USA: ALKALI in DENTAL BIOFILM

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Review

International Journal of Oral Science (2012) 4, 135–140; doi:10.1038/ijos.2012.54; published online 21 September 2012

Progress toward understanding the contribution of alkali generation in dental biofilms to inhibition of dental caries

Ya-Ling Liu¹, Marcelle Nascimento² and Robert A Burne¹

1. ¹Department of Oral Biology, College of Dentistry, University of Florida, Gainesville, USA
2. ²Department of Restorative Dental Sciences, Division of Operative Dentistry, College of Dentistry, University of Florida, Gainesville, USA

Correspondence: Dr RA Burne, Department of Oral Biology, University of Florida, PO Box 100424, Gainesville, FL 32610-0424, USA. E-mail: rburne@dental.ufl.edu

Received 21 June 2012; Accepted 15 August 2012
Advance online publication 21 September 2012

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Abstract

Alkali production by oral bacteria is believed to have a major impact on oral microbial ecology and to be inibitory to the initiation and progression of dental caries. A substantial body of evidence is beginning to accumulate that indicates the modulation of the alkalinogenic potential of dental biofilms may be a promising strategy for caries control. This brief review highlights recent progress toward understanding molecular genetic and physiologic aspects of important alkali-generating pathways in oral bacteria, and the role of alkali production in the ecology of dental biofilms in health and disease.

Keywords:

arginine; biofilm; dental caries; microbial ecology; urea

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Introduction

Dental biofilms, the microbial communities that colonize the surfaces of the teeth, exist in a dynamic equilibrium with host defenses and are generally compatible with the integrity of the tissues they colonize.^1,2,3,4 A strong correlation is evident between the compositional and metabolic changes of the dental biofilms and the transition from oral health to disease states, including dental caries and periodontal disease.^2,5 In the case of caries, frequent acidification of dental biofilms favors the emergence of an acidogenic and aciduric microflora, including mutans streptococci and Lactobacillus spp., which ferment dietary carbohydrates rapidly and lower the pH to values that accelerate tooth demineralization.^1,2,3,6,7 As might be predicted, the increase in the proportions of aciduric organisms appears to occur at the expense of species that are less aciduric and often associated with dental health.^8,9,10 Importantly, many of the organisms that are associated with dental health are able to use arginine or urea to generate ammonia via the arginine deiminase system or urease enzymes, respectively.¹ Alkali production by these bacteria can positively affect the balance between remineralization and demineralization of the tooth and may also help to prevent the emergence of a cariogenic microflora.^11,12,13,14

A substantial body of evidence suggests that the modulation of the alkali-generating potential of dental plaque may be a promising strategy for caries prevention. In light of the emerging recognition of the inverse correlation between alkali generation and caries, additional research efforts have been focused on the molecular biology, physiology, ecological impact and clinical relevance of alkali production in dental biofilms. The aim of this review is to highlight some of the more recent advances in these areas and immediate research needs.

Primary sources of alkali generation in dental biofilms

The two primary routes for alkali generation in dental plaque are the hydrolysis of urea by urease enzymes and the metabolism of arginine via the arginine deiminase system (ADS).^15,16,17,18 Urea is provided continuously in salivary secretions and gingival exudates at concentrations roughly equivalent to those in serum, which range from about 3 to10 mmol·L⁻¹ in healthy humans. Urea is rapidly converted to ammonia and CO₂ by bacterial ureases (Figure 1), which are produced by a small subset of oral bacteria that includes Streptococcus salivarius, Actinomyces naeslundii and oral haemophili.^19,20,21,22 Arginine is abundant in salivary secretions as polypeptides, and free arginine concentrations in ductal saliva average around 50 µmol·L⁻¹.¹⁸ Arginine in the oral cavity is catabolized primarily by the ADS to release ornithine, ammonia and CO₂ (Figure 1). Unlike urea breakdown by urease enzymes, arginine catabolism by the ADS provides bacteria with adenosine triphosphate (ATP).¹⁵ ADS-positive bacteria are abundant members of the normal oral flora that colonizes the teeth and soft tissues and include Streptococcus sanguinis, Streptococcus gordonii, Streptococcus parasanguis and Streptococcus mitis. Certain Lactobacillus and Actinomyces species, other oral streptococci and some oral spirochetes have been also identified as arginolytic.^15,23,24,25

Figure 1.

