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Biomedical subjects

Gregor Reid

Publications and source records attributed to Gregor Reid.

At least 19 recordsLinked to original sources
PubMed2006

Clinical study comparing probiotic Lactobacillus GR-1 and RC-14 with metronidazole vaginal gel to treat symptomatic bacterial vaginosis.

Bacterial vaginosis (BV) is particularly common in black women, and in Nigeria it is often caused by Mycoplasma, as well as Atopobium, Prevotella and Gardnerella sp. Antimicrobial metronidazole oral therapy is poorly effective in eradicating the condition and restoring the Lactobacillus microbiota in the vagina. In this study, 40 women diagnosed with BV by discharge, fishy odor, sialidase positive test and Nugent Gram stain scoring, were randomized to receive either two dried capsules containing Lactobacillus rhamnosus GR-1 and Lactobacillus reuteri RC-14 each night for 5 days, or 0.75% metronidazole gel, applied vaginally twice a day (in the morning and evening). Follow-up at day 6, 15 and 30 showed cure of BV in significantly more probiotic treated subjects (16, 17 and 18/20, respectively) compared to metronidazole treatment (9, 9 and 11/20: P=0.016 at day 6, P=0.002 at day 15 and P=0.056 at day 30). This is the first report of an effective (90%) cure of BV using probiotic lactobacilli. Given the correlation between BV and HIV, and the high risk of the latter in Nigeria, intravaginal use of lactobacilli could provide women with a self-use therapy, similar to over-the-counter anti-yeast medication, for treatment of urogenital infections.

Administration, Intravaginal↗
PubMed2006

G-CSF-mediated inhibition of JNK is a key mechanism for Lactobacillus rhamnosus-induced suppression of TNF production in macrophages.

Lactobacillus rhamnosus is a human commensal with known immunomodulatory properties. To date the mechanism of these immunomodulatory effects is not well understood. To unravel the immunomodulatory signalling mechanism, we investigated the effects of two strains of L. rhamnosus, L. rhamnosus GG and GR-1, in modulating production of tumour necrosis factor-alpha (TNF) in human monocytic cell line THP-1 and mouse macrophages. Live L. rhamnosus GG and GR-1 or their spent culture supernatant induced minuscule amounts of TNF production but large quantities of granulocyte-colony stimulating factor (G-CSF) in macrophages compared with those induced by pathogenic Escherichia coli GR-12 and Enterococcus faecalis. By using neutralizing antibodies and G-CSF receptor knockout mice, we demonstrated that G-CSF secreted from L. rhamnosus GG- and GR-1-exposed macrophages suppressed TNF production induced by E. coli- or lipopolysaccharide-activated macrophages through a paracrine route. The suppression of TNF production by G-CSF was mediated through activation of STAT3 and subsequent inhibition of c-Jun-N-terminal kinases (JNKs). The inhibition of JNK activation required STAT3alpha-mediated de novo protein synthesis. This demonstrates a novel role of G-CSF in L. rhamnosus-triggered anti-inflammatory effects and its mechanism in the suppression of TNF production in macrophages.

Animals↗
PubMed2006

Activity of HIV entry and fusion inhibitors expressed by the human vaginal colonizing probiotic Lactobacillus reuteri RC-14.

Novel therapeutic approaches are needed to combat the rapid increase in HIV sexual transmission in women. The probiotic organism Lactobacillus reuteri RC-14 which safely colonizes the human vagina and prevents microbial infections, has been genetically modified to produce anti-HIV proteins which were capable of blocking the three main steps of HIV entry into human peripheral blood mononuclear cells. The HIV entry or fusion inhibitors were fused to the native expression and secretion signals of BspA, Mlp or Sep in L. reuteri RC-14 and the expression cassettes were stably inserted into the chromosome. L. reuteri RC-14 expressed the HIV inhibitors in cell wall-associated and secreted forms. L. reuteri RC-14 expressing CD4D1D2-antibody-like fusion proteins were able to bind single or dual tropic coreceptor-using HIV-1 primary isolates. This is the first study to show that a well-documented and proven human vaginal probiotic strain can express potent functional viral inhibitors, which may potentially lower the sexual transmission of HIV.

