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Biomedical subjects

G Reid

Publications and source records attributed to G Reid.

At least 37 records · Page 2Linked to original sources

Cranberry juice consumption may reduce biofilms on uroepithelial cells: pilot study in spinal cord injured patients.

STUDY DESIGN: A pilot study of 15 spinal cord injured patients. OBJECTIVE: To determine whether alteration of fluid intake and use of cranberry juice altered the bacterial biofilm load in the bladder. SETTING: London, Ontario, Canada. METHODS: Urine samples were collected on day 0 (start of study), on day 7 following each patient taking one glass of water three times daily in addition to normal diet, and on day 15 following each patient taking one glass of cranberry juice thrice daily. One urine sample was sent for culture and a second processed to harvest, examine by light microscopy and Gram stain non-squamous uroepithelial cells to generate bacterial adhesion per 50 cells data. RESULTS: The results showed that cranberry juice intake significantly reduced the biofilm load compared to baseline (P=0.013). This was due to a reduction in adhesion of Gram negative (P=0.054) and Gram positive (P=0.022) bacteria to cells. Water intake did not significantly reduce the bacterial adhesion or biofilm presence. CONCLUSION: The findings provide evidence in support of further, larger clinical trials into the use of functional foods, particularly cranberry juice, to reduce the risk of UTI in a patient population highly susceptible to morbidity and mortality associated with drug resistant uropathogens. SPONSORSHIP: This study was funded by Ocean Spray Cranberries, Lakeville, MA, USA.

Acids↗

Drug treatment services for ethnic communities in Victoria, Australia: an examination of cultural and institutional barriers.

Under-representation of ethnic minorities at drug treatment services represents under-utilisation rather than a lower need. To explore barriers to drug treatment among ethnic communities we undertook a comprehensive review of international and Australian literature to identify problems their members experience upon the discovery of illicit drug use in their community, how drug treatment is addressed and challenges for improved drug treatment outcomes. The concepts and themes derived from the literature were then compared with our research findings from key informant interviews and consultations with non-illicit drug-using spokespersons from eight ethnic communities in Victoria, Australia. Intense shame and loss of face linked to illicit drug use was common in ethnic communities and as a consequence seeking help for drug treatment was fraught with difficulties. Accessing drug treatment services often occurred following a crisis, but a sense of despair and confusion often prevailed owing to a lack of knowledge of available assistance. Even when treatment services were accessed most key informants and ethnic communities viewed them as culturally insensitive, inflexible and with language barriers that obstructed the flow of effective information. Understanding of the ethnic family ethos was of pivotal importance but frequently ignored by treatment services, contributing to the exclusion of ethnic communities from appropriate assistance. Ethnic communities need to be assisted to participate in drug issue discussions and community development strategies in order for their utilisation of drug treatment services to be improved.

Communication Barriers↗

Probiotic agents to protect the urogenital tract against infection.

The urogenital microflora of a healthy woman comprises approximately 50 species of organisms, which differ in composition according to reproductive stages and exposure to several factors, including antibiotics and spermicides. Infections are very common with > 300 million cases of urinary tract infections, bacterial vaginosis, and yeast vaginitis worldwide per annum. At the time of infection in the bladder and vagina, the urogenital flora is often dominated by the infecting pathogens, in contrast with healthy phases when indigenous organisms dominate. Premenopausal women have a flora of mostly lactobacilli, and certain properties of these strains, including adhesive ability and production of acids, bacteriocins, hydrogen peroxide, and biosurfactants, appear important in conferring protection to the host. Efforts to artificially restore an unbalanced flora with the use of probiotics have met with mixed results but research aimed at selecting scientifically based strains could well provide a reliable alternative treatment and preventive regimen to antibiotics in the future.

Anti-Bacterial Agents↗

Probiotic Lactobacillus dose required to restore and maintain a normal vaginal flora.