Summary of alkali-generating pathways in the oral cavity. See text for details.
Full figure and legend (25K)

Agmatine catabolism may also have a significant effect on oral biofilm ecology, albeit not in the way that arginine or urea metabolism does.²⁶ Agmatine can be produced in dental biofilms from arginine by bacterial arginine decarboxylase enzymes, but it also occurs naturally in foods, such as rice, milk and beer.^27,28 Agmatine has been measured at concentrations of 0.75 µmol in dental plaque and 0.2 µmol in saliva when the samples were normalized to protein concentration (e.g. 0.75 µmol per mg of protein in plaque).²⁹ The primary route for agmatine utilization is through the agmatine deiminase system (AgDS), which is highly similar to the ADS, with end products being putrescine, ammonia, CO₂ and ATP (Figure 1). A survey of bacterial genomes and/or functional studies revealed that the AgDS is present in multiple oral bacteria, including Streptococcus mutans, Streptococcus sobrinus, Streptococcus downeii, Streptococcus rattus, Streptococcus uberis, Streptococcus mitis and Streptococcus cricetus, as well Lactobacillus salivarius and Lactobacillus brevis.²⁹ Notably, some of these species are strongly associated with dental caries and express the AgDS at relatively high levels. Only S. sanguinis and S. salivarius, which are associated with dental health, can also generate ammonia via the ADS or urease, respectively, in addition to the AgDS.²⁹ These oral bacteria were reported to be highly capable of generating ammonia through the ADS or urease, but had much lower capacities for agmatine utilization. Therefore, the AgDS may not play as important role in the physiology of these oral commensals as it does in cariogenic streptococci. In fact, it has been postulated that the AgDS, unlike the ADS or urease, does not produce sufficient quantities of alkali to impact the pH of oral biofilm. Rather, the AgDS may actually enhance the acid tolerance of certain cariogenic organisms through ATP generation and raising of the cytoplasmic pH, which could enhance the ability of the bacteria to continue to catabolize carbohydrates at low pH values.²⁶

It should also be noted that malate metabolism through malolactic fermentation (MLF) has recently been identified as another pathway to reduce the extent of acidification of dental biofilms, including S. mutans. Through MLF, L-malate can be catabolized to L-lactate and CO₂ by the malolactic enzyme^30,31 (Figure 1). Although the MLF does not produce ammonia, it has been proposed to contribute to cytoplasmic alkalinization, which has been postulated to support the generation of ATP by means of the F₁F₀-ATPase acting in the synthetic mode.^30,31

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Genetics and regulation of alkali generation

Urease

The genetics, biogenesis, biochemistry and effects on the host of bacterial ureases have been reviewed elsewhere,^32,33 while a previous review covered many of the specifics of oral bacterial ureolysis.¹⁵ Briefly, urease is a nickel-containing oligomeric enzyme and the biogenesis of a functional urease requires at least seven gene products that are usually encoded in operons. The urease apoenzyme is composed of α, β and γ-subunits encoded by the ureC-A and -B genes. The subunits are assembled into an (αβγ)₃ oligomeric complex with six-nickel ions coordinated at the active site. Four additional genes, ureDEFG, encode a chaperone complex that facilitates the incorporation of nickel and CO₂ at the active site.^34,35 The expression of oral bacterial ureases is often regulated by multiple inputs.^36,37,38,39 Commonly, the presence of urea or limitation for a nitrogen source can induce urease gene transcription. In some bacteria, urease expression is repressed at neutral pH values, but under acidic conditions the urease genes become activated. Urease gene expression can also be sensitive to carbohydrate availability and rate of growth.^36,37,38

Arginine metabolism

The ADS is widely distributed among prokaryotes, and the primary structures of the enzymes in the system have been conserved during evolution. The genes encoding the ADS are commonly arranged in an operon (For example, see Figure 2), although the gene order varies among species.^{40,41,42,43,44} The arcA gene encodes arginine deiminase, which hydrolyzes arginine to generate citrulline and ammonia. The arcB gene encodes a catabolic ornithine carbamyltransferase, which converts citrulline to ornithine and carbamoylphosphate, and arcC encodes the catabolic carbamate kinase that transfers a phosphate group from carbamylphosphate to ADP to generate ATP, CO₂ and ammonia. Many organisms also harbor an arginine/ornithine antiporter (ArcD) that is encoded in the same operon, and arginine aminopeptidases and transcriptional regulators are often encoded in ADS gene clusters.^41,44 Of note, the oral commensal S. gordonii was identified to be the only ADS-positive bacterium containing a queA homologue associated with the ADS gene cluster. QueA is a predicted S-adenosylmethionine:tRNA ribosyltransferase-isomerase responsible for queosine modification of tRNAs⁴⁵ and queA is cotranscribed with the gene for the ADS transcriptional regulator. It has been postulated that the association of QueA with the ADS is indicative of a link between translational efficiency and arginine catabolism.

Figure 2.

