Urinary type IV collagen is related to left ventricular diastolic function and brain natriuretic peptide in hypertensive patients with prediabetes.

PubMed

Iida, Masato; Yamamoto, Mitsuru; Ishiguro, Yuko S; Yamazaki, Masatoshi; Ueda, Norihiro; Honjo, Haruo; Kamiya, Kaichirou

2014-01-01

Urinary type IV collagen is an early biomarker of diabetic nephropathy. Concomitant prediabetes (the early stage of diabetes) was associated with left ventricular (LV) diastolic dysfunction and increased brain natriuretic peptide (BNP) in hypertensive patients. We hypothesized that urinary type IV collagen may be related to these cardiac dysfunctions. We studied hypertensive patients with early prediabetes (HbA1c <5.7% and fasting glucose >110, n=18), those with prediabetes (HbA1c 5.7-6.4, n=98), and those with diabetes (HbA1c>6.5 or on diabetes medications, n=92). The participants underwent echocardiography to assess left atrial volume/body surface area (BSA) and the ratio of early mitral flow velocity to mitral annular velocity (E/e'). Left ventricular diastolic dysfunction (LVDD) was defined if patients had E/e'≥15, or E/e'=9-14 accompanied by left atrial volume/BSA≥32ml/mm(2). Urinary samples were collected for type IV collagen and albumin, and blood samples were taken for BNP and HbA1c. Urinary type IV collagen and albumin increased in parallel with the deterioration of glycemic status. In hypertensive patients with prediabetes, subjects with LVDD had higher levels of BNP and urinary type IV collagen than those without LVDD. In contrast, in hypertensive patients with diabetes, subjects with LVDD had higher urinary albumin and BNP than those without LVDD. Urinary type IV collagen correlated positively with BNP in hypertensive patients with prediabetes, whereas it correlated with HbA1c in those with diabetes. In hypertensive patients with prediabetes, urinary type IV collagen was associated with LV diastolic dysfunction and BNP. Copyright © 2014 Elsevier Inc. All rights reserved.

A Fragment of the LG3 Peptide of Endorepellin Is Present in the Urine of Physically Active Mining Workers: A Potential Marker of Physical Activity

PubMed Central

Parker, Tony J.; Sampson, Dayle L.; Broszczak, Daniel; Chng, Yee L.; Carter, Shea L.; Leavesley, David I.; Parker, Anthony W.; Upton, Zee

2012-01-01

Biomarker analysis has been implemented in sports research in an attempt to monitor the effects of exertion and fatigue in athletes. This study proposed that while such biomarkers may be useful for monitoring injury risk in workers, proteomic approaches might also be utilised to identify novel exertion or injury markers. We found that urinary urea and cortisol levels were significantly elevated in mining workers following a 12 hour overnight shift. These levels failed to return to baseline over 24 h in the more active maintenance crew compared to truck drivers (operators) suggesting a lack of recovery between shifts. Use of a SELDI-TOF MS approach to detect novel exertion or injury markers revealed a spectral feature which was associated with workers in both work categories who were engaged in higher levels of physical activity. This feature was identified as the LG3 peptide, a C-terminal fragment of the anti-angiogenic/anti-tumourigenic protein endorepellin. This finding suggests that urinary LG3 peptide may be a biomarker of physical activity. It is also possible that the activity mediated release of LG3/endorepellin into the circulation may represent a biological mechanism for the known inverse association between physical activity and cancer risk/survival. PMID:22457785

Severe polyuria after the resection of adrenal pheochromocytoma.

PubMed

Tobe, Musashi; Ito, Keiichi; Umeda, Shun; Sato, Akinori; Adaniya, Noriaki; Tanaka, Yuji; Hayakawa, Masamichi; Asano, Tomohiko

2010-12-01

A 73-year-old male patient with hypertension and hyperglycemia was referred to our hospital because of a diagnosis regarding his left adrenal tumor. Because the levels of urinary metanephrine and normetanephrine were elevated, and (131) I-MIBG scintigraphy showed intense uptake in the adrenal tumor, the tumor was diagnosed as a pheochromocytoma. An adrenalectomy was carried out. Severe polyuria, which was accompanied by a rapid decrease in central venous pressure, started 1 hour after the operation. Urine output of more than 8000 mL/day continued until the 16th postoperative day. Plasma antidiuretic hormone (ADH) levels were within the normal range. Plasma human atrial natriuretic peptide (hANP) and brain natriuretic peptide (BNP) were elevated postoperatively, and the elevation of these peptides was one possible cause for the severe polyuria. Because ADH levels in the tumor fluid were not elevated, the tumor was not an ADH-secreting tumor. Urinary β2-microglobulin was significantly elevated after the operation, thus suggesting that renal tubule dysfunction might also have been involved in the polyuria. However, the mechanism of polyuria after the resection of adrenal pheochromocytoma is not fully understood. Polyuria after the resection of adrenal pheochromocytoma is extremely rare, and the present subject is the second case to date. © 2010 The Japanese Urological Association.

A fragment of the LG3 peptide of endorepellin is present in the urine of physically active mining workers: a potential marker of physical activity.

PubMed

Parker, Tony J; Sampson, Dayle L; Broszczak, Daniel; Chng, Yee L; Carter, Shea L; Leavesley, David I; Parker, Anthony W; Upton, Zee

2012-01-01

Biomarker analysis has been implemented in sports research in an attempt to monitor the effects of exertion and fatigue in athletes. This study proposed that while such biomarkers may be useful for monitoring injury risk in workers, proteomic approaches might also be utilised to identify novel exertion or injury markers. We found that urinary urea and cortisol levels were significantly elevated in mining workers following a 12 hour overnight shift. These levels failed to return to baseline over 24 h in the more active maintenance crew compared to truck drivers (operators) suggesting a lack of recovery between shifts. Use of a SELDI-TOF MS approach to detect novel exertion or injury markers revealed a spectral feature which was associated with workers in both work categories who were engaged in higher levels of physical activity. This feature was identified as the LG3 peptide, a C-terminal fragment of the anti-angiogenic/anti-tumourigenic protein endorepellin. This finding suggests that urinary LG3 peptide may be a biomarker of physical activity. It is also possible that the activity mediated release of LG3/endorepellin into the circulation may represent a biological mechanism for the known inverse association between physical activity and cancer risk/survival.

Clinical and genetic characteristics of GAD-antibody positive patients initially diagnosed as having type 2 diabetes.

PubMed

Hamaguchi, Kazuyuki; Kimura, Akinori; Kusuda, Yoichiro; Yamashita, Tsutomu; Yasunami, Michio; Takahasi, Megumi; Abe, Nobuyuki; Yoshimatsu, Hironobu

2004-11-01

The present study was conducted to clarify the clinical and genetic characteristics of the diabetic patients who have antibodies to glutamic acid decarboxylase (GADab) but are diagnosed initially as type 2 diabetes because of the slow progression. Fifty-five GADab+ patients and 137 GADab- patients were recruited. The GADab+ patients were divided into two subgroups according to their antibody titers. The high-titer subgroup (Ab > or = 20 U/ml) had lower urinary C-peptide concentrations, and was assigned insulin therapy more often than the GADab- patients. In contrast to the high-titer subgroup, clinical parameters in the low-titer subgroup were similar to the GADab- diabetic patients. The urinary C-peptide levels correlated negatively with the GADab titer in the GADab+ patients. Analysis of type 1 diabetes-susceptible HLA alleles revealed high frequencies of the B54 and DRB1*0405 allele, but not the B61 and DRB1*0901 alleles, in the high-titer subgroup, whereas the frequency of the protective DRB1*1502 allele was decreased. The GADab+ patients with the B54 allele had higher GADab titers and lower urinary C-peptide excretion than patients without this allele. These data indicated that patients with a high-GADab titer share the autoimmune background characteristic of type 1 diabetes.

Comparison of Urine and Plasma Peptidome Indicates Selectivity in Renal Peptide Handling.

PubMed

Magalhães, Pedro; Pontillo, Claudia; Pejchinovski, Martin; Siwy, Justyna; Krochmal, Magdalena; Makridakis, Manousos; Carrick, Emma; Klein, Julie; Mullen, William; Jankowski, Joachim; Vlahou, Antonia; Mischak, Harald; Schanstra, Joost P; Zürbig, Petra; Pape, Lars

2018-04-03

Urine is considered to be produced predominantly as a result of plasma filtration in the kidney. However, the origin of the native peptides present in urine has never been investigated in detail. Therefore, the authors aimed to obtain a first insight into the origin of urinary peptides based on a side-by-side comprehensive analysis of the plasma and urine peptidome. Twenty-two matched urine and plasma samples are analyzed for their peptidome using capillary electrophoresis coupled to mass spectrometry (CE-MS; for relative quantification) and CE or LC coupled to tandem mass spectrometry (CE- or LC-MS/MS; for peptide identification). The overlap and association of abundance of the different peptides present in these two body fluids are evaluated. The authors are able to identify 561 plasma and 1461 urinary endogenous peptides. Only 90 peptides are detectable in both urine and plasma. No significant correlation is found when comparing the abundance of these common peptides, with the exception of collagen fragments. This observation is also supported when comparing published peptidome data from both plasma and urine. Most of the plasma peptides are not detectable in urine, possibly due to tubular reabsorption. The majority of urinary peptides may in fact originate in the kidney. The notable exception is collagen fragments, which indicates potential selective exclusion of these peptides from tubular reabsorption. Experimental verification of this hypothesis is warranted. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

An endogenous ribonuclease inhibitor regulates the antimicrobial activity of ribonuclease 7 in the human urinary tract

PubMed Central

Spencer, John David; Schwaderer, Andrew L.; Eichler, Tad; Wang, Huanyu; Kline, Jennifer; Justice, Sheryl S.; Cohen, Daniel M.; Hains, David S.

2013-01-01

Recent studies stress the importance of antimicrobial peptides in protecting the urinary tract from infection. Previously, we have shown that ribonuclease 7 (RNase 7) is a potent antimicrobial peptide that has broad-spectrum antimicrobial activity against uropathogenic bacteria. The urothelium of the lower urinary tract and intercalated cells of the kidney produce RNase 7 but regulation of its antimicrobial activity has not been well defined. Here we characterize the expression of an endogenous inhibitor, ribonuclease inhibitor (RI), in the urinary tract and evaluate its effect on RNase 7’s antimicrobial activity. Using RNA isolated from non-infected human bladder and kidney tissue, quantitative real-time PCR showed that RNH1, the gene encoding RI, is constitutively expressed throughout the urinary tract. With pyelonephritis, RNH1 expression and RI peptide production significantly decrease. Immunostaining localized RI production to the umbrella cells of the bladder and intercalated cells of the renal collecting tubule. In vitro assays showed that RI bound to RNase 7 and suppressed its antimicrobial activity by blocking its ability to bind the cell wall of uropathogenic bacteria. Thus, these results demonstrate a new immunomodulatory role for RI and identified a unique regulatory pathway that may affect how RNase 7 maintains urinary tract sterility. PMID:24107847

Vitamin D-deficient mice have more invasive urinary tract infection.

PubMed

Hertting, Olof; Lüthje, Petra; Sullivan, Devin; Aspenström, Pontus; Brauner, Annelie

2017-01-01

Vitamin D deficiency is a common health problem with consequences not limited to bone and calcium hemostasis. Low levels have also been linked to tuberculosis and other respiratory infections as well as autoimmune diseases. We have previously shown that supplementation with vitamin D can induce the antimicrobial peptide cathelicidin during ex vivo infection of human urinary bladder. In rodents, however, cathelicidin expression is not linked to vitamin D and therefore this vitamin D-related effect fighting bacterial invasion is not relevant. To determine if vitamin D had further protective mechanisms during urinary tract infections, we therefore used a mouse model. In vitamin D-deficient mice, we detected more intracellular bacterial communities in the urinary bladder, higher degree of bacterial spread to the upper urinary tract and a skewed cytokine response. Furthermore, we show that the vitamin D receptor was upregulated in the urinary bladder and translocated into the cell nucleus after E. coli infection. This study supports a more general role for vitamin D as a local immune response mediator in the urinary tract.

Possible role of bioactive peptides in the regulation of human detrusor smooth muscle - functional effects in vitro and immunohistochemical presence.

PubMed

Uckert, Stefan; Stief, Christian G; Lietz, Burckhard; Burmester, Martin; Jonas, Udo; Machtens, Stefan A

2002-09-01

Results from basic research implicate a role for bioactive peptides in controlling the mammalian lower urinary tract. Although various peptides are assumed to be involved in the potentiaton or inhibition of cholinergic or purinergic activity in the urinary bladder, there is still much controversy regarding the mode of action and functional significance of such peptides in detrusor smooth muscle. Thus, we evaluated the functional effects of atrial natriuretic peptide (ANP), calcitonin gene related peptide (CGRP), endothelin 1 (ET-1), substance P (SP) and vasoactive intestinal polypeptide (VIP) on isolated strip preparations of human detrusor smooth muscle and determined the presence of those peptides in the human detrusor by means of immunohistochemistry. The effects of peptides on isometric tension of isolated detrusor strip preparations and on tissue levels of cyclic nucleotides cAMP and cGMP were compared to those of adenylyl cyclase activator forskolin (F), nitric oxide donor Na(+)-nitroprusside (SNP) and non-specific phosphodiesterase (PDE) inhibitor papaverine (P). The effects of the compounds on isometric tension of isolated human detrusor smooth muscle were examined using the organ bath technique. To determine time- and dose-dependent effects on cyclic nucleotide levels, bladder strips were exposed to increasing doses of F, SNP, P, ANP, CGRP and VIP, then rapidly frozen in liquid nitrogen and homogenised in the frozen state. cAMP and cGMP were extracted and assayed using specific radioimmunoassays. The presence of peptides was investigated by light microscopy using the Avidin-Biotin-Complex (ABC) method. F, P and VIP most effectively reversed the carbachol-induced tension of isolated human detrusor strips. Relaxing effects of ANP, CGRP and SNP were negligible. In contrast, ET-1 and SP elicited dose-dependent contractions of the tissue. The relaxing effects of F, P and VIP were accompanied by an increase in cAMP and cGMP levels, respectively. Light microscopy revealed positive immunostaining for CGRP, ET 1, VIP and SP in sections of the detrusor muscle coat. Our results suggest a possible importance of ET 1, SP and VIP in regulating detrusor smooth muscle contraction and relaxation. Even if a peptide is not synthesised, stored or released in a smooth muscle tissue and is, therefore, unable to reach its target cells under physiologic conditions, a functional effect on the tissue might be mediated by peptide-binding to specific cell surface receptors.

Current state of the art for enhancing urine biomarker discovery

PubMed Central

Harpole, Michael; Davis, Justin; Espina, Virginia

2016-01-01

Urine is a highly desirable biospecimen for biomarker analysis because it can be collected recurrently by non-invasive techniques, in relatively large volumes. Urine contains cellular elements, biochemicals, and proteins derived from glomerular filtration of plasma, renal tubule excretion, and urogenital tract secretions that reflect, at a given time point, an individual's metabolic and pathophysiologic state. High-resolution mass spectrometry, coupled with state of the art fractionation systems are revealing the plethora of diagnostic/prognostic proteomic information existing within urinary exosomes, glycoproteins, and proteins. Affinity capture pre-processing techniques such as combinatorial peptide ligand libraries and biomarker harvesting hydrogel nanoparticles are enabling measurement/identification of previously undetectable urinary proteins. Future challenges in the urinary proteomics field include a) defining either single or multiple, universally applicable data normalization methods for comparing results within and between individual patients/data sets, and b) defining expected urinary protein levels in healthy individuals. PMID:27232439

The clinical and laboratory correlates of an increased urinary 5-hydroxyindoleacetic acid.

PubMed Central

Tormey, W. P.; FitzGerald, R. J.

1995-01-01

Over a five-and-a-half-year period, there were 298 laboratory requests for urinary 5-hydroxyindoleacetic acid (5-HIAA). The clinical and laboratory associations of the 24 patients in which there were 43 urinary 5-HIAA 24-h collection results greater than the laboratory upper reference limit are detailed. Four were confirmed carcinoid tumours and two were phaeochromocytomas. Flushing was a prominent symptom in 46% and diarrhoea or altered bowel habit in 37%. Associated with the raised urinary 5-HIAA values were increased levels of 4-hydroxy-3-methoxymandelic acid and homovanillic acid in 14.3% and 21%, respectively, of those collections where the metabolites were requested. Diagnostic imaging was performed in 57%. While the specificity was 88%, 5-HIAA is relatively insensitive in the diagnosis of carcinoid tumours and a more widespread use of diagnostic imaging including isotope scanning with labelled metaiodo-benzylguanidine, vasoactive intestinal peptide and octreotide is suggested. PMID:7479466

Proteomic Candidate Biomarkers of Drug-Induced Nephrotoxicity in the Rat

PubMed Central

Rouse, Rodney; Siwy, Justyna; Mullen, William; Mischak, Harald; Metzger, Jochen; Hanig, Joseph

2012-01-01

Improved biomarkers of acute nephrotoxicity are coveted by the drug development industry, regulatory agencies, and clinicians. In an effort to identify such biomarkers, urinary peptide profiles of rats treated with two different nephrotoxins were investigated. 493 marker candidates were defined that showed a significant response to cis-platin comparing a cis-platin treated cohort to controls. Next, urine samples from rats that received three consecutive daily doses of 150 or 300 mg/kg gentamicin were examined. 557 potential biomarkers were initially identified; 108 of these gentamicin-response markers showed a clear temporal response to treatment. 39 of the cisplatin-response markers also displayed a clear response to gentamicin. Of the combined 147 peptides, 101 were similarly regulated by gentamicin or cis-platin and 54 could be identified by tandem mass spectrometry. Most were collagen type I and type III fragments up-regulated in response to gentamicin treatment. Based on these peptides, classification models were generated and validated in a longitudinal study. In agreement with histopathology, the observed changes in classification scores were transient, initiated after the first dose, and generally persistent over a period of 10–20 days before returning to control levels. The data support the hypothesis that gentamicin-induced renal toxicity up-regulates protease activity, resulting in an increase in several specific urinary collagen fragments. Urinary proteomic biomarkers identified here, especially those common to both nephrotoxins, may serve as a valuable tool to investigate potential new drug candidates for the risk of nephrotoxicity. PMID:22509332

Stability and reproducibility of a single-sample urinary C-peptide/creatinine ratio and its correlation with 24-h urinary C-peptide.

PubMed

McDonald, Tim J; Knight, Bridget A; Shields, Beverley M; Bowman, Pamela; Salzmann, Maurice B; Hattersley, Andrew T

2009-11-01

C-peptide measurement in blood or 24-h urine samples provides useful information regarding endogenous insulin secretion, but problems related to the rapid degradation of C-peptide in blood and difficulty of 24-h urine collection have limited widespread routine clinical use of this test. We assessed the feasibility of measuring urinary C-peptide (UCP) with correction for creatinine concentration in single urine samples. We analyzed UCP using a routine electrochemiluminescence immunoassay in samples from 21 healthy volunteers. We investigated the stability of UCP with different preservatives and storage conditions and compared the reproducibility of urinary C-peptide/creatinine ratio (UCPCR) in first- and second-void fasting urines, then assessed correlations with 24-h collections. UCPCR was unchanged at room temperature for 24 h and at 4 degrees C for 72 h even in the absence of preservative. UCPCR collected in boric acid was stable at room temperature for 72 h. UCPCR remained stable after 7 freeze-thaw cycles but decreased with freezer storage time and dropped to 82%-84% of baseline by 90 days at -20 degrees C. Second-void fasting UCPCRs were lower than first-void (median 0.78 vs 1.31, P = 0.0003) and showed less variation (CV 33% vs 52%), as second-void UCPCRs were not influenced by evening food-related insulin secretion. Second-void fasting UCPCR was highly correlated with 24-h UCP (r = 0.8, P = 0.00006). Second-void fasting UCPCR is a reproducible measure that correlates well with 24-h UCP in normal samples. The 3-day stability of UCPCR at room temperature greatly increases its potential clinical utility.

Vitamin D Induction of the Human Antimicrobial Peptide Cathelicidin in the Urinary Bladder

PubMed Central

Hertting, Olof; Holm, Åsa; Lüthje, Petra; Brauner, Hanna; Dyrdak, Robert; Jonasson, Aino Fianu; Wiklund, Peter; Chromek, Milan; Brauner, Annelie

2010-01-01

The urinary tract is frequently being exposed to potential pathogens and rapid defence mechanisms are therefore needed. Cathelicidin, a human antimicrobial peptide is expressed and secreted by bladder epithelial cells and protects the urinary tract from infection. Here we show that vitamin D can induce cathelicidin in the urinary bladder. We analyzed bladder tissue from postmenopausal women for expression of cathelicidin, before and after a three-month period of supplementation with 25-hydroxyvitamin D3 (25D3). Cell culture experiments were performed to elucidate the mechanisms for cathelicidin induction. We observed that, vitamin D per se did not up-regulate cathelicidin in serum or in bladder tissue of the women in this study. However, when the bladder biopsies were infected with uropathogenic E. coli (UPEC), a significant increase in cathelicidin expression was observed after 25D3 supplementation. This observation was confirmed in human bladder cell lines, even though here, cathelicidin induction occurred irrespectively of infection. Vitamin D treated bladder cells exerted an increased antibacterial effect against UPEC and colocalization to cathelicidin indicated the relevance of this peptide. In the light of the rapidly growing problem of resistance to common urinary tract antibiotics, we suggest that vitamin D may be a potential complement in the prevention of UTI. PMID:21179490

Inhibitors of peptidases: how they influence the biological activities of substance P, neurokinins, bradykinin and angiotensin in guinea pig, hamster and rat urinary bladders.

PubMed

Rouissi, N; Nantel, F; Drapeau, G; Rhaleb, N E; Dion, S; Regoli, D

1990-01-01

Neurokinins, bradykinin and angiotensins were tested in isolated urinary bladder of the guinea pig, the hamster and the rat, in the absence and in presence of a variety of peptidase inhibitors in order to establish if peptide degradation interferes with the bladder contractions elicited by the three types of peptides. Indeed, the effects of neurokinins, bradykinin and angiotensin I in the guinea pig bladder were significantly enhanced by captopril (4.6 x 10(-6) mol/l), chymostatin (1 mg/l), phosphoramidon (4.6 x 10(-6) mol/l) and thiorphan (1.0 x 10(-6) mol/l), while only captopril was found to potentiate the effects of the same peptides in the rat bladder. The four peptidase inhibitors, as well as bacitracin were found to modify the responses of the hamster urinary bladder to one or another or to all three groups of peptides and to DiMeC7. The present results suggest that the urinary bladders of various species have different types of active proteolytic enzymes: only the angiotensin-converting enzyme appears to be present in the rat bladder, while the same enzyme and possibly two additional endopeptidases interfere with the myotropic effects of neurokinins, kinins and angiotensins in the guinea pig and the hamster bladder.

The use of urinary proteomics in the assessment of suitability of mouse models for ageing.

PubMed

Nkuipou-Kenfack, Esther; Schanstra, Joost P; Bajwa, Seerat; Pejchinovski, Martin; Vinel, Claire; Dray, Cédric; Valet, Philippe; Bascands, Jean-Loup; Vlahou, Antonia; Koeck, Thomas; Borries, Melanie; Busch, Hauke; Bechtel-Walz, Wibke; Huber, Tobias B; Rudolph, Karl L; Pich, Andreas; Mischak, Harald; Zürbig, Petra

2017-01-01

Ageing is a complex process characterised by a systemic and progressive deterioration of biological functions. As ageing is associated with an increased prevalence of age-related chronic disorders, understanding its underlying molecular mechanisms can pave the way for therapeutic interventions and managing complications. Animal models such as mice are commonly used in ageing research as they have a shorter lifespan in comparison to humans and are also genetically close to humans. To assess the translatability of mouse ageing to human ageing, the urinary proteome in 89 wild-type (C57BL/6) mice aged between 8-96 weeks was investigated using capillary electrophoresis coupled to mass spectrometry (CE-MS). Using age as a continuous variable, 295 peptides significantly correlated with age in mice were identified. To investigate the relevance of using mouse models in human ageing studies, a comparison was performed with a previous correlation analysis using 1227 healthy subjects. In mice and humans, a decrease in urinary excretion of fibrillar collagens and an increase of uromodulin fragments was observed with advanced age. Of the 295 peptides correlating with age, 49 had a strong homology to the respective human age-related peptides. These ortholog peptides including several collagen (N = 44) and uromodulin (N = 5) fragments were used to generate an ageing classifier that was able to discriminate the age among both wild-type mice and healthy subjects. Additionally, the ageing classifier depicted that telomerase knock-out mice were older than their chronological age. Hence, with a focus on ortholog urinary peptides mouse ageing can be translated to human ageing.

A Murine Model of Inflammatory Bladder Disease: Cathelicidin Peptide Induced Bladder Inflammation and Treatment With Sulfated Polysaccharides

PubMed Central

Oottamasathien, Siam; Jia, Wanjian; McCoard, Lindsi; Slack, Sean; Zhang, Jianxing; Skardal, Aleksander; Job, Kathleen; Kennedy, Thomas P.; Dull, Randal O.; Prestwich, Glenn D.

2013-01-01

Purpose Studies show that LL-37 is a naturally occurring urinary defensin peptide that is up-regulated during urinary tract infections. Although normal urinary LL-37 levels are antimicrobial, we propose that increased LL-37 may trigger bladder inflammation. We further suggest that anti-inflammatory sulfated polysaccharides known as semi-synthetic glycosaminoglycan ether compounds can treat/prevent LL-37 mediated bladder inflammation. Materials and Methods C57BL/6 mice were catheterized/instilled with LL-37 (320 μM at 150 μl) for 45 minutes. Animals were sacrificed at 12 and 24 hours, and tissues were examined using hematoxylin and eosin. Separate experiments were performed for myeloperoxidase to quantify inflammation. GM-1111 semi-synthetic glycosaminoglycan ether treatments involved instillation of 10 mg/ml for 45 minutes directly before or after LL-37. Tissues were harvested at 24 hours. To compare semi-synthetic glycosaminoglycan ether efficacy experiments were performed using 10 mg/ml heparin. Finally, tissue localization of semi-synthetic glycosaminoglycan ether was examined using a fluorescent GM-1111-Alexa Fluor® 633 conjugate. Results Profound bladder inflammation developed after LL-37. Greater tissue inflammation occurred after 24 hours compared to that at 12 hours. Myeloperoxidase assays revealed a 21 and 61-fold increase at 12 and 24 hours, respectively. Semi-synthetic glycosaminoglycan ether treatment after LL-37 showed mild attenuation of inflammation with myeloperoxidase 2.5-fold below that of untreated bladders. Semi-synthetic glycosaminoglycan ether treatment before LL-37 demonstrated almost complete attenuation of inflammation. Myeloperoxidase results mirrored those in controls. In heparin treated bladders minimal attenuation of inflammation occurred. Finally, instillation of GM-1111-Alexa Fluor 633 revealed urothelial coating, significant tissue penetration and binding to endovasculature. Conclusions We developed what is to our knowledge a new model of inflammatory bladder disease by challenge with the naturally occurring urinary peptide LL-37. We also noted that a new class of anti-inflammatory sulfated polysaccharides prevents and mitigates bladder inflammation. PMID:21855919

The Gluten-Free, Casein-Free Diet in Autism: Results of a Preliminary Double Blind Clinical Trial

ERIC Educational Resources Information Center

Elder, Jennifer Harrison; Shankar, Meena; Shuster, Jonathan; Theriaque, Douglas; Burns, Sylvia; Sherrill, Lindsay

2006-01-01

This study tested the efficacy of a gluten-free and casein-free (GFCF) diet in treating autism using a randomized, double blind repeated measures crossover design. The sample included 15 children aged 2-16 years with autism spectrum disorder. Data on autistic symptoms and urinary peptide levels were collected in the subjects' homes over the 12…

C-Peptide Decline in Type 1 Diabetes Has Two Phases: An Initial Exponential Fall and a Subsequent Stable Phase.

PubMed

Shields, Beverley M; McDonald, Timothy J; Oram, Richard; Hill, Anita; Hudson, Michelle; Leete, Pia; Pearson, Ewan R; Richardson, Sarah J; Morgan, Noel G; Hattersley, Andrew T

2018-06-07

The decline in C-peptide in the 5 years after diagnosis of type 1 diabetes has been well studied, but little is known about the longer-term trajectory. We aimed to examine the association between log-transformed C-peptide levels and the duration of diabetes up to 40 years after diagnosis. We assessed the pattern of association between urinary C-peptide/creatinine ratio (UCPCR) and duration of diabetes in cross-sectional data from 1,549 individuals with type 1 diabetes using nonlinear regression approaches. Findings were replicated in longitudinal follow-up data for both UCPCR ( n = 161 individuals, 326 observations) and plasma C-peptide ( n = 93 individuals, 473 observations). We identified two clear phases of C-peptide decline: an initial exponential fall over 7 years (47% decrease/year [95% CI -51%, -43%]) followed by a stable period thereafter (+0.07%/year [-1.3, +1.5]). The two phases had similar durations and slopes in patients above and below the median age at diagnosis (10.8 years), although levels were lower in the younger patients irrespective of duration. Patterns were consistent in both longitudinal UCPCR ( n = 162; ≤7 years duration: -48%/year [-55%, -38%]; >7 years duration -0.1% [-4.1%, +3.9%]) and plasma C-peptide ( n = 93; >7 years duration only: -2.6% [-6.7%, +1.5%]). These data support two clear phases of C-peptide decline: an initial exponential fall over a 7-year period, followed by a prolonged stabilization where C-peptide levels no longer decline. Understanding the pathophysiological and immunological differences between these two phases will give crucial insights into understanding β-cell survival. © 2018 by the American Diabetes Association.

Spontaneously released substance P and bradykinin from isolated guinea-pig bladder.

PubMed

Saban, R; Franz, J; Bjorling, D E

1997-04-01

To investigate whether the isolated urinary bladder spontaneously releases substance P (SP) or bradykinin (BK), which can act as potent mediators of pain and inflammation of the urinary bladder, and whether peptidase inhibitors enhance peptide release. Urinary bladder segments (2 x 10 x 0.8-1 mm) were isolated from guinea pigs and studied in vitro; tissue contraction was assessed using force-displacement transducers and the release of peptides by specific enzyme immunoassays. In the absence of any exogenous agonists, the inhibition of neutral endopeptidase and angiotensin-converting enzyme by phosphoramidon and captopril, respectively, increased the frequency and magnitude of spontaneous motility of isolated bladder strips. Phosphoramidon increased the net release of SP-like immunoreactivity (SP-LI) and captopril increased the net release of SP-LI and BK-LI, concomitant with contraction. Peptide-LI was recovered primarily from bladder mucosa and to a lesser degree from detrusor smooth muscle. Similarly, peptidase inhibitors primarily affected the bladder mucosa; phosphoramidon induced a fourfold increase in SP-LI and captopril induced a significant increase of SP-LI and BK-LI from the mucosa. Tissues contracted in response to peptidase inhibitors in the presence of atropine and indomethacin, but contraction was reduced significantly by in vitro capsaicin desensitization or removal of bladder mucosa. BK stimulated SP-LI release from mucosa but not detrusor. SP stimulated increased BK-LI release from mucosa and detrusor. These findings indicate the basal release of peptide-like immunoreactivity by isolated bladder and further support the concept that peptidases located in the bladder mucosa are important in terminating the effects of endogenous peptides.

Experimental colitis triggers the release of substance P and calcitonin gene-related peptide in the urinary bladder via TRPV1 signaling pathways

PubMed Central

Pan, Xiao-Qing; Gonzalez, Jessica A.; Chang, Shaohua; Chacko, Samuel; Wein, Alan J.; Malykhina, Anna P.

2010-01-01

Clinical data provides evidence of high level of co-morbidity among genitourinary and gastrointestinal disorders characterized by chronic pelvic pain. The objective of this study was to test the hypothesis that colonic inflammation can impact the function of the urinary bladder via activation of TRPV1 signaling pathways followed by alterations in gene and protein expression of Substance P (SP) and calcitonin gene-related peptide (CGRP) in sensory neurons and in the bladder. Inflammation was induced by intracolonic instillation of trinitrobenzene sulfonic acid (TNBS, 12.5 mg/kg) and desensitization of TRPV1 receptors was evoked by intracolonic resiniferatoxin (RTX, 10−7 M). mRNA and protein concentrations of CGRP and SP were measured at 3, 5 and 30 days. RTX instillation in the colon caused 3-fold up-regulation of SP mRNA in the urinary bladder at day 5 (n=7, p≤0.05) followed by 35-fold increase at day 30 (n=5, p≤0.05). Likewise, TNBS colitis triggered 15.8-fold up-regulation of SP mRNA one month after TNBS (n=5, p≤0.05). Desensitization of colonic TRPV1 receptors prior to TNBS abolished SP increase in the urinary bladder. RTX led to 4.3-fold increase of CGRP mRNA at day 5 (n=7, p≤0.05 to control) in the bladder followed by 28-fold increase at day 30 post-RTX (n=4, p≤0.05). Colitis did not alter CGRP concentration during acute phase, however, at day 30 mRNA level was increased by 17.8±6.9 fold (n=5, p≤0.05) in parallel with 4-fold increase in CGRP protein (n=5, p≤0.01) in the detrusor. Protein concentration of CGRP in the spinal cord was diminished by 45–65% (p≤0.05) during colitis. RTX pretreatment did not affect CGRP concentration in the urinary bladder, however, caused a reduction in CGRP release from lumbosacral DRG neurons during acute phase (3 and 5 days post-TNBS). Our results clearly demonstrate that colonic inflammation triggers the release of pro-inflammatory neuropeptides SP and CGRP in the urinary bladder via activation of TRPV1 signaling mechanisms enunciating the neurogenic nature of pelvic organ cross-sensitization. PMID:20501335

Interleukin-6/Stat3 signaling has an essential role in the host antimicrobial response to urinary tract infection.

PubMed

Ching, Christina B; Gupta, Sudipti; Li, Birong; Cortado, Hanna; Mayne, Nicholas; Jackson, Ashley R; McHugh, Kirk M; Becknell, Brian

2018-06-01

The signaling networks regulating antimicrobial activity during urinary tract infection (UTI) are incompletely understood. Interleukin-6 (IL-6) levels increase with UTI severity, but the specific contributions of IL-6 to host immunity against bacterial uropathogens are unknown. To clarify this we tested whether IL-6 activates the Stat3 transcription factor, to drive a program of antimicrobial peptide gene expression in infected urothelium during UTI. Transurethral inoculation of uropathogenic Escherichia coli led to IL-6 secretion, urothelial Stat3 phosphorylation, and activation of antimicrobial peptide transcription, in a Toll-like receptor 4-dependent manner in a murine model of cystitis. Recombinant IL-6 elicited Stat3 phosphorylation in primary urothelial cells in vitro, and systemic IL-6 administration promoted urothelial Stat3 phosphorylation and antimicrobial peptide expression in vivo. IL-6 deficiency led to decreased urothelial Stat3 phosphorylation and antimicrobial peptide mRNA expression following UTI, a finding mirrored by conditional Stat3 deletion. Deficiency in IL-6 or Stat3 was associated with increased formation of intracellular bacterial communities, and exogenous IL-6 reversed this phenotype in IL-6 knockout mice. Moreover, chronic IL-6 depletion led to increased renal bacterial burden and severe pyelonephritis in C3H/HeOuJ mice. Thus, IL-6/Stat3 signaling drives a transcriptional program of antimicrobial gene expression in infected urothelium, with key roles in limiting epithelial invasion and ascending infection. Copyright © 2018 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

Pretransplant urinary proteome analysis does not predict development of chronic kidney disease after liver transplantation.

PubMed

Milongo, David; Bascands, Jean-Loup; Huart, Antoine; Esposito, Laure; Breuil, Benjamin; Moulos, Panagiotis; Siwy, Justyna; Ramírez-Torres, Adela; Ribes, David; Lavayssière, Laurence; Del Bello, Arnaud; Muscari, Fabrice; Alric, Laurent; Bureau, Christophe; Rostaing, Lionel; Schanstra, Joost P; Kamar, Nassim

2015-07-01

Chronic kidney disease (CKD) is a common complication after liver transplantation. Kidney biopsies cannot be easily performed before liver transplantation to predict patients at high risk for CKD. The aim of our study was to determine whether pre-, peri- and post-transplant factors, as well as peptides present in preliver transplant urine samples were associated with loss in kidney function at 6 months post-transplantation using proteome analysis. Eighty patients who underwent a liver transplantation and that had pretransplant glomerular filtration rate (GFR) value of ≥60 mL/min/1.73 m² (MDRD) were included in the study. GFR decreased significantly after transplantation. At month 6 post-transplantation, 40 patients displayed a CKD, i.e. eGFR of <60 mL/min/1.73 m², while the other 40 patients did not. Although thousands of peptides were identified, none was significantly associated with the development of CKD at 6 months after liver transplantation. Moreover, using a urinary peptidome classifier to detect preexisting CKD, no difference was found in CKD scores between the 2 groups. After analysis of a large number of pre-, peri- and post-transplant parameters, viral hepatitis as a cause for liver transplantation was the sole independent predictive factor for CKD. No difference in peptides with differential urinary abundance between patients who received a graft for virus related liver disease vs. all other causes of liver disease was observed. Urinary peptidome analysis before liver transplantation failed to identify a peptide pattern associated with the development of CKD at 6 months after liver transplantation. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Atrial Natriuretic Peptide Stimulates Dopamine Tubular Transport by Organic Cation Transporters: A Novel Mechanism to Enhance Renal Sodium Excretion

PubMed Central

Kouyoumdzian, Nicolás M.; Rukavina Mikusic, Natalia L.; Kravetz, María C.; Lee, Brenda M.; Carranza, Andrea; Del Mauro, Julieta S.; Pandolfo, Marcela; Gironacci, Mariela M.; Gorzalczany, Susana; Toblli, Jorge E.; Fernández, Belisario E.

2016-01-01

The aim of this study was to demonstrate the effects of atrial natriuretic peptide (ANP) on organic cation transporters (OCTs) expression and activity, and its consequences on dopamine urinary levels, Na+, K+-ATPase activity and renal function. Male Sprague Dawley rats were infused with isotonic saline solution during 120 minutes and randomized in nine different groups: control, pargyline plus tolcapone (P+T), ANP, dopamine (DA), D-22, DA+D-22, ANP+D-22, ANP+DA and ANP+DA+D-22. Renal functional parameters were determined and urinary dopamine concentration was quantified by HPLC. Expression of OCTs and D1-receptor in membrane preparations from renal cortex tissues were determined by western blot and Na+, K+-ATPase activity was determined using in vitro enzyme assay. 3H-DA renal uptake was determined in vitro. Compared to P+T group, ANP and dopamine infusion increased diuresis, urinary sodium and dopamine excretion significantly. These effects were more pronounced in ANP+DA group and reversed by OCTs blockade by D-22, demonstrating that OCTs are implied in ANP stimulated-DA uptake and transport in renal tissues. The activity of Na+, K+-ATPase exhibited a similar fashion when it was measured in the same experimental groups. Although OCTs and D1-receptor protein expression were not modified by ANP, OCTs-dependent-dopamine tubular uptake was increased by ANP through activation of NPR-A receptor and protein kinase G as signaling pathway. This effect was reflected by an increase in urinary dopamine excretion, natriuresis, diuresis and decreased Na+, K+-ATPase activity. OCTs represent a novel target that links the activity of ANP and dopamine together in a common mechanism to enhance their natriuretic and diuretic effects. PMID:27392042

PEPTIDE BINDING AS A MODE OF ACTION FOR THE CARCINOGENICITY AND TOXICITY OF ARSENIC

EPA Science Inventory

Arsenic exposure leads to tumors in human skin, lung, urinary bladder, kidney and liver. Three likely initial stages of arsenical-macromolecular interaction are (1) binding of trivalent arsenicals to the sulfhydryl groups of peptides and proteins, (2) arsenical-induced generation...

Human Alpha Defensin 5 Expression in the Human Kidney and Urinary Tract

PubMed Central

Porter, Edith; Bevins, Charles L.; DiRosario, Julianne; Becknell, Brian; Wang, Huanyu

2012-01-01

Background The mechanisms that maintain sterility in the urinary tract are incompletely understood. Recent studies have implicated the importance of antimicrobial peptides (AMP) in protecting the urinary tract from infection. Here, we characterize the expression and relevance of the AMP human alpha-defensin 5 (HD5) in the human kidney and urinary tract in normal and infected subjects. Methodology/Principal Findings Using RNA isolated from human kidney, ureter, and bladder tissue, we performed quantitative real-time PCR to show that DEFA5, the gene encoding HD5, is constitutively expressed throughout the urinary tract. With pyelonephritis, DEFA5 expression significantly increased in the kidney. Using immunoblot analysis, HD5 production also increased with pyelonephritis. Immunostaining localized HD5 to the urothelium of the bladder and ureter. In the kidney, HD5 was primarily produced in the distal nephron and collecting tubules. Using immunoblot and ELISA assays, HD5 was not routinely detected in non-infected human urine samples while mean urinary HD5 production increased with E.coli urinary tract infection. Conclusions/Significance DEFA5 is expressed throughout the urinary tract in non-infected subjects. Specifically, HD5 is expressed throughout the urothelium of the lower urinary tract and in the collecting tubules of the kidney. With infection, HD5 expression increases in the kidney and levels become detectable in the urine. To our knowledge, our findings represent the first to quantitate HD5 expression and production in the human kidney. Moreover, this is the first report to detect the presence of HD5 in infected urine samples. Our results suggest that HD5 may have an important role in maintaining urinary tract sterility. PMID:22359618

Development of a Targeted Urine Proteome Assay for kidney diseases.

PubMed

Cantley, Lloyd G; Colangelo, Christopher M; Stone, Kathryn L; Chung, Lisa; Belcher, Justin; Abbott, Thomas; Cantley, Jennifer L; Williams, Kenneth R; Parikh, Chirag R

2016-01-01

Since human urine is the most readily available biofluid whose proteome changes in response to disease, it is a logical sample for identifying protein biomarkers for kidney diseases. Potential biomarkers were identified by using a multiproteomics workflow to compare urine proteomes of kidney transplant patients with immediate and delayed graft function. Differentially expressed proteins were identified, and corresponding stable isotope labeled internal peptide standards were synthesized for scheduled MRM. The Targeted Urine Proteome Assay (TUPA) was then developed by identifying those peptides for which there were at least two transitions for which interference in a urine matrix across 156 MRM runs was <30%. This resulted in an assay that monitors 224 peptides from 167 quantifiable proteins. TUPA opens the way for using a robust mass spectrometric technology, MRM, for quantifying and validating biomarkers from among 167 urinary proteins. This approach, while developed using differentially expressed urinary proteins from patients with delayed versus immediate graft function after kidney transplant, can be expanded to include differentially expressed urinary proteins in multiple kidney diseases. Thus, TUPA could provide a single assay to help diagnose, prognose, and manage many kidney diseases. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

The innate immune response during urinary tract infection and pyelonephritis

PubMed Central

Spencer, John David; Schwaderer, Andrew L.; Becknell, Brian; Watson, Joshua; Hains, David S.

2013-01-01

Despite its proximity to the fecal flora, the urinary tract is considered sterile. The precise mechanisms by which the urinary tract maintains sterility are not well understood. Host immune responses are critically important in the antimicrobial defense of the urinary tract. During recent years, considerable advances have been made in our understanding of the mechanisms underlying immune homeostasis of the kidney and urinary tract. Dysfunctions in these immune mechanisms may result in acute disease, tissue destruction and overwhelming infection. The objective of this review is to provide an overview of the innate immune response in the urinary tract in response to microbial assault. In doing so, we focus on the role of antimicrobial peptides – a ubiquitous component of the innate immune response. PMID:23732397

The innate immune response during urinary tract infection and pyelonephritis.

PubMed

Spencer, John David; Schwaderer, Andrew L; Becknell, Brian; Watson, Joshua; Hains, David S

2014-07-01

Despite its proximity to the fecal flora, the urinary tract is considered sterile. The precise mechanisms by which the urinary tract maintains sterility are not well understood. Host immune responses are critically important in the antimicrobial defense of the urinary tract. During recent years, considerable advances have been made in our understanding of the mechanisms underlying immune homeostasis of the kidney and urinary tract. Dysfunctions in these immune mechanisms may result in acute disease, tissue destruction and overwhelming infection. The objective of this review is to provide an overview of the innate immune response in the urinary tract in response to microbial assault. In doing so, we focus on the role of antimicrobial peptides-a ubiquitous component of the innate immune response.

Urinary C-peptide levels in male bonobos (Pan paniscus) are related to party size and rank but not to mate competition.

PubMed

Surbeck, Martin; Deschner, Tobias; Behringer, Verena; Hohmann, Gottfried

2015-05-01

Within- and between-species variation in male mating strategies has been attributed to a multitude of factors including male competitive ability and the distribution of fertile females across space and time. Differences in energy balance across and within males allow for the identification of some of the trade-offs associated with certain social and mating strategies. Bonobos live in groups with a high degree of fission-fusion dynamics, there is co-dominance between the sexes and a linear dominance hierarchy among males. Males compete over access to females, breeding is aseasonal, and females exhibit sexual swellings over extended time periods. In this study we use urinary C-peptide (UCP) levels in male bonobos (Pan paniscus) obtained from 260 urine samples from a wild bonobo community, to quantify male energy balance during mate competition and levels of gregariousness in the species. Although high ranking males are more aggressive, spend more time in proximity to maximally tumescent females, and have higher mating frequencies, we found no indication that mate guarding or mate competition affected male energy balance. Our results showed a positive correlation between monthly mean UCP levels and mean party size. When traveling in large parties, high ranking males had higher UCP levels than those of the low ranking males. These results support the hypothesis that patterns of fission-fusion dynamics in bonobos are either linked to energy availability in the environment or to the energetic costs of foraging. The finding of a rank-bias in UCP levels in larger parties could also reflect an increase in contest competition among males over access to food. Copyright © 2015. Published by Elsevier Inc.

Involvement of Glucagon-Like Peptide-1 in the Regulation of Selective Excretion of Sodium or Chloride Ions by the Kidneys.

PubMed

Marina, A S; Kutina, A V; Shakhmatoba, E I; Natochin, Yu V

2017-02-01

An increase of total glucagon-like peptide-1 (GLP-1) concentration in the plasma in rats was revealed 5 min after oral, but not intraperitoneal administration of NaCl or Trizma HCl solutions. The increase in GLP-1 level was similar to that after oral glucose administration. After intraperitoneal administration of 2.5% NaCl, GLP-1 mimetic exenatide accelerated natriuresis and urinary chloride excretion. Under conditions of normonatriemia and hyperchloremia induced by injection of 6.7% Trizma HCl, exenatide stimulated chloride excretion and reabsorption of sodium ions in the kidneys. These findings suggest that GLP-1 participates in selective regulation of the balance of sodium and chloride ions.

Characterization of bombesin receptors in peripheral contractile organs.

PubMed Central

Rouissi, N.; Rhaleb, N. E.; Nantel, F.; Dion, S.; Drapeau, G.; Regoli, D.

1991-01-01

1 Guinea-pig and rat urinary bladders, rat stomach and the guinea-pig gall bladder, four isolated organs that show high sensitivity to bombesin, were used to characterize bombesin receptors in peripheral organs. 2 The order of potency of agonists was determined with several naturally occurring peptides of the bombesin series, namely bombesin (BBS), litorin (Lit), neuromedin B (NMB), the gastrin-releasing peptide (GRP 18-27), neuromedin C (NMC) and with some bombesin fragments. It was found that bombesin, neuromedin C, litorin and two bombesin fragments, BBS (6-14) and AcBBS (6-14) had similar activities in the four preparations, while neuromedin B and [Phe6]-neuromedin C were more active on the rat urinary bladder than on the other tissues. 3 The order of potency of agonists determined in the rat urinary bladder was as follows: BBS = NMB greater than Lit greater than NMC greater than [Phe6]NMC = GRP and it was found to be different from that observed in the other preparations: BBS greater than GRP = Lit greater than or equal to NMC much greater than NMB greater than [Phe6]NMC, suggesting the existence of two different bombesin receptors, BBS1 and BBS2. 4 This interpretation was convalidated by the finding that bombesin antagonists, namely Ac.GRP(20-26)OCH3 and Ac.GRP(20-26)OC2H5 reduced or blocked the effects of bombesin-related peptides on BBS2 receptor systems while being completely inactive on the rat urinary bladder (BBS1 system). PMID:1652341

Inflammatory response to Escherichia coli urinary tract infection in the neurogenic bladder of the spinal cord injured host.

PubMed

Chaudhry, Rajeev; Madden-Fuentes, Ramiro J; Ortiz, Tara K; Balsara, Zarine; Tang, Yuping; Nseyo, Unwanaobong; Wiener, John S; Ross, Sherry S; Seed, Patrick C

2014-05-01

Urinary tract infections cause significant morbidity in patients with spinal cord injury. An in vivo spinal cord injured rat model of experimental Escherichia coli urinary tract infection mimics human disease with enhanced susceptibility to urinary tract infection compared to controls. We hypothesized that a dysregulated inflammatory response contributes to enhanced susceptibility to urinary tract infection. Spinal cord injured and sham injured rats were inoculated transurethrally with E. coli. Transcript levels of 84 inflammatory pathway genes were measured in bladder tissue of each group before infection, 24 hours after infection and after 5 days of antibiotic therapy. Before infection quantitative polymerase chain reaction array revealed greater than twofold up-regulation in the proinflammatory factor transcripts slc11a1, ccl4 and il1β, and down-regulation of the antimicrobial peptides lcn2 and mpo in spinal cord injured vs control bladders. At 24 hours after infection spinal cord injured bladders showed an attenuated innate immune response with decreased expression of il6, slc11a1, il1β and lcn2, and decreased il10 and slpi expression compared to controls. Despite clearance of bacteriuria with antibiotics spinal cord injured rats had delayed induction of il6 transcription and a delayed anti-inflammatory response with decreased il10 and slpi transcript levels relative to controls. Spinal cord injured bladders fail to mount a characteristic inflammatory response to E. coli infection and cannot suppress inflammation after infection is eliminated. This may lead to increased susceptibility to urinary tract infection and persistent chronic inflammation through neural mediated pathways, which to our knowledge remain to be defined. Copyright © 2014 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Ranatensin-HL: A Bombesin-Related Tridecapeptide from the Skin Secretion of the Broad-Folded Frog, Hylarana latouchii.

PubMed

Lin, Yan; Chen, Tianbao; Zhou, Mei; Wang, Lei; Su, Songkun; Shaw, Chris

2017-07-04

Bombesin-related peptides are a family of peptides whose prototype was discovered in amphibian skin and which exhibit a wide range of biological activities. Since the initial isolation of bombesin from Bombina bombina skin, diverse forms of bombesin-related peptides have been found in the skins across Anura. In this study, a novel bombesin-related peptide of the ranatensin subfamily, named ranatensin-HL, was structurally-characterised from the skin secretion of the broad-folded frog, Hylarana latouchii , through combination of molecular cloning and mass spectrometric methodologies. It is composed of 13 amino acid residues, pGlu-RAGNQWAIGHFM-NH₂, and resembles an N-terminally extended form of Xenopus neuromedin B. Ranatensin-HL and its C-terminal decapeptide (ranatensin-HL-10) were chemically synthesised and subjected to in vitro smooth muscle assays in which they were found to display moderate stimulatory effects on rat urinary bladder and uterus smooth muscles with EC 50 values in the range of 1-10 nM. The prepro-ranatensin-HL was highly homological to a bombesin-like peptide from Rana catesbeiana at both nucleotide and amino acid levels, which might provide a clue for the taxonomic classification of ranid frogs in the future.

T Cell Epitope Mapping of JC Polyoma Virus-Encoded Proteome Reveals Reduced T Cell Responses in HLA-DRB1*04:01+ Donors

PubMed Central

Jelčić, Ilijas; Aly, Lilian; Binder, Thomas M. C.; Jelčić, Ivan; Bofill-Mas, Sílvia; Planas, Raquel; Demina, Victoria; Eiermann, Thomas H.; Weber, Thomas; Girones, Rosina; Sospedra, Mireia

2013-01-01

JC polyomavirus (JCV) infection is highly prevalent and usually kept in a persistent state without clinical signs and symptoms. It is only during immunocompromise and especially impaired CD4+ T cell function in the brain, as seen in AIDS patients or natalizumab-treated multiple sclerosis patients, that JCV may cause progressive multifocal leukoencephalopathy (PML), an often life-threatening brain disease. Since CD4+ T cells likely play an important role in controlling JCV infection, we here describe the T cell response to JCV in a group of predominantly HLA-DR-heterozygotic healthy donors (HD) by using a series of overlapping 15-mer peptides spanning all JCV-encoded open reading frames. We identified immunodominant epitopes and compared T cell responses with anti-JCV VP1 antibody production and with the presence of urinary viral shedding. We observed positive JCV-specific T cell responses in 28.6% to 77.6%, humoral immune response in 42.6% to 89.4%, and urinary viral shedding in 36.4% to 45.5% of HD depending on the threshold. Four immunodominant peptides were mapped, and at least one immunogenic peptide per HLA-DRB1 allele was detected in DRB1*01+, DRB1*07+, DRB1*11+, DRB1*13+, DRB1*15+, and DRB1*03+ individuals. We show for the first time that JCV-specific T cell responses may be directed not only against JCV VP1 and large T antigen but also against all other JCV-encoded proteins. Heterozygotic DRB1*04:01+ individuals showed very low T cell responses to JCV together with normal anti-VP1 antibody levels and no urinary viral shedding, indicating a dominant-negative effect of this allele on global JCV-directed T cell responses. Our data are potentially relevant for the development of vaccines against JCV. PMID:23302880

Neurohumoral mechanism in the natriuretic action of intracerebroventricular administration of renin.

PubMed

Zavala, Lida; Barbella, Yarisma; Israel, Anita

2004-03-01

Intracerebroventricular (i.v.t.) administration of renin (R) decreases urinary volume and increases urinary sodium excretion. We investigated whether i.v.t.-R-induced natriuresis could be associated with the release of atrial natriuretic peptide (ANP), its interaction with renal ANP-A receptors (ANPR-A) and the subsequent increase of urinary cyclic 3-5 guanosine monophosphate (cGMP). In i.v.t. cannulated rats, the left carotid artery was catheterised with PE-50 tubing for blood collection, renin was injected i.v.t. and arterial blood samples were collected at 0, 2, 5, 10 and 15 minutes of injection, and urinary sodium and cGMP excretion at 1-, 3- and 6-hour periods of urine collection. Plasma ANP levels and urinary cGMP were determined by radioimmunoassay, and each urine sample was analysed for sodium concentration using a flame photometer. Our results demonstrate that i.v.t.-R administration increases plasma ANP levels after two minutes of injection and urinary cGMP concentration at 1-, 3- and 6 hour period of urine collection. The natriuretic action induced by i.v.t.-R was blunted by peripheral administration of anantin, an ANPR-A antagonist. We assessed the role of brain angiotensin II (Ang II) AT1-receptors on the i.v.t.-induced antidiuresis, natriuresis and cGMP urinary excretion, the last as an indirect index of ANP secretion. Blockade of brain Ang II AT1-receptors with losartan (LOS; 120 microg/3 microl, i.v.t.), inhibited the antidiuretic action and blocked the increased urinary sodium and cGMP excretion induced by i.v.t.-R (7.14 mGU/5 microl). The increase in urinary cGMP was independent of nitric oxide synthase stimulation, since L-NAME pre-treatment did not alter the renal actions induced by i.v.t.-R. Our results suggest that there is a link between the brain and the kidney. The activation of brain angiotensinergic neurons and stimulation of AT1- receptors may stimulate the release of ANP to the circulation. The released ANP circulates to the kidneys where it acts through renal ANPR-As and the consequent increase in cGMP to produce natriuresis.

Prader-Willi syndrome with elevated follicle stimulating hormone levels and diabetes mellitus.

PubMed

Nagai, T; Mimura, N; Tomizawa, T; Monden, T; Mori, M

1998-12-01

A 21 -year-old man with Prader-Willi syndrome (PWS) was hospitalized due to hyperglycemia. After diet therapy and transient insulin administration, his blood glucose levels improved. Based on the fact that his urinary C-peptide levels increased, the diabetes mellitus may have been due to insulin resistance with obesity. In addition, his testes had become atrophied. Testosterone levels remained low even after human chorionic gonadotropin (HCG) administration. Luteinizing hormone (LH) levels were also low after LH releasing hormone (LHRH) administration. The LH response increased slightly after daily LHRH administration, indicating hypothalamic hypogonadism. Follicle stimulating hormone (FSH) levels were, however, high and increased after LHRH administration. The selective FSH elevation may have been due to the accompanying idiopathic oligospermia.

Tomato Juice Consumption Modifies the Urinary Peptide Profile in Sprague-Dawley Rats with Induced Hepatic Steatosis

PubMed Central

Martín-Pozuelo, Gala; González-Barrio, Rocío; Barberá, Gonzalo G.; Albalat, Amaya; García-Alonso, Javier; Mullen, William; Mischak, Harald; Periago, María Jesús

2016-01-01

Non-alcoholic fatty liver disease (NAFLD) is the most common liver disorder in Western countries, with a high prevalence, and has been shown to increase the risk of type 2 diabetes, cardiovascular disease (CVD), etc. Tomato products contain several natural antioxidants, including lycopene—which has displayed a preventive effect on the development of steatosis and CVD. Accordingly, the aim of the present work was to evaluate the effect of tomato juice consumption on the urinary peptide profile in rats with NAFLD induced by an atherogenic diet and to identify potential peptide biomarkers for diagnosis. Urine samples, collected weekly for four weeks, were analyzed by capillary electrophoresis (CE) coupled to a mass spectrometer (MS). A partial least squares-discriminant analysis (PLS-DA) was carried out to explore the association between differential peptides and treatments. Among the 888 peptides initially identified, a total of 55 were obtained as potential biomarkers. Rats with steatosis after tomato juice intake showed a profile intermediate between that of healthy rats and that of rats with induced hepatic steatosis. Accordingly, tomato products could be considered as a dietary strategy for the impairment of NAFLD, although further research should be carried out to develop a specific biomarkers panel for NAFLD. PMID:27792191

Metabolic acidosis stimulates the production of the antimicrobial peptide cathelicidin in rabbit urine.

PubMed

Peng, Hu; Purkerson, Jeffrey M; Schwaderer, Andy L; Schwartz, George J

2017-11-01

Intercalated cells of the collecting duct (CD) are critical for acid-base homeostasis and innate immune defense of the kidney. Little is known about the impact of acidosis on innate immune defense in the distal nephron. Urinary tract infections are mainly due to Escherichia coli and are an important risk factor for development of chronic kidney disease. While the effect of urinary pH on growth of E. coli is well established, in this study, we demonstrate that acidosis increases urine antimicrobial activity due, at least in part, to induction of cathelicidin expression within the CD. Acidosis was induced in rabbits by adding NH 4 Cl to the drinking water and reducing food intake over 3 days or by casein supplementation. Microdissected CDs were examined for cathelicidin mRNA expression and antimicrobial activity, and cathelicidin protein levels in rabbit urine were measured. Cathelicidin expression in CD cells was detected in kidney sections. CDs from acidotic rabbits expressed three times more cathelicidin mRNA than those isolated from normal rabbits. Urine from acidotic rabbits had significantly more antimicrobial activity (vs. E. coli ) than normal urine, and most of this increased activity was blocked by cathelicidin antibody. The antibody had little effect on antimicrobial activity of normal urine. Urine from acidotic rabbits had at least twice the amount of cathelicidin protein as did normal urine. We conclude that metabolic acidosis not only stimulates CD acid secretion but also induces expression of cathelicidin and, thereby, enhances innate immune defense against urinary tract infections via induction of antimicrobial peptide expression. Copyright © 2017 the American Physiological Society.

N-linked (N-) glycoproteomics of urinary exosomes. [Corrected].

PubMed

Saraswat, Mayank; Joenväära, Sakari; Musante, Luca; Peltoniemi, Hannu; Holthofer, Harry; Renkonen, Risto

2015-02-01

Epithelial cells lining the urinary tract secrete urinary exosomes (40-100 nm) that can be targeted to specific cells modulating their functionality. One potential targeting mechanism is adhesion between vesicle surface glycoproteins and target cells. This makes the glycopeptide analysis of exosomes important. Exosomes reflect the physiological state of the parent cells; therefore, they are a good source of biomarkers for urological and other diseases. Moreover, the urine collection is easy and noninvasive and urinary exosomes give information about renal and systemic organ systems. Accordingly, multiple studies on proteomic characterization of urinary exosomes in health and disease have been published. However, no systematic analysis of their glycoproteomic profile has been carried out to date, whereas a conserved glycan signature has been found for exosomes from urine and other sources including T cell lines and human milk. Here, we have enriched and identified the N-glycopeptides from these vesicles. These enriched N-glycopeptides were solved for their peptide sequence, glycan composition, structure, and glycosylation site using collision-induced dissociation MS/MS (CID-tandem MS) data interpreted by a publicly available software GlycopeptideId. Released glycans from the same sample was also analyzed with MALDI-MS. We have identified the N-glycoproteome of urinary exosomes. In total 126 N-glycopeptides from 51 N-glycosylation sites belonging to 37 glycoproteins were found in our results. The peptide sequences of these N-glycopeptides were identified unambiguously and their glycan composition (for 125 N-glycopeptides) and structures (for 87 N-glycopeptides) were proposed. A corresponding glycomic analysis with released N-glycans was also performed. We identified 66 unique nonmodified N-glycan compositions and in addition 13 sulfated/phosphorylated glycans were also found. This is the first systematic analysis of N-glycoproteome of urinary exosomes. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

Neuropeptides in Lower Urinary Tract (LUT) Function

PubMed Central

Arms, Lauren; Vizzard, Margaret A.

2014-01-01

Numerous neuropeptide/receptor systems including vasoactive intestinal polypeptide, pituitary adenylate cyclase-activating polypeptide, calcitonin gene-related peptide, substance P, neurokinin A, bradykinin, and endothelin-1 are expressed in the lower urinary tract (LUT) in both neural and non-neural (e.g., urothelium) components. LUT neuropeptide immunoreactivity is present in afferent and autonomic efferent neurons innervating the bladder and urethra and in the urothelium of the urinary bladder. Neuropeptides have tissue-specific distributions and functions in the LUT and exhibit neuroplastic changes in expression and function with LUT dysfunction following neural injury, inflammation and disease. LUT dysfunction with abnormal voiding including urinary urgency, increased voiding frequency, nocturia, urinary incontinence and pain may reflect a change in the balance of neuropeptides in bladder reflex pathways. LUT neuropeptide/receptor systems may represent potential targets for therapeutic intervention. PMID:21290237

Urinary sodium excretion after gastric bypass surgery.

PubMed

Docherty, Neil G; Fändriks, Lars; le Roux, Carel W; Hallersund, Peter; Werling, Malin

2017-09-01

Gut-kidney signaling is implicated in sodium homeostasis and thus blood pressure regulation. Roux-en-Y gastric bypass (RYGB) surgery for morbid obesity confers a pronounced and long-lasting blood pressure lowering effect in addition to significant weight loss. We set out to establish whether RYGB is associated with an intrinsic change in urinary sodium excretion that may contribute to the reported blood pressure lowering effects of the procedure. University hospital METHODS: Five female patients (age range: 28-50 yr) without metabolic or hypertensive co-morbidities were included in a study involving four 24-hour residential visits: once before surgery and 10 days, 3 months, and 20 months after surgery. Creatinine and sodium were measured in fasting plasma samples and 24-hour urine samples and creatinine clearance, estimated glomerular filtration rate, and indices of urinary sodium excretion were calculated. Fasting and 60-minute postprandial blood samples from each study day were assayed for pro-B-type natriuretic peptide (NT-proBNP). Increases in weight-normalized urinary sodium excretion of up to 2.3-fold in magnitude occurred at 20 months after surgery. Median fractional excretion of sodium at 20 months was double that seen before surgery. Fasting NT-proBNP levels were stable or increased (1.5- to 5-fold). Moreover, a small postprandial increase in NT-proBNP was observed after surgery. Renal fractional excretion of sodium is increased after RYGB. A shift toward increased postoperative basal and meal associated levels of NT-proBNP coincides with increased urinary sodium excretion. The data support a working hypothesis that an enhanced natriuretic gut-kidney signal after RYGB may be of mechanistic importance in the blood pressure lowering effects of this procedure. Copyright © 2017 American Society for Bariatric Surgery. Published by Elsevier Inc. All rights reserved.

A urine midmolecule osteocalcin assay shows higher discriminatory power than a serum midmolecule osteocalcin assay during short-term alendronate treatment of osteoporotic patients.

PubMed

Srivastava, A K; Mohan, S; Singer, F R; Baylink, D J

2002-07-01

We isolated and characterized a peptide fragment corresponding to amino acid sequence 14-28 of human osteocalcin in urine from Paget's disease, and developed a polyclonal antibody reactive to this peptide in urine. We used this antibody to measure urinary fragments of osteocalcin and compared to efficacy of the urinary osteocalcin assay with a serum osteocalcin (sOC) assay (ELISA-Osteo, Cis-Bio International) to monitor the short-term changes in bone turnover in response to alendronate treatment. The synthetic peptide-based urinary osteocalcin (uOC) radioimmunoassay (RIA) showed an analytical sensitivity of 6.25 ng/mL, standard curve range of 3.12-400 ng/mL, and mean intra- (n = 20) and interassay (n = 30) coefficient of variation (CV) of <15%. Urine osteocalcin concentrations in postmenopausal osteoporotic patients were approximately 90% higher than in normal premenopausal controls. Series of 24 h urine and matched serum samples were collected at baseline, 30 days, and 90 days after treatment of postmenopausal osteoporotic patients with daily dose of 10 mg alendronate. We measured urinary osteocalcin (uOc) levels and urinary N-telopeptide (uNTx, Ostex) in urine samples and serum N-telopeptide (sNTx), C-telopeptide (sCTx, Osteometer), serum osteocalcin (sOC) as well as bone-specific alkaline phosphatase (sALP) (Alkphose-B, Metra Biosystems) in serum samples. The percent change data obtained between baseline and 30 days (n = 18) posttreatment suggested a rapid decline in uOC concentration (-27%, p < 0.01) in response to alendronate treatment, as compared with a marginal and nonsignificant decrease in sOC (-7.2%, p = 0.417) or sALP (-3.4%, p = 0.689), two specific markers of bone formation. As expected, due to the coupling of bone formation and bone resorption, the concentration of all markers showed a 30%-45% decline compared with baseline values after 90 days (n = 16) of treatment. Correlation of markers after a 30 day treatment with alendronate revealed a higher correlation (r = 0.61, p < 0.01) between uOC and uNTx, as compared with sOC (r = 0.03, p = 0.447) or sALP (r = -0.14, p = 0.295) with uNTx. Similarly, correlation coefficients with r values between 0.48 and 0.55 (p < 0.05) were observed between uOC, sNTx, and sCTx, whereas no significant correlation was observed between sOC and sNTx or sCTx. These results provide indirect evidence that fragments measured by the urine assay probably originated from bone resorption, and suggest that the uOC assay could be used to assess short-term changes in bone metabolism with regard to osteocalcin.

Activation of the Endogenous Renin-Angiotensin-Aldosterone System or Aldosterone Administration Increases Urinary Exosomal Sodium Channel Excretion.

PubMed

Qi, Ying; Wang, Xiaojing; Rose, Kristie L; MacDonald, W Hayes; Zhang, Bing; Schey, Kevin L; Luther, James M

2016-02-01

Urinary exosomes secreted by multiple cell types in the kidney may participate in intercellular signaling and provide an enriched source of kidney-specific proteins for biomarker discovery. Factors that alter the exosomal protein content remain unknown. To determine whether endogenous and exogenous hormones modify urinary exosomal protein content, we analyzed samples from 14 mildly hypertensive patients in a crossover study during a high-sodium (HS, 160 mmol/d) diet and low-sodium (LS, 20 mmol/d) diet to activate the endogenous renin-angiotensin-aldosterone system. We further analyzed selected exosomal protein content in a separate cohort of healthy persons receiving intravenous aldosterone (0.7 μg/kg per hour for 10 hours) versus vehicle infusion. The LS diet increased plasma renin activity and aldosterone concentration, whereas aldosterone infusion increased only aldosterone concentration. Protein analysis of paired urine exosome samples by liquid chromatography-tandem mass spectrometry-based multidimensional protein identification technology detected 2775 unique proteins, of which 316 exhibited significantly altered abundance during LS diet. Sodium chloride cotransporter (NCC) and α- and γ-epithelial sodium channel (ENaC) subunits from the discovery set were verified using targeted multiple reaction monitoring mass spectrometry quantified with isotope-labeled peptide standards. Dietary sodium restriction or acute aldosterone infusion similarly increased urine exosomal γENaC[112-122] peptide concentrations nearly 20-fold, which correlated with plasma aldosterone concentration and urinary Na/K ratio. Urine exosomal NCC and αENaC concentrations were relatively unchanged during these interventions. We conclude that urinary exosome content is altered by renin-angiotensin-aldosterone system activation. Urinary measurement of exosomal γENaC[112-122] concentration may provide a useful biomarker of ENaC activation in future clinical studies. Copyright © 2016 by the American Society of Nephrology.

Activation of the Endogenous Renin-Angiotensin-Aldosterone System or Aldosterone Administration Increases Urinary Exosomal Sodium Channel Excretion

PubMed Central

Qi, Ying; Wang, Xiaojing; Rose, Kristie L.; MacDonald, W. Hayes; Zhang, Bing; Schey, Kevin L.

2016-01-01

Urinary exosomes secreted by multiple cell types in the kidney may participate in intercellular signaling and provide an enriched source of kidney-specific proteins for biomarker discovery. Factors that alter the exosomal protein content remain unknown. To determine whether endogenous and exogenous hormones modify urinary exosomal protein content, we analyzed samples from 14 mildly hypertensive patients in a crossover study during a high-sodium (HS, 160 mmol/d) diet and low-sodium (LS, 20 mmol/d) diet to activate the endogenous renin-angiotensin-aldosterone system. We further analyzed selected exosomal protein content in a separate cohort of healthy persons receiving intravenous aldosterone (0.7 μg/kg per hour for 10 hours) versus vehicle infusion. The LS diet increased plasma renin activity and aldosterone concentration, whereas aldosterone infusion increased only aldosterone concentration. Protein analysis of paired urine exosome samples by liquid chromatography-tandem mass spectrometry–based multidimensional protein identification technology detected 2775 unique proteins, of which 316 exhibited significantly altered abundance during LS diet. Sodium chloride cotransporter (NCC) and α- and γ-epithelial sodium channel (ENaC) subunits from the discovery set were verified using targeted multiple reaction monitoring mass spectrometry quantified with isotope-labeled peptide standards. Dietary sodium restriction or acute aldosterone infusion similarly increased urine exosomal γENaC[112–122] peptide concentrations nearly 20-fold, which correlated with plasma aldosterone concentration and urinary Na/K ratio. Urine exosomal NCC and αENaC concentrations were relatively unchanged during these interventions. We conclude that urinary exosome content is altered by renin-angiotensin-aldosterone system activation. Urinary measurement of exosomal γENaC[112–122] concentration may provide a useful biomarker of ENaC activation in future clinical studies. PMID:26113616

Effects of a Follow-On Formula Containing Isomaltulose (Palatinose™) on Metabolic Response, Acceptance, Tolerance and Safety in Infants: A Randomized-Controlled Trial

PubMed Central

Fleddermann, M.; Rauh-Pfeiffer, A.; Demmelmair, H.; Holdt, L.; Teupser, D.; Koletzko, B.

2016-01-01

Effects of the dietary glycaemic load on postprandial blood glucose and insulin response might be of importance for fat deposition and risk of obesity. We aimed to investigate the metabolic effects, acceptance and tolerance of a follow-on formula containing the low glycaemic and low insulinaemic carbohydrate isomaltulose replacing high glycaemic maltodextrin. Healthy term infants aged 4 to 8 completed months (n = 50) were randomized to receive the intervention follow-on formula (IF, 2.1g isomaltulose (Palatinose™)/100mL) or an isocaloric conventional formula (CF) providing 2.1g maltodextrin/100mL for four weeks. Plasma insulinaemia 60min after start of feeding (primary outcome) was not statistically different, while glycaemia adjusted for age and time for drinking/volume of meal 60min after start of feeding was 122(105,140) mg/dL in IF (median, interquartile range) and 111(100,123) in CF (p = 0.01). Urinary c-peptide:creatinine ratio did not differ (IF:81.5(44.7, 96.0) vs. CF:56.8(37.5, 129),p = 0.43). Urinary c-peptide:creatinine ratio was correlated total intake of energy (R = 0.31,p = 0.045), protein (R = 0.42,p = 0.006) and fat (R = 0.40,p = 0.01) but not with carbohydrate intake (R = 0.22,p = 0.16). Both formulae were well accepted without differences in time of crying, flatulence, stool characteristics and the occurrence of adverse events. The expected lower postprandial plasma insulin and blood glucose level due to replacement of high glycaemic maltodextrin by low glycaemic isomaltulose were not observed in the single time-point blood analysis. In infants aged 4 to 8 completed months fed a liquid formula, peak blood glucose might be reached earlier than 60min after start of feeding. Non-invasive urinary c-peptide measurements may be a suitable marker of nutritional intake during the previous four days in infants. Trial registration: ClinicalTrials.gov NCT01627015 PMID:26987056

The Association between Serum 25-Hydroxy Vitamin D Level and Urine Cathelicidin in Children with a Urinary Tract Infection.

PubMed

Övünç Hacıhamdioğlu, Duygu; Altun, Demet; Hacıhamdioğlu, Bülent; Çekmez, Ferhat; Aydemir, Gökhan; Kul, Mustafa; Müftüoğlu, Tuba; Süleymanoğlu, Selami; Karademir, Ferhan

2016-09-01

Cathelicidin is an important antimicrobial peptide in the urinary tract. Cathelicidin expression is strongly stimulated by 1,25-dihydroxy vitamin D in epithelial cells, macrophages/monocytes, and neutrophils. Vitamin D and cathelicidin status in children with urinary tract infection (UTI) caused by Escherichia coli is unknown. To establish the relationship between serum vitamin D and urine cathelicidin levels in children with a UTI caused by Escherichia coli. Serum 25-hydroxy vitamin D and urine cathelicidin levels were measured in 36 patients with UTI (mean age 6.8±3.6 years, range: 0.25-12.6 years) and 38 controls (mean age 6.3±2.8 years, range: 0.42-13 years). There were no significant differences in urine cathelicidin levels between the study and control groups (p>0.05). Eight (22.2%) patients in the study group and 21 (58.3%) children in the control group were found to have sufficient vitamin D (≥20 ng/mL). Patients with sufficient vitamin D had higher urine cathelicidin levels than the controls with sufficient vitamin D (respectively 262.5±41.1 vs. 168±31.6 ng/mL, p=0.001). There were no significant differences between the patients and controls with insufficient vitamin D (p>0.05). The children with vitamin D insufficiency may not be able to increase their urine cathelicidin level during UTI caused by Escherichia coli. There is a need of prospective studies in order to prove a beneficial effect of vitamin D supplementation for the restoration of cathelicidin stimulation and consequently for prevention of UTI recurrence.

A synthetic urinary probe–coated nanoparticles sensitive to fibroblast activation protein α for solid tumor diagnosis

PubMed Central

Feng, Xinwei; Wang, Qifan; Liao, Yuehua; Zhou, Xie; Wang, Yidan; Liu, Wanli; Zhang, Ge

2017-01-01

We developed fibroblast activation protein α (FAPα)-sensitive magnetic iron oxide nanoparticles (MNPs) by conjugating a substrate-reporter tandem peptide as a synthetic biomarker to the surface of MNPs (marker-MNPs). In vitro, the marker-MNPs showed stability when treated with serum or urine and exhibited high susceptibility and specificity for FAPα enzyme and 3T3/FAPα cell line. Furthermore, the marker-MNPs were administered to esophageal squamous cell carcinoma xenograft tumor mice; they reached the tumor tissues in the mice, where they were cleaved effectively by the local overexpressed FAPα to release the reporter peptide and filter it into the urine. The tumor targeting and biodistribution of marker-MNPs were verified by in vivo imaging. The cleaved reporter peptides in urine detected by enzyme-linked immunosorbent assay have high diagnostic accuracy for esophageal squamous cell carcinoma (area under the receiver-operating characteristic curve =1.0). Our study implies a promising strategy of utilizing the low-cost and noninvasive synthetic urinary probe–coated nanoparticles for the diagnosis of FAPα-positive solid tumors, except for in renal cancer. PMID:28794628

Tachykinin-independent activity of capsaicin on in-vitro lamb detrusor.

