Detection of Candida spp. in the vagina of a cohort of nulliparous pregnant women by culture and molecular methods: is there an association between maternal vaginal and infant oral colonisation?

BACKGROUND: Most studies describing vaginal Candida spp. in pregnancy focus on symptomatic vaginitis, rather than asymptomatic colonisation, and solely utilise microbiological culture. The extent to which asymptomatic vaginal carriage may represent a reservoir for infant oral colonisation has been highly debated. MATERIALS AND METHODS: This study formed part of the Candida and Staphylococcus Transmission Longitudinal Evaluation (CASTLE) study, in Melbourne, Australia, from 2009 to 2011 and used culture and molecular methods to examine vaginal swabs collected late in the third trimester of pregnancy for Candida spp. Oral swabs from infants were also examined using culture methods. RESULTS: Overall, 80 of 356 (22%) women were positive for Candida spp; the majority being Candida albicans (83%). Candida glabrata and other Candida spp. were also identified, but in much lower numbers. Molecular analysis identified numerous positive samples not detected by culture, including 13 cases of C. albicans. In addition, some positive samples only recorded to genus level by culture were accurately identified as either C. albicans or C. glabrata following molecular analyses. Eighteen infants recorded positive Candida spp. cultures, predominantly C. albicans. However, there were only four (25%) mother/infant dyads where C. albicans was detected. CONCLUSIONS: This study provides valuable data on asymptomatic colonisation rates of Candida spp. within an asymptomatic population of women late in pregnancy. The utilisation of molecular methods improved the rate of detection and provided a more accurate means for identification of non-albicans Candida spp. The low mother/infant colonisation rate suggests that non-maternal sources are likely involved in determining infant oral colonisation status.

Bypassing luminal barriers, delivery to a gut addressin by parenteral targeting elicits local IgA responses

Induction of mucosal immunity, particularly to subunit vaccines, has been problematic. The primary hurdle to successful mucosal vaccination is the effective delivery of vaccine antigen to the mucosal associated lymphoid tissue. Physical and chemical barriers restrict antigen access and, moreover, immune responses induced in the mucosa can be biased towards tolerance or non-reactivity. We proposed that these difficulties could be circumvented by targeting antigen to the gastrointestinal associated lymphoid tissue via systemic (parenteral) rather than alimentary routes, using antibodies specific for the mucosal addressin cellular adhesion molecule-1 (MAdCAM). After intravenous or intramuscular injection of such rat antibodies in mice, we found a greatly enhanced (up to 3 logs) anti-rat antibody response. MAdCAM targeting induces a rapid IgA antibody response in the gut and vastly improves the systemic antibody response. Targeting also enhanced T cell proliferation and cytokine responses. Parenteral targeting of mucosal addressins may represent a generic technique for bypassing mucosal barriers and eliminating the need for adjuvants in the induction of proximal and systemic immunity.

Novel agents that potentially inhibit irinotecan-induced diarrhea

Irinotecan (CPT-11, 7-ethyl-10-[4-(1-piperidino)-1-piperidino] carbonyloxycamptothecin) has exhibited clinical activities against a broad spectrum of carcinomas by inhibiting DNA topoisomerase I (Topo I). However, severe and unpredictable dosing-limiting toxicities (mainly myelosuppression and severe diarrhea) hinder its clinical use. The latter consists of early and late-onset diarrhea, occurring within 24 hr or ≥ 24 hr after CPT-11 administration, respectively. This review highlights novel agents potentially inhibiting CPT-11-induced diarrhea, which are designed and tested under guidance of disposition pathways and potential toxicity mechanisms. Early-onset diarrhea is observed immediately after CPT-11 infusion and probably due to the inhibition of acetylcholinesterase activity, which can be eliminated by administration of atropine. Lateonset diarrhea appears to be associated with intestinal exposure to SN-38 (7-ethyl-10-hydroxycamptothecin), the major active metabolite of CPT-11, which may bind to Topo I and induce apoptosis of intestinal epithelia, leading to the disturbance in the absorptive and secretory functions of mucosa. CPT-11 and SN-38 may also stimulate the production of pro-inflammatory cytokines and prostaglandins (PGs), thus inducing the secretion of Na⁺ and Cl^-. Early treatment of severe late-onset diarrhea with oral high-dose loperamide has decreased patient morbidity. Extensive studies have been conducted to identify other potential agents to ameliorate diarrhea in preclinical and clinical models. These include intestinal alkalizing agents, oral antibiotics, enzyme inducers, P-glycoprotein (PgP) inhibitors, cyclooxygenase-2 (COX-2) inhibitors, tumor necrosis factor-agr (TNF-α) inhibitors, or blockers of biliary excretion of SN-38. Further studies are needed to identify the molecular targets associated with CPT-11 toxicity and safe and effective agents for alleviating CPT-11-induced diarrhea.