Animals↗
PubMed2006

Megaplasmids encode differing combinations of lantibiotics in Streptococcus salivarius.

Streptococcus salivarius strains commonly produce bacteriocins as putative anti-competitor or signalling molecules. Here we report that bacteriocin production by the oral probiotic strain S. salivarius K12 is encoded by a large (ca. 190 kb) plasmid. Oral cavity transmission of the plasmid from strain K12 to a plasmid-negative variant of this bacterium was demonstrated in two subjects. Tests of additional S. salivarius strains showed large (up to ca. 220 kb) plasmids present in bacteriocin-producing isolates. Various combinations (up to 3 per plasmid) of loci encoding the known streptococcal lantibiotics salivaricin A, salivaricin B, streptin and SA-FF22 were localised to these plasmids. Since all bacteriocin-producing strains of S. salivarius tested to date appear to harbour plasmids, it appears that they may function as mobile repositories for bacteriocin loci, especially those of the lantibiotic class.

Bacterial Proteins↗
PubMed2006

Safe and efficacious probiotics: what are they?

Each year, >20 billion doses of probiotics are used by healthy people and by those diagnosed with a range of medical conditions. Compared to many pharmaceutical agents, probiotics are well tolerated and extremely safe, and serious adverse effects rarely occur. Nevertheless, as many new researchers enter the field and companies launch "probiotic" products, it is essential that standards are set for naming a product "probiotic" to show that it meets an acceptable level of safety and efficacy, and to understand the strengths and limitations of its activity. In this Opinion article, recommendations are made based upon the current understanding of scientific, clinical and regulatory issues, with a special focus on safety.

Animals↗
PubMed2006

Augmentation of antimicrobial metronidazole therapy of bacterial vaginosis with oral probiotic Lactobacillus rhamnosus GR-1 and Lactobacillus reuteri RC-14: randomized, double-blind, placebo controlled trial.

This study enrolled 125 premenopausal women diagnosed with bacterial vaginosis (BV) by presence of vaginal irritation, discharge and 'fishy' odor, and Nugent criteria and detection of sialidase enzyme. The subjects were treated with oral metronidazole (500 mg) twice daily from days 1 to 7, and randomized to receive oral Lactobacillus rhamnosus GR-1 (1 x 10(9)) and Lactobacillus reuteri RC-14 (1 x 10(9)) or placebo twice daily from days 1 to 30. Primary outcome was cure of BV as determined by normal Nugent score, negative sialidase test and no symptoms or signs of BV at day 30. A total of 106 subjects returned for 30-day follow-up, of which 88% were cured in the antibiotic/probiotic group compared to 40% in the antibiotic/placebo group (p<0.001). Of the remaining subjects, 30% subjects in the placebo group and none in the probiotic group had BV, while 30% in the placebo and 12% in the probiotic group fell into the intermediate category based upon Nugent score, sialidase result and clinical findings. High counts of Lactobacillus sp. (>10(5) CFU/ml) were recovered from the vagina of 96% probiotic-treated subjects compared to 53% controls at day 30. In summary, this study showed efficacious use of lactobacilli and antibiotic in the eradication of BV in black African women.

Adolescent↗
PubMed2006

Triclosan loaded ureteral stents decrease proteus mirabilis 296 infection in a rabbit urinary tract infection model.

PURPOSE: Infection and encrustation remain major limitations of ureteral stent use and to our knowledge no device has completely overcome these obstacles to date. Triclosan is a biocide currently used in a plethora of consumer and medical products that has recently been loaded into a ureteral stent. Using a rabbit model of UTI we examined the effects of triclosan impregnated stent segments on the growth and survival of Proteus mirabilis, a uropathogen commonly associated with device related UTI and encrustation. MATERIALS AND METHODS: A total of 48 male New Zealand White rabbits were instilled transurethrally with 1 x 10(6) P. mirabilis 296. A stent curl from a triclosan eluting, Percuflex Plus or Optima ureteral stent was placed intravesically. Urine was cultured on days 1, 3 and 7. On day 7 the stents were assessed for encrustation and viable organisms, while the bladders were scored for the degree of inflammation. RESULTS: Throughout the study urine isolated from the triclosan group contained significantly fewer viable organisms than controls with 7 of 13 animals completely clearing the infection by day 7. Similarly 9 of 13 triclosan eluting stents showed no viable organisms upon recovery and the remaining 4 showed significantly fewer organisms than controls. Urine and stents in all controls were positive for P. mirabilis at all time points. Although there was no significant difference in encrustation among the groups, bladders harvested from the triclosan group demonstrated significantly less inflammation. CONCLUSIONS: Triclosan eluting stents greatly decreased P. mirabilis growth and survival in a rabbit UTI model compared to controls. These stents may prove useful for decreasing device related P. mirabilis UTIs.

