The enteric flora comprises approximately 95% of the total number of cells in the human body and can elicit immune responses while protecting against microbial pathogens. However, the resident bacterial flora of the gastrointestinal tract may also be implicated in the pathogenesis of diseases such as inflammatory bowel disease (ulcerative colitis and Crohn disease). The objectives of the Probiotic Research Group based at University College Cork were to isolate and identify lactic acid bacteria exhibiting beneficial probiotic traits, such as bile tolerance in the absence of deconjugation activity, acid resistance, adherence to host epithelial tissue, and in vitro antagonism of pathogenic microorganisms or those suspected of promoting inflammation. To isolate potentially effective probiotic bacteria, we screened the microbial population adhering to surgically resected segments of the gastrointestinal tract (the environment in which they may subsequently be reintroduced and required to function). In total, 1500 bacterial strains from resected human terminal ilea were assessed. From among these organisms, Lactobacillus salivarius subsp. salivarius strain UCC118 was selected for further study. In mouse feeding trials, milk-borne L. salivarius strain UCC118 could successfully colonize the murine gastrointestinal tract. A human feeding study conducted in 80 healthy volunteers showed that yogurt can be used as a vehicle for delivery of strain UCC118 to the human gastrointestinal tract with considerable efficacy in influencing gut flora and colonization. In summary, we developed criteria for in vitro selection of probiotic bacteria that may reflect certain in vivo effects on the host such as modulation of gastrointestinal tract microflora.
BackgroundAetiology of births involving very low birthweight (VLBW) and extremely low birthweight (ELBW) infants is heterogeneous and preventive strategies remain elusive. Socioenvironmental measures implemented as Ireland’s response to the SARS-CoV-2 virus (COVID-19) pandemic represented a national lockdown, and have possibly influenced the health and well-being of pregnant women and unborn infants.MethodsRegional trends of VLBW and ELBW infants in one designated health area of Ireland over two decades were analysed. Poisson regression and rate ratio analyses with 95% CI were conducted. Regional data covering most of the lockdown period of 2020 were compared with historical regional and national data and forecasted national figures for 2020.ResultsPoisson regression analysis found that the regional historical VLBW rate per 1000 live births for January to April, 2001–2019 was 8.18 (95% CI 7.21 to 9.29). During January to April 2020, an unusually low VLBW rate of just 2.17 per 1000 live births was observed, reflecting a rate ratio of 3.77 (95% CI 1.21 to 11.75), p=0.022, representing a 73% reduction of VLBW during the first 4 months of 2020 compared with same period for the preceding two decades. There were no ELBW infants admitted to the regional neonatal intensive care unit. National Irish VLBW rate for 2020 is forecasted to be reduced to approximate 400 per 60 000 births compared with the historical 500–600 range.ConclusionAn unprecedented reduction in regional births of VLBW and ELBW infants was observed in Ireland coinciding with the COVID-19 lockdown. Potential determinants of this unique temporal trend possibly reside in the summative socioenvironmental impact of the COVID-19 lockdown. Our findings, if mirrored in other regions that have adopted a lockdown, demonstrate the potential to evaluate these implicated behavioural and socioenvironmental modifiers to positively influence VLBW and ELBW rates globally.
Background and AimsInclusion of the mesentery during resection for colorectal cancer is associated with improved outcomes but has yet to be evaluated in Crohn’s disease. This study aimed to determine the rate of surgical recurrence after inclusion of mesentery during ileocolic resection for Crohn’s disease.MethodsSurgical recurrence rates were compared between two cohorts. Cohort A [n = 30] underwent conventional ileocolic resection where the mesentery was divided flush with the intestine. Cohort B [n = 34] underwent resection which included excision of the mesentery. The relationship between mesenteric disease severity and surgical recurrence was determined in a separate cohort [n = 94]. A mesenteric disease activity index was developed to quantify disease severity. This was correlated with the Crohn’s disease activity index and the fibrocyte percentage in circulating white cells.ResultsCumulative reoperation rates were 40% and 2.9% in cohorts A and B [P = 0.003], respectively. Surgical technique was an independent determinant of outcome [P = 0.007]. Length of resected intestine was shorter in cohort B, whilst lymph node yield was higher [12.25 ± 13 versus 2.4 ± 2.9, P = 0.002]. Advanced mesenteric disease predicted increased surgical recurrence [Hazard Ratio 4.7, 95% Confidence Interval: 1.71–13.01, P = 0.003]. The mesenteric disease activity index correlated with the mucosal disease activity index [r = 0.76, p < 0.0001] and the Crohn’s disease activity index [r = 0.70, p < 0.0001]. The mesenteric disease activity index was significantly worse in smokers and correlated with increases in circulating fibrocytes.ConclusionsInclusion of mesentery in ileocolic resection for Crohn’s disease is associated with reduced recurrence requiring reoperation.
The enteric flora comprise approximately 95% of the total number of cells in the human body and are capable of eliciting immune responses while also protecting against microbial pathogens. However, the resident bacterial flora of the gastrointestinal tract (GIT) may also be implicated in the pathogenesis of several chronic conditions such as inflammatory bowel disease (IBD). The University College Cork-based Probiotic Research Group has successfully isolated and identified lactic acid bacteria (LAB) which exhibit beneficial probiotic traits. These characteristics include the demonstration of bile tolerance; acid resistance; adherence to host epithelial tissue; and in vitro antagonism of potentially-pathogenic micro-organisms or those which have been implicated in promoting inflammation. The primary objective of this report is to describe the strategy adopted for the selection of potentially effective probiotic bacteria. The study further describes the evaluation of two members of the resulting panel of micro-organisms (Lactobacillus salivarius subsp. salivarius UCCl18 and Bifidobacterium longum infantis 35624) under in vitro conditions and throughout in vivo murine and human feeding trials. Specifically, an initial feeding study completed in Balb/c mice focused upon (i) effective delivery of the probiotic micro-organisms to the GIT and evaluation of the ability of the introduced strains to survive transit through, and possibly colonise, the murine GIT; (ii) accepting the complexity of the hostile GIT and faecal environments, development of a method of enumerating the introduced bacterial strains using conventional microbiological techniques; and (iii) assessment of the effects of administered bacterial strains on the numbers of specific recoverable indigenous bacteria in the murine GIT and faeces. Additional research, exploiting the availability of murine models of inflammatory bowel disease, demonstrated the beneficial effects of administering probiotic combinations of Lactobacillus salivarius UCC1l8 and Bifidobacterium longum in/antis 35624 in prevention of illness-related weight loss. A further ethically-approved feeding trial, successfully conducted in 80 healthy volunteers, demonstrated that yoghurt can be used as a vehicle for delivery of Lactobacillus salivarius strain UCCl18 to the human GIT with considerable efficacy in influencing gut flora and colonisation.
Generic medicines are those where patent protection has expired, and which may be produced by manufacturers other than the innovator company. Use of generic medicines has been increasing in recent years, primarily as a cost saving measure in healthcare provision. Generic medicines are typically 20 to 90% cheaper than originator equivalents. Our objective is to provide a high-level description of what generic medicines are and how they differ, at a regulatory and legislative level, from originator medicines. We describe the current and historical regulation of medicines in the world’s two main pharmaceutical markets, in addition to the similarities, as well as the differences, between generics and their originator equivalents including the reasons for the cost differences seen between originator and generic medicines. Ireland is currently poised to introduce generic substitution and reference pricing. This article refers to this situation as an exemplar of a national system on the cusp of significant health policy change, and specifically details Ireland’s history with usage of generic medicines and how the proposed changes could affect healthcare provision.
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