Forty-two healthy women were randomized to receive one of three encapsulated Lactobacillus rhamnosus GR-1 plus Lactobacillus fermentum RC-14 probiotic dosage regimens or L. rhamnosus GG by mouth each day for 28 days. However, the vaginal flora, assessed by Nugent scoring, was only normal in 40% of the cases, and 14 patients had asymptomatic bacterial vaginosis. Treatment with L. rhamnosus GR-1/L. fermentum RC-14 once and twice daily correlated with a healthy vaginal flora in up to 90% of patients, and 7/11 patients with bacterial vaginosis converted to normal or intermediate scores within 1 month. Ingestion of L. rhamnosus GG failed to have an effect. This study confirms the potential efficacy of orally administered lactobacilli as a non-chemotherapeutic means to restore and maintain a normal urogenital flora, and shows that over 10(8) viable organisms per day is the required dose.

Adolescent↗

Oral probiotics can resolve urogenital infections.

We report the first clinical evidence that probiotic lactobacilli can be delivered to the vagina following oral intake. In 10 women with a history of recurrent yeast vaginitis, bacterial vaginosis (BV) and urinary tract infections, strains Lactobacillus rhamnosus GR-1 and Lactobacillus fermentum RC-14 suspended in skim milk and given twice daily for 14 days, were recovered from the vagina and identified by morphology and molecular typing within 1 week of commencement of therapy. In six cases of asymptomatic BV or intermediate BV (based upon Nugent scoring) was resolved within 1 week of therapy.

Administration, Oral↗

Minireview: genomic organization of the human ERalpha gene promoter region.

The ERalpha gene has been intensively studied for more than a decade. During this long time, multiple promoters used in ERalpha expression have been discovered in several species. Although an already large body of literature describing various aspects of the regulation of ERalpha expression and utilization of different promoters is constantly growing, the inconsistent terminology used by individual authors makes the interpretation and comparison of data very difficult. Furthermore, completion of the human genome project now allows all known human ERalpha promoters to be placed on a physical map. This review describes promoters used in the generation of ERalpha transcripts in human and in other species and suggests a consistent nomenclature. The possible role of multiple promoters in the differential expression of ERalpha in tissues and during development is also discussed.

Animals↗

ERalpha gene expression in human primary osteoblasts: evidence for the expression of two receptor proteins.

The beneficial influence of E2 in the maintenance of healthy bone is well recognized. However, the way in which the actions of this hormone are mediated is less clearly understood. Western blot analysis of ERalpha in osteoblasts clearly demonstrated that the well characterized 66-kDa ERalpha was only one of the ERalpha isoforms present. Here we describe a 46-kDa isoform of ERalpha, expressed at a level similar to the 66-kDa isoform, that is also present in human primary osteoblasts. This shorter isoform is generated by alternative splicing of an ERalpha gene product, which results in exon 1 being skipped with a start codon in exon 2 used to initiate translation of the protein. Consequently, the transactivation domain AF-1 of this ERalpha isoform is absent. Functional analysis revealed that human (h)ERalpha46 is able to heterodimerize with the full-length ERalpha and also with ERbeta. Further, a DNA-binding complex that corresponds to hERalpha46 is detectable in human osteoblasts. We have shown that hERalpha46 is a strong inhibitor of hERalpha66 when they are coexpressed in the human osteosarcoma cell line SaOs. As a functional consequence, proliferation of the transfected cells is inhibited when increasing amounts of hERalpha46 are cotransfected with hERalpha66. In addition to human bone, the expression of the alternatively spliced ERalpha mRNA variant is also detectable in bone of ERalpha knockout mice. These data suggest that, in osteoblasts, E2 can act in part through an ERalpha isoform that is markedly different from the 66-kDa receptor. The expression of two ERalpha protein isoforms may account, in part, for the differential action that estrogens and estrogen analogs have in different tissues. In particular, the current models of the action of estrogens should be reevaluated to take account of the presence of at least two ERalpha protein isoforms in bone and perhaps in other tissues.

Alternative Splicing↗

Could probiotics be an option for treating and preventing urogenital infections?

Considering the enormity of the problem in terms of women infected per year, urogenital infections receive far too little attention from scientists, government funding agencies, and the pharmaceutical industry. A recent resurgence in interest among clinicians is a result of consumer demands for better therapies, problems resulting from drug resistance, and the prospect of new diagnostics and treatments on the horizon. It is now recognized that the intestinal and urogenital microflora are critical for the health and well-being of humans. The concept of replenishing these flora with probiotic organisms seems to be an option that has a growing scientific basis. Although few strains have been selected and targeted for urogenital applications, and none are currently available on the market, evidence shows that probiotic therapy has the potential to make an impact on women's health.