PubMed

Tucci, Paolo; Evandri, Maria Grazia; Bolle, Paola

2002-08-01

The capsicum alkaloid capsaicin is an afferent fibre exciter. In the vesical bladder, capsaicin acts by releasing peptides stored in afferent fibres. The aim of this work was to verify the activity of capsaicin on in-vitro lamb urinary bladder and to ascertain whether this alkaloid evokes peptide release. Capsaicin relaxed about 80% of the lamb detrusor muscle preparations tested and contracted about 20%. Whereas neurokinin A and substance P antagonists, administered alone or together, left the contractile responses to capsaicin unchanged, atropine and tetrodotoxin totally inhibited contraction. Ruthenium red and indometacin abolished contractions and relaxation. The substance P and neurokinin A antagonists and the NO-synthesis inhibitor N omega-nitro-L-arginine methyl ester (L-NAME) left relaxation unchanged; conversely, the calcitonin gene-related peptide antagonist alpha h-CGRP (8-37) abolished this response. These results suggest that capsaicin relaxes lamb detrusor muscle not through tachykinins but by releasing CGRP from afferent fibres. Our observation that indometacin blocks the capsaicin response in in-vitro lamb urinary bladder also suggests a role of prostanoids.

Longitudinal Urinary Protein Variability in Participants of the Space Flight Simulation Program.

PubMed

Khristenko, Nina A; Larina, Irina M; Domon, Bruno

2016-01-04

Urine is a valuable material for the diagnosis of renal pathologies and to investigate the effects of their treatment. However, the variability in protein abundance in the context of normal homeostasis remains a major challenge in urinary proteomics. In this study, the analysis of urine samples collected from healthy individuals, rigorously selected to take part in the MARS-500 spaceflight simulation program, provided a unique opportunity to estimate normal concentration ranges for an extended set of urinary proteins. In order to systematically identify and reliably quantify peptides/proteins across a large sample cohort, a targeted mass spectrometry method was developed. The performance of parallel reaction monitoring (PRM) analyses was improved by implementing tight control of the monitoring windows during LC-MS/MS runs, using an on-the-fly correction routine. Matching the experimentally obtained MS/MS spectra with reference fragmentation patterns allowed dependable peptide identifications to be made. Following optimization and evaluation, the targeted method was applied to investigate protein abundance variability in 56 urine samples, collected from six volunteers participating in the MARS-500 program. The intrapersonal protein concentration ranges were determined for each individual and showed unexpectedly high abundance variation, with an average difference of 1 order of magnitude.

Highly sensitive radioimmunoassay for chorionic gonadotropin in human urine. [/sup 125/I tracer technique

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ayala, A.R.; Nisula, B.C.; Chen, H.C.

1978-10-01

The value of RIAs that measure hCG levels in human urine has been limited principally because of cross-reactivity with human LH. Recently, antisera generated to antigenic determinants on the intact hCG..beta.. subunit and its carboxyl-terminal peptide have been shown to exhibit substantially reduced human LH cross-reactivity. To take maximal advantage of these antisera and to minimize interference by nonspecific substances in urine, a procedure for extracting and concentrating hCG from 24-h urine samples was developed. The procedure involves preparation of a standard kaolin-acetone urine concentrate and adsorption of the hCG in the concentrate to Concanavalin A covalently linked to agarosemore » for purification and subsequent RIA. In urine samples obtained from patients with gestational trophoblastic disease, there was a direct correlation between hCG levels measured by RIA and those estimated by mouse uterine weight bioassy. In individual subjects, hCG levels were determined in serum and urine obtained the same day. When hCG was clearly detectable in the serum at levels greater than 1 ng/ml, the quantity of hCG measured in the urine concentrate exceeded 500 ng/24 h. The concentrates prepared from the urine of normal persons contained an hCG-like glycoprotein substance with antigenic determinants similar to those of the carboxyl-terminal peptide of hCG..beta... As the range of hCG immunoreactivity measured in the urine concentrates of normal subjects was 6 to 52 ng/24 h, specific and sensitive detection of urinary hCG could be accomplished in patients whose sera contained hCG undetectable by conventional RIA. Partial purification and concentration of urinary hCG by this procedure with subsequent RIA provides a sensitive and reliable method for detecting hCG in urine.« less

Immunohistochemical study of parathyroid hormone-related protein in vesical transitional epithelium of patients with spinal cord injury.

PubMed

Vaidyanathan, S; McCreavy, D T; McDicken, I W; Soni, B M; Mansour, P; Wlodarski, B; Carron, J A; Fraser, W D; Singh, G; Sett, P; Gallagher, J A

1999-11-01

Parathyroid hormone-related protein (PTHrP), in addition to the well-established role in endochrondral bone development, is believed to be an important mediator of cellular growth and differentiation in a number of non-bony tissues. To compare the immunohistochemical staining of vesical transitional epithelium to antibodies raised to synthetic peptides of PTHrP composed of amino acid sequences 43 - 52 and 127 - 138 in patients with spinal cord injury (SCI) and neuropathic bladder (n=14), and control patients with intact neuraxis and no history of bladder cancer (n=10). Male SCI patients registered with Regional Spinal Injuries Centre, Southport, England. Endoscopic cold cup biopsy from the trigone of the urinary bladder was taken from patients with SCI while they were undergoing a therapeutic procedure in the urinary bladder. The control samples of bladder biopsies were taken from the archives of the Department of Histopathology, District General Hospital, Southport. Immunohistochemistry was performed using rabbit antibodies raised against synthetic peptides of human PTHrP (43 - 52) and PTHrP (127 - 138). The biopsies were examined for immunostaining of transitional epithelium. Of the 14 biopsies of SCI patients, positive immunostaining using antibodies to both the PTHrP peptides was found in four cases; five biopsies showed positive immunostaining only to anti-PTHrP (43 - 52); and five biopsies showed no immunostaining with either of the PTHrP peptides. In contrast, transitional epithelium in the biopsy specimens of ten control subjects with no history of bladder cancer showed no immunostaining with either of the PTHrP peptides. This study revealed that the transitional epithelium of neuropathic urinary bladder exhibits increased predilection for positive immunohistochemical staining for PTHrP (43 - 52), and to a lesser extent, to PTHrP (127 - 138), as compared to the vesical transitional epithelium of able bodied individuals with no history of vesical malignancy. The possible role of PTHrP in the cellular differentiation of urothelium of neuropathic bladder, and thereby, in the pathogenesis of cystitis in SCI patients, needs to be explored.

Design and Evaluation of New Tc-99m-Labeled Lactam Bridge-Cyclized Alpha-MSH Peptides for Melanoma Imaging

PubMed Central

Guo, Haixun; Gallazzi, Fabio; Miao, Yubin

2013-01-01

The purpose of this study was to examine the melanoma targeting and imaging properties of new 99mTc-labeled lactam bridge-cyclized alpha-melanocyte stimulating hormone (α-MSH) peptides using bifunctional chelating agents. MAG3-GGNle-CycMSHhex, AcCG3-GGNle-CycMSHhex and HYNIC-GGNle-CycMSHhex peptides were synthesized and their melanocortin-1 (MC1) receptor binding affinities were determined in B16/F1 melanoma cells. The biodistribution of 99mTc-MAG3-GGNle-CycMSHhex, 99mTc-AcCG3-GGNle-CycMSHhex, 99mTc(CO)3-HYNIC-GGNle-CycMSHhex and 99mTc(EDDA)-HYNIC-GGNle-CycMSHhex were determined in B16/F1 melanoma-bearing C57 mice at 2 h post-injection to select a lead peptide for further evaluation. The melanoma targeting and imaging properties of 99mTc(EDDA)-HYNIC-GGNle-CycMSHhex were further examined because of its high melanoma uptake and fast urinary clearance. The IC50 values of MAG3-GGNle-CycMSHhex, AcCG3-GGNle-CycMSHhex and HYNIC-GGNle-CycMSHhex were 1.0 ± 0.05, 1.2 ± 0.19 and 0.6 ± 0.04 nM in B16/F1 melanoma cells, respectively. Among these four 99mTc-peptides, 99mTc(EDDA)-HYNIC-GGNle-CycMSHhex exhibited the highest melanoma uptake (14.14 ± 4.90% ID/g) and fastest urinary clearance (91.26 ± 1.96% ID) at 2 h post-injection. 99mTc(EDDA)-HYNIC-GGNle-CycMSHhex showed high tumor to normal organ uptake ratios except for the kidneys. The tumor/kidney uptake ratios of 99mTc(EDDA)-HYNIC-GGNle-CycMSHhex were 2.50 and 3.55 at 4 and 24 h post-injection. The melanoma lesions were clearly visualized by SPECT/CT using 99mTc(EDDA)-HYNIC-GGNle-CycMSHhex as an imaging probe at 2 h post-injection. Overall, high melanoma uptake coupled with fast urinary clearance of 99mTc(EDDA)-HYNIC-GGNle-CycMSHhex highlighted its potential for metastatic melanoma detection in the future. PMID:23418722

The impact of cathelicidin, the human antimicrobial peptide LL-37 in urinary tract infections.

PubMed

Babikir, Ibrahim H; Abugroun, Elsir A; Bilal, Naser Eldin; Alghasham, Abdullah Ali; Abdalla, Elmuataz Elmansi; Adam, Ishag

2018-01-08

The defense mechanisms of the urinary tract are attributed mainly to the innate immune system and the urinary tract urothelium which represent the first line of defense against invading pathogens and maintaining sterility of the urinary tract. There are only a few publications regarding cathelicidin (LL-37) and a urinary tract infection (UTI). This study was done to investigate the plasma and urine levels of human LL-37 in patients with UTI. A case-control study was conducted at Omdurman Hospital, Sudan during the period from August 2014 to May 2017. The cases were patients with confirmed UTI and the controls were healthy volunteers without UTI. Sociodemographic and clinical data were obtained from each participant using questionnaires. Urine cultures and antimicrobial susceptibility were tested. Plasma and urine levels of LL-37 were determined using an enzyme-linked immunosorbent assay (ELISA) kit. SPSS (version 16.0) was used for analyses. Cases and controls (87 in each arm) were matched according to their basic characteristics. Compared with controls, the median (inter-quartile) LL-37 level in plasma [2.100 (1.700-2.700) vs. 1.800 (1.000-2.200) ng/ml, P = 0.002] and in urine [0.900 (0.300-1.600) vs. 0.000 (0.000-1.000) ng/mg creatinine, P < 0.001] was significantly higher in cases. There was no significant difference in the median plasma [2.1 (1.7-2.9) vs. 2.000 (1.700-2.400) ng/ml, P = 0.561] and urine [0.850 (0.275-2.025) vs. 0.900 (0.250-1.350) ng/mg creatinine, P = 0.124]. The uropathogenic Escherichia coli (UPEC) was the predominant isolate, n = 38 (43.7%). LL-37 levels between the E. coli isolates and the other isolated organisms. There was no significant correlation between plasma and urine LL-37 levels (r = 0.221), even when the data of the cases were analyzed separately. LL-37 is notably increased among patients with UTI compared with normal control subjects. Severity of UTI increases the levels of LL-37. The increased level was not only in the patient's urine, but has also been observed in the patient's plasma. Detection of increased levels of LL-37 could help to differentiate subjects with suspected UTI. Accordingly, LL-37 could act as a good marker for diagnosing UTIs.

Role of Tyrosine Isomers in Acute and Chronic Diseases Leading to Oxidative Stress - A Review.

PubMed

Molnár, Gergő A; Kun, Szilárd; Sélley, Eszter; Kertész, Melinda; Szélig, Lívia; Csontos, Csaba; Böddi, Katalin; Bogár, Lajos; Miseta, Attila; Wittmann, István

2016-01-01

Oxidative stress plays a major role in the pathogenesis of a variety of acute and chronic diseases. Measurement of the oxidative stress-related end products may be performed, e.g. that of structural isomers of the physiological para-tyrosine, namely meta- and ortho-tyrosine, that are oxidized derivatives of phenylalanine. Recent data suggest that in sepsis, serum level of meta-tyrosine increases, which peaks on the 2(nd) and 3(rd) days (p<0.05 vs. controls), and the kinetics follows the intensity of the systemic inflammation correlating with serum procalcitonin levels. In a similar study subset, urinary meta-tyrosine excretion correlated with both need of daily insulin dose and the insulin-glucose product in non-diabetic septic cases (p<0.01 for both). Using linear regression model, meta-tyrosine excretion, urinary meta-tyrosine/para-tyrosine, urinary ortho-tyrosine/para-tyrosine and urinary (meta- + orthotyrosine)/ para-tyrosine proved to be markers of carbohydrate homeostasis. In a chronic rodent model, we tried to compensate the abnormal tyrosine isomers using para-tyrosine, the physiological amino acid. Rats were fed a standard high cholesterol-diet, and were given para-tyrosine or vehicle orally. High-cholesterol feeding lead to a significant increase in aortic wall meta-tyrosine content and a decreased vasorelaxation of the aorta to insulin and the glucagon-like peptide-1 analogue, liraglutide, that both could be prevented by administration of para-tyrosine. Concluding, these data suggest that meta- and ortho-tyrosine are potential markers of oxidative stress in acute diseases related to oxidative stress, and may also interfere with insulin action in septic humans. Competition of meta- and ortho-tyrosine by supplementation of para-tyrosine may exert a protective role in oxidative stress-related diseases.

Designer antibacterial peptides kill fluoroquinolone-resistant clinical isolates.

PubMed

Otvos, Laszlo; Wade, John D; Lin, Feng; Condie, Barry A; Hanrieder, Joerg; Hoffmann, Ralf

2005-08-11

A significant number of Escherichia coli and Klebsiella pneumoniae bacterial strains in urinary tract infections are resistant to fluoroquinolones. Peptide antibiotics are viable alternatives although these are usually either toxic or insufficiently active. By applying multiple alignment and sequence optimization steps, we designed multifunctional proline-rich antibacterial peptides that maintained their DnaK-binding ability in bacteria and low toxicity in eukaryotes, but entered bacterial cells much more avidly than earlier peptide derivatives. The resulting chimeric and statistical analogues exhibited 8-32 microg/mL minimal inhibitory concentration efficacies in Muller-Hinton broth against a series of clinical pathogens. Significantly, the best peptide, compound 5, A3-APO, retained full antibacterial activity in the presence of mouse serum. Across a set of eight fluoroquinolone-resistant clinical isolates, peptide 5 was 4 times more potent than ciprofloxacin. On the basis of the in vitro efficacy, toxicity, and pharmacokinetics data, we estimate that peptide 5 will be suitable for treating infections in the 3-5 mg/kg dose range.

A urinary peptide biomarker set predicts worsening of albuminuria in type 2 diabetes mellitus.

PubMed

Roscioni, S S; de Zeeuw, D; Hellemons, M E; Mischak, H; Zürbig, P; Bakker, S J L; Gansevoort, R T; Reinhard, H; Persson, F; Lajer, M; Rossing, P; Lambers Heerspink, H J

2013-02-01

Microalbuminuria is considered the first clinical sign of kidney dysfunction and is associated with a poor renal and cardiovascular prognosis in type 2 diabetes. Detection of patients who are prone to develop micro- or macroalbuminuria may represent an effective strategy to start or optimise therapeutic intervention. Here we assessed the value of a urinary proteomic-based risk score (classifier) in predicting the development and progression of microalbuminuria. We conducted a prospective case-control study. Cases (n = 44) and controls (n = 44) were selected from the PREVEND (Prevention of Renal and Vascular End-stage Disease) study and from the Steno Diabetes Center (Gentofte, Denmark). Cases were defined by transition from normo- to microalbuminuria or from micro- to macroalbuminuria over a follow-up of 3 years. Controls with no transitions in albuminuria were pair-matched for age, sex and albuminuria status. A model for the progression of albuminuria was built using a proteomic classifier based on 273 urinary peptides. The proteomic classifier was independently associated with transition to micro- or macroalbuminuria (OR 1.35 [95% CI 1.02, 1.79], p = 0.035). The classifier predicted the development and progression of albuminuria on top of albuminuria and estimated GFR (eGFR, area under the receiver operating characteristic [ROC] curve increase of 0.03, p = 0.002; integrated discrimination index [IDI]: 0.105, p = 0.002). Fragments of collagen and α-2-HS-glycoprotein showed significantly different expression between cases and controls. Although limited by the relatively small sample size, these results suggest that analysis of a urinary biomarker set enables early renal risk assessment in patients with diabetes. Further work is required to confirm the role of urinary proteomics in the prevention of renal failure in diabetes.

Deterioration of kidney function by the (pro)renin receptor blocker handle region peptide in aliskiren-treated diabetic transgenic (mRen2)27 rats.

PubMed

te Riet, Luuk; van den Heuvel, Mieke; Peutz-Kootstra, Carine J; van Esch, Joep H M; van Veghel, Richard; Garrelds, Ingrid M; Musterd-Bhaggoe, Usha; Bouhuizen, Angelique M; Leijten, Frank P J; Danser, A H Jan; Batenburg, Wendy W

2014-05-15

Dual renin-angiotensin system (RAS) blockade in diabetic nephropathy is no longer feasible because of the profit/side effect imbalance. (Pro)renin receptor [(P)RR] blockade with handle region peptide (HRP) has been reported to exert beneficial effects in various diabetic models in a RAS-independent manner. To what degree (P)RR blockade adds benefits on top of RAS blockade is still unknown. In the present study, we treated diabetic TGR(mREN2)27 rats, a well-established nephropathy model with high prorenin levels [allowing continuous (P)RR stimulation in vivo], with HRP on top of renin inhibition with aliskiren. Aliskiren alone lowered blood pressure and exerted renoprotective effects, as evidenced by reduced glomerulosclerosis, diuresis, proteinuria, albuminuria, and urinary aldosterone levels as well as diminished renal (P)RR and ANG II type 1 receptor expression. It also suppressed plasma and tissue RAS activity and suppressed cardiac atrial natriuretic peptide and brain natriuretic peptide expression. HRP, when given on top of aliskiren, did not alter the effects of renin inhibition on blood pressure, RAS activity, or aldosterone. However, it counteracted the beneficial effects of aliskiren in the kidney, induced hyperkalemia, and increased plasma plasminogen activator-inhibitor 1, renal cyclooxygenase-2, and cardiac collagen content. All these effects have been linked to (P)RR stimulation, suggesting that HRP might, in fact, act as a partial agonist. Therefore, the use of HRP on top of RAS blockade in diabetic nephropathy is not advisable. Copyright © 2014 the American Physiological Society.

Quantitative Evaluation of CART-Containing Cells in Urinary Bladder of Rats with Renovascular Hypertension

PubMed Central

Janiuk, I.; Kasacka, I.

2015-01-01

Recent biological advances make it possible to discover new peptides associated with hypertension. The cocaine- and amphetamine-regulated transcript (CART) is a known factor in appetite and feeding behaviour. Various lines of evidence suggest that this peptide participates not only in control of feeding behaviour but also in the regulation of the cardiovascular and sympathetic systems and blood pressure. The role of CART in blood pressure regulation led us to undertake a study aimed at analysing quantitative changes in CART-containing cells in urinary bladders (UB) of rats with renovascular hypertension. We used the Goldblatt model of arterial hypertension (two-kidney, one clip) to evaluate quantitative changes. This model provides researchers with a commonly used tool to analyse the renin-angiotensin system of blood pressure control and, eventually, to develop drugs for the treatment of chronic hypertension. The study was performed on sections of urinary bladders of rats after 3-, 14-, 28-, 42 and 91 days from hypertension induction. Immunohistochemical identification of CART cells was performed on paraffin for the UBs of all the study animals. CART was detected in the endocrine cells, especially numerous in the submucosa and muscularis layers, with a few found in the transitional epithelium and only occasionally in serosa. Hypertension significantly increased the number of CART-positive cells in the rat UBs. After 3 and 42 days following the procedure, statistically significantly higher numbers of CART-positive cells were identified in comparison with the control animals. The differences between the hypertensive rats and the control animals concerned not only the number density of CART-immunoreactive cells but also their localization. After a 6-week period, each of the rats subjected to the renal artery clipping procedure developed stable hypertension. CART appeared in numerous transitional epithelium cells. As this study provides novel findings, the question appears about the type of connection between hypertension and the functioning and activity of CART in the urinary tract (UT). The study gives rise to the assumption that high blood pressure can be a factor that intensifies CART secretion. In conclusion, the endocrine system of the urinary tract is modified by renovascular hypertension. This may affect the production of hormones and biologically active substances and contribute to the development of possible hypertension complications. In order to fully comprehend the role of the CART peptide in blood pressure regulation, further analyses are necessary. PMID:26150151

Quantitative evaluation of CART-containing cells in urinary bladder of rats with renovascular hypertension.

PubMed

Janiuk, I; Kasacka, I

2015-04-13

Recent biological advances make it possible to discover new peptides associated with hypertension. The cocaine- and amphetamine-regulated transcript (CART) is a known factor in appetite and feeding behaviour. Various lines of evidence suggest that this peptide participates not only in control of feeding behaviour but also in the regulation of the cardiovascular and sympathetic systems and blood pressure. The role of CART in blood pressure regulation led us to undertake a study aimed at analysing quantitative changes in CART-containing cells in urinary bladders (UB) of rats with renovascular hypertension. We used the Goldblatt model of arterial hypertension (two-kidney, one clip) to evaluate quantitative changes. This model provides researchers with a commonly used tool to analyse the renin-angiotensin system of blood pressure control and, eventually, to develop drugs for the treatment of chronic hypertension. The study was performed on sections of urinary bladders of rats after 3-, 14-, 28-, 42 and 91 days from hypertension induction. Immunohistochemical identification of CART cells was performed on paraffin for the UBs of all the study animals. CART was detected in the endocrine cells, especially numerous in the submucosa and muscularis layers, with a few found in the transitional epithelium and only occasionally in serosa. Hypertension significantly increased the number of CART-positive cells in the rat UBs. After 3 and 42 days following the procedure, statistically significantly higher numbers of CART-positive cells were identified in comparison with the control animals. The differences between the hypertensive rats and the control animals concerned not only the number density of CART-immunoreactive cells but also their localization. After a 6-week period, each of the rats subjected to the renal artery clipping procedure developed stable hypertension. CART appeared in numerous transitional epithelium cells. As this study provides novel findings, the question appears about the type of connection between hypertension and the functioning and activity of CART in the urinary tract (UT). The study gives rise to the assumption that high blood pressure can be a factor that intensifies CART secretion. In conclusion, the endocrine system of the urinary tract is modified by renovascular hypertension. This may affect the production of hormones and biologically active substances and contribute to the development of possible hypertension complications. In order to fully comprehend the role of the CART peptide in blood pressure regulation, further analyses are necessary.

Slowly progressive insulin-dependent diabetes mellitus associated with pernicious anemia.

PubMed

Kinoshita, Jun; Hata, Shoichi; Yamazaki, Hiroyuki; Tajima, Naoko

2010-01-01

A 59-year-old man was found to have diabetes mellitus five months after the diagnosis of pernicious anemia. Although the urinary C-peptide level corresponded to a non-insulin-dependent stage (39.9 microg/day), the markedly extremely elevated titers of GAD antibody suggested that this case very likely represented a non-insulin-dependent stage of slowly progressive insulin-dependent diabetes mellitus (SPIDDM). Because thyroid and adrenal functions were normal, this our case was not considered to be polyglandular autoimmune syndrome (PGAS). We report this case because patients with pernicious anemia and SPIDDM in the absence of PGAS are rare in Japan.

Expression and Antimicrobial Function of Beta-Defensin 1 in the Lower Urinary Tract

PubMed Central

Becknell, Brian; Spencer, John David; Carpenter, Ashley R.; Chen, Xi; Singh, Aspinder; Ploeger, Suzanne; Kline, Jennifer; Ellsworth, Patrick; Li, Birong; Proksch, Ehrhardt; Schwaderer, Andrew L.; Hains, David S.; Justice, Sheryl S.; McHugh, Kirk M.

2013-01-01

Beta defensins (BDs) are cationic peptides with antimicrobial activity that defend epithelial surfaces including the skin, gastrointestinal, and respiratory tracts. However, BD expression and function in the urinary tract are incompletely characterized. The purpose of this study was to describe Beta Defensin-1 (BD-1) expression in the lower urinary tract, regulation by cystitis, and antimicrobial activity toward uropathogenic Escherichia coli (UPEC) in vivo. Human DEFB1 and orthologous mouse Defb1 mRNA are detectable in bladder and ureter homogenates, and human BD-1 protein localizes to the urothelium. To determine the relevance of BD-1 to lower urinary tract defense in vivo, we evaluated clearance of UPEC by Defb1 knockout (Defb1 -/-) mice. At 6, 18, and 48 hours following transurethral UPEC inoculation, no significant differences were observed in bacterial burden in bladders or kidneys of Defb1 -/- and wild type C57BL/6 mice. In wild type mice, bladder Defb1 mRNA levels decreased as early as two hours post-infection and reached a nadir by six hours. RT-PCR profiling of BDs identified expression of Defb3 and Defb14 mRNA in murine bladder and ureter, which encode for mBD-3 and mBD-14 protein, respectively. MBD-14 protein expression was observed in bladder urothelium following UPEC infection, and both mBD-3 and mBD-14 displayed dose-dependent bactericidal activity toward UPEC in vitro. Thus, whereas mBD-1 deficiency does not alter bladder UPEC burden in vivo, we have identified mBD-3 and mBD-14 as potential mediators of mucosal immunity in the lower urinary tract. PMID:24204930

Factors Affecting Canagliflozin-Induced Transient Urine Volume Increase in Patients with Type 2 Diabetes Mellitus.

PubMed

Tanaka, Hiroyuki; Takano, Kazuhiko; Iijima, Hiroaki; Kubo, Hajime; Maruyama, Nobuko; Hashimoto, Toshio; Arakawa, Kenji; Togo, Masanori; Inagaki, Nobuya; Kaku, Kohei

2017-02-01

Sodium glucose co-transporter 2 (SGLT2) inhibitors exhibit diuretic activity, which is a possible mechanism underlying the cardiovascular benefit of these inhibitors. However, the osmotic diuresis-induced increase in urine volume, and the risk of dehydration have been of concern with SGLT2 inhibitor treatment. This study aimed to investigate the mechanism underlying SGLT2 inhibitor canagliflozin-induced diuresis in Japanese type 2 diabetes mellitus (T2DM) patients. Thirteen T2DM patients received a daily oral dose of 100 mg canagliflozin before breakfast for 6 days. Blood and urine samples were collected at predetermined time points. The primary endpoint was evaluation of correlations between changes from baseline in urine volume and factors that are known to affect urine volume and between actual urine volume and these factors. Canagliflozin transiently increased urine volume and urinary sodium excretion on Day 1 with a return to baseline levels thereafter. Canagliflozin administration increased urinary glucose excretion, which was sustained during repeated-dose administration. Plasma atrial natriuretic peptide (ANP) and N-terminal pro-b-type natriuretic peptide (NT-proBNP) levels decreased, while plasma renin activity increased. On Day 1 of treatment, changes in sodium and potassium excretion were closely correlated with changes in urine output. A post hoc multiple regression analysis showed changes in sodium excretion and water intake as factors that affected urine volume change at Day 1. Furthermore, relative to that at baseline, canagliflozin decreased blood glucose throughout the day and increased plasma total GLP-1 after breakfast. Canagliflozin induced transient sodium excretion and did not induce water intake at Day 1; hence, natriuresis rather than glucose-induced osmotic diuresis may be a major factor involved in the canagliflozin-induced transient increase in urine output. In addition, canagliflozin decreased plasma ANP and NT-proBNP levels and increased plasma renin activity, which may be a compensatory mechanism for sodium retention, leading to subsequent urine output recovery. UMIN000019462. Mitsubishi Tanabe Pharma Corporation.

Characterization of the tachykinin neurokinin-2 receptor in the human urinary bladder by means of selective receptor antagonists and peptidase inhibitors.

PubMed

Giuliani, S; Patacchini, R; Barbanti, G; Turini, D; Rovero, P; Quartara, L; Giachetti, A; Maggi, C A

1993-11-01

The tachykinin (NK2) receptor-mediating contraction of the human isolated bladder to NKA was investigated by studying the affinities of eight structurally different receptor-selective antagonists (linear peptides, cyclic peptides and pseudopeptides, nonpeptide NK2 receptor antagonists). The affinities of the antagonists were compared to those measured for the same ligands at the NK2 receptors previously characterized in the rabbit pulmonary artery and hamster trachea. In the presence of a cocktail of peptidase inhibitors (bestatin captopril and thiorphan, 1 microM each) no significant correlation was found between pA2 values measured in the human bladder vs. those measured in the other two NK2 receptor-bearing preparation. In the presence of the aminopeptidase inhibitor amastatin, however, pA2 values of linear antagonists bearing an N-terminal Asp residue MEN 10,207 and MEN 10,376 were significantly enhanced and these pA2 values were used for analysis; a significant correlation was found between pA2 values measured in the human urinary bladder and rabbit pulmonary artery. The pseudopeptide analog of NKA (4-10), MDL 28,564 which also bears a N-terminal Asp residue behaved as an agonist and its action was enhanced by amastatin. We conclude that the NK2 receptor-mediating contraction of the human urinary bladder smooth muscle is similar to that previously characterized in the rabbit pulmonary artery (NK2A receptor category); in the human bladder smooth muscle an amastatin-sensitive peptidase (possibly aminopeptidase A) limits biological activity of linear peptide derivatives of NKA bearing a N-terminal Asp residue.

Design and validation of an immunoaffinity LC-MS/MS assay for the quantification of a collagen type II neoepitope peptide in human urine: application as a biomarker of osteoarthritis.

PubMed

Nemirovskiy, Olga; Li, Wenlin Wendy; Szekely-Klepser, Gabriella

2010-01-01

Biomarkers play an increasingly important role for drug efficacy and safety evaluation in all stages of drug development. It is especially important to develop and validate sensitive and selective biomarkers for diseases where the onset of the disease is very slow and/or the disease progression is hard to follow, i.e., osteoarthritis (OA). The degradation of Type II collagen has been associated with the disease state of OA. Matrix metalloproteinases (MMPs) are enzymes that catalyze the degradation of collagen and therefore pursued as potential targets for the treatment of OA. Peptide biomarkers of MMP activity related to type II collagen degradation were identified and the presence of these peptides in MMP digests of human articular cartilage (HAC) explants and human urine were confirmed. An immunoaffinity LC/MS/MS assay for the quantification of the most abundant urinary type II collagen neoepitope (uTIINE) peptide, a 45-mer with 5 HO-proline residues was developed and clinically validated. The assay has subsequently been applied to analyze human urine samples from clinical studies. We have shown that the assay is able to differentiate between symptomatic OA and normal subjects, indicating that uTIINE can be used as potential biomarker for OA. This chapter discusses the assay procedure and provides information on the validation experiments used to evaluate the accuracy, precision, and selectivity data with attention to the specific challenges related to the quantification of endogenous protein/peptide biomarker analytes. The generalized approach can be used as a follow-up to studies whereby proteomics-based urinary biomarkers are identified and an assay needs to be developed. Considerations for the validation of such an assay are described.

PH-sauvagine from the skin secretion of Phyllomedusa hypochondrialis: A novel CRF-like peptide with smooth muscle contraction activity.

PubMed

Zhou, Yu; Shaw, Chris; Chen, Tianbao

2015-09-15

Amphibian skin, and particularly that of south/Central American phyllomedusine frogs, is supposed to be "a huge factory and store house of a variety of active peptides". The 40 amino acid amphibian CRF-like peptide, sauvagine, is a prototype member of a unique family of these Phyllomedusa skin peptides. In this study, we describe for the first time the structure of a mature novel peptide from the skin secretion of the South American orange-legged leaf frog, Phyllomedusa hypochondrialis, which belongs to the amphibian CRF/sauvagine family. Partial amino acid sequence from the N-terminal was obtained by automated Edman degradation with the following structure: pGlu-GPPISIDLNMELLRNMIEI-. The biosynthetic precursor of this novel sauvagine peptide, consisted of 85 amino acid residues and was deduced from cDNA library constructed from the same skin secretion. Compared with the standard sauvagine from the frog, Phyllomedusa sauvagei, this novel peptide was found to exert similar contraction effects on isolated guinea-pig colon and rat urinary bladder smooth muscle preparations. Copyright © 2015 Elsevier Ltd. All rights reserved.

The Effects of Tempol on Cyclophosphamide-Induced Oxidative Stress in Rat Micturition Reflexes

PubMed Central

Gonzalez, Eric J.; Peterson, Abbey; Malley, Susan; Daniel, Mitchel; Lambert, Daniel; Kosofsky, Michael; Vizzard, Margaret A.

2015-01-01

We hypothesized that cyclophosphamide- (CYP-) induced cystitis results in oxidative stress and contributes to urinary bladder dysfunction. We determined (1) the expression of oxidative stress markers 3-nitrotyrosine (3-NT), reactive oxygen species (ROS)/reactive nitrogen species (RNS), inflammatory modulators, neuropeptides calcitonin gene-related peptide (CGRP), substance P (Sub P), and adenosine triphosphate (ATP) that contribute to the inflammatory process in the urinary tract and (2) the functional role of oxidative stress in urinary bladder dysfunction with an antioxidant, Tempol, (1 mM in drinking water) combined with conscious cystometry. In CYP-treated (4 hr or 48 hr; 150 mg/kg, i.p.) rats, ROS/RNS and 3-NT significantly (P ≤ 0.01) increased in urinary bladder. CYP treatment increased ATP, Sub P, and CGRP expression in the urinary bladder and cystometric fluid. In CYP-treated rats, Tempol significantly (P ≤ 0.01) increased bladder capacity and reduced voiding frequency compared to CYP-treated rats without Tempol. Tempol significantly (P ≤ 0.01) reduced ATP expression, 3-NT, and ROS/RNS expression in the urinary tract of CYP-treated rats. These studies demonstrate that reducing oxidative stress in CYP-induced cystitis improves urinary bladder function and reduces markers of oxidative stress and inflammation. PMID:25973443

Analysis of urine composition in type Ⅱ diabetic mice after intervention therapy using holothurian polypeptides

NASA Astrophysics Data System (ADS)

Li, Yanyan; Xu, Jiajie; Su, Xiurong

2017-07-01

Hydrolysates and peptide fractions (PF) obtained from sea cucumber with commercial enzyme were studied on the hpyerglycemic and renal protective effects on db/db rats using urine metabolomics. Compared with the control group the polypeptides from the two species could significantly reduce the urine glucose and urea. We also tried to address the compositions of highly expressed urinary proteins using a proteomics approach. They were serum albumins, AMBP proteins, negative trypsin, elastase and urinary protein, GAPDH, a receptor of urokinase-type plasminogen activator (uPAR), and Ig kappa chain C region. We used the electronic nose to quickly detect changes in the volatile substances in mice urine after holothurian polypeptides fed, and the results show it can identify the difference between treatment groups with the control group without overlapping. The protein express mechanism of holothurian polypeptides treating diabetes was discussed, and we suggested these two peptides with the hypoglycemic and renal protective activity might be utilized as nutraceuticals.

Design and evaluation of new Tc-99m-labeled lactam bridge-cyclized alpha-MSH peptides for melanoma imaging.

PubMed

Guo, Haixun; Gallazzi, Fabio; Miao, Yubin

2013-04-01

The purpose of this study was to examine the melanoma targeting and imaging properties of new (99m)Tc-labeled lactam bridge-cyclized alpha-melanocyte stimulating hormone (α-MSH) peptides using bifunctional chelating agents. MAG3-GGNle-CycMSH(hex), AcCG3-GGNle-CycMSH(hex), and HYNIC-GGNle-CycMSH(hex) peptides were synthesized, and their melanocortin-1 (MC1) receptor binding affinities were determined in B16/F1 melanoma cells. The biodistribution of (99m)Tc-MAG3-GGNle-CycMSH(hex), (99m)Tc-AcCG3-GGNle-CycMSH(hex), (99m)Tc(CO)3-HYNIC-GGNle-CycMSH(hex), and (99m)Tc(EDDA)-HYNIC-GGNle-CycMSH(hex) were determined in B16/F1 melanoma-bearing C57 mice at 2 h postinjection to select a lead peptide for further evaluation. The melanoma targeting and imaging properties of (99m)Tc(EDDA)-HYNIC-GGNle-CycMSH(hex) were further examined because of its high melanoma uptake and fast urinary clearance. The IC50 values of MAG3-GGNle-CycMSH(hex), AcCG3-GGNle-CycMSH(hex), and HYNIC-GGNle-CycMSH(hex) were 1.0 ± 0.05, 1.2 ± 0.19, and 0.6 ± 0.04 nM in B16/F1 melanoma cells, respectively. Among these four (99m)Tc-peptides, (99m)Tc(EDDA)-HYNIC-GGNle-CycMSH(hex) exhibited the highest melanoma uptake (14.14 ± 4.90% ID/g) and fastest urinary clearance (91.26 ± 1.96% ID) at 2 h postinjection. (99m)Tc(EDDA)-HYNIC-GGNle-CycMSH(hex) showed high tumor to normal organ uptake ratios except for the kidneys. The tumor/kidney uptake ratios of (99m)Tc(EDDA)-HYNIC-GGNle-CycMSH(hex) were 2.50 and 3.55 at 4 and 24 h postinjection. The melanoma lesions were clearly visualized by SPECT/CT using (99m)Tc(EDDA)-HYNIC-GGNle-CycMSH(hex) as an imaging probe at 2 h postinjection. Overall, high melanoma uptake coupled with fast urinary clearance of (99m)Tc(EDDA)-HYNIC-GGNle-CycMSH(hex) highlighted its potential for metastatic melanoma detection in the future.

Clinical significance of serum and urinary HER2/neu protein levels in primary non-muscle invasive bladder cancer.

PubMed

Arikan, Ozgur; Yýldýrým, Asýf; Ýsbilen, Banu; Canakci, Cengiz; Atýs, Gokhan; Gurbuz, Cenk; Erol, Bulent; Ýsman, Ferruh Kemal; Ozkanli, Seyma; Caskurlu, Turhan

2015-01-01

We aimed to compare serum and urinary HER2/neu levels between healthy control group and patients with non-muscle invasive bladder cancer. Additionally, we evaluated relationship of HER2/neu levels with tumor stage, grade, recurrence and progression. Fourty-four patients with primary non-muscle invasive bladder tumors (Group 2) and 40 healthy control group (Group 1) were included the study. Blood and urinary samples were collected from all patients and HER2/neu levels were measured by ELISA method. Blood and urinary HER2/neu levels and additionally, ratio of urinary HER2/neu levels to urinary creatinine levels were recorded. Demographic data and tumor characteristics were recorded. Mean serum HER2/neu levels were similar between two groups and statistically significant difference wasn't observed. Urinary HER2/neu levels were significantly higher in group 2 than group 1. Ratio of urinary HER2/neu to urinary creatinine was significantly higher in group 2 than group 1, (p=0,021). Serum and urinary HER2/ neu levels were not associated with tumor stage, grade, recurrence and progression while ratio of urinary HER2/neu to urinary creatinin levels were significantly higher in high-grade tumors. HER2/neu, the sensitivity of the test was found to be 20.5%, and the specificity was 97.5%, also for the urinary HER2/neu/urinary creatinine ratio, the sensitivity and specificity of the test were found to be 31.8% and 87.5%, respectively. Urinary HER2/neu and ratio of urinary creatinine urine were significantly higher in patients with bladder cancer compared to healthy subjects. Large series and controlled studies are needed for use as a tumor marker.

Urinary Peptides As a Novel Source of T Cell Allergen Epitopes

PubMed Central

da Silva Antunes, Ricardo; Pham, John; McMurtrey, Curtis; Hildebrand, William H.; Phillips, Elizabeth; Mallal, Simon; Sidney, John; Busse, Paula; Peters, Bjoern; Schulten, Véronique; Sette, Alessandro

2018-01-01

Mouse allergy in both laboratory workers and in inner-city children is associated with allergic rhinitis and asthma, posing a serious public health concern. Urine is a major source of mouse allergens, as mice spray urine onto their surroundings, where the proteins dry up and become airborne on dust particles. Here, we tested whether oligopeptides that are abundant in mouse urine may contribute to mouse allergic T cell response. Over 1,300 distinct oligopeptides were detected by mass spectrometry analysis of the low molecular weight filtrate fraction of mouse urine (LoMo). Posttranslationally modified peptides were common, accounting for almost half of total peptides. A pool consisting of 225 unique oligopeptides of 13 residues or more in size identified within was tested for its capacity to elicit T cell reactivity in mouse allergic donors. Following 14-day in vitro stimulation of PBMCs, we detected responses in about 95% of donors tested, directed against 116 distinct peptides, predominantly associated with Th2 cytokines (IL-5). Peptides from non-urine related proteins such as epidermal growth factor, collagen, and Beta-globin accounted for the highest response (15.9, 9.1, and 8.1% of the total response, respectively). Peptides derived from major urinary proteins (MUPs), kidney androgen-regulated protein (KAP), and uromodulin were the main T cell targets from kidney or urine related sources. Further ex vivo analysis of enrichment of 4-1BB expressing cells demonstrated that LoMo pool-specific T cell reactivity can be detected directly ex vivo in mouse allergic but not in non-allergic donors. Further cytometric analysis of responding cells revealed a bone fide memory T cell phenotype and confirmed their Th2 polarization. Overall, these data suggest that mouse urine-derived oligopeptides are a novel target for mouse allergy-associated T cell responses, which may contribute to immunopathological mechanisms in mouse allergy. PMID:29755469

A review of the critical role of vitamin D in the functioning of the immune system and the clinical implications of vitamin D deficiency.

PubMed

Schwalfenberg, Gerry K

2011-01-01

This review looks at the critical role of vitamin D in improving barrier function, production of antimicrobial peptides including cathelicidin and some defensins, and immune modulation. The function of vitamin D in the innate immune system and in the epithelial cells of the oral cavity, lung, gastrointestinal system, genito-urinary system, skin and surface of the eye is discussed. Clinical conditions are reviewed where vitamin D may play a role in the prevention of infections or where it may be used as primary or adjuvant treatment for viral, bacterial and fungal infections. Several conditions such as tuberculosis, psoriasis, eczema, Crohn's disease, chest infections, wound infections, influenza, urinary tract infections, eye infections and wound healing may benefit from adequate circulating 25(OH)D as substrate. Clinical diseases are presented in which optimization of 25(OH)D levels may benefit or cause harm according to present day knowledge. The safety of using larger doses of vitamin D in various clinical settings is discussed. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Autistic Syndromes and Diet: A Follow-Up Study.

ERIC Educational Resources Information Center

Knivsberg, Ann-Mari; And Others

1995-01-01

Fifteen subjects ages 6 to 22 years with autistic syndromes and pathological urine patterns with increased urinary peptides were given diets free of gluten and casein and were evaluated at 1 and 4 years. Normalization of urine patterns, a decrease in odd behavior, and improvement in communication skills were found. (SLD)

MODES OF ACTION FOR THE CARCINOGENICITY AND TOXICITY OF ARSENIC - MOVING TOWARDS A MORE QUANTITATIVE RISK ASSESSMENT

EPA Science Inventory

Arsenic exposures can lead to human tumors in skin, lung, urinary bladder, kidney and liver. Three likely initial stages of arsenical¬macromolecular interaction are (1) binding of trivalent arsenicals to sulfhydryl groups of peptides and proteins, (2) arsenical-induced generation...

Polymerization-Incompetent Uromodulin in the Pregnant Stroke-Prone Spontaneously Hypertensive Rat

PubMed Central

Mary, Sheon; Small, Heather Yvonne; Siwy, Justyna; Mullen, William; Giri, Ashok

2017-01-01

The kidney is centrally involved in blood pressure regulation and undergoes extensive changes during pregnancy. Hypertension during pregnancy may result in an altered urinary peptidome that could be used to indicate new targets of therapeutic or diagnostic interest. The stroke-prone spontaneously hypertensive rat (SHRSP) is a model of maternal chronic hypertension. Capillary electrophoresis-mass spectrometry was conducted to interrogate the urinary peptidome in SHRSP and the control Wistar–Kyoto strain at three time points: prepregnancy and gestational days 12 and 18. The comparison within and between the Wistar–Kyoto and SHRSP peptidome at all time points detected 123 differentially expressed peptides (fold change >1.5; P<0.05). Sequencing of these peptides identified fragments of collagen α-chains, albumin, prothrombin, actin, serpin A3K, proepidermal growth factor, and uromodulin. Uromodulin peptides showed a pregnancy-specific alteration in SHRSP with a 7.8-fold (P<0.01) and 8.8-fold (P<0.05) increase at gestational days 12 and 18, respectively, relative to the Wistar–Kyoto. Further investigation revealed that these peptides belonged to the polymerization-inhibitory region of uromodulin. Two forms of uromodulin (polymerization competent and polymerization incompetent) were found in urine from both Wistar–Kyoto and SHRSP, where the polymerization-incompetent form was increased in a pregnancy-specific manner in SHRSP. Nifedipine-treated pregnant SHRSP showed only polymerization-competent uromodulin, indicating that calcium may be mechanistically involved in uromodulin polymerization. This study highlights, for the first time, a potential role of uromodulin and its polymerization in hypertensive pregnancy. PMID:28348009

The characterisation of novel secreted Ly-6 proteins from rat urine by the combined use of two-dimensional gel electrophoresis, microbore high performance liquid chromatography and expressed sequence tag data.

PubMed

Southan, Christopher; Cutler, Paul; Birrell, Helen; Connell, John; Fantom, Kenneth G M; Sims, Matthew; Shaikh, Narjis; Schneider, Klaus

2002-02-01

A proteomic study of rat urine was undertaken using two-dimensional gel electrophoresis, microbore high performance liquid chromatography, mass spectrometry and N-terminal sequencing. Five known urinary proteins were identified but two novel peptide fragments matched a large number of rat expressed sequence tags (ESTs) from a liver library. By combining protein chemical and nucleotide data, two 101-residue open reading frames with 90% amino acid identity were determined, rat urinary protein 1 (RUP-1) and RUP-2. The data established signal peptide removal and provided evidence for N-glycosylation. A third related sequence, rat spleen protein (RSP-1) was confirmed from EST searches. These three proteins have been submitted to SWISS-PROT as P81827, P81828 and Q9QXN2, respectively. A fourth novel homologue was found in porcine and bovine ESTs from embryo libraries. Alignment with known homologues showed conserved cysteine positions characteristic of a secreted subfamily of Ly-6 proteins. In two cases, antineoplastic urinary protein and caltrin, these homologues have unverified functional annotations. The RUP sequences showed high scoring matches to three unrelated rat mRNAs subsequently established to be chimeric. Two of these share extended sectional identity to RUP-1 but the third may represent another novel Ly-6 homologue. These chimeras have caused serious annotation errors in secondary databases.

Increased urinary levels of tissue polypeptide specific antigen (TPS) in alcoholics.

PubMed

Barros, Paula; Gonzalez-Quintela, Arturo; Mella, Carmen; Perez, Luis-Fernando

2006-01-01

Urinary levels of tissue polypeptide specific antigen (TPS, cytokeratin-18) have been proposed as a marker of urothelial malignancies. Previous studies have shown that serum TPS levels are elevated in alcoholics. This study was designed to determine whether alcoholics had elevated urinary TPS levels as well. Serum and urinary TPS levels were determined in 24 alcoholics and 15 healthy controls by means of a commercial chemiluminiscent immunoassay. Serum TPS levels were higher in alcoholics than in controls (median 332 U/L, range 51-21241 U/L versus median 17 U/L, range 15-65 U/L, respectively, p<0.001). Urinary TPS levels were also higher in alcoholics than in controls (median 244 U/L, range 22-1267 U/L versus median 66.5 U/L, range 15-600 U/L, respectively, p=0.001). Urinary TPS levels were correlated with serum TPS levels in alcoholics. Urinary TPS levels are elevated in alcoholics. Consequently, the specificity of urinary TPS as a tumor marker may be limited in alcoholics.

[Mechanisms of urinary tract sterility maintenance].

PubMed

Okrągła, Emilia; Szychowska, Katarzyna; Wolska, Lidia

2014-06-02

Physiologically, urine and the urinary tract are maintained sterile because of physical and chemical properties of urine and the innate immune system's action. The urinary tract is constantly exposed to the invasion of microorganisms from the exterior environment, also because of the anatomical placement of the urethra, in the vicinity of the rectum. Particularly vulnerable to urinary tract infections (UTI) are women (an additional risk factor is pregnancy), but also the elderly and children. The main pathogens causing UTI are bacteria; in 70-95% of cases it is the bacterium Escherichia coli. Infections caused by viruses and fungi are less common and are associated with decreased immunity, pharmacotherapy, or some diseases. Bacteria have evolved a number of factors that facilitate the colonization of the urinary tract: the cover and cell membrane antigens O and K1, lipopolysaccharide (LPS), fimbriae, pile and cilia. On the other hand, the human organism has evolved mechanisms to hinder colonization of the urinary tract: mechanisms arising from the anatomical structure of the urinary tract, the physicochemical properties of the urine and the activity of the innate immune system, also known as non-specific, which isolates and destroys pathogens using immunological processes, and the mechanisms for release of antimicrobial substances such as Tamm-Horsfall protein, mucopolysaccharides, immunoglobulins IgA and IgG, lactoferrin, lipocalin, neutrophils, cytokines and antimicrobial peptides. This review aims to analyze the state of knowledge on the mechanisms to maintain the sterility of the urinary tract used by the human organism and bacterial virulence factors to facilitate the colonization of the urinary tract.

IMAC fractionation in combination with LC-MS reveals H2B and NIF-1 peptides as potential bladder cancer biomarkers.

PubMed

Frantzi, Maria; Zoidakis, Jerome; Papadopoulos, Theofilos; Zürbig, Petra; Katafigiotis, Ioannis; Stravodimos, Konstantinos; Lazaris, Andreas; Giannopoulou, Ioanna; Ploumidis, Achilles; Mischak, Harald; Mullen, William; Vlahou, Antonia

2013-09-06

Improvement in bladder cancer (BC) management requires more effective diagnosis and prognosis of disease recurrence and progression. Urinary biomarkers attract special interest because of the noninvasive means of urine collection. Proteomic analysis of urine entails the adoption of a fractionation methodology to reduce sample complexity. In this study, we applied immobilized metal affinity chromatography in combination with high-resolution LC-MS/MS for the discovery of native urinary peptides potentially associated with BC aggressiveness. This approach was employed toward urine samples from patients with invasive BC, noninvasive BC, and benign urogenital diseases. A total of 1845 peptides were identified, corresponding to a total of 638 precursor proteins. Specific enrichment for proteins involved in nucleosome assembly and for zinc-finger transcription factors was observed. The differential expression of two candidate biomarkers, histone H2B and NIF-1 (zinc finger 335) in BC, was verified in independent sets of urine samples by ELISA and by immunohistochemical analysis of BC tissue. The results collectively support changes in the expression of both of these proteins with tumor progression, suggesting their potential role as markers for discriminating BC stages. In addition, the data indicate a possible involvement of NIF-1 in BC progression, likely as a suppressor and through interactions with Sox9 and HoxA1.

Urinary renin, but not angiotensinogen or aldosterone, reflects the renal renin-angiotensin-aldosterone system activity and the efficacy of renin-angiotensin-aldosterone system blockade in the kidney.

PubMed

van den Heuvel, Mieke; Batenburg, Wendy W; Jainandunsing, Sjaam; Garrelds, Ingrid M; van Gool, Jeanette M G; Feelders, Richard A; van den Meiracker, Anton H; Danser, A H Jan

2011-11-01

To study which renin-angiotensin-aldosterone system (RAAS) component best reflects renal RAAS activity. We measured urinary and plasma renin, prorenin, angiotensinogen, aldosterone, albumin and creatinine in 101 diabetic and nondiabetic patients with or without hypertension. Plasma prorenin was elevated in diabetic patients. Urinary prorenin was undetectable. Urinary albumin and renin were higher in diabetic patients. Men had higher plasma renin/prorenin levels, and lower plasma angiotensinogen levels than women. Plasma creatinine and albumin were also higher in men. Urinary RAAS components showed no sexual dimorphism, whereas urinary creatinine and albumin were higher in men. Angiotensin-converting enzyme inhibitors and angiotensin II type 1 receptor blockers increased plasma renin and decreased plasma angiotensinogen, without altering plasma aldosterone. In contrast, in urine, these drugs decreased renin and aldosterone without affecting angiotensinogen. When analyzing all patients together, urinary angiotensinogen excretion closely mimicked that of albumin, whereas urinary angiotensinogen and albumin levels both were 0.05% or less of their concomitant plasma levels. This may reflect the identical glomerular filtration and tubular handling of both proteins, which have a comparable molecular weight. In contrast, urinary renin excretion did not correlate with urinary albumin excretion, and the urinary/plasma concentration ratio of renin was more than 200 times the ratio of albumin, despite its comparable molecular weight. Urinary aldosterone excretion closely followed urinary creatinine excretion. The increased urinary renin levels in diabetes and the decreased urinary renin levels following RAAS blockade, occurring independently of changes in plasma renin, reflect the activated renal RAAS in diabetes and the success of RAAS blockade in the kidney, respectively. Urinary renin, therefore, more closely reflects renal RAAS activity than urinary angiotensinogen or aldosterone.

Decreased Bone Mineral Density in Prader-Willi Syndrome: Comparison With Obese Subjects

PubMed Central

Butler, Merlin G.; Haber, Lawrence; Mernaugh, Ray; Carlson, Michael G.; Price, Ron; Feurer, Irene D.

2016-01-01

Bone density, anthropometric data, and markers of bone turnover were collected on 21 subjects diagnosed with Prader-Willi syndrome (PWS) and compared with 9 subjects with obesity of unknown cause. In addition, urinary N-telopeptide levels were obtained in all subjects. N-telopeptides are the peptide fragments of type I collagen, the major bone matrix material. During periods of active bone degradation or high bone turnover, high levels of N-telopeptides are excreted in the urine. However, no significant difference was detected in the urinary N-telopeptide levels when corrected for creatinine excretion (raw or transformed data) between our subjects with obesity or PWS and the observed effect size of the between-group difference was small. Although N-telopeptide levels were higher but not significantly different in the subjects with PWS compared with obese controls, the subjects with PWS had significantly decreased total bone and spine mineral density and total bone mineral content (all P < 0.001). No differences in N- telopeptide levels or bone mineral density were observed between subjects with PWS and chromosome 15q deletion or maternal disomy. Thus, decreased bone mineral density in subjects with PWS may relate to the lack of depositing bone mineral during growth when bones are becoming more dense (e.g., during adolescence), possibly because of decreased production of sex or growth hormones and/or long-standing hypotonia. It may not be caused by loss, or active degradation, of bone matrix measurable by the methods described in this study further supporting the possible need for hormone therapy during adolescence. PMID:11745993

NOX2-mediated arterial dysfunction in smokers: acute effect of dark chocolate.

PubMed

Loffredo, Lorenzo; Carnevale, Roberto; Perri, Ludovica; Catasca, Elisa; Augelletti, Teresa; Cangemi, Roberto; Albanese, Fabiana; Piccheri, Cristina; Nocella, Cristina; Pignatelli, Pasquale; Violi, Francesco

2011-11-01

Cocoa seems to exert artery dilatation via oxidative stress inhibition but the mechanism is still unclear. To investigate whether in smokers, dark chocolate elicits artery dilatation via down-regulation of NOX2, the catalytic core of NADPH oxidase. Flow-mediated dilatation (FMD), oxidative stress (as assessed by urinary isoprostanes excretion), nitric oxide generation (as assessed by serum levels of nitrite/nitrate (NOx)), NOX2 activity (as assessed by blood levels of soluble NOX2 derived peptide (sNOX2-dp)) and serum epicatechin were studied in 20 smokers and 20 healthy subjects (HS) in a crossover, single-blind study. Patients were randomly allocated to 40 g dark chocolate (>85% cocoa) or 40 g of milk chocolate (≤35% cocoa). FMD, urinary isoprostanes, NOx and sNOX2-dp were assessed at baseline and 2 h after chocolate ingestion. Smokers had lower FMD and NOx and higher sNOX2-dp compared to HS. After dark chocolate intake, urinary isoprostanes and sNOX2-dp significantly decreased and FMD and NOx significantly increased in smokers but not in HS. No changes of the above variables were observed after milk chocolate intake. Multiple linear regression analysis showed that in smokers the only independent predictive variable associated with a change in FMD was a change in sNOX2-dp. Serum epicatechin increased in either group only after dark chocolate intake, reaching values higher than 0.1 μM. Platelets from smokers (n=5), but not from HS (n=5), showed lower p47(phox) translocation to platelet membrane and higher NOx when incubated with 0.1-10 μM epicatechin. Results suggest that in smokers, cocoa enhances artery dilatation by lowering of NOX2 activation.

Quantification of free and total desmosine and isodesmosine in human urine by liquid chromatography tandem mass spectrometry: a comparison of the surrogate-analyte and the surrogate-matrix approach for quantitation.

PubMed

Ongay, Sara; Hendriks, Gert; Hermans, Jos; van den Berge, Maarten; ten Hacken, Nick H T; van de Merbel, Nico C; Bischoff, Rainer

2014-01-24

In spite of the data suggesting the potential of urinary desmosine (DES) and isodesmosine (IDS) as biomarkers for elevated lung elastic fiber turnover, further validation in large-scale studies of COPD populations, as well as the analysis of longitudinal samples is required. Validated analytical methods that allow the accurate and precise quantification of DES and IDS in human urine are mandatory in order to properly evaluate the outcome of such clinical studies. In this work, we present the development and full validation of two methods that allow DES and IDS measurement in human urine, one for the free and one for the total (free+peptide-bound) forms. To this end we compared the two principle approaches that are used for the absolute quantification of endogenous compounds in biological samples, analysis against calibrators containing authentic analyte in surrogate matrix or containing surrogate analyte in authentic matrix. The validated methods were employed for the analysis of a small set of samples including healthy never-smokers, healthy current-smokers and COPD patients. This is the first time that the analysis of urinary free DES, free IDS, total DES, and total IDS has been fully validated and that the surrogate analyte approach has been evaluated for their quantification in biological samples. Results indicate that the presented methods have the necessary quality and level of validation to assess the potential of urinary DES and IDS levels as biomarkers for the progression of COPD and the effect of therapeutic interventions. Copyright © 2014 Elsevier B.V. All rights reserved.

Long-term AT1 receptor blockade improves metabolic function and provides renoprotection in Fischer-344 rats.

PubMed

Gilliam-Davis, Shea; Payne, Valerie S; Kasper, Sherry O; Tommasi, Ellen N; Robbins, Michael E; Diz, Debra I

2007-09-01

Fischer-344 (F344) rats exhibit proteinuria and insulin resistance in the absence of hypertension as they age. We determined the effects of long-term (1 yr) treatment with the angiotensin (ANG) II type 1 (AT(1)) receptor blocker L-158,809 on plasma and urinary ANG peptide levels, systolic blood pressure (SBP), and indexes of glucose metabolism in 15-mo-old male F344 rats. Young rats at 3 mo of age (n = 8) were compared with two separate groups of older rats: one control group (n = 7) and one group treated with L-158,809 (n = 6) orally (20 mg/l) for 1 yr. SBP was not different between control and treated rats but was higher in young rats. Serum leptin, insulin, and glucose levels were comparable between treated and young rats, whereas controls had higher glucose and leptin with a similar trend for insulin. Plasma ANG I and ANG II were higher in treated than untreated young or older rats, as evidence of effective AT(1) receptor blockade. Urinary ANG II and ANG-(1-7) were higher in controls compared with young animals, and treated rats failed to show age-related increases. Protein excretion was markedly lower in treated and young rats compared with control rats (young: 8 +/- 2 mg/day vs. control: 129 +/- 51 mg/day vs. treated: 9 +/- 3 mg/day, P < 0.05). Long-term AT(1) receptor blockade improves metabolic parameters and provides renoprotection. Differential regulation of systemic and intrarenal (urinary) ANG systems occurs during blockade, and suppression of the intrarenal system may contribute to reduced proteinuria. Thus, insulin resistance, renal injury, and activation of the intrarenal ANG system during early aging in normotensive animals can be averted by renin-ANG system blockade.

Dose-response relationship between urinary polycyclic aromatic hydrocarbons metabolites and urinary 8-hydroxy-2'-deoxyguanosine in a Chinese general population.

PubMed

Sun, Huizhen; Hou, Jian; Zhou, Yun; Yang, Yuqing; Cheng, Juan; Xu, Tian; Xiao, Lili; Chen, Weihong; Yuan, Jing

2017-05-01

Association of exposure to polycyclic aromatic hydrocarbons (PAHs) with increased urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG) formation has been reported in occupational population and children. However, studies on the association between them in general population are limited. A total of 1864 eligible subjects from the baseline Wuhan participants of the Wuhan-Zhuhai Cohort Study (n = 3053) were included in this study, after excluding individuals with certain disease and missing data on urinary monohydroxy PAHs (OH-PAHs) and 8-OHdG levels. Urinary monohydroxy PAHs and 8-OHdG levels were measured by gas chromatography-mass spectrometry and high performance liquid chromatography-electrochemical detection, respectively. Association of urinary OH-PAHs with urinary 8-OHdG was analyzed by multiple linear regression analysis. We found a dose-dependent relationship between urinary PAHs metabolites and urinary 8-OHdG (p < 0.05 for all). Furthermore, more evidence for the association of total concentrations of urinary OH-PAHs with 8-OHdG levels were observed in individuals with normal body mass index or central obesity (p < 0.01 for all). There was a dose-dependent relationship between urinary OH-PAHs levels and urinary 8-OHdG levels among a general Chinese population. Exposure to background PAHs may have a greater influence on urinary 8-OHdG levels in individuals with central obesity. Copyright © 2017 Elsevier Ltd. All rights reserved.

Different values of urinary fractionated metanephrines after unilateral adrenalectomy for pheochromocytoma according to time intervals after surgery.

PubMed

Cho, Yoon Y; Kim, Young N; Kim, Jung-Han; Jeong, Byong C; Lee, Soo-Youn; Kim, Jae H

2017-01-01

Background After adrenalectomy, urinary fractionated metanephrine concentrations are expected to be reduced. However, there are few studies suggesting cut-offs for adrenalectomy patients. Methods Urinary metanephrine and normetanephrine concentrations in adrenalectomy patients and two controls were compared and hormonal concentrations were evaluated via time intervals after surgery. Results The median urinary metanephrine level after unilateral adrenalectomy was lower than that of the non-pheochromocytoma controls but comparable to healthy controls. Urinary normetanephrine concentrations did not differ between adrenalectomy patients and non-pheochromocytoma controls, although both group had levels higher than those of healthy controls. The median urinary normetanephrine level in the immediate postoperative period was higher than in the later period. Conclusions Urinary metanephrine concentrations were lower after adrenalectomy, but urinary normetanephrine concentrations were not changed compared with the non-pheochromocytoma controls. However, urinary normetanephrine concentrations in the patient group were higher than levels in the heathy controls.

Identification of ageing-associated naturally occurring peptides in human urine

PubMed Central

Nkuipou-Kenfack, Esther; Bhat, Akshay; Klein, Julie; Jankowski, Vera; Mullen, William; Vlahou, Antonia; Dakna, Mohammed; Koeck, Thomas; Schanstra, Joost P.; Zürbig, Petra; Rudolph, Karl L.; Schumacher, Björn; Pich, Andreas; Mischak, Harald

2015-01-01

To assess normal and pathological peptidomic changes that may lead to an improved understanding of molecular mechanisms underlying ageing, urinary peptidomes of 1227 healthy and 10333 diseased individuals between 20 and 86 years of age were investigated. The diseases thereby comprised diabetes mellitus, renal and cardiovascular diseases. Using age as a continuous variable, 116 peptides were identified that significantly (p < 0.05; |ρ|≥0.2) correlated with age in the healthy cohort. The same approach was applied to the diseased cohort. Upon comparison of the peptide patterns of the two cohorts 112 common age-correlated peptides were identified. These 112 peptides predominantly originated from collagen, uromodulin and fibrinogen. While most fibrillar and basement membrane collagen fragments showed a decreased age-related excretion, uromodulin, beta-2-microglobulin and fibrinogen fragments showed an increase. Peptide-based in silico protease analysis was performed and 32 proteases, including matrix metalloproteinases and cathepsins, were predicted to be involved in ageing. Identified peptides, predicted proteases and patient information were combined in a systems biology pathway analysis to identify molecular pathways associated with normal and/or pathological ageing. While perturbations in collagen homeostasis, trafficking of toll-like receptors and endosomal pathways were commonly identified, degradation of insulin-like growth factor-binding proteins was uniquely identified in pathological ageing. PMID:26431327

Proteasix: a tool for automated and large-scale prediction of proteases involved in naturally occurring peptide generation.

PubMed

Klein, Julie; Eales, James; Zürbig, Petra; Vlahou, Antonia; Mischak, Harald; Stevens, Robert

2013-04-01

In this study, we have developed Proteasix, an open-source peptide-centric tool that can be used to predict in silico the proteases involved in naturally occurring peptide generation. We developed a curated cleavage site (CS) database, containing 3500 entries about human protease/CS combinations. On top of this database, we built a tool, Proteasix, which allows CS retrieval and protease associations from a list of peptides. To establish the proof of concept of the approach, we used a list of 1388 peptides identified from human urine samples, and compared the prediction to the analysis of 1003 randomly generated amino acid sequences. Metalloprotease activity was predominantly involved in urinary peptide generation, and more particularly to peptides associated with extracellular matrix remodelling, compared to proteins from other origins. In comparison, random sequences returned almost no results, highlighting the specificity of the prediction. This study provides a tool that can facilitate linking of identified protein fragments to predicted protease activity, and therefore into presumed mechanisms of disease. Experiments are needed to confirm the in silico hypotheses; nevertheless, this approach may be of great help to better understand molecular mechanisms of disease, and define new biomarkers, and therapeutic targets. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

A Pilot Study of Urinary Peptides as Biomarkers for Intelligence in Old Age

ERIC Educational Resources Information Center

Lopez, Lorna M.; Mullen, William; Zurbig, Petra; Harris, Sarah E.; Gow, Alan J.; Starr, John M.; Porteous, David J.; Mischak, Harald; Deary, Ian J.

2011-01-01

Intelligence is an important indicator of physical, mental and social well-being. In old age, intelligence is also associated with a higher quality of life and better health. Heritability studies have shown that there are strong genetic influences, yet unknown, on intelligence, including in old age. Other approaches may be useful to investigate…

Relationship between thyroid functions and urinary growth hormone secretion in patients with hyper- and hypothyroidism.

PubMed

Murao, K; Takahara, J; Sato, M; Tamaki, M; Niimi, M; Ishida, T

1994-10-01

Thyroid hormone plays an important role in growth hormone (GH) synthesis and secretion. To study the relationship between thyroid function and urinary GH secretion in the hyperthyroid and hypothyroid states, we measured thyroid hormones, simultaneously with serum and urinary GH levels, in 54 patients with thyroid diseases. GH-releasing hormone (GRH) test was performed in 18 patients in order to evaluate serum and urinary GH responses to GRH in hyper- and hypothyroid states. Serum thyroid hormone levels were strongly correlated with the urinary GH levels in the patients, and the correlation was greater than that between serum thyroid hormone and serum GH levels. Urinary GH levels were significantly higher in the hyperthyroid patients than in the euthyroid and hypothyroid patients, although serum GH levels were not significantly different among these three groups. Serum GH response to GRH was significantly decreased in hyperthyroid patients as compared to euthyroid patients. However, urinary GH levels after GRH administration were not decreased in the hyperthyroid patients. These results suggest that hyperthyroid states increase GH in urine and may accelerate the urinary clearance of GH.

Comparison of vildagliptin twice daily vs. sitagliptin once daily using continuous glucose monitoring (CGM): Crossover pilot study (J-VICTORIA study)

PubMed Central

2012-01-01

Background No previous studies have compared the DPP-4 inhibitors vildagliptin and sitagliptin in terms of blood glucose levels using continuous glucose monitoring (CGM) and cardiovascular parameters. Methods Twenty patients with type 2 diabetes mellitus were randomly allocated to groups who received vildagliptin then sitagliptin, or vice versa. Patients were hospitalized at 1 month after starting each drug, and CGM was used to determine: 1) mean (± standard deviation) 24-hour blood glucose level, 2) mean amplitude of glycemic excursions (MAGE), 3) fasting blood glucose level, 4) highest postprandial blood glucose level and time, 5) increase in blood glucose level after each meal, 6) area under the curve (AUC) for blood glucose level ≥180 mg/dL within 3 hours after each meal, and 7) area over the curve (AOC) for daily blood glucose level <70 mg/dL. Plasma glycosylated hemoglobin (HbA1c), glycoalbumin (GA), 1,5-anhydroglucitol (1,5AG), immunoreactive insulin (IRI), C-peptide immunoreactivity (CPR), brain natriuretic peptide (BNP), and plasminogen activator inhibitor-1 (PAI-1) levels, and urinary CPR levels, were measured. Results The mean 24-hour blood glucose level was significantly lower in patients taking vildagliptin than sitagliptin (142.1 ± 35.5 vs. 153.2 ± 37.0 mg/dL; p = 0.012). In patients taking vildagliptin, MAGE was significantly lower (110.5 ± 33.5 vs. 129.4 ± 45.1 mg/dL; p = 0.040), the highest blood glucose level after supper was significantly lower (206.1 ± 40.2 vs. 223.2 ± 43.5 mg/dL; p = 0.015), the AUC (≥180 mg/dL) within 3 h was significantly lower after breakfast (484.3 vs. 897.9 mg/min/dL; p = 0.025), and urinary CPR level was significantly higher (97.0 ± 41.6 vs. 85.2 ± 39.9 μg/day; p = 0.008) than in patients taking sitagliptin. There were no significant differences in plasma HbA1c, GA, 1,5AG, IRI, CPR, BNP, or PAI-1 levels between patients taking vildagliptin and sitagliptin. Conclusions CGM showed that mean 24-h blood glucose, MAGE, highest blood glucose level after supper, and hyperglycemia after breakfast were significantly lower in patients with type 2 diabetes mellitus taking vildagliptin than those taking sitagliptin. There were no significant differences in BNP and PAI-1 levels between patients taking vildagliptin and sitagliptin. Trial registration UMIN000007687 PMID:22867630

DA-1229, a dipeptidyl peptidase IV inhibitor, protects against renal injury by preventing podocyte damage in an animal model of progressive renal injury.

PubMed

Eun Lee, Jee; Kim, Jung Eun; Lee, Mi Hwa; Song, Hye Kyoung; Ghee, Jung Yeon; Kang, Young Sun; Min, Hye Sook; Kim, Hyun Wook; Cha, Jin Joo; Han, Jee Young; Han, Sang Youb; Cha, Dae Ryong

2016-05-01

Although dipeptidyl peptidase IV (DPPIV) inhibitors are known to have renoprotective effects, the mechanism underlying these effects has remained elusive. Here we investigated the effects of DA-1229, a novel DPPIV inhibitor, in two animal models of renal injury including db/db mice and the adriamycin nephropathy rodent model of chronic renal disease characterized by podocyte injury. For both models, DA-1229 was administered at 300 mg/kg/day. DPPIV activity in the kidney was significantly higher in diabetic mice compared with their nondiabetic controls. Although DA-1229 did not affect glycemic control or insulin resistance, DA-1229 did improve lipid profiles, albuminuria and renal fibrosis. Moreover, DA-1229 treatment resulted in decreased urinary excretion of nephrin, decreased circulating and kidney DPPIV activity, and decreased macrophage infiltration in the kidney. In adriamycin-treated mice, DPPIV activity in the kidney and urinary nephrin loss were both increased, whereas glucagon-like peptide-1 concentrations were unchanged. Moreover, DA-1229 treatment significantly improved proteinuria, renal fibrosis and inflammation associated with decreased urinary nephrin loss, and kidney DPP4 activity. In cultured podocytes, DA-1229 restored the high glucose/angiotensin II-induced increase of DPPIV activity and preserved the nephrin levels in podocytes. These findings suggest that activation of DPPIV in the kidney has a role in the progression of renal disease, and that DA-1229 may exert its renoprotective effects by preventing podocyte injury.

[Urinary leukotrience E(4) level in children with asthma].

PubMed

He, Mei-Juan; Chen, Qiang; Liu, Jian-Mei

2009-11-01

Cysteinyl leukotriene (CysLTs) plays an important role in airway inflammation and remodeling in asthma. Measurement of urinary leukotriene E(4) (LTE(4)) is a sensitive and noninvasive method of assaying total body CysLTs level. This study aimed to evaluate the clinical significance of urinary leukotriene E(4) (LTE(4)) in childhood asthma. Sixty children with acute asthma were randomly divided into montelukast (leukotriene receptor antagonist) treatment and conventional treatment groups (n = 30 each). Urinary LTE(4) levels were measured using ELISA and the airway resistance Rint was assessed by the lung function instrument at the acute and the convalescence phases. Twenty healthy children were used as the control group. Urinary LTE(4) levels in asthmatic children at the acute and the convalescence phases were significantly higher than those in the control group (p<0.01). The urinary LTE(4) levels at the convalescence phase were significantly reduced compared with those at the acute phase in asthmatic children (p<0.01). More significantly decreased urinary LTE(4) levels were noted in the montelukast treatment group than the conventional treatment group at the convalescence phase (p<0.01). In the acute phase, there was no correlation between urinary LTE4 level and Rint in asthmatic children. Urinary LTE(4) level is significantly increased in children with acute asthma. Urinary LTE(4) is a useful marker for the diagnosis of asthma and can be as a predictor of asthma control and marker of susceptibility to treatment with leukotriene receptor antagonists.

Urinary 8-hydroxy-2'-deoxyguanosine (8-oxodG) level can predict acute renal damage in young children with urinary tract infection.

PubMed

Chien, Jien-Wen; Wang, Lien-Yen; Cheng, Yu-Shan; Tsai, Yi-Giien; Liu, Chin-San

2014-06-01

There are no good biomarkers to predict renal parenchymal involvement in children with urinary tract infection (UTI). Children (N = 73) younger than 5 years with UTI were enrolled. Urinary levels of 8-hydroxy-2'-deoxyguanosine (8-oxodG) and total antioxidant capacity (TAC) were checked as markers of oxidative stress and antioxidant capacity, respectively. Tc99m-dimercaptosuccinic acid (DMSA) renal scintigraphy was used to find evidence of renal involvement. Patients with positive DMSA findings had higher levels of urinary 8-oxodG (p = 0.003) and higher urinary TAC (p = 0.001) than patients with normal DMSA findings. High level of urinary 8-oxodG may be a risk factor of severe renal damage.

Urinary angiotensinogen as a potential biomarker of intrarenal renin-angiotensin system activity in Chinese chronic kidney disease patients.

PubMed

Xu, Z; Xu, B; Xu, C

2015-06-01

Urinary angiotensinogen (AGT) mainly derives from the AGT produced in proximal tubular cells. Evidence exists that supports the correlation between urinary AGT and circulating AGT. To investigate the role of urinary AGT as a potential biomarker of intrarenal renin-angiotensin system activity in Chinese chronic kidney disease (CKD) patients. ELISA-based method used to quantify urinary AGT. Analyzed the relationship between urinary AGT and intrarenal angiotensin II (Ang II) activity in 128 CKD patients. ELISA was applied to measure the urinary and plasma renin activity, AGT, Ang II and aldosterone. Furthermore expression levels of intrarenal renin, AGT, Ang II and Ang II receptor were examined by immunohistochemistry staining (IHCS) in 72 CKD patients undergoing renal biopsy. The logarithmic transformation Log(urinary AGT/UCre) levels showed a normal distribution. Therefore, Log(urinary AGT/UCre) levels were used for the analyses. Average urinary AGT was 2.02 ± 0.55 ng/(mg Cr). Hypertension, urinary protein, urinary Ang II and urinary type IV collagen (Col IV) positively correlated with urinary AGT. Estimated glomerular filtration rate (eGFR), urinary sodium and serum AGT negatively correlated with urinary AGT. Multiple regression analysis indicated that low serum AGT, high urinary protein, urinary Ang II and urinary Col IV correlated significantly with high urinary AGT. We observed positive correlation between urinary AGT and positive IHCS area of AGT, Ang II and Ang II type 1 receptor in renal tissue. These data suggest that urinary AGT might be a potential biomarker of intrarenal Ang II activity in CKD patients.

N-terminal pro-brain natriuretic peptide in prevalent peritoneal dialysis patients.