Feminist poetics : symbolism in an emblematic journey reflecting self and vision

My thesis tilled Feminist Poetics: Symbolism in an Emblematic Journey Reflecting Self and Vision, consists of thirty oil paintings on canvas, several preparatory sketches and drawings in different media on paper, and is supported and elucidated by an exegesis. The paintings on unframed canvases reveal mise en scčnes and emblems that present to the viewer a drama about links between identities, differences, relationships and vision. Images of my daughter, friends and myself fill single canvases, suites of paintings, diptyches and triptychs. The impetus behind my research derives from my recognition of the cultural means by which women's experience is excluded from a representational norm or ideal. I use time-honoured devices, such as, illusionist imagery, aspects of portraiture, complex fractured atmospheric space, paintings and drawings within paintings, mirrors and reflective surfaces, shadows and architectural devices. They structure my compositions in a way that envelops the viewer in my internal world of ideas. Some of these features function symbolically, as emblems. A small part of the imagery relies on verisimilitude, such as my hands and their shadow and my single observing eye enclosed by my glasses. What remains is a fantasy world, ‘seen’ by the image of my other eye, or ‘faction’, based on memories and texts explaining the significance of ancient Minoan symbols. In my paintings, I base the subjects of this fantasy on my memories of the Knossos Labyrinth and matristic symbols, such as the pillar, snake, blood, eye and horn. They suggest the presence of a ritual where initiates descended into the adyton (holy of holies) or sunken areas in the labyrinth. The paintings attempt a ‘rewriting’ of sacrality and gender by adopting the symbolism of death, transformation and resurrection in the adyton. The significance of my emblematic imagery is that it constructs a foundation narrative about vision and insight. I sought symbolic attributes shared by European oil painting and Minoan antiquity. Both traditions share symbolic attributes with male dying gods in Greek myths and Medusa plays a central part in this linkage. I argue that her attributes seem identical to both those of the dying gods and Minoan goddesses. In the Minoan context these symbols suggest metaphors for the female body and the mother and daughter blood line. When the symbols align with the beheaded Medusa in a patriarchal context, both her image and her attributes represent cautionary tales about female sexuality that have repercussions for aspects of vision. In Renaissance and Baroque oil painting Medusa's image served as a vehicle for an allegory that personified the triumph of reason over the senses. In the twentieth century, the vagina dentata suggests her image, a personified image of irrational emotion that some male Surrealists celebrated as a muse. She is implicated in the male gaze as a site of castration and her representation suggests a symbolic form pertaining to perspective. Medusa's image, its negative sexual and violent connotations, seemed like a keystone linking iconographic codes in European oil painting to Minoan antiquity. I fused aspects of matristic Minoan antiquity with elements of European oil paintings in the form of disguised attribute gestures, objects and architectural environments. I selected three paintings, Dürer's Setf-Portrait, 1500, Gentileschi's Self-Portrait as the Allegory of Painting, 1630 and Velazquez's Las Meniruis, 1656 as models because 1 detected echoes of Minoan symbolism in the attributes of their subjects and backgrounds. My revision of Medusa's image by connecting it to Minoan antiquity established a feminist means of representation in the largely male-dominated tradition of oil painting. These paintings also suggested painting techniques that were useful to me. Through my representations of my emblematic journey I questioned the narrow focus placed on phallic symbols when I explored how their meanings may have been formed within a matricentric culture. I retained the key symbols of the patriarchal foundation narratives about vision but removed images of violence and their link to desire and replaced it with a ritual form of symbolic death. I challenged the binary oppositional defined Self as opposed to Other by constructing a complex, fluid Self that interacts with others. A multi-directional gaze between subjects, viewers and artist replaces the male gaze. Different qualities of paint, coagulation and random flow form a blood symbolism. Many layers of paint retaining some aspects of the Gaze and Glance, fuse and separate intermittently to construct and define form. The sense of motion and fluidity constructs a form of multi-faceted selves. The supporting document, the exegesis is in two parts. In the first part, I discuss the Minoan sources of my iconography and the symbolic gender specific meanings suggested by particular symbols and their changed meanings in European oil painting, I explain how I integrate Minoan symbols into European oil paintings as a form of disguised symbolism. In the second part I explain how my alternative use of symbolism and paint alludes to a feminist poetic.