Canada↗

Slowed inactivation at positive potentials in a rat axonal K+ channel is not due to preferential closed-state inactivation.

We have investigated slow inactivation in a rat axonal K+ channel, the I channel. Using voltage steps to potentials between -70 mV and +80 mV, from a holding potential of -100 mV, we observed a marked slowing of inactivation at positive potentials: the time constant was 4.5+/-0.4 s at -40 mV (mean +/- S.E.M.), increasing to 14.7+/-2.0 s at +40 mV. Slowed inactivation at positive potentials is not consistent with published descriptions of C-type inactivation, but can be explained by models in which inactivation is preferentially from closed states (which have been developed for Kv2.1 and some Ca2+ channels). We tested two predictions of preferential closed-state models: inactivation should be more rapid during a train of brief pulses than during a long pulse to the same potential, and the cumulative inactivation measured with paired pulses should be greater than the inactivation at the same time during a continuous pulse. The I channel does not behave according to these predictions, indicating that preferential closed-state inactivation does not explain the slowing of inactivation we observe at positive potentials. Inactivation of the I channel therefore differs both from C-type inactivation, as presently understood, and from the inactivation of Kv2.1.

Animals↗

Identification of a new isoform of the human estrogen receptor-alpha (hER-alpha) that is encoded by distinct transcripts and that is able to repress hER-alpha activation function 1.

A new isoform of the human estrogen receptor-alpha (hER-alpha) has been identified and characterized. This 46 kDa isoform (hERalpha46) lacks the N-terminal 173 amino acids present in the previously characterized 66 kDa isoform (hERalpha66). hERalpha46 is encoded by a new class of hER-alpha transcript that lacks the first coding exon (exon 1A) of the ER-alpha gene. We demonstrated that these Delta1A hER-alpha transcripts originate from the E and F hER-alpha promoters and are produced by the splicing of exon 1E directly to exon 2. Functional analysis of hERalpha46 showed that, in a cell context sensitive to the transactivation function AF-2, this receptor is an effective ligand-inducible transcription factor. In contrast, hERalpha46 is a powerful inhibitor of hERalpha66 in a cell context where the transactivating function of AF-1 predominates over AF-2. The mechanisms by which the AF-1 dominant-negative action is exerted may involve heterodimeri zation of the two receptor isoforms and/or direct competition for the ER-alpha DNA-binding site. hERalpha66/hERalpha46 ratios change with the cell growth status of the breast carcinoma cell line MCF7, suggesting a role of hERalpha46 in cellular proliferation.

Base Sequence↗

Purification and characterization of a surface-binding protein from Lactobacillus fermentum RC-14 that inhibits adhesion of Enterococcus faecalis 1131.

Lactobacilli have been shown to be important in the maintenance of the healthy urogenital flora. One strain, Lactobacillus fermentum RC-14, releases surface-active components which can inhibit adhesion of uropathogenic bacteria. Using a quantitative method for determining inhibition of adhesion, a protein with high anti-adhesive properties against Enterococcus faecalis 1131 was purified. The N-terminal sequence of the 29-kDa protein was identical to that of a collagen-binding protein from Lactobacillus reuteri NCIB 11951, and exhibited close homology with a basic surface protein from L. fermentum BR11. The results suggest that this anti-adhesive cell surface protein of Lactobacillus could protect against uropathogens by preventing their adhesion. the Federation of European Microbiological Societies.

Amino Acid Sequence↗

Genomic structure and in vivo expression of the human organic anion transporter 1 (hOAT1) gene.

