Browsing by Subject "Urine"

Now showing 1 - 6 of 6
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    Changes in proteinuria and albuminuria with initiation of antiretroviral therapy: data from a randomized trial comparing tenofovir disoproxil fumarate/emtricitabine versus abacavir/lamivudine
    (Ovid Technologies (Wolters Kluwer) - Lippincott Williams & Wilkins, 2014-09-01) Wyatt, Christina M.; Kitch, Douglas; Gupta, Samir K.; Tierney, Camlin; Daar, Eric S.; Sax, Paul E.; Ha, Belinda; Melbourne, Kathleen; McComsey, Grace A.; AIDS Clinical Trials Group Study A5224s Team; Department of Medicine, IU School of Medicine
    BACKGROUND: Antiretroviral therapy (ART) is associated with improved kidney function; however, the nucleotide reverse transcriptase inhibitor (NRTI) tenofovir disoproxil fumarate (TDF) has been associated with decreased kidney function and proteinuria. METHODS: We examined changes in urine protein:creatinine (UPCR) and urine albumin:creatinine (UACR) ratios in 245 ART-naive participants in A5202 randomized in a substudy to blinded NRTI (abacavir/lamivudine, ABC/3TC, n = 124 or TDF/emtricitabine, TDF/FTC, n = 121) with open-label protease inhibitor (PI) atazanavir/ritonavir or nonnucleoside reverse transcriptase inhibitor (NNRTI) efavirenz. RESULTS: At baseline, 18% of participants had clinically significant proteinuria (UPCR ≥200 mg/g), and 11% had clinically significant albuminuria (UACR ≥30 mg/g). The prevalence of clinically significant proteinuria and albuminuria decreased from baseline to week 96 in all treatment groups. In intention-to-treat analyses, there was a significant effect of NRTI component on fold change in UPCR (P = 0.011) and UACR (P = 0.018) from baseline to week 96, with greater improvements in participants randomized to ABC/3TC. There was no significant effect of NNRTI/PI component on fold change in UPCR (P = 0.23) or UACR (P = 0.88), and no significant interactions between NRTI and NNRTI/PI components. CONCLUSIONS: In this prespecified secondary analysis, ART initiation was associated with improvements in proteinuria and albuminuria, with significantly greater improvements in participants randomized to ABC/3TC versus TDF/FTC. These are the first data from a randomized trial to suggest that initiation of TDF/FTC may not be associated with the same degree of improvement in proteinuria and albuminuria that have been reported with other regimens. Future studies should consider the long-term clinical significance of these findings.
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    Mechanism by which shock wave lithotripsy can promote formation of human calcium phosphate stones
    (American Physiological Society, 2015-04-15) Evan, Andrew P.; Coe, Fredric L.; Connors, Bret A.; Handa, Rajash K.; Lingeman, James E.; Worcester, Elaine M.; Department of Anatomy & Cell Biology, IU School of Medicine
    Human stone calcium phosphate (CaP) content correlates with higher urine CaP supersaturation (SS) and urine pH as well as with the number of shock wave lithotripsy (SWL) treatments. SWL does damage medullary collecting ducts and vasa recta, sites for urine pH regulation. We tested the hypothesis that SWL raises urine pH and therefore Cap SS, resulting in CaP nucleation and tubular plugging. The left kidney (T) of nine farm pigs was treated with SWL, and metabolic studies were performed using bilateral ureteral catheters for up to 70 days post-SWL. Some animals were given an NH4Cl load to sort out effects on urine pH of CD injury vs. increased HCO3 (-) delivery. Histopathological studies were performed at the end of the functional studies. The mean pH of the T kidneys exceeded that of the control (C) kidneys by 0.18 units in 14 experiments on 9 pigs. Increased HCO3 (-) delivery to CD is at least partly responsible for the pH difference because NH4Cl acidosis abolished it. The T kidneys excreted more Na, K, HCO3 (-), water, Ca, Mg, and Cl than C kidneys. A single nephron site that could produce losses of all of these is the thick ascending limb. Extensive injury was noted in medullary thick ascending limbs and collecting ducts. Linear bands showing nephron loss and fibrosis were found in the cortex and extended into the medulla. Thus SWL produces tubule cell injury easily observed histopathologically that leads to functional disturbances across a wide range of electrolyte metabolism including higher than control urine pH.