Animals↗
PubMed2006

In-vitro activity of triclosan-eluting ureteral stents against common bacterial uropathogens.

BACKGROUND AND PURPOSE: Ureteral stents are commonly used in urology today, but the biofilms that form on them within hours of placement may harbor bacteria that can result in infection or encrustation. Triclosan is an antimicrobial commonly used in consumer and medical products that inhibits bacterial fatty-acid synthesis. The bactericidal and bacteriostatic effect of a triclosan-eluting ureteral stent was tested against clinical isolates of common bacterial uropathogens in an in-vitro setting. MATERIALS AND METHODS: Triclosan eluted from a drug-loaded ureteral stent was suspended in artificial urine with bacterial pathogens (Escherichia coli C1214, Proteus mirabilis 296, Enterococcus faecalis 1131, Klebsiella pneumoniae 280, Staphylococcus aureus Newman, Pseudomonas aeruginosa AK1) to assess growth, virulence-promoter activity, and bacterial adherence to the stent. Generic stents were utilized as controls. RESULTS: Triclosan inhibited the growth of E. faecalis, K. pneumoniae, S. aureus, and P. mirabilis in a dose-dependent manner. Pseudomonas aeruginosa demonstrated significant resistance. Lower concentrations of triclosan downregulated E. coli virulence-factor promoters of outer membrane protein X and p-fimbriae. Triclosan stents had significantly fewer adherent viable bacteria than control stents. CONCLUSIONS: Triclosan-eluting ureteral stents inhibit the growth of common bacterial uropathogens and thus may reduce the incidence of urinary-tract infections and, potentially, encrustation. This drug-eluting stent provides both mechanical drainage of the upper urinary tract and local antibiosis.

Anti-Infective Agents, Local↗
PubMed2006

Lactobacillus vaginal microbiota of women attending a reproductive health care service in Benin city, Nigeria.

OBJECTIVE: The objective of this study was to determine whether Lactobacillus species found in African women differ substantially to those of white decent, described in previous studies. The vaginal microbiota play an important role in female health, and when the naturally dominant lactobacilli are displaced resulting in bacterial vaginosis (BV), the host is more at risk of acquiring sexually transmitted diseases, including HIV. METHODS: Vaginal samples were collected from 241 healthy, premenopausal Nigerian women, which were then Gram-stained for Nugent scoring. Microbial DNA was extracted, amplified using polymerase chain reaction (PCR) and Lactobacillus primers, and processed by denaturing gradient gel electrophoresis (DGGE). Lactobacillus species were identified by DNA sequencing and BLAST algorithm. RESULTS: Of the samples, 207 (85.8%) had PCR products for lactobacilli, whereas 34 (14.2%) showed absence of lactobacilli, which correlated to the BV Nugent scores. On sequencing of amplicons, 149 subjects (72%) had sequence homologies to lactobacilli. Most women (64%) were colonized by L. iners as the predominant strain, similar to previous findings in Canadian and Swedish women. L. gasseri was found in 7.3% samples, followed by L. plantarum, L. suntoryeus, L. crispatus, L. rhamnosus, and other species. CONCLUSION: The findings indicate that even with geographic, racial, and other differences, the predominant vaginal Lactobacillus species is similar to species in women from Northern countries.

Adolescent↗
PubMed2006

Inhibition of expression of a staphylococcal superantigen-like protein by a soluble factor from Lactobacillus reuteri.