The human organic anion transporter 1 (hOAT1) plays a key role in the secretion of an array of potentially toxic organic anions including many clinically important drugs. Here we report on the genomic cloning of hOAT1. A human genomic library was used for screening of a PAC (P1 artificial chromosome) clone applying PCR techniques. Sequencing of several restriction subclones and of a PCR-generated clone revealed that the hOAT1 gene spans 8.2 kb and is composed of 10 exons divided by 9 introns. RT-PCR studies in a human kidney specimen led to the detection of two new splice variants, hOAT1-3 and hOAT1-4, showing a 132-bp in-frame deletion. Using fluorescence in situ hybridization (FISH) we mapped the hOAT1 gene as a single signal to chromosome 11q13.1-q13.2. Additionally, 600 bp of the 5' flanking region was analyzed, illustrating the probable transcription start site at nt -280, a NF-kappaB-site at nt -397 and several putative transcription factor binding sites.

Anion Transport Proteins↗

Synthesis, spectroscopic, and structural studies on transition metal complexes involving homoleptic tripodal selenoether and telluroether coordination.

The reaction of [MCl2(NCMe)2] (M = Pd or Pt) with 2 molar equiv of MeC(CH2ER)3 (E = Se, R = Me; E = Te, R = Me or Ph) and 2 molar equiv of TlPF6 affords the bis ligand complexes [M(MeC(CH2ER)3)2][PF6]2. The crystal structure of [Pt(MeC(CH2SeMe)3)2][PF6]2 (C16H36F12P2PtSe6, a = 12.272(10) A, b = 18.563(9) A, c = 15.285(7) A, beta = 113.18(3) degrees, monoclinic, P2(1)/n, Z = 4) confirms distorted square planar Se4 coordination at Pt(II), derived from two bidentate tripod selenoethers with the remaining arm not coordinated and directed away from the metal center. Solution NMR studies indicate that these species are fluxional and that the telluroether complexes are rather unstable in solution. The octahedral bis tripod complexes [Ru(MeC(CH2SMe)3)2][CF3-SO3]2 and [Ru(MeC(CH2TePh)3)2][CF3SO3]2 are obtained from [Ru(dmf)6][CF3SO3]3 and tripod ligand in EtOH solution. The thioether complex (C18H36F6O6RuS8, a = 8.658(3) A, b = 11.533(3) A, c = 8.659(2) A, alpha = 108.33(2) degrees, beta = 91.53(3) degrees, gamma = 106.01(2) degrees, triclinic, P1, Z = 1) is isostructural with its selenoether analogue, involving two facially coordinated trithioether ligands in the syn configuration. NMR spectroscopy confirms that this configuration is retained in solution for all of the bis tripod Ru(II) complexes. These low-spin d6 complexes show unusually high ligand field splittings. The hexaselenoether Rh(III) complex [Rh(MeC(CH2SeMe)3)2][PF6]3 was obtained by treatment of [Rh(H2O)6]3+ with 2 molar equiv of MeC(CH2SeMe)3 in aqueous MeOH in the presence of excess PF6- anion, while the iridium(III) analogue [Ir(MeC(CH2SeMe)3)2][PF6]3 was obtained via the reaction of the Ir(I) precursor [IrCl(C8H14)2]2 with the selenoether tripod in MeOH/aqueous HBF4. NMR studies reveal different invertomers in solution for both the Rh and Ir species. The Cu(I) complexes [Cu(MeC(CH2ER)3)2]PF6 were obtained from [Cu(NCMe)4]PF6 and tripod ligand in CH2Cl2 solution. The corresponding Ag(I) species [Ag(MeC(CH2TeR)3)2]CF3SO3 (R = Me or Ph) were obtained from Ag[CF3SO3] and tripod telluroether. In contrast, a similar reaction with 2 molar equiv of MeC(CH2SeMe)3 afforded only the 1:1 complex [Ag(MeC(CH2SeMe)3)]CF3SO3. The structure of this species (C9H18AgF3O3SSe3, a = 8.120(3) A, b = 15.374(3) A, c = 14.071(2) A, beta = 93.86(2) degrees, monoclinic, P2(1)/n, Z = 4) reveals a distorted trigonal planar geometry at Ag(I) derived from one bidentate selenoether and one monodentate selenoether. These units are then linked to adjacent Ag(I) ions to give a one-dimensional linear chain cation.

Journal Article↗

Rapid assessment of drug use and HIV vulnerability in south-east and east Asia.