Summary of ADS regulation in S. gordonii. Arrows indicate a positive influence on expression levels, while plain lines indicate a negative effects. See text for more detail.
Full figure and legend (26K)

The regulation of the ADS genes has been studied extensively in certain oral streptococci and in a variety of non-oral species.^41,42,43,46 In all cases examined so far, the ADS is subject to regulation by multiple environmental stimuli, although the modes and mechanisms of control vary between species. ADS expression in most bacteria, including oral streptococci, is induced by arginine and low pH. Similarly, the operon is sensitive to carbon catabolite repression (CCR) and downregulated in response to elevated oxygen levels, although the sensitivities to CCR and oxygen vary among species.^47,48 Interestingly, interspecies interactions, including coaggregation of S. gordonii with A. naeslundii, substantially enhanced ADS activity in S. gordonii, possibly by activating arginine biosythesis and ADS expression.⁴⁹

In S. gordonii, it was determined that ArcR is involved in the induction of the ADS genes by arginine and that CCR of the operon occurs primarily through CcpA (Figure 2).^41,47 An Fnr-like protein and the two-component system VicRK are required for the induction of the ADS in S. gordonii under anaerobic conditions (Figure 2).⁴⁷ Other two-component systems including CiaRH, ComDE and VicRK were found to be involved in the induction of the ADS in S. gordonii under acidic conditions (Figure 2).^50,51 QueA was also found to have a negative effect on arc gene transcription, possibly by impacting the translational efficiency of ADS genes or ADS regulatory genes (Figure 2).⁴⁵

AgDS

The AgDS does not appear to be as widely distributed in microbes as the ADS. Besides the oral species identified, only a few non-oral species, including Enterococcus faecalis, Pseudomonas aeruginosa, Bacillus cereus, Lactobacillus hilgardii and Helicobacter pylori have been reported to be AgDS-positive.^52,53,54,55 Like the ADS genes, the AgDS genes are typically encoded in an operon consisting of aguBDAC²⁶ (Figure 3). Free agmatine can enter the cell via an agmatine-putrescine antiporter (AguD) and is hydrolyzed to N-carbamoylputrescine and ammonia by the agmatine deiminase enzyme encoded by aguA. The N-carbamoylputrescine is then metabolized by the putrescine carbamoyltransferase, encoded by aguB, to yield putrescine and carbamoylphosphate. Finally, carbamate kinase, the product of the aguC gene, transfers a phosphate group from carbamoylphosphate to ADP to generate ATP, CO₂ and NH₃. The putrescine generated can be exchanged for agmatine via the antiporter.²⁶ The aguR gene, which is located upstream of, and in the opposite orientation to, the agu operon in S. mutans encodes a transcriptional activator of the agu genes.^56,57

Figure 3.

Summary of AgDS regulation in S. mutans. Arrows indicate a positive influence on expression levels, while plain lines indicate a negative effects. See text for more detail.
Full figure and legend (23K)

In oral streptococci, AgD activity is generally lower than arginine deiminase or urease activity,²⁶ although there is some variation among AgDS-positive species. Comparable levels of AgD activity were detected in S. mutans and S. rattus, but over 50-fold lower activity was observed in S. cricetus and S. sobrinus.²⁹ In S. mutans, AgDS activity is growth-phase dependent, as well as inducible by agmatine and certain environmental stresses, including low pH and heat shock (Figure 3).^26,56,57 Expression of the AgDS genes in S. mutans was also sensitive to CCR and influenced by CcpA and a putative CcpB orthologue (Figure 3).²⁶ The AgDS is also inducible by low pH and agmatine through a predicted interaction between AguR and AguD. In particular, it has been proposed that agmatine stimulates AguR binding to its target upstream of the agu operon, and that acidic conditions favor a configuration of AguR that enhances binding to its target.⁵⁷ In the absence of exogenous agmatine, the interaction of AguR with AguD may prevent an interation of AguR with its substate and/or its target.⁵⁷ Multiple two-component systems, including CiaRH, ComDE and VicRK, were disclosed to be involved in the induction of the AgDS genes by low pH, and CiaRH was also shown to contribute to optimal expression of the AgDS under thermal stress (Figure 3).⁵⁸

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Contribution of alkali generation to bacterial physiology and biofilm ecology

As reviewed previously, oral organisms harvest significant benefits from alkali generation in the form of protection against acid damage and enhancement to cell growth.¹⁵ Dental biofilms are complex ecosystems with hundreds of metabolically and physiologically diverse species, and there is believed to be considerable competition for nutrients. The ability of oral species to metabolize urea, arginine or agmatine at low pH could impart an advantage to these organisms through alkalinization of the cytoplasm by ammonia. The generation of ATP by the ADS would also enhance acid tolerance by providing energy for proton extrusion, growth or maintenance.^{26,41,59,60,61,62,63}

