sleator
Frontiers in Cellular and Infection Microbiology , 2014, DOI: 10.3389/fcimb.2014.00120
Abstract: It is well documented that open reading frames containing high GC content show poor expression in A+T rich hosts. Specifically, G+C-rich codon usage is a limiting factor in heterologous expression of Mycobacterium avium subsp. paratuberculosis (MAP) proteins using Lactobacillus salivarius. However, re-engineering opening reading frames through synonymous substitutions can offset codon bias and greatly enhance MAP protein production in this host. In this report, we demonstrate that codon-usage manipulation of MAP2121c can enhance the heterologous expression of the major membrane protein (MMP), analogous to the form in which it is produced natively by MAP bacilli. When heterologously over-expressed, antigenic determinants were preserved in synthetic MMP proteins as shown by monoclonal antibody mediated ELISA. Moreover, MMP is a membrane protein in MAP, which is also targeted to the cellular surface of recombinant L. salivarius at levels comparable to MAP. Additionally, we previously engineered MAP3733c (encoding MptD) and show herein that MptD displays the tendency to associate with the cytoplasmic membrane boundary under confocal microscopy and the intracellularly accumulated protein selectively adheres to the MptD-specific bacteriophage fMptD. This work demonstrates there is potential for L. salivarius as a viable antigen delivery vehicle for MAP, which may provide an effective mucosal vaccine against Johne's disease.
A Successful Pregnancy Outcome after Surgical Decompression of Type I Arnold-Chiari Malformation  [PDF]
Patricia Ip, Susmita Pankaja, Fidelma OMahony
Open Journal of Obstetrics and Gynecology (OJOG) , 2015, DOI: 10.4236/ojog.2015.51007
Abstract: Type I Arnold-Chiari malformation (ACM) usually presents in adulthood and consists of a downward displacement of the cerebellar tonsils through the foramen magnum. A 25-year-old woman presented with a 5-month history of headache associated with blurred vision, tinnitus and sickness. Imaging recognised the need for surgical intervention, but whilst awaiting for surgery she fell pregnant. Considering the risks of neurological deterioration, the woman underwent surgical decompression of type I ACM at 15 weeks gestation. She subsequently presented with progressively worsening headaches during late pregnancy from 35 weeks. The obstetric plan was initially induction of labour at term but since the onset of worsening symptoms, this date was brought forward to 39 + 1 weeks gestation. She proceeded to have a normal delivery with no neonatal complications and an uneventful puerperium followed. Since the delivery, the patient reported fewer symptoms, showed no signs of neurological deficit and a repeat magnetic resonance imaging of the head showed good relief of neural compression. This case illustrates how judicious selection of the appropriate mode of delivery of women following surgically corrected ACM and a multidisciplinary approach is critical in the successful management of the antepartum period and labour.
Investigating the Activity Spectrum for Ring-Substituted 8-Hydroxyquinolines
Robert Musiol,Josef Jampilek,Jacek E. Nycz,Matus Pesko,James Carroll,Katarina Kralova,Marcela Vejsova,Jim O'Mahony,Aidan Coffey,Anna Mrozek,Jaroslaw Polanski
Molecules , 2010, DOI: 10.3390/molecules15010288
Abstract: In this study, a series of fourteen ring-substituted 8-hydroxyquinoline derivatives were prepared. The synthesis procedures are presented. The compounds were analyzed using RP-HPLC to determine lipophilicity. They were tested for their activity related to inhibition of photosynthetic electron transport (PET) in spinach (Spinacia oleracea L.) chloroplasts. Primary in vitro screening of the synthesized compounds was also performed against four mycobacterial strains and against eight fungal strains. Several compounds showed biological activity comparable with or higher than the standards isoniazid or fluconazole. For all the compounds, the relationships between the lipophilicity and the chemical structure of the studied compounds are discussed.
Investigating Biological Activity Spectrum for Novel Styrylquinazoline Analogues
Josef Jampilek,Robert Musiol,Jacek Finster,Matus Pesko,James Carroll,Katarina Kralova,Marcela Vejsova,Jim O'Mahony,Aidan Coffey,Jiri Dohnal,Jaroslaw Polanski
Molecules , 2009, DOI: 10.3390/molecules14104246
Abstract: In this study, series of ring-substituted 2-styrylquinazolin-4(3H)-one and 4-chloro-2-styrylquinazoline derivatives were prepared. The syntheses of the discussed compounds are presented. The compounds were analyzed by RP-HPLC to determine lipophilicity. They were tested for their inhibitory activity on photosynthetic electron transport (PET) in spinach (Spinacia oleracea L.) chloroplasts. Primary in vitro screening of the synthesized compounds was also performed against four mycobacterial strains and against eight fungal strains. Several compounds showed biological activity comparable with or higher than that of the standard isoniazid. It was found that the electronic properties of the R substituent, and not the total lipophilicity of the compound, were decisive for the photosynthesis-inhibiting activity of tested compounds.
Infection control in general practices in Buffalo City and OR Tambo District Municipalities, South Africa
Don O'Mahony
African Journal of Primary Health Care & Family Medicine , 2012, DOI: 10.4102/phcfm.v4i1.268
Abstract: Background: Good infection control practices are effective in reducing rates of infection in health care settings. Studies in primary care in developed countries indicate that many general practitioners (GPs) do not comply with optimal infection control practices. There are no published studies from developing countries in Southern Africa. Objectives: The aim of this study was to describe infection control practices in private GP surgeries in the Buffalo City and OR Tambo District Municipalities in the Eastern Cape Province, South Africa. Method: A literature review was conducted to appraise current best practice with respect to Standard Infection Control and Transmission Based Precautions. A questionnaire, inquiring into GPs’ actual practices, was posted to each surgery. Results: The valid response rate was 34% (47/140). Methods used to sterilise instruments in 40 practices were: ultraviolet sterilisation (23), chemical disinfection (14), boiling water (7), and steam autoclave (2). Compounds used for chemical disinfection included organotin quaternary, chlorhexidine and benzyl ammonium chloride with a quaternary complex. Twenty-two (47%) used a hand rub. Sixteen (35%) GPs stated that they had a policy to promptly triage patients who are coughing, and 23 (50%) had a policy for airflow movement in the surgery. All practices appropriately disposed of sharps. Thirty-seven (80%) expressed interest in a seminar on infection control. Conclusions: Overall, GPs were aware of infection control precautions. Ultraviolet sterilisers and chlorhexidine are not recommended, however, for sterilisation or high level disinfection of medical instruments, and their use should be discontinued. Hand rubs are underutilised. GPs should implement Transmission Based Precautions to prevent airborne and droplet infections. Contr le des infections dans les cabinets de médecine générale dans les municipalités de Buffalo City et du district d’OR Tambo, en Afrique du Sud Contexte: De bonnes pratiques de contr le des infections sont efficaces pour réduire les taux d’infection dans les lieux administrant des soins de santé. Des études sur les soins primaires dans les pays développés indiquent que de nombreux médecins généralistes ne respectent pas les pratiques de contr le des infections optimales. Aucune étude émanant des pays en voie de développement en Afrique australe n’a jamais été publiée. Objectifs: L’objectif de cette étude consistait à décrire les pratiques de contr le des infections dans les cabinets de consultation de généralistes privés dans les municipalités de Buffalo City
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