PubMed

Adachi, Yoko; Nishio, Akira

2008-01-01

Previous reports have shown that N-terminal pro-brain natriuretic peptide (NT-Pro-BNP) is a predictive marker for mortality in both peritoneal dialysis (PD) and hemodialysis (HD) patients. The aim of the present study was to clarify whether NT-Pro-BNP reflects a specific status in PD patients. We analyzed 40 stable PD patients, allocating them to one of two groups (20 each) according to the median value of NT-Pro-BNP: group A below and group B above 5423 pg/mL. In group B as compared with group A, red blood cell (RBC) counts, hemoglobin, hematocrit, sodium, chlorine, albumin, and daily urinary volume were significantly lower, and cardiothoracic ratio (CTR) and daily ultrafiltration volume were significantly higher. Patients using icodextrin and diabetic patients showed significantly higher NT-Pro-BNP values. We observed significant correlations between NT-Pro-BNP and RBC count, hematocrit, hemoglobin, sodium, chlorine, albumin, lactate dehydrogenase, CTR, daily urinary volume, and ultrafiltration volume. Multiple regression analysis revealed that increasing CTR and hyponatremia were significant predictors of an increase in NT-Pro-BNP. Our results indicate that increased serum NT-Pro-BNP well reflects anemia status, water balance, hyponatremia, and hypoalbuminemia in prevalent PD patients.

Urine peptidome analysis predicts risk of end-stage renal disease and reveals proteolytic pathways involved in autosomal dominant polycystic kidney disease progression.

PubMed

Pejchinovski, Martin; Siwy, Justyna; Metzger, Jochen; Dakna, Mohammed; Mischak, Harald; Klein, Julie; Jankowski, Vera; Bae, Kyongtae T; Chapman, Arlene B; Kistler, Andreas D

2017-03-01

Autosomal dominant polycystic kidney disease (ADPKD) is characterized by slowly progressive bilateral renal cyst growth ultimately resulting in loss of kidney function and end-stage renal disease (ESRD). Disease progression rate and age at ESRD are highly variable. Therapeutic interventions therefore require early risk stratification of patients and monitoring of disease progression in response to treatment. We used a urine peptidomic approach based on capillary electrophoresis-mass-spectrometry (CE-MS) to identify potential biomarkers reflecting the risk for early progression to ESRD in the Consortium of Radiologic Imaging in Polycystic Kidney Disease (CRISP) cohort. A biomarker-based classifier consisting of 20 urinary peptides allowed the prediction of ESRD within 10-13 years of follow-up in patients 24-46 years of age at baseline. The performance of the biomarker score approached that of height-adjusted total kidney volume (htTKV) and the combination of the biomarker panel with htTKV improved prediction over either one alone. In young patients (<24 years at baseline), the same biomarker model predicted a 30 mL/min/1.73 m 2 glomerular filtration rate decline over 8 years. Sequence analysis of the altered urinary peptides and the prediction of the involved proteases by in silico analysis revealed alterations in distinct proteolytic pathways, in particular matrix metalloproteinases and cathepsins. We developed a urinary test that accurately predicts relevant clinical outcomes in ADPKD patients and suggests altered proteolytic pathways involved in disease progression. © The Author 2016. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.

Insulin and the phosphatidylinositol 3-kinase signaling pathway regulate Ribonuclease 7 expression in the human urinary tract.

PubMed

Eichler, Tad E; Becknell, Brian; Easterling, Robert S; Ingraham, Susan E; Cohen, Daniel M; Schwaderer, Andrew L; Hains, David S; Li, Birong; Cohen, Ariel; Metheny, Jackie; Tridandapani, Susheela; Spencer, John David

2016-09-01

Diabetes mellitus is a systemic disease associated with a deficiency of insulin production or action. Diabetic patients have an increased susceptibility to infection with the urinary tract being the most common site. Recent studies suggest that Ribonuclease 7 (RNase 7) is a potent antimicrobial peptide that plays an important role in protecting the urinary tract from bacterial insult. Because the impact of diabetes on RNase 7 expression and function are unknown, we investigated the effects of insulin on RNase 7 using human urine specimens. The urinary RNase 7 concentrations were measured in healthy control patients and insulin-deficient type 1 diabetics before and after starting insulin therapy. Compared with controls, diabetic patients had suppressed urinary RNase 7 concentrations, which increased with insulin. Using primary human urothelial cells, the mechanisms by which insulin stimulates RNase 7 synthesis were next explored. Insulin induced RNase 7 production via the phosphatidylinositide 3-kinase signaling pathway (PI3K/AKT) to shield urothelial cells from uropathogenic E. coli. In contrast, uropathogenic E. coli suppressed PI3K/AKT activity and RNase 7 production. Thus, insulin and PI3K/AKT signaling are essential for RNase 7 expression and increased infection risks in diabetic patients may be secondary to suppressed RNase 7 production. Our data may provide unique insight into novel urinary tract infection therapeutic strategies in at-risk populations. Copyright © 2016 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

Association of increased urine brain derived neurotrophic factor with lower urinary tract symptoms in men with benign prostatic hyperplasia.

PubMed

Wang, Long-Wang; Li, Jian-Long; Yu, Yi; Xiao, Rui-Hai; Huang, Hong-Wei; Kuang, Ren-Rui; Hai, Bo

2017-08-01

Urinary brain-derived neurotrophic factor (BDNF), an ubiquitous neurotrophin, was found to rise in patients with benign prostatic hyperplasia (BPH). We hypothesized that the urinary level of BDNF could be a potential biomarker for lower urinary tract symptoms (LUTS) in patients with BPH. Totally, 76 patients with BPH-caused LUTS and 32 male control subjects without BPH were enrolled. International Prostate Symptom Score (IPSS) was applied to assess the symptom severity of LUTS. Urodynamic tests were performed for the diagnosis of underlying detrusor overactivity (DO) in the patients with BPH. Urine samples were collected from all subjects. Urinary BDNF levels were measured using enzyme-linked immunosorbent assays and normalized by urinary creatinine (Cr) levels. Seventy-six BPH patients were divided into moderate LUTS group (n=51, 720) according to the IPSS. Of the 76 BPH patients, DO was present in 34 (44.7%) according to the urodynamic test. The urinary BDNF/Cr levels were significantly higher in BPH patients with moderate LUTS (8.29±3.635, P<0.0001) and severe LUTS (11.8±6.44, P<0.0001) than normal controls (1.71±0.555). Patients with severe LUTS tended to have higher urinary BDNF/Cr levels than patients with moderate LUTS (11.8±6.44 vs. 8.29±3.635, P=0.000). The conditions of BPH with LUTS correlated with elevated urinary BDNF levels, and urinary BDNF levels were even higher in BPH-DO patients. The results of this study have provided evidence to suggest that urinary BDNF level test could evaluate the severity of LUTS in BPH patients, and BDNF level can be used as a biomarker for the diagnosis of DO in BPH patients.

Are urinary PAHs biomarkers of controlled exposure to diesel exhaust?

PubMed Central

Lu, Sixin S.; Sobus, Jon R.; Sallsten, Gerd; Albin, Maria; Pleil, Joachim D.; Gudmundsson, Anders; Madden, Michael C.; Strandberg, Bo; Wierzbicka, Aneta; Rappaport, Stephen M.

2016-01-01

Urinary polycyclic aromatic hydrocarbons (PAHs) were evaluated as possible biomarkers of exposure to diesel exhaust (DE) in two controlled-chamber studies. We report levels of 14 PAHs from 28 subjects in urine that were collected before, immediately after and the morning after exposure. Using linear mixed-effects models, we tested for effects of DE exposure and several covariates (time, age, gender and urinary creatinine) on urinary PAH levels. DE exposures did not significantly alter urinary PAH levels. We conclude that urinary PAHs are not promising biomarkers of short-term exposures to DE in the range of 106–276 μg/m3. PMID:24754404

Biomimetic synthesis of struvite with biogenic morphology and implication for pathological biomineralization

NASA Astrophysics Data System (ADS)

Li, Han; Yao, Qi-Zhi; Wang, Yu-Ying; Li, Yi-Liang; Zhou, Gen-Tao

2015-01-01

Recent studies have found that certain urinary proteins can efficiently inhibit stone formation. These discoveries are significant for developing effective therapies for stone disease, but the inhibition mechanism of crystallization remains elusive. In the present study, polyaspartic acid (PASP) was employed as a model peptide to investigate the effect of urinary proteins on the crystallization and morphological evolution of struvite. The results demonstrate that selective adsorption/binding of PASP onto the {010} and {101} faces of struvite crystals results in arrowhead-shaped morphology, which further evolves into X-shaped and unusual tabular structures with time. Noticeably, these morphologies are reminiscent of biogenic struvite morphology. Concentration-dependent experiments show that PASP can inhibit struvite growth and the inhibitory capacity increases with increasing PASP concentration, whereas aspartic acid monomers do not show a significant effect. Considering that PASP is a structural and functional analogue of the subdomains of aspartic acid-rich proteins, our results reveal that aspartic acid-rich proteins play a key role in regulating biogenic struvite morphology, and aspartic acid residues contribute to the inhibitory capacity of urinary proteins. The potential implications of PASP for developing therapeutic agents for urinary stone disease is also discussed.

Biomimetic synthesis of struvite with biogenic morphology and implication for pathological biomineralization.

PubMed

Li, Han; Yao, Qi-Zhi; Wang, Yu-Ying; Li, Yi-Liang; Zhou, Gen-Tao

2015-01-16

Recent studies have found that certain urinary proteins can efficiently inhibit stone formation. These discoveries are significant for developing effective therapies for stone disease, but the inhibition mechanism of crystallization remains elusive. In the present study, polyaspartic acid (PASP) was employed as a model peptide to investigate the effect of urinary proteins on the crystallization and morphological evolution of struvite. The results demonstrate that selective adsorption/binding of PASP onto the {010} and {101} faces of struvite crystals results in arrowhead-shaped morphology, which further evolves into X-shaped and unusual tabular structures with time. Noticeably, these morphologies are reminiscent of biogenic struvite morphology. Concentration-dependent experiments show that PASP can inhibit struvite growth and the inhibitory capacity increases with increasing PASP concentration, whereas aspartic acid monomers do not show a significant effect. Considering that PASP is a structural and functional analogue of the subdomains of aspartic acid-rich proteins, our results reveal that aspartic acid-rich proteins play a key role in regulating biogenic struvite morphology, and aspartic acid residues contribute to the inhibitory capacity of urinary proteins. The potential implications of PASP for developing therapeutic agents for urinary stone disease is also discussed.

An association between urinary cadmium and urinary stone disease in persons living in cadmium-contaminated villages in northwestern Thailand: A population study

DOE Office of Scientific and Technical Information (OSTI.GOV)

Swaddiwudhipong, Witaya, E-mail: swaddi@hotmail.com; Mahasakpan, Pranee; Limpatanachote, Pisit

Excessive urinary calcium excretion is the major risk of urinary stone formation. Very few population studies have been performed to determine the relationship between environmental cadmium exposure and urinary stone disease. This population-based study examined an association between urinary cadmium excretion, a good biomarker of long-term cadmium exposure, and prevalence of urinary stones in persons aged 15 years and older, who lived in the 12 cadmium-contaminated villages in the Mae Sot District, Tak Province, northwestern Thailand. A total of 6748 persons were interviewed and screened for urinary cadmium and urinary stone disease in 2009. To test a correlation between urinarymore » excretion of cadmium and calcium, we measured urinary calcium content in 1492 persons, who lived in 3 villages randomly selected from the 12 contaminated villages. The rate of urinary stones significantly increased from 4.3% among persons in the lowest quartile of urinary cadmium to 11.3% in the highest quartile. An increase in stone prevalence with increasing urinary cadmium levels was similarly observed in both genders. Multiple logistic regression analysis revealed a positive association between urinary cadmium levels and stone prevalence, after adjusting for other co-variables. The urinary calcium excretion significantly increased with increasing urinary cadmium levels in both genders, after adjusting for other co-variables. Elevated calciuria induced by cadmium might increase the risk of urinary stone formation in this environmentally exposed population. - Research highlights: {yields} Excessive calciuria is the major risk of urinary stone formation. {yields} We examine cadmium-exposed persons for urinary cadmium, calcium, and stones. {yields} The rate of urinary stones increases with increasing urinary cadmium. {yields} Urinary calcium excretion increases with increasing urinary cadmium. {yields} Elevated calciuria induced by cadmium may increase the risk of urinary stones.« less

The evaluation of oxidative DNA damage in children with brain damage using 8-hydroxydeoxyguanosine levels.

PubMed

Fukuda, Miho; Yamauchi, Hiroshi; Yamamoto, Hitoshi; Aminaka, Masahito; Murakami, Hiroshi; Kamiyama, Noriko; Miyamoto, Yusaku; Koitabashi, Yasushi

2008-02-01

Urinary and cerebrospinal fluid (CSF) levels of 8-hydroxydeoxyguanosine (8-OHdG) were examined to estimate the relevance of oxidative stress in children with brain damage. Urinary 8-OHdG levels were measured in 51 children with various forms of central nervous system (CNS) disorders (status epilepticus [SE], hypoxic-ischemic encephalopathy [HIE], CNS infections and chronic epilepsy) and these levels were compared with those in 51 healthy children. CSF 8-OHdG levels were measured in 25 children with brain damage and in 19 control subjects. In addition, urinary and CSF levels of 8-OHdG were compared between the children with brain damage and healthy children. Finally, the relationship between urinary and CSF levels of 8-OHdG was determined in 12 children that provided both urinary and CSF samples. Our results showed that urinary 8-OHdG levels in children with HIE and CNS infections were higher than those of controls (Steel test; p < 0.05 and p < 0.05, respectively) and that CSF 8-OHdG levels were higher in children with SE, HIE, and CNS infections than in control subjects (Steel test; p < 0.01, 0.05 and 0.05, respectively). In addition, a positive correlation between the levels of urinary and CSF 8-OHdG was noted in the 12 children that provided both CSF and urinary samples (Spearman's rank correlation; rho = 0.82, p < 0.01). Further, we observed changes in the urinary 8-OHdG in a patient with HHV-6 encephalopathy, and found that the changes correlated well with the patient's clinical condition. These results suggest that oxidative stress is strongly related to acute brain damage in children, and that 8-OHdG is a useful marker of brain damage. Therefore, repeated measurements of urinary 8-OHdG may be helpful in estimating the extent of brain damage.

Associations of urinary cadmium with circulating sex hormone levels in pre- and postmenopausal Japanese women

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nagata, Chisato, E-mail: chisato@gifu-u.ac.jp

Background: Exposure to cadmium has been suspected as a risk factor for breast cancer. The present study examined the associations between urinary cadmium levels and circulating sex hormone levels that are linked to breast cancer risk in healthy women. Methods: The study subjects were 396 premenopausal Japanese women who had regular menstrual cycles less than 40 days long and 207 postmenopausal Japanese women. Urinary cadmium was measured using spot urine samples. Plasma estradiol, testosterone, and dehydroepiandrosterone sulfate were measured. Additionally, the follicle-stimulating hormone, luteinizing hormone, and sex hormone-binding globulin were measured for premenopausal women. Results: In premenopausal women, the urinarymore » cadmium level either expressed in μg per liter or per g of urine creatinine was significantly inversely associated with total and free testosterone levels after controlling for age, body mass index, smoking status, alcohol intake, and the phase of the menstrual cycle. Total and free testosterone levels were 14.6% and 15.0% lower, respectively, in women in the highest quartile of urinary cadmium per g creatinine in those in the lowest quartile. In postmenopausal women, the urinary cadmium in μg per liter as well as per g creatinine was significantly inversely associated with the estradiol level after controlling for covariates. The estradiol level was 25.8% lower in women in the highest tertile of urinary cadmium per g creatinine than in those in the lowest tertile. Conclusions: The data suggest inverse associations between urinary cadmium and the plasma estradiol or testosterone level in Japanese women. - Highlights: • Exposure to cadmium has been suspected as a risk factor for breast cancer. • Urinary cadmium and plasma sex-hormone levels were measured in Japanese women. • Urinary cadmium was inversely associated with testosterone in premenopausal women. • Urinary cadmium was inversely associated with estradiol in postmenopausal women.« less

Mining the human urine proteome for monitoring renal transplant injury

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sigdel, Tara K.; Gao, Yuqian; He, Jintang

The human urinary proteome reflects systemic and inherent renal injury perturbations and can be analyzed to harness specific biomarkers for different kidney transplant injury states. 396 unique urine samples were collected contemporaneously with an allograft biopsy from 396 unique kidney transplant recipients. Centralized, blinded histology on the graft was used to classify matched urine samples into categories of acute rejection (AR), chronic allograft nephropathy (CAN), BK virus nephritis (BKVN), and stable graft (STA). Liquid chromatography–mass spectrometry (LC-MS) based proteomics using iTRAQ based discovery (n=108) and global label-free LC-MS analyses of individual samples (n=137) for quantitative proteome assessment were used inmore » the discovery step. Selected reaction monitoring (SRM) was applied to identify and validate minimal urine protein/peptide biomarkers to accurately segregate organ injury causation and pathology on unique urine samples (n=151). A total of 958 proteins were initially quantified by iTRAQ, 87% of which were also identified among 1574 urine proteins detected in LC-MS validation. 103 urine proteins were significantly (p<0.05) perturbed in injury and enriched for humoral immunity, complement activation, and lymphocyte trafficking. A set of 131 peptides corresponding to 78 proteins were assessed by SRM for their significance in an independent sample cohort. A minimal set of 35 peptides mapping to 33 proteins, were modeled to segregate different injury groups (AUC =93% for AR, 99% for CAN, 83% for BKVN). Urinary proteome discovery and targeted validation identified urine protein fingerprints for non-invasive differentiation of kidney transplant injuries, thus opening the door for personalized immune risk assessment and therapy.« less

PACAP/Receptor System in Urinary Bladder Dysfunction and Pelvic Pain Following Urinary Bladder Inflammation or Stress

PubMed Central

Girard, Beatrice M.; Tooke, Katharine; Vizzard, Margaret A.

2017-01-01

Complex organization of CNS and PNS pathways is necessary for the coordinated and reciprocal functions of the urinary bladder, urethra and urethral sphincters. Injury, inflammation, psychogenic stress or diseases that affect these nerve pathways and target organs can produce lower urinary tract (LUT) dysfunction. Numerous neuropeptide/receptor systems are expressed in the neural pathways of the LUT and non-neural components of the LUT (e.g., urothelium) also express peptides. One such neuropeptide receptor system, pituitary adenylate cyclase-activating polypeptide (PACAP; Adcyap1) and its cognate receptor, PAC1 (Adcyap1r1), have tissue-specific distributions in the LUT. Mice with a genetic deletion of PACAP exhibit bladder dysfunction and altered somatic sensation. PACAP and associated receptors are expressed in the LUT and exhibit neuroplastic changes with neural injury, inflammation, and diseases of the LUT as well as psychogenic stress. Blockade of the PACAP/PAC1 receptor system reduces voiding frequency in preclinical animal models and transgenic mouse models that mirror some clinical symptoms of bladder dysfunction. A change in the balance of the expression and resulting function of the PACAP/receptor system in CNS and PNS bladder reflex pathways may underlie LUT dysfunction including symptoms of urinary urgency, increased voiding frequency, and visceral pain. The PACAP/receptor system in micturition pathways may represent a potential target for therapeutic intervention to reduce LUT dysfunction. PMID:29255407

Nocturnal Urinary Excretion of FSH and LH in Children and Adolescents With Normal and Early Puberty.

PubMed

Kolby, Nanna; Busch, Alexander S; Aksglaede, Lise; Sørensen, Kaspar; Petersen, Jorgen Holm; Andersson, Anna-Maria; Juul, Anders

2017-10-01

Clinical use of single serum gonadotropin measurements in children is limited by the pulsatile secretion of follicle-stimulating hormone (FSH) and luteinizing hormone (LH). However, first morning voided (FMV) urine may integrate the fluctuating gonadotropin serum levels. We aimed to evaluate urinary and serum gonadotropin levels according to age, sex, and pubertal stage in healthy children and to assess the clinical use of FMV urinary gonadotropins in children with disordered puberty. Cross-sectional part of the COPENHAGEN Puberty Study and longitudinal study of patients. Population-based and outpatient clinic. Eight hundred forty-three healthy children from the COPENHAGEN Puberty Study and 25 girls evaluated for central precocious puberty (CPP). Clinical pubertal staging, including serum and urinary gonadotropin levels. Urinary gonadotropins increased with advancing age and pubertal development and were detectable in FMV urine before physical signs of puberty. FMV urinary LH correlated strongly with basal (r = 0.871, P < 0.001) and gonadotropin-releasing hormone (GnRH)-stimulated serum LH (r = 0.82, P < 0.001). Urinary LH was superior to urinary FSH in differentiating the pubertal stage. Receiver operating curve analysis revealed that a cut-off standard deviation (SD) score of 2 for urinary LH (IU/L) gave a sensitivity of 75% and a specificity of 92% in predicting a positive GnRH stimulation test (LHmax > 5 IU/L). Urinary concentrations of LH decreased after 3 months of GnRH treatment to levels below +2 SDs. Urinary gonadotropin levels increased before the onset of puberty and were elevated in girls with CPP. We suggest urinary LH as an alternative noninvasive method to improve diagnosing and therapeutic management of children with disordered puberty. Copyright © 2017 Endocrine Society

Effects of cilnidipine on sympathetic nerve activity and cardiorenal function in hypertensive patients with type 2 diabetes mellitus: association with BNP and aldosterone levels.

PubMed

Tanaka, Masami; Sekioka, Risa; Nishimura, Takeshi; Ichihara, Atsuhiro; Itoh, Hiroshi

2014-12-01

Hypertension stimulates the sympathetic nervous system and this phenomenon is exacerbated by diabetes mellitus. We investigated the effects of cilnidipine, an N/L-type calcium channel blocker, on aspects of this system in patients with type 2 diabetes mellitus. In 33 hypertensive patients with type 2 diabetes mellitus treated with a calcium channel blocker other than cilnidipine, we evaluated the influence of switching to cilnidipine on blood pressure, heart rate, catecholamine, plasma renin and aldosterone concentration, brain natriuretic peptide, urine liver-type fatty acid binding protein, and urinary albumin excretion ratio in the same patients by a cross-over design. Other biochemical parameters were also evaluated. Switching to cilnidipine did not change blood pressure but caused reduction in catecholamine concentrations in blood and urine and plasma aldosterone concentration, accompanied by significant reduction in brain natriuretic peptide, urine liver-type fatty acid binding protein, and albumin excretion ratio. These parameters other than brain natriuretic peptide were significantly increased after cilnidipine was changed to the original calcium channel blocker. In 33 hypertensive patients with type 2 diabetes mellitus, compared to other calcium channel blockers, cilnidipine suppressed sympathetic nerve activity and aldosterone, and significantly improved markers of cardiorenal disorders. Therefore, cilnidipine may be an important calcium channel blocker for use in combination with renin-angiotensin-aldosterone system inhibitors when dealing with hypertension complicated with diabetes mellitus. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Urinary 8-hydroxy-2'-deoxyguanosine as a novel biomarker for predicting cardiac events and evaluating the effectiveness of carvedilol treatment in patients with chronic systolic heart failure.

PubMed

Susa, Takehisa; Kobayashi, Shigeki; Tanaka, Takeo; Murakami, Wakako; Akashi, Shintaro; Kunitsugu, Ichiro; Okuda, Shinichi; Doi, Masahiro; Wada, Yasuaki; Nao, Tomoko; Yamada, Jutaro; Ueyama, Takeshi; Okamura, Takayuki; Yano, Masafumi; Matsuzaki, Masunori

2012-01-01

The authors recently reported that urinary 8-hydroxy-2'-deoxyguanosine (U8-OHdG) derived from cardiac tissue reflects clinical status and cardiac dysfunction severity in patients with chronic heart failure (CHF). The aim of the present study was to investigate whether U8-OHdG levels can accurately predict cardiac events in CHF patients and their response to β-blocker treatment. Plasma brain natriuretic peptide (BNP) and U8-OHdG levels were measured in 186 consecutive CHF patients before discharge. Patients were then prospectively followed (median follow-up, 649 days) with endpoints of cardiac death or hospitalization due to progressive heart failure. From receiver operating characteristic curve analysis, cut-offs were 12.4ng/mg creatinine (Cr) for U8-OHdG and 207pg/ml for BNP. On multivariate Cox analysis, U8-OHdG and BNP were independent predictors of cardiac events. Patients were classified into 4 groups according to U8-OHdG and BNP cut-offs. The hazard ratio for cardiac events in patients with BNP ≥207pg/ml and U8-OHdG ≥12.4ng/mg Cr was 16.2 compared with approximately 4 for patients with only 1 indicator above its respective cut-off. Furthermore, carvedilol therapy was initiated in 30 CHF patients. In responders (≥10% increase in left ventricular ejection fraction [LVEF] or ≥1 class decrease in New York Heart Association [NYHA] class), U8-OHdG levels decreased significantly along with improved NYHA class, LVEF, and BNP levels after treatment. U8-OHdG may be a useful biomarker for predicting cardiac events and evaluating β-blocker therapy effectiveness in CHF patients.

Deficiency of aldose reductase exacerbates early pressure overload-induced cardiac dysfunction and autophagy in mice.

PubMed

Baba, Shahid P; Zhang, Deqing; Singh, Mahavir; Dassanayaka, Sujith; Xie, Zhengzhi; Jagatheesan, Ganapathy; Zhao, Jingjing; Schmidtke, Virginia K; Brittian, Kenneth R; Merchant, Michael L; Conklin, Daniel J; Jones, Steven P; Bhatnagar, Aruni

2018-05-01

Pathological cardiac hypertrophy is associated with the accumulation of lipid peroxidation-derived aldehydes such as 4-hydroxy-trans-2-nonenal (HNE) and acrolein in the heart. These aldehydes are metabolized via several pathways, of which aldose reductase (AR) represents a broad-specificity route for their elimination. We tested the hypothesis that by preventing aldehyde removal, AR deficiency accentuates the pathological effects of transverse aortic constriction (TAC). We found that the levels of AR in the heart were increased in mice subjected to TAC for 2 weeks. In comparison with wild-type (WT), AR-null mice showed lower ejection fraction, which was exacerbated 2 weeks after TAC. Levels of atrial natriuretic peptide and myosin heavy chain were higher in AR-null than in WT TAC hearts. Deficiency of AR decreased urinary levels of the acrolein metabolite, 3-hydroxypropylmercapturic acid. Deletion of AR did not affect the levels of the other aldehyde-metabolizing enzyme - aldehyde dehydrogenase 2 in the heart, or its urinary product - (N-Acetyl-S-(2-carboxyethyl)-l-cystiene). AR-null hearts subjected to TAC showed increased accumulation of HNE- and acrolein-modified proteins, as well as increased AMPK phosphorylation and autophagy. Superfusion with HNE led to a greater increase in p62, LC3II formation, and GFP-LC3-II punctae formation in AR-null than WT cardiac myocytes. Pharmacological inactivation of JNK decreased HNE-induced autophagy in AR-null cardiac myocytes. Collectively, these results suggest that during hypertrophy the accumulation of lipid peroxidation derived aldehydes promotes pathological remodeling via excessive autophagy, and that metabolic detoxification of these aldehydes by AR may be essential for maintaining cardiac function during early stages of pressure overload. Published by Elsevier Ltd.

Phytate levels and bone parameters: a retrospective pilot clinical trial.

PubMed

Lopez-Gonzalez, Angel A; Grases, Felix; Perello, Joan; Tur, Fernando; Costa-Bauza, Antonia; Monroy, Nieves; Mari, Bartolome; Vicente-Herrero, Teofila

2010-06-01

This study evaluated the relationship between phytate urinary levels and bone characteristics in a large population of postmenopausal women. The study population consisted of 180 postmenopausal women who participated in a descriptive cross-sectional study. A urine sample was collected from each subject to determine phytate levels and the volunteers were divided into two groups according to phytate urinary concentration (i.e., low and high levels). Bone mineral density was determined in the lumbar spine and femoral neck of groups with low and high phytate urinary levels. Urinary levels of phytate were linked to dietary phytate consumption. Hence, bone mineral density values were significantly higher in the lumbar spines and femoral necks of women who consumed high levels of phytate than in women with low urinary phytate concentrations. Higher urinary levels of phytate correlated with higher bone mineral density in the lumbar spine and femoral necks of postmenopausal women. This finding demonstrates the potential use of phytate in the treatment of bone related diseases, as it uses a mechanism of action similar to some bisphosphonates.

Biomarkers of oxidative stress in electroplating workers exposed to hexavalent chromium.

PubMed

Pan, Chih-Hong; Jeng, Hueiwang Anna; Lai, Ching-Huang

2018-01-01

This study evaluates levels of biomarkers of oxidative DNA damage and lipid peroxidation in 105 male workers at 16 electroplating companies who had been exposed to hexavalent chromium (Cr(VI)). The study participants were 230 non-smoking male workers, comprising 105 electroplating workers who had been exposed to chromium and 125 control subjects who performed office tasks. Personal air samples, spot urine samples, hair samples, fingernail samples and questionnaires were used to quantify exposure to Cr(VI), oxidative DNA damage, lipid peroxidation, and environmental pollutants. Both the geometric mean personal concentrations of Cr(VI) of the Cr-exposed workers and the total Cr concentrations in the air to which they were exposed significantly exceeded those for the control subjects. The geometric mean concentrations of Cr in urine, hair and fingernails, and the urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG), and malondialdehyde (MDA) levels in the Cr(VI) exposed workers exceeded those in the control subjects. Daily cumulative Cr(VI) exposure and urinary Cr were significantly correlated with urinary 8-OHdG levels following adjustments for covariates. A ten-fold increase in urinary Cr level was associated with a 1.73-fold increase in urinary 8-OHdG level. Daily cumulative Cr(VI) exposure and urinary Cr level were significantly correlated with urinary MDA level following adjustments for covariates. A ten-fold increase in urinary Cr was associated with a 1.45-fold increase in urinary MDA. Exposure to Cr(VI) increased oxidative DNA injury and the oxidative deterioration of lipids in electroplating workers.

Intraluminal proteome and peptidome of human urinary extracellular vesicles.

PubMed

Liu, Xinyu; Chinello, Clizia; Musante, Luca; Cazzaniga, Marta; Tataruch, Dorota; Calzaferri, Giulio; James Smith, Andrew; De Sio, Gabriele; Magni, Fulvio; Zou, Hequn; Holthofer, Harry

2015-06-01

Urinary extracellular vesicles (UEVs) are a novel source for disease biomarker discovery. However, Tamm-Horsfall protein (THP) is still a challenge for proteomic analysis since it can inhibit detection of low-abundance proteins. Here, we introduce a new approach that does not involve an ultracentrifugation step to enrich vesicles and that reduces the amount of THP to manageable levels. UEVs were dialyzed and ultrafiltered after reduction and alkylation. The retained fraction was digested with trypsin to reduce the remaining THP and incubated with deoxycholate (DOC). The internal peptidome and internal proteome were analyzed by LC-ESI-MS. A total of 942 different proteins and 3115 unique endogenous peptide fragments deriving from 973 different protein isoforms were identified. Around 82% of the key endosomal sorting complex required for transport components of UEVs generation could be detected from the intraluminal content. Our UEVs preparation protocol provides a simplified way to investigate the intraluminal proteome and peptidome, in particular the subpopulation of UEVs of the trypsin-resistant class of exosomes (positive for tumor susceptibility gene101) and eliminates the majority of interfering proteins such as THP. This method allows the possibility to study endoproteome and endopeptidome of UEVs, thus greatly facilitating biomarker discovery. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Association between urinary metabolic profile and the intestinal effects of cocoa in rats.

PubMed

Massot-Cladera, Malen; Mayneris-Perxachs, Jordi; Costabile, Adele; Swann, Jonathan R; Franch, Àngels; Pérez-Cano, Francisco J; Castell, Margarida

2017-03-01

The aim of this study was to elucidate the relationship between the urinary metabolic fingerprint and the effects of cocoa and cocoa fibre on body weight, hormone metabolism, intestinal immunity and microbiota composition. To this effect, Wistar rats were fed, for 3 weeks, a diet containing 10 % cocoa (C10) or two other diets with same the proportion of fibres: one based on cocoa fibre (CF) and another containing inulin as a reference (REF) diet. The rats' 24 h urine samples were analysed by an untargeted 1H NMR spectroscopy-based metabonomic approach. Concentrations of faecal IgA and plasma metabolic hormones were also quantified. The C10 diet decreased the intestinal IgA, plasma glucagon-like peptide-1 and glucagon concentrations and increased ghrelin levels compared with those in the REF group. Clear differences were observed between the metabolic profiles from the C10 group and those from the CF group. Urine metabolites derived from cocoa correlated with the cocoa effects on body weight, immunity and the gut microbiota. Overall, cocoa intake alters the host and bacterial metabolism concerning energy and amino acid pathways, leading to a metabolic signature that can be used as a marker for consumption. This metabolic profile correlates with body weight, metabolic hormones, intestinal immunity and microbiota composition.

Low Impact of Urinary Cortisol in the Assessment of Hydrocortisone Replacement Therapy.

PubMed

Haas, C S; Rahvar, A-H; Danneberg, S; Lehnert, H; Moenig, H; Harbeck, B

2016-09-01

Hydrocortisone replacement therapy is a cornerstone in the treatment of adrenal insufficiency (AI). While urinary cortisol has been used as a diagnostic tool for AI, it remains unclear whether it is a useful parameter to monitor hydrocortisone replacement therapy. Aim of this study was to evaluate possible differences in cortisol metabolism between adrenal insufficient patients and healthy subjects and to assess the value of urinary cortisol in AI management. In a case-control study, urinary cortisol excretion was determined in 14 patients with primary and secondary AI receiving hydrocortisone infusions from midnight to 8:00 AM. Results were correlated with serum cortisol levels and compared to urinary values obtained from 53 healthy volunteers. Urinary cortisol excretion in healthy subjects was 14.0±7.8 μg/8 h (range: 0.24-35.4), levels did not differ between 3 groups aged 20-34 years, 35-49 years, and ≥50 years. Patients with AI receiving hydrocortisone infusions demonstrated significantly higher rates of urinary cortisol excretion (51.6±37.8 μg/8 h; range 17.1-120.0, p<0.001); the values correlated with serum cortisol levels (r(2)=0.98). Of interest, patients with secondary AI showed significantly higher serum cortisol levels after hydrocortisone infusion than those with primary AI, conceivably due to residual adrenal function. In conclusion, we showed that: (i) there is a wide inter-individual variability in urinary cortisol excretion rates; (ii) cortisol metabolism in adrenal insufficient patients differs when compared to controls; (iii) there is a strong correlation between urinary and serum cortisol levels; and (iv) urinary cortisol levels despite their variability may help to discriminate between secondary and primary adrenal insufficiency. © Georg Thieme Verlag KG Stuttgart · New York.

The Clinical and Biochemical Predictors of Bone Mass in Preterm Infants.

PubMed

Czech-Kowalska, Justyna; Czekuc-Kryskiewicz, Edyta; Pludowski, Pawel; Zaniuk, Katarzyna; Jaworski, Maciej; Łuba, Anna; Grzybowska, Karolina; Piłat, Krystyna; Dobrzanska, Anna

2016-01-01

Metabolic bone disease of prematurity still occurs in preterm infants, although a significant improvement in neonatal care has been observed in recent decades. Dual-energy X-ray absorptiometry (DXA) is the precise technique for assessing bone mineral content (BMC) in preterm infants, but is not widely available. To investigate the clinical and biochemical parameters, including bone metabolism markers as potential predictors of BMC, in preterm infants up to 3 months corrected age (CA). Ca-P homeostasis, iPTH, 25-hydroxyvitamin D, osteocalcin, N-terminal propeptide, cross-linked C-telopeptide and amino-terminal pro C-type natriuretic peptide and the DXA scans were prospectively performed in 184 preterm infants (≤ 34 weeks' gestation) between term age and 3 mo CA. Lower bone mass was defined as BMC below or equal to respective median value for the whole study group, rounded to the nearest whole number. The appropriate quality DXA scans were available for 160 infants (87%) examined at term and for 130 (71%) tested at 3 mo CA. Higher iPTH level was the only independent predictor of lower BMC at term, whereas lower BMC at 3 mo CA was associated both with lower urinary phosphate excretion and higher serum osteocalcin level. ROC analysis showed that iPTH >43.6 pg/mL provided 40% sensitivity and 88% specificity in identification of preterm infants with lower BMC at term. In turn, urinary phosphate excretion (TRP>97% or UP/Cr ≤0.74 mg/mg) and serum osteocalcin >172 ng/mL provided 40% sensitivity and 93% specificity in identification of infants with decreased BMC at 3 mo CA. Serum iPTH might to be a simple predictor of reduced BMC in preterm infants at term age, but urinary phosphate excretion and serum osteocalcin might predict reduced BMC at 3 mo CA. These results represent a promising diagnostic tool based on simple, widely available biochemical measurements for bone mass assessment in preterm infants.

Urinary total arsenic and 8-hydroxydeoxyguanosine are associated with renal cell carcinoma in an area without obvious arsenic exposure

DOE Office of Scientific and Technical Information (OSTI.GOV)

Huang, Chao-Yuan; Department of Urology, National Taiwan University Hospital, College of Medicine National Taiwan University, Taipei, Taiwan; Su, Chien-Tien

2012-08-01

8-Hydroxydeoxyguanosine (8-OHdG) is one of the most reliable and abundant markers of DNA damage. The study was designed to explore the relationship between urinary 8-OHdG and renal cell carcinoma (RCC) and to investigate whether individuals with a high level of 8-OHdG would have a modified odds ratio (OR) of arsenic-related RCC. This case–control study was conducted with 132 RCC patients and 245 age- and sex-matched controls from a hospital-based pool between November 2006 and May 2009. Pathological verification of RCC was completed by image-guided biopsy or surgical resection of renal tumors. Urinary 8-OHdG levels were determined using liquid chromatography withmore » tandem mass spectrometry (LC–MS/MS). Concentrations of urinary arsenic species, including inorganic arsenic, monomethylarsonic acid (MMA) and dimethylarsinic acid (DMA), were determined by a high performance liquid chromatography-linked hydride generator and atomic absorption spectrometry. Level of urinary 8-OHdG was significantly associated with the OR of RCC in a dose–response relationship after multivariate adjustment. Urinary 8-OHdG was significantly related to urinary total arsenic. The greatest OR (3.50) was seen in the individuals with high urinary 8-OHdG and high urinary total arsenic. A trend test indicated that the OR of RCC was increased with one of these factors and was further increased with both (p = 0.002). In conclusion, higher urinary 8-OHdG was a strong predictor of the RCC. High levels of 8-OHdG combined with urinary total arsenic might be indicative of arsenic-induced RCC. -- Highlights: ► Urinary 8-OHdG was significantly related to urinary total arsenic. ► Higher urinary 8-OHdG was a strong predictor of RCC risk. ► Urinary 8-OHdG may modify arsenic related RCC risk.« less

Urinary Proteomic Biomarkers for Diagnosis and Risk Stratification of Autosomal Dominant Polycystic Kidney Disease: A Multicentric Study

PubMed Central

Kistler, Andreas D.; Serra, Andreas L.; Siwy, Justyna; Poster, Diane; Krauer, Fabienne; Torres, Vicente E.; Mrug, Michal; Grantham, Jared J.; Bae, Kyongtae T.; Bost, James E.; Mullen, William; Wüthrich, Rudolf P.; Mischak, Harald; Chapman, Arlene B.

2013-01-01

Treatment options for autosomal dominant polycystic kidney disease (ADPKD) will likely become available in the near future, hence reliable diagnostic and prognostic biomarkers for the disease are strongly needed. Here, we aimed to define urinary proteomic patterns in ADPKD patients, which aid diagnosis and risk stratification. By capillary electrophoresis online coupled to mass spectrometry (CE-MS), we compared the urinary peptidome of 41 ADPKD patients to 189 healthy controls and identified 657 peptides with significantly altered excretion, of which 209 could be sequenced using tandem mass spectrometry. A support-vector-machine based diagnostic biomarker model based on the 142 most consistent peptide markers achieved a diagnostic sensitivity of 84.5% and specificity of 94.2% in an independent validation cohort, consisting of 251 ADPKD patients from five different centers and 86 healthy controls. The proteomic alterations in ADPKD included, but were not limited to markers previously associated with acute kidney injury (AKI). The diagnostic biomarker model was highly specific for ADPKD when tested in a cohort consisting of 481 patients with a variety of renal and extrarenal diseases, including AKI. Similar to ultrasound, sensitivity and specificity of the diagnostic score depended on patient age and genotype. We were furthermore able to identify biomarkers for disease severity and progression. A proteomic severity score was developed to predict height adjusted total kidney volume (htTKV) based on proteomic analysis of 134 ADPKD patients and showed a correlation of r = 0.415 (p<0.0001) with htTKV in an independent validation cohort consisting of 158 ADPKD patients. In conclusion, the performance of peptidomic biomarker scores is superior to any other biochemical markers of ADPKD and the proteomic biomarker patterns are a promising tool for prognostic evaluation of ADPKD. PMID:23326375

Urinary peptidomics in a rodent model of diabetic nephropathy highlights epidermal growth factor as a biomarker for renal deterioration in patients with type 2 diabetes.

PubMed

Betz, Boris B; Jenks, Sara J; Cronshaw, Andrew D; Lamont, Douglas J; Cairns, Carolynn; Manning, Jonathan R; Goddard, Jane; Webb, David J; Mullins, John J; Hughes, Jeremy; McLachlan, Stela; Strachan, Mark W J; Price, Jackie F; Conway, Bryan R

2016-05-01

Many diabetic patients suffer from declining renal function without developing albuminuria. To identify alternative biomarkers for diabetic nephropathy (DN) we performed urinary peptidomic analysis in a rodent model in which hyperglycemia and hypertension synergize to promote renal pathologic changes consistent with human DN. We identified 297 increased and 15 decreased peptides in the urine of rats with DN compared with controls, including peptides derived from proteins associated with DN and novel candidate biomarkers. We confirmed by ELISA that one of the parent proteins, urinary epidermal growth factor (uEGF), was more than 2-fold reduced in rats with DN in comparison with controls. To assess the clinical utility of uEGF we examined renal outcomes in 642 participants from the Edinburgh Type 2 Diabetes Study who were normoalbuminuric and had preserved renal function at baseline. After adjustment for established renal risk factors, a lower uEGF to creatinine ratio was associated with new-onset estimated glomerular filtration rate less than 60 ml/min per 1.73m(2) (odds ratio 0.48; 95% confidence interval, 0.26-0.90), rapid (over 5% per annum) decline in renal function (odds ratio 0.44; 95% confidence interval, 0.27-0.72) or the composite of both outcomes (odds ratio 0.38; 95% confidence interval, 0.24-0.62). Thus, the utility of a low uEGF to creatinine ratio as a biomarker of progressive decline in renal function in normoalbuminuric patients should be assessed in additional populations. Copyright © 2016 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

Urinary Concentrations of Triclosan, Benzophenone-3, and Bisphenol A in Taiwanese Children and Adolescents

PubMed Central

Chang, Fu-Kuei; Shiea, Jentaie; Tsai, Hsin-Jen

2017-01-01

The purpose of this study was to determine the levels of urinary triclosan (TCS), benzophenone-3 (BP-3), and bisphenol A (BPA) in 52 children and 71 adolescents. The effects of age and sex on the levels of urinary TCS, BP-3, and BPA were explored, respectively. Results demonstrated the overall detection rates of urinary TCS, BP-3, and BPA were 18.7%, 8.1%, and 49.6%, respectively. The females had higher TCS concentrations than males (p = 0.051). The detection rate of urinary BP-3 in females (12.3%) was higher than that in males (0%) (p = 0.015). Moreover, the detection rate of urinary BP-3 in adolescents (14.1%) was higher than that in children (0%) (p = 0.005). For children, no urinary BP-3 was found. There were no differences in detection rates and concentrations of urinary TCS, BP-3, and BPA between males and females, respectively. For adolescents, urinary BP-3 was only found in the females. Urinary TCS levels in females were higher than those in males (p = 0.047). The present study showed that urinary TCS concentrations in females were significantly higher than those in males, respectively. In addition, BP-3 was only detected in urine samples of female adolescents. Sex and age were the important factors influencing urinary TCS and BP-3 concentrations. PMID:29232866

Assessment of renal response with urinary exosomes in patients with AL amyloidosis: A proof of concept.

PubMed

Ramirez-Alvarado, Marina; Barnidge, David R; Murray, David L; Dispenzieri, Angela; Marin-Argany, Marta; Dick, Christopher J; Cooper, Shawna A; Nasr, Samih H; Ward, Christopher J; Dasari, Surendra; Jiménez-Zepeda, Víctor H; Leung, Nelson

2017-06-01

Immunoglobulin light chain (AL) amyloidosis is a fatal complication of B-cell proliferation secondary to deposition of amyloid fibrils in various organs. Urinary exosomes (UEX) are the smallest of the microvesicles excreted in the urine. Previously, we found UEX of patients with AL amyloidosis contained immunoglobulin light chain (LC) oligomers that patients with multiple myeloma did not have. To further explore the role of the LC oligomers, UEX was isolated from an AL amyloidosis patient with progressive renal disease despite achieving a complete response. LC oligomers were identified. Mass spectrometry (MS) of the UEX and serum identified two monoclonal lambda LCs. Proteomics of the trypsin digested amyloid fragments in the kidney by laser microdissection and MS analysis identified a λ6 LC. The cDNA from plasma cell clone was from the IGLV- 6-57 family and it matched the amino acid sequences of the amyloid peptides. The predicted mass of the peptide product of the cDNA matched the mass of one of the two LCs identified in the UEX and serum. UEX combined with MS were able to identify 2 monoclonal lambda LCs that current clinical methods could not. It also identified the amyloidogenic LC which holds potential for response assessment in the future. © 2017 Wiley Periodicals, Inc.

Intestinal absorption of an arginine-containing peptide in cystinuria

PubMed Central

Asatoor, A. M.; Harrison, B. D. W.; Milne, M. D.; Prosser, D. I.

1972-01-01

Separate tolerance tests involving oral intake of the dipeptide, L-arginyl-L-aspartate, and of a corresponding free amino acid mixture, were carried out in a single type 2 cystinuric patient. Absorption of aspartate was within normal limits, whilst that of arginine was normal after the peptide but considerably reduced after the amino acid mixture. The results are compared with the increments of serum arginine found in eight normal subjects after the oral intake of the free amino acid mixture. Analyses of urinary pyrrolidine and of tetramethylenediamine in urine samples obtained after the two tolerance tests in the patient support the view that arginine absorption was subnormal after the amino acid mixture but within normal limits after the dipeptide. PMID:5045711

Hyperammonemia in Urinary Tract Infections.

PubMed

Kenzaka, Tsuneaki; Kato, Ken; Kitao, Akihito; Kosami, Koki; Minami, Kensuke; Yahata, Shinsuke; Fukui, Miho; Okayama, Masanobu

2015-01-01

The present study investigated the incidence of hyperammonemia in urinary tract infections and explored the utility of urinary obstruction relief and antimicrobial administration to improve hyperammonemia. This was an observational study. Subjects were patients who were diagnosed with urinary tract infection and hospitalized between June 2008 and June 2009. We measured plasma ammonia levels on admission in patients who were clinically diagnosed with urinary tract infection and hospitalized. We assessed each patient's level of consciousness on admission using the Glasgow Coma Scale (GCS) and performed urine and blood cultures. We also assessed hearing prior to hospitalization using the Eastern Cooperative Oncology Group performance status (ECOG-PS). In cases with high ammonia levels on admission, plasma ammonia and GCS were measured 24 hours and 5-7 days later. Sixty-seven candidates were enrolled; of these, 60 cases (89.6%) with bacterial cell counts ≥10(4) CFU/mL were studied. Five cases (8.3%) presented with high plasma ammonia levels. Cases with hyperammonemia were significantly more likely to present with low GCS scores and urinary retention rate. All five cases received antimicrobial therapy with an indwelling bladder catheter to relieve urinary retention. The case 5 patient died shortly after admission due to complicated aspiration pneumonia; in the remaining cases, plasma ammonia levels were rapidly normalized and the level of consciousness improved. The occurrence of hyperammonemia in urinary tract infections is not rare. The cause of hyperammonemia is urinary retention obstruction. Therefore, along with antimicrobial administration, relief of obstruction is important for the treatment of hyperammonemia caused by this mechanism.

Influence of nutritional status, laboratory parameters and dietary patterns upon urinary acid excretion in calcium stone formers.

PubMed

Tessaro, Carolini Zanette Warmling; Ramos, Christiane Ishikawa; Heilberg, Ita Pfeferman

2018-04-26

Obesity and Metabolic Syndrome (MS) are associated with low urinary pH and represent risk factors for nephrolithiasis, especially composed by uric acid. Acidogenic diets may also contribute to a reduction of urinary pH. Propensity for calcium oxalate precipitation has been shown to be higher with increasing features of the MS. A retrospective evaluation of anthropometric and body composition parameters, MS criteria and the dietary patterns of overweight and obese calcium stone formers and their impact upon urinary pH and other lithogenic parameters was performed. Data regarding anthropometry, body composition, serum and urinary parameters and 3-days dietary records were obtained from medical records of 102(34M/68F) calcium stone formers. A negative correlation was found between urinary pH, waist circumference and serum uric acid levels (males). The endogenous production of organic acids (OA) was positively correlated with triglycerides levels and number of features of MS (males), and with glucose, uric acid and triglycerides serum levels, and number of features of MS (females). No significant correlations were detected between Net Acid Excretion (NAE) or Potential Renal Acid Load of the diet with any of the assessed parameters. A multivariate analysis showed a negative association between OA and urinary pH. The endogenous production of OA and not an acidogenic diet were found to be independently predictive factors for lower urinary pH levels in calcium stone formers. Hypercalciuric and/or hyperuricosuric patients presented higher OA levels and lower levels of urinary pH.

Carnitine status in Thai adults.

PubMed

Tanphaichitr, V; Lerdvuthisopon, N; Dhanamitta, S; Broquist, H P

1980-04-01

Plasma carnitine and urinary carnitine levels were measured in Thai adults living in Bangkok city and Ubol villages. The mean plasma carnitine and urinary carnitine levels expressed in micromoles per liter in Bangkok adults were higher than those in Ubol adults. Their mean plasma carnitine levels were 56.6 +/- 1.8 and 50.3 +/- 1.7 whereas urinary carnitine levels were 161 +/- 19 and 127 +/- 18 micromole/liter, respectively. The nutritional status in Ubol adults was inadequate. This was evidenced by the significant decrease in urinary creatinine excretion, serum albumin, and hematocrit levels. The dietary assessment agreed with the biochemical findings. Since rice, limiting in carnitine, was the main protein and energy source consumed by Ubol adults their inadequate carnitine status could be due to the low carnitine intake. Sex affects plasma carnitine levels in Bangkok adults and urinary carnitine excretion in both groups. This could be related to the lean body mass in which most of the body carnitine resides. This is supported by the higher urinary creatinine excretion in males and the significant positive correlation between carnitine excretion and creatinine-height index.

Does exposure to phthalates influence thyroid function and growth hormone homeostasis? The Taiwan Environmental Survey for Toxicants (TEST) 2013.

PubMed

Huang, Han-Bin; Pan, Wen-Harn; Chang, Jung-Wei; Chiang, Hung-Che; Guo, Yue Leon; Jaakkola, Jouni J K; Huang, Po-Chin

2017-02-01

Previous epidemiologic and toxicological studies provide some inconsistent evidence that exposure to phthalates may affect thyroid function and growth hormone homeostasis. To assess the relations between exposure to phthalates and indicators of thyroid function and growth hormone homeostasis disturbances both among adults and minors. We conducted a population-based cross-sectional study of 279 Taiwanese adults (≥18 years old) and 79 minors (<18 years old) in 2013. Exposure assessment was based on urinary biomarkers, 11 phthalate metabolites measured by using online liquid chromatography/tandem mass spectrometry. Indicators of thyroid function included serum levels of thyroxine (T 4 ), free T 4 , triiodothyronine, thyroid-stimulating hormone, and thyroxine-binding globulin (TBG). Growth hormone homeostasis was measured as the serum levels of insulin-like growth factor 1 (IGF-1) and insulin-like growth factor binding protein 3 (IGFBP3). We applied multivariate linear regression models to examine these associations after adjusting for covariates. Among adults, serum T 4 levels were negatively associated with urinary mono-(2-ethyl-5-hydroxyhexyl) phthalate (β=-0.028, P=0.043) and the sum of urinary di-(2-ethylhexyl) phthalate (DEHP) metabolite (β=-0.045, P=0.017) levels. Free T 4 levels were negatively associated with urinary mono-ethylhexyl phthalate (MEHP) (β=-0.013, P=0.042) and mono-(2-ethyl-5-oxohexyl) phthalate (β=-0.030, P=0.003) levels, but positively associated with urinary monoethyl phthalate (β=0.014, P=0.037) after adjustment for age, BMI, gender, urinary creatinine levels, and TBG levels. Postive associations between urinary MEHP levels and IGF-1 levels (β=0.033, P=0.006) were observed. Among minors, free T 4 was positively associated with urinary mono benzyl phthalate levels (β=0.044, P=0.001), and IGF-1 levels were negatively associated with the sum of urinary DEHP metabolite levels (β=-0.166, P=0.041) after adjustment for significant covariance and IGFBP3. Our results are consistent with the hypothesis that exposure to phthalates influences thyroid function and growth hormone homeostasis. Copyright © 2016 Elsevier Inc. All rights reserved.

Correlates of N-Terminal Prohormone Brain Natriuretic Peptides in African Americans with Hypertensive Chronic Kidney Disease: The African American Study of Kidney Disease and Hypertension

PubMed Central

Yi, S.; Contreras, G.; Miller, E.R.; Appel, L.J.; Astor, B.C.

2009-01-01

Background/Aims The N-amino-terminal fragment of the prohormone B-type natriuretic peptide (NT-proBNP) is a marker of cardiac stress and elevated levels are indicative of heart failure. Few correlates of NT-proBNP levels have been identified in persons with moderate chronic kidney disease (CKD), and data from those without heart failure and from African Americans are especially limited. Methods The African American Study of Kidney Disease and Hypertension (AASK) enrolled nondiabetic African Americans with hypertensive kidney disease (glomerular filtration rate [GFR] = 20–65 ml/min/1.73 m2) and no evidence of clinical heart failure. NT-proBNP was measured in 982 AASK participants. Results In unadjusted analyses, GFR (r = −0.39; p < 0.001), hematocrit (r = −0.21; p < 0.001) and body mass index (BMI; r = −0.07; p = 0.04) were inversely correlated, and systolic blood pressure (r = 0.30; p < 0.001) and log UPCR (r = 0.32; p < 0.001) were positively correlated with log NT-proBNP levels. After adjustment for potential confounders, lower GFR and hematocrit and higher systolic blood pressure and protein:creatinine ratio remained significantly associated with higher NT-proBNP. Conclusion Lower GFR and hematocrit, and higher urinary protein excretion may be associated with volume expansion in CKD. These results suggest that these processes are associated with increased NT-proBNP in CKD and may play a role in the development of heart failure. PMID:18824845

Increased cartilage type II collagen degradation in patients with osteogenesis imperfecta used as a human model of bone type I collagen alterations.

PubMed

Rousseau, Jean-Charles; Chevrel, Guillaume; Schott, Anne-Marie; Garnero, Patrick

2010-04-01

We investigated whether cartilage degradation is altered in adult patients with mild osteogenesis imperfecta (OI) used as a human model of bone type I collagen-related osteoarthritis (OA). Sixty-four adult patients with OI (39% women, mean age+/-SD: 37+/-12 years) and 64 healthy age-matched controls (54% women, 39+/-7 years) were included. We also compared data in 87 patients with knee OA (73% women, 63+/-8 years, mean disease duration: 6 years) and 291 age-matched controls (80% women, 62+/-10 years). Urinary C-terminal cross-linked telopeptide of type II collagen (CTX-II), a marker of cartilage degradation, urinary helical peptide of type I collagen (Helix-I), a marker of bone resorption, and the urinary ratio between non-isomerised/isomerised (alpha/beta CTX-I) type I collagen C-telopeptide, a marker of type I collagen maturation, were measured. Patients with OI had CTX-II levels similar to those of subjects with knee OA (p=0.89; mean+/-SEM; 460+/-57 ng/mmol Cr for OI group and 547+/-32 ng/mmol Cr for OA group) and significantly higher than both young (144+/-7.8 ng/mmol Cr, p<0.0001) and old controls (247+/-7 ng/mmol Cr, p<0.0001). In patients with OI, increased Helix-I (p<0.0001) and alpha/beta CTX-I (p=0.0067) were independently associated with increased CTX-II and together explained 26% of its variance (p< 0.0001). In patients with knee OA, increased levels of alpha/beta CTX-I ratio were also associated with higher CTX-II levels. Adult patients with OI or knee OA are characterized by increased cartilage type II collagen degradation, which is associated with increased type I collagen degradation for OI and lower type I collagen maturation for both OI and OA. These data suggest that both quantitative and qualitative alterations of bone type I collagen metabolism are involved in increased cartilage degradation in patients with OI or knee OA. Copyright 2009 Elsevier Inc. All rights reserved.

Cytokines profile and its correlation with endothelial damage and oxidative stress in patients with type 1 diabetes mellitus and nephropathy.

PubMed

Pestana, Rodrigo M C; Domingueti, Caroline P; Duarte, Rita C F; Fóscolo, Rodrigo B; Reis, Janice S; Rodrigues, Ana Maria S; Martins, Laís B; Sousa, Lirlândia P; Lage, Daniela P; Ferreira, Cláudia N; Ferreira, Adaliene V M; Fernandes, Ana P; Gomes, Karina B

2016-08-01

The aim of the present study was to investigate the association between the presence of albuminuria and cytokines profile with biomarkers of endothelial damage and oxidative stress in patients with type 1 diabetes mellitus (DM1). The sample was composed by 35 healthy individuals, 63 DM1 patients with normoalbuminuria (<30 mg of albumin/g of creatinine) and 62 DM1 patients with micro- and macroalbuminuria (≥30 mg of albumin/g of creatinine). Plasma and urinary cytokines (TNF-α, IL-6 and IL-10) and thrombomodulin levels were determined by ELISA. Oxidative status was evaluated using the TBARS and MTT assays. Diabetic patients were characterized by elevated levels of urinary cytokines TNF-α, IL-6 and IL-10. Those with macroalbuminuria presented significantly higher TNF-α and IL-10 urinary levels when compared to other groups. Urinary and plasmatic levels of TNF-α were positively correlated with plasma levels of cystatin C, creatinine, urea and albuminuria, while they were negatively correlated with estimated glomerular filtration rate. Urinary IL-10 levels proved positive correlation with fasting glucose, HbA1c, thrombomodulin and TBARS, while IL-6 plasma levels were positively correlated with HbA1c and albuminuria. Only urinary TNF-α levels were associated with the presence and severity of macroalbuminuria, after logistic regression analysis. This finding suggests that measurement of urinary TNF-α level may be helpful to evaluate progression to nephropathy in DM1 patients.

The influence of season and living environment on children's urinary 1-hydroxypyrene levels in Ulaanbaatar, Mongolia.

PubMed

Chen, Yi-Ting; Huang, Yu-Kai; Luvsan, Munkh-Erdene; Gombojav, Enkhjargal; Ochir, Chimedsuren; Bulgan, Jargal; Chan, Chang-Chuan

2015-02-01

Heating indoor living environments elevates air pollution in Ulaanbaatar, Mongolia. This study was conducted to investigate the influence of season and living environment on children's urinary 1-hydroxypyrene (1-OHP) levels in Ulaanbaatar, Mongolia. Our study subjects were 320 children aged 11-15 years living in gers, brick houses and apartments, in ger and non-ger areas of Ulaanbaatar. Spot urine samples and questionnaires were collected three times from each subject in three seasons, September (warm) and December (cold) in 2011 and March (moderate) in 2012. Urinary 1-OHP was analyzed by high-performance liquid chromatography with fluorescent detection (HPLC/FLD). Generalized estimating equation (GEE) models were applied to estimate the seasonal and residential effects on 1-OHP levels, adjusting for demographic and environmental factors. Children's urinary 1-OHP levels showed significant seasonal differences with 0.30 ± 0.57 μmol/mol creatinine in cold season, 0.14 ± 0.12 μmol/mol creatinine in moderate season, and 0.14 ± 0.21 μmol/mol creatinine in warm season. After controlling confounding factors, the GEE model showed that season, living area, and housing type had significant influence on children's urinary 1-OHP levels. Urinary 1-OHP levels in the cold and moderate seasons were, respectively 2.13 and 1.37 times higher than the warm season. Urinary 1-OHP levels for children living in ger areas were 1.27 times higher than those living in non-ger areas. Children who lived in gers or brick houses had 1.58 and 1.34 times higher 1-OHP levels, respectively, compared with those living in apartments. Children's urinary 1-OHP levels were associated with either estimated NO2 or SO2 concentrations at their home addresses in Ulaanbaatar. Mongolian children's urinary 1-OHP levels were significantly elevated during the cold season, and for those living in ger areas, gers, or brick houses in Ulaanbaatar. Children's urinary 1-OHP levels were associated PAH co-pollutants SO2 and NO2, suggesting elevated 1-OHP levels may be attributable to PAH emissions from coal burning and traffic respectively, with indoor emissions from stoves further contributing to elevated 1-OHP in some children. Copyright © 2014 Elsevier Inc. All rights reserved.

PBPK-MODEL ESTIMATES OF BROMODICHLOROMETHANE (BDCM) DELIVERY TO THE HUMAN URINARY BLADDER

EPA Science Inventory

Recent data indicate that noningestion exposure to trihalomethanes (THMs), including BDCM is highly correlated with urinary THM levels. Characterizing urinary levels of drinking water disinfection byproducts (DBPs) will likely be important for understanding DBP-associated bladde...

Increased Klk9 Urinary Excretion Is Associated to Hypertension-Induced Cardiovascular Damage and Renal Alterations.

PubMed

Blázquez-Medela, Ana M; García-Sánchez, Omar; Quirós, Yaremi; Blanco-Gozalo, Victor; Prieto-García, Laura; Sancho-Martínez, Sandra M; Romero, Miguel; Duarte, Juan M; López-Hernández, Francisco J; López-Novoa, José M; Martínez-Salgado, Carlos

2015-10-01

Early detection of hypertensive end-organ damage and secondary diseases are key determinants of cardiovascular prognosis in patients suffering from arterial hypertension. Presently, there are no biomarkers for the detection of hypertensive target organ damage, most outstandingly including blood vessels, the heart, and the kidneys.We aimed to validate the usefulness of the urinary excretion of the serine protease kallikrein-related peptidase 9 (KLK9) as a biomarker of hypertension-induced target organ damage.Urinary, plasma, and renal tissue levels of KLK9 were measured by the Western blot in different rat models of hypertension, including angiotensin-II infusion, DOCA-salt, L-NAME administration, and spontaneous hypertension. Urinary levels were associated to cardiovascular and renal injury, assessed by histopathology. The origin of urinary KLK9 was investigated through in situ renal perfusion experiments.The urinary excretion of KLK9 is increased in different experimental models of hypertension in rats. The ACE inhibitor trandolapril significantly reduced arterial pressure and the urinary level of KLK9. Hypertension did not increase kidney, heart, liver, lung, or plasma KLK9 levels. Hypertension-induced increased urinary excretion of KLK9 results from specific alterations in its tubular reabsorption, even in the absence of overt nephropathy. KLK9 urinary excretion strongly correlates with cardiac hypertrophy and aortic wall thickening.KLK9 appears in the urine in the presence of hypertension as a result of subtle renal handling alterations. Urinary KLK9 might be potentially used as an indicator of hypertensive cardiac and vascular damage.

Insulin and the PI3K/AKT Signaling Pathway Regulate Ribonuclease 7 Expression in the Human Urinary Tract

PubMed Central

Eichler, Tad; Becknell, Brian; Easterling, Robert S.; Ingraham, Susan E.; Cohen, Daniel M.; Schwaderer, Andrew; Hains, David S.; Li, Birong; Cohen, Ariel; Metheny, Jackie; Trindandapani, Susheela; Spencer, John David

2017-01-01

Diabetes mellitus is a systemic disease associated with a deficiency of insulin production or action. Diabetic patients have an increased susceptibility to infection with the urinary tract being the most common site of infection. Recent studies suggest that Ribonuclease 7 (RNase 7) is a potent antimicrobial peptide that plays an important role in protecting the urinary tract from bacterial insult. The impact of diabetes on RNase 7 expression and function are unknown. Here, we investigate the effects of insulin on RNase 7. Using human urine specimens, we measured urinary RNase 7 concentrations in healthy control patients and insulin-deficient type 1 diabetics before and after starting insulin therapy. Compared to controls, diabetic patients had suppressed urinary RNase 7 concentrations, which increased with insulin. Using primary human urothelial cells, we explored the mechanisms by which insulin induces RNase 7. Insulin induces RNase 7 production via the phosphatidylinositide 3-kinase signaling pathway (PI3K/AKT) to shield urothelial cells from uropathogenic E. coli. In contrast, we show that uropathogenic E. coli suppresses PI3K/AKT and RNase 7. Together, these results indicate that insulin and PI3K/AKT signaling are essential for RNase 7 expression. They also suggest that increased infection risks in diabetic patients may be secondary to suppressed RNase 7 production. These data may provide unique insight into novel UTI therapeutic strategies in at risk populations. PMID:27401534

Porphyrinuria in childhood autistic disorder is not associated with urinary creatinine deficiency.

PubMed

Nataf, Robert; Skorupka, Corinne; Lam, Alain; Springbett, Anthea; Lathe, Richard

2008-08-01

Urinary metabolite measurements are often normalized to levels of the ubiquitous metabolite creatinine (CRT) to take account of variations in fluid export. Following CRT normalization, excesses of porphyrins and isoprostanes have been reported in the urines of children with neurodevelopmental disorders. It was suggested (Whiteley et al., 2006, Pediatr. Int. 2006; 48: 292-297) that urinary CRT levels may be depressed in children with autism spectrum disorders. This prompted re-evaluation of CRT levels in such children. First matinal urinary CRT levels were compared between subjects in different diagnostic categories including autistic disorder, pervasive developmental disorder not otherwise specified (PDD-NOS) and hyperactivity, before and after correction for age and gender. A larger reference group, consisting of subjects with unrelated disorders and Asperger disorder, with no reported porphyrin excess, was also compared to the group with autistic disorder, both for CRT and for porphyrin (coproporphyrin, COPRO) excess. No significant difference in CRT was observed between any of the categories analyzed, also when corrected for age and gender. In contrast, urinary COPRO levels were significantly higher in autistic disorder versus reference groups, either when expressed as absolute values (independent of CRT levels) or when normalized to CRT. These data do not support a systematic reduction in urinary CRT levels in subjects with autism spectrum disorders including autistic disorder and PDD-NOS. Urinary COPRO excess in autistic disorder was not associated with or consequent upon urinary CRT deficiency. Differences between affected and control subjects in age and sampling time, as reported by Whiteley et al., may underlie the apparent CRT reduction.

Targeting and synergistic action of an antifungal peptide in an antibiotic drug-delivery system.

PubMed

Park, Seong-Cheol; Kim, Young-Min; Lee, Jong-Kook; Kim, Nam-Hong; Kim, Eun-Ji; Heo, Hun; Lee, Min-Young; Lee, Jung Ro; Jang, Mi-Kyeong

2017-06-28

Amphotericin B (AmB) has been widely used against fungal infections throughout almost the entire body, including the skin, nails, oral cavity, respiratory tract, and urinary tract. However, the development of AmB-loaded nanoparticles demands a novel technique that reduces its toxicity and other associated problems. Here, we developed a pH-responsive and redox-sensitive polymer-based AmB-delivery carrier system. In particular, this system was functionalized by conjugation with the antifungal peptide histatin 5, which acts both as a targeting ligand and a synergistic antifungal molecule against Candida albicans, a major systemic fungal pathogen of humans. Our results in vitro and in vivo suggest that this drug-delivery system may serve as a novel tool to facilitate the use of antimicrobial peptides as targeting ligands to pathogenic microbes, which would open new avenues of investigation in the field of drug delivery. Copyright © 2017 Elsevier B.V. All rights reserved.

Urinary C‑X‑C motif chemokine 13 is a noninvasive biomarker of antibody‑mediated renal allograft rejection.

PubMed

Chen, Dajin; Zhang, Jian; Peng, Wenhan; Weng, Chunhua; Chen, Jianghua

2018-06-22

Noninvasive monitoring methods of immune status are preferred by transplant recipients. The present study investigated whether urinary C‑X‑C motif chemokine 13 (CXCL13) had the potential to reflect ongoing immune processes within renal allografts. Using an ELISA assay, the level of urinary CXCL13 was quantified in a total of 146 renal allograft recipients and 40 healthy controls at scheduled intervals and at the time of the indicated or protocol biopsy. The results of the present study revealed that urinary CXCL13/creatinine (Cr) was lower in normal transplants compared with in those with acute tubular necrosis (ATN; P=0.001), chronic allograft nephropathy (CAN; P=0.01), and acute rejection (AR; P<0.0001), which was associated with a good diagnostic performance for AR [area under the curve (AUC)=0.818, P<0.0001). In addition, urinary CXCL13/Cr levels in patients with AR were also higher than that of patients with graft dysfunction but no rejection, including ATN and CAN (P=0.034). Notably, urinary CXCL13 distinguished between acute antibody‑mediated rejection (ABMR) and acute cellular rejection, with an AUC of 0.856. Furthermore, patients with steroid‑resistant AR exhibited significantly increased urinary CXCL13/Cr levels than patients with reversible AR (P=0.001). Additionally, elevated levels of urinary CXCL13/Cr within the first month of transplant were predictive of graft function at 3 and 6 months (P=0.044 and P=0.04, respectively). Collectively, the findings of the present study indicated that the noninvasive investigation of urinary CXCL13/Cr may be valuable for the detection of AR, particularly ABMR. In addition, high urinary CXCL13/Cr levels predicted a poor response to steroid treatment and compromised graft function.

Urinary Liver Type Fatty Acid Binding Protein Is Negatively Associated With Estimated Glomerular Filtration Rate in Renal Transplant Recipients With Graft Loss.

PubMed

Huang, Y-C; Chang, Y-S; Chen, C-C; Tsai, S-F; Yu, T-M; Wu, M-J; Chen, C-H

2018-05-01

Liver type fatty acid binding protein (L-FABP) is abundant not only in the liver but also in the kidney and is excreted in urine. Its primary function is to facilitate intracellular long chain fatty acid transport and it might also act as an endogenous antioxidant molecular. The purpose of this study was to investigate whether plasma or urinary L-FABP levels were associated with graft function in renal transplant recipients. Sixty-seven renal transplant recipients with a mean age of 48.8 years were recruited. The mean duration of renal transplantation was 4131 days. Recipients were divided into 2 groups based on their estimated glomerular filtration rate (eGFR) values: moderate graft function (eGFR ≥60 mL/min/1.73 m 2 ) and low graft function (eGFR <60 mL/min/1.73 m 2 ). Fasting plasma and urinary L-FABP levels were measured. There was no significant difference in plasma L-FABP level between the 2 groups, although recipients in the low graft function group had significantly lower urinary L-FABP level when compared with recipients in the moderate graft function group. Plasma and urinary L-FABP levels were not associated with eGFR in the 67 recipients; however, urinary L-FABP level (β = -1.24, P = .037) and level adjusted by urinary creatinine (β = -0.75, P = .046) were significantly negatively associated with eGFR in recipients with low graft function after adjusting for potential confounders. Increased urinary L-FABP level seems to be a significant indicator of decreased graft function in renal transplant recipients with loss of graft function. Copyright © 2018 Elsevier Inc. All rights reserved.

Convenient radioimmunoassay for urinary human choriogonadotropin without interference by urinary human lutropin

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wehmann, R.E.; Harman, S.M.; Birken, S.

1981-12-01

We have devised a radioimmunoassay (RIA) for human choriogonadotropin (hCG) in first morning-voided urine specimens. Concanavalin A, a lectin, is used to extract and concentrate the hCG from urine. A high-affinity antiserum is used, directed to the hCG..beta.. carboxy-terminal peptide, a unique immunological determinant not shared by the beta subunit of human lutropin. This ensures that urinary human lutropin-related molecules, which interfere with RIAs involving antisera to the intact hCG..beta.. subunit, will not cross react in this assay. A concentration of hCG as low as 0.4 ..mu..g/L can be detected in the first morning-voided urine. The effective sensitivity of thismore » assay for the unequivocal detection of hCG production is somewhat better than that achieved with the serum hCG RIA involving antisera to the hCG..beta.. subunit. The improved specificity and sensitivity of this assay, and the greater convenience of collecting samples of urine rather than blood, are clinically useful advantages of this approach to assessing hCG production in humans.« less

Urinary 8-hydroxydeoxyguanosine and urothelial carcinoma risk in low arsenic exposure area

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chung, C.-J.; Huang, C.-J.; Pu, Y.-S.

2008-01-01

Arsenic is a well-documented human carcinogen and is known to cause oxidative stress in cultured cells and animals. A hospital-based case-control study was conducted to evaluate the relationship among the levels of urinary 8-hydroxydeoxyguanosine (8-OHdG), the arsenic profile, and urothelial carcinoma (UC). Urinary 8-OHdG was measured by using high-sensitivity enzyme-linked immunosorbent assay (ELISA) kits. The urinary species of inorganic arsenic and their metabolites were analyzed by high-performance liquid chromatography (HPLC) and hydride generator-atomic absorption spectrometry (HG-AAS). This study showed that the mean urinary concentration of total arsenics was significantly higher, at 37.67 {+-} 2.98 {mu}g/g creatinine, for UC patients thanmore » for healthy controls of 21.10 {+-} 0.79 {mu}g/g creatinine (p < 0.01). Urinary 8-OHdG levels correlated with urinary total arsenic concentrations (r = 0.19, p < 0.01). There were significantly higher 8-OHdG levels, of 7.48 {+-} 0.97 ng/mg creatinine in UC patients, compared to healthy controls of 5.95 {+-} 0.21 ng/mg creatinine. Furthermore, female UC patients had higher 8-OHdG levels of 9.22 {+-} 0.75 than those of males at 5.76 {+-} 0.25 ng/mg creatinine (p < 0.01). Multiple linear regression analyses revealed that high urinary 8-OHdG levels were associated with increased total arsenic concentrations, inorganic arsenite, monomethylarsonic acid (MMA), and dimethylarsenate (DMA) as well as the primary methylation index (PMI) even after adjusting for age, gender, and UC status. The results suggest that oxidative DNA damage was associated with arsenic exposure, even at low urinary level of arsenic.« less

Association of urinary metals levels with type 2 diabetes risk in coke oven workers.

PubMed

Liu, Bing; Feng, Wei; Wang, Jing; Li, Yaru; Han, Xu; Hu, Hua; Guo, Huan; Zhang, Xiaomin; He, Meian

2016-03-01

Studies indicated that occupationally exposed to metals could result in oxidative damage and inflammation and increase cardiovascular diseases risk. However, epidemiological studies about the associations of metals exposure with diabetes risk among coke oven workers were limited. This study aims to investigate the potential associations of 23 metals levels with the risk of diabetes among coke oven workers. The analysis was conducted in a cross-sectional study including 1493 participants. Urinary metals and urinary polycyclic aromatic hydrocarbons (PAHs) metabolites levels were determined by inductively coupled plasma mass spectrometer and gas chromatograph-mass spectrometer respectively. Multivariate logistic regression was used to investigate the associations of urinary metal levels with diabetes risk with adjustment for potential confounding factors including gender, age, BMI, education, smoking, drinking, physical activity, hypertension, hyperlipidemia and urinary PAHs metabolites levels. Compared with the normoglycemia group, the levels of urinary copper, zinc, arsenic, selenium, molybdenum, and cadmium were significantly higher in the diabetes group (all p < 0.05). Participants with the highest tertile of urinary copper and zinc had 2.12 (95%CI: 1.12-4.01) and 5.43 (95%CI: 2.61-11.30) fold risk of diabetes. Similar results were found for hyperglycemia risk. Besides, participants with the highest tertile of manganese, barium, and lead had 1.65(1.22-2.23), 1.60(1.19-2.16) and 1.45(1.05-1.99) fold risk of hyperglycemia when compared with the lowest tertlie. The results indicated that the urinary copper and zinc levels were positively associated with the risk of diabetes and hyperglycemia among coke oven workers. Urinary manganese, barium and lead levels were also associated with increased risk of hyperglycemia independently of other traditional risk factors. These findings need further validation in prospective study with larger sample size. Copyright © 2015 Elsevier Ltd. All rights reserved.

