Characterization of autoimmune inflammation induced prostate stem cell expansion

BACKGROUND

The presence of inflammation in prostate cancer (PCa) and benign prostate hyperplasia (BPH) has been well described but the cellular mechanisms by which inflammation modulates the prostate are currently unclear. Prostate stem cells (PSC) not only maintain prostate homeostasis but also are considered to be the cell of origin of PCa and an important contributor to BPH. However, the impact of inflammation on PSC is not well understood. Therefore, we initiated studies to evaluate the effect of inflammation on PSC.

METHOD

Ovalbumin specific CD8⁺ T cells were intravenously delivered to intact and castrated prostate ovalbumin expressing transgenic‐3 (POET‐3) mice to induce inflammation. Lin (CD45/CD31)^?Sca1⁺CD49f⁺ cells (LSC) and progenitor cells within LSC were determined by flow cytometry. Sorted LSC were subjected to a prostate sphere forming assay to evaluate PSC clonal propagation, proliferation, immediate differentiation, and self‐renewal ability. Density of individual spheres was measured by a cantilever‐based resonator weighing system. Morphology and characterization of prostate spheres was determined by hematoxylin and eosin (H&E) staining and immunohistochemistry (IHC). Finally, immediate PSC differentiation in sphere formation was determined by immunofluorescence for epithelial cytokeratin markers cytokeratin (CK) 5 and CK8.

RESULT

Data presented here demonstrate a significant expansion of the proliferative (BrdU⁺) LSC population, including CK5⁺, p63⁺, CK18⁺ cells, as well as intermediate cells (CK5⁺/CK8⁺) in inflamed prostates. Histological images reveal that PSC from inflamed prostates produce significantly larger spheres, indicating that the enhanced proliferation observed in LSC is sustained in vitro in the absence of inflammatory mediators. In addition, cultures from inflamed PSC yielded increased number of tubule‐like spheres. These tube‐like spheres grown from PSCs isolated from inflamed mice exhibited stratification of a CK8⁺ luminal‐like layer and a CK5⁺ basal‐like layer. Notably, the numbers of spheres formed by inflamed and non‐inflamed PSC were equal, suggesting that even though proliferation is enhanced by inflammation, the homeostatic level of PSC is maintained.

CONCLUSION

Induction of inflammation promotes PSC expansion and immediate differentiation through highly proliferative progenitor cells while the homeostasis of PSC is maintained. Prostate 75:1620–1631, 2015. © 2015 The Authors. The Prostate, published by Wiley Periodicals, Inc.

     

Is nocturia of young adulthood a remnant of childhood nocturnal enuresis?

Introduction and hypothesis

Nocturia and nocturnal enuresis (NE) share similar aetiopathological factors, and may represent two different situations involving the same underlying issue. In this study, we tried to evaluate the relation between NE of childhood and nocturia of young adulthood.

Methods

A total of 577 female university students aged 17–24 years were included in the survey. A face-to-face questionnaire was administered concerning present nocturia and past NE history. A non-validated questionnaire, created by the authors, was used to evaluate the presence and the frequency of childhood NE and present nocturia. All participant data were checked by telephone contact with their parents.

Results

The overall prevalence rates of nocturia and history of nocturnal enuresis in the study population were 8.6 % and 15 % respectively. Sixteen per cent of nocturics and 15 % of non-nocturics had a history of childhood NE (p?=?0.837). The childhood NE was graded as severe or infrequent. The presence of nocturia was compared between participants with severe NE and infrequent NE, and no significant difference was observed (11.1 % vs 7.8 %, p?=?0.713). Nocturia frequency was compared with the history of childhood NE and we found that as the nocturia frequency increased, the rate of childhood NE also increased.

Conclusions

There was no relation between young adulthood nocturia and childhood NE in our study population, but as the severity of nocturia increased, the relation between nocturia and NE became more relevant.     

Pattern of isthmus conduction recovery using open cooled and solid large-tip catheters for radiofrequency ablation of typical atrial flutter