There is reason to believe that the contributions of the ADS, urease and AgDS to oral biofilm pH homeostasis and ecology may be quite different. For example, in some oral commensals, such as S. salivarius and S. gordonii, urease and the ADS, respectively, cleary can provide the bacteria with protection from environmental acidification.^19,47 At the same time, other less-aciduric species in the biofilm community benefit from arginine or urea breakdown because sufficient ammonia is sufficient to stabilize the pH of the local environment.^19,47 However, the caries pathogens S. mutans and S. sobrinus have no urease or ADS, but carry an AgDS that is expressed in vitro at a lower level than the ADS or urease is in oral commensals.^26,29 Further, agmatine, which arises primarily from the decarboxylation of arginine, is present at concentrations much lower than that of arginine in the oral cavity.¹⁸ Consequently, ammonia generation from agmatine in dental biofilms probably does not cause significant alkalinization of the environment. However, it could enhance the ability of S. mutans to continue to engage in glycolysis at low pH values, thus enhancing acid production. Similarly, MLF may not have much of a beneficial effect on biofilm pH, and like the AgDS, the benefits may be restricted to enhancing the growth and metabolism of the species that possess them.

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Observations on the relationship of alkali generation to caries status

Evidence continues to accumulate from in vitro studies and clinical observations that caries risk is associated with reduced alkali-generating capacity of the oral microbiome.^{11,17,18,64,65,66,67,68} For example, indirect evidence that the oral metabolism of urea may enhance caries resistance was obtained from a study with chronic renal failure patients, who rarely develop caries even with carbohydrate-rich diet, but who also produce some 10- to 50-fold greater salivary urea levels than healthy subjects.^67,69 In another study, higher resting pH values in the dental plaque of caries-free (CF) individuals compared with those of caries-active (CA) individuals was noted, and the increased pH was shown to be correlated with elevated ammonia released in plaque.¹⁷ Elevated levels of free arginine in saliva were revealed to be strongly correlated with caries resistance.¹⁸ Noticeably, a potent inhibitory effect on caries development was observed in rats that were infected with a genetically-engineered strain of S. mutans expressing the urease genes of S. salivarius.^16,68 Specifically, rats colonized by the S. mutans strain expressing high levels of urease had fewer caries lesions and lower caries severity scores than those of control animals.

Investigators have now begun exploring whether there are clinical correlations between oral alkali-generating capacity and caries susceptibility. In studies with young adult subjects, higher urease and ADS activity levels were detected in pooled supragingival plaque and whole saliva of CF individuals compared to those of CA individuals.^64,66 More recently, a positive correlation between oral arginine metabolism and dental health was also observed in children⁷⁰ when supragingival plaque was collected from specific tooth sites. Ammonia generation via plaque urease activity has also been correlated with reduced risk⁷¹ for dental caries in a longitudinal study with children. A few recent studies have begun to explore the effects of including arginine in confections of oral health care products. Acevedo et al.^72,73 demonstrated in randomize clinical trials that toothpaste⁶⁷ and sugarless mints⁶⁸ containing arginine bicarbonate can have potent anti-caries effects. A very recent report showed that addition of arginine-bicarbonate to mouth rinse at concentrations as low as 2% can effectively raise the plaque pH above the critical pH for enamel dissolution following a sucrose challenge.⁷⁴

One of the major challenges facing caries researchers today is to understand the microbiological and molecualr basis for the differences in alkali-generating potential in the dental biofilms of CA versus CF individuals. Although a number of studies have shown positive correlations of arginolytic species, e.g. S. sanguinis, with health and a decrease in the proportions of these species in caries, analysis of the oral microbiome has not revealed consistent changes in cultivable, non-cultivable or cultivated arginolytic taxa in CF and CA subjects.⁷⁵ Likewise, real-time PCR quantification showed no differences in the percentage of certain known arginolytic organisms in dental plaque of CF versus CA groups.⁶⁴ Thus, there may be reasons that CA subjects have higher ADS activity than CF subject other than simple decreases in the proportions of ADS-positive bacteria in carious tooth sites. For example, there may be additional arginolytic species beyond those previously identified that effect the bulk of arginolysis, although this seems unlikely as the microbiome data have been carefully analyzed. Alternatively, the oral environment of the host could influence the arginolytic capacity of the oral bacteria by affecting the expression of the genes or the activity of the enzymes involved in alkali production. Finally, there may be high- and low-producing strains of known ADS-positive species that are abundant in dental plaque but cannot be differentiated on the basis of 16S sequence, and health may be associated with colonization by high-producing strains. These high-producing strains may have constitutionally high expression or express comparatively high activity in response to pH, oxygen, carbohydrate and substrate availability versus the low-producing strains.^25,76

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Epilogue

Alkali generation is widespread among oral species and is important in the physiology, ecology and pathogenicity of dental biofilms. A substantial body of evidence from microbiological, genetic, biochemical analyses and clinical studies has accumulated to confirm that the modulation of the alkalinogenic potential of dental biofilms is a promising strategy for caries control. One of the strengths of alkali production as a strategy for control of caries is that it attacks the problem in two very important ways (Figure 4). First, it directly increases the pH of dental plaque, which tips the balance in favor of remineralization and away from demineralization. Secondly, alkali generation favors the persistence of health-associated bacteria while discouraging the outgrowth of those cariogenic bacteria that depend on low pH to gain an ecological advantage, e.g. S. mutans.