Large-Scale SRM Screen of Urothelial Bladder Cancer Candidate Biomarkers in Urine.

PubMed

Duriez, Elodie; Masselon, Christophe D; Mesmin, Cédric; Court, Magali; Demeure, Kevin; Allory, Yves; Malats, Núria; Matondo, Mariette; Radvanyi, François; Garin, Jérôme; Domon, Bruno

2017-04-07

Urothelial bladder cancer is a condition associated with high recurrence and substantial morbidity and mortality. Noninvasive urinary tests that would detect bladder cancer and tumor recurrence are required to significantly improve patient care. Over the past decade, numerous bladder cancer candidate biomarkers have been identified in the context of extensive proteomics or transcriptomics studies. To translate these findings in clinically useful biomarkers, the systematic evaluation of these candidates remains the bottleneck. Such evaluation involves large-scale quantitative LC-SRM (liquid chromatography-selected reaction monitoring) measurements, targeting hundreds of signature peptides by monitoring thousands of transitions in a single analysis. The design of highly multiplexed SRM analyses is driven by several factors: throughput, robustness, selectivity and sensitivity. Because of the complexity of the samples to be analyzed, some measurements (transitions) can be interfered by coeluting isobaric species resulting in biased or inconsistent estimated peptide/protein levels. Thus the assessment of the quality of SRM data is critical to allow flagging these inconsistent data. We describe an efficient and robust method to process large SRM data sets, including the processing of the raw data, the detection of low-quality measurements, the normalization of the signals for each protein, and the estimation of protein levels. Using this methodology, a variety of proteins previously associated with bladder cancer have been assessed through the analysis of urine samples from a large cohort of cancer patients and corresponding controls in an effort to establish a priority list of most promising candidates to guide subsequent clinical validation studies.

Renal and blood pressure effects from environmental cadmium exposure in Thai children

DOE Office of Scientific and Technical Information (OSTI.GOV)

Swaddiwudhipong, Witaya, E-mail: swaddi@hotmail.com; Mahasakpan, Pranee; Jeekeeree, Wanpen

Very few studies have shown renal and blood pressure effects from environmental cadmium exposure in children. This population study examined associations between urinary cadmium excretion, a good biomarker of long-term cadmium exposure, and renal dysfunctions and blood pressure in environmentally exposed Thai children. Renal functions including urinary excretion of β{sub 2}-microglobulin, calcium (early renal effects), and total protein (late renal effect), and blood pressure were measured in 594 primary school children. Of the children studied, 19.0% had urinary cadmium ≥1 μg/g creatinine. The prevalence of urinary cadmium ≥1 μg/g creatinine was significantly higher in girls and in those consuming ricemore » grown in cadmium-contaminated areas. The geometric mean levels of urinary β{sub 2}-microglobulin, calcium, and total protein significantly increased with increasing tertiles of urinary cadmium. The analysis did not show increased blood pressure with increasing tertiles of urinary cadmium. After adjusting for age, sex, and blood lead levels, the analysis showed significant positive associations between urinary cadmium and urinary β{sub 2}-microglobulin and urinary calcium, but not urinary total protein nor blood pressure. Our findings provide evidence that environmental cadmium exposure can affect renal functions in children. A follow-up study is essential to assess the clinical significance and progress of renal effects in these children. - Highlights: • Few studies show renal effects from environmental cadmium exposure in children. • We report renal and blood pressure effects from cadmium exposure in Thai children. • Urinary β{sub 2}-microglobulin and calcium increased with increasing urinary cadmium. • The study found no association between urinary cadmium levels and blood pressure. • Environmental cadmium exposure can affect renal functions in children.« less

Evidence of the Impact of Diet, Fluid Intake, Caffeine, Alcohol and Tobacco on Lower Urinary Tract Symptoms: A Systematic Review.

PubMed

Bradley, Catherine S; Erickson, Bradley A; Messersmith, Emily E; Pelletier-Cameron, Anne; Lai, H Henry; Kreder, Karl J; Yang, Claire C; Merion, Robert M; Bavendam, Tamara G; Kirkali, Ziya

2017-11-01

Diet, fluid intake and caffeine, alcohol and tobacco use may have effects on lower urinary tract symptoms. Constructive changes in these modifiable nonurological factors are suggested to improve lower urinary tract symptoms. To better understand the relationship between nonurological factors and lower urinary tract symptoms, we performed a systematic literature review to examine, grade and summarize reported associations between lower urinary tract symptoms and diet, fluid intake and caffeine, tobacco and alcohol use. We performed PubMed® searches for eligible articles providing evidence on associations between 1 or more nonurological factors and lower urinary tract symptoms. A modified Oxford scale was used to grade the evidence. We reviewed 111 articles addressing diet (28 studies), fluid intake (21) and caffeine (21), alcohol (26) and tobacco use (44). The evidence grade was generally low (6% level 1, 24% level 2, 11% level 3 and 59% level 4). Fluid intake and caffeine use were associated with urinary frequency and urgency in men and women. Modest alcohol use was associated with decreased likelihood of benign prostatic hyperplasia diagnosis and reduced lower urinary tract symptoms in men. Associations between lower urinary tract symptoms and ingestion of certain foods and tobacco were inconsistent. Evidence of associations between lower urinary tract symptoms and diet, fluid intake and caffeine, alcohol and tobacco use is sparse and mostly observational. However, there is evidence of associations between increased fluid and caffeine intake and urinary frequency/urgency, and between modest alcohol intake and decreased benign prostatic hyperplasia diagnosis and lower urinary tract symptoms. Given the importance of these nonurological factors in daily life, and their perceived impact on lower urinary tract symptoms, higher quality evidence is needed. Copyright © 2017 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Women with high early pregnancy urinary iodine levels have an increased risk of hyperthyroid newborns: the population-based Generation R Study.

PubMed

Medici, Marco; Ghassabian, Akhgar; Visser, Willy; de Muinck Keizer-Schrama, Sabine M P F; Jaddoe, Vincent W V; Visser, W Edward; Hooijkaas, Herbert; Hofman, Albert; Steegers, Eric A P; Bongers-Schokking, Jacoba J; Ross, H Alec; Tiemeier, Henning; Visser, Theo J; de Rijke, Yolanda B; Peeters, Robin P

2014-04-01

Iodine deficiency during pregnancy results in thyroid dysfunction and has been associated with adverse obstetric and foetal effects, leading to worldwide salt iodization programmes. As nowadays 69% of the world's population lives in iodine-sufficient regions, we investigated the effects of variation in iodine status on maternal and foetal thyroid (dys)function in an iodine-sufficient population. Urinary iodine, serum TSH, free T4 (FT4) and TPO-antibody levels were determined in early pregnancy (13·3 (1·9) week; mean (SD)) in 1098 women from the population-based Generation R Study. Newborn cord serum TSH and FT4 levels were determined at birth. The median urinary iodine level was 222·5 μg/l, indicating an iodine-sufficient population. 30·8% and 11·5% had urinary iodine levels <150 and >500 μg/l, respectively. When comparing mothers with urinary iodine levels <150 vs ≥150 μg/l, and >500 vs ≤500 μg/l, there were no differences in the risk of maternal increased or decreased TSH, hypothyroxinaemia or hyperthyroidism. Mothers with urinary iodine levels >500 μg/l had a higher risk of a newborn with decreased cord TSH levels (5·6 ± 1·4 (mean ± SE) vs 2·1 ± 0·5%, P = 0·04), as well as a higher risk of a hyperthyroid newborn (3·1 ± 0·9 vs 0·6 ± 0·3%, P = 0·02). These mothers had newborns with higher cord FT4 levels (21·7 ± 0·3 vs 21·0 ± 0·1 pm, P = 0·04). Maternal urinary iodine levels <150 μg/l were not associated with newborn thyroid dysfunction. In an iodine-sufficient population, higher maternal urinary iodine levels are associated with an increased risk of a hyperthyroid newborn. © 2013 John Wiley & Sons Ltd.

Urinary interleukin-6 as a predictor of radiographic progression in rheumatoid arthritis: A 3-year evaluation.

PubMed

Park, Yune-Jung; Yoo, Seung-Ah; Kim, Ga-Ram; Cho, Chul-Soo; Kim, Wan-Uk

2016-10-12

Previously, we demonstrated that the urine proteome signature of patients with rheumatoid arthritis (RA) reflects inflammation-related cellular processes. Here, we measured interleukin (IL)-6, IL-8, and chemokine ligand 2 (CCL2) concentrations in the urine of RA patients and prospectively investigated their role in predicting RA activity and prognosis. One hundred seventy-three RA patients and 62 non-RA controls were recruited. Urinary IL-6, CCL2, and IL-8 levels were elevated in RA patients and correlated well with disease activity. Urinary IL-6 level at presentation was an independent risk factor of radiographic progression at 1 and 3 years. High urinary IL-6 level increased the risk ratio of radiographic progression by 2.9-fold, which was comparable to high serum CRP. Moreover, combination of urinary IL-6 and serum CRP measures synergistically increased the predictability of radiographic progression. In a subgroup with normal ESR, patients with the highest tertile of urinary IL-6 were at 6.4-fold greater risk of radiographic progression. Conclusively, high urinary IL-6 level at presentation is an independent risk factor for radiographic progression of RA, reflecting disease activity. Urinary IL-6 in combination with serum CRP may be a useful parameter for estimating RA prognosis.

Peptidase activity as a determinant of agonist potencies in some smooth muscle preparations.

PubMed

Hall, J M; Fox, A J; Morton, I K

1990-02-06

The influence of degradation by peptidases on concentration-response relationships for peptide agonists of the tachykinin and bombesin-like families was investigated. The combined presence of three peptidase inhibitors, phosphoramidon (1 microM), captopril (1 microM) and bestatin (100 microM), had no significant effect on the onset rates or peak contractile responses to these peptides in the rat urinary bladder and guinea-pig taenia caeci preparations, or on their peak potentiation of the contractile response to field-stimulation in the guinea-pig vas deferens preparation. However, rates of offset of the response to tachykinins were markedly prolonged in tissues treated with peptidase inhibitors. In experiments designed to estimate clearance of applied peptide from the organ bath, there was an initial rate of loss with the guinea-pig vas deferens and taenia caeci which, measured over the first 5 min, had a half-time of 2-3 min which was then prolonged to 6-8 min in the presence of peptidase inhibitors. These results show that although peptide breakdown can be demonstrated in these systems, it seems not to be an important determinant of relative pharmacological activity measured in terms of peak response.

Novel urinary biomarkers and their association with urinary heavy metals in chronic kidney disease of unknown aetiology in Sri Lanka: a pilot study

PubMed

Wanigasuriya, K; Jayawardene, I; Amarasiriwardena, C; Wickremasinghe, R

2017-12-26

Chronic kidney disease of unknown etiology (CKDu) has emerged as a significant public health problem in Sri Lanka. The role of environmental exposure to cadmium and arsenic in the aetiology of CKDu is still unclear. Identification of a panel of novel urinary biomarkers would be invaluable in the study of toxin mediated damage postulated to be the aetiology of CKDu. The aims of this study were to evaluate the profile of novel urinary biomarkers in CKDu patients and identify any association with environmental exposure to heavy metals. Thirty seven randomly selected CKDu patients attending a renal clinic in the North Central Province and two control groups namely a farmer group (n=39) and a non-farmer group (n=40) from a non-endemic area were included in this comparative cross sectional study. Urine samples were analyzed for heavy metals and five urinary biomarkers. CKDu patients had significantly elevated urinary levels of fibrinogen (198.2 ng/mg creatinine p<0.001), clusterin (3479 ng/mg creatinine p<0.001), cystatin-C (5124.8 ng/mg creatinine p<0.001) and β2-microglobulin (9913.4 ng/mg creatinine p<0.001) compared to the control groups. Fibrinogen and β2-microglobulin were the best to discriminate CKDu patients from normal individuals with the receiver operator areas under the curve being 0.867 and 0.853, respectively. Urinary fibrinogen and KIM-1 levels correlated positively with urinary arsenic levels. KIM-1 levels correlated positively with urinary mercury and lead levels but no correlation was seen with urinary cadmium levels. Fibrinogen and β2-microglobulin have the potential of being a screening tool for detection of CKDu and may aid the early diagnosis of toxin mediated tubular injury in CKDu. Their usefulness need to be further validated in a larger epidemiological study of patients with early stages of CKDu.

[A case of hyperammonemia resulting from urinary tract infection caused by urease-producing bacteria in a Parkinson's disease patient with drug-induced urinary retention].

PubMed

Yasunishi, Masahiro; Koumura, Akihiro; Hayashi, Yuichi; Nishida, Shohei; Inuzuka, Takashi

2017-01-01

A 71-year-old woman with a 9-year history of Parkinson's disease was admitted to our hospital emergently because of consciousness disturbance. Her consciousness level was 200 on the Japan coma scale (JCS), and she presented with tenderness and distension of the lower abdomen. Brain computed tomography showed normal findings. Blood tests showed an increased ammonia level (209 μg/dl) with normal AST and ALT levels. We catheterized the bladder for urinary retention. Five hours after admission, the blood ammonia level decreased to 38 μg/dl, and her consciousness level improved dramatically. Corynebacterium urearyticum, a bacterial species that produces urease, was detected by urine culture. Therefore, she was diagnosed with hyperammonemic encephalopathy resulting from urinary tract infection caused by urease-producing bacteria. In this case, urologic active agents had been administered to treat neurogenic bladder. We suspect that these drugs caused urinary obstruction and urinary tract infection. It is important to recognize that obstructive urinary tract infection caused by urease-producing bacteria can cause hyperammonemia. Neurological disorders, such as Parkinson's disease, tend to complicate neurogenic bladder. This disease should be considered in elderly patients with Parkinson's disease who are receiving urologic active drugs.

Urinary glicosaminoglycans levels in women with urinary tract infection and non urinary tract infection

NASA Astrophysics Data System (ADS)

Pasaribu, H. P.; Hanifa, A.; Tala, R. Z.; Ardiansyah, E.; Simanjuntak, R. Y.; Effendy, I. H.

2018-03-01

UTI is an infection that occurs in the urinary tract due to the proliferation of a microorganism. Female is fourteen times more vulnerable to UTI than male, because their urethra is shorter. Bladder epithelium is coated with a thin layer of glycosaminoglycans which act as a non-specific anti-adherence factor and nonspecific defense mechanisms against infection and can be found in the urine. An analytic study with cross sectional approach was conducted in 46 patients (23 with UTI and 23 non UTI) from June 2016 to determine differences in levels of urinary glycosaminoglycans between two groups. Urine samples were taken and tested for UTI and non UTI strips test. Laboratory examination of urine GAGs levels using ELISA kit for Human Glycosaminoglycans, then tabulated and analyzed using SPSS. The result showed no significant differences in the characteristics of women between two groups. There are significant differences in the mean levels of urinary GAGs in women with UTI compared with Non-UTI (69.74 ± 21.34; 21.39 ± 2.61 mg/l; p <0.001). There was no significant relationship between the sexual status and UTI incidence, with low odds ratio values and no significant difference in the mean of urinary glicosaminoglycans level based on sexual status.

Urinary bisphenol A levels in Turkish girls with premature thelarche.

PubMed

Durmaz, E; Asci, A; Erkekoglu, P; Balcı, A; Bircan, I; Koçer-Gumusel, B

2018-01-01

There is a growing concern over the timing of pubertal breast development and its possible association with exposure to endocrine disrupting chemicals (EDCs), such as bisphenol A (BPA). BPA is abundantly used to harden plastics. The aim of this study was to investigate the relation between premature thelarche (PT) and BPA by comparing the urinary BPA levels of PT girls with those of healthy subjects. Twenty-five newly diagnosed nonobese PT subjects (aged 4-8 years) who were admitted to the Pediatric Endocrinology Department at Akdeniz University were recruited. The control group composed of 25 age-matched girls without PT and other endocrine disorders. Urinary BPA levels were measured by high pressure liquid chromatography. The median urinary concentrations of BPA were found to be significantly higher in the PT group compared to the healthy control group (3.2 vs. 1.62 μg/g creatinine, p < 0.05). We observed a weak positive correlation between uterus volume and urinary BPA levels. There was a weak correlation between estradiol and urinary BPA levels ( r = 0.166; p = 0.37); and luteinizing hormone and urinary BPA levels ( r = 0.291; p = 0.08) of PT girls. Our results suggest that exposure to BPA might be one of the underlying factors of early breast development in prepubertal girls and EDCs may be considered as one of the etiological factors in the development of PT.

Predictors of Urinary 3-Phenoxybenzoic Acid Levels in 50 North Carolina Adults

PubMed Central

Morgan, Marsha; Jones, Paul; Sobus, Jon; Boyd Barr, Dana

2016-01-01

Limited data are available on the non-chemical stressors that impact adult exposures to pyrethroid insecticides based on urinary biomonitoring. The urinary metabolite, 3-phenoxybenzoic acid (3-PBA), is commonly used to assess human exposure to a number of pyrethroids. In a further analysis of published study data, we quantified urinary 3-PBA levels of 50 adults over a single, 24-h sampling period and examined the associations between the biomarker measurements and selected non-chemical stressors (demographic, lifestyle, and dietary factors). A convenience sample of 50 adults was recruited in North Carolina in 2009–2011. Participants collected individual urine voids (up to 11) and filled out activity, food, and pesticide use diaries over a 24-h sampling period. Urine voids (n = 326) were analyzed for 3-PBA concentrations using high-performance liquid chromatography-tandem mass spectrometry. 3-PBA was detected in 98% of the 24-h composited urine samples. The geometric mean urinary 3-PBA level was 1.68 ng/mL in adults. Time spent outside (p = 0.0006) was a highly significant predictor of natural log-transformed (ln) urinary 3-PBA levels, while consumption of coffee (p = 0.007) and breads (p = 0.019) and ln creatinine levels (p = 0.037) were significant predictors of urinary 3-PBA levels. In conclusion, we identified specific factors that substantially increased adult exposures to pyrethroids in their everyday environments. PMID:27886113

Increased Klk9 Urinary Excretion Is Associated to Hypertension-Induced Cardiovascular Damage and Renal Alterations

PubMed Central

Blázquez-Medela, Ana M.; García-Sánchez, Omar; Quirós, Yaremi; Blanco-Gozalo, Victor; Prieto-García, Laura; Sancho-Martínez, Sandra M.; Romero, Miguel; Duarte, Juan M.; López-Hernández, Francisco J.; López-Novoa, José M.; Martínez-Salgado, Carlos

2015-01-01

Abstract Early detection of hypertensive end-organ damage and secondary diseases are key determinants of cardiovascular prognosis in patients suffering from arterial hypertension. Presently, there are no biomarkers for the detection of hypertensive target organ damage, most outstandingly including blood vessels, the heart, and the kidneys. We aimed to validate the usefulness of the urinary excretion of the serine protease kallikrein-related peptidase 9 (KLK9) as a biomarker of hypertension-induced target organ damage. Urinary, plasma, and renal tissue levels of KLK9 were measured by the Western blot in different rat models of hypertension, including angiotensin-II infusion, DOCA-salt, L-NAME administration, and spontaneous hypertension. Urinary levels were associated to cardiovascular and renal injury, assessed by histopathology. The origin of urinary KLK9 was investigated through in situ renal perfusion experiments. The urinary excretion of KLK9 is increased in different experimental models of hypertension in rats. The ACE inhibitor trandolapril significantly reduced arterial pressure and the urinary level of KLK9. Hypertension did not increase kidney, heart, liver, lung, or plasma KLK9 levels. Hypertension-induced increased urinary excretion of KLK9 results from specific alterations in its tubular reabsorption, even in the absence of overt nephropathy. KLK9 urinary excretion strongly correlates with cardiac hypertrophy and aortic wall thickening. KLK9 appears in the urine in the presence of hypertension as a result of subtle renal handling alterations. Urinary KLK9 might be potentially used as an indicator of hypertensive cardiac and vascular damage. PMID:26469898

Changes in urinary Cu, Zn, and Se levels in cancer patients after treatment with Sha Shen Mai Men Dong Tang

PubMed Central

Lai, Tung-Yuan; Kuo, Hsien-Wen

2015-01-01

Sha Shen Mai Men Dong Tang (SMD-2; 沙參麥冬湯 shā shēn mài dōng tāng) is a Chinese medicinal herb (CMH; 中草藥 zhōng cǎo yào) used to treat symptoms associated with cancer therapy. The objective of this study was to assess the effect of SMD-2 on the levels of urinary copper (Cu), zinc (Zn), and selenium (Se) in lung cancer patients and head and neck cancer patients receiving chemoradiotherapy. Forty-two head and neck cancer patients and 10 lung cancer patients participated in our clinical trial. Each patient received chemoradiotherapy for 4 weeks. In addition, each patient was treated with SMD-2 for 8 weeks, including 2 weeks prior to and after the chemoradiotherapy treatment. Comparison of urinary Cu, Zn, and Se levels and the ratios of Zn to Cu and Se to Cu at three time points in the two types of cancer were assessed using the generalized estimating equations (GEEs). After the patients received chemoradiotherapy for 4 weeks, SMD-2 treatment was found to be associated with a significant decrease in urinary Cu levels, whereas urinary Zn and Se levels increased significantly. In addition, the ratios of Zn to Cu and Se to Cu in the urine samples of these patients also increased significantly. Both the urinary Zn levels and the ratio of Zn to Cu in head and neck cancer patients were significantly higher than in lung cancer patients. Urinary Zn and Se levels and the ratios of Zn to Cu and Se to Cu, but not urinary Cu levels, increased significantly during and after treatment when assessed using the GEE model. The SMD-2 treatments significantly increased Zn and Se levels in the urine of head and neck cancer patients. Increased Zn and Se levels in urine strengthened immune system. PMID:27114935

The correlation between urinary 5-hydroxyindoleacetic acid and sperm quality in infertile men and rotating shift workers.

PubMed

Ortiz, Águeda; Espino, Javier; Bejarano, Ignacio; Lozano, Graciela M; Monllor, Fabián; García, Juan F; Pariente, José A; Rodríguez, Ana B

2010-11-08

Serotonin is a neurotransmitter that modulates a wide range of neuroendocrine functions. However, excessive circulating serotonin levels may induce harmful effects in the male reproductive system. The objective of this study was to evaluate whether the levels of urinary 5-hydroxyindoleacetic acid (5-HIIA), a major serotonin metabolite, correlate with different classical seminal parameters. Human ejaculates were obtained from 40 men attending infertility counselling and rotating shift workers by masturbation after 4-5 days of abstinence. Urinary 5- HIIA concentration was quantified by using a commercial ELISA kit. Forward motility was assessed by a computer-aided semen analysis (CASA) system. Sperm concentration was determined using the haemocytometer method. Sperm morphology was evaluated after Diff-Quik staining, while sperm vitality was estimated after Eosin-Nigrosin vital staining. Our results show that urinary 5-HIIA levels obtained from a set of 20 volunteers negatively correlated with sperm concentration, forward motility, morphology normal range and sperm vitality. On the other hand, we checked the relationship between male infertility and urinary 5-HIIA levels in 20 night shift workers. Thus, urinary 5-HIIA levels obtained from 10 recently-proven fathers were significantly lower than those found in 10 infertile males. Additionally, samples from recent fathers exhibited higher sperm concentration, as well as better forward motility and normal morphology rate. In the light of our findings, we concluded that high serotonin levels, indirectly measured as urinary 5-HIIA levels, appear to play a role as an infertility determinant in male subjects.

Anhydrous polymer-based coating with sustainable controlled release functionality for facile, efficacious impregnation, and delivery of antimicrobial peptides.

PubMed

Lim, Kaiyang; Saravanan, Rathi; Chong, Kelvin K L; Goh, Sharon H M; Chua, Ray R Y; Tambyah, Paul A; Chang, Matthew W; Kline, Kimberly A; Leong, Susanna S J

2018-04-17

Anhydrous polymers are actively explored as alternative materials to overcome limitations of conventional hydrogel-based antibacterial coating. However, the requirement for strong organic solvent in polymerization reactions often necessitates extra protection steps for encapsulation of target biomolecules, lowering encapsulation efficiency, and increasing process complexity. This study reports a novel coating strategy that allows direct solvation and encapsulation of antimicrobial peptides (HHC36) into anhydrous polycaprolactone (PCL) polymer-based dual layer coating. A thin 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) film is layered onto the peptide-impregnated PCL as a diffusion barrier, to modulate and enhance release kinetics. The impregnated peptides are eventually released in a controlled fashion. The use of 2,2,2-trifluoroethanol (TFE), as polymerization and solvation medium, induces the impregnated peptides to adopt highly stable turned conformation, conserving peptide integrity, and functionality during both encapsulation and subsequent release processes. The dual layer coating showed sustained antibacterial functionality, lasting for 14 days. In vivo assessment using an experimental mouse wounding model demonstrated good biocompatibility and significant antimicrobial efficacy of the coating under physiological conditions. The coating was translated onto silicone urinary catheters and showed promising antibacterial efficacy, even outperforming commercial silver-based Dover cather. This anhydrous polymer-based platform holds immense potential as an effective antibacterial coating to prevent clinical device-associated infections. The simplicity of the coating process enhances its industrial viability. © 2018 Wiley Periodicals, Inc.

Urinary metabolite levels and symptoms in Filipino workers using organic solvents.

PubMed

Cucueco, M T; Espinosa, N C; Villanueva, M B; Castro, F T; Sison, S Y; Ortega, V S; Hisanaga, N

1993-01-01

To compare symptoms with urinary metabolite levels, 900 workers from 7 organic solvent-using industries were studied. Urinary metabolites were determined using a high performance liquid chromatograph. Urinary hippuric acid concentrations exceeding the reference value (2.5 g/g creatinine) were found in 78 (8.7%) workers. However, only 3 (0.3%) and 1 (0.1%) of the participants exceeded the reference value for mandelic (0.8 g/g creatinine) and total methylhippuric acid (1.5 g/g creatinine), respectively. The sum of the values of the ratio of measured urinary metabolite concentration to the corresponding ACGIH's biological exposure indices (BEI) [(HA/BEI of HA + MHA/BEI of MHA + MA/BEI of MA)] exceeded 1.0 in 166 (18.4%) workers. Majority of them were from the footwear manufacturing industry (63/129 or 49.2%). Questionnaire interviews were also administered to determine the prevalence of symptoms while at work (acute symptoms) or within the past 6 months (chronic symptoms). Urinary metabolite levels of individual and mixed solvents were compared with the symptoms of all workers. Analysis using Spearman's rank correlation showed in workers whose urinary hippuric acid exceeded 3.75 g/g creatine (1.5 x BEI), significant correlation between their hippuric acid levels and subjective complaints. Workers whose sum of the values of the ratio of measured urinary metabolite concentration to corresponding BEI exceeded 1.5 were selected and comparing this level with their symptoms, significant correlation was also noted in some complaints.

Urinary YKL-40 as a Candidate Biomarker for Febrile Urinary Tract Infection in Young Children.

PubMed

Kim, Hyun Hee; Chung, Mi Hae; Bin, Joong Hyun; Cho, Kyoung Soon; Lee, Juyoung; Suh, Jin Soon

2018-01-01

Given that YKL-40 is a known marker of inflammation, we sought to determine its association with urinary tract infection (UTI) in febrile children. In total, 44 children aged 0 to 24 months with febrile UTI and 35 age- and sex-matched controls with fever from other causes were enrolled in the study. ELISA was performed to determine the level of YKL-40 in urine collected from each child. The ratio of urinary YKL-40 to creatinine (Cr) was higher in the children with a UTI than in the controls (P<0.001). The area under the ROC curve for detecting UTI was 0.88 for the urinary YKL-40/Cr ratio, 0.86 for pyuria, and 0.71 for positive nitrite on urinalysis. We applied a cut-off value of 125.23 pg/mg to urinary YKL-40/Cr for detecting UTI. Eight of nine children in the control group with pyuria had urinary YKL-40/Cr levels lower than 125.23 pg/mg, and the one child in the UTI group without pyuria or positive nitrite had a urinary YKL-40/Cr level greater than 125.23 pg/mg. Determining the levels of urinary YKL-40/Cr may help identify true cases of UTI in febrile young children, especially when they have pyuria but not nitrite, or have neither pyuria nor nitrite in the urine. © The Korean Society for Laboratory Medicine

Urinary YKL-40 as a Candidate Biomarker for Febrile Urinary Tract Infection in Young Children

PubMed Central

Kim, Hyun Hee; Chung, Mi Hae; Bin, Joong Hyun; Cho, Kyoung Soon; Lee, Juyoung

2018-01-01

Background Given that YKL-40 is a known marker of inflammation, we sought to determine its association with urinary tract infection (UTI) in febrile children. Methods In total, 44 children aged 0 to 24 months with febrile UTI and 35 age- and sex-matched controls with fever from other causes were enrolled in the study. ELISA was performed to determine the level of YKL-40 in urine collected from each child. Results The ratio of urinary YKL-40 to creatinine (Cr) was higher in the children with a UTI than in the controls (P<0.001). The area under the ROC curve for detecting UTI was 0.88 for the urinary YKL-40/Cr ratio, 0.86 for pyuria, and 0.71 for positive nitrite on urinalysis. We applied a cut-off value of 125.23 pg/mg to urinary YKL-40/Cr for detecting UTI. Eight of nine children in the control group with pyuria had urinary YKL-40/Cr levels lower than 125.23 pg/mg, and the one child in the UTI group without pyuria or positive nitrite had a urinary YKL-40/Cr level greater than 125.23 pg/mg. Conclusions Determining the levels of urinary YKL-40/Cr may help identify true cases of UTI in febrile young children, especially when they have pyuria but not nitrite, or have neither pyuria nor nitrite in the urine. PMID:29071817

Original Research: Potential of urinary nephrin as a biomarker reflecting podocyte dysfunction in various kidney disease models

PubMed Central

Wada, Yusuke; Moritani, Hiroshi; Mitori, Hikaru; Kondo, Mitsuhiro; Tanaka-Amino, Keiko; Eguchi, Megumi; Imasato, Akira; Inoki, Yutaka; Kajiyama, Hiroshi; Mimura, Toshihide; Tomura, Yuichi

2016-01-01

Urinary nephrin is a potential non-invasive biomarker of disease. To date, however, most studies of urinary nephrin have been conducted in animal models of diabetic nephropathy, and correlations between urinary nephrin-to-creatinine ratio and other parameters have yet to be evaluated in animal models or patients of kidney disease with podocyte dysfunction. We hypothesized that urinary nephrin-to-creatinine ratio can be up-regulated and is negatively correlated with renal nephrin mRNA levels in animal models of kidney disease, and that increased urinary nephrin-to-creatinine ratio levels are attenuated following administration of glucocorticoids. In the present study, renal nephrin mRNA, urinary nephrin-to-creatinine ratio, urinary protein-to-creatinine ratio, and creatinine clearance ratio were measured in animal models of adriamycin nephropathy, puromycin aminonucleoside nephropathy, anti-glomerular basement membrane glomerulonephritis, and 5/6 nephrectomy. The effects of prednisolone on urinary nephrin-to-creatinine ratio and other parameters in puromycin aminonucleoside (single injection) nephropathy rats were also investigated. In all models tested, urinary nephrin-to-creatinine ratio and urinary protein-to-creatinine ratio increased, while renal nephrin mRNA and creatinine clearance ratio decreased. Urinary nephrin-to-creatinine ratio exhibited a significant negative correlation with renal nephrin mRNA in almost all models, as well as a significant positive correlation with urinary protein-to-creatinine ratio and a significant negative correlation with creatinine clearance ratio. Urinary protein-to-creatinine ratio exhibited a significant negative correlation with renal nephrin mRNA. Following the administration of prednisolone to puromycin aminonucleoside (single injection) nephropathy rats, urinary nephrin-to-creatinine ratio was significantly suppressed and exhibited a significant positive correlation with urinary protein-to-creatinine ratio. In addition, the decrease in number of glomerular Wilms tumor antigen-1-positive cells was attenuated, and urinary nephrin-to-creatinine ratio exhibited a significant negative correlation in these cells. In conclusion, these results suggest that urinary nephrin-to-creatinine ratio level is a useful and reliable biomarker for predicting the amelioration of podocyte dysfunction by candidate drugs in various kidney disease models with podocyte dysfunction. This suggestion will also be validated in a clinical setting in future studies. PMID:27216597

Assessment of urinary thiodiglycolic acid exposure in school-aged children in the vicinity of a petrochemical complex in central Taiwan

DOE Office of Scientific and Technical Information (OSTI.GOV)

Huang, Po-Chin, E-mail: pchuang@nhri.org.tw

Background: School-aged children living in the vicinity of vinyl chloride (VCM)/polyvinyl chloride (PVC) factories may have an increased risk of exposure to hazardous air pollutants. Objectives: We aimed to evaluate the urinary thiodiglycolic acid (TDGA) level, as TDGA is a major metabolite of VCM, for students at elementary schools near a petrochemical complex in central Taiwan. Methods: We recruited 343 students from 5 elementary schools based on distance to the VCM/PVC factory. First-morning urine and blood samples were obtained from our subjects from October 2013 to September 2014. Urine samples were analyzed for urinary creatinine and TDGA using LC/MS–MS. Hepatitismore » virus infection were assessed using blood samples. We determined their vitamin consumption, resident location, parent’s employment, and other demographic or lifestyle characteristics using a questionnaire. Results: Median urinary TDGA levels for 316 students at 5 elementary schools from the closest (<.9 km) to the farthest (∼8.6 km) with respect to the petrochemical complex were 147.6, 95.5, 115.5, 86.8, and 17.3 μg/g creatinine, respectively. After adjusting for age, gender, hepatitis virus infection, vitamin B consumption, passive smoking, and home to source distance, we found that urinary TDGA levels for the closest students was significantly higher than those at other schools. Further, median urinary TDGA levels for students during school time were 4.1-fold higher than those during summer vacation. Conclusions: After adjusting for confounders, urinary TDGA levels for the school-aged children decreased with increasing distances between the elementary schools and the petrochemical complex. - Highlights: • We conducted a bio-monitoring survey of students nearby a petrochemical complex. • We measured thiodiglycolic acid (TDGA) as a biomarker of vinyl chloride monomer. • Increased urinary TDGA levels in students nearby a VCM factory was found. • Significantly lower urinary TDGA levels for students on summer vacation was found. • Spatial variation of urinary TGDA in students was found after adjustment.« less

Urinary 1-hydroxypyrene and malondialdehyde in male workers in Chinese restaurants

PubMed Central

Pan, C-H; Chan, C-C; Huang, Y-L; Wu, K-Y

2008-01-01

Objectives: To assess internal dose and oxidative stress in male restaurant workers exposed to polycyclic aromatic hydrocarbons (PAHs) from cooking oil fumes (COFs) in Chinese restaurants. Methods: The study participants included 288 male restaurant workers (171 kitchen and 117 service staff) in Chinese restaurants in Taiwan. Airborne particulate PAHs were measured over 12 h on each of two consecutive work days and then identified using high performance liquid chromatography. Urinary 1-hydroxypyrene (1-OHP) measurements were used to indicate COF exposure, and urinary malondialdehyde (MDA) was adopted as an oxidative stress marker. Multiple regression models were used to assess the relationship between MDA and 1-OHP levels after adjusting for key personal covariates. Results: Summed particulate PAH levels in kitchens (median 23.9 ng/m3) were significantly higher than those in dining areas (median 4.9 ng/m3). For non-smoking kitchen staff, mean MDA and 1-OHP levels were 344.2 (SD 243.7) and 6.0 (SD 8.0) μmol/mol creatinine, respectively. These levels were significantly higher than those for non-smoking service staff, which were 244.2 (SD 164.4) and 2.4 (SD 4.3) μmol/mol creatinine, respectively. Urinary 1-OHP levels were significantly associated with work in kitchens (p<0.05). Furthermore, urinary MDA levels were significantly associated with urinary 1-OHP levels (p<0.001) and working hours per day (p<0.05). Conclusions: These findings indicate that urinary 1-OHP and MDA levels reflect occupational exposure to PAHs from COFs and oxidative stress in workers in Chinese restaurants. PMID:18940956

Urinary 1-hydroxypyrene and malondialdehyde in male workers in Chinese restaurants.

PubMed

Pan, C-H; Chan, C-C; Huang, Y-L; Wu, K-Y

2008-11-01

To assess internal dose and oxidative stress in male restaurant workers exposed to polycyclic aromatic hydrocarbons (PAHs) from cooking oil fumes (COFs) in Chinese restaurants. The study participants included 288 male restaurant workers (171 kitchen and 117 service staff) in Chinese restaurants in Taiwan. Airborne particulate PAHs were measured over 12 h on each of two consecutive work days and then identified using high performance liquid chromatography. Urinary 1-hydroxypyrene (1-OHP) measurements were used to indicate COF exposure, and urinary malondialdehyde (MDA) was adopted as an oxidative stress marker. Multiple regression models were used to assess the relationship between MDA and 1-OHP levels after adjusting for key personal covariates. Summed particulate PAH levels in kitchens (median 23.9 ng/m(3)) were significantly higher than those in dining areas (median 4.9 ng/m(3)). For non-smoking kitchen staff, mean MDA and 1-OHP levels were 344.2 (SD 243.7) and 6.0 (SD 8.0) mumol/mol creatinine, respectively. These levels were significantly higher than those for non-smoking service staff, which were 244.2 (SD 164.4) and 2.4 (SD 4.3) mumol/mol creatinine, respectively. Urinary 1-OHP levels were significantly associated with work in kitchens (p<0.05). Furthermore, urinary MDA levels were significantly associated with urinary 1-OHP levels (p<0.001) and working hours per day (p<0.05). These findings indicate that urinary 1-OHP and MDA levels reflect occupational exposure to PAHs from COFs and oxidative stress in workers in Chinese restaurants.

Impact of radiotherapy and chemotherapy on biomarkers of oxidative DNA damage in lung cancer patients.

PubMed

Crohns, Marika; Saarelainen, Seppo; Erhola, Marina; Alho, Hannu; Kellokumpu-Lehtinen, Pirkko

2009-07-01

To assess oxidative damage to DNA during lung cancer (LC) treatments. Urinary levels of 8-oxoguanine (8-oxoGua) and levels of 8-oxo-2'-deoxyguanosine (8-oxodG) from urine and whole blood were determined in 36 non-cancer controls and 65 LC patients before any treatments. Samples were also obtained of LC patients during and after radiotherapy (RT, n=33) and chemotherapy (CT, n=16). Stage IV LC patients had higher urinary 8-oxoGua and 8-oxodG levels than patients with stage I-III disease (p=0.044 and p=0.034, respectively). Urinary 8-oxodG levels increased during the first week of RT (p<0.001). Nuclear 8-oxodG increased during RT and 3 months after start of RT. Nuclear 8-oxodG levels also rose between the first two CT cycles (p=0.043), and urinary 8-oxodG levels during the sixth CT cycle (p=0.009). Urinary DNA damage biomarker levels may be associated with LC stage. Both RT and CT increase the parameters of DNA oxidation.

Risk of death in heart disease is associated with elevated urinary globotriaosylceramide.

PubMed

Schiffmann, Raphael; Forni, Sabrina; Swift, Caren; Brignol, Nastry; Wu, Xiaoyang; Lockhart, David J; Blankenship, Derek; Wang, Xuan; Grayburn, Paul A; Taylor, Matthew R G; Lowes, Brian D; Fuller, Maria; Benjamin, Elfrida R; Sweetman, Lawrence

2014-02-04

Elevated urinary globotriaosylceramide (Gb3) has been considered a hallmark of Fabry disease, an X-linked lysosomal disorder that is a risk factor for most types of heart disease. We screened 1421 consecutive patients with common forms of heart disease for Fabry disease by measuring urinary Gb3 in whole urine using tandem mass spectrometry, α-galactosidase A activity in dried blood spots, and we looked for GLA mutations by parallel sequencing of the whole gene (exons and introns) in pooled genomic DNA samples followed by Sanger sequencing verification. GLA variants were found in 13 patients. In the 1408 patients without GLA mutations, urinary Gb3 levels were significantly higher in heart disease patients compared to 116 apparently healthy controls (median difference=10.0 ng/mL and P<0.001). Urinary lipid profiling showed that levels of 5 other lipids significantly distinguished between urine of patients with Fabry disease (n=7) and heart disease patients with elevated urinary Gb3 (n=6). Sphingomyelin and Gb3 levels were abnormal in the left ventricular wall of patients with ischemic heart failure. Elevated levels of urinary Gb3 were independently associated with increased risk of death in the average follow-up of 17 months (hazard ratio=1.59 for increase in Gb3 of 200, 95% CI=1.36 and 1.87, and P<0.0001). In heart disease patients who do not have Fabry disease or GLA gene mutations, a higher level of urinary Gb3 is positively associated with near-term mortality. The elevation of urinary Gb3 and that of other lipids suggests that heart disease is associated with multiorgan lipid abnormalities. clinicaltrials.gov. Unique Identifier: NCT01019629.

Risk of Death in Heart Disease is Associated With Elevated Urinary Globotriaosylceramide

PubMed Central

Schiffmann, Raphael; Forni, Sabrina; Swift, Caren; Brignol, Nastry; Wu, Xiaoyang; Lockhart, David J.; Blankenship, Derek; Wang, Xuan; Grayburn, Paul A.; Taylor, Matthew R. G.; Lowes, Brian D.; Fuller, Maria; Benjamin, Elfrida R.; Sweetman, Lawrence

2014-01-01

Background Elevated urinary globotriaosylceramide (Gb3) has been considered a hallmark of Fabry disease, an X‐linked lysosomal disorder that is a risk factor for most types of heart disease. Methods and Results We screened 1421 consecutive patients with common forms of heart disease for Fabry disease by measuring urinary Gb3 in whole urine using tandem mass spectrometry, α‐galactosidase A activity in dried blood spots, and we looked for GLA mutations by parallel sequencing of the whole gene (exons and introns) in pooled genomic DNA samples followed by Sanger sequencing verification. GLA variants were found in 13 patients. In the 1408 patients without GLA mutations, urinary Gb3 levels were significantly higher in heart disease patients compared to 116 apparently healthy controls (median difference=10.0 ng/mL and P<0.001). Urinary lipid profiling showed that levels of 5 other lipids significantly distinguished between urine of patients with Fabry disease (n=7) and heart disease patients with elevated urinary Gb3 (n=6). Sphingomyelin and Gb3 levels were abnormal in the left ventricular wall of patients with ischemic heart failure. Elevated levels of urinary Gb3 were independently associated with increased risk of death in the average follow‐up of 17 months (hazard ratio=1.59 for increase in Gb3 of 200, 95% CI=1.36 and 1.87, and P<0.0001). Conclusions In heart disease patients who do not have Fabry disease or GLA gene mutations, a higher level of urinary Gb3 is positively associated with near‐term mortality. The elevation of urinary Gb3 and that of other lipids suggests that heart disease is associated with multiorgan lipid abnormalities. Clinical Trial Registration URL: clinicaltrials.gov. Unique Identifier: NCT01019629. PMID:24496231

Age-related changes in urinary testosterone levels suggest differences in puberty onset and divergent life history strategies in bonobos and chimpanzees.

PubMed

Behringer, V; Deschner, T; Deimel, C; Stevens, J M G; Hohmann, G

2014-08-01

Research on age-related changes in morphology, social behavior, and cognition suggests that the development of bonobos (Pan paniscus) is delayed in comparison to chimpanzees (Pan troglodytes). However, there is also evidence for earlier reproductive maturation in bonobos. Since developmental changes such as reproductive maturation are induced by a number of endocrine processes, changes in hormone levels are indicators of different developmental stages. Age-related changes in testosterone excretion are an indirect marker for the onset of puberty in human and non-human primates. In this study we investigated patterns of urinary testosterone levels in male and female bonobos and chimpanzees to determine the onset of puberty. In contrast to other studies, we found that both species experience age-related changes in urinary testosterone levels. Older individuals of both sexes had significantly higher urinary testosterone levels than younger individuals, indicating that bonobos and chimpanzees experience juvenile pause. The males of both species showed a similar pattern of age-related changes in urinary testosterone levels, with a sharp increase in levels around the age of eight years. This suggests that species-differences in aggression and male mate competition evolved independently of developmental changes in testosterone levels. Females showed a similar pattern of age-related urinary testosterone increase. However, in female bonobos the onset was about three years earlier than in female chimpanzees. The earlier rise of urinary testosterone levels in female bonobos is in line with reports of their younger age of dispersal, and suggests that female bonobos experience puberty at a younger age than female chimpanzees. Copyright © 2014 Elsevier Inc. All rights reserved.

Domestic nitrogen oxide exposure, urinary nitrate, and asthma prevalence in preschool children.

PubMed

Ciuk, J; Volkmer, R E; Edwards, J W

2001-01-01

A South Australian preschool study carried out in 1993 showed that the prevalence of respiratory symptoms was significantly associated with use of unflued gas appliances for cooking and heating. The authors sought to determine an association between domestic exposure to nitrogen dioxide and the excretion of total urinary nitrate and nitrite, and their association with asthma prevalence. The results indicated that the geometric mean concentrations of nitrogen dioxide were much higher in homes that had natural gas appliance(s) and other types of appliances (i.e., electric and solid fuel). Higher levels of nitrogen dioxide were found in homes of suburban areas with higher prevalence of asthma and respiratory symptoms. Nitrogen dioxide levels were lower in the summer, and there was a higher level in kitchens than in bedrooms. Urinary nitrate excretion was evaluated in 1,335 preschool children from the same sampling areas. No association existed between nitrogen dioxide levels and urinary nitrates, nor was there a relationship between urinary nitrates and asthma prevalence. These findings confirm that there is a positive association between nitrogen dioxide exposure from gas appliances and the prevalence of respiratory symptoms, but urinary nitrate is not a useful biomarker of exposure at these levels.

Chromium Exposure and Hygienic Behaviors in Printing Workers in Southern Thailand

PubMed Central

Decharat, Somsiri

2015-01-01

Objectives. The main objective of this study was to assess the chromium exposure levels in printing workers. The study evaluated the airborne, serum, and urinary chromium levels and determines any correlation between level of chromium in specimen and airborne chromium levels. Material and Methods. A cross-sectional study was conducted with 75 exposed and 75 matched nonexposed subjects. Air breathing zone was measured by furnace atomic absorption spectrophotometer. Serum and urine samples were collected to determine chromium levels by graphite furnaces atomic absorption spectrometer chromium analyzer. Results and Discussion. The printing workers' urinary chromium levels (6.86 ± 1.93 μg/g creatinine) and serum chromium levels (1.24 ± 1.13 μg/L) were significantly higher than the control group (p < 0.001 and p < 0.001). Work position, duration of work, personal protective equipment (PPE), and personal hygiene were significantly associated with urinary chromium level and serum chromium levels (p < 0.001 and p < 0.001). This study found a correlation between airborne chromium levels and urinary chromium levels (r = 0.247, p = 0.032). A multiple regression model was constructed. Significant predictors of urinary and serum chromium levels were shown in this study. Conclusion. Improvements in working conditions, occupational health training, and PPE use are recommended to reduce chromium exposure. PMID:26448746

Urinary Angiotensinogen Excretion Level Is Associated With Elevated Blood Pressure in the Normotensive General Population.

PubMed

Sato, Emiko; Wang, An Yi; Satoh, Michihiro; Nishikiori, Yoko; Oba-Yabana, Ikuko; Yoshida, Mai; Sato, Hiroshi; Ito, Sadayoshi; Hida, Wataru; Mori, Takefumi

2018-05-07

Inflammation, intrarenal renin-angiotensin system (RAS) activation, oxidative stress, and carbonyl stress have been postulated to play a fundamental role in controlling blood pressure. However, little is known about the association among renal RAS activation, carbonyl stress, and blood pressure elevation. We evaluated the relationship between blood pressure elevation and either renal RAS activity or carbonyl stress in the general population (N = 355) in Japan. To minimize the effect of antihypertensive drug therapy, we divided participants into 3 groups (normotensive, hypertensive-with-non-medication, and hypertensive-with-medication). Intrarenal RAS activity and carbonyl stress were indicated by the urinary angiotensinogen (AGT) and carbonyl compound excretion levels, respectively. The urinary AGT and carbonyl compound excretion levels were significantly associated with blood pressure. Using a stepwise multiple regression analysis, we found that the urinary AGT excretion levels were strongly associated with blood pressure elevation, compared with inflammation, oxidative stress, and carbonyl stress markers, in all groups. Urinary carbonyl compound excretion was significantly associated with blood pressure in only the hypertensive-without-medication group. Furthermore, blood pressure was significantly increased in these participants, and both the urinary AGT and carbonyl compound levels were high. The urinary AGT excretion levels were strongly associated with elevated blood pressure in normotensive people, and inappropriate renal RAS activity and carbonyl stress independently contributed to the development of hypertension. These findings suggest that RAS activation, particularly renal RAS activation exert a fundamental role in the pathogenesis of hypertension in the general population.

Urinary cadmium and blood pressure: results from the NHANES II survey.

PubMed Central

Whittemore, A S; DiCiccio, Y; Provenzano, G

1991-01-01

Relationships between urinary cadmium levels and blood pressure were examined in a sample of 951 adult men and women who participated in the Second National Health and Nutritional Examination Survey (NHANES II). Among all participants, positive relationships were seen between urinary cadmium levels and both systolic and diastolic blood pressure (p less than 0.05 and p less than 0.01, respectively), after adjusting for age, sex, race, relative body weight, smoking status, and hypertensive medication use. However, analyses for subgroups determined by sex and smoking status were inconsistent. Among current smokers, urinary cadmium levels were significantly positively associated with both systolic and diastolic blood pressure for women, and with diastolic blood pressure for men. Yet among former smokers and lifelong nonsmokers of both sexes, urinary cadmium was not significantly associated with either systolic or diastolic blood pressure. Evidence that some hypertensive medications increase urinary cadmium excretion suggests that the positive associations seen among current smokers may reflect high urinary cadmium levels among hypertensives induced by hypertensive treatment. After treated hypertensives were removed from the analysis, regression coefficients relating blood pressure to cadmium dropped by a factor of two and lost statistical significance. We conclude that the present data provide little support for a causal association between systemic cadmium and hypertension at nonoccupational exposure levels. Further, conflicting results of previous studies may reflect failure to control adequately for age, smoking status, and hypertensive treatment. PMID:2040243

Can lemon juice be an alternative to potassium citrate in the treatment of urinary calcium stones in patients with hypocitraturia? A prospective randomized study.

PubMed

Aras, Bekir; Kalfazade, Nadir; Tuğcu, Volkan; Kemahli, Eray; Ozbay, Bedi; Polat, Hakan; Taşçi, Ali Ihsan

2008-12-01

To investigate that lemon juice could be an alternative to potassium citrate in the treatment of urinary calcium stones in patients with hypocitraturia, 30 patients with hypocitraturic urinary calcium stones were enrolled into study. The patients were divided into three groups equally. Exactly 60 mEq/day fresh lemon juice ( approximately 85 cc/day) and potassium citrate (60 mEq/day) were given to the patients of first and second group, respectively. Dietary recommendations were made for the third group. Blood and 24-h urine tests were performed before treatment and repeated 3 months later. The differences between demographic datas of groups were not significant. There was no significant difference between values of blood tests performed before and after treatment in all groups. Statistically significant differences were found between pre- and post-treatment urine values in each group. Although there was no significant difference between pre-treatment citrate levels of the groups. A significant difference was found between post-treatment citrate levels of the groups. There was 2.5-, 3.5- and 0.8-fold increase in urinary citrate level of lemon juice, potassium citrate and dietary recommendation groups, respectively. Urinary calcium level was decreased only in lemon juice and potassium citrate groups after treatment. While there was no significant difference between pre- and post-treatment urinary oxalate levels in all groups, a significant decrease in urinary uric acid levels was determined in all groups. We suggest that lemon juice can be an alternative in the treatment of urinary calcium stones in patients with hypocitraturia. Additionally, dietary recommendations can increase effectiveness of the treatment.

The correlation between urinary 5-hydroxyindoleacetic acid and sperm quality in infertile men and rotating shift workers

PubMed Central

2010-01-01

Background Serotonin is a neurotransmitter that modulates a wide range of neuroendocrine functions. However, excessive circulating serotonin levels may induce harmful effects in the male reproductive system. The objective of this study was to evaluate whether the levels of urinary 5-hydroxyindoleacetic acid (5-HIIA), a major serotonin metabolite, correlate with different classical seminal parameters. Methods Human ejaculates were obtained from 40 men attending infertility counselling and rotating shift workers by masturbation after 4-5 days of abstinence. Urinary 5- HIIA concentration was quantified by using a commercial ELISA kit. Forward motility was assessed by a computer-aided semen analysis (CASA) system. Sperm concentration was determined using the haemocytometer method. Sperm morphology was evaluated after Diff-Quik staining, while sperm vitality was estimated after Eosin-Nigrosin vital staining. Results Our results show that urinary 5-HIIA levels obtained from a set of 20 volunteers negatively correlated with sperm concentration, forward motility, morphology normal range and sperm vitality. On the other hand, we checked the relationship between male infertility and urinary 5-HIIA levels in 20 night shift workers. Thus, urinary 5-HIIA levels obtained from 10 recently-proven fathers were significantly lower than those found in 10 infertile males. Additionally, samples from recent fathers exhibited higher sperm concentration, as well as better forward motility and normal morphology rate. Conclusions In the light of our findings, we concluded that high serotonin levels, indirectly measured as urinary 5-HIIA levels, appear to play a role as an infertility determinant in male subjects. PMID:21059225

Effect of Age, Educational Status, Parity and BMI on Development of Urinary Incontinence - a Cross Sectional Study in Saudi Population.

PubMed

Saadia, Zaheera

2015-08-01

The research article looks at the background of women with urinary incontinence and exposed to different demographic factors. Women who had urinary incontinence and women without urinary incontinence were compared with regards to their demographic features and risk of development of urinary problems. These risk factors can either cause short term or temporary urinary incontinence or they can cause long term or permanent urinary incontinence. This article explores the association of age, educational status, body mass index (BMI) and parity on the development of urinary incontinence. This study aimed at conducting an analysis into the risk factors that are related to urinary incontinence. Z-tests were conducted for every demographic factor and the results are then discussed comprehensively citing various studies that have been conducted before. Analysis shows that age and BMI increase chances of urinary infection and consequently urinary incontinence. Women of lower educational levels record more cases of urinary incontinence due to lack of general information about the condition. Women with higher parity levels also record more cases of urinary infections and subsequently urinary incontinence. From the analysis above, it can be seen that these factors usually play great roles in the existence and absence of urinary incontinence especially in women in Saudi Arabia. Most important is that, its prevention is mostly by use of the risk factors mentioned here in the research. This will usually involve observing a given risk factor to a state that makes it unfavorable for urinary incontinence to occur.

Platelet-derived growth factor receptor beta: a novel urinary biomarker for recurrence of non-muscle-invasive bladder cancer.

PubMed

Feng, Jiayu; He, Weifeng; Song, Yajun; Wang, Ying; Simpson, Richard J; Zhang, Xiaorong; Luo, Gaoxing; Wu, Jun; Huang, Chibing

2014-01-01

Non-muscle-invasive bladder cancer (NMIBC) is one of the most common malignant tumors in the urological system with a high risk of recurrence, and effective non-invasive biomarkers for NMIBC relapse are still needed. The human urinary proteome can reflect the status of the microenvironment of the urinary system and is an ideal source for clinical diagnosis of urinary system diseases. Our previous work used proteomics to identify 1643 high-confidence urinary proteins in the urine from a healthy population. Here, we used bioinformatics to construct a cancer-associated protein-protein interaction (PPI) network comprising 16 high-abundance urinary proteins based on the urinary proteome database. As a result, platelet-derived growth factor receptor beta (PDGFRB) was selected for further validation as a candidate biomarker for NMIBC diagnosis and prognosis. Although the levels of urinary PDGFRB showed no significant difference between patients pre- and post-surgery (n = 185, P>0.05), over 3 years of follow-up, urinary PDGFRB was shown to be significantly higher in relapsed patients (n = 68) than in relapse-free patients (n = 117, P<0.001). The levels of urinary PDGFRB were significantly correlated with the risk of 3-year recurrence of NMIBC, and these levels improved the accuracy of a NMIBC recurrence risk prediction model that included age, tumor size, and tumor number (area under the curve, 0.862; 95% CI, 0.809 to 0.914) compared to PDGFR alone. Therefore, we surmise that urinary PDGFRB could serve as a non-invasive biomarker for predicting NMIBC recurrence.

The Role of Nitric Oxide and Hydrogen Sulfide in Urinary Tract Function.

PubMed

Fernandes, Vítor S; Hernández, Medardo

2016-10-01

This MiniReview focuses on the role played by nitric oxide (NO) and hydrogen sulfide (H 2 S) in physiology of the upper and lower urinary tract. NO and H 2 S, together with carbon monoxide, belong to the group of gaseous autocrine/paracrine messengers or gasotransmitters, which are employed for intra- and intercellular communication in almost all organ systems. Because they are lipid-soluble gases, gaseous transmitters are not constrained by cellular membranes, so that their storage in vesicles for later release is not possible. Gasotransmitter signals are terminated by falling concentrations upon reduction in production that are caused by reacting with cellular components (essentially reactive oxygen species and NO), binding to cellular components or diffusing away. NO and, more recently, H 2 S have been identified as key mediators in neurotransmission of the urinary tract, involved in the regulation of ureteral smooth muscle activity and urinary flow ureteral resistance, as well as by playing a crucial role in the smooth muscle relaxation of bladder outlet region. Urinary bladder function is also dependent on integration of inhibitory mediators, such as NO, released from the urothelium. In the bladder base and distal ureter, the co-localization of neuronal NO synthase with substance P and calcitonin gene-related peptide in sensory nerves as well as the existence of a high nicotinamide adenine dinucleotide phosphate-diaphorase activity in dorsal root ganglion neurons also suggests the involvement of NO as a sensory neurotransmitter. © 2016 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).

Urinary Levels of N-Nitroso Compounds in Relation to Risk of Gastric Cancer: Findings from the Shanghai Cohort Study

PubMed Central

Xu, Ling; Qu, Yong-Hua; Chu, Xin-Di; Wang, Renwei; Nelson, Heather H.; Gao, Yu-Tang; Yuan, Jian-Min

2015-01-01

Background N-Nitroso compounds are thought to play a significant role in the development of gastric cancer. Epidemiological data, however, are sparse in examining the associations between biomarkers of exposure to N-nitroso compounds and the risk of gastric cancer. Methods A nested case-control study within a prospective cohort of 18,244 middle-aged and older men in Shanghai, China, was conducted to examine the association between urinary level of N-nitroso compounds and risk of gastric cancer. Information on demographics, usual dietary intake, and use of alcohol and tobacco was collected through in-person interviews at enrollment. Urinary levels of nitrate, nitrite, N-nitroso-2-methylthiazolidine-4-carboxylic acid (NMTCA), N-nitrosoproline (NPRO), N-nitrososarcosine (NSAR), N-nitrosothiazolidine-4-carboxylic acid (NTCA), as well as serum H. pylori antibodies were quantified in 191 gastric cancer cases and 569 individually matched controls. Logistic regression method was used to assess the association between urinary levels of N-nitroso compounds and risk of gastric cancer. Results Compared with controls, gastric cancer patients had overall comparable levels of urinary nitrate, nitrite, and N-nitroso compounds. Among individuals seronegative for antibodies to H. pylori, elevated levels of urinary nitrate were associated with increased risk of gastric cancer. The multivariate-adjusted odds ratios for the second and third tertiles of nitrate were 3.27 (95% confidence interval = 0.76–14.04) and 4.82 (95% confidence interval = 1.05–22.17), respectively, compared with the lowest tertile (P for trend = 0.042). There was no statistically significant association between urinary levels of nitrite or N-nitroso compounds and risk of gastric cancer. Urinary NMTCA level was significantly associated with consumption of alcohol and preserved meat and fish food items. Conclusion The present study demonstrates that exposure to nitrate, a precursor of N-nitroso compounds, may increase the risk of gastric cancer among individuals without a history of H. pylori infection. PMID:25658333

Urinary levels of N-nitroso compounds in relation to risk of gastric cancer: findings from the shanghai cohort study.

PubMed

Xu, Ling; Qu, Yong-Hua; Chu, Xin-Di; Wang, Renwei; Nelson, Heather H; Gao, Yu-Tang; Yuan, Jian-Min

2015-01-01

N-Nitroso compounds are thought to play a significant role in the development of gastric cancer. Epidemiological data, however, are sparse in examining the associations between biomarkers of exposure to N-nitroso compounds and the risk of gastric cancer. A nested case-control study within a prospective cohort of 18,244 middle-aged and older men in Shanghai, China, was conducted to examine the association between urinary level of N-nitroso compounds and risk of gastric cancer. Information on demographics, usual dietary intake, and use of alcohol and tobacco was collected through in-person interviews at enrollment. Urinary levels of nitrate, nitrite, N-nitroso-2-methylthiazolidine-4-carboxylic acid (NMTCA), N-nitrosoproline (NPRO), N-nitrososarcosine (NSAR), N-nitrosothiazolidine-4-carboxylic acid (NTCA), as well as serum H. pylori antibodies were quantified in 191 gastric cancer cases and 569 individually matched controls. Logistic regression method was used to assess the association between urinary levels of N-nitroso compounds and risk of gastric cancer. Compared with controls, gastric cancer patients had overall comparable levels of urinary nitrate, nitrite, and N-nitroso compounds. Among individuals seronegative for antibodies to H. pylori, elevated levels of urinary nitrate were associated with increased risk of gastric cancer. The multivariate-adjusted odds ratios for the second and third tertiles of nitrate were 3.27 (95% confidence interval = 0.76-14.04) and 4.82 (95% confidence interval = 1.05-22.17), respectively, compared with the lowest tertile (P for trend = 0.042). There was no statistically significant association between urinary levels of nitrite or N-nitroso compounds and risk of gastric cancer. Urinary NMTCA level was significantly associated with consumption of alcohol and preserved meat and fish food items. The present study demonstrates that exposure to nitrate, a precursor of N-nitroso compounds, may increase the risk of gastric cancer among individuals without a history of H. pylori infection.

Metabolism of growth hormone releasing peptides.

PubMed

Thomas, Andreas; Delahaut, Philippe; Krug, Oliver; Schänzer, Wilhelm; Thevis, Mario

2012-12-04

New, potentially performance enhancing compounds have frequently been introduced to licit and illicit markets and rapidly distributed via worldwide operating Internet platforms. Developing fast analytical strategies to follow these new trends is one the most challenging issues for modern doping control analysis. Even if reference compounds for the active drugs are readily obtained, their unknown metabolism complicates effective testing strategies. Recently, a new class of small C-terminally amidated peptides comprising four to seven amino acid residues received considerable attention of sports drug testing authorities due to their ability to stimulate growth hormone release from the pituitary. The most promising candidates are the growth hormone releasing peptide (GHRP)-1, -2, -4, -5, -6, hexarelin, alexamorelin, and ipamorelin. With the exemption of GHRP-2, the entity of these peptides represents nonapproved pharmaceuticals; however, via Internet providers, all compounds are readily available. To date, only limited information on the metabolism of these substances is available and merely one metabolite for GHRP-2 is established. Therefore, a comprehensive in vivo (po and iv administration in rats) and in vitro (with human serum and recombinant amidase) study was performed in order to generate information on urinary metabolites potentially useful for routine doping controls. The urine samples from the in vivo experiments were purified by mixed-mode cation-exchange solid-phase extraction and analyzed by ultrahigh-performance liquid chromatography (UHPLC) separation followed by high-resolution/high-accuracy mass spectrometry. Combining the high resolution power of a benchtop Orbitrap mass analyzer for the first metabolite screening and the speed of a quadrupole/time-of-flight (Q-TOF) instrument for identification, urinary metabolites were screened by means of a sensitive full scan analysis and subsequently confirmed by high-accuracy product ion scan experiments. Two deuterium-labeled internal standards (triply deuterated GHRP-4 and GHRP-2 metabolite) were used to optimize the extraction and analysis procedure. Overall, 28 metabolites (at least three for each GHRP) were identified from the in vivo samples and main metabolites were confirmed by the human in vitro model. All identified metabolites were formed due to exopeptidase- (amino- or carboxy-), amidase-, or endopeptidase activity.

Current Metabolic Status Affects Urinary Liver-Type Fatty-Acid Binding Protein in Normoalbuminuric Patients With Type 2 Diabetes

PubMed Central

Ito, Hiroyuki; Yamashita, Hitomi; Nakashima, Mina; Takaki, Akifusa; Yukawa, Chiduko; Matsumoto, Suzuko; Omoto, Takashi; Shinozaki, Masahiro; Nishio, Shinya; Abe, Mariko; Antoku, Shinichi; Mifune, Mizuo; Togane, Michiko

2017-01-01

Background We aimed to study the association between urinary liver-type fatty acid-binding protein (L-FABP), a biomarker of tubulointerstitial injury, and the clinical characteristics of normoalbuminuric and albuminuric patients with type 2 diabetes in order to detect the factors affecting urinary L-FABP. Methods Urinary L-FABP levels were measured in 788 patients with type 2 diabetes and again in 666 patients at 6 months after the initial measurement. The association between the urinary L-FABP level and the clinical parameters was investigated in a retrospective cross-sectional study and a subsequent observation. Results The HbA1c (odds ratio (OR): 1.42; 95% confidence interval (CI): 1.11 - 1.79; P < 0.01), systolic blood pressure (OR: 1.03; 95% CI: 1.01 - 1.05; P < 0.01) levels and estimated glomerular filtration rate (OR: 0.98; 95% CI: 0.96 - 1.00; P = 0.01) were significantly associated with the high levels of urinary L-FABP (> 8.4 μg/gCr) in normoalbuminuric patients. However, a logistic regression analysis revealed that use of renin-angiotensin system (RAS) inhibitors (OR: 2.22; 95% CI: 1.16 - 4.89; P = 0.02), urinary albumin-to-creatinine ratio (ACR) (OR: 1.01; 95% CI: 1.00 - 1.01; P < 0.01) and serum HDL-cholesterol concentration (OR: 0.33; 95% CI: 0.11 - 0.89; P = 0.03) were significantly associated in albuminuric patients. In the follow-up observation, the change in urinary L-FABP was found to be significantly (P < 0.01) influenced by the change in the HbA1c level in both the normoalbuminuric and albuminuric patients. Conclusions High urinary L-FABP is associated with part of the current metabolic abnormalities, including high levels of HbA1c and systolic blood pressure among normoalbuminuric patients with type 2 diabetes. PMID:28270898

Levels of plasma selenium and urinary total arsenic interact to affect the risk for prostate cancer.

PubMed

Hsueh, Yu-Mei; Su, Chien-Tien; Shiue, Horng-Sheng; Chen, Wei-Jen; Pu, Yeong-Shiau; Lin, Ying-Chin; Tsai, Cheng-Shiuan; Huang, Chao-Yuan

2017-09-01

This study investigated whether plasma selenium levels modified the risk for prostate cancer (PC) related to arsenic exposure. We conducted a case-control study that included 318 PC patients and 318 age-matched, healthy control subjects. Urinary arsenic profiles were examined using HPLC-HG-AAS and plasma selenium levels were measured by ICP-MS. We found that plasma selenium levels displayed a significant dose-dependent inverse association with PC. The odds ratio (OR) and 95% confidence interval (CI) for PC was 0.07 (0.04-0.13) among participants with a plasma selenium level >28.06 μg/dL vs. ≤19.13 μg/dL. A multivariate analysis showed that participants with a urinary total arsenic concentration >29.28 μg/L had a significantly higher OR (1.75, 1.06-2.89) for PC than participants with ≤29.89 μg/L. The combined presence of a low plasma selenium level and a high urinary total arsenic concentration exponentially increased the OR for PC, and additively interacted with PSA at levels ≥20 ng/mL. This is the first epidemiological study to examine the combined effects of plasma selenium and urinary total arsenic levels on the OR for PC. Our data suggest a low plasma selenium level coupled with a high urinary total arsenic concentration creates a significant risk for aggressive PC. Copyright © 2017 Elsevier Ltd. All rights reserved.

Fibroblast Growth Factor 23 Levels Associate with AKI and Death in Critical Illness.

PubMed

Leaf, David E; Jacob, Kirolos A; Srivastava, Anand; Chen, Margaret E; Christov, Marta; Jüppner, Harald; Sabbisetti, Venkata S; Martin, Aline; Wolf, Myles; Waikar, Sushrut S

2017-06-01

Elevated plasma levels of the osteocyte-derived hormone fibroblast growth factor 23 (FGF23) have emerged as a powerful biomarker of cardiovascular disease and death in patients with CKD. Whether elevated urinary or plasma FGF23 levels are prospectively associated with AKI and death in critically ill patients is unknown. We therefore conducted a prospective cohort study of 350 critically ill patients admitted to intensive care units at an academic medical center to investigate whether higher urinary FGF23 levels associate with the composite end point of AKI or in-hospital mortality (AKI/death). We measured urinary FGF23 levels within 24 hours of admission to the intensive care unit. In a subcohort ( n =131) we also measured plasma levels of FGF23, calcium, phosphate, parathyroid hormone, and vitamin D metabolites. Urinary and plasma FGF23 levels, but not other mineral metabolites, significantly associated with AKI/death. In multivariate analyses, patients in the highest compared with the lowest quartile of urinary FGF23 had a 3.9 greater odds (95% confidence interval, 1.6 to 9.5) of AKI/death. Higher urinary FGF23 levels also independently associated with greater hospital, 90-day, and 1-year mortality; longer length of stay; and several other important adverse outcomes. In conclusion, elevated FGF23 levels measured in the urine or plasma may be a promising novel biomarker of AKI, death, and other adverse outcomes in critically ill patients. Copyright © 2017 by the American Society of Nephrology.

HPLC method for urinary theobromine determination: Effect of consumption of cocoa products on theobromine urinary excretion in children.

PubMed

Rodriguez, Adrian; Costa-Bauza, Antonia; Saez-Torres, Concepcion; Rodrigo, Dolores; Grases, Felix

2015-11-01

To validate a simple method of urinary theobromine determination, to assess urinary theobromine levels in 80 healthy children and to relate these levels to consumption of cocoa products. Urine samples were diluted, directly injected into an HPLC system, separated by gradient elution on a C18 column, and detected by UV spectrometry. The method was validated for linearity, limits of detection and quantification, imprecision, accuracy, recovery and interferences. The proposed method was used to assess 12-h day and 12-h night urinary theobromine excretion by 80 healthy children, divided into four groups based on consumption of cocoa products. In addition, urinary excretion of magnesium and oxalate, also present in cocoa, was measured in these four groups. The method was linear to a theobromine concentration of 278μmol/L (50mg/L). LOD and LOQ for urine samples, diluted 1:5 (vol/vol) with water, were 1.1 and 3.6μmol/L respectively. Within-run and between-run imprecisions (CV) were each <2%. Average recovery was 99%, and analysis of a certified reference sample showed an error <2.5%. Theobromine excretion levels were significantly higher in healthy children with higher consumption of cocoa products (p<0.001), but oxalate (p=0.098) and magnesium (p=0.068) excretion levels did not differ significantly. This validated method resulted in urinary theobromine determination with 100% recovery, without sample pretreatment. Urinary theobromine levels in healthy children were directly related to their consumption of cocoa products. Copyright © 2015 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

Urinary Liver-Type Fatty Acid-Binding Protein Level as a Predictive Biomarker of Acute Kidney Injury in Patients with Acute Decompensated Heart Failure.

PubMed

Hishikari, Keiichi; Hikita, Hiroyuki; Nakamura, Shun; Nakagama, Shun; Mizusawa, Masahumi; Yamamoto, Tasuku; Doi, Junichi; Hayashi, Yosuke; Utsugi, Yuya; Araki, Makoto; Sudo, Yuta; Kimura, Shigeki; Takahashi, Atsushi; Ashikaga, Takashi; Isobe, Mitsuaki

2017-10-01

There are no biological markers to predict the onset of acute kidney injury (AKI) in patients with acute decompensated heart failure (ADHF). Liver-type fatty acid-binding protein (L-FABP) levels are markedly upregulated in the proximal tubules after renal ischemia. We investigated whether urinary L-FABP is a suitable marker to predict AKI in ADHF patients. We examined 281 consecutive patients with ADHF. Serum creatinine (Cr) and L-FABP levels were measured at admission and 24 and 48 h after admission. AKI developed in 104 patients (37%). Urinary L-FABP levels at admission were significantly higher in patients with AKI than in those without (33.0 vs. 5.2 μg/g Cr; p < 0.001). Multivariate analysis showed that baseline urinary L-FABP level was an independent predictor of AKI in ADHF patients (odds ratio 1.08, 95% confidence interval 1.05-1.12; p < 0.001). Receiver operating characteristic analysis showed that baseline urinary L-FABP level exhibited 94.2% sensitivity and 87.0% specificity at a cutoff value of 12.5 μg/g Cr. Urinary L-FABP level is useful for predicting the onset of AKI in patients with ADHF. The results of our study could help clinicians diagnose AKI in ADHF patients earlier, leading to possible improvements in the treatment of this group of patients.

A pilot study examining the relationship among Crohn disease activity, glucagon-like peptide-2 signalling and intestinal function in pediatric patients

PubMed Central

Sigalet, David L; Kravarusic, Dragan; Butzner, Decker; Hartmann, Bolette; Holst, Jens J; Meddings, Jon

2013-01-01

BACKGROUND/OBJECTIVES: The relationship between the enteroendocrine hormone glucagon-like peptide 2 (GLP-2) and intestinal inflammation is unclear. GLP-2 promotes mucosal growth, decreases permeability and reduces inflammation in the intestine; physiological stimulation of GLP-2 release is triggered by nutrient contact. The authors hypothesized that ileal Crohn disease (CD) affects GLP-2 release. METHODS: With ethics board approval, pediatric patients hospitalized with CD were studied; controls were recruited from local schools. Inclusion criteria were endoscopy-confirmed CD (primarily of the small intestine) with a disease activity index >150. Fasting and post-prandial GLP-2 levels and quantitative urinary recovery of orally administered 3-O-methyl-glucose (active transport) and lactulose/mannitol (passive) were quantified during the acute and remission phases. RESULTS: Seven patients (mean [± SD] age 15.3±1.3 years) and 10 controls (10.3±1.6 years) were studied. In patients with active disease, fasting levels of GLP-2 remained stable but postprandial levels were reduced. Patients with active disease exhibited reduced glucose absorption and increased lactulose/mannitol recovery; all normalized with disease remission. The change in the lactulose/mannitol ratio was due to both reduced lactulose and increased mannitol absorption. CONCLUSIONS: These findings suggest that pediatric patients with acute ileal CD have decreased postprandial GLP-2 release, reduced glucose absorption and increased intestinal permeability. Healing of CD resulted in normalization of postprandial GLP-2 release and mucosal functioning (nutrient absorption and permeability), the latter due to an increase in mucosal surface area. These findings have implications for the use of GLP-2 and feeding strategies as a therapy in CD patients; further studies of the effects of inflammation and the GLP-2 axis are recommended. PMID:24106731

Clinical utility of urinary soluble Fas in screening for bladder cancer.

PubMed

Srivastava, Anupam Kumar; Singh, Pankaj Kumar; Singh, Dhramveer; Dalela, Divakar; Rath, Srikanta Kumar; Bhatt, Madan Lal Brahma

2016-06-01

Early diagnosis of carcinoma of urinary bladder remains a challenge. Urine cytology, as an adjunct to cystoscopy, is less sensitive for low-grade tumors. Soluble Fas (sFas), a cell-surface receptor and member of the tumor necrosis factor superfamily, is frequently expressed in urinary bladder carcinoma. The objective of this study was to investigate the urinary sFas for diagnosis of transitional cell carcinoma (TCC) of urinary bladder. We examined urinary sFas concentration in 74 controls and 117 cases of TCC, both primary and recurrent disease, by using enzyme-linked immunosorbent assay and compared it with urinary cytology. Urinary sFas concentration was found to be significantly higher in the patient as compared to control group (P < 0.05). An optimal cutoff value of 174.0 pg/mL was proposed. The urinary sFas level was found to have an approximate sensitivity and specificity of 88.03% and 89.19% (P < 0.001), whereas urine cytology had sensitivity of 66.67% and specificity of 95.95%. sFas had better sensitivity in higher grade and both primary and recurrent cases of urinary bladder cancer in comparison with cytology. Out of 15 node positive bladder cancer cases, 13 had high urinary sFas levels, whereas 12 were urinary cytology positive for malignancy. Urinary sFas can be used as a non-invasive diagnostic biomarker for TCC of urinary bladder, both for primary and recurrent disease. © 2014 Wiley Publishing Asia Pty Ltd.

Effect of urinary pH and nicotine excretion rate on plasma nicotine during cigarette smoking and chewing nicotine gum

PubMed Central

Feyerabend, C.; Russell, M. A. H.