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    One-Pot Analytical Pipeline for Efficient and Sensitive Proteomic Analysis of Extracellular Vesicles
    (American Chemical Society, 2023) Liu, Yi-Kai; Wu, Xiaofeng; Hadisurya, Marco; Li, Li; Kaimakliotis, Hristos; Iliuk, Anton; Tao, W. Andy; Urology, School of Medicine
    Extracellular vesicle (EV) proteomics emerges as an effective tool for discovering potential biomarkers for disease diagnosis, monitoring, and therapeutics. However, the current workflow of mass spectrometry-based EV proteome analysis is not fully compatible in a clinical setting due to inefficient EV isolation methods and a tedious sample preparation process. To streamline and improve the efficiency of EV proteome analysis, here we introduce a one-pot analytical pipeline integrating a robust EV isolation approach, EV total recovery and purification (EVtrap), with in situ protein sample preparation, to detect urinary EV proteome. By incorporating solvent-driven protein capture and fast on-bead digestion, the one-pot pipeline enabled the whole EV proteome analysis to be completed within one day. In comparison with the existing workflow, the one-pot pipeline was able to obtain better peptide yield and identify the equivalent number of unique EV proteins from 1 mL of urine. Finally, we applied the one-pot pipeline to profile proteomes in urinary EVs of bladder cancer patients. A total of 2774 unique proteins were identified in 53 urine samples using a 15 min gradient library-free data-independent acquisition method. Taken altogether, our novel one-pot analytical pipeline demonstrated its potential for routine and robust EV proteomics in biomedical applications.
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    Prostate cancer-associated urinary proteomes differ before and after prostatectomy
    (Sage, 2022-10-27) Feng, Yan; Liu, Shengzhi; Zha, Rongrong; Sun, Xun; Li, Kexin; Wu, Di; Aryal, Uma K.; Koch, Michael; Li, Bai-Yan; Yokota, Hiroki; Biomedical Engineering, School of Engineering and Technology
    Background: A wide range of disorders can be detected in the urine. Tumor-modifying proteins in the urine may serve as a diagnostic tool for cancer patients and the alterations in their profiles may indicate efficacies of chemotherapy, radiotherapy, and surgery. Methods: We focused on urinary proteomes of patients with prostate cancer and identified tumor-modifying proteins in the samples before and after prostatectomy. Protein array analysis was conducted to evaluate a differential profile of tumor-promoting cytokines, while mass spectrometry-based global proteomics was conducted to identify tumor-suppressing proteins. Results: The result revealed striking differences by prostatectomy. Notably, the urine from the post-prostatectomy significantly decreased the tumorigenic behaviors of prostate tumor cells as well as breast cancer cells. We observed that angiogenin, a stimulator of blood vessel formation, was reduced in the post-prostatectomy urine. By contrast, the levels of three cell-membrane proteins such as prostasin (PRSS8), nectin 2 (PVRL2), and nidogen 1 (NID1) were elevated and they acted as extracellular tumor-suppressing proteins. These three proteins, given extracellularly, downregulated tumorigenic genes such as Runx2, Snail, and transforming growth factor beta and induced apoptosis of tumor cells. However, the role of NID1 differed depending on the location, and intracellular NID1 was tumorigenic and reduced the percent survival. Conclusions: This study demonstrated that prostatectomy remarkably altered the profile of urinary proteomes, and the post-prostatectomy urine provided tumor-suppressive proteomes. The result sheds novel light on the dynamic nature of the urinary proteomes and a unique strategy for predicting tumor suppressors.