Figure 4.

The role of alkali generation in caries prevention. Dental biofilms in a healthy host displays a balance in pH and microflora conducive to a favorable demineralization/remineralization dynamic. With repeated acidification and exposure to other stresses, a shift in the composition and biochemical activities of the microflora creates conditions where demineralization is favored over remineralization, allowing for the initiation and/or progression of a caries lesion. Alkali generation by oral biofilm bacteria directly impacts plaque pH while preventing the emergence of a cariogenic microflora.
Full figure and legend (40K)

Despite recent progress in this area, there remain major gaps in our knowledge on the microbiological and ecological basis for differences in the alkalinogenic potential of dental plaque of different populations. In addition, we currently have a poor understanding of the otogeny of the alkalinogenic microflora. Likewise, additional clinical studies are needed: (i) to confirm that the supplementation of arginine to plaque bacteria is in fact effective against caries in adults and children; (ii) to ensure that arginine does not diminish the impact of fluoride in the oral cavity; and (iii) to optimize the formulations for caries control. Other areas worthy of investigation include exploring probiotic applications to enhance oral arginolysis and prevent the development of caries lesions. Collectively, this information will facilitate the rationale design of strategies that rely on alkali production for caries risk assessment and interventions.

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Liu Y, Burne RA. Multiple two-component systems modulate alkali generation in Streptococcus gordonii in response to environmental stresses. J Bacteriol 2009; 191(23): 7353–7362. | Article | PubMed |

Liu Y, Burne RA. The major autolysin of Streptococcus gordonii is subject to complex regulation and modulates stress tolerance, biofilm formation, and extracellular-DNA release. J Bacteriol 2011; 193(11): 2826–2837. | Article | PubMed |

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Driessen AJ, Smid EJ, Konings WN. Transport of diamines by Enterococcus faecalis is mediated by an agmatine-putrescine antiporter. J Bacteriol 1988; 170(10): 4522–4527. | PubMed | CAS |

Nakada Y, Jiang Y, Nishijyo T et al. Molecular characterization and regulation of the aguBA operon, responsible for agmatine utilization in Pseudomonas aeruginosa PAO1. J Bacteriol 2001; 183(22): 6517–6524. | Article | PubMed |

Arena ME, Fiocco D, Manca de Nadra MC et al. Characterization of a Lactobacillus plantarum strain able to produce tyramine and partial cloning of a putative tyrosine decarboxylase gene. Curr Microbiol 2007; 55(3): 205–210. | Article | PubMed |

Griswold AR, Jameson-Lee M, Burne RA. Regulation and physiologic significance of the agmatine deiminase system of Streptococcus mutans UA159. J Bacteriol 2006; 188(3): 834–841. | Article | PubMed |

Liu Y, Zeng L, Burne RA. AguR is required for induction of the Streptococcus mutans agmatine deiminase system by low pH and agmatine. Appl Environ Microbiol 2009; 75(9): 2629–2637. | Article | PubMed |

Liu Y, Burne RA. Multiple two-component systems of Streptococcus mutans regulate agmatine deiminase gene expression and stress tolerance. J Bacteriol 2009; 191(23): 7363–7366. | Article | PubMed |

Liu YL, Hu T, Zhang JY et al. A preliminary study of the modulation of Actinomyces naeslundii urease to the pH balance of dental biofilm. Shanghai Kou Qiang Yi Xue 2005; 14(6): 605–607. | PubMed |

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Acknowledgements

This work was supported by National Institute of Dental and Craniofacial Research Grant DE10362.

CANADIAN PRIVATE MONEY SUBSIDIZES STATE MEDICINE.

The Brain Canada Foundation (referred to throughout as “Brain Canada”) is a national, charitable organization with the goal of funding research aimed at unlocking the mystery of the brain, and developing diagnostics, treatments and ultimately cures for brain disorders.

