Effect of aging on endogenous level of 5 alpha-dihydrotestosterone, testosterone, estradiol, and estrone in epithelium and stroma of normal and hyperplastic human prostate.

associated with aging. Thus, the question arises whether or not a correlation exists between the well known prostatic androgen and estrogen accumulation and aging. To address this question, we measured 5a-dihydrotestosterone (DHT), testosterone, estradiol, and estrone in epithelium and stroma of six normal (NPR) and 19 BPH and correlated the values with the age of the donors (26-87 yr). The mean DHT level in NPR epithelium was significantly higher than in NPR stroma, and also significantly higher than in epithelium and stroma of BPH. The epithelial DHT level of NPR and BPH decreased with age, the correlation being statistically significant. The stromal DHT level of NPR and BPH showed no correlation with age. Concerning testosterone, generally rather low values were found which showed no correlation with age. The mean levels of estradiol and estrone were significantly higher in BPH stroma as compared to BPH epithelium as well as to NPR epithelium and stroma. In NPR, the mean levels of estradiol and estrone were significantly higher in epithelium than stroma. In NPR and BPH, the stromal estradiol and estrone levels increased significantly with age. In epithelium such a correlation between the estrogen levels and age was not found. Our results indicate that the prostatic accumulation of DHT, estradiol, and estrone is in part intimately correlated with aging, leading with increasing age to a dramatic increase of the estrogen/androgen ratio particularly in stroma of BPH

An Early Synovitis Clinic: Differentiating Persistent From Self-Limiting Synovitis

Background: My interest in differentiating between persistent and self-limiting synovitis (PS and SLS) developed from the Bath experience, where Professor Bacon and Dr Blake ran an early synovitis clinic. A proportion of the patients were noted (in an epidemic year) to have had Human Parvovirus B19 (B19) infection coinciding with the start of their synovitis (White DG et al. Lancet 1985; 1; 419-22). A minority of the B19 patients had persisting symptoms a year later adding to speculation on the possible role of viruses in the aetiology of chronic rheumatic diseases

High dose rate brachytherapy as monotherapy for localised prostate cancer : a hypofractionated two-implant approach in 351 consecutive patients

BACKGROUND: To report the clinical outcome of high dose rate brachytherapy as sole treatment for clinically localised prostate cancer. METHODS: Between March 2004 and January 2008, a total of 351 consecutive patients with clinically localised prostate cancer were treated with transrectal ultrasound guided high dose rate brachytherapy. The prescribed dose was 38.0 Gy in four fractions (two implants of two fractions each of 9.5 Gy with an interval of 14 days between the implants) delivered to an intraoperative transrectal ultrasound real-time defined planning treatment volume. Biochemical failure was defined according to the Phoenix Consensus and toxicity evaluated using the Common Toxicity Criteria for Adverse Events version 3. RESULTS: The median follow-up time was 59.3 months. The 36 and 60 month biochemical control and metastasis-free survival rates were respectively 98%, 94% and 99%, 98%. Toxicity was scored per event with 4.8% acute Grade 3 genitourinary and no acute Grade 3 gastrointestinal toxicity. Late Grade 3 genitourinary and gastrointestinal toxicity were respectively 3.4% and 1.4%. No instances of Grade 4 or greater acute or late adverse events were reported. CONCLUSIONS: Our results confirm high dose rate brachytherapy as safe and effective monotherapy for clinically organ-confined prostate cancer

Progression-dependent altered metabolism in osteosarcoma resulting in different nutrient source dependencies

Osteosarcoma (OS) is a primary malignant bone tumor and OS metastases are mostly found in the lung. The limited understanding of the biology of metastatic processes in OS limits the ability for effective treatment. Alterations to the metabolome and its transformation during metastasis aids the understanding of the mechanism and provides information on treatment and prognosis. The current study intended to identify metabolic alterations during OS progression by using a targeted gas chromatography mass spectrometry approach. Using a female OS cell line model, malignant and metastatic cells increased their energy metabolism compared to benign OS cells. The metastatic cell line showed a faster metabolic flux compared to the malignant cell line, leading to reduced metabolite pools. However, inhibiting both glycolysis and glutaminolysis resulted in a reduced proliferation. In contrast, malignant but non-metastatic OS cells showed a resistance to glycolytic inhibition but a strong dependency on glutamine as an energy source. Our in vivo metabolic approach hinted at a potential sex-dependent metabolic alteration in OS patients with lung metastases (LM), although this will require validation with larger sample sizes. In line with the in vitro results, we found that female LM patients showed a decreased central carbon metabolism compared to metastases from male patients

Convenanten in de transitie naar een circulaire economie: Een innovatie systeem analyse van convenanten in de matrassen-, beton- en plasticsector

Dit rapport presenteert de rol van vrijwillige convenanten in de transitie naar circulaire economie in Nederland, specifiek voor het Circulair Ketenoverleg Matrassen (Utrecht Sustainability Institute, 2016), Betonakkoord (2018) en het Plastic Pact NL (2019). De bevindingen in dit rapport vormen input voor de Integrale CE Rapportage (ICER) 2023. Om de transitie naar een circulaire economie te versnellen is er in een aantal sectoren een convenant getekend tussen overheid, producenten en verwerkers waarin een aantal (beleids-)doelstellingen zijn opgenomen. Vanwege de vrijwilligheid van deze convenanten is men kritisch naar de effectiviteit ervan voor de transitie. Dit rapport dient als een reflectie op de functionaliteit en effectiviteit van deze convenanten voor de transitie naar een circulaire economie. Om de functionaliteit en effectiviteit van de convenanten in deze transitie goed in beeld te krijgen, wordt de methodiek van een Missie-gedreven Innovatie Systeem raamwerk gebruikt. Het MIS wordt gedefinieerd als het netwerk van actoren en regels die gezamenlijk bijdragen aan de ontwikkeling en verspreiding van innovatieve oplossingen en de transformatie van de huidige manier van produceren en consumeren om daarmee de missie te volbrengen. De convenanten zijn een onderdeel van de activiteiten die gezamenlijk ondernomen worden door actoren binnen een bepaalde sector of doelgroep. Met behulp van een MIS analyse zal dit onderzoek de bevorderingen en belemmeringen van bovengenoemde convenanten identificeren om aanknopingspunten te geven voor het beoordelen en het eventueel aanscherpen van de aanpak om op die manier bij te dragen aan het volbrengen van de missie