INTRODUCTION: Open cooled-tip and solid 8-mm-tip catheters have demonstrated safety and effectiveness for radiofrequency current (RFC) ablation of typical atrial flutter (AFL). However, data from prospective and randomized studies in this setting are lacking. METHODS AND RESULTS: One hundred thirty consecutive patients (104 men; 61 +/- 11 years) with AFL were randomized to undergo RFC catheter ablation either using a solid 8-mm-tip catheter (group A, 65 degrees C, 70 W, 60 s) or an open irrigated-tip catheter (group B, 65 degrees C, 50 W, 60 s, 17 mL/min flow). Endpoint was bidirectional conduction isthmus block. In cases of repeated (two times) transient isthmus block, the catheter was changed (crossed over) to the catheter used in the other randomization arm, but patients remained in the original group following intention-to-treat analysis. The selected endpoint could be achieved in all patients after 12 +/- 6 RFC pulses in group A and 10 +/- 7 RFC pulses in group B (P = 0.11). Procedure times were longer (159 +/- 38 min vs 138 +/- 37 min, P = 0.002) and x-ray exposures higher in group A (fluoroscopy time 25 +/- 17 min vs 21 +/- 10 min, P = 0.08; x-ray dosage 3,133 +/- 2,576 cGy.cm2 vs 2,326 +/- 1,405 cGy.cm2, P = 0.03). Transient isthmus block was observed in 23 group A patients and 12 group B patients (P = 0.03). Onset time of transient isthmus block ranged from 0.5 to 27 minutes. Repeated transient isthmus block occurred in 8 of the 23 patients in group A after 19 +/- 3 RFC applications. After crossover to the cooled-tip catheter, the endpoint was reached another 5 +/- 1 RFC pulses. In group B, all patients could be treated without change of ablation catheter. After a follow-up of 14 +/- 2 months, 2 patients (3%) in group A and 1 patient (1.5%) in group B presented with AFL recurrence. CONCLUSION: Open cooled-tip catheters are more effective than solid large-tip catheters for AFL ablation. The greater effectiveness is evident in cases showing repeated conduction recovery within the cavotricuspid isthmus. Primary use of open irrigated-tip catheters should be considered for AFL ablation.     

The effect of adipose derived stromal vascular fraction on stasis zone in an experimental burn model

Background

Stasis zone is the surrounding area of the coagulation zone which is an important part determining the extent of the necrosis in burn patients. In our study we aim to salvage the stasis zone by injecting adipose derived stromal vascular fraction (ADSVF).

Health Effects of Infant Formula Supplemented with Probiotics or Synbiotics in Infants and Toddlers: Systematic Review with Network Meta-Analysis

Supplementation of infant and follow-up formula with probiotics or synbiotics has become a common practice. In 2011 and 2017, the evidence regarding the impact of these interventions was analysed systematically. Recently new evidence was published. To evaluate through a systematic review with network meta-analysis the evidence on the impact of infant formula supplemented with probiotics or synbiotics for healthy infants and 36-month-old toddlers. RCTs published between 1999–2019 for infant formulas supplemented with probiotics alone or synbiotics in healthy infants and toddlers were identified. Data analysis included clinical (gastrointestinal symptoms, risk reduction of infectious diseases, use of antibiotics, weight/height gain and frequency of adverse events) and non-clinical outcomes (changes in faecal microbiota and immune parameters). A random effect model was used. Hedges’ standard mean difference (SMD) and risk ratio (RR) were calculated. Rank analysis was performed to evaluate the superiority of each intervention. Twenty-six randomised controlled trials with 35 direct comparisons involving 1957 children receiving probiotic-supplemented formula and 1898 receiving control formula were reviewed. The mean duration of intervention was 5.6 ± 2.84 months. Certain strains demonstrated a reduction in episodes of colic, number of days with fever and use of antibiotics; however, there was considerable heterogeneity which reduced the level of certainty of effect. No significant effects were observed on weight, height or changes in faecal proportions of Bifidobacteria, Lactobacillus, Bacteroides or Clostridia. Although there is some evidence that may support a potential benefit of probiotic or synbiotic supplementation of infant formulas, variation in the quality of existing trials and the heterogeneity of the data preclude the establishment of robust recommendations.     

Clinical features of generalized lipodystrophy in Turkey: A cohort analysis

Aim

To describe the Turkish generalized lipodystrophy (GL) cohort with the frequency of each complication and the death rate during the period of the follow-up.

Methods

This study reports on 72 patients with GL (47 families) registered at different centres in Turkey that cover all regions of the country. The mean ± SD follow-up was 86 ± 78 months.

Results

The Kaplan–Meier estimate of the median time to diagnosis of diabetes and/or prediabetes was 16 years. Hyperglycaemia was not controlled in 37 of 45 patients (82.2%) with diabetes. Hypertriglyceridaemia developed in 65 patients (90.3%). The Kaplan–Meier estimate of the median time to diagnosis of hypertriglyceridaemia was 14 years. Hypertriglyceridaemia was severe (≥ 500 mg/dl) in 38 patients (52.8%). Seven (9.7%) patients suffered from pancreatitis. The Kaplan–Meier estimate of the median time to diagnosis of hepatic steatosis was 15 years. Liver disease progressed to cirrhosis in nine patients (12.5%). Liver disease was more severe in congenital lipodystrophy type 2 (CGL2). Proteinuric chronic kidney disease (CKD) developed in 32 patients (44.4%) and cardiac disease in 23 patients (31.9%). Kaplan–Meier estimates of the median time to diagnosis of CKD and cardiac disease were 25 and 45 years, respectively. Females appeared to have a more severe metabolic disease, with an earlier onset of metabolic abnormalities. Ten patients died during the follow-up period. Causes of death were end-stage renal disease, sepsis (because of recurrent intestinal perforations, coronavirus disease, diabetic foot infection and following coronary artery bypass graft surgery), myocardial infarction, heart failure because of dilated cardiomyopathy, stroke, liver complications and angiosarcoma.

Conclusions

Standard treatment approaches have only a limited impact and do not prevent the development of severe metabolic abnormalities and early onset of organ complications in GL.