The
News

December 21st, 2012

Harper Government Applauds One of the Largest Ever Public Private Investments in Health Research
The Chagnon Family and the Azrieli Foundation commit $46 million to Support Canadian Brain Research

Brain Canada (based in MONTREAL,PQ) is pleased to announce the Chagnon Family - Brain Canada, Multi-Investigator Research Initiative (MIRI) on Interventions for Prevention of Alzheimer Disease and Related Disorders.
The purpose of these MIRI grants is to accelerate novel and transformative intervention research that will improve the prevention of Alzheimer Disease and Related Disorders (ADRD).  This initiative will reward “outside the box” ideas by supporting research that is truly innovative and may challenge standard paradigms.
Over the next five years, $25 million will be provided by the Chagnon Family and Brain Canada, through the Canada Brain Research Fund.  This will be the largest investment in interventions for prevention of ADRD ever made in this country and sets forth a challenge to fast-track a quantum leap in the field.
Key dates:  deadline for letters of intent, February 22, 2013; and for full applications, July 12, 2013; funding to begin on or after October 14, 2013.
View the full announcement
Request for Applications:  ADRD_MIRI_RFA_EN.pdf
For further Information:
About Brain Canada and the Canada Brain Research Fund: http://braincanada.ca
About this competition: ADRD_query@braincanada.ca

Brain Canada is pleased to announce The Azrieli Neurodevelopmental Research Program, Multi-Investigator Research Initiative (MIRI).
The Azrieli Foundation in partnership with Brain Canada will support excellent systems or translational research in the area of neurodevelopmental disorders, with a special focus on ASD and Fragile X syndrome. The ultimate goal of the initiative is to develop new diagnostics, treatment and prevention strategies for neurodevelopmental disorders, to reduce their economic and social burden on Canadians, and to improve the quality of life for those affected by neurodevelopmental disorders and their families.
Over the next five years, $7.5 million will be provided by The Azrieli Foundation and Brain Canada, through the Canada Brain Research Fund.
Key dates:  deadline for letters of intent, April 5, 2013; and for full applications, August 16, 2013; funding to begin on or after November 18, 2013.
View the full announcement
Request for Applications:  NEURODEV_MIRI_RFA_EN.pdf
For further Information:
About Brain Canada and the Canada Brain Research Fund: http://braincanada.ca/
About this competition: Neurodev@braincanada.ca.

UK: ASIATIC FAKE CONDOMS

Tuesday, Jan 08 2013 

Millions of fake condoms smuggled into UK over last 18 months raising risk of STIs

• Fake condoms from Far East use cheaper materials that burst more easily
• MHRA has employed sniffer dogs trained to spot counterfeit condoms

By Daily Mail Reporter
PUBLISHED: 13:19 GMT, 7 January 2013 | 

Soaring numbers of counterfeit condoms are being smuggled into the UK, the government's health regulator warned yesterday.
For the Medicines and Healthcare products Regulation Agency claims that millions of the fakes have been illegally imported in the last 18 months.
The bogus condoms use cheaper materials and could increase the risk of users passing on STIs or lead to unwanted pregnancies, warn family planning experts.

Surge in demand? Millions of fake condoms have been illegally imported in the last 18 months

Counterfeiters have managed to copy well-known brands like Durex to convince people that the fake products are the genuine article.
BBC Radio 1 Newsbeat reported that tests carried out on many of the fakes show they have a high burst rate.
Senior investigator Danny Lee-Frost says: 'These products are made in the Far East for pennies and then sold over here for pounds.
'They will cut corners. They will cut costs. They will use cheaper ingredients and materials.'

More...

He said it was vital that people only bought condoms from reputable retailers and pharmacies as the fakes have mainly been found on sale in corner shops and on market stalls.
Trading Standards are regularly intercepting fake hauls across the country. In August 2012, £1.5m worth of counterfeit condoms were seized at Heathrow Airport, with a similar amount found in Yorkshire.
The MHRA have employed the help of the UK's first sniffer dogs trained to try to tackle the problem.
Paul Maddox is responsible for the dogs' training. He told the BBC: 'I was really surprised when I found out about the problem. I've heard about counterfeit medicines but I never thought condoms would ever be an issue.

'When we've trained the dogs up we managed to find a chink in the counterfeiters' armour and we've exploited that. That's why the dogs have been successful.'
But while the dogs can tell the difference, authorities are worried unwary shoppers could easily fall for the realistic fakes and want to raise awareness of the issue.