Lactobacillus reuteri RC-14 has previously been shown to inhibit Staphylococcus aureus infection in a rat surgical-implant model. To investigate the basis for this, communication events between the two bacterial species were examined. L. reuteri RC-14 and Staph. aureus Newman were grown in a co-culture apparatus that physically separates the two species, while allowing the passage of soluble compounds. Using two-dimensional gel electrophoresis (2D-E), protein expression changes in Staph. aureus were analysed in response to co-culture with medium alone, L. reuteri RC-14, and a Lactobacillus strain that did not inhibit Staph. aureus infection in the rat model. It was observed that one protein in particular, identified as staphylococcal superantigen-like protein 11 (SSL11), showed a dramatic decrease in expression in response to growth with L. reuteri RC-14. Genetic reporters that placed both gfp and lux under the transcriptional control of the SSL11 promoter confirmed the 2D-E results. Interestingly, using similar reporter gene experiments, it was observed that the Staph. aureus P3 promoter from the staphylococcal accessory gene regulator (agr) locus also showed a decrease in expression in response to growth in the presence of L. reuteri RC-14. It was further demonstrated that L. reuteri RC-14 supernatant contained small unidentified molecules that were able to repress the SSL11 and P3 promoters, but the repression of SSL11 occurred independently of the agr system. These results suggest that L. reuteri RC-14 has the potential to alter the virulence of Staph. aureus via secretion of cell-cell signalling molecules.

Anti-Bacterial Agents↗
PubMed2006

Selecting, testing and understanding probiotic microorganisms.

The interest in probiotics and the modulation of microbiota for restoring and maintaining health continues to gain momentum. Research is fueled by a need to develop alternatives to antibiotics and drugs that have severe side effects. It is recognised that bacteria play a major role in human and animal health, and how scientific advances help to explain how and when probiotics work. This minireview provides an update on critical studies, particularly since 2002, that are helping to explain the mechanisms of action of probiotic organisms.

Adult↗
PubMed2005

Probiotics to prevent urinary tract infections: the rationale and evidence.

For over 30 years, urologists have recognized in females, that urinary pathogens almost always infect the host through ascension from the rectum, vagina to the urethra and bladder. Likewise, the Lactobacillus organisms that predominate in the vagina of healthy women, spread from the rectum and perineum and form a barrier in the vagina to bladder entry by uropathogens. The concept of artificially boosting the lactobacilli numbers through probiotic instillation has long been conceived, but only in recent years shown to be possible. Not all lactobacilli are effective, and to date clinical efficacy only exists for Lactobacillus rhamnosus GR-1 and Lactobacillus reuteri B-54 and RC-14. These strains are only commercially available in Austria, and therefore for most urologists, while some probiotic organisms may reduce the recurrences of bladder cancer or oxaluria, no probiotics can be recommended widely to prevent UTI at present.

Administration, Intravaginal↗
PubMed2005

Modulation of the microbial ecology of the human colon by probiotics, prebiotics and synbiotics to enhance human health: an overview of enabling science and potential applications.

The application of probiotics and prebiotics to the manipulation of the microbial ecology of the human colon has recently seen many scientific advances. The sequencing of probiotic genomes is providing a wealth of new information on the biology of these microorganisms. In addition, we are learning more about the interactions of probiotics with human cells and with pathogenic bacteria. An alternative means of modulating the colonic microbial community is by the use of prebiotic oligosaccharides. Increasing knowledge of the metabolism of prebiotics by probiotics is allowing us to consider specifically targeting such dietary intervention tools at specific population groups and specific disease states.

Colon↗
PubMed2005

Complexity of vaginal microflora as analyzed by PCR denaturing gradient gel electrophoresis in a patient with recurrent bacterial vaginosis.

OBJECTIVE: Gardnerella vaginalis has long been the most common pathogen associated with bacterial vaginosis (BV). We aimed to test our hypothesis that symptoms and signs of BV do not necessarily indicate colonization by this organism, and often will not respond to standard metronidazole or clindamycin treatment. METHODS: Using a relatively new molecular tool, PCR denaturing gradient gel electrophoresis (DGGE), the vaginal microflora of a woman with recalcitrant signs and symptoms of BV was investigated over a 6-week timeframe. RESULTS: The vagina was colonized by pathogenic enterobacteriaceae, staphylococci and Candida albicans. The detection of the yeast by PCR-DGGE is particularly novel and enhances the ability of this tool to examine the true nature of the vaginal microflora. The patient had not responded to antifungal treatment, antibiotic therapy targeted at anaerobic Gram-negative pathogens such as Gardnerella, nor daily oral probiotic intake of Lactobacillus rhamnosus GG. The failure to find the GG strain in the vagina indicated it did not reach the site, and the low counts of lactobacilli demonstrated that therapy with this probiotic did not appear to influence the vaginal flora. CONCLUSIONS: BV is not well understood in terms of its causative organisms, and further studies appear warranted using non-culture, molecular methods. Only when the identities of infecting organisms are confirmed can effective therapy be devized. Such therapy may include the use of probiotic lactobacilli, but only using strains which confer a benefit on the vagina of pre- and postmenopausal women.

