The Human Tissue-Biomaterial Interface : A Role for PPARγ-Dependent Glucocorticoid Receptor Activation in Regulating the CD163(+) M2 Macrophage Phenotype

In vivo studies of implanted acellular biological scaffolds in experimental animals have shown constructive remodeling mediated by anti-inflammatory macrophages. Little is known about the human macrophage response to such biomaterials, or the nature of the signaling mechanisms that govern the macrophage phenotype in this environment. The cellular events at the interface of a tissue and implanted decellularized biomaterial were examined by establishing a novel ex vivo tissue culture model in which surgically excised human urinary tract tissue was combined with porcine acellular bladder matrix (PABM). Evaluation of the tissue-biomaterial interface showed a time-dependent infiltration of the biomaterial by CD68(+) CD80(-) macrophages. The migration of CD68(+) cells from the tissue to the interface was accompanied by maturation to a CD163(hi) phenotype, suggesting that factor(s) associated with the biomaterial or the wound edge was/were responsible for the active recruitment and polarization of local macrophages. Glucocorticoid receptor (GR) and peroxisome proliferator activated receptor gamma (PPARγ) signaling was investigated as candidate pathways for integrating inflammatory responses; both showed intense nuclear labeling in interface macrophages. GR and PPARγ activation polarized peripheral blood-derived macrophages from a default M1 (CD80(+)) toward an M2 (CD163(+)) phenotype, but PPARγ signaling predominated, as its antagonism blocked any GR-mediated effect. Seeding on PABM was effective at polarizing peripheral blood-derived macrophages from a default CD80(+) phenotype on glass to a CD80(-) phenotype, with intense nuclear localization of PPARγ. These results endorse in vivo observations that the infiltration of decellularized biological scaffolds, exemplified here by PABM, is pioneered by macrophages. Thus, it appears that natural factors present in PABM are involved in the active recruitment and polarization of macrophages to a CD163(+) phenotype, with activation of PPARγ identified as the candidate pathway. The harnessing of these natural matrix-associated factors may be useful in enhancing the integration of synthetic and other natural biomaterials by polarizing macrophage activation toward an M2 regulatory phenotype

Health-related quality of life and Chlamydia trachomatis infection in sexually experienced female inner-city students: a community-based cross-sectional study.

This cross-sectional study was undertaken to compare health-related quality of life (EQ-5D) in women with and without undiagnosed Chlamydia trachomatis infection. We analysed data from 2401 multi-ethnic sexually active female students aged 16-27 years who were recruited to a randomised controlled trial of chlamydia screening - the prevention of pelvic infection trial in 2004-2006. At recruitment, all participants were asked to provide self-taken vaginal swabs for chlamydia testing and to complete a sexual health questionnaire including quality of life (EQ-5D). Most women (69%) had an EQ-5D of one representing 'perfect health' in the five dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. We therefore compared the proportion of women with an EQ-5D score < 1 implying 'less than perfect health' in women with and without chlamydia infection, and women with symptomatic chlamydia versus the remainder. The proportion of women with EQ-5D score < 1 was similar in women with and without undiagnosed chlamydia: 34% (47/138) versus 31% (697/2263; RR 1.11, 95% CI 0.87 to 1.41). However, more women with symptomatic chlamydia had EQ-5D score < 1 than the remainder: 45% (25/55) versus 31% (714/2319; RR 1.47, CI 1.10 to 1.98). In this community-based study, EQ-5D scores were similar in women with and without undiagnosed chlamydia. However, a higher proportion of women with symptomatic chlamydia infection had 'less than perfect health'. Undiagnosed chlamydia infection may not have a major short-term effect on health-related quality of life, but EQ-5D may not be the best tool to measure it in this group

Detection of epithelial cancer cells in peripheral blood by reverse transcriptase-polymerase chain reaction.

Circulating cancer cells in the blood play a central role in the metastatic process. Their number can be very small and techniques for their detection need to be both sensitive and specific. Polymerase chain reaction (PCR) has been successfully used to detect small numbers of tumour cells in haematological cancer in which abnormalities in DNA are sufficiently consistent to make this possible. For most solid tumours this not yet feasible. However, we have found that reverse transcriptase (RT)-PRC for tissue-specific gene expression is a useful technique for identifying small numbers of circulating cells in melanoma and neuroblastoma patients. In this report we describe detection of colon carcinoma cells by RT-PCR using CK 20 mRNA as a marker. Unlike other cytokeratin genes examined (CK 8 and CK 19), CK 20 was not transcribed in normal haematopoietic cells. This suggests a role for RT-PCR in the detection of colon carcinoma metastasis in blood and bone marrow, using CK 20 as the target gene. Future analysis of clinical material will determine the clinical significance of this technique