1978-01-01

1 Plasma nicotine levels produced by chewing nicotine gum were compared with those obtained by cigarette smoking under conditions of controlled urinary pH. 2 Although absorption was slower, plasma levels comparable to cigarette smoking were built up on 4 mg (but not 2 mg) nicotine gum. 3 Urinary excretion of nicotine was influenced markedly by pH and the rate of urine flow. 4 Plasma nicotine was higher under alkaline compared to acidic conditions (P < 0.001) but the rate of urinary nicotine excretion appeared to have little effect on the plasma level.

[Multidisciplinary approach to the treatment of colorectal cancer, complicated by urinary tract invasion].

PubMed

Likhter, M S; Shelygin, Iu A; Achkasov, S I

2012-01-01

Results of treatment of 277 patients with colorectal cancer stage IV complicated by the urinary tract invasion, were analyzed. Men were 168 (60.7%); women - 109 (39.3%). Patients aged 31-79 years (59.6±5.7) years. All patients were operated on radically with the resection of the invaded parts of the urinary tract en bloc. Both abdominal surgeons and urologists took part in the operation. The study proved that the invasion of the urinary tract by colorectal cancer should not become a reason for the surgery refusal. The subtotal resection of the urinary bladder by its cancer invasion demonstrated the appropriate radicalism and functional postoperative results. The efficacy of such combined operations was proved by the high level of social adaptation of the operated patients - 18 (51.4%) of 35 followed up patients came back to the previous level of social activity. Urinary tracts' resection did not influenced the level of postoperative lethality.

Original Research: Potential of urinary nephrin as a biomarker reflecting podocyte dysfunction in various kidney disease models.

PubMed

Wada, Yusuke; Abe, Masaki; Moritani, Hiroshi; Mitori, Hikaru; Kondo, Mitsuhiro; Tanaka-Amino, Keiko; Eguchi, Megumi; Imasato, Akira; Inoki, Yutaka; Kajiyama, Hiroshi; Mimura, Toshihide; Tomura, Yuichi

2016-10-01

Urinary nephrin is a potential non-invasive biomarker of disease. To date, however, most studies of urinary nephrin have been conducted in animal models of diabetic nephropathy, and correlations between urinary nephrin-to-creatinine ratio and other parameters have yet to be evaluated in animal models or patients of kidney disease with podocyte dysfunction. We hypothesized that urinary nephrin-to-creatinine ratio can be up-regulated and is negatively correlated with renal nephrin mRNA levels in animal models of kidney disease, and that increased urinary nephrin-to-creatinine ratio levels are attenuated following administration of glucocorticoids. In the present study, renal nephrin mRNA, urinary nephrin-to-creatinine ratio, urinary protein-to-creatinine ratio, and creatinine clearance ratio were measured in animal models of adriamycin nephropathy, puromycin aminonucleoside nephropathy, anti-glomerular basement membrane glomerulonephritis, and 5/6 nephrectomy. The effects of prednisolone on urinary nephrin-to-creatinine ratio and other parameters in puromycin aminonucleoside (single injection) nephropathy rats were also investigated. In all models tested, urinary nephrin-to-creatinine ratio and urinary protein-to-creatinine ratio increased, while renal nephrin mRNA and creatinine clearance ratio decreased. Urinary nephrin-to-creatinine ratio exhibited a significant negative correlation with renal nephrin mRNA in almost all models, as well as a significant positive correlation with urinary protein-to-creatinine ratio and a significant negative correlation with creatinine clearance ratio. Urinary protein-to-creatinine ratio exhibited a significant negative correlation with renal nephrin mRNA. Following the administration of prednisolone to puromycin aminonucleoside (single injection) nephropathy rats, urinary nephrin-to-creatinine ratio was significantly suppressed and exhibited a significant positive correlation with urinary protein-to-creatinine ratio. In addition, the decrease in number of glomerular Wilms tumor antigen-1-positive cells was attenuated, and urinary nephrin-to-creatinine ratio exhibited a significant negative correlation in these cells. In conclusion, these results suggest that urinary nephrin-to-creatinine ratio level is a useful and reliable biomarker for predicting the amelioration of podocyte dysfunction by candidate drugs in various kidney disease models with podocyte dysfunction. This suggestion will also be validated in a clinical setting in future studies. © 2016 by the Society for Experimental Biology and Medicine.

Renal function in urinary schistosomiasis in the Natal Province of South Africa.

PubMed

Coopan, R M; Naidoo, K; Jialal, I

1987-11-01

Renal function was assessed in 101 schoolchildren with active urinary schistosomiasis by measuring serum creatinine, urate, urea, and B2-microglobulin, urinary B2 microglobulin, and the glomerular filtration rate. Glomerular function in all subjects was normal as were serum creatinine, urate, and urea levels. Serum B2-microglobulin was elevated in only 8% of subjects while urinary B2-microglobulin only was raised in 7% of subjects, indicating proximal tubular dysfunction, a previously unreported feature in urinary schistosomiasis. Urinary tract abnormalities were found in 43% of subjects consenting to an excretory urogram but no correlation with biochemical parameters of renal function was noted. Serum angiotensin converting enzyme level measured in 70 subjects was elevated in 11% of subjects and was regarded as a possible measure of increased granulomatous activity.

The prevalence of and factors associated with urinary cotinine-verified smoking in Korean adults: The 2008-2011 Korea National Health and Nutrition Examination Survey.

PubMed

Hong, Jae Won; Noh, Jung Hyun; Kim, Dong-Jun

2018-01-01

Smoking rate based on self-reporting questionnaire might be underestimated. Cotinine is the principal metabolite of nicotine and is considered an accurate biomarker of exposure to cigarette smoke. This study evaluated the prevalence of and factors associated with urinary cotinine-verified smoking in Korean adults. We analyzed data from 12,110 adults in the 2008-2011 Korea National Health and Nutrition Examination Survey (KNHANES), using three threshold levels of urinary cotinine ≥100ng/ml, ≥50ng/ml, and ≥30ng/ml. The weighted prevalence of urinary cotinine levels of ≥100, ≥50, and ≥30 ng/mL in the whole study population was 34.7%, 37.1%, and 41.1%, respectively. Male sex, younger age, elementary school graduation, household income in the ≤24th percentile, service and sales workers and assembly workers, and high-risk alcohol drinking were associated with a higher prevalence of urinary cotinine level of ≥ 50 or 30 ng/mL, after we adjusted for age, sex, education level, number of family members, household income, occupation, and alcohol drinking. Logistic regression analyses were performed using the aforementioned variables as covariates to identify factors independently associated with cotinine-verified smoking. Men had a higher risk than women of having a urinary cotinine level of ≥50 ng/mL (OR 4.67, 95% CI 4.09-5.32, p < 0.001). When subjects ages 19-29 years were used as controls, adults ages 30-39 years had a 1.19-fold (CI 1.02-1.39, p = 0.026) higher risk of having a urinary cotinine level of ≥50 ng/mL. College graduates had a 32% lower risk of having a urinary cotinine level of ≥50 ng/mL than elementary school graduates (p < 0.001). A household income in the 25-49th percentile (OR 0.82, 95% CI 0.69-0.98, p = 0.026), 50-74th percentile (OR 0.64, 95% CI 0.53-0.76, p < 0.001), or ≥75th percentile (OR 0.64, 95% CI 0.53-0.77, p < 0.001) was associated with a lower risk of having a urinary cotinine level of ≥50 ng/mL compared to a household income in the ≤24th percentile. High-risk (OR 2.75, 95% CI 2.37-3.18, p < 0.001) and intermediate-risk (OR 2.04, 95% CI 1.82-2.30, p < 0.001) alcohol drinking were associated with having a urinary cotinine level of ≥50 ng/mL compared to low-risk alcohol drinking. Similar to the results of the logistic regression analyses of urinary cotinine ≥50 ng/mL, male sex, younger age, elementary school education, household income in the ≤24th percentile, and high-risk alcohol drinking were significantly associated with having a urinary cotinine level of ≥30 ng/mL. Service and sales workers (OR 1.22, 95% CI 1.01-1.48, p = 0.041) had a significantly higher risk of having a urinary cotinine level of ≥30 ng/mL. Based on a threshold urinary cotinine level of 50 ng/mL, the prevalence of cotinine-verified smoking in a representative sample of Korean adults was 37.1% (men 52.7%, women 15.4%). Younger age, male sex, low education level, service and sales workers, low household income, and high-risk alcohol drinking were associated with the risk of smoking.

Predictors of urinary levels of 2,4-dichlorophenoxyacetic acid, 3,5,6-trichloro-2-pyridinol, 3-phenoxybenzoic acid, and pentachlorophenol in 121 adults in Ohio.

PubMed

Morgan, Marsha K

2015-07-01

Limited data exist on the driving factors that influence the non-occupational exposures of adults to pesticides using urinary biomonitoring. In this work, the objectives were to quantify the urinary levels of 2,4-dichlorophenoxyacetic acid (2,4-D), 3,5,6-trichloro-2-pyridinol (TCP), 3-phenoxybenzoic acid (3-PBA), and pentachlorophenol (PCP) in 121 adults over a 48-h monitoring period and to examine the associations between selected sociodemographic and lifestyle factors and urinary levels of each pesticide biomarker. Adults, ages 20-49 years old, were recruited from six counties in Ohio (OH) in 2001. The participants collected 4-6 spot urine samples and completed questionnaires and diaries at home over a 48-h monitoring period. Urine samples were analyzed for 2,4-D, TCP, 3-PBA, and PCP by gas chromatography/mass spectrometry. Multiple regression modeling was used to determine the impact of selected sociodemographic and lifestyle factors on the log-transformed (ln) levels of each pesticide biomarker in adults. The pesticide biomarkers were detected in ≥ 89% of the urine samples, except for 3-PBA (66%). Median urinary levels of 2,4-D, TCP, 3-PBA, and PCP were 0.7, 3.4, 0.3, and 0.5 ng/mL, respectively. Results showed that 48-h sweet/salty snack consumption, 48-h time spend outside at home, and ln(creatinine) levels were significant predictors (p < 0.05), and race was a marginally significant predictor (p = 0.093) of the adults' ln(urinary 2,4-D) concentrations. Strong predictors (p < 0.05) of the adults' ln(urinary TCP) concentrations were urbanicity, employment status, sampling season, and ln(creatinine) levels. For 3-PBA, sampling season, pet ownership and removal of shoes before entering the home were significant predictors (p < 0.05) of the adults' ln(urinary 3-PBA) levels. Finally for PCP, removal of shoes before entering the home and ln(creatinine) levels were significant predictors (p < 0.05), and pet ownership was a marginally significant predictor (p = 0.056) of the adults' ln(urinary PCP) concentrations. In conclusion, specific sociodemographic and lifestyle factors were identified that increased the exposures of these adults to several different pesticides in their daily environments. Published by Elsevier GmbH.

Circadian rhythm of blood pressure and the renin-angiotensin system in the kidney.

PubMed

Ohashi, Naro; Isobe, Shinsuke; Ishigaki, Sayaka; Yasuda, Hideo

2017-05-01

Activation of the intrarenal renin-angiotensin system (RAS) has a critical role in the pathophysiology of the circadian rhythm of blood pressure (BP) and renal injury, independent of circulating RAS. Although it is clear that the circulating RAS has a circadian rhythm, reports of a circadian rhythm in tissue-specific RAS are limited. Clinical studies evaluating intrarenal RAS activity by urinary angiotensinogen (AGT) levels have indicated that urinary AGT levels were equally low during both the daytime and nighttime in individuals without chronic kidney disease (CKD) and that urinary AGT levels were higher during the daytime than at nighttime in patients with CKD. Moreover, urinary AGT levels of the night-to-day (N/D) ratio of urinary AGT were positively correlated with the levels of N/D of urinary protein, albumin excretion and BP. In addition, animal studies have demonstrated that the expression of intrarenal RAS components, such as AGT, angiotensin II (AngII) and AngII type 1 receptor proteins, increased and peaked at the same time as BP and urinary protein excretion during the resting phase, and the amplitude of the oscillations of these proteins was augmented in a chronic progressive nephritis animal compared with a control. Thus, the circadian rhythm of intrarenal RAS activation may lead to renal damage and hypertension, which both are associated with diurnal variations in BP. It is possible that augmented glomerular permeability increases AGT excretion levels into the tubular lumen and that circadian fluctuation of glomerular permeability influences the circadian rhythm of the intrarenal RAS.

Bisphenol A and Peripheral Arterial Disease: Results from the NHANES

PubMed Central

Teppala, Srinivas; Sabanayagam, Charumathi

2012-01-01

Background: Bisphenol A (BPA) is a common chemical used in the manufacture of polycarbonate plastics and epoxy resins, and > 93% of U.S. adults have detectable levels of urinary BPA. Recent animal studies have suggested that BPA exposure may have a role in several mechanisms involved in the development of cardiovascular disease (CVD), including weight gain, insulin resistance, thyroid dysfunction, endothelial dysfunction, and oxidative stress. However, few human studies have examined the association between markers of BPA exposure and CVD. Peripheral arterial disease (PAD) is a subclinical measure of atherosclerotic vascular disease and a strong independent risk factor for CVD and mortality. Objective: We examined the association between urinary BPA levels and PAD in a nationally representative sample of U.S. adults. Methods: We analyzed data from 745 participants in the National Health and Nutritional Examination Survey 2003–2004. We estimated associations between urinary BPA levels (in tertiles) and PAD (ankle–brachial index < 0.9, n = 63) using logistic regression models adjusted for potential confounders (age, sex, race/ethnicity, education, smoking, body mass index, diabetes mellitus, hypertension, urinary creatinine, estimated glomerular filtration rate, and serum cholesterol levels). Results: We observed a significant, positive association between increasing levels of urinary BPA and PAD before and after adjusting for confounders. The multivariable-adjusted odds ratio for PAD associated with the highest versus lowest tertile of urinary BPA was 2.69 (95% confidence interval: 1.02, 7.09; p-trend = 0.01). Conclusions: Urinary BPA levels were significantly associated with PAD, independent of traditional CVD risk factors. PMID:22645278

Glycemic Control and Urinary Tract Infections in Women with Type 1 Diabetes: Results from the DCCT/EDIC.

PubMed

Lenherr, Sara M; Clemens, J Quentin; Braffett, Barbara H; Cleary, Patricia A; Dunn, Rodney L; Hotaling, James M; Jacobson, Alan M; Kim, Catherine; Herman, William; Brown, Jeanette S; Wessells, Hunter; Sarma, Aruna V

2016-10-01

We examined the relationship between glycemic control and urinary tract infections in women with type 1 diabetes mellitus. Women enrolled in the Epidemiology of Diabetes Interventions and Complications study, the observational followup of the Diabetes Control and Complications Trial, were surveyed to assess the rate of physician diagnosed urinary tract infections in the preceding 12 months. The relationship between glycated hemoglobin levels and number of urinary tract infections in the previous 12 months was assessed using a multivariable Poisson regression model. A total of 572 women were evaluated at year 17. Mean age was 50.7 ± 7.2 years, mean body mass index was 28.6 ± 5.9 kg/m(2), mean type 1 diabetes duration was 29.8 ± 5.0 years and mean glycated hemoglobin was 8.0% ± 0.9%. Of these women 86 (15.0%) reported at least 1 physician diagnosed urinary tract infection during the last 12 months. Higher glycated hemoglobin levels were significantly associated with number of urinary tract infections such that for every unit increase (1%) in recent glycated hemoglobin level, there was a 21% (p=0.02) increase in urinary tract infection frequency in the previous 12 months after adjusting for race, hysterectomy status, urinary incontinence, sexual activity in the last 12 months, peripheral and autonomic neuropathy, and nephropathy. The frequency of urinary tract infections increases with poor glycemic control in women with type 1 diabetes. This relationship is independent of other well described predictors of urinary tract infections and suggests that factors directly related to glycemic control may influence the risk of lower urinary tract infections. Copyright © 2016 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Dermal Exposure to Jet Fuel JP-8 Significantly Contributes to the Production of Urinary Naphthols in Fuel-Cell Maintenance Workers

PubMed Central

Chao, Yi-Chun E.; Kupper, Lawrence L.; Serdar, Berrin; Egeghy, Peter P.; Rappaport, Stephen M.; Nylander-French, Leena A.

2006-01-01

Jet propulsion fuel 8 (JP-8) is the major jet fuel used worldwide and has been recognized as a major source of chemical exposure, both inhalation and dermal, for fuel-cell maintenance workers. We investigated the contributions of dermal and inhalation exposure to JP-8 to the total body dose of U.S. Air Force fuel-cell maintenance workers using naphthalene as a surrogate for JP-8 exposure. Dermal, breathing zone, and exhaled breath measurements of naphthalene were obtained using tape-strip sampling, passive monitoring, and glass bulbs, respectively. Levels of urinary 1- and 2-naphthols were determined in urine samples and used as biomarkers of JP-8 exposure. Multiple linear regression analyses were conducted to investigate the relative contributions of dermal and inhalation exposure to JP-8, and demographic and work-related covariates, to the levels of urinary naphthols. Our results show that both inhalation exposure and smoking significantly contributed to urinary 1-naphthol levels. The contribution of dermal exposure was significantly associated with levels of urinary 2-naphthol but not with urinary 1-naphthol among fuel-cell maintenance workers who wore supplied-air respirators. We conclude that dermal exposure to JP-8 significantly contributes to the systemic dose and affects the levels of urinary naphthalene metabolites. Future work on dermal xenobiotic metabolism and toxicokinetic studies are warranted in order to gain additional knowledge on naphthalene metabolism in the skin and the contribution to systemic exposure. PMID:16451852

Dermal exposure to jet fuel JP-8 significantly contributes to the production of urinary naphthols in fuel-cell maintenance workers.

PubMed

Chao, Yi-Chun E; Kupper, Lawrence L; Serdar, Berrin; Egeghy, Peter P; Rappaport, Stephen M; Nylander-French, Leena A

2006-02-01

Jet propulsion fuel 8 (JP-8) is the major jet fuel used worldwide and has been recognized as a major source of chemical exposure, both inhalation and dermal, for fuel-cell maintenance workers. We investigated the contributions of dermal and inhalation exposure to JP-8 to the total body dose of U.S. Air Force fuel-cell maintenance workers using naphthalene as a surrogate for JP-8 exposure. Dermal, breathing zone, and exhaled breath measurements of naphthalene were obtained using tape-strip sampling, passive monitoring, and glass bulbs, respectively. Levels of urinary 1- and 2-naphthols were determined in urine samples and used as biomarkers of JP-8 exposure. Multiple linear regression analyses were conducted to investigate the relative contributions of dermal and inhalation exposure to JP-8, and demographic and work-related covariates, to the levels of urinary naphthols. Our results show that both inhalation exposure and smoking significantly contributed to urinary 1-naphthol levels. The contribution of dermal exposure was significantly associated with levels of urinary 2-naphthol but not with urinary 1-naphthol among fuel-cell maintenance workers who wore supplied-air respirators. We conclude that dermal exposure to JP-8 significantly contributes to the systemic dose and affects the levels of urinary naphthalene metabolites. Future work on dermal xenobiotic metabolism and toxicokinetic studies are warranted in order to gain additional knowledge on naphthalene metabolism in the skin and the contribution to systemic exposure.

Biodegradable Hydrophilic Polyurethane PEGU25 Loading Antimicrobial Peptide Bmap-28: A Sustained-release Membrane Able to Inhibit Bacterial Biofilm Formation in Vitro

PubMed Central

Wang, Jianzhong; Liu, Qinyu; Tian, Ye; Jian, Zhongyu; Li, Hong; Wang, Kunjie

2015-01-01

Catheter-related infection makes up a large part of hospital infection and contributes 80% to all nosocomial urological infection, costing hundreds of millions dollar per year for treatment. Biodegradable hydrophilic material incorporating antibiotic substance is a promising way to prevent catheter-related infection. And antimicrobial peptide seems an optimal drug for its desirable antibiotic effect. In the current research, we produced a new kind of antibiotic material by incorporating antimicrobial peptide Bmap-28 with polyurethane PEGU25 and tested its effect on Proteus mirabilis in vitro. Compared with the control group, PEGU25 membrane incorporating Bmap-28 had a significant lower bacteria load after co-cultured with the Proteus mirabilis. And its antibiotic effect could be observed throughout the whole 7-day test. Also the Bmap-28 membrane could delay catheter obstruction caused by encrustation. Our findings reveal that PEGU25 incorporating Bmap-28 can well inhibit bacterial biofilm formation of common pathogens for catheter-related urinary tract infection in vitro, which makes it a promising antibiotic material for medical tubes for urology. PMID:25727362

Design of peptide-conjugated glycol chitosan nanoparticles for near infrared fluorescent (NIRF) in vivo imaging of bladder tumors

NASA Astrophysics Data System (ADS)

Key, Jaehong; Dhawan, Deepika; Knapp, Deborah W.; Kim, Kwangmeyung; Kwon, Ick Chan; Choi, Kuiwon; Leary, James F.

2012-03-01

Enhanced permeability and retention (EPR) effects for tumor treatment have been utilized as a representative strategy to accumulate untargeted nanoparticles in the blood vessels around tumors. However, the EPR effect itself was not sufficient for the nanoparticles to penetrate into cancer cells. For the improvement of diagnosis and treatment of cancer using nanoparticles, many more nanoparticles need to specifically enter cancer cells. Otherwise, can leave the tumor area and not contribute to treatment. In order to enhance the internalization process, specific ligands on nanoparticles can help their specific internalization in cancer cells by receptor-mediated endocytosis. We previously developed glycol chitosan based nanoparticles that suggested a promising possibility for in vivo tumor imaging using the EPR effect. The glycol chitosan nanoparticles showed a long circulation time beyond 1 day and they were accumulated predominantly in tumor. In this study, we evaluated two peptides for specific targeting and better internalization into urinary bladder cancer cells. We conjugated the peptides on to the glycol chitosan nanoparticles; the peptide-conjugated nanoparticles were also labeling with near infrared fluorescent (NIRF) dye, Cy5.5, to visualize them by optical imaging in vivo. Importantly real-time NIRF imaging can also be used for fluorescence (NIRF)-guided surgery of tumors beyond normal optical penetration depths. The peptide conjugated glycol chitosan nanoparticles were characterized with respect to size, stability and zeta-potential and compared with previous nanoparticles without ligands in terms of their internalization into bladder cancer cells. This study demonstrated the possibility of our nanoparticles for tumor imaging and emphasized the importance of specific targeting peptides.

Assessment of exposure to organophosphate insecticides during spraying in Haiti: monitoring of urinary metabolites and blood cholinesterase levels*

PubMed Central

Warren, McWilson; Spencer, Harrison C.; Churchill, Frederick C.; Francois, Velly Jean; Hippolyte, Robert; Staiger, Michael A.

1985-01-01

Measurement of blood cholinesterase activity and of the urinary metabolites of fenitrothion (p-nitrocresol) and malathion (monocarboxylic acid) was used to assess the exposure to these insecticides of workers in the Haitian malaria control programme and of residents in the sprayed houses. Cholinesterase activity was significantly reduced at the end of the working week in 3 out of 28 fenitrothion workers. Urinary levels of p-nitrocresol (PNC) in the spraymen ranged from 2.2 to 25.2 mg/l. In fenitrothion workers who had no direct contact with spraying (weighers and supervisors), the cholinesterase activity remained ≥ 75% of the normal control value, and the urinary PNC levels were relatively low. Urinary malathion monocarboxylic acid (MCA) levels at the end of the working week ranged between 1.1 and 5.3 mg/l in workers using malathion and their blood cholinesterase activity remained essentially normal. In both groups of workers the cholinesterase levels improved and the urinary excretion of metabolites decreased after 2 days of rest from the spraying operations. In the residents of the sprayed houses, low concentrations of PNC and MCA were detected in the urine 1 day after spraying and measurable but reduced levels were still present after 7 days. In all these cases the cholinesterase activity remained ≥ 75% of the normal control value. PMID:3874716

The relationship between 63days of 24-h urinary free cortisol and hair cortisol levels in 10 healthy individuals.

PubMed

van Ockenburg, S L; Schenk, H M; van der Veen, A; van Rossum, E F C; Kema, I P; Rosmalen, J G M

2016-11-01

Interest in measuring cortisol in scalp hair is increasing because of its assumed ability to provide a historical timeline of previous systemic levels of cortisol. Yet, it remains uncertain how well hair cortisol represents the total systemic secretion of cortisol over time. Ten healthy individuals collected 24-h urine samples for 63 consecutive days and provided a hair sample at the end of the study period. 24-h urinary creatinine levels in every urine sample were determined to assess completeness of the samples. Cortisol levels in 24-h urine samples and in hair were measured with liquid chromatography tandem mass spectrometry. The correlations between urinary cortisol and hair cortisol were calculated using Kendall's tau. We found a nonsignificant moderate correlation between average urinary cortisol secretion and average hair cortisol concentration r т =0.422, p=0.089. Hair cortisol concentration correlates low to moderately with 24-h urinary cortisol concentration over a period of 63days. Copyright © 2016 Elsevier Ltd. All rights reserved.

[Urinary iodine levels and its influencing factors among residents over age of 15 years in Shenzhen City].

PubMed

Luo, Yiqi; Xu, Jian; He, Shan; Wang, Jun; Fang, Xiaoheng

2014-11-01

To understand the status of iodine nutrition and the affective factors of urinary iodine concentration among residents over age of 15 years in Shenzhen City. Totally 8152 residents from 73 communities were selected with stratified cluster random sampling. The morning urinary iodine was determined and the dietary assessment of iodine using a food frequency questionnaire were carried out. The range of urinary iodine was 9. 65 - 4039.09 μg/L and the median of urinary iodine was 194.59 μg/L among the residents. The percentages of the residents with urinary iodine < 50,50 - 100,100 - 199, 200 - 300, and ≥ 300 μg/L were 2.49%, 12.12%, 40.16%, 26.94% and 20.78%, respectively. There was significant difference in the medians of iodine between different gender (P = 0.0001), the medians of urinary iodine of men (201.32 μg/L) was slightly higher. There was no significant difference in urinary iodine levels (186.59 - 197.44 μg/L) among all age groups, the medians of urinary iodine of all age groups were within the recommended adequate intake. Along with the increase in age, the medians of urinary iodine of all age groups was gradually decreased. Sex, alcohol consumption and daily dietary iodine intake was significant in the final regression model. The iodine nutrition of residents in Shenzhen City was in good condition, populations with low or high iodine still exist. The monitoring is needed and the influencing factors of the urine iodine levels need much exploration.

Predictors of urinary levels of 2,4-dichlorophenoxyacetic acid, 3,5,6-trichloro-2-pyridinol, 3-phenoxybenzoic acid, and pentachlorophenol in 121 adults in Ohio

EPA Science Inventory

Limited data exist on the driving factors that influence the non-occupational exposures of adults to pesticides using urinary biomonitoring. In this work, the objectives were to quantify the urinary levels of 2,4-dichlorophenoxyacetic acid (2,4-D), 3,5,6-trichloro-2-pyridinol (TC...

Bradykinin-forming components in Kuwaiti patients with type 2 diabetes.

PubMed

Sharma, J N; Al-Shoumer, K A S; Matar, K M; Al-Gharee, H Y; Madathil, N V

2013-01-01

Diabetes is the most common risk factor in inducing hypertension, nephropathy and retinopathy. The bradykinin (BK)-forming system has been proposed to protect cardiovascular and renal functions. We therefore evaluated urinary active and proactive kallikrein, total kininogen, plasma tissue kallikrein, plasma creatinine, plasma glucose and plasma HbA1c in newly diagnosed untreated type 2 diabetic patients and healthy subjects. In diabetic patients, urinary and plasma tissue kallikrein concentrations were significantly increased. In addition, plasma prekallikrein levels were also significantly higher. However, urinary kininogen values were significantly reduced in diabetic patients when compared with healthy subjects. This is the first investigation among Kuwaiti Arab patients with type 2 diabetes showing abnormal activities in the BK-forming system. High levels of plasma prekallikrein may be a risk factor for developing high blood pressure as well as nephropathy. The urinary and plasma tissue kallikrein concentrations were higher in diabetic patients, which could indicate the hyperactivities of these components, and may result in increased levels of plasma glucose to induce diabetes. Furthermore, the urinary kininogen levels were reduced in diabetic patients. These alterations might reflect the utilization of urinary kininogen to form BK, a potent inflammatory agent. However, this hypothesis needs further investigation.

Urinary heavy metal levels and relevant factors among people exposed to e-waste dismantling.

PubMed

Wang, Hongmei; Han, Mei; Yang, Suwen; Chen, Yanqing; Liu, Qian; Ke, Shen

2011-01-01

Primitive electronic waste (e-waste) recycling has become a growing environmental concern, and toxic heavy metals released from e-waste activities may continue to threaten the health of local people. To study the impact of heavy metals in people around e-waste sites, 349 people from e-waste recycling sites (exposure group) and 118 people from a green plantation (control group) were surveyed, and their urinary levels of lead (UPb), cadmium (UCd), manganese (UMn), copper (UCu), and Zinc (UZn) were assayed. Questionnaire surveys for risk factors were also performed and analyzed by using the Pearson correlation analysis. Results indicated that the levels of urinary Cd in both occupational dismantling people {GM(GSD) 0.72(0.71) ug/L} and non-occupational dismantling people {GM(GSD) 0.50(0.79) ug/L} were higher than the control group {GM(GSD) 0.27(0.85) ug/L}. Further analyses of correlations between urinary heavy metal levels and exposure factors in the exposed group revealed positive relationship between the duration of dismantling and the level of UPb (p < 0.05). Meanwhile, rice sources from local village have a positive correlation with the level of UPb and UCd (p < 0.01). Other factors, however, may also have influences on heavy metal burden, and not all urinary heavy metal levels can be contributed to e-waste dismantling exposure levels. Primitive e-waste recycling activities may contribute to the changes of urinary heavy metal levels and increase the health risk for those chronically working on e-waste dismantling. Copyright © 2010 Elsevier Ltd. All rights reserved.

Does raising awareness in families reduce environmental tobacco smoke exposure in wheezy children?

PubMed Central

Can, Demet; Gunay, Ilker; Karkıner, Canan Sule Unsal; Gunay, Turkan; Cimrin, Dilek; Nalcabasmaz, Tugba

2017-01-01

Introduction Environmental tobacco smoke (ETS) is thought to increase the severity and number of attacks in wheezy children. Objective assessments are needed to change the behavior of families to reduce the exposure of wheezy children to ETS. Aim To determine whether informing families about their children’s urinary cotinine levels curtailed the exposure of children to ETS. Material and methods A survey was used to determine the ETS exposure level, and the urinary cotinine level of each patient was tested. Children with positive urinary cotinine levels were included in the second part of the study. The families were randomly divided into two groups: an intervention group that was advised about urinary cotinine levels by telephone and a non-intervention group that was not so advised. The groups were followed-up 2 months later, and urinary cotinine levels were measured once again. Results The intervention group contained 65 children of average age of 24.4 ±8.9 months, of whom 46 (70.8%) were male. The non-intervention group contained 69 children of average age of 25.3 ±9.8 months (p > 0.05), of whom 52 (75.4%) were male. The urinary cotinine levels at the time of the second interview were lower in both groups. The number of cigarettes that fathers smoked at home decreased in the intervention group (p = 0.037). Conclusions Presenting objective evidence on ETS exposure to families draws attention to their smoking habits. Measurement of cotinine levels is cheap, practical, and noninvasive. Combined with education, creating awareness by measuring cotinine levels may be beneficial. PMID:28951711

Mercury Exposure among Garbage Workers in Southern Thailand

PubMed Central

2012-01-01

Objectives 1) To determine mercury levels in urine samples from garbage workers in Southern Thailand, and 2) to describe the association between work characteristics, work positions, behavioral factors, and acute symptoms; and levels of mercury in urine samples. Methods A case-control study was conducted by interviewing 60 workers in 5 hazardous-waste-management factories, and 60 matched non-exposed persons living in the same area of Southern Thailand. Urine samples were collected to determine mercury levels by cold-vapor atomic absorption spectrometer mercury analyzer. Results The hazardous-waste workers' urinary mercury levels (10.07 µg/g creatinine) were significantly higher than the control group (1.33 µg/g creatinine) (p < 0.001). Work position, duration of work, personal protective equipment (PPE), and personal hygiene, were significantly associated with urinary mercury level (p < 0.001). The workers developed acute symptoms - of headaches, nausea, chest tightness, fatigue, and loss of consciousness at least once a week - and those who developed symptoms had significantly higher urinary mercury levels than those who did not, at p < 0.05. A multiple regression model was constructed. Significant predictors of urinary mercury levels included hours worked per day, days worked per week, duration of work (years), work position, use of PPE (mask, trousers, and gloves), and personal hygiene behavior (ate snacks or drank water at work, washed hands before lunch, and washed hands after work). Conclusion Changing garbage workers' hygiene habits can reduce urinary mercury levels. Personal hygiene is important, and should be stressed in education programs. Employers should institute engineering controls to reduce urinary mercury levels among garbage workers. PMID:23251842

Urinary serotonin level is associated with serotonin syndrome after moclobemide, sertraline, and citalopram overdose.

PubMed

Brvar, Miran; Stajer, Dusan; Kozelj, Gordana; Osredkar, Josko; Mozina, Martin; Bunc, Matjaz

2007-01-01

Altered mental status, autonomic dysfunction, and neuromuscular abnormalities are a characteristic triad of serotonin syndrome. No laboratory tests confirm the diagnosis of serotonin syndrome. A 35-year-old woman took moclobemide, sertraline, and citalopram in a suicide attempt. She was conscious with mild tachycardia, hypertension, and tachypnea one hour after ingestion. In the second hour after ingestion diaphoresis, mydriasis, horizontal nystagmus, trismus, hyperreflexia, clonus, and tremor appeared. She became agitated and unresponsive. In the third hour after ingestion she became comatose and hyperthermic. She was anesthetized, paralyzed, intubated, and ventilated for 24 hours. Serum moclobemide, sertraline, and citalopram levels were above therapeutic levels. The serum serotonin level was within normal limits and the urinary 5-hydroxyindoleacetic acid:creatinine ratio was below the average daily value. The urinary serotonin:creatinine ratio was increased on arrival (1 mg/g). The urinary serotonin level is increased in serotonin syndrome due to a monoamine oxidase inhibitor and selective serotonin-reuptake inhibitors overdose. It is possible that urinary serotonin concentration could be used as a biochemical marker of serotonin syndrome.

Evans Blue Attachment Enhances Somatostatin Receptor Subtype-2 Imaging and Radiotherapy.

PubMed

Tian, Rui; Jacobson, Orit; Niu, Gang; Kiesewetter, Dale O; Wang, Zhantong; Zhu, Guizhi; Ma, Ying; Liu, Gang; Chen, Xiaoyuan

2018-01-01

Purpose: Radionuclide therapy directed against tumors that express somatostatin receptors (SSTRs) has proven effective for the treatment of advanced, low- to intermediate-grade neuroendocrine tumors in the clinic. In clinical usage, somatostatin peptide-based analogs, labeled with therapeutic radionuclides, provide an overall response rate of about 30%, despite the high cumulative activity injected per patient. We set out to improve the effectiveness of somatostatin radiotherapy by preparing a chemical analog that would clear more slowly through the urinary tract and, concomitantly, have increased blood circulation half-life and higher targeted accumulation in the tumors. Experimental Design: We conjugated a common, clinically-used SST peptide derivative, DOTA-octreotate, to an Evans blue analog (EB), which reversibly binds to circulating serum albumin. The resulting molecule was used to chelate 86 Y and 90 Y, a diagnostic and a therapeutic radionuclide, respectively. The imaging capabilities and the radiotherapeutic efficacy of the resulting radioligand was evaluated in HCT116/SSTR2, HCT116, and AR42J cell lines that express differing levels of SST2 receptors. Results: The synthesized radiopharmaceutical retained affinity and specificity to SSTR2. The new molecule also retained the high internalization rate of DOTA-octreotate, and therefore, showed significantly higher accumulation in SSTR2-positive tumors. Labeling of our novel EB-octreotate derivative with the therapeutic, pure beta emitter, 90 Y, resulted in improved tumor response and survival rates of mice bearing SSTR2 xenografts and had long term efficacy when compared to DOTA-octreotate itself. Conclusions: The coupling of a targeted peptide, a therapeutic radionuclide, and the EB‑based albumin binding provides for effective treatment of SSTR2-containing tumors.

Increase in dermcidin-derived peptides in sweat of patients with atopic eczema caused by a humorous video.

PubMed

Kimata, Hajime

2007-01-01

Dermcidin (DCD)-derived peptide is an antimicrobial peptide produced by the sweat glands. However, the levels of DCD-derived peptide in sweat were decreased in patients with atopic eczema (AE). The effect of viewing a humorous video on the levels of DCD-derived peptide was studied. Twenty patients with AE viewed an 87-min humorous video (Modern Times, featuring Charlie Chaplin). Just before and immediately after viewing, sweat was collected, and the levels of DCD-derived peptide and total protein in sweat were measured. Viewing a humorous video increased the levels of DCD-derived peptide without affecting the levels of total protein in sweat. Viewing a humorous video increased DCD-derived peptide in sweat of patients with AE, and thus, it may be helpful in the treatment of skin infection of AE.

Decreased fucosylated PSA as a urinary marker for high Gleason score prostate cancer.

PubMed

Fujita, Kazutoshi; Hayashi, Takuji; Matsuzaki, Kyosuke; Nakata, Wataru; Masuda, Mika; Kawashima, Atsunari; Ujike, Takeshi; Nagahara, Akira; Tsuchiya, Mutsumi; Kobayashi, Yuka; Nojima, Satoshi; Uemura, Motohide; Morii, Eiichi; Miyoshi, Eiji; Nonomura, Norio

2016-08-30

Fucosylation is an important oligosaccharide modification associated with cancer and inflammation. We investigated whether urinary fucosylated PSA (Fuc-PSA) levels could be used for the detection of high Gleason score prostate cancer. Urine samples were collected from men with abnormal digital rectal examination findings or elevated serum PSA levels, before prostate biopsy. Lectin-antibody ELISA was used to quantify the Lewis-type or core-type fucosylated PSA (PSA-AAL) and core-type fucosylated PSA (PSA-PhoSL) in the urine samples. Both types of urinary Fuc-PSA were significantly decreased in the men with prostate cancer compared with the men whose biopsies were negative for cancer (P = 0.026 and P < 0.001, respectively). Both were also significantly associated with the Gleason scores of the biopsy specimens (P = 0.001 and P < 0.001, respectively). Multivariate analysis showed that PSA density, urinary PSA-AAL, and urinary PSA-PhoSL were independent predictors of high Gleason score prostate cancer. The area under the receiver-operator characteristic curve (AUC) value for the prediction of cancers of Gleason score ≥ 7 was 0.69 for urinary PSA-AAL and 0.72 for urinary PSA-PhoSL. In contrast, the AUC value was 0.59 for serum PSA, 0.63 for PSA density, and 0.58 for urinary PSA. In conclusion, a decreased urinary Fuc-PSA level is a potential marker for the detection of high Gleason score prostate cancer.

Decreased fucosylated PSA as a urinary marker for high Gleason score prostate cancer

PubMed Central

Fujita, Kazutoshi; Hayashi, Takuji; Matsuzaki, Kyosuke; Nakata, Wataru; Masuda, Mika; Kawashima, Atsunari; Ujike, Takeshi; Nagahara, Akira; Tsuchiya, Mutsumi; Kobayashi, Yuka; Nojima, Satoshi; Uemura, Motohide; Morii, Eiichi; Miyoshi, Eiji; Nonomura, Norio

2016-01-01

Fucosylation is an important oligosaccharide modification associated with cancer and inflammation. We investigated whether urinary fucosylated PSA (Fuc-PSA) levels could be used for the detection of high Gleason score prostate cancer. Urine samples were collected from men with abnormal digital rectal examination findings or elevated serum PSA levels, before prostate biopsy. Lectin-antibody ELISA was used to quantify the Lewis-type or core-type fucosylated PSA (PSA-AAL) and core-type fucosylated PSA (PSA-PhoSL) in the urine samples. Both types of urinary Fuc-PSA were significantly decreased in the men with prostate cancer compared with the men whose biopsies were negative for cancer (P = 0.026 and P < 0.001, respectively). Both were also significantly associated with the Gleason scores of the biopsy specimens (P = 0.001 and P < 0.001, respectively). Multivariate analysis showed that PSA density, urinary PSA-AAL, and urinary PSA-PhoSL were independent predictors of high Gleason score prostate cancer. The area under the receiver-operator characteristic curve (AUC) value for the prediction of cancers of Gleason score ≥ 7 was 0.69 for urinary PSA-AAL and 0.72 for urinary PSA-PhoSL. In contrast, the AUC value was 0.59 for serum PSA, 0.63 for PSA density, and 0.58 for urinary PSA. In conclusion, a decreased urinary Fuc-PSA level is a potential marker for the detection of high Gleason score prostate cancer. PMID:27494861

Changes in plasma and urinary nitrite after birth in premature infants at risk for necrotizing enterocolitis

PubMed Central

Pun, Priti; Jones, Jesica; Wolfe, Craig; Deming, Douglas D.; Power, Gordon G.; Blood, Arlin B.

2016-01-01

Background Plasma nitrite serves as a reservoir of nitric oxide (NO) bioactivity. Because nitrite ingestion is markedly lower in newborns than adults, we hypothesized plasma nitrite levels would be lower in newborns than in adults, and that infants diagnosed with necrotizing enterocolitis (NEC), a disease characterized by ischemia and bacterial invasion of intestinal walls, would have lower levels of circulating nitrite in the days prior to diagnosis. Methods Single blood and urine samples were collected from 9 term infants and 12 adults, 72 preterm infants every 5 d for 3 wk, and from 13 lambs before and after cord occlusion. Results Nitrite fell 50% relative to cord levels in the first day after birth; and within 15 min after cord occlusion in lambs. Urinary nitrite was higher in infants than adults. Plasma and urinary nitrite levels in infants who developed NEC were similar to those of preterm control infants on days 1 and 5, but significantly elevated at 15 and 20 d after birth. Conclusion Plasma nitrite falls dramatically at birth while newborn urinary nitrite levels are significantly greater than adults. Acute NEC is associated with elevated plasma and urinary nitrite levels. PMID:26539663

[Prevalence and characteristics of urinary incontinence in community-dwelling-elderly as determined by comprehensive health examination and interview for the prevention of geriatric syndrome and bed-ridden state].

PubMed

Yoshida, Yuko; Kim, Hunkyung; Iwasa, Hajime; Kwon, Jinhee; Sugiura, Miho; Furuna, Taketo; Yoshida, Hideyo; Suzuki, Takao

2007-01-01

We examined the prevalence and characteristics of urinary incontinence in community-dwelling elderly individuals. The participants were 1,783 individuals (768 men and 1,015 women) aged over 70 years who participated in a comprehensive health examination involving a medical examination and interview, plus physical performance tests. Differences in characteristics between individuals with and without urinary incontinence were examined, and multivariate logistic regression models were used to describe the characteristics associated with urinary incontinence. The prevalence of urinary incontinence was 13.4% in men and 23.3% in women. Urinary incontinence was significantly associated with a lower level of physical fitness. Multivariate logistic regression showed that urinary incontinence was significantly associated with a slower walking speed (Odds Ratio (OR) = 0.19, 95% Confidence Intervals (CI) 0.08-0.48) and lower serum albumin level (OR = 0.40, 95% CI 0.16-0.99) in men, and with a slower walking speed (OR = 0.29, 95% CI 0.15-0.56), a higher BMI (OR = 1.09, 95% CI 1.04-1.14), depression (OR = 3.06, 95% CI 1.40-6.69), and lack of physical activity (OR = 0.70, 95% CI 0.50-0.98) in women. The characteristics of urinary incontinence in this cohort of community-dwelling elderly individuals were a low level of physical fitness and poor nutritional state in men, and a low level of physical fitness, a tendency to be obese, a poor mental health state, and lack of physical activity in women.

Relationships between perioperative physical activity and urinary incontinence after radical prostatectomy: an observational study

PubMed Central

2013-01-01

Background Higher physical activity levels are continence-protective in non-prostate cancer populations. Primary aims of this study were to investigate changes in physical activity levels over the perioperative period in patients having radical prostatectomy, and relationships between perioperative physical activity levels and post-prostatectomy urinary incontinence. Methods A prospective analysis of patients having radical prostatectomy and receiving perioperative physiotherapy including pelvic floor muscle training and physical activity prescription (n = 33). Physical activity levels were measured using the International Physical Activity Questionnaire and/or the SenseWear Pro3 Armband at four timepoints: before preoperative physiotherapy, the week before surgery, and 3 and 6 weeks postoperatively. Urinary incontinence was measured at 3 and 6 weeks postoperatively using a 24-hour pad test and the International Consultation on Incontinence Questionnaire – Urinary Incontinence Short Form (ICIQ). Results Physical activity levels changed significantly over the perioperative period (p < 0.001). At 6 weeks postoperatively, physical activity levels did not differ significantly from baseline (p = 0.181), but remained significantly lower than the week before surgery (p = 0.002). There was no significant interaction effect between preoperative physical activity category and time on the 24-hour pad test (p = 0.726) or ICIQ (p = 0.608). Nor were there any significant correlations between physical activity levels and the 24-hour pad test and ICIQ at 3 or 6 weeks postoperatively. Conclusions This study provides novel data on perioperative physical activity levels for patients having radical prostatectomy. There was no relationship between perioperative physical activity levels and post-prostatectomy urinary incontinence, although participants had high overall preoperative physical activity levels and low overall urinary incontinence. PMID:24289104

Measurements of the levels of organic solvent vapours by personal air samplers and the levels of urinary metabolites of workers. Part 2. Toluene vapour in a shipbuilding yard (author's transl).

PubMed

Kira, S

1977-05-01

Personal air samplers were applied to shipyard's painters putting on gas masks during the spraying work, and the levels of toluene vapour surrounding the workers were measured. On the other hand, levels of urinary hippuric acid (metabolites of toluene) of the workers were measured, and the levels of toluene vapour inhaled were calculated from the levels of urinary hippuric acid. Then the actual removing-efficiencies of toluene vapours by the use of gas masks were estimated from these two levels (i.e., toluene vapours exposed and inhaled). The values of removing-efficiencies were found to be 65.9-98.1%. The concentrations of hippuric and methylhippuric acids in the urine of workers exposed to toluene and xylene for 3 hours, collected just after the exposure, are valuable indices of these organic solvent vapours inhaled. A minute amount of urinary methylhippuric acid can be determined by means of gas chromatography.

Separation methods applicable to urinary creatine and creatinine.

PubMed

Smith-Palmer, Truis

2002-12-05

Urinary creatinine has been analyzed for many years as an indicator of glomerular filtration rate. More recently, interest in studying the uptake of creatine as a result of creatine supplementation, a practice increasingly common among bodybuilders and athletes, has lead to a need to measure urinary creatine concentrations. Creatine levels are of the same order of magnitude as creatinine levels when subjects have recently ingested creatine, while somewhat elevated urinary creatine concentrations in non-supplementing subjects can be an indication of a degenerative disease of the muscle. Urinary creatine and creatinine can be analyzed by HPLC using a variety of columns. Detection methods include absorption, fluorescence after post-column derivatization, and mass spectrometry, and some methods have been automated. Capillary zone electrophoresis and micellar electrokinetic capillary chromatography have also been used to analyze urinary creatine and creatinine. Creatine and creatinine have also been analyzed in serum and tissue using HPLC and CE, and many of these separations could also be applicable to urinary analysis.

Urinary Netrin-1: A New Biomarker for the Early Diagnosis of Renal Damage in Obese Children.

PubMed

Övünç Hacıhamdioğlu, Duygu; Hacıhamdioğlu, Bülent; Altun, Demet; Müftüoğlu, Tuba; Karademir, Ferhan; Süleymanoğlu, Selami

2016-09-01

Urinary netrin-1 is a new marker to demonstrate early tubular damage. The aim of this study was to determine whether urinary netrin-1 is increased in obese children. A total of 68 normoalbuminuric and normotensive obese patients and 65 controls were included in the study. Urine samples were collected for assessment of urinary phosphorus, sodium, potassium, creatinine, albumin, and netrin-1. Blood samples were collected for measurements of fasting glucose, insulin, lipid, phosphorus, sodium, potassium, and creatinine levels. Homeostatic model assessment insulin resistance index was calculated. Gender and age were similar between obese and control groups (12.01±3.03 vs. 11.7±3.2 years, p=0.568 and 33 vs. 35 girls, p=0.543, respectively). Obese patients had significantly higher netrin-1 excretion than the controls (841.68±673.17 vs. 228.94±137.25 pg/mg creatinine, p=0.000). Urinary netrin-1 level was significantly higher in obese subjects with insulin resistance compared to those without insulin resistance (1142±1181 vs. 604.9±589.91 pg/mg creatinine, p=0.001). In normotensive and normoalbuminuric obese children, urinary netrin-1 level can increase before onset of albuminuria. Urinary netrin-1 excretion appears to be affected predominantly by insulin resistance and hyperinsulinemia. Urinary netrin-1 may be a new biomarker for determining early tubular injury in obese children.

Nicotine Dependence and Urinary Nicotine, Cotinine and Hydroxycotinine Levels in Daily Smokers.

PubMed

Van Overmeire, Ilse P I; De Smedt, Tom; Dendale, Paul; Nackaerts, Kristiaan; Vanacker, Hilde; Vanoeteren, Jan F A; Van Laethem, Danny M G; Van Loco, Joris; De Cremer, Koen A J

2016-09-01

Nicotine dependence and smoking frequency are critical factors for smoking cessation. The aims of this study are (1) to determine if nicotine dependence Fagerström Test for Nicotine Dependence (FTND) scores are associated with urinary levels of nicotine metabolites, (2) to assess the relationship of hydroxycotinine/cotinine ratio with FTND score and cigarettes smoked per day (CPD), and (3) to identify significant predictors of cigarettes per day among biomarker concentrations and individual FTND items. Urine samples and questionnaire data of 239 daily smokers were obtained. Nicotine, cotinine and hydroxycotinine urinary levels were determined by UPLC MS/MS.Multiple linear regression models were developed to explore the relationship between nicotine, cotinine, hydroxycotinine levels and separate FTND scores (for all six items). We found significant correlations between the different urinary biomarker concentrations, and the FTND score. The time before the first cigarette after waking (TTFC) was significantly associated with the nicotine, cotinine and hydroxycotinine concentrations. No association was found between the ratio of hydroxycotinine to cotinine and either the FTND or the CPD. A model including four FTND questions, sex, age, and the cotinine concentration, accounted for 45% of the variance of CPD. There are significant relationships between urinary levels of nicotine, cotinine, and hydroxycotinine and the FTND score. Especially the FTND question about TTFC is relevant for explaining the biomarker concentrations. CPD (below 15) was significantly explained by four FTND dependence items and urinary cotinine levels in a regression model. We investigated associations between urinary levels of nicotine, cotinine, and hydroxycotinine in daily smokers and the FTND scores for nicotine dependence. We did not find association between the hydroxycotinine/cotinine ratio and CPD. We developed a model that explains the cigarettes smoked daily (CPD) in a group of light smokers by combining FTND items, urinary cotinine levels, sex, and age. Our results might be of importance for clinical use or future studies on larger smoking populations. © The Author 2016. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Novel alpha-MSH peptide analogs for melanoma targeting

NASA Astrophysics Data System (ADS)

Flook, Adam Michael

Skin cancer is the one of the most diagnosed cancers in the United States with increasing incidence over the past two decades. There are three major forms of skin cancer but melanoma is the deadliest. It is estimated that 76,690 new diagnoses of melanoma and 9,480 deaths will occur in 2013. Melanoma accounts for approximately 1.6% of all cancer related deaths and is the 5 th leading diagnosed cancer in the United States. The mean survival rate of patients diagnosed with metastatic melanoma is six months, with five year survival rates of less than 5%. In this project, we describe the design and characterization of novel melanoma-targeting peptide analogs for use in diagnostic imaging of both primary and metastatic melanoma lesions. Novel alpha-MSH peptide conjugates were designed to target the melanocortin-1 receptor present and over-expressed on melanoma cells. These peptides were synthesized and their in-vitro melanocortin-1 receptor binding affinities were established in murine melanoma cells. Once binding affinities were determined, the peptides were radiolabeled with 99mTc utilizing a novel direct radiolabeling technique developed in our laboratory. The peptides were purified via reverse-phase high performance liquid chromatography and in-vivo melanoma targeting and pharmacokinetic properties were determined in B16/F1 melanoma-bearing female C57BL/6 mice. Biodistribution and SPECT/CT imaging studies were performed with the promising 99m Tc-labeled peptide conjugates. All alpha-MSH peptide conjugates tested showed low nanomolar binding affinity for the melanocortin-1 receptor. All peptides were readily radiolabeld with 99mTc with greater than 95% radiochemical purity. All 99mTc-labeled peptides displayed high specific in-vivo melanoma tumor uptake while maintaining low normal organ accumulation, and were excreted through the urinary system in a timely fashion. In addition, all tested 99mTc-labeld alpha-MSH peptides demonstrated clear visualization of in-vivo tumor lesions with SPECT/CT. While all peptides exhibited high melanoma uptake, extremely high non-specific renal uptake was of concern. After synthesis of alpha-MSH peptide conjugates containing a different amino acid linker, renal uptake was drastically reduced and a lead compound had emerged, showing favorable in-vivo melanoma targeting and uptake properties with limited amounts of non-specific renal accumulation.

Excretion of anti-angiogenic proteins in patients with chronic allograft dysfunction.

PubMed

Moskowitz-Kassai, Eliza; Mackelaite, Lina; Chen, Jun; Patel, Kaushal; Dadhania, Darshana M; Gross, Steven S; Chander, Praveen; Delaney, Vera; Deng, Luqin; Chen, Ligong; Cui, Xiangqin; Suthanthiran, Manikkam; Goligorsky, Michael S

2012-02-01

We have recently documented the appearance of an anti-angiogenic peptide, endorepellin, in the urine of patients with chronic allograft dysfunction (CAD). Here, we analyzed using enzyme-linked immunosorbent assay the excretion of anti-angiogenic peptides endostatin, pigment epithelium-derived factor (PEDF) and Kruppel-like factor-2 (KLF-2), in healthy individuals, patients with stable graft function and patients with various degrees of CAD. In healthy subjects and patients with CAD-0, endostatin, PEDF and KLF-2 excretions were at the level of detection. In contrast, there were significant differences between the patients with CAD-3 and CAD-0, CAD-1 and healthy controls for endostatin and CAD-0 versus CAD-3 for PEDF, but no differences in KLF-2 excretion. Receiver operating characteristic (ROC) curve analyses demonstrated a highly discriminative profile for all three biomarkers: the combination of these parameters offered 83% sensitivity and 90% specificity in distinguishing CAD-0 from CAD-1-3. The quality of these potential biomarkers of CAD was, however, highest in discriminating CAD status in biopsy-proven cases and dropped when CAD-0 was diagnosed based on clinical criteria. In conclusion, these findings indicate the diagnostic potential of urinary detection of endostatin, PEDF and to lesser degree KLF-2 and suggest a mechanistic role played by anti-angiogenic substances in the developing vasculopathy and vascular rarefaction in patients with CAD.

Utility of urinary transferrin and ceruloplasmin in patients with systemic lupus erythematosus for differentiating patients with lupus nephritis.

PubMed

Urrego, Tomás; Ortiz-Reyes, Blanca; Vanegas-García, Adriana L; Muñoz, Carlos H; González, Luis A; Vásquez, Gloria; Gómez-Puerta, José A

2018-03-09

Diagnosis of lupus nephritis (LN) is usually based on renal biopsy, which is an invasive technique that involves multiple risks. Therefore, different biomarkers have emerged as alternatives for the diagnosis of LN. Nonetheless, studies regarding urinary biomarkers in Latin American patients are limited. The objective of this study was to assess the diagnostic value of urinary transferrin and ceruloplasmin to differentiate patients who have renal involvement from those who do not. Systemic lupus erythematosus (SLE) patients that met the revised American College of Rheumatology (ACR) classification criteria were recruited. Patients with another autoimmune disease, active infection (urinary tract or systemic infection), renal replacement therapy, human immunodeficiency virus infection or pregnancy were excluded. A urine sample was collected from each patient. LN was diagnosed according to ACR criteria. The activity and chronicity of LN were measured using the Austin indices. Urinary transferrin and ceruloplasmin levels were measured using commercial enzyme-linked immunosorbent assay (ELISA) kits. Mann-Whitney U test and Student's t-test were used to compare data. Spearman's rank correlation was used to determine associations. Lastly, receiver operating characteristic (ROC) curves were created. The study involved 120 SLE patients. In all, 85% were female, 76% mestizo, the mean age was 32.8±12.1years and mean systemic lupus erythematosus disease activity index (SLEDAI) was 8.4±8.9; 64% had renal involvement. Urinary levels of the two biomarkers were significantly higher in patients with LN compared to those without LN. Similarly, urinary levels of both biomarkers were significantly higher in patients with active LN compared to those with inactive LN. Furthermore, urinary transferrin levels were significantly higher in Afro-Latin American patients. On the other hand, urinary transferrin levels correlated with SLEDAI and proteinuria, and transferrin and ceruloplasmin levels correlated with each other. The diagnostic value of ROC curves for these urinary biomarkers for LN were good. In our cohort of SLE patients, we found that transferrin and ceruloplasmin were potential biomarkers for LN, and can even differentiate active LN. Copyright © 2018 Elsevier España, S.L.U. and Sociedad Española de Reumatología y Colegio Mexicano de Reumatología. All rights reserved.

Urinary ß2-microglobulin in very preterm neonates with chorioamnionitis.

PubMed

Nishimaki, Shigeru; Shima, Yoshio; Sato, Miho; An, Hiromi; Fujita, Shujiro; Iwasaki, Shiho; Horiguchi, Haruko; Seki, Kazuo; Yokota, Shumpei

2011-12-01

It is important to identify premature infants with prenatal inflammation as it contributes to short- and long-term complications. Our object was to study how prenatal inflammation affects the urinary β(2)-microglobulin (β(2)-MG) level. Preterm neonates were divided based on the presence of chorioamnionitis (CAM) into the CAM (n = 100) and non-CAM groups (n = 117). These were further subdivided into five groups each: 30 preterm neonates of 23-26; 42 neonates of 27-28; 54 neonates of 29-30; 51 neonates of 31-32; and 40 neonates of 33-34 weeks' gestation. The urinary β(2)-MG level within 48 h of birth was significantly higher in the CAM group than in the non-CAM group among the neonates of 23-26 weeks' gestation (18.3 ± 6.9 vs 10.0 ± 5.6 × 10(4) μg/gCr, p = 0.0018) and the neonates of 27-28 weeks' gestation (16.2 ± 10.8 vs 8.8 ± 3.3 × 10(4) μg/gCr, p = 0.0101). However, there was no difference in urinary β(2)-MG level between the CAM and the non-CAM group among the neonates ≥ 29 weeks 'gestation. Moreover, the elevated urinary β(2)-MG level in the neonates ≤ 28 weeks ' gestation with CAM had disappeared by 1 week after birth. The reasons for the increase in urinary β(2)-MG level within 48 h of birth in very preterm neonates (≤ 28 weeks' gestation) with CAM are believed to be not only prematurity, but also prenatal inflammation. It is suggested that the urinary β(2)-MG level during the early postnatal period can identify prenatal inflammation.

Urinary adiponectin and albuminuria in non-diabetic hypertensive patients: an analysis of the ESPECIAL trial.

PubMed

Han, Seung Seok; Bae, Eunjin; Ahn, Shin Young; Kim, Sejoong; Park, Jung Hwan; Shin, Sung Joon; Lee, Sang Ho; Choi, Bum Soon; Chin, Ho Jun; Lim, Chun Soo; Kim, Suhnggwon; Kim, Dong Ki

2015-08-01

Although adiponectin levels have been reported to be correlated with albuminuria, this issue remains unresolved in non-diabetic hypertensive subjects, particularly when urinary adiponectin is considered. Urinary adiponectin levels were examined using an enzyme-linked immunosorbent assay in 229 participants. who used olmesartan as a hypertensive agent. Their albuminuria levels were measured for 16 weeks after randomization and initiation of conventional or intensive diet education. Linear or logistic regression models were applied, as appropriate, to explore the relationship with albuminuria itself or its response after the intervention. Urinary adiponectin levels were positively related to baseline albuminuria level (r = 0.529). After adjusting for several covariates, the adiponectin level was associated with the albuminuria level (β = 0.446). Among the 159 subjects with baseline macroalbuminuria, the risk of consistent macroalbuminuria (> 300 mg/day) at 16 weeks was higher in the 3(rd) tertile of adiponectin than in the 1(st) tertile (odds ratio = 6.9), despite diet education. In contrast, among all subjects, the frequency of the normoalbuminuria achievement (< 30 mg/day) at 16 weeks was higher in the 1(st) tertile than in the 3(rd) tertile (odds ratio = 13.0). Urinary adiponectin may be a useful biomarker for albuminuria or its response after treatment in non-diabetic hypertensive patients.

Biomonitoring of urinary metals in a population living in the vicinity of industrial sources: a comparison with the general population of Andalusia, Spain.

PubMed

Aguilera, Inmaculada; Daponte, Antonio; Gil, Fernando; Hernández, Antonio F; Godoy, Patricia; Pla, Antonio; Ramos, Juan Luis

2008-12-15

The Ria of Huelva (south-west Spain) is one of the most polluted fluvial-estuarine systems in the world. Industrial activity delivers huge amounts of pollutants to the local environment, particularly heavy metals and arsenic. Here we aimed to determine urinary levels of As, Cd, Cr, Cu and Ni in a representative sample (n=857) of adults living in the Ria of Huelva. Levels were compared to those from a representative sample of 861 adults of the general urban population of Andalusia (southern Spain) and multiple regression models were developed to identify individual factors associated with urinary levels of these elements. Arsenic levels were significantly higher in the Ria of Huelva as compared to other Andalusian cities, whereas Cd and Ni levels were significantly lower. Despite these differences, levels in both groups were similar to the reference values reported in previous studies for general population. Age, gender, diet and lifestyle were the major factors contributing to the interindividual variation in urinary metals. In conclusion, despite living in a highly polluted area, the population of the Ria of Huelva failed to show higher urinary levels of the studied metals as compared to a reference urban population of the same region.

The impact of organizational factors on the urinary incontinence care quality in long-term care hospitals: a longitudinal correlational study.

PubMed

Yoon, Ju Young; Lee, Ji Yun; Bowers, Barbara J; Zimmerman, David R

2012-12-01

With the rapid increase in the number of long-term care hospitals in Korea, care quality has become an important issue. Urinary incontinence is an important condition affecting many residents' quality of life. Thus, it is important that urinary incontinence be amenable to improving conditions with appropriate interventions, since a change in urinary incontinence status can reflect care quality in long-term care facilities if patient level factors are adjusted. We aim to examine the impact of organizational factors on urinary incontinence care quality defined as the improvement of urinary incontinence status or maintenance of continent status post-admission to Korean long-term care hospitals. DESIGN AND DATA: This is a longitudinal correlation study. Data came from two sources: monthly patient assessment reports using the Patient Assessment Instrument and the hospital information system from the Health Insurance Review and Assessment Services. The final analysis includes 5271 elderly adults without indwelling urinary catheter or urostomy who were admitted to 534 Korean long-term care hospitals in April 2008. Multi-level logistic analysis was used to explore the organizational factors that influence urinary incontinence care quality controlling for patient level factors. With respect to the organizational factors, the findings showed that location and RN/total nursing staff ratio variables were statistically significant, controlling for risk factors at the patient level. The odds of urinary incontinence improvement from admission in urban long-term care hospitals were 1.28 times higher than rural long-term care hospitals. In addition, when a long-term care hospital increased one standard deviation (0.19) in the RN ratio, the odds of urinary incontinence status improvement or maintenance of continence status from admission increased about 1.8 times. The most significant finding was that a higher RN to patient ratio and urban location were associated with better resident outcomes of urinary incontinence among organizational factors. For a better understanding of how these significant organizational factors influence positive care outcomes and provide more practical implications, studies should examine concrete care process measures as well as structure and outcome measures based on systematic conceptual models. Copyright © 2012 Elsevier Ltd. All rights reserved.

Dramatic elevation in urinary amino terminal titin fragment excretion quantified by immunoassay in Duchenne muscular dystrophy patients and in dystrophin deficient rodents.

PubMed

Robertson, Alan S; Majchrzak, Mark J; Smith, Courtney M; Gagnon, Robert C; Devidze, Nino; Banks, Glen B; Little, Sean C; Nabbie, Fizal; Bounous, Denise I; DiPiero, Janet; Jacobsen, Leslie K; Bristow, Linda J; Ahlijanian, Michael K; Stimpson, Stephen A

2017-07-01

Enzyme-linked and electrochemiluminescence immunoassays were developed for quantification of amino (N-) terminal fragments of the skeletal muscle protein titin (N-ter titin) and qualified for use in detection of urinary N-ter titin excretion. Urine from normal subjects contained a small but measurable level of N-ter titin (1.0 ± 0.4 ng/ml). A 365-fold increase (365.4 ± 65.0, P = 0.0001) in urinary N-ter titin excretion was seen in Duchene muscular dystrophy (DMD) patients. Urinary N-ter titin was also evaluated in dystrophin deficient rodent models. Mdx mice exhibited low urinary N-ter titin levels at 2 weeks of age followed by a robust and sustained elevation starting at 3 weeks of age, coincident with the development of systemic skeletal muscle damage in this model; fold elevation could not be determined because urinary N-ter titin was not detected in age-matched wild type mice. Levels of serum creatine kinase and serum skeletal muscle troponin I (TnI) were also low at 2 weeks, elevated at later time points and were significantly correlated with urinary N-ter titin excretion in mdx mice. Corticosteroid treatment of mdx mice resulted in improved exercise performance and lowering of both urinary N-ter titin and serum skeletal muscle TnI concentrations. Low urinary N-ter titin levels were detected in wild type rats (3.0 ± 0.6 ng/ml), while Dmd mdx rats exhibited a 556-fold increase (1652.5 ± 405.7 ng/ml, P = 0.002) (both at 5 months of age). These results suggest that urinary N-ter titin is present at low basal concentrations in normal urine and increases dramatically coincident with muscle damage produced by dystrophin deficiency. Urinary N-ter titin has potential as a facile, non-invasive and translational biomarker for DMD. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

Urinary Calcium and Oxalate Excretion in Healthy Adult Cats Are Not Affected by Increasing Dietary Levels of Bone Meal in a Canned Diet

PubMed Central

Passlack, Nadine; Zentek, Jürgen

2013-01-01

This study aimed to investigate the impact of dietary calcium (Ca) and phosphorus (P), derived from bone meal, on the feline urine composition and the urinary pH, allowing a risk assessment for the formation of calcium oxalate (CaOx) uroliths in cats. Eight healthy adult cats received 3 canned diets, containing 12.2 (A), 18.5 (B) and 27.0 g Ca/kg dry matter (C) and 16.1 (A), 17.6 (B) and 21.1 g P/kg dry matter (C). Each diet was fed over 17 days. After a 7 dayś adaptation period, urine and faeces were collected over 2×4 days (with a two-day rest between), and blood samples were taken. Urinary and faecal minerals, urinary oxalate (Ox), the urinary pH and the concentrations of serum Ca, phosphate and parathyroid hormone (PTH) were analyzed. Moreover, the urine was microscopically examined for CaOx uroliths. The results demonstrated that increasing levels of dietary Ca led to decreased serum PTH and Ca and increased faecal Ca and P concentrations, but did not affect the urinary Ca or Ox concentrations or the urinary fasting pH. The urinary postprandial pH slightly increased when the diet C was compared to the diet B. No CaOx crystals were detected in the urine of the cats. In conclusion, urinary Ca excretion in cats seems to be widely independent of the dietary Ca levels when Ca is added as bone meal to a typical canned diet, implicating that raw materials with higher contents of bones are of subordinate importance as risk factors for the formation of urinary CaOx crystals. PMID:23940588

Urinary 1-hydroxypyrene and 8-hydroxydeoxyguanosine levels among coke-oven workers for 2 consecutive days.

PubMed

Nguyen, Thi-To-Uyen; Kawanami, Shoko; Kawai, Kazuaki; Kasai, Hiroshi; Li, Yun-Shan; Inoue, Jinro; Ngoan, Le Tran; Horie, Seichi

2014-01-01

This study evaluated the levels of exposure to polycyclic aromatic hydrocarbons (PAHs) and their relationship with oxidative DNA damage among Vietnamese coke-oven workers. We collected urine from 36 coke-oven workers (exposed group) at the beginning and end of the shift on 2 consecutive days. We also collected urine from 78 medical staff (control group). Information was collected by questionnaire about smoking status, drinking habit, and working position. Urinary 1-hydroxypyrene (1-OHP) and 8-hydroxydeoxyguanosine (8-OH-dG) were measured using HPLC. All statistical analyses were performed with SPSS version 19. Urinary 1-OHP was significantly higher in the coke-oven workers than in the control group (p<0.05). Top-oven workers had the highest levels of internal exposure to PAHs, followed by side-oven and then bottom-oven workers (5.41, 4.41 and 1.35 ng/mg creatinine, respectively, at the end of the shift on day 2). Urinary 8-OH-dG was significantly higher in top- and side-oven workers at the end of the shift on day 2 (4.63 and 5.88 ng/mg creatinine, respectively) than in the control group (3.85 ng/mg creatinine). Based on a multi-regression analysis, smoking status had a significant effect on urinary 8-OH-dG (p=0.049). Urinary 1-OHP tended to have a positive correlation with urinary 8-OH-dG (p=0.070). Vietnamese coke-oven workers were exposed to PAHs during their work shift. Urinary 1-OHP exceeded the recommended limit, and elevated oxidative DNA damage occurred in top- and side-oven workers on the second day of work. A tendency for positive correlation was found between urinary 1-OHP and urinary 8-OH-dG.

Relationship of 24-hour urinary free cortisol to 4-hour salivary morning and afternoon cortisol and cortisone as measured by a time-integrated oral diffusion sink.

PubMed

Kathol, R G; Poland, R E; Stokes, P E; Wade, S

1995-05-01

The relationship between salivary corticosteroids integrated over 4-hour periods and urinary free cortisol collected over 24 hours was investigated in normal controls. Twenty-one normal volunteers wore "oral diffusion sink" sampling devices in their mouths for two 4-hour periods (08:00-12:00 hours and 13:00-17:00 hours) and on the same day collected a 24-hour urine specimen. Time-integrated salivary corticosteroid concentrations were determined from the sample devices and urinary free cortisol was measured. Salivary corticosteroids were not consistently higher in the morning than in the afternoon period and did not differ between men and women. Urinary free cortisol levels were higher in women. No salivary corticosteroids measure was significantly correlated with urinary free cortisol. We conclude that time-integrated salivary corticosteroids do not reflect urinary free cortisol levels in normal controls.

Effect of salt intake and potassium supplementation on urinary renalase and serum dopamine levels in Chinese adults.

PubMed

Wang, Yang; Wang, Dan; Chu, Chao; Mu, Jian-Jun; Wang, Man; Liu, Fu-Qiang; Xie, Bing-Qing; Yang, Fan; Dong, Zhen-Zhen; Yuan, Zu-Yi

2015-01-01

The aim of our study was to assess the effects of altered salt and potassium intake on urinary renalase and serum dopamine levels in humans. Forty-two subjects (28–65 years of age) were selected from a rural community of northern China. All subjects were sequentially maintained on a low-salt diet for 7 days (3.0 g/day of NaCl), a high-salt diet for an additional 7 days (18.0 g/day of NaCl), and a high-salt diet with potassium supplementation for a final 7 days (18.0 g/day of NaCl + 4.5 g/day of KCl). Urinary renalase excretions were significantly higher during the high-salt diet intervention than during the low-salt diet. During high-potassium intake, urinary renalase excretions were not significantly different from the high-salt diet, whereas they were significantly higher than the low-salt levels. Serum dopamine levels exhibited similar trends across the interventions. Additionally, a significant positive relationship was observed between the urine renalase and serum dopamine among the different dietary interventions. Also, 24-hour urinary sodium excretion positively correlated with urine renalase and serum dopamine in the whole population. The present study indicates that dietary salt intake and potassium supplementation increase urinary renalase and serum dopamine levels in Chinese subjects. © 2015 S. Karger AG, Basel

Urinary 1-hydroxypyrene concentrations in Chinese coke oven workers relative to job category, respirator usage, and cigarette smoking

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bo Chen; Yunping Hu; Lixing Zheng

1-Hydroxypyrene (1-OHP) is a biomarker of recent exposure to polycyclic aromatic hydrocarbons (PAHs). We investigated whether urinary 1-OHP concentrations in Chinese coke oven workers (COWs) are modulated by job category, respirator usage, and cigarette smoking. The present cross-sectional study measured urinary 1-OHP concentrations in 197 COWs from Coking plant I and 250 COWs from Coking plant II, as well as 220 unexposed referents from Control plant I and 56 referents from Control plant II. Urinary 1-OHP concentrations (geometric mean, {mu}mol/mol creatinine) were 5.18 and 4.21 in workers from Coking plants I and II, respectively. The highest 1-OHP levels in urinemore » were found among topside workers including lidmen, tar chasers, and whistlers. Benchmen had higher 1-OHP levels than other workers at the sideoven. Above 75% of the COWs exceeded the recommended occupational exposure limit of 2.3 {mu}mol/mol creatinine. Respirator usage and increased body mass index (BMI) slightly reduced 1-OHP levels in COWs. Cigarette smoking significantly increased urinary 1-OHP levels in unexposed referents but had no effect in COWs. Chinese COWs, especially topside workers and benchmen, are exposed to high levels of PAHs. Urinary 1-OHP concentrations appear to be modulated by respirator usage and BMI in COWs, as well as by smoking in unexposed referents.« less

Hydration and urinary pseudoephedrine levels after a simulated team game.

PubMed

Jolley, Daniel; Dawson, Brian; Maloney, Shane K; White, James; Goodman, Carmel; Peeling, Peter

2014-06-01

This study investigated the influence of dehydration on urinary levels of pseudoephedrine (PSE) after prolonged repeated effort activity. Fourteen athletes performed a simulated team game circuit (STGC) outdoors over 120 min under three different hydration protocols: hydrated (HYD), dehydrated (DHY) and dehydrated + postexercise fluid bolus (BOL). In all trials, a 60 mg dose of PSE was administered 30 min before trial and at half time of the STGC. Urinary PSE levels were measured before drug administration and at 90 min postexercise. In addition, body mass (BM) changes and urinary specific gravity (USG), osmolality (OSM), creatinine (Cr), and pH values were recorded. No differences in PSE levels were found 90 min postexercise between conditions (HYD: 208.5 ± 116.5; DHY: 238.9 ± 93.5; BOL: 195.6 ± 107.3 μg · ml(-1)), although large variations were seen within and between participants across conditions (range: 33-475 μg · ml(-1): ICC r = .03-0.16, p > .05). There were no differences between conditions in USG, OSM, pH or PSE/Cr ratio. In conclusion, hydration status did not influence urinary PSE levels after prolonged repeated effort activity, with ~70% of samples greater than the WADA limit (>150 μg · ml(-1)), and ~30% under. Due to the unpredictability of urinary PSE values, athletes should avoid taking any medications containing PSE during competition.

Adrenal cortical response to stress at Three Mile Island.

PubMed

Schaeffer, M A; Baum, A

1984-01-01

The present study examined the relationship between biochemical, psychologic, and behavioral components of chronic stress associated with living near the damaged nuclear power plant at Three Mile Island (TMI). Relative to control subjects, TMI subjects had higher levels of urinary cortisol, which correlated significantly with urinary catecholamines, self-report of physical and mental symptoms, and decrements in task performance. Further, it was found that males had higher urinary cortisol levels than females at TMI, while at the control sites, levels of cortisol were comparable between males and females. Finally, no significant relationship between coping style and urinary cortisol was detected. Levels of stress response among TMI are residents, though significantly greater than control subjects, were within normal ranges and thus should be considered subclinical in intensity. Their persistence over 17 months, however, suggests some cause for concern.

Changes in Urinary Phthalate Metabolite Levels Before and After the Phthalate Contamination Event and Identification of Exposure Sources in a Cohort of Taiwanese Children.