Candida albicans↗
PubMed2005

Probiotics for the developing world.

Every minute of every day more and more children die of diarrheal diseases and women, and girls become infected by HIV. An estimated 7,000 women become infected each day. While many valiant efforts are being made to address these issues, until now they have proved to be markedly ineffective. The notion that lactic acid bacteria, formulated into food or dietary supplements, could have a role to play in slowing the morbidity and mortality associated with HIV/AIDS and gastroenteritis, is built upon sound clinical findings and scientific investigations, yet no international efforts have been placed in this approach, to date. We hereby summarize the reasons why such efforts should be made, provide an example of one model being set up in sub-Saharan Africa, and challenge the international community to consider the potential benefits of probiotics, especially for communities not reached by governmental and nongovernmental agencies.

Developing Countries↗
PubMed2005

Vaginal microbial diversity among postmenopausal women with and without hormone replacement therapy.

Urogenital infections in postmenopausal women remain problematic. The use of estrogen replacement therapy has been shown to lower these infection rates, corresponding to increasing colonization by Lactobacillus species. Despite the gut's 500 microbial species and the proximity of the anus to the vagina, only a relatively few microbial strains appear to be able to colonize the urogenital area. In the present study, the sparsity of microbes in the vagina was confirmed by denaturing gradient gel electrophoresis analysis of swabs taken at time zero and monthly for 3 months from 40 postmenopausal subjects receiving Premarin (conjugated equine estrogen in combination with progesterone) hormone replacement therapy (HRT) and 20 who were not on HRT. Lactobacilli were recovered from the vagina of 95% or more women in both groups, but in the HRT group, Lactobacillus were more often the dominant and only colonizers and significantly fewer bacteria with pathogenic potential were found. The incidence of bacterial vaginosis was significantly lower in the HRT group than in the non-HRT-treated women (5.6% versus 31%). The use of HRTs has recently come under criticism. The ability of drugs such as Premarin to help recover the lactobacilli vaginal microbiota appears to be at least one benefit of HRT use. In women not using HRTs, use of probiotics may be the only way to restore a nonpathogen-dominated flora.

Adult↗
PubMed2005

The importance of guidelines in the development and application of probiotics.

Probiotics, defined as "Live microorganisms which when administered in adequate amounts confer a health benefit on the host" have many attributes including the lack of adverse side effects associated with their use. While probiotics have proven benefits, the optimism associated with their use is counterbalanced by the fact that many so-called "probiotic" products are unreliable in content and unproven clinically. Therefore much remains to be done to gain the acceptance of the broader medical community. Recognition of the obvious product inequality and the lack of any regulatory guidelines lead to the development of Operating Standards in 2002 (FAO/WHO), that would ensure product safety, reliability and a level playing field for all companies producing probiotic products. The guidelines constitute a set of parameters required for a product/strain to be termed "probiotic" and also the clinically relevant steps to be followed to move probiotics closer to being embraced by the medical community. These include i) implementation of Guidelines for use of probiotics; ii) phase I, II and III clinical trials to prove health benefits that are as good as or better than standard prevention or treatments for a particular condition or disease; iii) Good Manufacturing Practice and production of high quality products; iv) studies to identify mechanism of action in vivo; v) informative/ precise labelling; vi) development of probiotic organisms that can carry vaccines to hosts and/or anti- viral probiotics; vii) expansion of proven strains to benefit the oral cavity, nasopharynx, respiratory tract, stomach, vagina, bladder and skin as well as for cancer, allergies and recovery from surgery/ injury.

Drug Industry↗