Read more: http://www.dailymail.co.uk/health/article-2258424/Counterfeit-condoms-consumers-risk-STIs-millions-imported-18-months.html#ixzz2HLWMcRn5
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UK:FAILURE of STATE MEDICINE

Hospitals face closure for covering up medical mistakes after review into NHS trust where 1,200 died from neglect

From UK DAILY MAIL

Probe into deaths at Mid Staffordshire NHS Foundation Trust
By Daily Mail Reporter
PUBLISHED: 11:55 GMT, 6 January 2013 | UPDATED: 12:08 GMT, 6 January 2013

Hospitals that cover up mistakes by staff should be fined or even closed, a public inquiry into one of Britain's worst medical scandals will recommend.
The report into the deaths of up to 1,200 patients at Mid Staffordshire NHS Foundation Trust will paint a devastating picture of a health service run under a culture of fear, bullying and secrecy, according to The Sunday Times.
It is expected the document, which will be handed to the Government later this month, will say the trust attempted to stifle evidence of rising death rates among vulnerable patients, many of whom were denied enough food and drink in a pattern of continuous neglect.
In a bid to stop such a widespread tragedy happening again, Robert Francis QC, the inquiry chairman, will recommend a raft of initiatives.

Read more: http://www.dailymail.co.uk/news/article-2257939/Hospitals-face-closure-covering-medical-mistakes.html#ixzz2HDC0rWBe
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UK:HANTAVIRUS

Hantavirus in England: detection of a UK strain of Seoul virus in wild brown rats (Rattus norvegicus)

Hantaviruses (genus Hantavirus, family Bunyaviridae) are a group of rodent-borne viruses with a wide global distribution. There are more than 40 recognised species of hantavirus and each species appears to be specific to a different host, and therefore limited to the host distribution [1]. At least 21 hantaviruses are confirmed to be human pathogens, four of which are known to occur in Europe (table 1) [2].
Human infection most often occurs when breathing in dried aerosolised excreta from infected rodents however the direct introduction into broken skin or conjunctiva is also a possible route of transmission. Disease in humans was first recognised in Korea in the early 1950's, although the virus was not identified until 1976 [3]. Two clinical syndromes are associated with severe disease [2]: haemorrhagic fever with renal syndrome (HFRS) in Europe and Asia caused predominantly by infection with Hantaan virus (HTNV), Dobrava virus (DOBV), Saaremaa virus (SAAV), Seoul virus (SEOV) and Puumala virus (PUUV); and, hantavirus cardiopulmonary syndrome (HCPS) in the Americas caused predominantly by infection with serotypes Sin Nombre virus (SNV) and Andes virus (ANDV). The majority of hantavirus infections in humans are likely to be asymptomatic or present with mild and non-specific symptoms including fever, headache, blurred vision, gastrointestinal symptoms and back pain.
Table 1. Known types of hantavirus associated with disease in Europe [4]

Virus	Disease	Distribution	Host species
DOBV	Severe	Eastern Europe	Apodemus flavicolis
PUUV	Mild	Europe	Myodes glareolus
SAAV	Moderate	Europe	Apodemus agrarius
SEOV	Moderate	Worldwide	Rattus norvegicus

Hantavirus is notifiable in England and Wales. Laboratory confirmation of acute cases is provided by the Rare and Imported Pathogens Laboratory (RIPL), HPA Microbiology Services Porton. Between 2009 and 2010 there were two confirmed cases with no travel history recorded: one from London and one from the Yorkshire and the Humber region. In January 2012, a second confirmed autochthonous case from Yorkshire and the Humber was reported with high titres (>10,000) and symptoms consistent with hantavirus infection (RIPL data).
Following the detection of a second case in the Yorkshire and the Humber region, in collaboration with North Yorkshire and the Humber Health Protection Unit and the HPA's Rare and Imported Pathogens Laboratory (RIPL), an investigation led by Virology and Pathogenesis, HPA Microbiology Services Porton was undertaken. Trapping and testing of rodents from the patient's home led to the detection of the first UK strain of hantavirus in wild Rattus norvegicus (brown rat) [5]. Further collaboration with the National Collection of Pathogenic Viruses (NCPV), Microbiology Services Porton, led to the culture and isolation of the virus now designated strain ‘Humber'. Complete sequencing and genetic analysis confirmed the virus was a Seoul hantavirus.
Due to the high levels of cross-reactivity between hantavirus species and the lack of viral detection in any published UK study, it has previously been impossible to confirm and identify the presence of a hantavirus in the UK. Cases are likely to be under-reported due to mild cases presenting with non-specific symptoms and a lack of awareness of hantavirus as a potential diagnosis in the absence of travel. Given that R. norvegicus are ubiquitous in the UK, research is ongoing to determine the extent of human exposure to this virus.
Further information on hantaviruses can be found on the HPA website [6].
This article is a contribution from Microbiology Research Services, HPA Porton.