PubMed

Huang, Chian-Feng; Wang, I-Jen

2017-08-19

In 2011, the Taiwan Food and Drug Administration inadvertently discovered that, for decades, manufacturers had replaced expensive natural emulsifiers in food products with diethylhexyl phthalate (DEHP). We wanted to compare urinary phthalate metabolite levels of children before and after the DEHP food contamination event and identify source(s) of phthalate exposure in addition to the illegal food additives. In the present study, morning urine samples were collected from a cohort of 453 children in 2010 in Taipei. After the DEHP food contamination event, there were 200 cohort children left at follow-up in 2013. The geometric means (GMs) of urinary mono(2-ethyl-5-hydroxyhexyl) phthalate (5OH-MEHP) levels before and after the event were 9.39 and 13.34 µg/g of creatinine, respectively, with no significant difference ( p = 0.093). After the DEHP food contamination event, we found that urinary phthalate metabolite levels were significantly higher in people who frequently consumed microwave-heated food and used fragrance-containing products ( p < 0.05). In addition, children who did not frequently wash hands before eating had significantly higher urinary phthalate metabolite levels than those who did ( p < 0.05). These results demonstrate that urinary phthalate metabolite levels did not decrease after the DEHP food contamination event, thus, other sources must contribute to phthalate exposure in daily life. Public awareness of approaches to reducing phthalate exposure is necessary.

Urinary NGAL and hematic ADMA levels: an early sign of cardio-renal syndrome in young adults born preterm?

PubMed

Bassareo, Pier Paolo; Fanos, Vassilios; Mussap, Michele; Flore, Giovanna; Noto, Antonio; Puddu, Melania; Saba, Luca; Mercuro, Giuseppe

2013-10-01

Prematurity at birth is a known risk factor for the development of an early chronic renal disease. Urinary neutrophil gelatinase-associated lipocalin (NGAL) is a well established biomarker of kidney injury, while high blood levels of asymmetric dimethylarginine (ADMA) are associated with the future development of adverse cardiovascular events and cardiac death. (1) to verify the presence of statistically significant differences between urinary NGAL and hematic ADMA levels in young adults born preterm at extremely low birth weight (<1000 g; ex-ELBW) and those of a control group of healthy adults born at term (C) (2) to seek correlations between NGAL and ADMA levels, which would indicate the presence of an early cardio-renal involvement in ex-ELBW. Twelve ex-ELBW subjects (six males and six female, mean age: 23.9 ± 3.2 years) were compared with 12 C (six males and six female). Urinary NGAL and hematic ADMA levels were assessed. Urinary NGAL levels were higher in ex- ELBW subjects compared to C (p < 0.05), as well as hematic ADMA concentrations (p < 0.05). A statistically significant correlation was found between urinary NGAL and ADMA (r = -0.60, p < 0.04). Our preliminary findings support the hypothesis that in ex-ELBW subjects the development of an early chronic kidney disease contributes towards inducing an increase in the atherosclerotic process and in the risk of future adverse cardiovascular events.

Transcriptome of Proteus mirabilis in the Murine Urinary Tract: Virulence and Nitrogen Assimilation Gene Expression▿†

PubMed Central

Pearson, Melanie M.; Yep, Alejandra; Smith, Sara N.; Mobley, Harry L. T.

2011-01-01

The enteric bacterium Proteus mirabilis is a common cause of complicated urinary tract infections. In this study, microarrays were used to analyze P. mirabilis gene expression in vivo from experimentally infected mice. Urine was collected at 1, 3, and 7 days postinfection, and RNA was isolated from bacteria in the urine for transcriptional analysis. Across nine microarrays, 471 genes were upregulated and 82 were downregulated in vivo compared to in vitro broth culture. Genes upregulated in vivo encoded mannose-resistant Proteus-like (MR/P) fimbriae, urease, iron uptake systems, amino acid and peptide transporters, pyruvate metabolism enzymes, and a portion of the tricarboxylic acid (TCA) cycle enzymes. Flagella were downregulated. Ammonia assimilation gene glnA (glutamine synthetase) was repressed in vivo, while gdhA (glutamate dehydrogenase) was upregulated in vivo. Contrary to our expectations, ammonia availability due to urease activity in P. mirabilis did not drive this gene expression. A gdhA mutant was growth deficient in minimal medium with citrate as the sole carbon source, and loss of gdhA resulted in a significant fitness defect in the mouse model of urinary tract infection. Unlike Escherichia coli, which represses gdhA and upregulates glnA in vivo and cannot utilize citrate, the data suggest that P. mirabilis uses glutamate dehydrogenase to monitor carbon-nitrogen balance, and this ability contributes to the pathogenic potential of P. mirabilis in the urinary tract. PMID:21505083

Urine Sample Preparation in 96-Well Filter Plates for Quantitative Clinical Proteomics

PubMed Central

2015-01-01

Urine is an important, noninvasively collected body fluid source for the diagnosis and prognosis of human diseases. Liquid chromatography mass spectrometry (LC-MS) based shotgun proteomics has evolved as a sensitive and informative technique to discover candidate disease biomarkers from urine specimens. Filter-aided sample preparation (FASP) generates peptide samples from protein mixtures of cell lysate or body fluid origin. Here, we describe a FASP method adapted to 96-well filter plates, named 96FASP. Soluble urine concentrates containing ∼10 μg of total protein were processed by 96FASP and LC-MS resulting in 700–900 protein identifications at a 1% false discovery rate (FDR). The experimental repeatability, as assessed by label-free quantification and Pearson correlation analysis for shared proteins among replicates, was high (R ≥ 0.97). Application to urinary pellet lysates which is of particular interest in the context of urinary tract infection analysis was also demonstrated. On average, 1700 proteins (±398) were identified in five experiments. In a pilot study using 96FASP for analysis of eight soluble urine samples, we demonstrated that protein profiles of technical replicates invariably clustered; the protein profiles for distinct urine donors were very different from each other. Robust, highly parallel methods to generate peptide mixtures from urine and other body fluids are critical to increase cost-effectiveness in clinical proteomics projects. This 96FASP method has potential to become a gold standard for high-throughput quantitative clinical proteomics. PMID:24797144

Quantification of Inflammasome Adaptor Protein ASC in Biological Samples by Multiple-Reaction Monitoring Mass Spectrometry.

PubMed

Ulke-Lemée, Annegret; Lau, Arthur; Nelson, Michelle C; James, Matthew T; Muruve, Daniel A; MacDonald, Justin A

2018-06-09

Inflammation is an integral component of many diseases, including chronic kidney disease (CKD). ASC (apoptosis-associated speck-like protein containing CARD, also PYCARD) is the key inflammasome adaptor protein in the innate immune response. Since ASC specks, a macromolecular condensate of ASC protein, can be released by inflammasome-activated cells into the extracellular space to amplify inflammatory responses, the ASC protein could be an important biomarker in diagnostic applications. Herein, we describe the development and validation of a multiple reaction monitoring mass spectrometry (MRM-MS) assay for the accurate quantification of ASC in human biospecimens. Limits of detection and quantification for the signature DLLLQALR peptide (used as surrogate for the target ASC protein) were determined by the method of standard addition using synthetic isotope-labeled internal standard (SIS) peptide and urine matrix from a healthy donor (LOQ was 8.25 pM, with a ~ 1000-fold linear range). We further quantified ASC in the urine of CKD patients (8.4 ± 1.3 ng ASC/ml urine, n = 13). ASC was positively correlated with proteinuria and urinary IL-18 in CKD samples but not with urinary creatinine. Unfortunately, the ASC protein is susceptible to degradation, and patient urine that was thawed and refrozen lost 85% of the ASC signal. In summary, the MRM-MS assay provides a robust means to quantify ASC in biological samples, including clinical biospecimens; however, sample collection and storage conditions will have a critical impact on assay reliability.

The requirement of ammonium or other cations linked with p-cresol sulfate for cross-reactivity with a peptide of myelin basic protein.

PubMed

Jackson, Patricia L; Cao, Ligong; Blalock, J Edwin; Whitaker, John N

2003-10-15

Urinary myelin basic protein-like material (MBPLM), so designated because of its immunoreactivity with a polyclonal antibody directed against a cryptic epitope located in residues 83-89 of myelin basic protein (MBP), exists in humans normally but increases in concentration in patients with multiple sclerosis who have progressive disease. Given its possible role in reflecting events of neural tissue destruction occurring in multiple sclerosis, urinary MBPLM is a candidate surrogate marker for this phase of the disease. Previously, it has been demonstrated that p-cresol sulfate (PCS) is the dominant component of MBPLM; however, another component(s) was essential in enabling p-cresol sulfate to have molecular mimicry with MBP peptide 83-89 detected by immunoreactivity. In the present investigation, this remaining component(s) was characterized by a combination of high performance size exclusion chromatography followed by nuclear magnetic resonance spectroscopy and shown to be ammonium. The monovalent cation ammonium could be substituted in vitro by several different monovalent and divalent cations, most notably zinc, in restoring to deprotonated p-cresol sulfate its immunoreactivity as MBPLM. These findings indicate the basis for the unexpected molecular mimicry between an epitope of an encephalitogenic protein and a complex containing a small organic molecule, p-cresol sulfate. Furthermore, the reaction of either ammonium or other cations with p-cresol sulfate may represent an in vivo process directly related to damage of axonal membranes.

[Establishment of enzyme-linked immunosorbent assay (ELISA) for measuring human urinary uromodulin and application of the method in patients with IgA nephropathy].

PubMed

Liu, Ying; Chen, Yu-qing; Zhou, Jing-jing; Han, Jia; Liang, Yu; Li, Xue-ying; Zhang, Hong

2012-04-18

To establish a method of enzyme-linked immunosorbent assay (ELISA) to measure urinary uromodulin and explore the urinary uromudulin level in IgA nephropathy. The rabbit anti-human uromodulin polyclonal antibodies were coated on plates to capture uromodulin and the mouse anti-human uromodulin monoclonal antibody was used as detecting antibody to set up ELISA procedure. The precision and repeatability of this ELISA method were evaluated, and then this method was compared with the commercialized Tamm-Horsfall Glycoprotein ELISA Kit by examining urinary uromodulin levels in 55 individuals. Finally, the urinary uromodulin level in 166 IgA nephropathy patients were detected as well as 48 normal controls with this established method. The detecting range of uromodulin was 0.78-12.5 μg/L by this method. The coefficient of variation within-run was 7.5%, and between-run of coefficient of variation was 7.9%. Correlation of this method and comercialized kit was good (r=0.615, P<0.001). The urinary uromodulin/urinary creatinine ratio in IgA nephropathy was significantly lower than that in normal controls. The established ELISA method is sensitive and repeatable, and can be used in further studies.

Preproghrelin Leu72Met polymorphism is not associated with type 2 diabetes mellitus.

PubMed

Kim, Sun-Young; Jo, Dae-Sun; Hwang, Pyoung Han; Park, Ji Hyun; Park, Sung Kwang; Yi, Ho Keun; Lee, Dae-Yeol

2006-03-01

Ghrelin is a novel gut-brain peptide, which exerts somatotropic, orexigenic, and adipogenic effects. Genetic variants of ghrelin have been associated with both obesity and insulin metabolism. In this study, we determined a role of preproghrelin Leu72Met polymorphism on type 2 diabetes mellitus and its relationship to variables studied. Genotypes were assessed by polymerase chain reaction. Frequencies of the Leu72Met polymorphism were found to be 35.4% in the type 2 diabetic patients and 32.5% in the normal controls. The Leu72Met polymorphism was not associated with hypertension, macroangiopathy, retinopathy, serum cholesterol, triglyceride, blood urea nitrogen, HbA(1c), lipoprotein (a), fasting insulin, or 24-hour urinary protein levels in the type 2 diabetic group. However, the Leu72Met polymorphism was clearly associated with serum creatinine levels in the diabetic group, as the Met72 carriers exhibited lower serum creatinine levels than the Met72 noncarriers. Our data indicate that the preproghrelin Leu72Met polymorphism is not associated with type 2 diabetes mellitus. However, the Leu72Met polymorphism is associated with serum creatinine levels. These data suggest that Met72 carrier status may be a predictable marker for diabetic nephropathy or renal impairment in type 2 diabetes mellitus.

Detection of PCT and urinary β2 -MG enhances the accuracy for localization diagnosing pediatric urinary tract infection.

PubMed

Fang, Jian; Luan, Jiangwei; Zhu, Gaohong; Qi, Chang; Wang, Dandan

2017-09-01

The purpose of this article was to investigate whether the combination of urinary beta 2 microglobulin (urinary β 2 -MG) and procalcitonin (PCT) diagnosis could enhance the localization diagnostic precision of pediatric urinary tract infection comparing with single diagnosis. A study was conducted in the Nephrology Department of Wuhan women and children's health care centre. This study incorporated 85 participants, including 35 children who were diagnosed as upper urinary tract infection (UUTI) with the symptom of fever and 50 children who conducted lower urinary tract infection (LUTI). Levels of PCT and urinary β 2 -MG in both UUTI and LUTI patients were measured and compared. The level of PCT and β 2 -MG were both significantly higher in UUTI group compared with in LUTI group. AUC of urinary β 2 -MG ROC (sensitivity of 71.4%, specificity of 90.0%) was significantly smaller than that of PCT ROC (sensitivity of 77.1%, specificity of 96.0%) in the single diagnosis. Although in the combined diagnosis, the sensitivity and specificity increased to 88.6% and 98%, respectively. Both PCT and β 2 -MG could be used to localize the UTI. Introducing urinary β 2 -MG into PCT diagnosis could increase the sensitivity and specificity of UTI lesion diagnosis in clinical practice. © 2016 The Authors Journal of Clinical Laboratory Analysis Published by Wiley Periodicals, Inc.

Two-level QSAR network (2L-QSAR) for peptide inhibitor design based on amino acid properties and sequence positions.

PubMed

Du, Q S; Ma, Y; Xie, N Z; Huang, R B

2014-01-01

In the design of peptide inhibitors the huge possible variety of the peptide sequences is of high concern. In collaboration with the fast accumulation of the peptide experimental data and database, a statistical method is suggested for peptide inhibitor design. In the two-level peptide prediction network (2L-QSAR) one level is the physicochemical properties of amino acids and the other level is the peptide sequence position. The activity contributions of amino acids are the functions of physicochemical properties and the sequence positions. In the prediction equation two weight coefficient sets {ak} and {bl} are assigned to the physicochemical properties and to the sequence positions, respectively. After the two coefficient sets are optimized based on the experimental data of known peptide inhibitors using the iterative double least square (IDLS) procedure, the coefficients are used to evaluate the bioactivities of new designed peptide inhibitors. The two-level prediction network can be applied to the peptide inhibitor design that may aim for different target proteins, or different positions of a protein. A notable advantage of the two-level statistical algorithm is that there is no need for host protein structural information. It may also provide useful insight into the amino acid properties and the roles of sequence positions.

Proteasome inhibitors alter levels of intracellular peptides in HEK293T and SH-SY5Y cells.

PubMed

Dasgupta, Sayani; Castro, Leandro M; Dulman, Russell; Yang, Ciyu; Schmidt, Marion; Ferro, Emer S; Fricker, Lloyd D

2014-01-01

The proteasome cleaves intracellular proteins into peptides. Earlier studies found that treatment of human embryonic kidney 293T (HEK293T) cells with epoxomicin (an irreversible proteasome inhibitor) generally caused a decrease in levels of intracellular peptides. However, bortezomib (an antitumor drug and proteasome inhibitor) caused an unexpected increase in the levels of most intracellular peptides in HEK293T and SH-SY5Y cells. To address this apparent paradox, quantitative peptidomics was used to study the effect of a variety of other proteasome inhibitors on peptide levels in HEK293T and SH-SY5Y cells. Inhibitors tested included carfilzomib, MG132, MG262, MLN2238, AM114, and clasto-Lactacystin β-lactone. Only MG262 caused a substantial elevation in peptide levels that was comparable to the effect of bortezomib, although carfilzomib and MLN2238 elevated the levels of some peptides. To explore off-target effects, the proteosome inhibitors were tested with various cellular peptidases. Bortezomib did not inhibit tripeptidyl peptidase 2 and only weakly inhibited cellular aminopeptidase activity, as did some of the other proteasome inhibitors. However, potent inhibitors of tripeptidyl peptidase 2 (butabindide) and cellular aminopeptidases (bestatin) did not substantially alter the peptidome, indicating that the increase in peptide levels due to proteasome inhibitors is not a result of peptidase inhibition. Although we cannot exclude other possibilities, we presume that the paradoxical increase in peptide levels upon treatment with bortezomib and other inhibitors is the result of allosteric effects of these compounds on the proteasome. Because intracellular peptides are likely to be functional, it is possible that some of the physiologic effects of bortezomib and carfilzomib arise from the perturbation of peptide levels inside the cell.

Proteasome Inhibitors Alter Levels of Intracellular Peptides in HEK293T and SH-SY5Y Cells

PubMed Central

Dasgupta, Sayani; Castro, Leandro M.; Dulman, Russell; Yang, Ciyu; Schmidt, Marion; Ferro, Emer S.; Fricker, Lloyd D.

2014-01-01

The proteasome cleaves intracellular proteins into peptides. Earlier studies found that treatment of human embryonic kidney 293T (HEK293T) cells with epoxomicin (an irreversible proteasome inhibitor) generally caused a decrease in levels of intracellular peptides. However, bortezomib (an antitumor drug and proteasome inhibitor) caused an unexpected increase in the levels of most intracellular peptides in HEK293T and SH-SY5Y cells. To address this apparent paradox, quantitative peptidomics was used to study the effect of a variety of other proteasome inhibitors on peptide levels in HEK293T and SH-SY5Y cells. Inhibitors tested included carfilzomib, MG132, MG262, MLN2238, AM114, and clasto-Lactacystin β-lactone. Only MG262 caused a substantial elevation in peptide levels that was comparable to the effect of bortezomib, although carfilzomib and MLN2238 elevated the levels of some peptides. To explore off-target effects, the proteosome inhibitors were tested with various cellular peptidases. Bortezomib did not inhibit tripeptidyl peptidase 2 and only weakly inhibited cellular aminopeptidase activity, as did some of the other proteasome inhibitors. However, potent inhibitors of tripeptidyl peptidase 2 (butabindide) and cellular aminopeptidases (bestatin) did not substantially alter the peptidome, indicating that the increase in peptide levels due to proteasome inhibitors is not a result of peptidase inhibition. Although we cannot exclude other possibilities, we presume that the paradoxical increase in peptide levels upon treatment with bortezomib and other inhibitors is the result of allosteric effects of these compounds on the proteasome. Because intracellular peptides are likely to be functional, it is possible that some of the physiologic effects of bortezomib and carfilzomib arise from the perturbation of peptide levels inside the cell. PMID:25079948

The roles of serum and urinary carbohydrate antigen 19-9 in the management of patients with antenatal hydronephrosis.

PubMed

Atar, Arda; Oktar, Tayfun; Kucukgergin, Canan; Kalelioglu, Ibrahim; Seckin, Sule; Ander, Haluk; Ziylan, Orhan; Kadioglu, Teoman Cem

2015-06-01

Serum carbohydrate antigen (CA) 19-9 has been clinically applied as a valuable tumor marker for pancreatic and gastrointestinal carcinoma. CA 19-9 is expressed in normal excretory epithelium tissues. Increased CA 19-9 has also been observed in uroepithelial tumors as well as in nonmalignant conditions including hydronephrosis secondary to ureteral stones. The purpose of this article is to evaluate the role of urinary CA 19-9 as a non-invasive biomarker in the postnatal differentiation of obstructive and non-obstructive hydronephrosis in patients with unilateral antenatal hydronephrosis. Infants with isolated renal pelvic dilatation, defined as the presence of anteroposterior pelvic diameter (APPD) equal to or greater than 7 mm based on antenatal ultrasound after 28 weeks' gestation, underwent systematic investigation for uropathies and were prospectively followed up. The pyeloplasty group consisted of 17 patients with ureteropelvic junction (UPJ) obstruction who had undergone pyeloplasty. The non-obstructive dilatation (NOD) group consisted of 17 patients with non-obstructive hydronephrosis, and the control group consisted of 21 healthy children. Commercial enzyme-linked immunosorbent assay (ELISA) kits were used to measure the urinary and serum CA 19-9 levels. In both hydronephrosis groups (pyeloplasty and non-obstructive dilatation), the correlations between urinary and serum CA 19-9 levels with the anteroposterior pelvic diameter measured at the third trimester and the postnatal initial evaluation and differential renal function were investigated. The initial median urinary CA 19-9 levels were significantly greater in children who underwent pyeloplasty than in both the non-obstructive hydronephrosis (143 ± 38 vs. 68 ± 23, respectively; p = 0.007) and the healthy control groups (143 ± 38 vs. 13 ± 3, respectively; p = 0.001) (Figure). Three months after surgery, the urinary CA 19-9 levels had decreased significantly according to the preoperative levels in the pyeloplasty group (143 ± 38 vs. 55 ± 16, p = 0.039). In both the pyeloplasty and NOD groups, there was a correlation of urinary CA 19-9 levels with differential renal function and a correlation of serum CA 19-9 levels with the initial anteroposterior pelvic diameter. Receiver operator characteristic (ROC) analysis revealed a better diagnostic profile for the urinary CA 19-9 level than for the serum CA 19-9 level in terms of identifying obstruction in the hydronephrosis groups (areas under the curve = 0.8 and 0.7, respectively). The best cut-off value of for urinary CA 19-9 was 85.5 U/mL with 76% sensitivity, 85% specificity. The negative predictive value was 80%. The results suggest that voided urine CA 19-9 levels seems to be a more useful marker than serum CA 19-9 in obstructive dilatation. An appropriate decrease in urinary CA 19-9 levels after pyeloplasty may be used as a predictor of surgical outcome. In addition, the results have a number of important diagnostic implications that should be further validated in a larger study population. Based on these results, we suggest that a high urinary CA 19-9 level is a non-invasive clinically applicable marker for differentiating between obstruction and non-obstructive dilatation. Copyright © 2015 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.

Relationship between urinary bisphenol A levels and diabetes mellitus.

PubMed

Shankar, Anoop; Teppala, Srinivas

2011-12-01

Bisphenol A (BPA) is a widely used chemical in the manufacture of polycarbonate plastics and epoxy resins. Recent animal studies have suggested that BPA exposure may have a role in the development of weight gain, insulin resistance, pancreatic endocrine dysfunction, thyroid hormone disruption, and several other mechanisms involved in the development of diabetes. However, few human studies have examined the association between markers of BPA exposure and diabetes mellitus. We examined the association between urinary BPA levels and diabetes mellitus in the National Health and Nutritional Examination Survey (NHANES) 2003-2008. Urinary BPA levels were examined in quartiles. The main outcome of interest was diabetes mellitus defined according the latest American Diabetes Association guidelines. Overall, we observed a positive association between increasing levels of urinary BPA and diabetes mellitus, independent of confounding factors such as age, gender, race/ethnicity, body mass index, and serum cholesterol levels. Compared to quartile 1 (referent), the multivariate-adjusted odds ratio (95% confidence interval) of diabetes associated with quartile 4 was 1.68 (1.22-2.30) (p-trend = 0.002). The association was present among normal-weight as well as overweight and obese subjects. Urinary BPA levels are found to be associated with diabetes mellitus independent of traditional diabetes risk factors. Future prospective studies are needed to confirm or disprove this finding.

99mTc-HYNIC-(tricine/EDDA)-FROP peptide for MCF-7 breast tumor targeting and imaging.

PubMed

Ahmadpour, Sajjad; Noaparast, Zohreh; Abedi, Seyed Mohammad; Hosseinimehr, Seyed Jalal

2018-02-19

Breast cancer is the most common malignancy among women in the world. Development of novel tumor-specific radiopharmaceuticals for early breast tumor diagnosis is highly desirable. In this study we developed 99m Tc-HYNIC-(tricine/EDDA)-Lys-FROP peptide with the ability of specific binding to MCF-7 breast tumor. The FROP-1 peptide was conjugated with the bifunctional chelator hydrazinonicotinamide (HYNIC) and labeled with 99m Tc using tricine/EDDA co-ligand. The cellular specific binding of 99m Tc-HYNIC-FROP was evaluated on different cell lines as well as with blocking experiment on MCF-7 (human breast adenocarcinoma). The tumor targeting and imaging of this labeled peptide were performed on MCF-7 tumor bearing mice. Radiochemical purity for 99m Tc-HYNIC-(tricine/EDDA)-FROP was 99% which was determined with ITLC method. This radiolabeled peptide showed high stability in normal saline and serum about 98% which was monitored with HPLC method. In saturation binding experiments, the binding constant (K d ) to MCF-7 cells was determined to be 158 nM. Biodistribution results revealed that the 99m Tc-HYNIC-FROP was mainly exerted from urinary route. The maximum tumor uptake was found after 30 min post injection (p.i.); however maximum tumor/muscle ratio was seen at 15 min p.i. The tumor uptake of this labeled peptide was specific and blocked by co-injection of excess FROP. According to the planar gamma imaging result, tumor was clearly visible due to the tumor uptake of 99m Tc-HYNIC-(tricine/EDDA)-FROP in mouse after 15 min p.i. The 99m Tc-HYNIC-(tricine/EDDA)-FROP is considered a promising probe with high specific binding to MCF-7 breast cancer cells.

Utility of urinary biomarkers as a diagnostic tool for early diabetic nephropathy in patients with type 2 diabetes mellitus.

PubMed

Vijay, Soorampally; Hamide, Abdoul; Senthilkumar, Gandhipuram Periyasamy; Mehalingam, Vadivelan

2018-04-12

Renal tubulo-interstitial damage has an important role in the pathogenesis of early diabetic nephropathy. Urinary biomarkers can help in the detection of early nephropathy in type 2 diabetic patients. The aim of this study was to estimate the levels of urinary neutrophil gelatinase associated lipocalin (NGAL) and cystatin-C in type 2 diabetic patients with early diabetic nephropathy & to compare them with diabetic patients without nephropathy and to correlate urinary NGAL and cystatin-C levels with microalbuminuria in them. Cross-sectional comparative study. The study was conducted on 126 patients with type 2 diabetes along with 30 control subjects attending the outpatient care department of a tertiary care teaching hospital. There were 3 study groups-diabetic patients with microalbuminuria, diabetic patients without albuminuria and control subjects who were non-diabetic without any renal disease. Details on duration of diabetes and glycemic status were obtained from the patients. Urine examination was done for subjects in all the groups to look for microalbuminuria along with estimation of NGAL and cystatin-C levels. Samples were stored at -20 °C in the deep freezer. Urinary NGAL and cystatin-C levels were significantly elevated in patients with microalbuminuria (228.18 & 3.23 ng/ml) as compared to those without albuminuria (146.12 & 2.61 ng/ml) and in control subjects (26.56 & 0.30 ng/ml). Urinary NGAL and cystatin-C levels showed a linear correlation with microalbuminuria in diabetic patients. Urinary NGAL and cystatin-C levels were increased in type 2 diabetic patients with early diabetic nephropathy as compared to patients without nephropathy. Urine NGAL and cystatin-C levels also showed a positive correlation with microalbuminuria (urine albumin-creatinine ratio) in patients with type 2 diabetes mellitus. Copyright © 2018 Diabetes India. Published by Elsevier Ltd. All rights reserved.

Protective role of AgRP neuron's PDK1 against salt-induced hypertension.

PubMed

Zhang, Boyang; Nakata, Masanori; Lu, Ming; Nakae, Jun; Okada, Takashi; Ogawa, Wataru; Yada, Toshihiko

2018-06-12

In the hypothalamic arcuate nucleus (ARC), orexigenic agouti-related peptide (AgRP) neurons regulate feeding behavior and energy homeostasis. The 3-phosphoinositide-dependent protein kinase-1 (PDK1) in AgRP neurons serves as a major signaling molecule for leptin and insulin, the hormones regulating feeding behavior, energy homeostasis and circulation. However, it is unclear whether PDK1 in AGRP neurons is also involved in regulation of blood pressure. This study explored it by generating and analyzing AgRP neuron-specific PDK1 knockout (Agrp-Pdk1 flox/flox ) mice and effect of high salt diet on blood pressure in KO and WT mice was analyzed. Under high salt diet feeding, systolic blood pressure (SBP) of Agrp-Pdk1 flox/flox mice was significantly elevated compared to Agrp-Cre mice. When the high salt diet was switched to control low salt diet, SBP of Agrp-Pdk1 flox/flox mice returned to the basal level observed in Agrp-Cre mice within 1 week. In Agrp-Pdk1 flox/flox mice, urinary noradrenalin excretion and NUCB2 mRNA expression in hypothalamic paraventricular nucleus (PVN) were markedly upregulated. Moreover, silencing of NUCB2 in the PVN counteracted the rises in urinary noradrenalin excretions and SBP. These results demonstrate a novel role of PDK1 in AgRP neurons to counteract the high salt diet-induced hypertension by preventing hyperactivation of PVN nesfatin-1 neurons. Copyright © 2018 Elsevier Inc. All rights reserved.

Elevated urinary neutrophil gelatinase-associated lipocalcin after acute heart failure treatment is associated with worsening renal function and adverse events

PubMed Central

Collins, Sean P.; Hart, Kimberly W.; Lindsell, Christopher J.; Fermann, Gregory J.; Weintraub, Neal L.; Miller, Karen F.; Roll, Susan N.; Sperling, Matthew I.; Sawyer, Douglas B.; Storrow, Alan B.

2012-01-01

Aims Reliable detectors of worsening renal function (WRF) in Emergency Department (ED) patients with acute heart failure (AHF) are limited. We hypothesized that initial urinary neutrophil gelatinase-associated lipocalcin (NGAL) levels, and changes in urinary NGAL levels after initial ED AHF therapy, would be associated with WRF and adverse events. Methods and results Urinary NGAL upon ED presentation and 12–24 h after ED treatment was measured in a cohort of ED patients with AHF. NGAL was corrected for urinary creatinine (uCr). WRF was defined as RIFLE stages 1, 2, or 3, or a creatinine increase of ≥0.3 mg/dL. Patients were prospectively followed for 5- and 30-day adverse cardiovascular events. The 399 patients had a median age of 63 years, 50% were Caucasian, and 62% were male. Those with WRF at 72–96 h were more likely to have a higher initial NGAL value (71 vs. 32 ng NGAL/mg uCr) (P = 0.005), and a higher NGAL level at 12–24 h after ED therapy (107 vs. 25ng NGAL/mg uCr, P < 0.001). In a multivariable model, NGAL at 12–24 h remained a significant predictor of WRF (P = 0.012). Of all variables available 12–24 h after initial therapy, the only significant predictor of 30-day events was an elevated urinary NGAL level (P = 0.02). Conclusions Urinary NGAL levels determined 12–24 h after ED therapy are significantly associated with both WRF at 72–96 h and 30-day adverse events. This suggests that early management strategies may have an impact on subsequent WRF and outcomes. If confirmed, NGAL may have a role for guiding therapeutic decisions. PMID:22733980

Urinary Sodium and Potassium Excretion and Carotid Atherosclerosis in Chinese Men and Women

PubMed Central

Dai, Xiao-Wei; Wang, Cheng; Xu, Ying; Guan, Ke; Su, Yi-Xiang; Chen, Yu-Ming

2016-01-01

Limited studies have examined the association between sodium (Na) and potassium (K) levels and the risk of atherosclerosis. This study examined whether higher Na and Na/K levels and low K levels were independent risk factors for atherosclerosis. This community-based cross-sectional study included 3290 subjects (1067 men and 2223 women) 40 to 75 years of age in Guangzhou, China, between 2011 and 2013. Urinary excretion of Na and K were measured from the first morning void, and creatinine-adjusted values were used. The intima-media thickness (IMT) of the carotid common artery and the carotid bifurcation was measured with high-resolution B-mode ultrasonography. Dietary K and Na intake and other covariates were obtained by face-to-face interviews. A significant positive association was seen between urinary Na excretion and carotid atherosclerosis after adjustment for age, sex, and other lifestyle covariates. The odds ratios (OR) and 95% confidence interval (CI) of the highest (vs. lowest) quartile of urinary Na were 1.32 (1.04–1.66) for carotid plaques, 1.48 (1.18–1.87) for increased common carotid artery IMT, and 1.55 (1.23–1.96) for increased carotid bifurcation IMT (all p-trend < 0.01). A similar positive association was observed between urinary Na/K levels and carotid plaque and increased IMT, and between dietary Na intake and increased bifurcation IMT. Regarding potassium data, we only found a significantly lower presence of carotid plaque (OR 0.72, 95% CI 0.57–0.91) for quartile 2 (vs. 1) of urinary K. Our findings suggest that higher levels of urinary excretion Na and Na/K are significantly associated with greater presence of carotid atherosclerosis in Chinese adults. PMID:27706075

The role of serum C-reactive protein in women with lower urinary tract symptoms.

PubMed

Hsiao, Sheng-Mou; Lin, Ho-Hsiung; Kuo, Hann-Chorng

2012-07-01

Some lower urinary tract dysfunction (LUTD) subtypes may be associated with low-grade inflammation. This study aimed to investigate the role of serum C-reactive protein (CRP) levels in women with lower urinary tract symptoms (LUTS). A total of 197 consecutive women with non-stress urinary incontinence (non-SUI) LUTS and 18 healthy women without LUTS (normal controls) were enrolled. LUTS include urinary storage, voiding, and post-micturition symptoms. Patients with previous bladder or urethral surgery, active urinary tract infections, or possible neurogenic lesions were excluded. Serum CRP levels were measured before any treatment was given. Patients were stratified to LUTD subgroups based on a 3-day voiding diary, uroflowmetry, and selective videourodynamic studies. Median CRP levels were significantly higher in women with overactive bladder (OAB) wet (i.e., with urgency incontinence, n = 30, 0.12 mg/dl) than those in women with bladder oversensitivity (n = 68, 0.075 mg/dl, P = 0.008) and the control group (0.055 mg/dl, P = 0.032). Further analysis revealed that body mass index and maximum flow rate were two independent factors that affected CRP levels. The area under the receiver-operating characteristic curve for using CRP to predict OAB wet was 0.55, and the most predictive cutoff point for CRP was 0.15 mg/dl (sensitivity 43.5 %, specificity 72.7 %). High serum CRP levels were found in women with OAB wet, and they were related to lower maximum urinary flow rates and higher body mass indices in non-SUI LUTD. However, serum CRP is not a suitable biomarker for discriminating between subtypes of non-SUI LUTD.

Assessment of urinary thiodiglycolic acid exposure in school-aged children in the vicinity of a petrochemical complex in central Taiwan.

PubMed

Huang, Po-Chin; Liu, Li-Hsuan; Shie, Ruei-Hao; Tsai, Chih-Hsin; Liang, Wei-Yen; Wang, Chih-Wen; Tsai, Cheng-Hsien; Chiang, Hung-Che; Chan, Chang-Chuan

2016-10-01

School-aged children living in the vicinity of vinyl chloride (VCM)/polyvinyl chloride (PVC) factories may have an increased risk of exposure to hazardous air pollutants. We aimed to evaluate the urinary thiodiglycolic acid (TDGA) level, as TDGA is a major metabolite of VCM, for students at elementary schools near a petrochemical complex in central Taiwan. We recruited 343 students from 5 elementary schools based on distance to the VCM/PVC factory. First-morning urine and blood samples were obtained from our subjects from October 2013 to September 2014. Urine samples were analyzed for urinary creatinine and TDGA using LC/MS-MS. Hepatitis virus infection were assessed using blood samples. We determined their vitamin consumption, resident location, parent's employment, and other demographic or lifestyle characteristics using a questionnaire. Median urinary TDGA levels for 316 students at 5 elementary schools from the closest (<.9km) to the farthest (∼8.6km) with respect to the petrochemical complex were 147.6, 95.5, 115.5, 86.8, and 17.3μg/g creatinine, respectively. After adjusting for age, gender, hepatitis virus infection, vitamin B consumption, passive smoking, and home to source distance, we found that urinary TDGA levels for the closest students was significantly higher than those at other schools. Further, median urinary TDGA levels for students during school time were 4.1-fold higher than those during summer vacation. After adjusting for confounders, urinary TDGA levels for the school-aged children decreased with increasing distances between the elementary schools and the petrochemical complex. Copyright © 2015 Elsevier Inc. All rights reserved.

Urinary β-2 Microglobulin Levels Sensitively Altered in an Osteomalacia Patient Receiving Add-on Adefovir Dipivoxil Therapy for Hepatitis B Virus Infection.

PubMed

Takagi, Junko; Morita, Hiroyuki; Ito, Kiyoaki; Ohashi, Tomohiko; Hirase, Sho; Ito, Tatsuo; Morishima, Takkan; Otake, Kazuo; Yoneda, Masashi

2016-01-01

Adefovir dipivoxil (ADV) is effective for hepatitis B virus (HBV) infection; however, ADV may provoke renal injury resulting in osteomalacia, and this side effect is seldom recognized until bone fractures emerge. We herein present a 66-year-old woman with HBV infection who received ADV for 6 years. Although she exhibited no sign of bone fractures, her urinary β-2 microglobulin (β2MG) level increased to 83,837 μg/L and scintigraphy revealed minimal fractures of the third rib. ADV was subsequently reduced and her urinary β2MG rapidly fell to 3,637 μg/L. Conversely, her urinary N-acetyl-β-D-glucosaminidase, and serum phosphate, alkaline phosphatase levels did not respond.

Definition of reference ranges for free T4, TSH, and thyroglobulin levels in healthy subjects of the Jaén Health District.

PubMed

Olmedo Carrillo, Pablo; Santiago Fernández, Piedad; García Fuentes, Eduardo; Ureña Fernández, Tomás; Gutiérrez Alcántara, Carmen; Sánchez-Malo, Carolina; Gassó Campos, Manuela; Martínez Ramírez, María José

2017-10-01

The treatment guidelines for thyroid dysfunction recommend defining reference ranges for thyroid hormones in each area through assessment of local population data considering the iodine nutritional status. The aim of this study was to define the reference ranges of free thyroxine (FT4), TSH, and thyroglobulin levels in a general population from Jaen, an area of southern Spain with an adequate iodine nutritional status, and whether they were associated with urinary iodine levels. A cross-sectional study was conducted in 1,003 subjects of the general population of the Jaen Health District. Levels of urinary iodine, FT4, TSH, thyroglobulin, and thyroid peroxidase (TPO) antibodies were measured according to age and sex. Median and mean urinary iodine levels were 110.59μg/L and 130.11μg/L respectively. Median TSH level was 1.83μIU/mL (p2.5=0.56μIU/mL, p97.5=4.66μIU/mL). Median FT4 level was 0.84ng/dL (p2.5=0.62ng/dL, p97.5=1.18ng/dL). TPO antibodies were detected in 5.7% of subjects. There was no correlation between urinary iodine levels and FT4, TSH or TPO antibodies. Subjects with positive TPO antibodies had higher TSH levels (3.34μIU/L versus 2.14μIU/mL, P=.001; odds ratio=2.42). Urinary iodine levels in Jaen are optimal according to World Health Organization standards. Reference ranges of FT4, TSH, and thyroglobulin do not differ from those reported in the literature and are no associated to urinary iodine levels. The prevalence of positive TPO antibodies was similar to that reported in other Spanish areas. Copyright © 2017 SEEN y SED. Publicado por Elsevier España, S.L.U. All rights reserved.

Evaluation and validation of a method for determining platelet catecholamine in patients with obstructive sleep apnea and arterial hypertension.

PubMed

Feres, Marcia C; Cintra, Fatima D; Rizzi, Camila F; Mello-Fujita, Luciane; Lino de Souza, Altay A; Tufik, Sergio; Poyares, Dalva

2014-01-01

Measurements of plasma and urinary catecholamine are susceptible to confounding factors that influence the results, complicating the interpretation of sympathetic nervous system (SNS) activity in the Obstructive sleep apnea (OSA) and arterial hypertension (HYP) conditions. In this study, we validated a test for platelet catecholamine and compared the catecholamine levels (adrenaline and noradrenaline) in urine, plasma and platelets in patients with OSA and HYP compared with controls. In the validation, 30 healthy, nonsmoking volunteers who were not currently undergoing treatment or medication were selected as the control group. One hundred fifty-four individuals (114 OSA, 40 non-OSA) were consecutively selected from the outpatient clinic of the Sleep Institute and underwent clinical, polysomnographic and laboratory evaluation, including the urinary, plasma and platelet levels of adrenaline (AD) and noradrenaline (NA). Patients were then allocated to groups according to the presence of OSA and/or hypertension. A logistic regression model, controlled for age and BMI, showed that urinary AD and urinary NA were risk factors in the OSA+HYP group and the HYP group; however, the model showed higher levels of platelet NA for OSA without HYP. After 1 year of CPAP (continuous upper airway pressure) treatment, patients (n = 9) presented lower levels of urinary NA (p = 0.04) and platelet NA (p = 0.05). Urinary NA and AD levels were significantly associated with the condition of hypertension with and without OSA, whereas platelet NA with OSA without comorbidity. These findings suggest that platelet catecholamine levels might reflect nocturnal sympathetic activation in OSA patients without hypertension.

Twenty-four-hour urinary water-soluble vitamin levels correlate with their intakes in free-living Japanese schoolchildren.

PubMed

Tsuji, Tomiko; Fukuwatari, Tsutomu; Sasaki, Satoshi; Shibata, Katsumi

2011-02-01

To examine the association between 24 h urinary water-soluble vitamin levels and their intakes in free-living Japanese schoolchildren. All foods consumed for four consecutive days were recorded accurately by a weighed food record. A single 24 h urine sample was collected on the fourth day, and the urinary levels of water-soluble vitamins were measured. An elementary school in Inazawa City, Japan. A total of 114 healthy, free-living, Japanese elementary-school children aged 10-12 years. The urinary level of each water-soluble vitamin was correlated positively to its mean intake in the past 2-4 d (vitamin B1: r = 0·42, P < 0·001; vitamin B2: r = 0·43, P < 0·001; vitamin B6: r = 0·49, P < 0·001; niacin: r = 0·32, P < 0·001; niacin equivalents: r = 0·32, P < 0·001; pantothenic acid: r = 0·32, P < 0·001; folic acid: r = 0·27, P < 0·01; vitamin C: r = 0·39, P < 0.001), except for vitamin B12 (r = 0·10, P = NS). Estimated mean intakes of water-soluble vitamins calculated using urinary levels and recovery rates were 97-102 % of their 3 d mean intake, except for vitamin B12 (79 %). The results show that urinary levels of water-soluble vitamins, except for vitamin B12, reflected their recent intakes in free-living Japanese schoolchildren and could be used as a potential biomarker to estimate mean vitamin intake.

Urine Fibrosis Markers and Risk of Allograft Failure in Kidney Transplant Recipients: A Case-Cohort Ancillary Study of the FAVORIT Trial.

PubMed

Ix, Joachim H; Katz, Ronit; Bansal, Nisha; Foster, Meredith; Weiner, Daniel E; Tracy, Russell; Jotwani, Vasantha; Hughes-Austin, Jan; McKay, Dianne; Gabbai, Francis; Hsu, Chi-Yuan; Bostom, Andrew; Levey, Andrew S; Shlipak, Michael G

2017-03-01

Kidney tubulointerstitial fibrosis marks risk for allograft failure in kidney transplant recipients, but is poorly captured by estimated glomerular filtration rate (eGFR) or urine albumin-creatinine ratio (ACR). Whether urinary markers of tubulointerstitial fibrosis can noninvasively identify risk for allograft failure above and beyond eGFR and ACR is unknown. Case-cohort study. The FAVORIT (Folic Acid for Vascular Outcome Reduction in Transplantation) Trial was a randomized double-blind trial testing vitamin therapy to lower homocysteine levels in stable kidney transplant recipients. We selected a subset of participants at random (n=491) and all individuals with allograft failure during follow-up (cases; n=257). Using spot urine specimens from the baseline visit, we measured 4 urinary proteins known to correlate with tubulointerstitial fibrosis on biopsy (urine α 1 -microglobulin [A1M], monocyte chemoattractant protein 1 [MCP-1], and procollagen type III and type I amino-terminal amino pro-peptide). Death-censored allograft failure. In models adjusted for demographics, chronic kidney disease risk factors, eGFR, and ACR, higher concentrations of urine A1M (HR per doubling, 1.73; 95% CI, 1.43-2.08) and MCP-1 (HR per doubling, 1.60; 95% CI, 1.32-1.93) were strongly associated with allograft failure. When additionally adjusted for concentrations of other urine fibrosis and several urine injury markers, urine A1M (HR per doubling, 1.76; 95% CI, 1.27-2.44]) and MCP-1 levels (HR per doubling, 1.49; 95% CI, 1.17-1.89) remained associated with allograft failure. Urine procollagen type III and type I levels were not associated with allograft failure. We lack kidney biopsy data, BK titers, and HLA antibody status. Urine measurement of tubulointerstitial fibrosis may provide a noninvasive method to identify kidney transplant recipients at higher risk for future allograft failure, above and beyond eGFR and urine ACR. Published by Elsevier Inc.

[Clinical laboratory examination of diabetic patients in conjunction with metabolic syndrome].

PubMed

Kishitani, Yuzuru

2009-11-01

Diabetic patients tend to show a reduced QOL because of macrovascular complications such as cerebral and myocardial infarction, as well as marked microvascular complications. It is important for the prevention and amelioration of these complications to diagnose diabetes mellitus (DM) early and effectively control glycemia, the blood pressure, lipids, and body weight. We examine fasting plasma glucose (FPG) and HbA1c for a diagnosis of diabetes at any time, but examine 75gOGTT for impaired glucose tolerance or DM. Examination to be necessary for a pathologic classification of DM is islet-associated antibody, namely, GAD antibody, IA-2 antibody and the measurement of IRI, blood/urinary C-peptide to evaluate insulin secretory ability. HOMA-R is an index of insulin resistance, and HOMA-beta is an index of insulin secretory ability which can be calculated from FPG and IRI, but we need to be aware that the insulin secretory ability of the patient may have decreased already. HbA1c is a standard index of glycemic control, but glycoalbumin measurement is suitable for disease states such as anemia and liver cirrhosis, and 1,5-anhydroglucitol is suitable for detecting changes in levels of urinary glucose. Examinations necessary for the evaluation of diabetic nephropathy are microalbumin and 24hr Ccr in the urine, but eGFR has been recently recommended instead of 24hr Ccr. We measure small dense LDL-C, RLP-C, and Lp (a) as well as conduct conventional lipid analyses for dislipidemia combined with DM for qualitative as well as quantitative data. Metabolic syndrome is caused by the life habits of overeating and lack of exercise, leading to atherosclerotic disease, because insulin resistance advances from visceral fat accumulation. TNF-alpha and leptin levels as insulin resistance advances and adiponectin levels as insulin resistance improves are measured as adipocytokines secreted by visceral fat tissue.

[The role of urinary markers in the assessment and follow-up of lower urinary tract disorders: a literature review].

PubMed

Peyronnet, B; Bendavid, C; Manunta, A; Damphousse, M; Cheensse, C; Brochard, C; Castel-Lacanal, E; Siproudhis, L; Bensalah, K; Gamé, X

2015-03-01

To conduct a literature review on the role of urinary biomarkers in the initial assessment and follow-up of lower urinary tract symptoms. A literature review was conducted in August 2014 using the Medline/Pubmed database limiting the search to work in English or French. Most studies were of level of evidence 2 or 3 (prospective cohort, controlled or not) and mainly about overactive bladder and bladder pain syndrome. Nerve Growth Factor (NGF) was the most studied and apparently the most promising in the evaluation of overactive bladder (OAB) and neurogenic detrusor overactivity (NDO). Urinary levels of ATP, prostaglandin E2 (PGE2), Brain-Derived Neurotrophic Factor (BDNF) and some cytokines were also significantly higher in most studies in patients with NDO or OAB. Epidermal Growth Factor (EGF), Heparin-Binding EGF (HBEGF) and Antiproliferative Factor (APF) were the most studied urinary markers in bladder pain syndrome, with a significant increase (EGF APF) or decrease (HBEGF) in cases of interstitial cystitis (compared to healthy controls). The urinary N-terminal-telopeptide (NTx) could be predictive of a failed mid-urethral sling. However, few studies reported the diagnostic values of the markers, their association with urodynamic parameters were rarely evaluated and the existence of a publication bias is likely. No randomized controlled study has so far compared the urinary markers to urodynamic evaluation. In the future, urinary markers could complete or replace urodynamic examination. However, to date, there is no high level of evidence study comparing these markers to urodynamics and their use can therefore not be recommended in daily practice. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

Are physical activity, smoking and alcohol consumption associated with lower urinary tract symptoms in men or women? Results from a population based observational study.

PubMed

Maserejian, Nancy N; Kupelian, Varant; Miyasato, Gavin; McVary, Kevin T; McKinlay, John B

2012-08-01

Lower urinary tract symptoms are highly prevalent and reduce quality of life. Lifestyle behaviors and the development of lower urinary tract symptoms have been largely unexamined. We investigated physical activity, smoking and alcohol drinking in relation to the development of lower urinary tract symptoms in men and women. Data were obtained from the BACH (Boston Area Community Health) Survey, a longitudinal observational study. Baseline (2002 to 2005) in-person interviews assessed activity, smoking and alcohol consumption. Five-year followup interviews (2006 to 2010 in 4,145) assessed new reports of moderate to severe lower urinary tract symptoms defined by the AUASI (AUA symptom index). Analysis was conducted using multivariable logistic regression. Lower urinary tract symptoms developed in 7.7% and 12.7% of at-risk men and women, respectively. Women were 68% less likely to experience lower urinary tract symptoms (OR 0.32; 95% CI 0.17, 0.60; p <0.001) if they had high vs low levels of physical activity. Although the association was similar among men, it was not statistically significant upon adjustment for medical or sociodemographic characteristics in the multivariable model. Women smokers were twice as likely to experience lower urinary tract symptoms, particularly storage symptoms (OR 2.15; 95% CI 1.30, 3.56; p = 0.003), compared to never smokers. Among men, smoking was not associated with lower urinary tract symptoms. Results for alcohol intake were inconsistent by intake level and symptom subtype. A low level of physical activity was associated with a 2 to 3 times greater likelihood of lower urinary tract symptoms. Smoking may contribute to the development of lower urinary tract symptoms in women but not in men. Clinicians should continue to promote physical activity and smoking cessation, noting the additional potential benefits of the prevention of lower urinary tract symptoms, particularly for women. Copyright © 2012 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Diagnostic value of potassium level in a spot urine sample as an index of 24-hour urinary potassium excretion in unselected patients hospitalized in a hypertension unit

PubMed Central

Symonides, Bartosz; Wojciechowska, Ewa; Gryglas, Adam; Gaciong, Zbigniew

2017-01-01

Background Primary hyperaldosteronism may be associated with elevated 24-hour urinary potassium excretion. We evaluated the diagnostic value of spot urine (SU) potassium as an index of 24-hour urinary potassium excretion. Methods We measured SU and 24-hour urinary collection potassium and creatinine in 382 patients. Correlations between SU and 24-hour collections were assessed for potassium levels and potassium/creatinine ratios. We used the PAHO formula to estimate 24-hour urinary potassium excretion based on SU potassium level. The agreement between estimated and measured 24-hour urinary potassium excretion was evaluated using the Bland-Altman method. To evaluate diagnostic performance of SU potassium, we calculated areas under the curve (AUC) for SU potassium/creatinine ratio and 24-hour urinary potassium excretion estimated using the PAHO formula. Results Strongest correlation between SU and 24-hour collection was found for potassium/creatinine ratio (r = 0.69, P<0.001). The PAHO formula underestimated 24-hour urinary potassium excretion by mean 8.3±18 mmol/d (95% limits of agreement -28 to +44 mmol/d). Diagnostic performance of SU potassium/creatinine ratio was borderline good only if 24-hour urinary potassium excretion was largely elevated (AUC 0.802 for 120 mmol K+/24 h) but poor with lower values (AUC 0.696 for 100 mmol K+/24 h, 0.636 for 80 mmol K+/24 h, 0.675 for 40 mmol K+/24 h). Diagnostic performance of 24-hour urinary potassium excretion estimated by the PAHO formula was excellent with values above 120 mmol/d and good with lower values (AUC 0.941 for 120 mmol K+/24 h, 0.819 for 100 mmol K+/24 h, 0.823 for 80 mmol K+/24 h, 0.836 for 40 mmol K+/24 h). Conclusions Spot urine potassium/creatinine ratio might be a marker of increased 24-hour urinary potassium excretion and a potentially useful screening test when reliable 24-hour urine collection is not available. The PAHO formula allowed estimation of the 24-hour urinary potassium excretion based on SU measurements with reasonable clinical accuracy. PMID:28662194

Exploring the Potential of (99m)Tc(CO)3-Labeled Triazolyl Peptides for Tumor Diagnosis.

PubMed

Gaonkar, Raghuvir H; Ganguly, Soumya; Baishya, Rinku; Dewanjee, Saikat; Sinha, Samarendu; Gupta, Amit; Ganguly, Shantanu; Debnath, Mita C

2016-04-01

In recent years the authors have reported on (99m)Tc(CO)3-labeled peptides that serve as carriers for biomolecules or radiopharmaceuticals to the tumors. In continuation of that work they report the synthesis of a pentapeptide (Met-Phe-Phe-Gly-His; pep-1), a hexapeptide (Met-Phe-Phe-Asp-Gly-His; pep-2), and a tetrapeptide (Asp-Gly-Arg-His; pep-3) and the attachment of 3-amino-1,2,4-triazole to the β carboxylic function of the aspartic acid unit of pep-2 and pep-3. The pharmacophores were radiolabeled in high yields with [(99m)Tc(CO)3(H2O)3](+) metal aqua ion, characterized for their stability in serum and saline, as well as in His solution, and found to be substantially stable. B16F10 cell line binding studies showed favorable uptake and internalization. In vivo behavior of the radiolabeled triazolyl peptides was assessed in mice bearing induced tumor. The (99m)Tc(CO)3-triazolyl pep-3 demonstrated rapid urinary clearance and comparatively better tumor uptake. Imaging studies showed visualization of the tumor using (99m)Tc(CO)3-triazolyl pep-3, but due to high abdominal background, low delineation occurred. Based on the results further experiments will be carried out for targeting tumor with triazolyl peptides.

Phosphonopeptides as Antibacterial Agents: Alaphosphin and Related Phosphonopeptides

PubMed Central

Allen, John G.; Atherton, Frank R.; Hall, Michael J.; Hassall, Cedric H.; Holmes, Simon W.; Lambert, Robert W.; Nisbet, Louis J.; Ringrose, Peter S.

1979-01-01

Alaphosphin, l-alanyl-l-1-aminoethylphosphonic acid, was selected from a range of phosphonopeptides for evaluation in humans on the basis of its antibacterial activity, pharmacokinetics, and stability to intestinal and kidney peptidases. In vitro, the antibacterial action was antagonized by small peptides, resulting in low activity on peptone media. On an antagonist-free medium alaphosphin was bactericidal and rapidly lysed most susceptible gram-negative bacteria, but it was largely bacteriostatic and essentially nonlytic against gram-positive organisms. Its spectrum included most strains normally isolated from urinary tract infections, but potency was greatly reduced by very high inoculum levels and by alkaline pH. Although strains of Proteus and Pseudomonas were less susceptible to alaphosphin than were other common gram-negative bacteria, like other species they formed spheroplasts when exposed under appropriate conditions. Alaphosphin was equally effective against penicillin-susceptible and -resistant strains and showed no cross-resistance with known antibiotics. Good synergy and increased bactericidal activity were demonstrated with combinations of alaphosphin and d-cycloserine or β-lactam antibiotics. Images PMID:43113

Seed predation by bonobos (Pan paniscus) at Kokolopori, Democratic Republic of the Congo.

PubMed

Georgiev, Alexander V; Thompson, Melissa Emery; Lokasola, Albert Lotana; Wrangham, Richard W

2011-10-01

We compared the feeding ecology of the Hali-Hali community of bonobos (Pan paniscus) at Kokolopori, a new field site in the Democratic Republic of the Congo, between two periods 5 months apart. During the first study period (SP1), bonobos relied heavily on the dry seeds of Guibourtia (Caesalpiniaceae), mostly eaten from the ground. The second period (SP2) was characterized by high consumption of ripe tree fruit. Terrestrial herbaceous vegetation (THV) contributed little to the diet in either study period. The low amount of ripe fruit and the high reliance on seeds in the diet during SP1 were associated with high cortisol production and low levels of urinary C-peptide in females, suggesting nutritional stress. However, female gregariousness was not constrained during the fruit-poor period, probably because high seed abundance on the ground ameliorated scramble feeding competition. This is the first description of extensive seed predation by bonobos. It suggests that bonobo feeding ecology may be more similar to that of chimpanzees than previously recognized.

Assessment of urinary microparticles in normotensive patients with type 1 diabetes.

PubMed

Lytvyn, Yuliya; Xiao, Fengxia; Kennedy, Christopher R J; Perkins, Bruce A; Reich, Heather N; Scholey, James W; Cherney, David Z; Burger, Dylan

2017-03-01

Assessment of urinary extracellular vesicles including exosomes and microparticles (MPs) is an emerging approach for non-invasive detection of renal injury. We have previously reported that podocyte-derived MPs are increased in diabetic mice in advance of albuminuria. Here, we hypothesised that type 1 diabetes and acute hyperglycaemia would increase urinary podocyte MP levels in uncomplicated diabetes. In this post hoc exploratory analysis, we examined archived urine samples from normoalbuminuric patients with uncomplicated type 1 diabetes studied under clamped euglycaemia and hyperglycaemia and compared with healthy controls. Urinary vesicles were assessed by electron microscopy and nanoparticle tracking while podocyte MPs were assessed by flow cytometry. Neither vesicle size nor total number were significantly altered in type 1 diabetes or acute hyperglycaemia. By contrast, urinary podocyte MP levels were higher in type 1 diabetes (0.47 [0.00-3.42] MPs/μmol creatinine [Cr]) compared with healthy controls (0.00 [0.00-0.00] MPs/μmol Cr, p < 0.05) and increased under hyperglycaemic clamp (0.36 [0.00-4.15] MPs/μmol Cr during euglycaemia vs 2.70 [0.00-15.91] MPs/μmol Cr during hyperglycaemia, p < 0.05). Levels of urinary albumin to creatinine ratio and nephrin (surrogates of podocyte injury) were unchanged by type 1 diabetes or acute hyperglycaemia. Taken together, our data show that urinary podocyte MP levels are higher in patients with type 1 diabetes in advance of changes in other biomarkers (albuminuria, nephrin). Examination of podocyte MPs may serve as an early biomarker of glomerular injury in uncomplicated type 1 diabetes.

Decreased fractional urinary calcium excretion and serum 1,25-dihydroxyvitamin D and IGF-I levels in preeclampsia.

PubMed

Halhali, Ali; Díaz, Lorenza; Avila, Euclides; Ariza, Ana Carolina; Garabédian, Michèle; Larrea, Fernando

2007-03-01

During preeclampsia several alterations of calcium metabolism have been described, the most common of them is hypocalciuria, which pathophysiology is still unclear. In order to assess the contribution of calciotropic hormones to urinary calcium excretion, a cross-sectional study was done including 26 preeclamptic Mexican women (PE group) and 26 normotensive control pregnant women (NT group). Total and fractional urinary calcium excretion were significantly lower (P<0.0001) in the PE group than in the NT group (82+/-7 versus 171+/-7 mg/24h and 0.62+/-0.38 versus 1.38+/-0.71%, respectively), without significant differences in creatinine clearance, urinary sodium excretion and phosphate tubular reabsorption. In addition, serum 1,25-(OH)(2)D and IGF-I levels were significantly (P<0.05) lower in the PE than in NT group (43+/-9 versus 50+/-9 pg/mL and 195+/-67 versus 293+/-105 ng/mL, respectively), without significant differences in serum PTH levels. In the NT group, association analysis showed that total and fractional urinary calcium excretions positively correlated with serum levels of 1,25-(OH)(2)D (P<0.01) and IGF-I (P<0.001). In the PE group, total urinary calcium excretion positively correlated only with serum 1,25-(OH)(2)D (P<0.05). In conclusion, the results obtained in this study confirm that PE is associated with hypocalciuria and suggest that 1,25-(OH)(2)D and/or IGF-I may be involved in the regulation of urinary calcium excretion.

Influence of body mass index status on urinary creatinine and specific gravity for epidemiological study of children.

PubMed

Wang, Bin; Tang, Chuanxi; Wang, Hexing; Zhou, Wei; Chen, Yue; Zhou, Ying; Jiang, Qingwu

2015-11-01

In epidemiological studies, urinary biomonitoring is a valid approach to assess the association between environmental chemical exposure and children's health. Many clinical biomarkers (e.g., endogenous metabolites) are also based on analysis of urine. Considering the variability in urinary output, urinary concentrations of chemicals are commonly adjusted by creatinine and specific gravity (SG). However, there is a lack of systematic evaluation of their appropriateness for children. Furthermore, urinary SG and creatinine excretion could be influenced by body mass index (BMI), but the effect of BMI status on the two correction factors is unknown. We measured SG and creatinine concentrations of repeated first morning urine samples collected from 243 primary school children (8-11 years) over 5 consecutive weekdays. Urinary SG presented a higher temporal consistency compared with creatinine. Urinary SG was associated with sex (p < 0.001), whereas sex (p =0.034) and BMI (p = 00.008) were associated with urinary creatinine levels. Inter-day collection time was not associated with SG or creatinine after excluding the effect of Monday as a confounder. When stratified by BMI status, none of the factors were associated with creatinine among the overweight and obese children. Generally, SG is preferable for correcting the variability in urinary output for children although creatinine correction may also perform well in overweight and obese children. SG correction is recommended for epidemiological exposure analysis in children based on urinary levels of exogenous or endogenous metabolites.

Characterization of the Mouse Beta Defensin 1, Defb1, Mutant Mouse Model

PubMed Central

Morrison, Gillian; Kilanowski, Fiona; Davidson, Donald; Dorin, Julia

2002-01-01

Beta defensins are small cationic antimicrobial peptides present in the respiratory system which have been proposed to be dysfunctional in the environment of the cystic fibrosis lung. Defb1, a murine homologue to the human beta defensins, has also been found to be expressed in the respiratory system and, in order to examine the function of beta defensins in vivo, gene targeting was used to generate Defb1-deficient (Defb1tm1Hgu/Defb1tm1Hgu [Defb1−/−]) mice. The Defb1 synthetic peptide was shown to have a salt-sensitive antimicrobial activity that was stronger against Staphylococcus aureus than against Escherichia coli or Pseudomonas aeruginosa. Defb1−/− mice were found, however, to be effective in the clearance of the cystic fibrosis relevant pathogen S. aureus from the airways after nebulization. Although no overt deleterious phenotype was evident in the Defb1−/− mice, the number of mutant mice found to harbor bacteria of the Staphylococcus species in the bladder was significantly higher (P = 0.008) than that of controls, suggesting a role for these peptides in resistance to urinary tract infection. PMID:12010997

Factors Related to Urinary Incontinence among the Malaysian Elderly.

PubMed

Eshkoor, S A; Hamid, T A; Shahar, S; Mun, C Y

2017-01-01

Urinary incontinence is a prevalent condition in the elderly that is the spontaneous leakage of urine. It is an age-related problem and increases especially in people aged above 65 years. It can cause many psychological, behavioral, biological, economic and social effects. The treatment of urinary incontinence can reduce morbidity and mortality. Thus, this study aimed to determine the effects of variables including age, ethnicity, gender, education, marital status, body weight, blood elements and nutritional parameters on urinary incontinence among the Malaysian elderly. The study was on 2322 non-institutionalized Malaysian elderly. The hierarchy logistic regression analysis was applied to estimate the risk of independent variables for urinary incontinence among respondents. The findings indicated that approximately 3.80% of subjects had urinary incontinence. In addition, constipation was found a significant factor that increased the risk of urinary incontinence in samples (p=0.006; OR=3.77). The increase in dietary monounsaturated fat (p=0.038; OR=0.59) and plasma triglyceride levels (p=0.029; OR=0.56) significantly reduced the risk of incontinence in subjects. Many of suspected variables including socio-demographic factors, diseases, nutritional minerals, blood components and body weight were non-relevant factors to urinary incontinence in respondents. Constipation increased the risk of urinary incontinence in subjects, and increase in dietary monounsaturated fat and plasma triglyceride levels decreased the risk.

PBPK-MODEL ESTIMATES OF BROMODICHLOROMETHANE (BDCM) DISTRIBUTION IN URINE AND BLADDER TISSUE

EPA Science Inventory

Recent data indicate that noningestion exposure to trihalomethanes (THMs), including BDCM is highly correlated with urinary THM levels. Characterizing urinary levels of drinking water disinfection byproducts (DBPs) will likely be important for understanding DBP-associated bladde...

C-reactive protein levels in girls with lower urinary tract symptoms.

PubMed

Tarhan, H; Ekin, R G; Can, E; Cakmak, O; Yavascan, O; Mutlubas Ozsan, F; Helvaci, M; Zorlu, F

2016-04-01

Daytime lower urinary tract (LUT) conditions are identified as daytime incontinence problems for children in whom any cause of neuropathy and uropathy has been excluded. C-reactive protein (CRP) is a common marker of acute or chronic inflammation and infection. Increased CRP levels have been detected in the studies conducted on adults diagnosed with overactive bladders and interstitial cystitis. This study aimed to investigate the role of serum CRP levels in girls suffering from daytime LUT conditions. Out of the 752 patients who presented to the outpatient clinics with lower urinary tract symptoms, 709 were excluded due to: being boys, having previous urinary tract surgery, an active urinary tract infection, a neurological anomaly, a urinary system anomaly, having rheumatic disease, any chronic disease, any febrile infection over the past week, a history of constipation, and enuresis nocturna. Forty-three girls with LUT conditions and aged 8-10 years were included in the study as the patient group. Forty girls who attended the urology outpatient clinic without LUT conditions, or active urinary tract infections and any chronic disease requiring follow-up constituted the control group. Under the control of the parents, all subjects were asked to fill out 3-day voiding diaries. The voiding diaries identified frequency, urgency, urgency urinary incontinence, and functional bladder capacity data. All subjects also completed a dysfunctional voiding scoring system (DVSS). The serum CRP levels of all subjects were measured. There was a significant difference in serum CRP levels and DVSS between the patient group and the control group (P = 0.001, P = 0.001). The mean serum CRP levels showed a significant increase when frequency and urgency scores were ≥8, the urge incontinence score was ≥2 and the DVS score DVSS was ≥14 in the voiding diaries of the patient group (Table). Lower urinary tract dysfunction is defined as a condition involving abnormalities of filling and/or emptying of the bladder. This frequently encountered problem constitutes >40% of all pediatric urology outpatient visits. The relationship between LUT conditions and serum CRP in both genders has been detected. However, it is believed that to our knowledge, this is the first study looking at the relationship between daytime LUTS and increased CRP levels in children. The most important limitations of the study were: having a small number of patients, and the sample consisting of only one gender and a specific age group. The serum CRP levels were significantly higher in the girls with daytime LUT conditions than in the control group. Also, the CRP levels significantly increased as DVSS, frequency, urgency, and urge incontinence scores increased. Copyright © 2015 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.

Exposure of flight attendants to pyrethroid insecticides on commercial flights: urinary metabolite levels and implications

PubMed Central

Wei, Binnian; Mohan, Krishnan R.; Weisel, Clifford P.

2011-01-01

Pyrethroid insecticides have been used for disinsection of commercial aircrafts. However, little is known about the pyrethroids exposure of flight attendants. The objective of the study was to assess pyrethroids exposure of flight attendants working on commercial aircrafts through monitoring the urinary pyrethroids metabolite levels. Eighty four urine samples were collected from 28 flight attendants, 18 – 65 years of age, with seventeen working on planes that were non-disinsected, and eleven working on planes that had been disinsected. Five urinary metabolites of pyrethroids were measured using gas chromatographic–mass spectrometric method: 3-phenoxybenzoic acid (3-PBA), cis-/trans-3-(2,2-Dichlorovinyl)-2,2-dimethylcyclo-propane carboxylic acid (cis-/trans-Cl2CA), cis-3-(2,2-dibromovinyl)-2,2-dimethylcyclo-propane-1-carboxylic acid (cis-Br2CA) and 4-fluoro-3-phenoxybenzoic acid (4F-3-PBA). Flight attendants working on disinsected planes had significantly higher urinary levels of 3-PBA, cis- and trans-Cl2CA in pre, post- and 24hr-post flight samples than those on planes which did not report having been disinsected. Urinary levels of cis-Br2CA and 4F-3-PBA did not show significant differences between the two groups. Flight attendants working on international flights connected to Australia had higher urinary levels of 3-PBA, cis- and trans-Cl2CA than those on either domestic and other international flights flying among Asia, Europe and North America. Post-disinsection duration (number of days from disinsection date to flight date) was the most significant factor affecting the urinary pyrethroid metabolites levels of 3-PBA, cis- and trans-Cl2CA of the group flying on disinsected aircraft. It was concluded that working on commercial aircrafts disinsected by pyrethroids resulted in elevated body burden of 3-PBA, cis- and trans-Cl2CA. PMID:21937269

Isotope-dilution assay for urinary methylmalonic acid in the diagnosis of vitamin B12 deficiency. A prospective clinical evaluation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Matchar, D.B.; Feussner, J.R.; Millington, D.S.

1987-05-01

Vitamin B12 deficiency is a frequently considered diagnosis for which there is no single, commonly available and accurate test. A urinary methylmalonic acid assay using gas chromatography-mass spectrometry has been proposed as the preferred test. We reviewed vitamin B12 assays on 1599 consecutive patients and prospectively studied all patients with low serum B12 levels (n = 75) and a random sample of patients with normal levels (n = 68). Of 96 evaluable patients, 7 had clinical deficiency. All 7 deficient patients had urinary methylmalonic acid levels greater than 5 micrograms/mg creatine (sensitivity, 100%; confidence interval, 65% to 100%). Of themore » 89 patients who were not clinically deficient, 88 had urinary methylmalonic acid levels less than or equal to 5 micrograms/mg creatinine (specificity, 99%). The overall test accuracy in this population was 99%. If the high sensitivity and specificity of the gas chromatography-mass spectrometry assay for urinary methylmalonic acid is supported by other clinical studies, the methylmalonic acid assay may become the reference standard for the diagnosis of vitamin B12 deficiency.« less

Predictors of Urinary 3-Phenoxybenzoic Acid Levels in 50 North Carolina Adults

EPA Science Inventory

Limited data are available on the non-chemical stressors that impact adult exposures to pyrethroid insecticides based on urinary biomonitoring. The urinary metabolite, 3-phenoxybenzoic acid (3-PBA), is commonly used to assess human exposure to a number of pyrethroids. In a furthe...

Phaeochromocytoma with hypercortisolism and hypercalcaemia.

PubMed

Edafe, Ovie; Webster, Jonathan; Fernando, Malee; Vinayagam, Ragu; Balasubramanian, Sabapathy P

2015-10-07

We report a case of phaeochromocytoma associated with hypercortisolism and hypercalcaemia in a 62-year-old man. The patient presented to clinic, with a 3-year history of exertional headaches, and a 4-month history of increasing fatigue, sweating and palpitations, loss of appetite and weight, and sleepiness. He did not have a medical, family or social history that could account for these symptoms. 24 h urinary catecholamines, plasma metanephrines, 24 h urinary cortisol and adjusted serum calcium, were elevated. Overnight low-dose dexamethasone suppression test did not suppress morning plasma cortisol. Serum intact parathyroid hormone and parathyroid hormone-related peptide were low, and adrenocorticotropic hormone was normal. The patient was treated with intravenous 0.9% sodium chloride and disodium pamidronate to control hypercalcaemia. CT showed a 10 cm left adrenal mass. Following inpatient treatment with phenoxybenzamine, he underwent a left adrenectomy and histology confirmed a phaeochromocytoma. Postoperatively, he required long-term steroids for contralateral adrenal suppression. Adjusted serum calcium returned to normal postoperatively. 2015 BMJ Publishing Group Ltd.

Cardiac natriuretic peptide response to water restriction in the hormonal adaptation of two semidesert rodents from West Africa (Steatomys caurinus, Taterillus gracilis).

PubMed

Lacas, S; Allevard, A M; Ag'Atteinine, S; Gallo-Bona, N; Gauquelin-Koch, G; Hardin-Pouzet, H; Gharib, C; Sicard, B; Maurel, D

2000-11-01

Two African rodents, Taterillus gracilis and Steatomys caurinus, native to regions of alternate dry and wet seasons, were studied under laboratory conditions. These species differ in estivation behavior, one undergoing pseudoestivation and the other strong estivation. One group of animals of each species was provided with unlimited access to seed and vegetables rich in water, mimicking the food availability of the wet season (control group). A second group of animals of each species was subjected to water restriction for 8 days, mimicking the natural drought that occurs during the dry-hot season. The effects of water restriction on osmoregulation and body water content were assessed from hematocrit, and plasma and urinary osmolalities (PO, UO). Whether the natriuretic peptide system was modified by the osmoregulator adaptation to aridity of these semidesert rodents was examined from measurements of atrial natriuretic peptide (ANP) levels in plasma, atria, and ventricles, in parallel with morphological studies. In both species, UO was increased by water restriction. In water-deprived T. gracilis, ANP levels were about twice (right atria: 1.08 +/- 0.16 microg/mg protein vs control: 0.40 +/- 0.06 microg/mg protein) and plasma concentrations half (0.28 +/- 0.06 ng/ml vs control: 0.64 +/- 0.07 ng/ml) those in control animals. In S. caurinus these variables were not affected by water availability (right atria water restricted: 2. 20 +/- 0.15 microg/mg protein vs control: 2.86 +/- 0.37 microg/mg protein; plasma ANP water restricted: 0.80 +/- 0.12 ng/ml vs control: 0.90 +/- 0.16 ng/ml). Consistent with these quantitative results, immunohistochemical and ultrastructural observations showed an increase in immunostaining for both the N- and the C-terminal ANP and a larger number of granules in the atria of T. gracilis following water restriction, whereas there was no visible change in S. caurinus. Thus, water restriction induced a decrease in ANP secretion in T. gracilis, increasing cardiac storage alongside a reduced urine production. In contrast, in S. caurinus, the natriuretic system was not affected by an 8-day period of water restriction. Copyright 2000 Academic Press.

Urinary cotinine in narguila or chicha tobacco smokers.

PubMed

Macaron, C; Macaron, Z; Maalouf, M T; Macaron, N; Moore, A

1997-01-01

Urinary levels of nicotine metabolites were measured in nonsmokers and smokers of tobacco either as cigarettes or as the Middle-Eastern water pipes (narguila). Levels of urinary cotinine were similar for the smokers of cigarettes (median 30 cigarettes per day) and narguila (median 2 pipes per day, or around 40 grams of tobacco). Use of water pipes may remove a small amount of nicotine, but smokers appear to titrate dose to effect. It is unlikely that narguila smoking confers any less risk.

Effects of oral contraceptives on natriuretic peptide levels in women with hypothalamic amenorrhea: a pilot study.

PubMed

Lin, Eleanor; Grinspoon, Steven; Wang, Thomas; Miller, Karen K

2011-06-30

Natriuretic peptides, which are important regulators of salt handling and blood pressure, are 60%-75% higher in healthy young women than in men, consistent with a gender dimorphism. In this randomized, placebo-controlled study in women with functional hypothalamic amenorrhea, we show that administration of oral contraceptives (OC) increases natriuretic peptide levels and that end-of-study free T levels are inversely associated with amino-terminal pro-B-type natriuretic peptide levels, consistent with the hypothesis that natriuretic peptide levels may be mediated by differences in gonadal steroid concentrations-estrogens (E) or androgens. Copyright © 2011 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Using Peptide-Level Proteomics Data for Detecting Differentially Expressed Proteins.

PubMed

Suomi, Tomi; Corthals, Garry L; Nevalainen, Olli S; Elo, Laura L

2015-11-06

The expression of proteins can be quantified in high-throughput means using different types of mass spectrometers. In recent years, there have emerged label-free methods for determining protein abundance. Although the expression is initially measured at the peptide level, a common approach is to combine the peptide-level measurements into protein-level values before differential expression analysis. However, this simple combination is prone to inconsistencies between peptides and may lose valuable information. To this end, we introduce here a method for detecting differentially expressed proteins by combining peptide-level expression-change statistics. Using controlled spike-in experiments, we show that the approach of averaging peptide-level expression changes yields more accurate lists of differentially expressed proteins than does the conventional protein-level approach. This is particularly true when there are only few replicate samples or the differences between the sample groups are small. The proposed technique is implemented in the Bioconductor package PECA, and it can be downloaded from http://www.bioconductor.org.

Urinary fibronectin levels in patients treated with intravesical bacillus Calmette-Guérin for superficial bladder cancer.

