The aim of this study was to evaluate the effect of weight reduction on urinary incontinence in moderately obese women. This prospective cohort study enrolled moderately obese women experiencing four or more incontinence episodes per week. BMI and a 7-day urinary diary were collected at baseline and on the completion of weight reduction. The study included 10 women with a mean (+/-SD) baseline BMI of 38.3 (+/-10.1) kg/m2 and 13 (+/-10) incontinent episodes per week. Participants had a mean BMI reduction of 5.3 (+/-6.2) kg/ m2 (P < 0.03). Among women achieving a weight loss of > or = 5%, 6/6 had > or = 50% reduction in incontinence frequency compared to 1 in 4 women with < 5% weight loss (P < 0.03). Incontinence episodes decreased to 8 (+/-10) per week following weight reduction (P < 0.07). The study demonstrated an association between weight reduction and improved urinary incontinence. Weight reduction should be considered for moderately obese women as part of non-surgical therapy for incontinence.
Progressive HIV disease has been associated with loss of memory T cell responses to Ag. To better characterize and quantify long-lived memory T cells in vivo, we have refined an in vivo labeling technique to study the kinetics of phenotypically distinct, low-frequency CD8+ T cell subpopulations in humans. HIV-negative subjects and antiretroviral-untreated HIV-infected subjects in varying stages of HIV disease were studied. After labeling the DNA of dividing cells with deuterated water (2H2O), 2H-label incorporation and die-away kinetics were quantified using a highly sensitive FACS/mass spectrometric method. Two different populations of long-lived memory CD8+ T cells were identified in HIV-negative subjects: CD8+CD45RA−CCR7+CD28+ central memory (TCM) cells expressing IL-7Rα and CD8+CD45RA+CCR7−CD28− RA effector memory (TEMRA) cells expressing CD57. In pilot studies in HIV-infected subjects, TCM cells appeared to have a shorter half-life and reduced abundance, particularly in those with high viral loads; TEMRA cells, by contrast, retained a long half-life and accumulated in the face of progressive HIV disease. These data are consistent with the hypothesis that IL-7Rα+ TCM cells represent true memory CD8+ T cells, the loss of which may be responsible in part for the progressive loss of T cell memory function during progressive HIV infection.
Progress in neurodegenerative disease research is hampered by the lack of biomarkers of neuronal dysfunction. We here identified a class of cerebrospinal fluid-based (CSF-based) kinetic biomarkers that reflect altered neuronal transport of protein cargo, a common feature of neurodegeneration. After a pulse administration of heavy water ( 2 H 2 O), distinct, newly synthesized 2 H-labeled neuronal proteins were transported to nerve terminals and secreted, and then appeared in CSF. In 3 mouse models of neurodegeneration, distinct 2 H-cargo proteins displayed delayed appearance and disappearance kinetics in the CSF, suggestive of aberrant transport kinetics. Microtubule-modulating pharmacotherapy normalized CSF-based kinetics of affected 2 H-cargo proteins and ameliorated neurodegenerative symptoms in mice. After 2 H 2 O labeling, similar neuronal transport deficits were observed in CSF of patients with Parkinson's disease (PD) compared with non-PD control subjects, which indicates that these biomarkers are translatable and relevant to human disease. Measurement of transport kinetics may provide a sensitive method to monitor progression of neurodegeneration and treatment effects.
Background--Reverse cholesterol transport from peripheral tissues is considered the principal atheroprotective mechanism of high-density lipoprotein, but quantifying reverse cholesterol transport in humans in vivo remains a challenge. We describe here a method for measuring flux of cholesterol though 3 primary components of the reverse cholesterol transport pathway in vivo in humans: tissue free cholesterol (FC) efflux, esterification of FC in plasma, and fecal sterol excretion of plasma-derived FC.Methods and Results--A constant infusion of [2,[3][4][5][6][7][8][9][10][11][12][13] C 2 ]-cholesterol was administered to healthy volunteers. Three-compartment SAAM II (Simulation, Analysis, and Modeling software; SAAM Institute, University of Washington, WA) fits were applied to plasma FC, red blood cell FC, and plasma cholesterol ester 13 C-enrichment profiles. Fecal sterol excretion of plasma-derived FC was quantified from fractional recovery of intravenous [2,[3][4][5][6][7][8][9][10][11][12][13] C 2 ]-cholesterol in feces over 7 days. We examined the key assumptions of the method and evaluated the optimal clinical protocol and approach to data analysis and modeling. A total of 17 subjects from 2 study sites (n=12 from first site, age 21 to 75 years, 2 women; n=5 from second site, age 18 to 70 years, 2 women) were studied. Tissue FC efflux was 3.79±0.88 mg/kg per hour (mean ± standard deviation), or %8 g/d. Red blood cell-derived flux into plasma FC was 3.38±1.10 mg/kg per hour. Esterification of plasma FC was %28% of tissue FC efflux (1.10±0.38 mg/kg per hour). Recoveries were 7% and 12% of administered [2,[3][4][5][6][7][8][9][10][11][12][13] C 2 ]-cholesterol in fecal bile acids and neutral sterols, respectively.Conclusions--Three components of systemic reverse cholesterol transport can be quantified, allowing dissection of this important function of high-density lipoprotein in vivo. Effects of lipoproteins, genetic mutations, lifestyle changes, and drugs on these components can be assessed in humans. ( J Am Heart Assoc. 2012;1:e001826 doi: 10.1161/JAHA.112.001826)Key Words: cholesterol efflux • esterification • reverse cholesterol transport • isotope labeling, stable • sterol excretion T he regulation of cellular cholesterol homeostasis is crucial for membrane function and cell survival and is maintained by multiple mechanisms, including control of uptake, synthesis, storage, and efflux. Compared to the pathways of cellular uptake and de novo synthesis of cholesterol, however, less information exists about the control of flux though pathways that remove cholesterol from cells and from the whole organism, 1,2 particularly in humans. [3][4][5] These pathways collectively have been termed reverse cholesterol transport (RCT). RCT is postulated to play a fundamental role in cholesterol homeostasis and distribution among tissues 5 and thereby in the development and reversal of atherosclerosis. 6,7 The atheroprotective effects of high-density lipoprotein cholesterol (HDL-C) in both human and animal studies often hav...
This direct kinetic assessment confirms a course of spermatogenesis that is on the shorter side of traditional estimates based on prior analyses. In addition, the variability observed in healthy men suggests that characteristics such as the epididymal reservoir effect may influence the modeling of in vivo spermatogenesis.
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