Praziquantel: its use in control of schistosomiasis in sub-Saharan Africa and current research needs

Treatment with praziquantel (PZQ) has become virtually the sole basis of schistosomiasis control in sub-Saharan Africa and elsewhere, and the drug is reviewed here in the context of the increasing rate that it is being used for this purpose. Attention is drawn to our relative lack of knowledge about the mechanisms of action of PZQ at the molecular level, the need for more work to be done on schistosome isolates that have been collected recently from endemic areas rather than those maintained in laboratory conditions for long periods, and our reliance for experimental work mainly on Schistosoma mansoni, little work having been done on S. haematobium. There is no evidence that resistance to PZQ has been induced in African schistosomes as a result of its large-scale use on that continent to date, but there is also no assurance that PZQ and/or schistosomes are in any way unique and that resistant organisms will not be selected as a result of widespread drug usage. The failure of PZQ to produce complete cures in populations given a routine treatment should therefore solicit considerable concern. With few alternatives to PZQ currently available and/or on the horizon, methods to monitor drug-susceptibility in African schistosomes need to be devised and used to help ensure that this drug remains effective for as long a time as possibl

A provisional database for the silicon content of foods in the United Kingdom

Si may play an important role in bone formation and connective tissue metabolism. Although biological interest in this element has recently increased, limited literature exists on the Si content of foods. To further our knowledge and understanding of the relationship between dietary Si and human health, a reliable food composition database, relevant for the UK population, is required. A total of 207 foods and beverages, commonly consumed in the UK, were analysed for Si content. Composite samples were analysed using inductively coupled plasma&ndash;optical emission spectrometry following microwave-assisted digestion with nitric acid and H2O2. The highest concentrations of Si were found in cereals and cereal products, especially less refined cereals and oat-based products. Fruit and vegetables were highly variable sources of Si with substantial amounts present in Kenyan beans, French beans, runner beans, spinach, dried fruit, bananas and red lentils, but undetectable amounts in tomatoes, oranges and onions. Of the beverages, beer, a macerated whole-grain cereal product, contained the greatest level of Si, whilst drinking water was a variable source with some mineral waters relatively high in Si. The present study provides a provisional database for the Si content of UK foods, which will allow the estimation of dietary intakes of Si in the UK population and investigation into the role of dietary Si in human health.<br /

Giant mediastinal mature teratoma with increased exocrine pancreatic activity presenting in a young woman: a case report

Abstract Introduction Mediastinal mature teratoma is a benign, slow-growing tumor typically affecting 20- to 40-year-old adults. Fluid examination from the cystic masses rarely shows enzymatic activity as we describe in this report. Case presentation We report a case of a giant mediastinal germ cell tumor (measuring 15 cm × 14 cm × 8 cm) detected in a 35-year-old Caucasian woman. Microscopic examination showed that the lesion resembled a mature cystic teratoma with areas of pancreatic tissue with mature ductal and acinar structures intermixed with islets of Langerhans. Fluid from the cysts in the mass was examined after removal showed amylase activity of 599 U/l despite normal serum levels. The post-operative period was free of complications, and the patient was discharged on post-operative day 10. Conclusion Complete surgical removal is the treatment of choice for mature cystic teratomas, with optimal results and acceptable surgical risk. Exocrine pancreatic function may be an aid to pre-operative or intra-operative diagnosis; however, these findings have no impact on survival or the therapeutic pathway.</p

A two-lab direct replication attempt of Southgate, Senju and Csibra (2007)

The study by Southgate et al. (2007 Psychol. Sci. 18, 587–592. (doi:10.1111/j.1467-9280.2007.01944.x)) has been widely cited as evidence for false-belief attribution in young children. Recent replication attempts of this paradigm have yielded mixed results: several studies did not replicate the original findings, raising doubts about the suitability of the paradigm to assess non-verbal action prediction and Theory of Mind. In a preregistered collaborative study including two of the original authors, we tested one hundred and sixty 24- to 26- month-olds across two locations using the original stimuli, procedure and analyses as closely as possible. We found no evidence for action anticipation: only roughly half of the infants looked to the location of an agent’s impending action when action prediction did not require taking into account the agent’s beliefs and a similar number when the agent held a false-belief. These results and other non-replications suggest that this paradigm does not reliably elicit action prediction and thus cannot assess false-belief understanding in 2-year- olds. While the present results do not support any claim regarding the presence or absence of Theory of Mind in infants, we conclude that an important piece of evidence that has to date supported arguments for the existence of this competence can no longer serve that function