PubMed

Danişman, A; Bulut, K; Kukul, E; Ozen, I; Sevük, M

2000-01-01

Intravesical bacillus Calmette-Guérin (BCG) has been shown to be an effective treatment for superficial transitional cell carcinoma (TCC) of the bladder, but the precise mechanism of action of BCG remains poorly understood. Fibronectin (FN), an important component of the extracellular matrix, has been found to play a role in BCG therapy. Some studies have shown that the soluble form of FN can compete efficiently with the matrix form of binding to the specific receptors on the bacteria and could consequently diminish the effect of BCG treatment. To evaluate a possible correlation between the urinary levels of FN and the efficacy of BCG therapy, we determined prospectively the urinary FN levels in 38 patients with TCC of the bladder and in 25 control subjects without malignancy matched for age and sex. All TCC patients were treated with transurethral tumor resection plus 6 weekly intravesical BCG instillations. After an average follow-up of 30 months, 8 patients (21.1%) had recurrent tumors, while 30 (78.9%) were free of tumor after intravesical BCG therapy. Urinary levels of FN in cancer patients have been shown to be significantly higher than controls (p < 0.001). These elevated levels were not decreased significantly after the operation (p > 0. 05). It was also found that the mean urinary FN levels were not statistically significant between patients with recurrence and complete remission. The data suggest that BCG-bladder tumor cell binding is not influenced by soluble fibronectin and urinary FN may not be a ideal marker for selecting patients to BCG therapy. Copyright 2000 S. Karger AG, Basel

The relationship between serum and urinary Fetuin-A levels and kidney stone formation among kidney stone patients.

PubMed

Mehrsai, Abdolrasoul; Guitynavard, Fateme; Nikoobakht, Mohammad Reza; Gooran, Shahram; Ahmadi, Ayat

2017-01-01

Mineralization inhibitors are required to prevent the precipitation of minerals and inhibit the formation of kidney stones and other ectopic calcifications. In laboratory studies, Fetuin-A as a glycoprotein has inhibited hydroxyapatite precipitation in calcium and phosphate supersaturated solutions; however, information about patients with kidney stones is limited. The aim of this study was to investigate the association of serum and urinary Fetuin-A levels with calcium oxalate kidney stones. In this case-control study, 30 patients with kidney stones and 30 healthy individuals without any history of urolithiasis who were referred to the urology ward of Sina Hospital of Tehran, Iran, in 2015 were entered into the study. All patients underwent computerized tomography scans. After collecting demographic information, serum and urine levels of Fetuin-A and some other calcification inhibitors and promoters, were measured and compared using T-test, Mann-Whitney and logistic regression between the two study groups. Patients with kidney stones, on average, had lower levels of Serum Fetuin-A (1522.27 ±755.39 vs. 1914.64 ±733.76 μg/ml; P = 0.046) as well as lower levels of Urine Fetuin-A (944.62 ±188.5 vs. 1409.68 ±295.26 μg/ml; P <0.001). Multivariate logistic analysis showed that urinary calcium and serum creatinine are the risk factors and Fetuin-A is a urinary protective factor for kidney stones. PFC Our study showed that patients with kidney stones had lower serum and urinary levels of Fetuin-A. In the logistic regression model, urinary Fetuin-A was reported as a protective factor for kidney stones.

Associations between sperm quality, DNA damage, and CYP1A1, GSTT1 and GSTM1 polymorphisms with 1-hydroxypyrene urinary levels in men occupationally exposed to polycyclic aromatic hydrocarbons.

PubMed

Recio-Vega, Rogelio; Olivas-Calderon, Edgar; Michel-Ramirez, Gladis; Martinez-Salinas, Rebeca Isabel; Gallegos-Arreola, Martha Patricia; Ocampo-Gomez, Guadalupe Leticia; Perez-Morales, Rebeca

2018-05-29

During recent decades, several reports have suggested a decrease in semen quality and DNA damage due in part to environmental toxicants and industrial chemicals. Among these xenobiotics, polycyclic aromatic hydrocarbons (PAHs) are of particular concern because of their remarkable mutagenic and carcinogenic properties and because several experimental and epidemiological studies have reported adverse effects of PAHs on male reproductive health and DNA structure. The aim of the study was to evaluate the association between 1-hydroxypyrene (1-OHP) urinary levels and sperm quality, DNA damage and the frequency of CYP1A1, GSTT1, and GSTM1 polymorphisms. Semen, urine and blood samples were taken for sperm-quality assessment, 1-OHP urinary level measurement, DNA damage evaluation and polymorphism frequency analysis of three genes implicated in PAH metabolism in a total of 70 Mexican subjects exposed and nonexposed to PAHs. A significant decrease in sperm quality and increased DNA damage were registered in occupationally exposed volunteers. Polymorphisms modified the 1-OHP urinary levels; however, no associations were found between them. Inverse associations were registered between the sperm concentration/mL and 1-OHP levels and between tail lengths and the GSMT1 null genotype. Our data showed an inverse association between 1-OHP urinary levels and both sperm quality and the DNA integrity. Additionally, the heterozygote variants of CYP1A1-m1 and CYP1A1-m2 significantly increased the urinary excretion of 1-OHP, and the GSTM1 null variant was inversely associated with the comet parameters evaluated.

[Effects of n-hexane exposure on human serum myelin basic proteins].

PubMed

Zhou, Wei; Yi, Juan; Huang, Hui-Ping; Xiang, Ying-Ping; He, Jia-Xi; Liu, Qing-Jun; Huang, Xian-Qing

2011-06-01

To explore the effects of n-hexane on expression of serum myelin proteins (MBP) in workers occupationally exposed to n-hexane. In this study, 269 workers exposed to n-hexane for more than one year and 104 subjects not exposed to n-hexane served as the exposure group and the control group, respectively. The urinary 2,5-hexanedione levels in all subjects were detected. On the basis of urinary 2,5-hexanedione levels, the exposure group was divided into the high exposure sub-group and low exposure sub-group. The serum myelin basic protein (MBP) levels were measured by ELISA kit. The mean concentration of urinary 2,5-hexanedione in the exposed group was (3.10 +/- 1.35) mg/L. The concentration of urinary 2,5-hexanedione in the control group was undetectable. The levels of serum MBP in the high exposure sub-group and low exposure sub-group were (2.43 +/- 0.24) and (1.62 +/- 0.23) microg/L, respectively, which were significantly higher than that (0.78 +/- 0.12) microg/L in the controls (P < 0.01). Pearson correlation analysis showed the positive correlation between serum MBP levels and urinary 2,5-hexanedione levels (r = 0.781, P < 0.01). The results of present study showed that the serum MBP levels of workers occupationally exposed to n-hexane significantly elevated, and the serum MBP can serve as the effective biomarker of n-hexane exposure.

Elevated urinary level of vitamin D-binding protein as a novel biomarker for diabetic nephropathy

PubMed Central

TIAN, XIAO-QIN; ZHAO, LI-MIN; GE, JIA-PU; ZHANG, YAN; XU, YAN-CHENG

2014-01-01

Improving the early prediction and detection of diabetic nephropathy (DN) remains a great challenge in disease management. The aim of this study was to evaluate the early detection power of urinary vitamin D-binding protein (VDBP) for the diagnosis of DN. Urine samples were obtained from 45 healthy volunteers and 105 diabetic patients with normoalbuminuria (DM group), microalbuminuria (DN1 group) and macroalbuminuria (DN2 group) (n=35 per group). The VDBP expression patterns in urine from patients and controls were quantified by western blot analysis. The excretion levels of urinary VDBP were quantified with enzyme-linked immunosorbent assay. The quantification results were obtained by correcting for creatinine expression and showed that urinary VDBP levels were significantly elevated in the patients of the DN1 and DN2 groups compared with those of the DM group and normal controls (1,011.33±325.30 and 1,406.34±239.66 compared with 466.54±213.63 and 125.48±98.27 ng/mg, respectively) (P<0.001). Receiver operating characteristic analysis of urinary VDBP levels for the diagnosis of DN rendered an optimum cut-off value of 552.243 ng/mg corresponding to 92.86% sensitivity and 85.00% specificity, which also showed an area under the ROC curve of 0.966. In conclusion, the findings of the present study suggest that urinary VDBP may be a potential biomarker for the early detection and prevention of DN. Further studies are required to examine the pathogenic mechanisms of elevated VDBP levels and their role in the diagnosis of DN. PMID:24396416

Exposure related mutagens in urine of rubber workers associated with inhalable particulate and dermal exposure

PubMed Central

Vermeulen, R; Bos, R; Pertijs, J; Kromhout, H

2003-01-01

Aims: To determine the relation of the inhalation and dermal exposure routes and mutagenic activity in the urine of rubber workers (n = 105). Methods: Mutagenic activity of ambient total suspended particulate matter (TSPM), surface contamination wipes, and Sunday and weekday urine samples was assessed with S typhimurium YG1041 in the presence of a metabolic activation system. Each subject was grouped into one of two exposure categories for dermal exposure (high (≥25 revertants/cm2), low (<25 revertants/cm2)) based on the mutagenic activity detected on likely skin contact surfaces and into two airborne mutagenic exposure categories (high (≥210 revertants/m3), low (<210 revertants/m3)). The potential influence of skin aberrations and acetylation status (NAT2) on urinary mutagenicity levels was also evaluated. Results: A non-significant increase of +1605 revertants/g creatinine in urinary mutagenicity during the workweek relative to levels observed on Sunday was observed for the total population. Subsequent multivariate regression analyses, with the subjects' weekday urinary mutagenicity levels as the dependent variable, revealed associations with environmental and mainstream tobacco smoke exposure, with the level of mutagenic contamination on surfaces with which the subjects had likely contact, with the subjects' inhalable particulate exposure level, with observed mild skin aberrations, and when the subjects had a slow acetylation phenotype. Similar associations, although weaker were observed with Sunday urinary mutagenicity levels as well, except for the association with slow acetylation phenotype. Based on measured exposure levels it could be estimated that a high potential for exposure to surface contamination with mutagenic activity increased weekday urinary mutagenicity by about 62% when compared to low exposed workers, while high inhalable particulate exposure levels increased weekday urinary mutagenicity levels by about 21%. Subjects with mild skin aberrations had an additional, non-significant, increase in weekday urinary mutagenic activity compared to subjects without any skin aberrations. Discussion: Results suggest that the dermal exposure route may contribute more to the level of genotoxic compounds in urine of rubber workers than the inhalation route. Although the study was limited in size, the results warrant further investigation in the importance of and ways to effectively control the dermal exposure route in the rubber industry. PMID:12554836

Urinary levels of nickel and chromium associated with dental restoration by nickel–chromium based alloys

PubMed Central

Chen, Bo; Xia, Gang; Cao, Xin-Ming; Wang, Jue; Xu, Bi-Yao; Huang, Pu; Chen, Yue; Jiang, Qing-Wu

2013-01-01

This paper aims to investigate if the dental restoration of nickel–chromium based alloy (Ni–Cr) leads to the enhanced excretions of Ni and Cr in urine. Seven hundred and ninety-five patients in a dental hospital had single or multiple Ni–Cr alloy restoration recently and 198 controls were recruited to collect information on dental restoration by questionnaire and clinical examination. Urinary concentrations of Ni and Cr from each subject were measure by graphite furnace atomic absorption spectrometry. Compared to the control group, the urinary level of Ni was significantly higher in the patient group of <1 month of the restoration duration, among which higher Ni excretions were found in those with either a higher number of teeth replaced by dental alloys or a higher index of metal crown not covered with the porcelain. Urinary levels of Cr were significantly higher in the three patient groups of <1, 1 to <3 and 3 to <6 months, especially in those with a higher metal crown exposure index. Linear curve estimations showed better relationships between urinary Ni and Cr in patients within 6-month groups. Our data suggested significant increased excretions of urinary Ni and Cr after dental restoration. Potential short- and long-term effects of Ni–Cr alloy restoration need to be investigated. PMID:23579466

Urinary excretion of 5-hydroxyindoleacetic acid, serotonin and 6-sulphatoxymelatonin in normoserotonemic and hyperserotonemic autistic individuals.

PubMed

Mulder, Erik J; Anderson, George M; Kemperman, Ramses F J; Oosterloo-Duinkerken, Alida; Minderaa, Ruud B; Kema, Ido P

2010-01-01

A substantial proportion of individuals with autism have elevated levels of platelet serotonin (5-HT). We examined whether platelet hyperserotonemia is associated with increased gut 5-HT synthesis, altered 5-HT catabolism or altered melatonin production. Urinary excretion of 5-hydroxyindoleacetic acid (5-HIAA) and 5-HT was compared in 10 normoserotonemic and 10 hyperserotonemic age-matched autistic individuals. The relationship of urinary 6-sulfatoxymelatonin (6-SM) excretion to platelet 5-HT, and to urinary 5-HT and 5-HIAA excretion, was also examined. In the hyperserotonemic group, significant increases at trend level in urinary excretion of 5-HIAA (p = 0.061) and 5-HT (p = 0.071) and a significant decrease for 6-SM were found (p = 0.027). The urinary 5-HIAA:5-HT ratio was similar in the normo- versus the hyperserotonemic groups. The catabolism of 5-HT does not differ in the groups, but greater exposure of the platelet to 5-HT cannot be ruled out as a cause of the platelet hyperserotonemia of autism. Although only trend level significant, the data point to a need for larger studies to examine more thoroughly the relationships between platelet hyperserotonemia, gut 5-HT synthesis and melatonin production. (c) 2009 S. Karger AG, Basel.

Correlation between Serum Calcineurin Activity and Left Ventricular Hypertrophy in Hypertensive Patients and Its Clinical Significance.

PubMed

Cao, Jia-Li; Yang, Yu-Qing; Nabeel, Dookhun Muhammad; Sun, Ya-Li; Zou, Hua-Yi-Yang; Kong, Xiang-Qing; Lu, Xin-Zheng

The aim of this study is to investigate the correlation between calcineurin (CaN) and hypertension with left ventricular hypertrophy (HLVH) and to evaluate its potential clinical significance. The study involved 160 patients diagnosed with hypertension and 42 controls. Based on the exclusion criteria, 42 were not eligible for this study. The remaining 118 hypertensive patients were categorized into 2 subgroups based on left ventricular mass index and relative ventricular wall thickness: a normal model subgroup with hypertension (HNM) and an HLVH subgroup. Serum CaN levels were determined by enzyme-linked immunosorbent assay, while serum CaN activity was determined by malachite green colorimetric assay. Among the HNM and HLVH subgroups, a positive correlation was demonstrated between serum CaN activity, but not serum CaN level, and HLVH. Moreover, the HLVH subgroup displayed a remarkable increase in the levels of brain natriuretic peptide, cystatin C, urinary albumin/creatinine ratio, and left atrium diameter compared to the HNM subgroup and controls. There was a positive correlation between serum CaN activity and LVH in hypertensive patients. Activated CaN could play an important role in the pathophysiologic mechanism of HLVH. Serum CaN activity could be a clinically useful diagnostic and prognostic biomarker for LVH. © 2018 S. Karger AG, Basel.

NON-RESIDENTIAL ORGANOPHOSPHOROUS PESTICIDE USE AS A PREDICTOR OF CHILDREN'S URINARY METABOLITE LEVELS

EPA Science Inventory

NON-RESIDENTIAL ORGANOPHOSPHORUS PESTICIDE USE AS A PREDICTOR OF CHILDREN'S URINARY METABOLITE LEVELS.
Julie A. Baker, Pauline Mendola, Dana Barr, Debra Walsh, John Creason, and Larry Needham. (University at Buffalo, US Environmental Protection Agency, and Centers for Disease ...

Lingual dyskinesia and tics: a novel presentation of copper-metabolism disorder.

PubMed

Goez, Helly R; Jacob, Francois D; Yager, Jerome Y

2011-02-01

Copper is a trace element that is required for cellular respiration, neurotransmitter biosynthesis, pigment formation, antioxidant defense, peptide amidation, and formation of connective tissue. Abnormalities of copper metabolism have been linked with neurologic disorders that affect movement, such as Wilson disease and Menkes disease; however, the diagnosis of non-Wilson, non-Menkes-type copper-metabolism disorders has been more elusive, especially in cases with atypical characteristics. We present here the case of an adolescent with a novel presentation of copper-metabolism disorder who exhibited acute severe hemilingual dyskinesia and prominent tics, with ballismus of the upper limbs, but had normal brain and spinal MRI results and did not show any signs of dysarthria or dysphagia. His serum copper and ceruloplasmin levels were low, but his urinary copper level was elevated after penicillamine challenge. We conclude that copper-metabolism disorders should be included in the differential diagnosis for movement disorders, even in cases with highly unusual presentations, because many of them are treatable. Moreover, a connection between copper-metabolism disorders and tics is presented, to our knowledge, for the first time in humans; further investigation is needed to better establish this connection and understand its underlying pathophysiology.

Therapeutic effects of calcium dobesilate on diabetic nephropathy mediated through reduction of expression of PAI-1

PubMed Central

ZHANG, XIAOQIAN

2013-01-01

The aim of this study was to investigate whether calcium dobesilate (calcium dihydroxy-2,5-benzenesulfonate) may be used to treat diabetic nephropathy. A total of 121 patients with type 2 diabetic nephropathy received calcium dobesilate (500 mg, 3 times a day) for 3 months. The levels of glycated hemoglobin, fasting serum C peptide, triglyceride, total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, alanine aminotransferase, γ-glutamyl transferase, urea nitrogen, creatinine, hematocrit, plasma viscosity, whole blood reduced viscosity, high, medium and low shear rate whole blood viscosity, fibrinogen, plasminogen activator inhibitor-1 (PAI-1) and endothelin were determined. The urinary albumin excretion rate (UAER) was also determined once a month during the study. The UAER and medium and low shear rate whole blood viscosity were significantly lower in the treated patients. The rate of microalbuminuria normalization was 90%. During the treatment, the UAERs decreased. The results revealed that calcium dobesilate has therapeutic effects on type 2 diabetes patients with microalbuminuria. In addition, the benefit was positively correlated with the calcium dobesilate treatment time. The therapeutic effect may be due to decreases in the levels of PAI-1. PMID:23251286

Fluorescent imaging of high-grade bladder cancer using a specific antagonist for chemokine receptor CXCR4.

PubMed

Nishizawa, Koji; Nishiyama, Hiroyuki; Oishi, Shinya; Tanahara, Noriko; Kotani, Hirokazu; Mikami, Yoshiki; Toda, Yoshinobu; Evans, Barry J; Peiper, Stephen C; Saito, Ryoichi; Watanabe, Jun; Fujii, Nobutaka; Ogawa, Osamu

2010-09-01

We previously reported that the expression of CXC chemokine receptor-4 (CXCR4) was upregulated in invasive bladder cancers and that the small peptide T140 was a highly sensitive antagonist for CXCR4. In this study, we identified that CXCR4 expression was induced in high-grade superficial bladder tumors, including carcinoma in situ and invasive bladder tumors. To visualize the bladder cancer cells using urinary sediments from the patients and chemically induced mouse bladder cancer model, a novel fluorescent CXCR4 antagonist TY14003 was developed, that is a T140 derivative. TY14003 could label bladder cancer cell lines expressing CXCR4, whereas negative-control fluorescent peptides did not label them. When labeling urinary sediments from patients with invasive bladder cancer, positive-stained cells were identified in all patients with bladder cancer and positive urine cytology but not in controls. Although white blood cells in urine were also labeled with TY14003, they could be easily discriminated from urothelial cells by their shape and size. Finally, intravesical instillation of TY14003 into mouse bladder, using N-butyl-N-(4-hydroxybutyl) nitrosamine (BBN)-induced bladder cancer model, demonstrated that fluorescent signals were detected in the focal areas of bladder of all mice examined at 12 weeks of BBN drinking by confocal microscopy and fluorescent endoscopy. On the contrary, all the normal bladders were found to be negative for TY14003 staining. In conclusion, these results indicate that TY14003 is a promising diagnostic tool to visualize small or flat high-grade superficial bladder cancer.

Urinary matrix metalloproteinase 9 and tissue inhibitor of metalloproteinase 1 biomarkers for predicting renal scar in children with urinary tract infection

PubMed Central

Abedi, Seyed Mohammad; Mohammadjafari, Hamid; Rafiei, Alireza; Bazi, Sara; Yazdani, Pooneh

2017-01-01

Objective Urinary tract infection occurs in 1.8–6.6% of children under 6 years old. The aim of this study was to assess the urinary concentrations of matrix metalloproteinase 9 (MMP9) and tissue inhibitor of metalloproteinase 1 (TIMP1), in children with acute pyelonephritis (APN) and the potential to develop renal scarring. Material and methods Children who had experienced an episode of APN were divided into 2 groups. Group 1 included children with APN who exhibited scarring and group 2 included children with APN who had a normal 99mTechnetium dimercaptosuccinic acid scan. Urinary levels of MMP9 and TIMP1 were measured in the acute phase of infection. A receiver operating characteristic curve was generated to allow calculation of cut-off values. Results Sixty-one children were enrolled across the 2 groups: group 1 contained 16 patients (all female); group 2, 38 children (36 female and 2 male). Urinary levels of MMP9 and TIMP1 were significantly higher in group 1 than in group 2 (p=0.037 and 0.022 respectively). For comparison of groups 1 and 2, the cut-off values were measured as 75.5 ng/mL (sensitivity 62.5%, specificity 71.1%, positive predictive value, PPV, 48%, negative predictive value, NPV, 82%), 16.1 ng/mL (sensitivity 75%, specificity 55.3%, PPV 41%, NPV 84%), and 1310.7 ng/mL (sensitivity 75% specificity 60.5%, PPV 44%, NPV 85%) for MMP9, TIMP1, and MMP9×TIMP1 levels, respectively. Conclusion Evaluation of urinary MMP9 and TIMP1 levels may help to identify children with APN who are at risk of developing renal scarring. PMID:29201521

Urinary matrix metalloproteinase 9 and tissue inhibitor of metalloproteinase 1 biomarkers for predicting renal scar in children with urinary tract infection.

PubMed

Abedi, Seyed Mohammad; Mohammadjafari, Hamid; Rafiei, Alireza; Bazi, Sara; Yazdani, Pooneh

2017-12-01

Urinary tract infection occurs in 1.8-6.6% of children under 6 years old. The aim of this study was to assess the urinary concentrations of matrix metalloproteinase 9 (MMP9) and tissue inhibitor of metalloproteinase 1 (TIMP1), in children with acute pyelonephritis (APN) and the potential to develop renal scarring. Children who had experienced an episode of APN were divided into 2 groups. Group 1 included children with APN who exhibited scarring and group 2 included children with APN who had a normal 99m Technetium dimercaptosuccinic acid scan. Urinary levels of MMP9 and TIMP1 were measured in the acute phase of infection. A receiver operating characteristic curve was generated to allow calculation of cut-off values. Sixty-one children were enrolled across the 2 groups: group 1 contained 16 patients (all female); group 2, 38 children (36 female and 2 male). Urinary levels of MMP9 and TIMP1 were significantly higher in group 1 than in group 2 (p=0.037 and 0.022 respectively). For comparison of groups 1 and 2, the cut-off values were measured as 75.5 ng/mL (sensitivity 62.5%, specificity 71.1%, positive predictive value, PPV, 48%, negative predictive value, NPV, 82%), 16.1 ng/mL (sensitivity 75%, specificity 55.3%, PPV 41%, NPV 84%), and 1310.7 ng/mL (sensitivity 75% specificity 60.5%, PPV 44%, NPV 85%) for MMP9, TIMP1, and MMP9×TIMP1 levels, respectively. Evaluation of urinary MMP9 and TIMP1 levels may help to identify children with APN who are at risk of developing renal scarring.

Temporal variability in urinary levels of drinking water disinfection byproducts dichloroacetic acid and trichloroacetic acid among men

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wang, Yi-Xin; Zeng, Qiang; Wang, Le

Urinary haloacetic acids (HAAs), such as dichloroacetic acid (DCAA) and trichloroacetic acid (TCAA), have been suggested as potential biomarkers of exposure to drinking water disinfection byproducts (DBPs). However, variable exposure to and the short elimination half-lives of these biomarkers can result in considerable variability in urinary measurements, leading to exposure misclassification. Here we examined the variability of DCAA and TCAA levels in the urine among eleven men who provided urine samples on 8 days over 3 months. The urinary concentrations of DCAA and TCAA were measured by gas chromatography coupled with electron capture detection. We calculated the intraclass correlation coefficientsmore » (ICCs) to characterize the within-person and between-person variances and computed the sensitivity and specificity to assess how well single or multiple urine collections accurately determined personal 3-month average DCAA and TCAA levels. The within-person variance was much higher than the between-person variance for all three sample types (spot, first morning, and 24-h urine samples) for DCAA (ICC=0.08–0.37) and TCAA (ICC=0.09–0.23), regardless of the sampling interval. A single-spot urinary sample predicted high (top 33%) 3-month average DCAA and TCAA levels with high specificity (0.79 and 0.78, respectively) but relatively low sensitivity (0.47 and 0.50, respectively). Collecting two or three urine samples from each participant improved the classification. The poor reproducibility of the measured urinary DCAA and TCAA concentrations indicate that a single measurement may not accurately reflect individual long-term exposure. Collection of multiple urine samples from one person is an option for reducing exposure classification errors in studies exploring the effects of DBP exposure on reproductive health. - Highlights: • We evaluated the variability of DCAA and TCAA levels in the urine among men. • Urinary DCAA and TCAA levels varied greatly over a 3-month period. • Single measurement may not accurately reflect personal long-term exposure levels. • Collecting multiple samples from one person improved the exposure classification.« less

Klotho and S100A8/A9 as Discriminative Markers between Pre-Renal and Intrinsic Acute Kidney Injury

PubMed Central

Kim, Ae Jin; Ro, Han; Kim, Hyunsook; Chang, Jae Hyun; Lee, Hyun Hee; Chung, Wookyung; Jung, Ji Yong

2016-01-01

Early detection and accurate differentiation of the cause of AKI may improve the prognosis of the patient. However, to date, there are few reliable biomarkers that can discriminate between pre-renal and intrinsic AKI. In this study, we determined whether AKI is associated with altered serum and urinary levels of Klotho, S100A8/A9 (an endogenous ligand of toll-like receptor 4), and neutrophil gelatinase-associated lipocalin (NGAL), which may allow differentiation between pre-renal and intrinsic AKI. A volume-depleted pre-renal AKI model was induced in male Sprague Dawley rats fed a low-salt diet (0.03%) without water 96 h before two intraperitoneal (IP) injections of furosemide (20 mg/kg) at a 24 h interval. In contrast, in the cisplatin-induced intrinsic AKI model, animals were given a single IP injection of cisplatin (5 mg/kg). All of the animals were euthanized 72 h after the first IP injection. Serum and urinary levels of Klotho, S100A8/A9, and NGAL were measured using an enzyme-linked immunosorbent assay. We also performed a proof-of-concept cross-sectional study to measure serum and urinary biomarkers in 61 hospitalized patients with established AKI. Compared to the intrinsic AKI group, the pre-renal AKI group showed a marked depression in urinary Klotho levels (13.21±17.32 vs. 72.97±17.96 pg/mL; P = 0.002). In addition, the intrinsic AKI group showed marked elevation of S100A8/A9 levels compared to the pre-renal AKI group (2629.97±598.05 ng/mL vs. 685.09±111.65 ng/mL; P = 0.002 in serum; 3361.11±250.86 ng/mL vs. 741.72±101.96 ng/mL; P = 0.003 in urine). There was no difference in serum and urinary NGAL levels between the pre-renal and intrinsic AKI groups. The proof-of-concept study with the hospitalized AKI patients also demonstrated decreased urinary Klotho in pre-renal AKI patients and increased urinary S100A8/A9 concentrations in intrinsic AKI patients. The attenuation of urinary Klotho and increase in urinary S100A8/A9 may allow differentiation between pre-renal and intrinsic AKI. PMID:26799323

Effect of Oestrogen on Altering the Serum and Urinary Levels of Calcium, Phosphate and Magnesium in Hysterectomised Women Compared to Natural Menopausal South Indian Women: A Case Control Study.

PubMed

Sonu, Yeldose; Avinash, S S; Sreekantha; Arun Kumar, K; Malathi, M; Shivashankara, A R

2016-07-01

Given the paucity of studies conducted to know the effect of suddenness and earlier onset of endocrinological changes associated with hysterectomy, on the serum and urinary levels of calcium, magnesium and phosphate the present study was conducted to compare the levels of calcium, magnesium and phosphate in serum and urine of hysterectomised and natural menopausal south Indian women. This is a cross-sectional observational study. The study included three groups of 30 healthy premenopausal, 30 early surgical menopausal and 30 natural post menopausal women. Women suffering from any endocrine disease were excluded. Analysis was performed in serum and urine sample. The levels of calcium, magnesium and phosphate in serum and calcium/creatinine, magnesium/creatinine and phosphate/creatinine ratio were estimated in urine by spectrophotometric method. Hysterectomised women (serum calcium: 8.7 ± 0.09 mg/dl; urine calcium/creatinine: 0.16 ± 0.02) have significantly low serum calcium (p < 0.001) and high urinary calcium/creatinine (p = 0.002) ratio and post menopausal women (serum magnesium: 2.1 ± 0.03; serum phosphate: 4.4 ± 0.16; urinary calcium/creatinine: 0.17 ± 0.02; urinary magnesium/creatinine: 0.09 ± 0.01) have significantly high serum magnesium (p = 0.016), serum phosphate (p = 0.043) and high urinary calcium/creatinine (p = 0.002), magnesium/creatinine ratio (p = 0.025) compared to healthy pre menopausal women. Post menopausal women (serum calcium: 9.1 ± 0.08) have significantly high serum calcium and phosphate compared to hysterectomised women (serum phosphate: 3.93 ± 0.11). Hysterectomised women have significantly low serum calcium, oestrogen and high urinary calcium/creatinine ratio compared to healthy premenopausal women and low serum calcium and low serum phosphate compared to natural postmenopausal women. Natural postmenopausal women had low serum oestrogen and high serum magnesium, serum phosphate, urinary calcium creatinine ratio and urinary magnesium creatinine ratio compared to healthy premenopausal women.

Urinary Amino Acid Alterations in 3-Year-Old Children with Neurodevelopmental Effects due to Perinatal Dioxin Exposure in Vietnam: A Nested Case-Control Study for Neurobiomarker Discovery

PubMed Central

Nishijo, Muneko; Tai, Pham The; Anh, Nguyen Thi Nguyet; Nghi, Tran Ngoc; Nakagawa, Hideaki; Van Luong, Hoang; Anh, Tran Hai; Morikawa, Yuko; Waseda, Tomoo; Kido, Teruhiko; Nishijo, Hisao

2015-01-01

In our previous study of 3-year-old children in a dioxin contamination hot spot in Vietnam, the high total dioxin toxic equivalent (TEQ-PCDDs/Fs)-exposed group during the perinatal period displayed lower Bayley III neurodevelopmental scores, whereas the high 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-exposed group displayed increased autistic traits. In autistic children, urinary amino acid profiles have revealed metabolic alterations in the amino acids that serve as neurotransmitters in the developing brain. Therefore, our present study aimed to investigate the use of alterations in urinary amino acid excretion as biomarkers of dioxin exposure-induced neurodevelopmental deficits in highly exposed 3-year-old children in Vietnam. A nested case-control study of urinary analyses was performed for 26 children who were selected from 111 3-year-old children whose perinatal dioxin exposure levels and neurodevelopmental status were examined in follow-up surveys conducted in a dioxin contaminated hot spot. We compared urinary amino acid levels between the following 4 groups: (1) a high TEQ-PCDDs/Fs and high TCDD-exposed group; (2) a high TEQ-PCDDs/Fs but low TCDD-exposed group; (3) a low TEQ-PCDDs/Fs exposed and poorly developed group; and (4) a low TEQ-PCDDs/Fs exposed and well-developed group. Urinary levels of histidine and tryptophan were significantly decreased in the high TEQ-PCDDs/Fs and high TCDD group, as well as in the high TEQ-PCDDs/Fs but low TCDD group, compared with the low TEQ-PCDDs/Fs and well-developed group. However, the ratio of histidine to glycine was significantly lower only in the high TEQ-PCDDs/Fs and high TCDD group. Furthermore, urinary histidine levels and the ratio of histidine to glycine were significantly correlated with neurodevelopmental scores, particularly for language and fine motor skills. These results indicate that urinary histidine is specifically associated with dioxin exposure-induced neurodevelopmental deficits, suggesting that urinary histidine may be a useful marker of dioxin-induced neurodevelopmental deficits and that histaminergic neurotransmission may be an important pathological contributor to dioxin-mediated neurotoxicity. PMID:25584822

Urinary amino acid alterations in 3-year-old children with neurodevelopmental effects due to perinatal dioxin exposure in Vietnam: a nested case-control study for neurobiomarker discovery.

PubMed

Nishijo, Muneko; Tai, Pham The; Anh, Nguyen Thi Nguyet; Nghi, Tran Ngoc; Nakagawa, Hideaki; Van Luong, Hoang; Anh, Tran Hai; Morikawa, Yuko; Waseda, Tomoo; Kido, Teruhiko; Nishijo, Hisao

2015-01-01

In our previous study of 3-year-old children in a dioxin contamination hot spot in Vietnam, the high total dioxin toxic equivalent (TEQ-PCDDs/Fs)-exposed group during the perinatal period displayed lower Bayley III neurodevelopmental scores, whereas the high 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-exposed group displayed increased autistic traits. In autistic children, urinary amino acid profiles have revealed metabolic alterations in the amino acids that serve as neurotransmitters in the developing brain. Therefore, our present study aimed to investigate the use of alterations in urinary amino acid excretion as biomarkers of dioxin exposure-induced neurodevelopmental deficits in highly exposed 3-year-old children in Vietnam. A nested case-control study of urinary analyses was performed for 26 children who were selected from 111 3-year-old children whose perinatal dioxin exposure levels and neurodevelopmental status were examined in follow-up surveys conducted in a dioxin contaminated hot spot. We compared urinary amino acid levels between the following 4 groups: (1) a high TEQ-PCDDs/Fs and high TCDD-exposed group; (2) a high TEQ-PCDDs/Fs but low TCDD-exposed group; (3) a low TEQ-PCDDs/Fs exposed and poorly developed group; and (4) a low TEQ-PCDDs/Fs exposed and well-developed group. Urinary levels of histidine and tryptophan were significantly decreased in the high TEQ-PCDDs/Fs and high TCDD group, as well as in the high TEQ-PCDDs/Fs but low TCDD group, compared with the low TEQ-PCDDs/Fs and well-developed group. However, the ratio of histidine to glycine was significantly lower only in the high TEQ-PCDDs/Fs and high TCDD group. Furthermore, urinary histidine levels and the ratio of histidine to glycine were significantly correlated with neurodevelopmental scores, particularly for language and fine motor skills. These results indicate that urinary histidine is specifically associated with dioxin exposure-induced neurodevelopmental deficits, suggesting that urinary histidine may be a useful marker of dioxin-induced neurodevelopmental deficits and that histaminergic neurotransmission may be an important pathological contributor to dioxin-mediated neurotoxicity.

Urinary chromium concentrations in humans following ingestion of safe doses of hexavalent and trivalent chromium: Implications for biomonitoring

DOE Office of Scientific and Technical Information (OSTI.GOV)

Finley, B.L.; Scott, P.K.; Norton, R.L.

1996-08-09

This study evaluates the significance of increased urinary chromium concentrations as a marker of chromium exposure and potential health risk. Six human volunteers ingested trivalent chromium [Cr(III)] and hexavalent chromium [Cr(VI)] at doses that are known to be safe but higher than typical levels. The following dosing regimen was used: d 1-7, 200 {mu}g/d chromium picolinate; d 8-10, Cr(VI) ingestion at the U.S. Environmental Protection Agency (EPA) reference dose (RfD) of 0.005 mg/kg/d; d 11-13, no dose; d 14-16, Cr(III) ingestion at the U.S. EPA RfD of 1.0 mg/kg/d; and 17-18, postdose. Findings are as follows: (1) ingestion of 200more » {mu}g/d of chromium picolinate yielded significantly elevated urine concentrations such that each participant routinely exceeded background, (2) ingestion of the Cr(VI) RfD (0.005 mg/kg/d) yielded individual mean urinary chromium levels (1.2-2.3 {mu}g/L) and a pooled mean urinary chromium level (2.4 {mu}g/L) that significantly exceeded background, and (3) ingestion of the Cr(III) RfD yielded no significantly exceeded background, and (3) ingestion of the Cr(III) RfD yielded no significant increase in urinary chromium concentrations, indicating that little, if any, absorption occurred. Our work identified three critical issues that need to be accounted for in any future studies that will use urinary chromium as a marker of exposure. First, a minimum urinary chromium concentration of approximately 2 {mu}g/L should be used as a screening level to critically identify individuals who may have experienced elevated exposures to chromium. Second, if Cr(III) levels in soils are known to be less than 80,000 ppm and the Cr(III) is insoluble, urinary chromium concentrations are not an appropriate marker of exposure. Third, newer forms of chromium supplements that contain organic forms of Cr(III) must be considered potential confounders and their contribution to residential chromium uptake must be carefully evaluated. 19 refs., 7 figs., 3 tabs.« less

Food sharing is linked to urinary oxytocin levels and bonding in related and unrelated wild chimpanzees

PubMed Central

Wittig, Roman M.; Crockford, Catherine; Deschner, Tobias; Langergraber, Kevin E.; Ziegler, Toni E.; Zuberbühler, Klaus

2014-01-01

Humans excel in cooperative exchanges between unrelated individuals. Although this trait is fundamental to the success of our species, its evolution and mechanisms are poorly understood. Other social mammals also build long-term cooperative relationships between non-kin, and recent evidence shows that oxytocin, a hormone involved in parent–offspring bonding, is likely to facilitate non-kin as well as kin bonds. In a population of wild chimpanzees, we measured urinary oxytocin levels following a rare cooperative event—food sharing. Subjects showed higher urinary oxytocin levels after single food-sharing events compared with other types of social feeding, irrespective of previous social bond levels. Also, urinary oxytocin levels following food sharing were higher than following grooming, another cooperative behaviour. Therefore, food sharing in chimpanzees may play a key role in social bonding under the influence of oxytocin. We propose that food-sharing events co-opt neurobiological mechanisms evolved to support mother–infant bonding during lactation bouts, and may act as facilitators of bonding and cooperation between unrelated individuals via the oxytocinergic system across social mammals. PMID:24430853

Synthesis and characterization of an 111In-labeled peptide for the in vivo localization of human cancers expressing the urokinase-type plasminogen activator receptor (uPAR)

PubMed Central

Liu, Dijie; Overbey, Douglas; Watkinson, Lisa; Giblin, Michael F.

2009-01-01

This study describes the synthesis and preliminary biologic evaluation of an 111Inlabeled peptide antagonist of the urokinase-type plasminogen activator receptor (uPAR) as a potential probe for assessing metastatic potential of human breast cancer in vivo. The peptide (NAc-dD-CHA-F-dS-dR-Y-L-W-S-βAla)2-K-K(DOTA)-NH2 was synthesized and conjugated with the DOTA chelating moiety via conventional Solid-Phase Peptide Synthesis (SPPS), purified by reversed-phase HPLC, and characterized by MALDI-TOF MS and receptor binding assay. In vitro receptor binding studies demonstrated an IC50 of 240 ± 125 nM for the peptide, compared with IC50’s of 0.44 ± 0.02 and 0.75 ± 0.01 nM for the amino terminal fragment (ATF) of the urokinase-type plasminogen activator (uPA) and full-length uPA, respectively. In vivo biodistribution studies were carried out using SCID mice bearing MDA-MB-231 human breast cancer xenografts. Biodistribution data was collected at 1, 4, and 24 hr post-injection of 111In-DOTA-peptide, and compared with data obtained using a scrambled control peptide, as well as with data obtained using wild-type ATF radiolabeled with I-125. Biodistribution studies showed rapid elimination of the 111In-labeled peptide from the blood pool, with 0.12 ± 0.06% ID/g remaining in blood at 4 hr pi. Elimination was seen primarily via the renal/urinary route, with 83.9 ± 2.2%ID in the urine at the same timepoint. Tumor uptake at this time was 0.53 ± 0.11%ID/g, resulting in tumor: blood and tumor: muscle ratios of 4.2 and 9.4, respectively. Uptake in tumor was significantly higher than that obtained using a scrambled control peptide that showed no specific binding to uPAR (p < 0.05). In vitro and ex vivo results both suggested that the magnitude of tumor-specific binding was reduced in this model by endogenous expression of uPA. The results indicate that radiolabeled peptide uPAR antagonists may find application in the imaging and therapy of uPAR-expressing breast cancers in vivo. PMID:19354275

Investigation on the frailty status of the elderly inpatients in Shanghai using the FRAIL (fatigue, resistance, ambulation, illness, and loss) questionnaire.

PubMed

Wei, Yin; Cao, Yanpei; Yang, Xiaoli; Xu, Yan

2018-05-01

This study was to investigate the frailty status of inpatients older than 65 years old in Shanghai.A 6-month cross-sectional survey was conducted using FRAIL (fatigue, resistance, ambulation, illness, and loss) questionnaire. Totally 587 patients were included. The data, including demographic characteristics, constipation, urinary retention, urinary incontinence, grip strength, and muscle strength, were collected. The data of serum prealbumin, serum albumin, serum total protein, and hemoglobin were obtained from laboratory blood tests.The incidence of nonfrailty, prefrailty, and frailty was 0.249, 0.417, and 0.334, respectively. The high incidence age of frailty was 86 to 90 years old (0.342), and the high incidence age of prefrailty was 65 to 70 years old (0.282). There was significant difference in the grip strength among different degrees of frailty (P < .01). The influencing factors related to prefrailty included prealbumin, grip strength, urinary retention, constipation and education level of illiterate (P < .05). The populations with high prealbumin level, high grip strength and illiteracy population were not easy to enter the prefrailty period, while those with constipation (OR (odds ratio) = 1.867, 95% CI (confidence interval): 1.046-3.330) and urinary retention (OR = 7.007, 95% CI: 1.137-2.757) were more likely to enter the prefrailty period. Factors associated with frailty included age, prealbumin, grip strength, muscle strength, urinary incontinence, urinary retention, and constipation (P < .05). The populations with high prealbumin level, high grip strength, and high muscle strength were not easy to enter frailty period, while those with older age (OR = 1.141, 95% CI: 1.085-1.200), urinary incontinence (OR = 10.314, 95% CI: 1.950-54.548), urinary retention (OR = 3.058, 95% CI: 1.571-5.952), and constipation (OR = 3.004, 95% CI: 1.540-5.857) were easy to enter frailty period.The high incidence ages of frailty and prefrailty are 86 to 90 years old and 65 to 70 years old, respectively. Age, low education level, low grip strength, low muscle strength, low serum prealbumin, urinary retention, urinary incontinence, and constipation are the risk factors of frailty. It is recommended to include frailty as an indicator in the existing assessment to rate the disease and develop a disease observation plan.

Relationship among bacterial virulence, bladder dysfunction, vesicoureteral reflux and patterns of urinary tract infection in children.

PubMed

Storm, Douglas W; Patel, Ashay S; Horvath, Dennis J; Li, Birong; Koff, Stephen A; Justice, Sheryl S

2012-07-01

We hypothesized that virulence levels of Escherichia coli isolates causing pediatric urinary tract infections differ according to severity of infection and also among various uropathies known to contribute to pediatric urinary tract infections. We evaluated these relationships using in vitro cytokine interleukin-6 elicitation. E. coli isolates were cultured from children presenting with urinary tract infections. In vitro cytokine (interleukin-6) elicitation was quantified for each isolate and the bacteria were grouped according to type of infection and underlying uropathy (neurogenic bladder, nonneurogenic bowel and bladder dysfunction, primary vesicoureteral reflux, no underlying etiology). A total of 40 E. coli isolates were collected from children with a mean age of 61.5 months (range 1 to 204). Mean level of in vitro cytokine elicitation from febrile urinary tract infection producing E. coli was significantly lower than for nonfebrile strains (p = 0.01). The interleukin-6 response to E. coli in the neurogenic bladder group was also significantly higher than in the vesicoureteral reflux (p = 0.01) and no underlying etiology groups (p = 0.02). In vitro interleukin-6 elicitation, an established marker to determine bacterial virulence, correlates inversely with clinical urinary tract infection severity. Less virulent, high cytokine producing E. coli were more likely to cause cystitis and were more commonly found in patients with neurogenic bladder and nonneurogenic bowel and bladder dysfunction, whereas higher virulence isolates were more likely to produce febrile urinary tract infections and to affect children with primary vesicoureteral reflux and no underlying etiology. These findings suggest that bacteria of different virulence levels may be responsible for differences in severity of pediatric urinary tract infections and may vary among different underlying uropathies. Copyright © 2012 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Suppression of the PI3K pathway in vivo reduces cystitis-induced bladder hypertrophy and restores bladder capacity examined by magnetic resonance imaging.

PubMed

Qiao, Zhongwei; Xia, Chunmei; Shen, Shanwei; Corwin, Frank D; Liu, Miao; Guan, Ruijuan; Grider, John R; Qiao, Li-Ya

2014-01-01

This study utilized magnetic resonance imaging (MRI) to monitor the real-time status of the urinary bladder in normal and diseased states following cyclophosphamide (CYP)-induced cystitis, and also examined the role of the phosphoinositide 3-kinase (PI3K) pathway in the regulation of urinary bladder hypertrophy in vivo. Our results showed that under MRI visualization the urinary bladder wall was significantly thickened at 8 h and 48 h post CYP injection. The intravesical volume of the urinary bladder was also markedly reduced. Treatment of the cystitis animals with a specific PI3K inhibitor LY294002 reduced cystitis-induced bladder wall thickening and enlarged the intravesical volumes. To confirm the MRI results, we performed H&E stain postmortem and examined the levels of type I collagen by real-time PCR and western blot. Inhibition of the PI3K in vivo reduced the levels of type I collagen mRNA and protein in the urinary bladder ultimately attenuating cystitis-induced bladder hypertrophy. The bladder mass calculated according to MRI data was consistent to the bladder weight measured ex vivo under each drug treatment. MRI results also showed that the urinary bladder from animals with cystitis demonstrated high magnetic signal intensity indicating considerable inflammation of the urinary bladder when compared to normal animals. This was confirmed by examination of the pro-inflammatory factors showing that interleukin (IL)-1α, IL-6 and tumor necrosis factor (TNF)α levels in the urinary bladder were increased with cystitis. Our results suggest that MRI can be a useful technique in tracing bladder anatomy and examining bladder hypertrophy in vivo during disease development and the PI3K pathway has a critical role in regulating bladder hypertrophy during cystitis.

A case of sleep apnea syndrome manifesting severe hypertension with high plasma norepinephrine levels.

PubMed

Makino, Shinya; Iwata, Masanobu; Fujiwara, Masayoshi; Ike, Shinpei; Tateyama, Hitone

2006-06-01

A 55-year-old female was admitted to our hospital with severe hypertension (274/140 mmHg). Endocrinological examination revealed that her plasma levels of norepinephrine (NE) was elevated with high levels of urinary NE, normetanephrine and vanillylmandelic acid (VMA), suggesting the presence of pheochromocytoma. However, neither computed tomography nor MIBG scintigraphy detected any catecholamine-producing tumor in or outside the adrenal glands. She was screened with full polysomnography because of heavy snoring, and the diagnosis of severe obstructive sleep apnea syndrome (OSAS) was made. She was treated with calcium channel blocker for three weeks, but severe hypertension persisted. After treatment with nasal continuous positive airway pressure (CPAP) was added, her blood pressure gradually lowered week by week. Concomitantly, the levels of plasma and urinary NE, urinary normetanephrine and urinary VMA were normalized following nasal CPAP therapy for 2 weeks. Additional treatments with alpha-adrenergic blocker further decreased her home blood pressure. After a year, she continued nasal CPAP therapy and her blood pressure was nearly below 160/100 mmHg. Urinary NE level was slightly above normal range and other catecholamines stayed within the normal range. This case shows that patients with OSAS could develop severe hypertension through elevated sympathetic tone, mimicking pheochromocytoma. Nasal CPAP therapy is recommended not only to improve hypertension and catecholamine excess but also to distinguish the condition from pheochromocytoma.

Preparation and evaluation of the tumor-specific antigen-derived synthetic mucin 1 peptide: A potential candidate for the targeting of breast carcinoma.

PubMed

Okarvi, Subhani M; Al Jammaz, Ibrahim

2016-07-01

The goal of this study was to prepare a synthetic peptide derived from breast tumor associated antigen and to evaluate its potential as a breast cancer imaging agent. A mucin 1 derived peptide was synthesized by solid-phase peptide synthesis and examined for its radiochemical and metabolic stability. The tumor cell binding affinity of (99m)Tc-MUC1 peptide was investigated on MUC1-positive T47D and MCF7 breast cancer cell lines. In vivo biodistribution was studied in normal Balb/c mice and in vivo tumor targeting and imaging in MCF7 and T47D tumor-bearing nude mice. The synthesized MUC1-derived peptide displayed high radiochemical and metabolic stability. In vitro tumor cell-binding on T47D and MCF7 cell lines demonstrated high affinity of (99m)Tc-MUC1 peptide towards human breast cancer cells (binding affinities in nanomolar range). Pharmacokinetic studies performed on Balb/c mice are characterized by an efficient clearance from the blood and excretion predominantly through the urinary system. In vivo tumor uptake in nude mice with MCF7 tumor xenografts was 2.77±0.63% ID/g as early as 1h p.i. whereas in nude mice with T47D human ductal breast epithelial cancer cells, the accumulation in the tumor was found to be 2.65±0.54% ID/g at 1h p.i. Also tumor lesion was detectable in γ-camera imaging. The tumor uptake values were always higher than the blood and muscle uptake, with good tumor retention and good tumor-to-blood and tumor-to-muscle ratios. A low to moderate (<5% ID/g) accumulation and retention of (99m)Tc-MUC1 was found in the major organs (i.e., lungs, stomach, liver, intestines, kidneys, etc.) in both normal and tumor-bearing mice. This study suggests that (99m)Tc-MUC1 tumor-antigen peptide may be a potential candidate for the targeted imaging of MUC1-positive human tumors and warrants further investigation. Copyright © 2016 Elsevier Inc. All rights reserved.

A case of hyperammonemia with obstructive urinary tract infection by urease-producing bacteria.

PubMed

Goda, Toshiaki; Watanabe, Kotaro; Kobayashi, Junya; Nagai, Yasuharu; Ohara, Nobuyuki; Takahashi, Daisuke

2017-03-28

A 79-year-old woman was admitted emergently for disturbance of consciousness. Her consciousness level was Japan coma scale 20, and she presented with hypermyotonia. Brain magnetic resonance imaging and cerebrospinal fluid examination showed normal findings. Her blood tests showed an increased ammonia level of 291 μg/dl with normal liver function. We catheterized the bladder for urinary retention. Eight hours after admission, the blood level of ammonia decreased to 57 μg/dl and the patient's consciousness level improved. Corynebacterium pseudodiphtheriticum, which is a bacteria producing urease, was detected from a urine culture. It is important to recognize that obstructive urinary tract infection caused by urease-producing bacteria can cause hyperammonemia.

Relationship between urinary bisphenol A levels and prediabetes among subjects free of diabetes.

PubMed

Sabanayagam, Charumathi; Teppala, Srinivas; Shankar, Anoop

2013-08-01

Bisphenol A (BPA) is a high volume production chemical used in the manufacture of polycarbonate plastics and epoxy resins. Recent experimental studies have suggested that BPA affects glucose metabolism through diverse mechanisms including insulin resistance, pancreatic β-cell dysfunction, adipogenesis, inflammation and oxidative stress. Prediabetes is a stage earlier in the hyperglycemia continuum associated with increased future risk of developing diabetes. Therefore, we examined the association between BPA exposure and prediabetes among subjects free of diabetes. We examined the association between urinary BPA levels and prediabetes in 3,516 subjects from the National Health and Nutritional Examination Survey 2003-2008. Urinary BPA levels were examined in tertiles. Prediabetes was defined as fasting glucose concentration 100-125 mg/dL or 2-h glucose concentration of 140-199 mg/dL or an A1C value of 5.7-6.4 %. Overall, we observed a positive association between higher levels of urinary BPA and prediabetes, independent of potential confounders including body mass index, alcohol intake, blood pressure and serum cholesterol levels. Compared to tertile 1 (referent), the multivariate-adjusted odds ratio (95 % confidence interval) of prediabetes associated with tertile 3 of BPA was 1.34 (1.03-1.73), p-trend = 0.02. In subgroup analysis, this association was stronger among women and obese subjects. Higher urinary BPA levels are found to be associated with prediabetes independent of traditional diabetes risk factors. Future prospective studies are needed to confirm or disprove this finding.

iAMP-2L: a two-level multi-label classifier for identifying antimicrobial peptides and their functional types.

PubMed

Xiao, Xuan; Wang, Pu; Lin, Wei-Zhong; Jia, Jian-Hua; Chou, Kuo-Chen

2013-05-15

Antimicrobial peptides (AMPs), also called host defense peptides, are an evolutionarily conserved component of the innate immune response and are found among all classes of life. According to their special functions, AMPs are generally classified into ten categories: Antibacterial Peptides, Anticancer/tumor Peptides, Antifungal Peptides, Anti-HIV Peptides, Antiviral Peptides, Antiparasital Peptides, Anti-protist Peptides, AMPs with Chemotactic Activity, Insecticidal Peptides, and Spermicidal Peptides. Given a query peptide, how can we identify whether it is an AMP or non-AMP? If it is, can we identify which functional type or types it belong to? Particularly, how can we deal with the multi-type problem since an AMP may belong to two or more functional types? To address these problems, which are obviously very important to both basic research and drug development, a multi-label classifier was developed based on the pseudo amino acid composition (PseAAC) and fuzzy K-nearest neighbor (FKNN) algorithm, where the components of PseAAC were featured by incorporating five physicochemical properties. The novel classifier is called iAMP-2L, where "2L" means that it is a 2-level predictor. The 1st-level is to answer the 1st question above, while the 2nd-level is to answer the 2nd and 3rd questions that are beyond the reach of any existing methods in this area. For the conveniences of users, a user-friendly web-server for iAMP-2L was established at http://www.jci-bioinfo.cn/iAMP-2L. Copyright © 2013 Elsevier Inc. All rights reserved.

Urinary catecholamines, plasma insulin and environmental factors in relation to body fat distribution.

PubMed

Leonetti, D L; Bergstrom, R W; Shuman, W P; Wahl, P W; Jenner, D A; Harrison, G A; Fujimoto, W Y

1991-05-01

The relationship of body fat distribution to insulin and the catecholamines, hormones that affect lipolysis differentially by fat site, was examined within an environmental context, including factors of medication use, physical activity, dietary intake, educational attainment, and age. Four cross-sectional body fat areas (cm2) were determined by three computed tomography (CT) scans (subcutaneous chest fat at the level of the nipples, subcutaneous and intra-abdominal fat at the level of the umbilicus, and subcutaneous left mid-thigh fat) in 191 second-generation Japanese-American men aged 45-74 years. The site-specific fat measurements were first examined in relation to use of beta-adrenergic antagonists, then to fasting plasma insulin and C-peptide levels and to urinary epinephrine and norepinephrine levels from a 24-h urine collection made during usual daily activities. Greater fat stores in the intra-abdominal area, even after adjustment for body mass index (BMI, weight/height2) and presence of coronary heart disease, were found to be related to use of beta-adrenergic antagonists. In men taking no adrenergic antagonists (n = 157), after adjustment for BMI, truncal fat measurements of the chest (partial r = -0.16, P less than 0.05) and intra-abdominal area (partial r = -0.21, P less than 0.05) were found to be inversely related to epinephrine, and intra-abdominal fat (partial r = 0.25, P less than 0.01) alone was directly related to fasting plasma insulin. With respect to other environmental variables, the significant inverse relationship of intra-abdominal fat (adjusted for BMI) with physical activity (partial r = -0.17, P less than 0.05) and the significant difference in intra-abdominal fat by educational attainment (college 102.3 +/- 5.7 vs no college 115.7 +/- 6.1 cm2, P = 0.03) became non-significant with adjustment, using multiple regression analysis, for insulin in the case of physical activity and epinephrine in the case of educational attainment. Thus, intra-abdominal fat showed a unique set of relationships to metabolic parameters which could be further related to certain environmental variables.

Strong positive associations between seafood, vegetables, and alcohol with blood mercury and urinary arsenic levels in the Korean adult population.

PubMed

Park, Sunmin; Lee, Byung-Kook

2013-01-01

Blood mercury and urinary arsenic levels are more than fivefold greater in the Korean population compared with those of the United States. This may be related to the foods people consumed. Therefore, we examined the associations between food categories and mercury and arsenic exposure in the Korean adult population. Data regarding nutritional, biochemical, and health-related parameters were obtained from a cross-sectional study, the 2008-2009 Korean National Health and Nutrition Examination Survey (3,404 men and women age ≥ 20 years). The log-transformed blood mercury and urinary arsenic levels were regressed against the frequency tertiles of each food group after covariate adjustment for sex, age, residence area, education level, smoking status, and drinking status using food-frequency data. Blood mercury levels in the high consumption groups compared to the low consumption groups were elevated by about 20 percents with salted fish, shellfish, whitefish, bluefish, and alcohol, and by about 9-14 percents with seaweeds, green vegetables, fruits and tea, whereas rice did not affect blood mercury levels. Urinary arsenic levels were markedly increased with consumption of rice, bluefish, salted fish, shellfish, whitefish, and seaweed, whereas they were moderately increased with consumption of grains, green and white vegetables, fruits, coffee, and alcohol. The remaining food categories tended to lower these levels only minimally. In conclusion, the typical Asian diet, which is high in rice, salted fish, shellfish, vegetables, alcoholic beverages, and tea, may be associated with greater blood mercury and urinary arsenic levels. This study suggests that mercury and arsenic contents should be monitored and controlled in soil and water used for agriculture to decrease health risks from heavy-metal contamination.

Effects of Oral Contraceptives on Natriuretic Peptide Levels in Women with Hypothalamic Amenorrhea: A Pilot Study

PubMed Central

Lin, Eleanor; Grinspoon, Steven; Wang, Thomas; Miller, Karen K.

2011-01-01

Natriuretic peptides, which are important regulators of salt handling and blood pressure, are 60 – 75% higher in healthy young women than in men, consistent with a gender dimorphism. In this randomized, placebo-controlled study in women with functional hypothalamic amenorrhea, we show that administration of oral contraceptives increases natriuretic peptide levels and that end-of-study free testosterone levels are inversely associated with NT-proBNP levels, consistent with the hypothesis that natriuretic peptide levels may be mediated by differences in gonadal steroid concentrations – estrogens or androgens. PMID:21620395

Urinary cadmium in the 1999–2008 U.S. National Health and Nutrition Examination Survey (NHANES)

EPA Science Inventory

Chronic low-level cadmium (Cd) exposure is linked to kidney and cardiovascular disease, fractures, and cancer. Diet and smoking are primary sources of exposure in the general population. We analyzed urinary Cd in NHANES 1999-2008 to determine whether levels declined significantly...

Association between Perchlorate and indirect indicators of thyroid dysfunction in NHANES 2001-2002, a Cross-Sectional, Hypothesis-Generating Study

EPA Science Inventory

Background: A previous study observed associations of urinary perchlorate with thyroid hormones based on the National Health and Nutrition Examination Survey (NHANES) 2001-2002. Increased levels of urinary perchlorate were associated with increased levels of thyroid stimulating h...

Increased levels of urinary biomarkers of lipid peroxidation products among workers occupationally exposed to diesel engine exhaust.

PubMed

Bin, Ping; Shen, Meili; Li, Haibin; Sun, Xin; Niu, Yong; Meng, Tao; Yu, Tao; Zhang, Xiao; Dai, Yufei; Gao, Weimin; Gu, Guizhen; Yu, Shanfa; Zheng, Yuxin

2016-08-01

Diesel engine exhaust (DEE) was found to induce lipid peroxidation (LPO) in animal exposure studies. LPO is a class of oxidative stress and can be reflected by detecting the levels of its production, such as malondialdehyde (MDA) and 4-hydroxynonenal (4-HNE), and etheno-DNA adducts including 1,N(6)-etheno-2'-deoxyadenosine (ɛdA) and 3,N(4)-etheno-2'-deoxycytidine (ɛdC). However, the impact of DEE exposure on LPO has not been explored in humans. In this study, we evaluated urinary MDA, 4-HNE, ɛdA, and ɛdC levels as biomarkers of LPO among 108 workers with exclusive exposure to DEE and 109 non-DEE-exposed workers. Results showed that increased levels of urinary MDA and ɛdA were observed in subjects occupationally exposed to DEE before and after age, body mass index (BMI), smoking status, and alcohol use were adjusted (all p < 0.001). There was a statistically significant relationship between the internal exposure dose (urinary ΣOH-PAHs) and MDA, 4-HNE, and ɛdA (all p < 0.001). Furthermore, significant increased relations between urinary etheno-DNA adduct and MDA, 4-HNE were observed (all p < 0.05). The findings of this study suggested that the level of LPO products (MDA and ɛdA) was increased in DEE-exposed workers, and urinary MDA and ɛdA might be feasible biomarkers for DEE exposure. LPO induced DNA damage might be involved and further motivated the genomic instability could be one of the pathogeneses of cancer induced by DEE-exposure. However, additional investigations should be performed to understand these observations.

Accumulation of human T lymphotropic virus (HTLV)-I-specific T cell clones in HTLV-I-associated myelopathy/tropical spastic paraparesis patients.

PubMed

Höger, T A; Jacobson, S; Kawanishi, T; Kato, T; Nishioka, K; Yamamoto, K

1997-08-15

Human T lymphotropic virus type I (HTLV-I)-associated myelopathy/tropical spastic paraperesis (HAM/TSP) is a slowly progressive neurologic disorder following infection with HTLV-I. It is characterized by spasticity and hyper-reflexia of the lower extremities, urinary bladder disturbance, lower extremity muscle weakness, and sensory disturbances. HTLV-I, as an inducer of a strong humoral and cytotoxic response, is a well-known pathogenic factor for the progression of HAM/TSP. Peptides derived from proviral tax and env genes provide epitopes recognized by T cells. We herein report an accumulation of distinct clonotypes of alpha/beta TCR+ peripheral blood T lymphocytes from HAM/TSP patients in comparison with that observed in both asymptomatic carriers and healthy controls, using the reverse-transcriptase PCR/single-strand conformation polymorphism method. We also found that some of the accumulated T cell clones in the peripheral blood and cerebrospinal fluid are HTLV-I Tax(11-19) peptide specific. Such clones were found to expand strongly after being cultured with an HTLV-I Tax(11-19) peptide. Moreover, the cultured samples exhibited a strong MHC class I-restricted cytotoxic activity against HTLV-I Tax(11-19) peptide-expressing targets, and therefore most likely also include the disease-associated T cell clones observed in the patients. This is the first report of a direct assessment of Ag-specific T cell responses in fresh PBL and cerebrospinal fluid.

Binational arsenic exposure survey: methodology and estimated arsenic intake from drinking water and urinary arsenic concentrations.

PubMed

Roberge, Jason; O'Rourke, Mary Kay; Meza-Montenegro, Maria Mercedes; Gutiérrez-Millán, Luis Enrique; Burgess, Jefferey L; Harris, Robin B

2012-04-01

The Binational Arsenic Exposure Survey (BAsES) was designed to evaluate probable arsenic exposures in selected areas of southern Arizona and northern Mexico, two regions with known elevated levels of arsenic in groundwater reserves. This paper describes the methodology of BAsES and the relationship between estimated arsenic intake from beverages and arsenic output in urine. Households from eight communities were selected for their varying groundwater arsenic concentrations in Arizona, USA and Sonora, Mexico. Adults responded to questionnaires and provided dietary information. A first morning urine void and water from all household drinking sources were collected. Associations between urinary arsenic concentration (total, organic, inorganic) and estimated level of arsenic consumed from water and other beverages were evaluated through crude associations and by random effects models. Median estimated total arsenic intake from beverages among participants from Arizona communities ranged from 1.7 to 14.1 µg/day compared to 0.6 to 3.4 µg/day among those from Mexico communities. In contrast, median urinary inorganic arsenic concentrations were greatest among participants from Hermosillo, Mexico (6.2 µg/L) whereas a high of 2.0 µg/L was found among participants from Ajo, Arizona. Estimated arsenic intake from drinking water was associated with urinary total arsenic concentration (p < 0.001), urinary inorganic arsenic concentration (p < 0.001), and urinary sum of species (p < 0.001). Urinary arsenic concentrations increased between 7% and 12% for each one percent increase in arsenic consumed from drinking water. Variability in arsenic intake from beverages and urinary arsenic output yielded counter intuitive results. Estimated intake of arsenic from all beverages was greatest among Arizonans yet participants in Mexico had higher urinary total and inorganic arsenic concentrations. Other contributors to urinary arsenic concentrations should be evaluated.

Binational Arsenic Exposure Survey: Methodology and Estimated Arsenic Intake from Drinking Water and Urinary Arsenic Concentrations

PubMed Central

Roberge, Jason; O’Rourke, Mary Kay; Meza-Montenegro, Maria Mercedes; Gutiérrez-Millán, Luis Enrique; Burgess, Jefferey L.; Harris, Robin B.

2012-01-01

The Binational Arsenic Exposure Survey (BAsES) was designed to evaluate probable arsenic exposures in selected areas of southern Arizona and northern Mexico, two regions with known elevated levels of arsenic in groundwater reserves. This paper describes the methodology of BAsES and the relationship between estimated arsenic intake from beverages and arsenic output in urine. Households from eight communities were selected for their varying groundwater arsenic concentrations in Arizona, USA and Sonora, Mexico. Adults responded to questionnaires and provided dietary information. A first morning urine void and water from all household drinking sources were collected. Associations between urinary arsenic concentration (total, organic, inorganic) and estimated level of arsenic consumed from water and other beverages were evaluated through crude associations and by random effects models. Median estimated total arsenic intake from beverages among participants from Arizona communities ranged from 1.7 to 14.1 µg/day compared to 0.6 to 3.4 µg/day among those from Mexico communities. In contrast, median urinary inorganic arsenic concentrations were greatest among participants from Hermosillo, Mexico (6.2 µg/L) whereas a high of 2.0 µg/L was found among participants from Ajo, Arizona. Estimated arsenic intake from drinking water was associated with urinary total arsenic concentration (p < 0.001), urinary inorganic arsenic concentration (p < 0.001), and urinary sum of species (p < 0.001). Urinary arsenic concentrations increased between 7% and 12% for each one percent increase in arsenic consumed from drinking water. Variability in arsenic intake from beverages and urinary arsenic output yielded counter intuitive results. Estimated intake of arsenic from all beverages was greatest among Arizonans yet participants in Mexico had higher urinary total and inorganic arsenic concentrations. Other contributors to urinary arsenic concentrations should be evaluated. PMID:22690182

Epigenetic Mechanisms Regulate Innate Immunity against Uropathogenic and Commensal-Like Escherichia coli in the Surrogate Insect Model Galleria mellonella.

PubMed

Heitmueller, Miriam; Billion, André; Dobrindt, Ulrich; Vilcinskas, Andreas; Mukherjee, Krishnendu

2017-10-01

Innate-immunity-related genes in humans are activated during urinary tract infections (UTIs) caused by pathogenic strains of Escherichia coli but are suppressed by commensals. Epigenetic mechanisms play a pivotal role in the regulation of gene expression in response to environmental stimuli. To determine whether epigenetic mechanisms can explain the different behaviors of pathogenic and commensal bacteria, we infected larvae of the greater wax moth, Galleria mellonella , a widely used model insect host, with a uropathogenic E. coli (UPEC) strain that causes symptomatic UTIs in humans or a commensal-like strain that causes asymptomatic bacteriuria (ABU). Infection with the UPEC strain (CFT073) was more lethal to larvae than infection with the attenuated ABU strain (83972) due to the recognition of each strain by different Toll-like receptors, ultimately leading to differential DNA/RNA methylation and histone acetylation. We used next-generation sequencing and reverse transcription (RT)-PCR to correlate epigenetic changes with the induction of innate-immunity-related genes. Transcriptomic analysis of G. mellonella larvae infected with E. coli strains CFT073 and 83972 revealed strain-specific variations in the class and expression levels of genes encoding antimicrobial peptides, cytokines, and enzymes controlling DNA methylation and histone acetylation. Our results provide evidence for the differential epigenetic regulation of transcriptional reprogramming by UPEC and ABU strains of E. coli in G. mellonella larvae, which may be relevant to understanding the different behaviors of these bacterial strains in the human urinary tract. Copyright © 2017 American Society for Microbiology.

Control of sodium excretion in patients with cranial diabetes insipidus maintained on desamino-[8-D-arginine]vasopressin.

PubMed

Sutters, M; Brace, C; Hatfield, E; Whitehurst, A; Lightman, S L; Peart, W S

1993-11-01

1. We have studied the response of six patients with cranial diabetes insipidus and six age-matched control subjects to dietary sodium restriction during constant administration of the synthetic vasopressin analogue desamino-[8-D-arginine]vasopressin. 2. Urine flow increased on the first low salt day in the normal control subjects but not in the patients with cranial diabetes insipidus. Body weight fell 1.35 kg in the control subjects but was constant in the patients with cranial diabetes insipidus. 3. Urinary sodium excretion fell at the same rate in both groups. Diurnal variation of urinary sodium excretion and creatinine clearance was present in the control subjects but not in the patients with cranial diabetes insipidus. 4. Changes in plasma sodium concentration and osmolality were similar. Plasma protein concentration increased more in the control subjects (from 69.1 +/- 1.5 to 73 +/- 1.2 versus from 71.7 +/- 1 to 73.2 +/- 1.1 milligrams). The responses of plasma atrial natriuretic peptide, plasma renin activity and salivary aldosterone concentration were similar between the two groups. Salivary aldosterone concentration levels were consistently higher in the patients with cranial diabetes insipidus. 5. We confirm that the low salt diuresis is triggered by release from the antidiuretic activity of arginine vasopressin. In the patients with cranial diabetes insipidus extracellular fluid osmoregulation appeared to be achieved by the movement of water out of and sodium into the extracellular fluid. 6. Absent posterior pituitary function and hypothalamic disturbances did not alter renal sodium conservation.(ABSTRACT TRUNCATED AT 250 WORDS)

Hyperammonemia associated with distal renal tubular acidosis or urinary tract infection: a systematic review.

PubMed

Clericetti, Caterina M; Milani, Gregorio P; Lava, Sebastiano A G; Bianchetti, Mario G; Simonetti, Giacomo D; Giannini, Olivier

2018-03-01

Hyperammonemia usually results from an inborn error of metabolism or from an advanced liver disease. Individual case reports suggest that both distal renal tubular acidosis and urinary tract infection may also result in hyperammonemia. A systematic review of the literature on hyperammonemia secondary to distal renal tubular acidosis and urinary tract infection was conducted. We identified 39 reports on distal renal tubular acidosis or urinary tract infections in association with hyperammonemia published between 1980 and 2017. Hyperammonemia was detected in 13 children with distal renal tubular acidosis and in one adult patient with distal renal tubular acidosis secondary to primary hyperparathyroidism. In these patients a negative relationship was observed between circulating ammonia and bicarbonate levels (P < 0.05). In 31 patients (19 children, 12 adults), an acute urinary tract infection was complicated by acute hyperammonemia and symptoms and signs of acute neuronal dysfunction, such as an altered level of consciousness, convulsions and asterixis, often associated with signs of brain edema, such as anorexia and vomiting. Urea-splitting bacteria were isolated in 28 of the 31 cases. The urinary tract was anatomically or functionally abnormal in 30 of these patients. This study reveals that both altered distal renal tubular acidification and urinary tract infection may be associated with relevant hyperammonemia in both children and adults.

Whey versus soy protein diets and renal status in rats.

PubMed

Aparicio, Virginia A; Nebot, Elena; Tassi, Mohamed; Camiletti-Moirón, Daniel; Sanchez-Gonzalez, Cristina; Porres, Jesús M; Aranda, Pilar

2014-09-01

Different dietary protein sources can promote different renal statuses. We examined the effects of whey protein (WP) and soy protein (SP) intake on plasma, urinary, and morphological renal parameters in rats. One hundred and twenty Wistar rats were randomly distributed into 2 experimental groups fed with either WP or SP diets over 12 weeks. These diets were based on commercial WP or SP isolates. The urinary calcium content was higher in the WP diet compared to the SP diet group (P<.001) whereas the urinary citrate level was lower (P<.001). The urinary pH was more acidic in the WP diet group compared to the SP diet group (P<.001); however, no differences were observed between the groups for any of the renal morphological parameters analyzed (all, P>.05) or other plasma renal markers such as albumin or urea concentrations. The increase of acid and urinary calcium and the lower urinary citrate level observed in the WP diet group could increase the incidence of nephrolithiasis compared to the SP diet group. Despite the WP showed poorer acid-base profile, no significant morphological renal changes were observed. These results suggest that the use of SP instead of WP appears to promote a more alkaline plasma and urinary profile, with their consequent renal advantages.

Cause-effect relations between 55 kD soluble TNF receptor concentrations and specific and unspecific symptoms in a patient with mild SLE disease activity: an exploratory time series analysis study.

PubMed

Schubert, Christian; Haberkorn, Julia; Ocaña-Peinado, Francisco M; König, Paul; Sepp, Norbert; Schnapka-Köpf, Mirjam; Fuchs, Dietmar

2015-09-21

This integrative single-case study investigated the 12 h-to-12 h cause-effect relations between 55 kD soluble tumor necrosis factor receptor type 1 (sTNF-R55) and specific and unspecific symptoms in a 52-year-old Caucasian woman with mild systemic lupus erythematosus (SLE) disease activity. The patient collected her entire urine for 56 days in 12 h-intervals to determine sTNF-R55/creatinine and protein/creatinine levels (ELISA, HPLC). Additionally, twice a day, she took notes on oral ulceration and facial rash; answered questionnaires (VAS) on fatigue, weakness, and joint pain; and measured body temperature orally. Time series analysis consisted of ARIMA modeling and cross-correlational analyses (significance level = p < 0.05). Time series analysis revealed both a circadian and a circasemiseptan rhythm in the urinary sTNF-R55 data. Moreover, several significant lagged correlations between urinary sTNF-R55 concentrations and SLE symptoms in both directions of effect were identified. Specifically, increased urinary sTNF-R55 concentrations preceded decreased urinary protein levels by 36-48 h (r = -0.213) and, in the opposite direction of effect, increased protein levels preceded increased sTNF-R55 concentrations by 24-36 h (r = +0.202). In addition, increased urinary sTNF-R55 levels preceded increased oral ulcers by 36-48 h (r = +0.277) and, conversely, increased oral ulceration preceded decreased sTNF-R55 levels by 36-48 h (r = -0.313). Moreover, increased urinary sTNF-R55 levels preceded decreased facial rash by 36-48 h (r = -0.223) and followed increased body temperature after 36-48 h (r = +0.209). Weakness, fatigue and joint pain were not significantly correlated with urinary sTNF-R55 levels. This study gathered first evidence of real-life, long-term feedback loops between cytokines and SLE symptoms in mild SLE disease activity. Such insights into the potential role of sTNF-R55 in SLE would not have been possible had we applied a pre-post design group study. These findings require replication before firm conclusions can be drawn.

Biological monitoring of smoke exposure among wildland firefighters: A pilot study comparing urinary methoxyphenols with personal exposures to carbon monoxide, particulate matter, and levoglucosan.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Neitzel, R.; Naeher, L., P.; Paulsen, M.

2009-04-01

Urinary methoxyphenols (MPs) have been proposed as biomarkers of woodsmoke exposure. However, few field studies have been undertaken to evaluate the relationship between woodsmoke exposure and urinary MP concentrations. We conducted a pilot study at the US Forest ServiceFSavannah River Site, in which carbon monoxide (CO), levoglucosan (LG), and particulate matter (PM2.5) exposures were measured in wildland firefighters on prescribedburn days. Pre- and post-shift urine samples were collected from each subject, and cross-shift changes in creatinine-corrected urinary MP concentrations were calculated. Correlations between exposure measures and creatine-adjusted urinary MP concentrations were explored, and regression models were developed relating changes inmore » urinary MP concentrations to measured exposure levels. Full-shift measurements were made on 13 firefighters over 20 work shifts in winter 2004 at the US Forest Service Savannah River site, a National Environmental Research Park. The average workshift length across the 20 measured shifts was 701±95 min. LG and CO exposures were significantly correlated for samples where the filter measurement captured at least 60% of the work shift (16 samples), as well as for the smaller set of full-shift exposure samples (n¼9). PM2.5 and CO exposures were not significantly correlated, and LG and PM2.5 exposures were only significantly correlated for samples representing at least 60% of the work shift. Creatinine-corrected urinary concentrations for 20 of the 22 MPs showed cross-shift increases, with 14 of these changes showing statistical significance. Individual and summed creatinine-adjusted guaiacol urinary MPs were highly associated with CO (and, to a lesser degree, LG) exposure levels, and random-effects regression models including CO and LG exposure levels explained up to 80% of the variance in cross-shift changes in summed creatinine-adjusted guaiacol urinary MP concentrations. Although limited by the small sample size, this pilot study demonstrates that urinary MP concentrations may be effective biomarkers of occupational exposure to wood smoke among wildland firefighters.« less

Biological monitoring of smoke exposure among wildland firefighters: Apilot study comparing urinary methoxyphenols with personal exposures to carbon monoxide, particulate matter, and levoglucosan.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Neitzel, R.; Naeher, L., P.; Paulsen, M.