In an 8-week period in late 1997, an assessment of the situation of drug use and HIV vulnerability in east and south-east Asia was carried out for the United Nations Joint Programme on AIDS (UNAIDS). It served to assist UNAIDS' Asia-Pacific team in setting priorities for action at a regional level, it having been realised that epidemics of HIV among injecting drug users (IDUs) were playing an important role in the development of the AIDS epidemic in Asia at both country and regional levels. Though essentially a desk exercise, contact with the extensive membership of the Asian Harm Reduction Network allowed a deeper and more efficient investigation than would otherwise have been possible, with access to key informants and 'grey' literature. The assessment found a situation of massive epidemics of HIV among IDUs either occurring, or about to occur, in most Asian countries; and parlous or non-existent public health responses to these problems in a context void of policy. As well as providing evidence to guide UNAIDS, and useful for advocacy by a wide range of people, the process of the situation assessment also generated interest and in some cases activity on the part of many individuals and institutions throughout the region. It is hoped that this will be the beginning of an ongoing monitoring of the situation.

Journal Article↗

Advances in ureteral stent technology.

This review focuses on technological advances and relevant research related to ureteral stents. The importance of physical and chemical biomaterial type, biocompatibility, material coatings such as hydrogels, and infection related to indwelling ureteral stents are discussed. Recent in vitro and in vivo research has focused on materials that will reduce encrustation and bacterial biofilm formation. The adsorption of antimicrobials onto devices holds promise of reducing infection rates, but multidrug resistant bacteria, short leaching times and adverse side effects make it essential that alternative strategies be investigated. Just so, encrustation limits the long-term use of urinary materials, and a better understanding of factors involved in encrustation are needed to reduce the problem.

Biocompatible Materials↗

Inhibition of uropathogenic biofilm growth on silicone rubber in human urine by lactobacilli--a teleologic approach.

The ability of three Lactobacillus strains to inhibit the adhesion and growth of naturally occurring uropathogens on silicone rubber was investigated in human urine. The importance of biosurfactant production by Lactobacillus in discouraging uropathogen growth was determined in relation to the binding affinities of the lactobacilli for silicone rubber. L. fermentum B54 markedly inhibited uropathogen growth on the silicone rubber disks after 8 days for all five men included in the study, albeit to various extents ranging from 77% to 100%. In urine from women, however, this inhibition was less clear, as it was absent for two of the four women participating in this study. L. casei rhamnosus 36 completely discouraged uropathogen growth on the disks after 8 days for three of the four women, whereas its effect in urine from men was less pronounced (inhibition ranged from 48% to 100% and was absent for one man). L. casei rhamnosus ATCC 7469T was the least inhibitory Lactobacillus strain tested and inhibition was absent for a number of both male and female participants, possibly as a result of the low binding affinity of this strain for silicone rubber and of its inability to release biosurfactants. We conclude that the inhibition of uropathogen growth is dependent on the Lactobacillus strain involved, and for L. fermentum B54 it was demonstrated to be sex-related. Hence, inhibition must be considered a multifactorial process.

Adult↗

Probiotic Therapy and Functional Foods for Prevention of Urinary Tract Infections: State of the Art and Science.

In the past year, interest has heightened in the potential for probiotics to prevent urinary tract infection (UTI). Mainly, this has been due to concerns about antibiotic resistance and recognition of the scientific efficacy of probiotics. The critical factors in any successful application of probiotics to patient care are the scientific basis for selecting probiotic strains and clinical verification that they are effective against the recurrence of UTI. Three strains--Lactobacillus rhamnosus GR-1 and Lactobacillus fermentum B-54 and RC-14--have been shown to colonize the vagina and act as a barrier to the ascension of uropathogens into the bladder. Their ability to produce growth and adhesion antagonists against urogenital pathogens is clinically important, because these appear to be important mechanisms of action. Probiotic therapy has been shown to be safe, but too few reliable products are on the market, and none are yet available for use against UTI. Given the right strains and delivery system, probiotic therapy could provide the first new UTI-prevention system in 40 years, and may help in the management of recurrent UTI.

Journal Article↗