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    Relationships between renal parameters and serum and urine markers of inflammation in those with and without HIV infection
    (Mary Ann Liebert, 2015-04) Shinha, Takashi; Mi, Deming; Liu, Ziyue; Orschell, Christie M.; Lederman, Michael M.; Gupta, Samir K.; Department of Medicine, IU School of Medicine
    We sought to determine the relationships among intrarenal and systemic inflammation and renal disease in HIV. We compared paired serum and urinary levels (normalized to urine creatinine) of monocyte chemotactic protein-1 (MCP-1), regulated on activation normal T cell expressed and secreted (RANTES), interferon-γ-induced protein-10 (IP-10), interleukin-8 (IL-8), and β2-microglobulin (B2M) between two groups of HIV-infected subjects not receiving antiretroviral therapy (ART) [A: not expecting to initiate ART immediately due to having CD4 cell counts ≥350/μl, N=26; B: about to initiate ART, N=19], a group of HIV-infected subjects receiving virologically suppressive antiretroviral therapy [C, N=30], and a group of HIV-uninfected, healthy volunteers [D, N=45]. We then correlated these inflammatory biomarker levels with urine protein/creatinine ratios (uPCR), urine albumin/creatinine ratios (uACR), and estimated glomerular filtration rates (eGFR). Urine inflammatory biomarker levels were highest in Group B. When combining all four study groups, statistically significant positive correlations included uPCR with urine IL-8, urine MCP-1, urine IP-10, and serum IP-10 and uACR with urine IL-8, urine B2M, serum IP-10, and serum B2M. eGFR was statistically significantly negatively correlated with serum MCP-1 and serum B2M. Paired serum and urine levels of IP-10 and B2M (but not IL-8, RANTES, or MCP-1) were significantly correlated with each other in the overall group. The levels of urine inflammatory markers tested differed by HIV status and use of virologically suppressive ART. These urine and serum inflammatory markers were differentially correlated with uPCR, uACR, and eGFR, suggesting that different intrarenal and systemic inflammatory pathways may contribute to different measures of nephropathy.
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    Urinary Volatile Organic Compounds for Detection of Breast Cancer and Monitoring Chemical and Mechanical Cancer Treatments in Mice
    (2019-05) Teli, Meghana; Yokota, Hiroki; Agarwal, Mangilal; Ji, Julie
    The aim of this study is to identify metabolic transformations in breast cancer through urinary volatile organic compounds in mammary pad or bone tumor mice models. Subsequently, it focuses on investigating the efficacy of therapeutic intervention through identified potential biomarkers. Methods for monitoring tumor development and treatment responses have technologically advanced over the years leading to significant increase in percent survival rates. Although these modalities are reliable, it would be beneficial to observe disease progression from a new perspective to gain greater understanding of cancer pathogenesis. Analysis of cellular energetics affected by cancer using bio-fluids can non-invasively help in prognosis and selection of treatment regimens. The hypothesis is altered profiles of urinary volatile metabolites is directly related to disrupted metabolic pathways. Additionally, effectiveness of treatments can be indicated through changes in concentration of metabolites. In this ancillary experiment, mouse urine specimens were analyzed using gas chromatography-mass spectrometry, an analytical chemistry tool in identifying volatile organic compounds. Female BALB/c mice were injected with 4T1.2 murine breast tumor cells in the mammary fat pad. Consecutively, 4T1.2 cells were injected in the right iliac artery of BALB/c mice and E0771 tumor cells injected in the tibia of C57BL/6 mice to model bone tumor. The effect of two different modes of treatment: chemical drug and mechanical stimulation was investigated through changes in compound profiles. Chemical drug therapy was conducted with dopamine agents, Triuoperazine, Fluphenazine and a statin, Pitavastatin. Mechanical stimulation included tibia and knee loading at the site of tumor cell injection were given to mice. A biological treatment mode included administration of A5 osteocyte cell line. A set of potential volatile organic compounds biomarkers differentiating mammary pad or bone confined tumors from healthy controls was identified using forward feature selection. Effect of treatments was demonstrated through hierarchical heat maps and multivariate data analysis. Compounds identified in series of experiments belonged to the class of terpenoids, precursors of cholesterol molecules. Terpene synthesis is a descending step of mevalonate pathway suggesting its potential role in cancer pathogenesis. This thesis demonstrates the ability of urine volatilomics to indicate signaling pathways inflicted in tumors. It proposes a concept of using urine to detect tumor developments at two distinct locations as well as to monitor treatment efficacy.