Baseline comorbidities in a population-bases cohort of rheumatoid arthritis patients receiving biological therapy: data from the Australian Rheumatology Association database

Aims: To describe the baseline characteristics of an Australian population-based cohort of rheumatoid arthritis (RA) patients commencing biological therapy.

Methods: Descriptive analysis from the Australian Rheumatology Association Database (ARAD).

Results: Up to October 2006, there were 681 RA patients taking biologics enrolled in ARAD. Baseline data were available for 624 (72% female, mean (SD) age 57.0 (12.5) years). Of these, 59.5% reported at least one comorbid condition, most commonly hypertension (35.7%) and osteoporosis (30.4%); 61 (9.8%) had a history of malignancy (35 nonmelanoma skin, 5 breast, 4 bowel, 5 cervix, 3 melanoma, 3 prostate and 1 each of lip, lung, myeloma, testis, uterus, vagina). Self-reported infections within the previous 6 months were common (71.5%).

Conclusions: History of comorbidities, including recent infections, is common among Australian RA patients commencing biologics, and 10% have a history of malignancy. This may impact future evaluations of health outcomes among this population, including attribution of adverse events of biologic therapy.

Oxidised mannan as a novel adjuvant inducing mucosal IgA production.

Mannan, oxidatively coupled to recombinant protein antigens, has here been tested as a possible adjuvant for the production of antibody on the mucosa. Given intranasally, but not intraperitoneally, mannan markedly enhanced the production of IgA, IgG1 and IgG2a in the serum, and IgA locally in the lung and at remote mucosal sites, including tears, vaginal and salivary secretions. Oxidative coupling was critical to its action, since neither mannan simply mixed with protein nor mannan–protein conjugates which had been reduced by treatment with sodium borohydride, acted as adjuvants. Oxidatively coupled mannan was compared with the widely studied mucosal adjuvant, cholera toxin (CT). The use of oxidised mannan as an adjuvant induced better responses than CT judged by the induction of IgA in serum, vaginal washings and saliva. Thus, oxidised mannan, which is non-toxic and can be administered without injection, is a suitable adjuvant coupled with protective antigens for vaccinating against a number of infections that occur via the mucous membranes.

The effect of folic acid supplementation on dna biomarkers of colorectal cancer risk (uracil misincorporation, global and gene-specific dna hypomethylation) : a randomised intervention study

Background - Alterations in folate status are associated with colorectal carcinogenesis. Folate’s role has been postulated to be either via prevention of changes in DNA methylation or uracil misincorporation.
Objective - To investigate the effect of folic acid supplementation on colonocyte folate status and DNA biomarkers.
Design - Twenty individuals harbouring colonic adenomas were randomised to receive folic acid (600 g daily) or placebo for 6 months post polypectomy. Systemic and colonocyte folate status was determined at baseline and following the intervention. Modified Comet assays were used to determine uracil misincorporation and global DNA hypomethylation at the site adjacent to the polyp and a site distal to the polyp.
Outcomes - Supplementation resulted in increased colonocyte folate, which approached significance, at the site adjacent to the polyp (P= 0.06) but not distal to the polyp (P= 0.36); correspondingly there was a reduction in uracil misincorporation at the site adjacent to the polyp (P = 0.02) and the distal site showed no such trend (P= 0.39). There were no significant changes in global DNA hypomethylation at either site post-intervention.
Conclusions - Folic acid supplementation resulted in increased colonocyte folate and decreased uracil misincorporation at the site of the adenoma but not distal to the adenoma. This supports the hypothesis that localised areas of folate deficiency may exist in human colonic mucosa which respond to folic acid supplementation through increasing colonocyte folate and improving folate-related DNA biomarkers of cancer risk.