References
1 . Dearing MD, and Dizney L (2010). Ecology of hantavirus in a changing world. Annals NY Acad Sci 1195, 99-112.
2. Jonsson CB, Fugueiredo LTM, Vapalahati O (2010). A global perspective on hantavirus ecology epidemiology and disease. Clin Micro Rev 23, 412-41.
3. Lee HW, Lee PW, Johnson KM (1978). Isolation of the etiologic agent of Korean Hemorrhagic fever. J Infect Dis 137, 298.
4. Vaheri A, Henttonen H, Voutilainen L, Mustonen J, Sironen T, Vapalahti O (2012). Hantavirus infections in Europe and their impact on public health. Rev Med Virol doi: 10.1002/rmv.1722.
5. Jameson LJ, Logue CH, Atkinson B, Baker N, Galbraith SE, Carroll MW, et al (2013). The continued emergence of hantaviruses: isolation of a UK Seoul virus implicated in human disease, United Kingdom, October 2012. Euro Surveill. 18(3).
6. HPA. Hantaviruses. HPA website: Home › Topics › Infectious Diseases › Infections A-Z › Hantaviruses.

UK TEACHING HOSPITAL NURSE with DYSLEXIA & POOR MEMORY

From UK DAILY MAIL

Friday, Jan 04 2013 9PM  17°C 12AM 17°C 5-Day Forecast

Nurse was so incompetent she gave dialysis patient Lucozade instead of glucose drip and couldn't even take a pulse

• Juleth McKenzie didn't know difference between milligrams and micrograms
• Eleven allegations of errors were either admitted or found proved
• She worked at Bradford Teaching Hospitals NHS Foundation Trust

By Leon Watson
PUBLISHED: 11:39 GMT, 4 January 2013 | UPDATED: 16:11 GMT, 4 January 2013


A nurse trained to grade five standard of care was so incompetent she couldn't even calculate a patient's heart rate, a disciplinary hearing heard.
Juleth McKenzie was hauled in front of the Nursing and Midwifery Council after she gave a dialysis patient a drink of Lucozade instead of a glucose drip.
The nurse, who worked at Bradford Teaching Hospitals NHS Foundation Trust, didn't know the difference between milligrams and micrograms and checked a patient's temperature instead of blood pressure - despite having qualified eight years ago.

Juleth Deborah Mckenzie was hauled in front of The Nursing and Midwivery Council after she gave a dialysis patient a drink of Lucozade instead of a glucose drip

Eleven allegations of incompetent errors against McKenzie were either admitted or found proved against the nurse.
Following an NMC hearing in November last year, at which McKenzie was not present or represented at, her fitness to practise was found impaired by lack of competence.
She was handed a 12 month suspension order, according to the findings of the hearing which have now been released.

More...

• Former nurse groped women by placing them in a trance using the trigger words 'drop for me'
• Senior NHS nurse tormented mentally ill patients by performing Nazi goose-step and groped a male colleague

The allegations heard by an NMC conduct and competence panel included giving medication to patients she was not authorised to do so, prioritising getting personal details of a patient over stemming bleeding and assessing a patient with Parkinson's disease as being independent and needing no care or support.
She was also accused of attempting to give drugs which had already been given, preparing drugs for oral administration for a patient who was nil by mouth, being unfamiliar with equipment on a resuscitation trolley, making four errors in relation to giving Heparin, giving prescription eye drops when not authorised and giving them to the wrong patient, failing to register patients and putting the wrong hospital number on a patient's wristband and not being aware of the difference between milligrams and micrograms and checking a patient's temperature instead of blood pressure.

McKenzie worked at Bradford Teaching Hospitals NHS Foundation Trust and was found to not know the difference between milligrams and micrograms

McKenzie was placed on the Trust's poor performance plan and was diagnosed with dyslexia and poor short-term visual memory

Miss McKenzie's patients on the renal ward and senior colleagues described how she 'places patients at risk every time she put them on dialysis'.
While others said she was a very caring person who wanted to deliver good practice, she was 'out of her depth and lacking in ability' and was described as 'getting muddled and panicked'.
Patients on the dialysis ward had even gone as far as to ask to not be treated by Miss McKenzie.
The panel heard how the job on the renal ward was Miss McKenzie's first substantive post after qualifying in 2005.
She was required to complete a new starters programme which most nurses complete within three months, but after six months concerns remained about her ability as a registered nurse.
By December 2006, she had been placed on the Trust's poor performance plan and was diagnosed with dyslexia and poor short-term visual memory.
McKenzie was redeployed to a less acute area on ward 18 but she continued to make fundamental errors.
She became a healthcare assistant but even in this capacity concern was expressed about her competence and she left the Trust on November 30, 2008.
The Royal College of Nursing's career framework outlines nine levels of nursing. McKenzie was a level 5 nurse, qualified to 'provide general nursing services to defined groups'.

Read more: http://www.dailymail.co.uk/news/article-2257082/Nurse-incompetent-gave-dialysis-patient-Lucozade-instead-glucose-drip-pulse.html#ixzz2H3FcmpDa
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