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Ageing is often accompanied by an increase in bone marrow fat together with reduced bone volume and diseases of the bone such as osteoporosis. As mesenchymal stem cells (MSCs) are capable of forming bone, cartilage and fat tissue, studying these cells is of great importance to understand the underlying mechanisms behind age-related bone diseases. However, inter-donor variation has been found when handling MSCs. Therefore, the aim of this study was to investigate the effects of donor age and sex by comparing in vitro characteristics of human bone marrow-derived MSCs (hBMSCs) from a large donor cohort (n = 175). For this, hBMSCs were analysed for CFU-F capacity, proliferation, differentiation capacity and surface antigen expression under standardized culture conditions. The results demonstrated a significantly reduced CFU-F number for hBMSCs of female compared to male donors. Furthermore, there was a significant decrease in the proliferation rate, adipogenic differentiation potential and cell surface expression of SSEA-4, CD146 and CD274 of hBMSCs with an increase in donor age. Interestingly, all these findings were exclusive to hBMSCs from female donors. Further research should focus on postmenopausal-related effects on hBMSCs, as the results imply a functional loss and immunophenotypic change of hBMSCs particularly in aged women.

Melatonin had previously been shown to reduce up to four 2,2- azino-bis-(3-ethylbenzthiazoline-6-sulfonic acid) cation radicals (ABTS• + ) via a scavenger cascade ending with N 1 -acetyl-N 2 -formyl-5- methoxykynuramine (AFMK). However, when melatonin is added to the reaction system in much lower quantities than ABTS• + , the number of radicals scavenged per melatonin molecule is considerably higher and can attain a value of ten. Under conditions allowing for such a stoichiometry, novel products have been detected which derive from AFMK (1). These were separated by repeated chromatography and the major compounds were characterized by spectroscopic methods, such as mass spectrometry (HPLC- MS, EI-MS and ESI-HRMS), 1 H nuclear magnetic resonance (NMR) and 13 C NMR, heteronuclear multiple bond connectivity (HMBC) correlations. The identified substances are formed by re-cyclization and represent 3- indolinones carrying the side chain at C2; the N-formyl group can be maintained, but deformylated analogs seem to be also generated, according to MS. The primary product from AFMK (1 )i sN-(1-formyl-5-methoxy-3- oxo-2,3-dihydro-1H-indol-2-ylidenemethyl)-acetamide (2), which is obtained after purification as E- and Z-isomers (2a, 2b); a secondary product has been identified as N-(1-formyl-2-hydroxy-5-methoxy-3-oxo-2,3-dihydro-1H-indol- 2-ylmethyl)-acetamide (3). When H2O2 is added to the ABTS• + reaction mixture in quantities not already leading to substantial reduction of this radical, compound 3 is isolated as the major product, whereas 2a and 2b are virtually absent. The substances formed differ from all previously known oxidation products which derive from melatonin and are, among these, the first 3-indolinones. Moreover, the aliphatic side chain at C2 is reminiscent of other substances which have been synthesized in the search for melatonin receptor ligands.

Aims Our aims were to determine whether subjects with painful bladder syndrome (PBS) demonstrate characteristics of visceral pain syndromes: visceral hyperalgesia, expanded loci of referral of bladder sensation, increased bladder pain with repetitive filling, lower thresholds to cutaneous stimulation in relevant dermatomes, abnormal response to repetitive cutaneous stimulation in relevant dermatomes, and also to develop easily applied measures for PBS pain evaluation and management. Methods We recruited PBS subjects and control subjects with no bladder pain and with either stress urinary incontinence (SUI) or no incontinence. Subjects underwent three bladder fills up to maximum 300 ml and mapped bladder fullness/discomfort, rating any pain present. Cutaneous current perception thresholds (CPTs) were tested at 2000 Hz, 250 Hz, 5 Hz at C5, T6, T10, T12, S3 dermatomes. Repetitive supra-threshold stimulation in trains of 15 stimuli 2 sec apart were then administered to T12, S3 dermatomes. Results PBS subjects demonstrated hyperalgesia to bladder filling and tended to sense bladder discomfort at both suprapubic and vulvar/urethral sites. There was no difference in CPTs at any dermatome at any stimulating frequency. PBS and SI subjects tended not to habituate to repetitive stimuli, while asymptomatic controls tended to habituate to repetitive stimulation. Conclusions PBS subjects demonstrate bladder hyperalgesia and may sense bladder discomfort at sites other than suprapubic. Rating of bladder discomfort and sensory mapping during cystometry usefully distinguishes between PBS subjects and controls. Neurourol. Urodynam. © 2005 Wiley-Liss, Inc.