Does Candida and/or Staphylococcus play a role in nipple and breast pain in lactation? A cohort study in Melbourne, Australia

Objective: To investigate Candida species and Staphylococcus aureus and the development of 'nipple and breast thrush' among breastfeeding women. Design: Prospective longitudinal cohort study. Setting: Two hospitals in Melbourne, Australia (one public, one private) with follow-up in the community. Participants: 360 nulliparous women recruited at 36 weeks' gestation from November 2009 to June 2011. Participants were followed up six times: in hospital, at home weekly until 4 weeks postpartum and by telephone at 8 weeks. Main outcome measures: Case definition 'nipple and breast thrush': burning nipple pain and breast pain (not related to mastitis); detection of Candida spp (using culture and PCR) in the mother's vagina, nipple or breast milk or in the baby's mouth; detection of S aureus in the mother' nipple or breast milk. Results: Women with the case definition of nipple/ breast thrush were more likely to have Candida spp in nipple/breast milk/baby oral samples (54%) compared to other women (36%, p=0.014). S aureus was common in nipple/breast milk/baby samples of women with these symptoms as well as women without these symptoms (82% vs 79%) (p=0.597). Time-to-event analysis examined predictors of nipple/breast thrush up to and including the time of data collection. Candida in nipple/breast milk/baby predicted incidence of the case definition (rate ratio (RR) 1.87 (95% CI 1.10 to 3.16, p=0.018). We do not have evidence that S aureus colonisation was a predictor of these symptoms (RR 1.53, 95% CI 0.88 to 2.64, p=0.13). Nipple damage was also a predictor of these symptoms, RR 2.30 (95% CI 1.19 to 4.43, p=0.012). In the multivariate model, with all three predictors, the RRs were very similar to the univariate RRs. This indicates that Candida and nipple damage are independent predictors of our case definition.

Defining the interaction of HIV-1 with the mucosal barriers of the female reproductive tract

Worldwide, HIV-1 infects millions of people annually, the majority of whom are women. To establish infection in the female reproductive tract (FRT), HIV-1 in male ejaculate must overcome numerous innate and adaptive immune factors, traverse the genital epithelium, and establish infection in underlying CD4(+) target cells. How the virus achieves this remains poorly defined. By utilizing a new technique, we define how HIV-1 interacts with different tissues of the FRT using human cervical explants and in vivo exposure in the rhesus macaque vaginal transmission model. Despite previous claims of the squamous epithelium being an efficient barrier to virus entry, we reveal that HIV-1 can penetrate both intact columnar and squamous epithelial barriers to depths where the virus can encounter potential target cells. In the squamous epithelium, we identify virus entry occurring through diffusive percolation, penetrating areas where cell junctions are absent. In the columnar epithelium, we illustrate that virus does not transverse barriers as well as previously thought due to mucus impediment. We also show a statistically significant correlation between the viral load of inocula and the ability of HIV-1 to pervade the squamous barrier. Overall, our results suggest a diffusive percolation mechanism for the initial events of HIV-1 entry. With these data, we also mathematically extrapolate the number of HIV-1 particles that penetrate the mucosa per coital act, providing a biological description of the mechanism for HIV-1 transmission during the acute and chronic stages of infection.

The orexinergic system in rainbow trout Oncorhynchus mykiss and its regulation by dietary lipids

In this study, we report the distribution of orexin A (OXA), orexin B (OXB), and orexin receptor (OX2R) immunoreactive (ir) cells in the hypothalamus and gastrointestinal tract of Oncorhynchus mykiss fed diets with different dietary fatty acid compositions. Trout were fed five iso-energetic experimental diets containing fish oil, or one of four different vegetable oils (olive, sunflower, linseed, and palm oils) as the added dietary lipid source for 12 weeks. OXA, OXB, and OX2R immunoreactive neurons and nervous fibers were identified in the lateral and ventro-medial hypothalamus. OXA, OXB, and OX2R ir cells were found in the mucosa and glands of the stomach and in the mucosa of both the pyloric cecae and intestine. OX2R ir cells were localized in the mucosa layer of both the pyloric cecae and intestine. These immunohistochemical (IHC) results were confirmed via Western blotting. Antibodies against preproorexin (PPO) crossreacted with a band of ∼16 kDa in the hypothalamus, stomach, pyloric cecae, and intestine. Antibodies against OX2R crossreacted with a band of ∼38 kDa in the hypothalamus, pyloric cecae, and intestine. The presence and distribution of OXA, OXB, and OX2R ir cells in the hypothalamus and gastrointestinal tract did not appear to be affected by dietary oils. The presence of orexin system immunoreactive cells in the stomach, pyloric cecae, and intestine of rainbow trout, but not in the enteric nervous system, could suggest a possible role of these peptides as signaling of gastric emptying or endocrine modulation, implying a main local action played by orexins.