2009-04-01

Urinary methoxyphenols (MPs) have been proposed as biomarkers of woodsmoke exposure. However, few field studies have been undertaken to evaluate the relationship between woodsmoke exposure and urinary MP concentrations. We conducted a pilot study at the US Forest Service Savannah River Site, in which carbon monoxide (CO), levoglucosan (LG), and particulate matter (PM2.5) exposures were measured in wildland firefighters on prescribed burn days. Pre- and post-shift urine samples were collected from each subject, and cross-shift changes in creatinine-corrected urinary MP concentrations were calculated. Correlations between exposure measures and creatine-adjusted urinary MP concentrations were explored, and regression models were developed relatingmore » changes in urinary MP concentrations to measured exposure levels. Full-shift measurements were made on 13 firefighters over 20 work shifts in winter 2004 at the US Forest Service Savannah River site, a National Environmental Research Park. The average workshift length across the 20 measured shifts was 701±95 min. LG and CO exposures were significantly correlated for samples where the filter measurement captured at least 60% of the work shift (16 samples), as well as for the smaller set of full-shift exposure samples (n¼9). PM2.5 and CO exposures were not significantly correlated, and LG and PM2.5 exposures were only significantly correlated for samples representing at least 60% of the work shift. Creatinine-corrected urinary concentrations for 20 of the 22 MPs showed cross-shift increases, with 14 of these changes showing statistical significance. Individual and summed creatinine-adjusted guaiacol urinary MPs were highly associated with CO (and, to a lesser degree, LG) exposure levels, and random-effects regression models including CO and LG exposure levels explained up to 80% of the variance in cross-shift changes in summed creatinine-adjusted guaiacol urinary MP concentrations. Although limited by the small sample size, this pilot study demonstrates that urinary MP concentrations may be effective biomarkers of occupational exposure to wood smoke among wildland firefighters.« less

Biological monitoring of smoke exposure among wildland firefighters: A pilot study comparing urinary methoxyphenols with personal exposures to carbon monoxide, particulate matter, and levoglucosan.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Neitzel, R.; Naeher, L., P.; Paulsen, M.

2009-04-01

Urinary methoxyphenols (MPs) have been proposed as biomarkers of woodsmoke exposure. However, few field studies have been undertaken to evaluate the relationship between woodsmoke exposure and urinary MP concentrations. We conducted a pilot study at the US Forest Service Savannah River Site, in which carbon monoxide (CO), levoglucosan (LG), and particulate matter (PM2.5) exposures were measured in wildland firefighters on prescribed burn days. Pre- and post-shift urine samples were collected from each subject, and cross-shift changes in creatinine-corrected urinary MP concentrations were calculated. Correlations between exposure measures and creatine-adjusted urinary MP concentrations were explored, and regression models were developed relatingmore » changes in urinary MP concentrations to measured exposure levels. Full-shift measurements were made on 13 firefighters over 20 work shifts in winter 2004 at the US Forest Service Savannah River site, a National Environmental Research Park. The average workshift length across the 20 measured shifts was 701±95 min. LG and CO exposures were significantly correlated for samples where the filter measurement captured at least 60% of the work shift (16 samples), as well as for the smaller set of full-shift exposure samples (n¼9). PM2.5 and CO exposures were not significantly correlated, and LG and PM2.5 exposures were only significantly correlated for samples representing at least 60% of the work shift. Creatinine-corrected urinary concentrations for 20 of the 22 MPs showed cross-shift increases, with 14 of these changes showing statistical significance. Individual and summed creatinine-adjusted guaiacol urinary MPs were highly associated with CO (and, to a lesser degree, LG) exposure levels, and random-effects regression models including CO and LG exposure levels explained up to 80% of the variance in cross-shift changes in summed creatinine-adjusted guaiacol urinary MP concentrations. Although limited by the small sample size, this pilot study demonstrates that urinary MP concentrations may be effective biomarkers of occupational exposure to wood smoke among wildland firefighters.« less

Biological monitoring of smoke exposure among wildland firefighters: Apilot study comparing urinary methoxyphenols with personal exposures to carbon monoxide, particulate matter, and levoglucosan.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Neitzel, R.; Naeher, L., P.; Paulsen, M.

2009-04-01

Urinary methoxyphenols (MPs) have been proposed as biomarkers of woodsmoke exposure. However, few field studies have been undertaken to evaluate the relationship between woodsmoke exposure and urinary MP concentrations. We conducted a pilot study at the US Forest ServiceFSavannah River Site, in which carbon monoxide (CO), levoglucosan (LG), and particulate matter (PM2.5) exposures were measured in wildland firefighters on prescribed burn days. Pre- and post-shift urine samples were collected from each subject, and cross-shift changes in creatinine-corrected urinary MP concentrations were calculated. Correlations between exposure measures and creatine-adjusted urinary MP concentrations were explored, and regression models were developed relating changesmore » in urinary MP concentrations to measured exposure levels. Full-shift measurements were made on 13 firefighters over 20 work shifts in winter 2004 at the US Forest Service Savannah River site, a National Environmental Research Park. The average workshift length across the 20 measured shifts was 701±95 min. LG and CO exposures were significantly correlated for samples where the filter measurement captured at least 60% of the work shift (16 samples), as well as for the smaller set of full-shift exposure samples (n¼9). PM2.5 and CO exposures were not significantly correlated, and LG and PM2.5 exposures were only significantly correlated for samples representing at least 60% of the work shift. Creatinine-corrected urinary concentrations for 20 of the 22 MPs showed cross-shift increases, with 14 of these changes showing statistical significance. Individual and summed creatinine-adjusted guaiacol urinary MPs were highly associated with CO (and, to a lesser degree, LG) exposure levels, and random-effects regression models including CO and LG exposure levels explained up to 80% of the variance in cross-shift changes in summed creatinine-adjusted guaiacol urinary MP concentrations. Although limited by the small sample size, this pilot study demonstrates that urinary MP concentrations may be effective biomarkers of occupational exposure to wood smoke among wildland firefighters.« less

Biological monitoring of smoke exposure among wildland firefighters: Apilot study comparing urinary methoxyphenols with personal exposures to carbon monoxide, particulate matter, and levoglucosan.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Neitzel, R.; Naeher, L., P.; Paulsen, M.

2008-04-01

Urinary methoxyphenols (MPs) have been proposed as biomarkers of woodsmoke exposure. However, few field studies have been undertaken to evaluate the relationship between woodsmoke exposure and urinary MP concentrations. We conducted a pilot study at the US Forest Service Savannah River Site, in which carbon monoxide (CO), levoglucosan (LG), and particulate matter (PM2.5) exposures were measured in wildland firefighters on prescribed burn days. Pre- and post-shift urine samples were collected from each subject, and cross-shift changes in creatinine-corrected urinary MP concentrations were calculated. Correlations between exposure measures and creatine-adjusted urinary MP concentrations were explored, and regression models were developed relatingmore » changes in urinary MP concentrations to measured exposure levels. Full-shift measurements were made on 13 firefighters over 20 work shifts in winter 2004 at the US Forest Service Savannah River site, a National Environmental Research Park. The average workshift length across the 20 measured shifts was 701±95 min. LG and CO exposures were significantly correlated for samples where the filter measurement captured at least 60% of the work shift (16 samples), as well as for the smaller set of full-shift exposure samples (n¼9). PM2.5 and CO exposures were not significantly correlated, and LG and PM2.5 exposures were only significantly correlated for samples representing at least 60% of the work shift. Creatinine-corrected urinary concentrations for 20 of the 22 MPs showed cross-shift increases, with 14 of these changes showing statistical significance. Individual and summed creatinine-adjusted guaiacol urinary MPs were highly associated with CO (and, to a lesser degree, LG) exposure levels, and random-effects regression models including CO and LG exposure levels explained up to 80% of the variance in cross-shift changes in summed creatinine-adjusted guaiacol urinary MP concentrations. Although limited by the small sample size, this pilot study demonstrates that urinary MP concentrations may be effective biomarkers of occupational exposure to wood smoke among wildland firefighters.« less

A urinary metabolite of phenanthrene as a biomarker of polycyclic aromatic hydrocarbon metabolic activation in workers exposed to residual oil fly ash.

PubMed

Kim, Jee Young; Hecht, Stephen S; Mukherjee, Sutapa; Carmella, Steven G; Rodrigues, Ema G; Christiani, David C

2005-03-01

Residual oil fly ash is a chemically complex combustion product containing a significant component of potentially carcinogenic transition metals and polycyclic aromatic hydrocarbons (PAH). Various biomarkers of PAH exposure have been investigated previously, most notably 1-hydroxypyrene (1-OHP), in urine. In this study, we assessed the utility of r-1,t-2,3,c-4-tetrahydroxy-1,2,3,4-tetrahydrophenanthrene (trans, anti-PheT), a metabolite of phenanthrene, to detect occupational PAH exposure. Urine samples collected across the workweek were analyzed for 1-OHP and trans, anti-PheT in boilermakers (n = 20) exposed to residual oil fly ash. Median baseline urinary trans, anti-PheT concentrations were 0.50 microg/g creatinine in current tobacco smokers and 0.39 microg/g creatinine in nonsmokers. Median baseline urinary 1-OHP concentrations in smokers and nonsmokers were 0.31 and 0.13 microg/g creatinine, respectively. To study further the effect of smoking exposure on the urinary PAH markers, urinary cotinine was used. Although urinary trans, anti-PheT and 1-OHP concentrations were correlated (Spearman r = 0.63; P < 0.001) for all subjects, the regression coefficient between log-transformed trans, anti-PheT and log 1-OHP was statistically significant only for subjects with low levels of urinary cotinine or for nonsmokers. Each 1-unit increase in log 1-OHP was associated with a 0.77-unit increase (95% confidence interval, 0.45-1.09) in log trans, anti-PheT in subjects with low levels of urinary cotinine (P < 0.001). In these subjects, dichotomized occupational exposure status was a significant predictor of log trans, anti-PheT (P = 0.02) but not of log 1-OHP (P = 0.2). In conclusion, we found that urinary trans, anti-PheT was detected in levels comparable with 1-OHP in occupationally exposed workers, particularly nonsmokers. This study shows that urinary trans, anti-PheT may be an effective biomarker of uptake and metabolic activation of PAHs.

Urinary concentrations of cyclohexane-1,2-dicarboxylic acid monohydroxy isononyl ester, a metabolite of the non-phthalate plasticizer di(isononyl)cyclohexane-1,2-dicarboxylate (DINCH), and markers of ovarian response among women attending a fertility center

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mínguez-Alarcón, Lidia, E-mail: lminguez@hsph.harv

Di(isononyl)cyclohexane-1,2-dicarboxylate (DINCH), a non-phthalate plasticizer, was introduced commercially in 2002 as an alternative to ortho-phthalate esters because of its favorable toxicological profile. However, the potential health effects from DINCH exposure remain largely unknown. We explored the associations between urinary concentrations of metabolites of DINCH on markers of ovarian response among women undergoing in vitro fertilization (IVF) treatments. Between 2011 and 2015, 113 women enrolled a prospective cohort study at the Massachusetts General Hospital Fertility Center and provided up to two urine samples prior to oocyte retrieval. The urinary concentrations of two DINCH metabolites, cyclohexane-1,2-dicarboxylic acid monohydroxy isononyl ester (MHiNCH) andmore » cyclohexane-1,2-dicarboxylic acid monocarboxyisooctyl ester (MCOCH), were quantified by isotope dilution tandem mass spectrometry. We used generalized linear mixed models to evaluate the association between urinary metabolite concentrations and markers of ovarian response, accounting for multiple IVF cycles per woman via random intercepts. On average, women with detectable urinary MHiNCH concentrations, as compared to those below LOD, had a lower estradiol levels (−325 pmol/l, p=0.09) and number of retrieved oocytes (−1.8, p=0.08), with a stronger association among older women. However, urinary MHiNCH concentrations were unrelated to mature oocyte yield and endometrial wall thickness. In conclusion, we found suggestive negative associations between urinary MHiNCH concentrations and peak estradiol levels and number of total oocyte yields. This is the first study evaluating the effect of DINCH exposure on human reproductive health and raises the need for further experimental and epidemiological studies to better understand the potential effects of this chemical on health. - Highlights: • Women with detectable urinary MHiNCH concentrations had a lower estradiol levels and number of retrieved oocytes. • The negative association between urinary MHiNCH concentrations and total oocyte yield was stronger in older women. • Urinary MHiNCH concentrations were unrelated to mature oocyte yield and endometrial wall thickness.« less

Identification of a sensitive urinary biomarker, selenium-binding protein 1, for early detection of acute kidney injury.

PubMed

Kim, Kyeong Seok; Yang, Hun Yong; Song, Hosup; Kang, Ye Rim; Kwon, JiHoon; An, JiHye; Son, Ji Yeon; Kwack, Seung Jun; Kim, Young-Mi; Bae, Ok-Nam; Ahn, Mee-Young; Lee, Jaewon; Yoon, Sungpil; Lee, Byung Mu; Kim, Hyung Sik

2017-01-01

Acute kidney injury (AKI) is associated with increased mortality rate in patients but clinically available biomarkers for disease detection are currently not available. Recently, a new biomarker, selenium-binding protein 1 (SBP1), was identified for detection of nephrotoxicity using proteomic analysis. The aim of this study was to assess the sensitivity of urinary SBP1 levels as an early detection of AKI using animal models such as cisplatin or ischemia/reperfusion (I/R). Sprague-Dawley rats were injected with cisplatin (6 mg/kg, once i.p.) and sacrificed at 1, 3, or 5 days after treatment. Ischemia was achieved by bilaterally occluding both kidneys with a microvascular clamp for 45 min and verified visually by a change in tissue color. After post-reperfusion, urine samples were collected at 9, 24, and 48 hr intervals. Urinary excretion of protein-based biomarkers was measured by Western blot analysis. In cisplatin-treated rats, mild histopathologic alterations were noted at day 1 which became severe at day 3. Blood urea nitrogen (BUN) and serum creatinine (SCr) levels were significantly increased at day 3. Levels of urinary excretion of SBP1, neutrophil gelatinase-associated lipocalin (NGAL), and a tissue inhibitor of metalloproteinase-1 (TIMP-1) were markedly elevated at day 3 and 5 following drug treatment. In the vehicle-treated I/R group, serum levels of BUN and SCr and AST activity were significantly increased compared to sham. Urinary excretion of SBP1 and NGAL rose markedly following I/R. The urinary levels of SBP1, NGAL, TIMP-1, and KIM-1 proteins excreted by AKI patients and normal subjects were compared. Among these proteins, a marked rise in SBP1 was observed in urine of patients with AKI compared to normal subjects. Based upon receiver-operator curves (ROC), SBP1 displayed a higher area under the curve (AUC) scores than levels of SCr, BUN, total protein, and glucose. In particular, SBP1 protein was readily detected in small amounts of urine without purification. Data thus indicate that urinary excretion of SBP1 may be useful as a reliable biomarker for early diagnosis of AKI in patients.

Teaching strategies for assessing and managing urinary incontinence in older adults.

PubMed

Bradway, Christine; Cacchione, Pamela

2010-07-01

Urinary incontinence is common and affects many aspects of older adults' lives; therefore, it is essential that nursing faculty include this content in classroom and clinical teaching situations. This article describes innovative strategies for teaching upper-level nursing students (e.g., junior and senior undergraduates) about urinary incontinence in older adults, specifically, the relevant anatomy and physiology of continence and associated pathophysiology of urinary incontinence, risk factors and consequences, definitions and types, and effective nursing assessment and management strategies. Copyright 2010, SLACK Incorporated.

Urinary Incontinence and Levels of Regular Physical Exercise in Young Women.

PubMed

Da Roza, T; Brandão, S; Mascarenhas, T; Jorge, R N; Duarte, J A

2015-08-01

The purpose of this study was to determine the influence of different levels of regular physical exercise on the frequency of urinary incontinence in young nulliparous women from the northern region of Portugal. Participants (n=386) self-reported demographic variables, frequency, and time spent practicing organized exercise per week, as well as completed the International Consultation on Incontinence Questionnaire-Short Form. The level of exercise was calculated based on the time (in minutes) usually spent per week in organized exercise. 19.9% of Portuguese nulliparous women reported incontinence symptoms. Considering the distribution of urinary incontinence among the different quartiles of organized exercise, women from the 4(th)quartile (those who train for competitive purposes) demonstrated highest relative frequency (p=0.000) and a 2.53 greater relative risk to develop (95% CIs,1.3-2.7) incontinence compared to women from the 1(st) quartile (inactive). Women who practice exercise for recreational purposes (2(nd) and 3(rd) quartiles) did not show significant differences in the urinary incontinence prevalence and relative risk of developing it compared to women from the 1(st) quartile. The results showed that women participating in organized exercise involving high volume training for competition are potentially at risk of developing urinary incontinence, although organized exercise undertaken without the intent to compete seems to be safe for maintaining urinary continence. © Georg Thieme Verlag KG Stuttgart · New York.

Technical Basis Document: A Statistical Basis for Interpreting Urinary Excretion of Plutonium Based on Accelerator Mass Spectrometry (AMS) for Selected Atoll Populations in the Marshall Islands

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bogen, K; Hamilton, T F; Brown, T A

2007-05-01

We have developed refined statistical and modeling techniques to assess low-level uptake and urinary excretion of plutonium from different population group in the northern Marshall Islands. Urinary excretion rates of plutonium from the resident population on Enewetak Atoll and from resettlement workers living on Rongelap Atoll range from <1 to 8 {micro}Bq per day and are well below action levels established under the latest Department regulation 10 CFR 835 in the United States for in vitro bioassay monitoring of {sup 239}Pu. However, our statistical analyses show that urinary excretion of plutonium-239 ({sup 239}Pu) from both cohort groups is significantly positivelymore » associated with volunteer age, especially for the resident population living on Enewetak Atoll. Urinary excretion of {sup 239}Pu from the Enewetak cohort was also found to be positively associated with estimates of cumulative exposure to worldwide fallout. Consequently, the age-related trends in urinary excretion of plutonium from Marshallese populations can be described by either a long-term component from residual systemic burdens acquired from previous exposures to worldwide fallout or a prompt (and eventual long-term) component acquired from low-level systemic intakes of plutonium associated with resettlement of the northern Marshall Islands, or some combination of both.« less

Modulation of calcium oxalate dihydrate growth by selective crystal-face binding of phosphorylated osteopontin and polyaspartate peptide showing occlusion by sectoral (compositional) zoning.

PubMed

Chien, Yung-Ching; Masica, David L; Gray, Jeffrey J; Nguyen, Sarah; Vali, Hojatollah; McKee, Marc D

2009-08-28

Calcium oxalate dihydrate (COD) mineral and the urinary protein osteopontin/uropontin (OPN) are commonly found in kidney stones. To investigate the effects of OPN on COD growth, COD crystals were grown with phosphorylated OPN or a polyaspartic acid-rich peptide of OPN (DDLDDDDD, poly-Asp(86-93)). Crystals grown with OPN showed increased dimensions of the {110} prismatic faces attributable to selective inhibition at this crystallographic face. At high concentrations of OPN, elongated crystals with dominant {110} faces were produced, often with intergrown, interpenetrating twin crystals. Poly-Asp(86-93) dose-dependently elongated crystal morphology along the {110} faces in a manner similar to OPN. In crystal growth studies using fluorescently tagged poly-Asp(86-93) followed by imaging of crystal interiors using confocal microscopy, sectoral (compositional) zoning in COD was observed resulting from selective binding and incorporation (occlusion) of peptide exclusively into {110} crystal sectors. Computational modeling of poly-Asp(86-93) adsorption to COD {110} and {101} surfaces also suggests increased stabilization of the COD {110} surface and negligible change to the natively stable {101} surface. Ultrastructural, colloidal-gold immunolocalization of OPN by transmission electron microscopy in human stones confirmed an intracrystalline distribution of OPN. In summary, OPN and its poly-Asp(86-93) sequence similarly affect COD mineral growth; the {110} crystallographic faces become enhanced and dominant attributable to {110} face inhibition by the protein/peptide, and peptides can incorporate into the mineral phase. We, thus, conclude that the poly-Asp(86-93) domain is central to the OPN ability to interact with the {110} faces of COD, where it binds to inhibit crystal growth with subsequent intracrystalline incorporation (occlusion).

Aptamer based peptide enrichment for quantitative analysis of gonadotropin-releasing hormone by LC-MS/MS.

PubMed

Richards, S L; Cawley, A T; Cavicchioli, R; Suann, C J; Pickford, R; Raftery, M J

2016-04-01

Over recent years threats to racing have expanded to include naturally occurring biological molecules, such as peptides and proteins, and their synthetic analogues. Traditionally, antibodies have been used to enable detection of these compounds as they allow purification and concentration of the analyte of interest. The rapid expansion of peptide-based therapeutics necessitates a similarly rapid development of suitable antibodies or other means of enrichment. Potential alternative enrichment strategies include the use of aptamers, which offer the significant advantage of chemical synthesis once the nucleic acid sequence is known. A method was developed for the enrichment, detection and quantitation of gonadotropin-releasing hormone (GnRH) in equine urine using aptamer-based enrichment and LC-MS/MS. The method achieved comparable limits of detection (1 pg/mL) and quantification (2.5 pg/mL) to previously published antibody-based enrichment methods. The intra- and inter-assay precision achieved was less than 10% at both 5 and 20 pg/mL, and displayed a working dynamic range of 2.5-100 pg/mL. Significant matrix enhancement (170 ± 8%) and low analytical recovery (29 ± 15%) was observed, although the use of an isotopically heavy labelled GnRH peptide, GnRH (Pro(13)C5,(15)N), as the internal standard provides compensation for these parameters. Within the current limits of detection GnRH was detectable up to 1h post administration in urine and identification of a urinary catabolite extended this detection window to 4h. Based on the results of this preliminary investigation we propose the use of aptamers as a viable alternative to antibodies in the enrichment of peptide targets from equine urine. Copyright © 2016 Elsevier B.V. All rights reserved.

Widening and diversifying the proteome capture by combinatorial peptide ligand libraries via Alcian Blue dye binding.

PubMed

Candiano, Giovanni; Santucci, Laura; Petretto, Andrea; Lavarello, Chiara; Inglese, Elvira; Bruschi, Maurizio; Ghiggeri, Gian Marco; Boschetti, Egisto; Righetti, Pier Giorgio

2015-01-01

Combinatorial peptide ligand libraries (CPLLs) tend to bind complex molecules such as dyes due to their aromatic, heterocyclic, hydrophobic, and ionic nature that may affect the protein capture specificity. In this experimental work Alcian Blue 8GX, a positively charged phthalocyanine dye well-known to bind to glycoproteins and to glucosaminoglycans, was adsorbed on a chemically modified CPLL solid phase, and the behavior of the resulting conjugate was then investigated. The control and dye-adsorbed beads were used to harvest the human urinary proteome at physiological pH, this resulting in a grand total of 1151 gene products identified after the capture. Although the Alcian Blue-modified CPLL incremented the total protein capture by 115 species, it particularly enriched some families among the harvested proteins, such as glycoproteins and nucleotide-binding proteins. This study teaches that it is possible, via the two combined harvest mechanisms, to drive the CPLL capture toward the enrichment of specific protein categories.

Autism and urinary exogenous neuropeptides: development of an on-line SPE-HPLC-tandem mass spectrometry method to test the opioid excess theory.

PubMed

Dettmer, K; Hanna, D; Whetstone, P; Hansen, R; Hammock, B D

2007-08-01

Autism is a complex neurodevelopmental disorder with unknown etiology. One hypothesis regarding etiology in autism is the "opioid peptide excess" theory that postulates that excessive amounts of exogenous opioid-like peptides derived from dietary proteins are detectable in urine and that these compounds may be pathophysiologically important in autism. A selective LC-MS/MS method was developed to analyze gliadinomorphin, beta-casomorphin, deltorphin 1, and deltorphin 2 in urine. The method is based on on-line SPE extraction of the neuropeptides from urine, column switching, and subsequent HPLC analysis. A limit of detection of 0.25 ng/mL was achieved for all analytes. Analyte recovery rates from urine ranged between 78% and 94%, with relative standard deviations of 0.2-6.8%. The method was used to screen 69 urine samples from children with and without autism spectrum disorders for the occurrence of neuropeptides. The target neuropeptides were not detected above the detection limit in either sample set.

The Association between Urinary Sodium Excretion and Metabolic Syndrome in Korean Adults from the 2010–2011 Korean National Health and Nutrition Examination Survey

PubMed Central

Seo, Jeong Eun; Lee, Hong Soo; Lee, Sang Wha; Shim, Kyung Won; Byun, A Ri; Kim, Jung Hwa; An, Hee Jeong

2017-01-01

Background The sodium intake of Koreans was higher than that recommended by the World Health Organization. Urinary sodium, which is correlated with sodium intake, can be easily calculated by the Tanaka's equation. This study aimed to evaluate the association between urinary sodium and metabolic syndrome in Korean adults using the 2010–2011 Korean National Health and Nutrition Examination Survey (KNHANES). Methods A total of 5,870 participants from the 2010–2011 KNHANES were included in this study. Twenty-four hour urinary sodium was calculated by the Tanaka's equation using spot urine. Participants were divided into tertiles based on urinary sodium levels. The association between urinary sodium and metabolic syndrome was analyzed using multivariate logistic regression analysis. Results The odds ratios (ORs) and 95% confidence intervals (CIs) of metabolic syndrome for the 2nd and 3rd tertile of urinary sodium levels was 1.51 (1.16–1.97) and 1.56 (1.23–1.97) compared to the lowest tertile of urinary sodium in men. The ORs and 95% CIs of metabolic syndrome in women were 1.20 (0.95–1.51) for the 2nd tertile and 2.16 (1.68–2.78) for the 3rd tertile. These associations remained statistically significant, even after adjusting for multiple covariates such as age, education, regular exercise, smoking, and alcohol consumption. Conclusion These findings indicate that urinary sodium is significantly associated with metabolic syndrome in Korean adults. PMID:28775809

Lower urinary tract symptoms are associated with low levels of serum serotonin, high levels of adiponectin and fasting glucose, and benign prostatic enlargement.

PubMed

Haghsheno, Mohammad-Ali; Mellström, Dan; Peeker, Ralph; Hammarsten, Jan; Lorentzon, Mattias; Sundh, Valter; Karlsson, Magnus; Ohlsson, Claes; Damber, Jan-Erik

2015-04-01

The aim of this study was to test whether lower urinary tract symptoms (LUTS) and urinary incontinence are associated with the metabolic syndrome (MetS). The association between LUTS and benign prostatic enlargement (BPE) was also investigated. A cross-sectional, representative risk factor analysis of LUTS, as measured by the International Prostate Symptom Score (IPSS), and urinary incontinence was conducted. Among 950 representative individuals, aged 69-81 years, the association between clinical, anthropometric, endocrine, metabolic and inflammatory factors on the one hand, as both major and minor aspects of MetS, and LUTS and urinary incontinence, on the other hand, was analysed. The prostate gland volume was measured in a subgroup of 155 randomly selected individuals and the association between LUTS and BPE was estimated. No significant association was found between LUTS or urinary incontinence and the major aspects of the MetS. However, in a multivariate analysis, serum serotonin showed an independent negative correlation with LUTS and with urinary incontinence while fasting serum glucose and serum adiponectin showed a positive correlation with LUTS. Furthermore, in a subgroup of 155 individuals, the prostate gland volume correlated positively with LUTS. The study did not show an association between LUTS or urinary incontinence and the major components of the MetS. However, serum serotonin showed an independent negative correlation with LUTS and with urinary incontinence while fasting serum glucose and serum adiponectin showed a positive correlation with LUTS. The data confirm the general knowledge that BPE may be one of the causative factors of LUTS.

Effect of fasting on the urinary excretion of water-soluble vitamins in humans and rats.

PubMed

Fukuwatari, Tsutomu; Yoshida, Erina; Takahashi, Kei; Shibata, Katsumi

2010-01-01

Recent studies showed that the urinary excretion of the water-soluble vitamins can be useful as a nutritional index. To determine how fasting affects urinary excretion of water-soluble vitamins, a human study and an animal experiment were conducted. In the human study, the 24-h urinary excretion of water-soluble vitamins in 12 healthy Japanese adults fasting for a day was measured. One-day fasting drastically decreased urinary thiamin content to 30%, and increased urinary riboflavin content by 3-fold. Other water-soluble vitamin contents did not show significant change by fasting. To further investigate the alterations of water-soluble vitamin status by starvation, rats were starved for 3 d, and water-soluble vitamin contents in the liver, blood and urine were measured during starvation. Urinary excretion of thiamin, riboflavin, vitamin B(6) metabolite 4-pyridoxic acid, nicotinamide metabolites and folate decreased during starvation, but that of vitamin B(12), pantothenic acid and biotin did not. As for blood vitamin levels, only blood vitamin B(1), plasma PLP and plasma folate levels decreased with starvation. All water-soluble vitamin contents in the liver decreased during starvation, whereas vitamin concentrations in the liver did not decrease. Starvation decreased only concentrations of vitamin B(12) and folate in the skeletal muscle. These results suggest that water-soluble vitamins were released from the liver, and supplied to the peripheral tissues to maintain vitamin nutrition. Our human study also suggested that the effect of fasting should be taken into consideration for subjects showing low urinary thiamin and high urinary riboflavin.

Potential Biomarker Peptides Associated with Acute Alcohol-Induced Reduction of Blood Pressure

PubMed Central

Wakabayashi, Ichiro; Marumo, Mikio; Nonaka, Daisuke; Shimomura, Tomoko; Eguchi, Ryoji; Lee, Lyang-Ja; Tanaka, Kenji; Hatake, Katsuhiko

2016-01-01

The purpose of this study was to explore the peptides that are related to acute reduction of blood pressure after alcohol drinking. Venous blood was collected from male healthy volunteers before and after drinking white wine (3 ml/kg weight) containing 13% of ethanol. Peptidome analysis for serum samples was performed using a new target plate, BLOTCHIP®. Alcohol caused significant decreases in systolic and diastolic blood pressure levels at 45 min. The peptidome analysis showed that the levels of three peptides of m/z 1467, 2380 and 2662 changed significantly after drinking. The m/z 1467 and 2662 peptides were identified to be fragments of fibrinogen alpha chain, and the m/z 2380 peptide was identified to be a fragment of complement C4. The intensities of the m/z 2380 and m/z 1467 peptides before drinking were associated with % decreases in systolic and diastolic blood pressure levels at 45 min after drinking compared with the levels before drinking, while there were no significant correlations between the intensity of the m/z 2662 peptide and % decreases in systolic and diastolic blood pressure levels after drinking. The m/z 1467 and 2380 peptides are suggested to be markers for acute reduction of blood pressure after drinking alcohol. PMID:26815288

Consumer product exposures associated with urinary phthalate levels in pregnant women

PubMed Central

Buckley, Jessie P.; Palmieri, Rachel T.; Matuszewski, Jeanine M.; Herring, Amy H.; Baird, Donna D.; Hartmann, Katherine E.; Hoppin, Jane A.

2012-01-01

Human phthalate exposure is ubiquitous, but little is known regarding predictors of urinary phthalate levels. To explore this, 50 pregnant women aged 18–38 years completed two questionnaires on potential phthalate exposures and provided a first morning void. Urine samples were analyzed for 12 phthalate metabolites. Associations with questionnaire items were evaluated via Wilcoxon tests and t-tests, and r-squared values were calculated in multiple linear regression models. Few measured factors were statistically significantly associated with phthalate levels. Individuals who used nail polish had higher levels of mono-butyl phthalate (p=0.048) than non-users. Mono-benzyl phthalate levels were higher among women who used eye makeup (p=0.034) or used makeup on a regular basis (p=0.004). Women who used cologne or perfume had higher levels of di-(2-ethylhexyl) phthalate metabolites. Household products, home flooring or paneling, and other personal care products were also associated with urinary phthalates. The proportion of variance in metabolite concentrations explained by questionnaire items ranged between 0.31 for mono-ethyl phthalate and 0.42 for mono-n-methyl phthalate. Although personal care product use may be an important predictor of urinary phthalate levels, most of the variability in phthalate exposure was not captured by our relatively comprehensive set of questionnaire items. PMID:22760436

Intelligence quotient and iodine intake: a cross-sectional study in children.

PubMed

Santiago-Fernandez, Piedad; Torres-Barahona, Rosario; Muela-Martínez, J Antonio; Rojo-Martínez, Gemma; García-Fuentes, Eduardo; Garriga, M José; León, Ana García; Soriguer, Federico

2004-08-01

The association between iodine deficiency and poor mental and psychomotor development is known. However, most studies were undertaken in areas of very low iodine intake. We investigated whether a similar association is found in schoolchildren from southern Europe with a median urinary iodine output of 90 microg/liter. Urinary iodine levels were measured in 1221 children who also completed a questionnaire about their usual dietary habits. Intelligence quotient (IQ) was measured by Cattell's g factor test. IQ was significantly higher in children with urinary iodine levels above 100 microg/liter. The risk of having an IQ below the 25th percentile was significantly related to the intake of noniodized salt and drinking milk less than once a day. As expected, the risk of having an IQ below 70 was greater in children with urinary iodine levels less than 100 microg/liter. In conclusion, this study demonstrates that the IQ of schoolchildren in a developed country can be influenced by iodine intake. The results support the possibility of improving the IQ of many children from areas with mild iodine deficiency by ensuring an iodine intake sufficient to achieve a urinary iodine concentration greater than 100 microg/liter.

The elementome of calcium-based urinary stones and its role in urolithiasis

PubMed Central

Ramaswamy, Krishna; Killilea, David W.; Kapahi, Pankaj; Kahn, Arnold J.; Chi, Thomas; Stoller, Marshall L.

2016-01-01

Urolithiasis affects around 10% of the US population with an increasing rate of prevalence, recurrence and penetrance. The causes for the formation of most urinary calculi remain poorly understood, but obtaining the chemical composition of these stones might help identify key aspects of this process and new targets for treatment. The majority of urinary stones are composed of calcium that is complexed in a crystalline matrix with organic and inorganic components. Surprisingly, mitigation of urolithiasis risk by altering calcium homeostasis has not been very effective. Thus, studies to identify other therapeutic stone-specific targets, using proteomics, metabolomics and microscopy techniques, have been conducted, revealing a high level of complexity. The data suggest that numerous metals other than calcium and many nonmetals are present within calculi at measurable levels and several have distinct distribution patterns. Manipulation of the levels of some of these elemental components of calcium-based stones has resulted in clinically beneficial changes in stone chemistry and rate of stone formation. The elementome—the full spectrum of elemental content—of calcium-based urinary calculi is emerging as a new concept in stone research that continues to provide important insights for improved understanding and prevention of urinary stone disease. PMID:26334088

Normal Pubertal Development in Daughters of Women With PCOS: A Controlled Study.

PubMed

Legro, Richard S; Kunselman, Allen R; Stetter, Christy M; Gnatuk, Carol L; Estes, Stephanie J; Brindle, Eleanor; Vesper, Hubert W; Botelho, Julianne C; Lee, Peter A; Dodson, William C

2017-01-01

Daughters of women with polycystic ovary syndrome (PCOS) are thought to be at increased risk for developing stigmata of the syndrome, but the ontogeny during puberty is uncertain. We phenotyped daughters (n = 76) of mothers with PCOS and daughters (n = 80) from control mothers for reproductive and metabolic parameters characteristic of PCOS. We performed a matched case/control study at Penn State Hershey Medical Center that included non-Hispanic, white girls 4 to 17 years old. We obtained birth history, biometric, ovarian ultrasounds, whole-body dual-energy X-ray absorptiometry scan for body composition, 2-hour glucose challenged salivary insulin levels, and two timed urinary collections (12 hours overnight and 3 hours in the morning) for gonadotropins and sex steroids. We measured integrated urinary levels of adrenal (dehydroepiandrosterone sulfate) and ovarian [testosterone (TT)] steroids. Other endpoints included integrated salivary insulin levels and urinary luteinizing hormone levels. There were no differences in detection rates or mean levels for gonadotropins and sex steroids in timed urinary collections between PCOS daughters and control daughters, nor were there differences in integrated salivary insulin levels. Results showed that 69% of Tanner 4/5 PCOS daughters vs 31% of control daughters had hirsutism defined as a Ferriman-Gallwey score >8 (P = 0.04). There were no differences in body composition as determined by dual-energy X-ray absorptiometry between groups in the three major body contents (i.e., bone, lean body mass, and fat) or in ovarian volume between groups. Matched for pubertal stage, PCOS daughters have similar levels of urinary androgens and gonadotropins as well as glucose-challenged salivary insulin levels. Copyright © 2017 by the Endocrine Society

Urinary N-terminal fragment of titin is a marker to diagnose muscular dystrophy in patients with cardiomyopathy.

PubMed

Yoshihisa, Akiomi; Kiko, Takatoyo; Sato, Takamasa; Oikawa, Masayoshi; Kobayashi, Atsushi; Takeishi, Yasuchika

2018-06-02

The differential diagnosis of cardiomyopathy is important. It has been recently reported that urinary titin N (U-TN) is increased in patients with muscular dystrophy (MD), and is associated with muscular damage. We aimed to clarify whether U-TN is useful as a diagnostic tool for distinguishing MD from various cardiomyopathies [e.g. dilated cardiomyopathy (DCM), hypertrophic cardiomyopathy (HCM)]. We measured and compared the U-TN/creatinine ratio (U-TN/Cr; pmol/mg/dl) in 278 control subjects and 331 patients with various cardiomyopathies (DCM, n = 199; sarcoidosis, n = 18; HCM, n = 86; amyloidosis, n = 15; Fabry disease, n = 6; MD, n = 7). The U-TN/Cr was significantly higher in MD patients than in patients with various cardiomyopathies and the control subjects (P < 0.001). From the ROC analysis, the U-TN/Cr (with a cut-off value of 8.7) identified MD with 100% sensitivity, 82% specificity, and an area under the curve (AUC) of 0.92 (95% CI 0.87-0.98, P < 0.001). The AUC of the U-TN/Cr that was able to predict MD was superior to those of U-TN, creatinine kinase, B-type natriuretic peptide, and troponin I. Urinary Titin-N is a novel marker to diagnose MD. Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.

Soy foods and urinary isoprostanes: results from a randomized study in premenopausal women.

PubMed

Sen, Cherisse; Morimoto, Yukiko; Heak, Sreang; Cooney, Robert V; Franke, Adrian A; Maskarinec, Gertraud

2012-05-01

In addition to their antiestrogenic effects, soy isoflavones may protect against cancer through alternate biological actions, for example, antioxidant properties. This randomized crossover study explored the relationship between dietary isoflavone intake through common soy foods and oxidative stress quantified by urinary isoprostane levels. Eighty-two women aged 39.2 ± 6.1 years were randomly selected to receive a high soy diet of 2 soy food servings per day and a low soy diet of <3 servings per week for 6 months each, separated by a 1-month washout period. Urine samples were collected at baseline and at the end of each dietary period. Urinary isoprostane levels were measured using enzyme-linked immunosorbent assays (ELISA) and adjusted for creatinine levels. Mixed models using log-transformed values were applied to evaluate the effect of the high soy diet. Unadjusted isoprostane excretion levels were lower during the high rather than the low soy diet, but this effect was not statistically significant (p = 0.81). After adjustment for urinary creatinine, isoprostane excretion was slightly higher during the high soy diet (p = 0.02), an observation that was confirmed in a regression analysis between urinary isoflavones and isoprostanes during the high soy diet. The original association remained significant when restricted to adherent participants, however this effect disappeared after exclusion of three extreme values. In agreement with several previous reports, these findings do not support the hypothesis that soy exerts antioxidant effects, as measured by urinary isoprostane excretions, but additional markers of oxidative stress need to be investigated in future studies.

Soy Foods and Urinary Isoprostanes: Results from a Randomized Study in Premenopausal Women

PubMed Central

Sen, Cherisse; Morimoto, Yukiko; Heak, Sreang; Cooney, Robert V.; Franke, Adrian A.; Maskarinec, Gertraud

2013-01-01

In addition to their antiestrogenic effects, soy isoflavones may protect against cancer through alternate biologic actions including antioxidant properties. This randomized, crossover study explored the relation between dietary isoflavone intake through common soy foods and oxidative stress quantified by urinary isoprostane levels. Eighty-two women aged 39.2±6.1 years were randomized to a high soy diet of 2 soy food servings per day and a low soy diet of <3 servings per week for 6 months each, separated by a 1 month washout period. Urine samples were collected at baseline and at the end of each dietary period. Urinary isoprostane levels were measured using enzyme-linked immunosorbent assays (ELISA) and adjusted for creatinine levels. Mixed models using log-transformed values were applied to evaluate the effect of the high soy diet. Unadjusted isoprostane excretion levels were lower during the high than the low soy diet, but this effect was not statistically significant (p=0.81). After adjustment for urinary creatinine, isoprostane excretion was slightly higher during the high soy diet (p=0.02), an observation that was confirmed in a regression analysis between urinary isoflavones and isoprostanes during the high soy diet. The original association remained significant when restricted to adherent participants; however, this effect disappeared after exclusion of three extreme values. In agreement with several previous reports, these findings do not support the hypothesis that soy exerts antioxidant effects as measured by urinary isoprostane excretions, but additional markers of oxidative stress need to be investigated in future studies. PMID:22331037

Combined effect of urinary monohydroxylated polycyclic aromatic hydrocarbons and impaired lung function on diabetes.

PubMed

Hou, Jian; Sun, Huizhen; Xiao, Lili; Zhou, Yun; Yin, Wenjun; Xu, Tian; Cheng, Juan; Chen, Weihong; Yuan, Jing

2016-07-01

Associations of type 2 diabetes with exposure to polycyclic aromatic hydrocarbons and reduced lung function have been reported. The aim of the present study was to investigate effect of reduced lung function and exposure to background PAHs on diabetes. A total of 2730 individuals were drawn from the Wuhan-Zhuhai (WHZH) Cohort Study (n=3053). Participants completed physical examination, measurement of lung function and urinary monohydroxylated polycyclic aromatic hydrocarbons (OH-PAHs). Risk factors for type 2 diabetes were identified by multiple logistic regression analysis, and the presence of additive interaction between levels of urinary OH-PAHs and lower lung function was evaluated by calculation of the relative excess risk due to interaction (RERI) and attributable proportion due to interaction (AP). Urinary OH-PAHs levels was positively associated with type 2 diabetes among individuals with impaired lung function (p<0.05). Forced expiratory volume in one second (FEV1, odd ratio (OR): 0.664, 95% confidence interval (CI): 0.491-0.900) and forced vital capacity (FVC, OR: 0.693, 95% CI: 0.537-0.893) were negatively associated with diabetes among individuals. Additive interaction of higher urinary levels of OH-PAHs and lower FVC (RERI: 0.679, 95% CI: 0.120-1.238); AP: 0.427, 95% CI: 0.072-0.782) was associated with diabetes. Exposure to background PAHs was related to diabetes among individuals with lower lung function. Urinary levels of OH-PAHs and reduced lung function had an additive effect on diabetes. Copyright © 2016 Elsevier Inc. All rights reserved.

Passive smoking induces leukotriene production in children: influence of asthma.

PubMed

Hernández-Alvídrez, Elizabeth; Alba-Reyes, Georgina; Muñoz-Cedillo, Bernardo C; Arreola-Ramírez, José Luis; Furuya, María Elena Yuriko; Becerril-Ángeles, Martín; Vargas, Mario H

2013-05-01

Passive smoking is associated with poor asthma control in children, but the mechanism is unknown. Leukotrienes are involved in the asthma pathogenesis and their synthesis is increased in adult subjects who actively smoke. To evaluate whether passive smoking, as assessed by urinary cotinine levels, increases leukotriene production in children with or without asthma. This was a prospective, cross-sectional study in which children with stable intermittent asthma (without exacerbation) and healthy control children were studied through spirometry and urinary concentrations of cotinine and leukotriene E(4) (LTE(4)). Both groups were balanced to include children with and without passive smoking. Ninety children (49 with asthma and 41 controls, 54.4% females) aged 9 years (range, 5-13 years) were studied. Urinary LTE(4) concentrations were progressively higher as cotinine levels increased (r(S) = 0.23, p = .03). LTE(4) also correlated with body mass index (BMI) (r(S) = 0.30, p = .004), and multiple regression analysis revealed that BMI was even more influential than cotinine for determining LTE(4) levels. LTE(4) concentrations were unrelated with gender, age, or spirometry. In turn, cotinine inversely correlated with forced expiratory volume in one second (FEV(1)) (r(S) = -0.22, p = .04) and forced vital capacity (FVC) (r(S) = -0.25, p = .02), but when analyzed by groups, these relationships were statistically significant only in children with asthma. Exposure to environmental tobacco smoke, as assessed by urinary cotinine levels, was associated with an increased urinary concentration of LTE(4), although BMI exerted more influence in determining its concentration. Urinary cotinine was associated with decreased lung function, mainly in children with asthma.

Urinary Angiostatin - A Novel Putative Marker of Renal Pathology Chronicity in Lupus Nephritis*

PubMed Central

Wu, Tianfu; Du, Yong; Han, Jie; Singh, Sandeep; Xie, Chun; Guo, Yuyuan; Zhou, Xin J.; Ahn, Chul; Saxena, Ramesh; Mohan, Chandra

2013-01-01

There is a critical need to identify biomarkers for Systemic Lupus Erythematosus (SLE) which has a high prevalence of renal failure. When urine from patients with lupus nephritis was recently screened for the levels of ∼280 molecules using an exploratory array-based proteomic platform, elevated angiostatin levels were noted. Angiostatin is a bioactive fragment of plasminogen, and has been known to have modulatory function in angiogenesis and inflammation. The significant elevation in urinary angiostatin was next validated in an independent cohort of SLE patients (n = 100) using ELISA. Among patients with SLE, urine angiostatin was significantly increased in active SLE compared with inactive SLE, correlating well with the SLEDAI disease activity index and SLICC renal activity score (r = 0.66, p < 0.0001). ROC curve analysis further confirmed that urinary angiostatin had the capacity to discriminate patients with active SLE from those with inactive disease. Patients with Class IV lupus nephritis exhibited the highest levels of urinary angiostatin. Immunohistochemistry staining localized angiostatin expression to the renal tubular cells in these patients. Finally, when paired urine-kidney samples procured concurrently from patients with LN were next examined, urine angiostatin levels correlated strongly with the renal pathology chronicity index, but not with the activity index. Given that Class IV lupus nephritis and renal pathology chronicity changes forebode poor renal and patient survival, urinary angiostatin emerges as a novel noninvasive marker of renal disease in SLE. Longitudinal studies are in progress to further assess the disease-predictive potential of urinary angiostatin. PMID:23345539

Mercury in dental amalgam: Are our health care workers at risk?

PubMed

Sahani, M; Sulaiman, N S; Tan, B S; Yahya, N A; Anual, Z F; Mahiyuddin, W R Wan; Khan, M F; Muttalib, K A

2016-11-01

Dental amalgam in fillings exposes workers to mercury. The exposure to mercury was investigated among 1871 dental health care workers. The aim of the study was to evaluate the risk of mercury exposure among dental compared to nondental health care workers and to determine other risk factors for mercury exposure. Respondents answered questionnaires to obtain demographic, personal, professional, and workplace information and were examined for their own amalgam fillings. Chronic mercury exposure was assessed through urinary mercury levels. In total, 1409 dental and 462 nondental health care workers participated in the study. Median urine mercury levels for dental and nondental health care workers were 2.75 μg/L (interquartile range [IQR] = 3.0175) and 2.66 μg/L (IQR = 3.04) respectively. For mercury exposure, there were no significant risk factor found among the workers involved within the dental care. The Mann-Whitney test showed that urine mercury levels were significantly different between respondents who eat seafood more than 5 times per week compared to those who eat it less frequently or not at all (p = 0.003). The urinary mercury levels indicated significant difference between dental workers in their practice using squeeze cloths (Mann-Whitney test, p = 0.03). Multiple logistic regression showed that only the usage of cosmetic products that might contain mercury was found to be significantly associated with the urinary mercury levels (odds ratio [OR] = 15.237; CI: 3.612-64.276). Therefore, mean urinary mercury levels of health care workers were low. Exposure to dental amalgam is not associated with high mercury exposure. However, usage of cosmetic products containing mercury and high seafood consumption may lead to the increase of exposure to mercury. Exposure to the high levels of mercury from dental amalgam can lead to serious health effects among the dental health care workers. Nationwide chronic mercury exposure among dental personnel was assessed through urinary mercury levels. Findings suggest low urinary mercury levels of these health care workers. Exposure to dental amalgam is not associated with high mercury exposure. However, the usage of cosmetic products containing mercury and high seafood consumption may lead to the increase of exposure to mercury.

Serum and Urinary Levels of Tumor Necrosis Factor-Alpha in Renal Transplant Patients.

PubMed

Senturk Ciftci, Hayriye; Demir, Erol; Savran Karadeniz, Meltem; Tefik, Tzevat; Yazici, Halil; Nane, Ismet; Savran Oguz, Fatma; Aydin, Filiz; Turkmen, Aydin

2017-12-18

Allograft rejection is an important cause of early and long-term graft loss in kidney transplant recipients. Tumor necrosis factor-alpha promotes T-cell activation, the key reaction leading to allograft rejection. Here, we investigated whether serum and urinary tumor necrosis factor-alpha levels can predict allograft rejection. This study included 65 living related-donor renal transplant recipients with mean follow-up of 26 ± 9 months. Serum and urinary tumor necrosis factor-alpha levels were measured at pretransplant and at posttransplant time points (days 1 and 7 and months 3 and 6); serum creatinine levels were also monitored during posttransplant follow-up. Standard enzyme-linked immunoabsorbent assay was used to detect tumor necrosis factor-alpha levels. Clinical variables were monitored. Nine of 65 patients (13.8%) had biopsy-proven rejection during follow-up. Preoperative serum and urinary tumor necrosis factor-alpha levels were not significantly different when we compared patients with and without rejection. Serum tumor necrosis factor-alpha levels (in pg/mL) were significantly higher in the allograft rejection versus nonrejection group at day 7 (11.5 ± 4.7 vs 15.4 ± 5.8; P = .029) and month 1 (11.1 ± 4.8 vs 17.8 ± 10.9; P =.003). Urinary tumor necrosis factor-alpha levels (in pg/mL) were also elevated in the allograft rejection versus the nonrejection group at days 1 (10.2 ± 2.5 vs 14.1 ± 6.8; P = .002) and 7 (9.8 ± 2.2 vs 14.5 ± 2.7; P < .001) and at months 1 (8.0 ± 1.7 vs 11.8 ± 2.4; P < .001), 3 (7.7 ± 1.6 vs 9.6 ± 1.7; P = .002), and 6 (7.4 ± 1.6 vs 8.9 ± 0.9; P = .005). Our preliminary findings suggest that tumor necrosis factor-alpha has a role in diagnosing renal transplant rejection. Serum and urinary tumor necrosis factor-alpha levels may be a possible predictor for allograft rejection.

The Synthetic Antimicrobial Peptide 19-2.5 Interacts with Heparanase and Heparan Sulfate in Murine and Human Sepsis.

PubMed

Martin, Lukas; De Santis, Rebecca; Koczera, Patrick; Simons, Nadine; Haase, Hajo; Heinbockel, Lena; Brandenburg, Klaus; Marx, Gernot; Schuerholz, Tobias

2015-01-01

Heparanase is an endo-β-glucuronidase that cleaves heparan sulfate side chains from their proteoglycans. Thereby, heparanase liberates highly potent circulating heparan sulfate-fragments (HS-fragments) and triggers the fatal and excessive inflammatory response in sepsis. As a potential anti-inflammatory agent for sepsis therapy, peptide 19-2.5 belongs to the class of synthetic anti-lipopolysaccharide peptides; however, its activity is not restricted to Gram-negative bacterial infection. We hypothesized that peptide 19-2.5 interacts with heparanase and/or HS, thereby reducing the levels of circulating HS-fragments in murine and human sepsis. Our data indicate that the treatment of septic mice with peptide 19-2.5 compared to untreated control animals lowers levels of plasma heparanase and circulating HS-fragments and reduces heparanase activity. Additionally, mRNA levels of heparanase in heart, liver, lung, kidney and spleen are downregulated in septic mice treated with peptide 19-2.5 compared to untreated control animals. In humans, plasma heparanase level and activity are elevated in septic shock. The ex vivo addition of peptide 19-2.5 to plasma of septic shock patients decreases heparanase activity but not heparanase level. Isothermal titration calorimetry revealed a strong exothermic reaction between peptide 19-2.5 and heparanase and HS-fragments. However, a saturation character has been identified only in the peptide 19-2.5 and HS interaction. In conclusion, the findings of our current study indicate that peptide 19-2.5 interacts with heparanase, which is elevated in murine and human sepsis and consecutively attenuates the generation of circulating HS-fragments in systemic inflammation. Thus, peptide 19-2.5 seems to be a potential anti-inflammatory agent in sepsis.

Effect of dietary supplementation of gallic acid on nitrogen balance, nitrogen excretion pattern and urinary nitrogenous constituents in beef cattle.

PubMed

Wei, Chen; Yang, Kai; Zhao, Guangyong; Lin, Shixin; Xu, Zhiwei

2016-10-01

The objective of the trial was to study the effects of dietary supplementation of gallic acid (GA) on nitrogen (N) balance, N excretion pattern and urinary N constituents in beef cattle. In a 4 × 4 Latin square design, four male 30-month-old Simmental cattle (443 ± 22 kg live weight) received four levels of GA (purity ≥ 98.5%), i.e. 0, 5.3, 10.5, 21.1 g/kg DM, added to a basal ration. Each experimental period lasted 17 d, consisting of 12 d adaptation and 5 d sampling. The results showed that supplementation of GA at 5.3, 10.5 or 21.1 g/kg DM did not affect the N balance but regulated the N excretion pattern by increasing the ratio of faecal N/urinary N and decreasing the ratio of urinary urea N/total urinary N in beef cattle fed at maintenance level.

Levels and source apportionment of children's lead exposure: could urinary lead be used to identify the levels and sources of children's lead pollution?

PubMed

Cao, Suzhen; Duan, Xiaoli; Zhao, Xiuge; Wang, Beibei; Ma, Jin; Fan, Delong; Sun, Chengye; He, Bin; Wei, Fusheng; Jiang, Guibin

2015-04-01

As a highly toxic heavy metal, the pollution and exposure risks of lead are of widespread concern for human health. However, the collection of blood samples for use as an indicator of lead pollution is not always feasible in most cohort or longitudinal studies, especially those involving children health. To evaluate the potential use of urinary lead as an indicator of exposure levels and source apportionment, accompanying with environmental media samples, lead concentrations and isotopic measurements (expressed as (207)Pb/(206)Pb, (208)Pb/(206)Pb and (204)Pb/(206)Pb) were investigated and compared between blood and urine from children living in the vicinities of a typical coking plant and lead-acid battery factory. The results showed urinary lead might not be a preferable proxy for estimating blood lead levels. Fortunately, urinary lead isotopic measurements could be used as an alternative for identifying the sources of children's lead exposure, which coincided well with the blood lead isotope ratio analysis. Copyright © 2015 Elsevier Ltd. All rights reserved.

Urinary fibrogenic cytokines ET-1 and TGF-β1 are associated with urinary angiotensinogen levels in obese children.

PubMed

Correia-Costa, Liane; Morato, Manuela; Sousa, Teresa; Cosme, Dina; Guimarães, João Tiago; Guerra, António; Schaefer, Franz; Afonso, Alberto Caldas; Azevedo, Ana; Albino-Teixeira, António

2016-03-01

Fibrogenic cytokines are recognized as putative drivers of disease activity and histopathological deterioration in various kidney diseases. We compared urinary transforming growth factor β1 (U-TGF-β1) and endothelin 1 (U-ET-1) levels across body mass index classes and assessed their association with the level of urinary angiotensinogen (U-AGT), a biomarker of intrarenal renin-angiotensin-aldosterone system (RAAS). The was a cross-sectional evaluation of 302 children aged 8-9 years. Ambulatory blood pressure (BP), insulin resistance (HOMA-IR), aldosterone level and renal function were evaluated. U-ET-1, U-TGF-β1 and U-AGT levels were determined by immunoenzymatic methods. Obese children presented with the lowest levels of U-ET-1 and U-TGF-β1, but the difference was only significant for U-ET-1. In obese children, the median levels of both U-ET-1 and U-TGF-β1 tended to increase across tertiles (T1-T3) of U-AGT (U-ET-1: T1, 19.9 (14.2-26.3); T2, 32.5 (23.3-141.6); T3, 24.8 (18.7-51.5) ng/g creatinine, p = 0.007; U-TGF-β1: T1, 2.2 (1.8-4.0); T2, 4.3 (2.7-11.7); T3, 4.9 (3.8-10.1) ng/g creatinine, p = 0.004]. In multivariate models, in the obese group, U-ET-1 was associated with HOMA-IR and aldosterone and U-AGT levels, and U-TGF-β1 was associated with U-AGT levels and 24 h-systolic BP. Whereas the initial hypothesis of higher levels of urinary fibrogenic cytokines in obese children was not confirmed in our study, both TGF-β1 and U-ET-1 levels were associated with U-AGT level, which likely reflects an early interplay between tissue remodeling and RAAS in obesity-related kidney injury.

Triiodothyronine and brain natriuretic peptide: similar long-term prognostic values for chronic heart failure.

PubMed

Kozdag, Guliz; Ertas, Gokhan; Kilic, Teoman; Acar, Eser; Sahin, Tayfun; Ural, Dilek

2010-01-01

Although low levels of free triiodothyronine and high levels of brain natriuretic peptide have been shown as independent predictors of death in chronic heart failure patients, few studies have compared their prognostic values. The aim of this prospective study was to measure free triiodothyronine and brain natriuretic peptide levels and to compare their prognostic values among such patients.A total of 334 patients (mean age, 62 ± 13 yr; 218 men) with ischemic and nonischemic dilated cardiomyopathy were included in the study. The primary endpoint was a major cardiac event.During the follow-up period, 92 patients (28%) experienced a major cardiac event. Mean free triiodothyronine levels were lower and median brain natriuretic peptide levels were higher in patients with major cardiac events than in those without. A significant negative correlation was found between free triiodothyronine and brain natriuretic peptide levels. Receiver operating characteristic curve analysis showed that the predictive cutoff values were < 2.12 pg/mL for free triiodothyronine and > 686 pg/mL for brain natriuretic peptide. Cumulative survival was significantly lower among patients with free triiodothyronine < 2.12 pg/mL and among patients with brain natriuretic peptide > 686 pg/mL. In multivariate analysis, the significant independent predictors of major cardiac events were age, free triiodothyronine, and brain natriuretic peptide.In the present study, free triiodothyronine and brain natriuretic peptide had similar prognostic values for predicting long-term prognosis in chronic heart failure patients. These results also suggested that combining these biomarkers may provide an important risk indicator for patients with heart failure.

Human host defense peptides - role in maintaining human homeostasis and pathological processes.

PubMed

Dawgul, Malgorzata Anna; Greber, Katarzyna Ewa; Sawicki, Wieslaw; Kamysz, Wojciech

2016-12-12

The human body expresses over 100 host defense peptides and proteins (antimicrobial peptides, AMPs). The compounds are produced by tissues and mucosal surfaces, e.g. skin, the digestive and urinary tract, the ocular surface and neutrophils, and are believed to play a crucial role in defense from microbial infection. They are considered to protect the human body against microbial infections due to their antimicrobial and immunomodulatory activities. As well as having strong antimicrobial activity towards a broad spectrum of microorganisms, AMPs have been found to interact with neutrophils, monocytes and T-cells and promote the production of cytokines. They also neutralize the action of lipopolysaccharide (LPS) and play a crucial role in wound healing processes. In response to the microbial stimuli the AMPs are released in order to fight the infection, however there are several microorganisms evading the human immune system by downregulation of AMPs. Decreased or elevated expression of AMPs is associated also with several non-infectious diseases. Despite numerous studies conducted in the field of AMPs over the last few decades, their exact role in physiological and pathological processes remains to be explained. In this paper, we review the most significant human AMPs and their potential roles in maintaining human homeostasis as well as in pathological processes.

An in-vitro urinary catheterization model that approximates clinical conditions for evaluation of innovations to prevent catheter-associated urinary tract infections.

PubMed

Chua, R Y R; Lim, K; Leong, S S J; Tambyah, P A; Ho, B

2017-09-01

Catheter-associated urinary tract infections (CAUTI) account for approximately 25% of nosocomial infections globally, and often result in increased morbidity and healthcare costs. An additional concern is the presence of microbial biofilms which are major reservoirs of bacteria, especially antibiotic-resistant bacteria, in catheters. Since introduction of the use of closed drainage systems, innovations to combat CAUTI have not led to significant improvements in clinical outcomes. The lack of a robust laboratory platform to test new CAUTI preventive strategies may impede development of novel technologies. To establish an in-vitro catheterization model (IVCM) for testing of technological innovations to prevent CAUTI. The IVCM consists of a continuous supply of urine medium flowing into a receptacle (bladder) where the urine is drained through a urinary catheter connected to an effluent collection vessel (drainage bag). Test organism(s) can be introduced conveniently into the bladder via a rubber septa port. Development of bacteriuria and microbial biofilm on the catheter can be determined subsequently. With an initial inoculum of Escherichia coli [∼5×10 5  colony-forming units (cfu)/mL] into the bladder, a 100% silicone catheter and a commercially available silver-hydrogel catheter showed heavy biofilm colonization (∼10 8  cfu/cm and ∼10 7  cfu/cm, respectively) with similar bacterial populations in the urine (bacteriuria) (∼10 8  cfu/mL and ∼10 7  cfu/mL, respectively) within three days. Interestingly, an antimicrobial peptide (CP11-6A)-coated catheter showed negligible biofilm colonization and no detectable bacteriuria. The IVCM is a useful preclinical approach to evaluate new strategies for the prevention of CAUTI. Copyright © 2017 The Healthcare Infection Society. Published by Elsevier Ltd. All rights reserved.

Urinary Biomarkers and Obstructive Sleep Apnea in Patients with Down Syndrome

PubMed Central

Elsharkawi, Ibrahim; Gozal, David; Macklin, Eric A.; Voelz, Lauren; Weintraub, Gil; Skotko, Brian G.

2017-01-01

Study Objectives The study aim was to compare urinary biomarkers in individuals with Down syndrome (DS) with and without obstructive sleep apnea (OSA) to those of age- and sex-matched neurotypically developing healthy controls (HC). We further investigated whether we could predict OSA in individuals with DS using these biomarkers. Methods Urine samples were collected from 58 individuals with DS the night before or the morning after their scheduled overnight polysomnogram or both, of whom 47 could be age- and sex-matched to a sample of 43 HC. Concentrations of 12 neurotransmitters were determined by enzyme-linked immunosorbent assay. Log-transformed creatinine-corrected assay levels were normalized. Normalized z-scores were compared between individuals with DS vs. HC, between individuals with DS with vs. without OSA, and to derive composite models to predict OSA. Results Most night-sampled urinary biomarkers were elevated among individuals with DS relative to matched HC. No urinary biomarker levels differed between individuals with DS with vs. without OSA. A combination of four urinary biomarkers predicted AHI > 1 with a positive predictive value of 90% and a negative predictive value of 68%. Conclusions Having DS, even in the absence of concurrent OSA, is associated with a different urinary biomarker profile when compared to HC. Therefore, while urinary biomarkers may be predictive of OSA in the general pediatric population, a different approach is needed in interpreting urinary biomarker assays in individuals with DS. Certain biomarkers also seem promising to be predictive of OSA in individuals with DS. PMID:28522103

Breast-feeding improves gut maturation compared with formula feeding in preterm babies.

PubMed

Reisinger, Kostan W; de Vaan, Loes; Kramer, Boris W; Wolfs, Tim G A M; van Heurn, L W Ernest; Derikx, Joep P M

2014-12-01

The incidence of necrotizing enterocolitis (NEC) is higher in formula-fed babies than in breast-fed babies, which may be caused by breast-feeding-induced gut maturation. The effect of breast-feeding on gut maturation has been widely studied in animal models. This study aimed to assess the effects of breast-feeding on intestinal maturation in prematurely born babies by evaluating postnatal changes in urinary intestinal fatty acid binding protein (I-FABP) levels, a specific enterocyte marker. Gut maturation in 40 premature babies (<37 weeks of gestation) without gastrointestinal morbidity was studied, of whom 21 were exclusively breast-fed and 19 were formula-fed infants. Urinary I-FABP levels as the measure of gut maturation were measured at 5, 12, 19, and 26 days after birth. In breast-fed infants, there was a significant increase in median urinary I-FABP levels between 5 and 12 days after birth (104 [78-340] pg/mL to 408 [173-1028] pg/mL, P = 0.002), whereas I-FABP concentration in formula-fed infants increased between 12 and 19 days after birth (105 [44-557] pg/mL, 723 [103-1670] pg/mL, P = 0.004). Breast-fed babies had significantly higher median urinary I-FABP levels at postnatal day 12 (P = 0.01). The time course of the postnatal increase in urinary I-FABP levels reflecting gut maturation was significantly delayed in formula-fed babies, suggesting a delayed physiological response in formula-fed compared with breast-fed infants.

Body iodine status in women with postmenopausal osteoporosis.

PubMed

Arslanca, Tufan; Korkmaz, Vakkas; Arslanca, Seyma B; Karadag, Burak; Ergün, Yusuf

2018-03-01

Postmenopausal osteoporosis is a frequent cause of morbidity and can negatively impact life expectancy; iodine is an essential element for bone mineralization, and iodine deficiency is frequently observed. The aim of the present study was to understand the connection between postmenopausal osteoporosis and the level of iodine in the body. A total of 132 participants were divided into three groups: group 1 consisted of healthy postmenopausal women (n = 34), group 2 comprised osteopenic women (n = 38), and group 3 included women with postmenopausal osteoporosis (n = 60). The three groups were compared according to demographic, clinical, and laboratory findings. The urinary iodine levels were recorded as 216.1 ± 125.2 in the control group, 154.6 ± 76.6 in the osteopenic group, and 137.5 ± 64.9 in the postmenopausal osteoporosis group (P < 0.001). These differences were maintained after adjustment for body mass index (P < 0.001). The urinary iodine level accurately correlated with the total T-score for the lumbar spine (r = 0.236, P = 0.008). Multiple regression analysis showed that corrected for body mass index, alkaline phosphatase isoenzyme, and urinary deoxypyridinoline, the urinary iodine level was significantly associated with total T-score (beta coefficient = 0.270, P = 0.006). The urinary iodine level was significantly lower in women with postmenopausal osteoporosis, and iodine replacement may be important in preventing osteoporosis in areas where iodine deficiency is endemic.

[Analysis for related factors of upper urinary tract deterioration in patients with spinal cord injury].

PubMed

Jing, Hua-fang; Liao, Li-min; Fu, Guang; Wu, Juan; Ju, Yan-he; Chen, Guo-qing

2014-08-18

To evaluate the related factors of upper urinary tract deterioration in spinal cord injured patients. Medical records of spinal cord injured patients from Jan.2002 to Sep.2009 were retrospectively reviewed. All the patients were divided into the upper urinary tract deterioration group and non-deterioration group according to the diagnostic criteria. Indexes such as demographic characteristic (gender, age), spinal cord injury information (cause, level, completeness), statuses of urinary tract system (bladder management, urine routine, urine culture, ultrasound, serum creatinine, fever caused by urinary tract infection) and urodynamics information(bladder compliance, bladder stability, bladder sensation, detrusor sphincter dyssynergia, detrusor leak point pressure, maximum cystometric capacity, relative safe bladder capacity, maximum flow rate, maximum urethra closure pressure) were compared between the two groups.Then Logistic regression analysis were performed. There was significantly difference between the two groups in spinal cord injury level(χ(2) = 8.840, P = 0.031),bladder management(χ(2) = 11.362, P = 0.045), urinary rutine(χ(2) = 17.983, P = 0.000), fever caused by urinary tract infection(χ(2)= 64.472, P = 0.000), bladder compliance(χ(2) = 6.531, P = 0.011), bladder sensation(χ(2) = 11.505, P = 0.009), maximum cystometric capacity(t = 2.209, P = 0.043), and detrusor-sphincter dyssynergia(χ(2) = 4.247, P = 0.039). The multiple-factor non-conditional Logistic regression analysis showed that bladder management (OR = 1.114, P = 0.006), fever caused by urinary tract infection(OR = 1.018,P = 0.000), bladder compliance (OR = 1.588, P = 0.040) and detrusor-sphincter dyssynergia(OR = 1.023, P = 0.034) were the key factors of upper urinary tract deterioration in spinal cord injured patients. Urinary tract infection, lower bladder compliance, detrusor-sphincter dyssynergia and unreasonable bladder management are the risk factors of upper urinary tract deterioration in spinal cord injured patients.

Association of urinary calcium excretion with serum calcium and vitamin D levels.

PubMed

Rathod, Anita; Bonny, Olivier; Guessous, Idris; Suter, Paolo M; Conen, David; Erne, Paul; Binet, Isabelle; Gabutti, Luca; Gallino, Augusto; Muggli, Franco; Hayoz, Daniel; Péchère-Bertschi, Antoinette; Paccaud, Fred; Burnier, Michel; Bochud, Murielle

2015-03-06

Population-based data on urinary calcium excretion are scarce. The association of serum calcium and circulating levels of vitamin D [25(OH)D2 or D3] with urinary calcium excretion in men and women from a population-based study was explored. Multivariable linear regression was used to explore factors associated with square root-transformed 24-hour urinary calcium excretion (milligrams per 24 hours) taken as the dependent variable with a focus on month-specific vitamin D tertiles and serum calcium in the Swiss Survey on Salt Study. In total, 624 men and 669 women were studied with mean ages of 49.2 and 47.0 years, respectively (age range=15-95 years). Mean urinary calcium excretion was higher in men than in women (183.05 versus 144.60 mg/24 h; P<0.001). In adjusted models, the association (95% confidence interval) of square root urinary calcium excretion with protein-corrected serum calcium was 1.78 (95% confidence interval, 1.21 to 2.34) mg/24 h per milligram per deciliter in women and 0.59 (95% confidence interval, -0.11 to 1.29) mg/24 h per milligram per deciliter in men. Men in the third 25(OH)D3 tertile had higher square root urinary calcium excretion than men in the first tertile (0.99; 95% confidence interval, 0.36 to 1.63 mg/24 h per nanogram per milliliter), and the corresponding association was 0.32 (95% confidence interval, -0.22 to 0.85) mg/24 h per nanogram per milliliter in women. These sex differences were more marked under conditions of high urinary sodium or urea excretions. There was a positive association of serum calcium with urinary calcium excretion in women but not men. Vitamin 25(OH)D3 was associated with urinary calcium excretion in men but not women. These results suggest important sex differences in the hormonal and dietary control of urinary calcium excretion. Copyright © 2015 by the American Society of Nephrology.

Triiodothyronine and thyroxine in urine. II. Renal handling, and effect of urinary protein.

PubMed

Burke, C W; Shakespear, R A

1976-03-01

Mean urinary clearances of T3 were 164 ml/min in normal subjects, 177 in pregnancy, 221 in thyrotoxicosis, 174 in hypothyroidism, and 194 in 3 persons with undetectable T4 but normal T3 levels. T4 clearances were 38 ml/min in normal subjects, 48 in thyrotoxicosis, and 138 in hypothyroidism. Low creatinine clearance was associated with low clearances of T4 and T3. The data suggest urinary excretion of T3 by glomerular filtration of serum unbound T3 with added tubular excretion; and T4 excretion by glomerular filtration of unbound T4 and tubular reabsorption. However, 3-9% of urinary T3 and 5-12% of urinary T4 were bound to urinary proteins, and increased protein excretion caused markedly increased T4 excretion. In addition, 52% of urinary T3 and 68% of urinary T4 were bound to other substances of approximate mol wt 500-2,000, which may influence tubular handling of T3 or T4.

In utero and early childhood exposure to arsenic decreases lung function in children

PubMed Central

Recio-Vega, Rogelio; Gonzalez-Cortes, Tania; Olivas-Calderon, Edgar; Lantz, R. Clark; Gandolfi, A. Jay; Gonzalez-De Alba, Cesar

2016-01-01

Background The lung is a target organ for adverse health outcomes following exposure to arsenic. Several studies have reported a high prevalence of respiratory symptoms and diseases in subjects highly exposed to arsenic through drinking water, however, most studies to date has been performed in exposed adults, with little information on respiratory effects in children. The objective of the study was to evaluate the association between urinary levels of arsenic and its metabolites with lung function in children exposed in utero and in early childhood to high arsenic levels through drinking water. Methods A total of 358 healthy children were included in our study. Individual exposure was assessed based on urinary concentration of inorganic arsenic. Lung function was assessed by spirometry. Results Participants were exposed since pregnancy until early childhood to an average water As concentration of 152.13 μg/L. The mean urinary arsenic level registered in the studied subjects was 141.2 μg/L and only 16.7% had a urinary concentration below the national concern level. Forced vital capacity was significantly decreased in the studied population and it was negatively associated with the percent of inorganic arsenic. More than 57% of the subjects had a restrictive spirometric pattern. The urinary As level was higher in those children with restrictive lung patterns when compared with the levels registered in subjects with normal spirometric patterns. Conclusion Exposure to arsenic through drinking water during in utero and early life was associated with a decrease in FVC and with a restrictive spirometric pattern in the children evaluated. PMID:25131850

In utero and early childhood exposure to arsenic decreases lung function in children.

PubMed

Recio-Vega, Rogelio; Gonzalez-Cortes, Tania; Olivas-Calderon, Edgar; Lantz, R Clark; Gandolfi, A Jay; Gonzalez-De Alba, Cesar

2015-04-01

The lung is a target organ for adverse health outcomes following exposure to As. Several studies have reported a high prevalence of respiratory symptoms and diseases in subjects highly exposed to As through drinking water; however, most studies to date has been performed in exposed adults, with little information on respiratory effects in children. The objective of the study was to evaluate the association between urinary levels of As and its metabolites with lung function in children exposed in utero and in early childhood to high As levels through drinking water. A total of 358 healthy children were included in our study. Individual exposure was assessed based on urinary concentration of inorganic As. Lung function was assessed by spirometry. Participants were exposed since pregnancy until early childhood to an average water As concentration of 152.13 µg l⁻¹. The mean urinary As level registered in the studied subjects was 141.2 µg l⁻¹ and only 16.7% had a urinary concentration below the national concern level. Forced vital capacity was significantly decreased in the studied population and it was negatively associated with the percentage of inorganic As. More than 57% of the subjects had a restrictive spirometric pattern. The urinary As level was higher in those children with restrictive lung patterns when compared with the levels registered in subjects with normal spirometric patterns. Exposure to As through drinking water during in utero and early life was associated with a decrease in forced vital capacity and with a restrictive spirometric pattern in the children evaluated. Copyright © 2014 John Wiley & Sons, Ltd.

Assessment of iodine nutritional status in the general population in the province of Jaén.

PubMed

Olmedo Carrillo, Pablo; García Fuentes, Eduardo; Gutiérrez Alcántara, Carmen; Serrano Quero, Manuel; Moreno Martínez, Macarena; Ureña Fernández, Tomás; Santiago Fernández, Piedad

2015-10-01

Iodine deficiency affecting both pregnant women and schoolchildren has been reported in Jaén. Iodine deficiency is one of the leading causes of thyroid dysfunction and goiter, and adequate iodine prophylaxis with iodized salt, milk, and dairy products, or iodine supplementation have been shown to significantly improve iodine status in pregnancy. The purpose of this study was to assess iodine nutritional status in the general population of a iodine-deficient area with no previous institutional campaigns of iodine prophylaxis. A descriptive, cross-sectional study. Urinary iodine levels were measured in subjects from the Jaén healthcare district. The data were stratified by sex and age groups, and a survey was conducted on iodized salt consumption. Median and mean urinary iodine levels were 110.59 mcg/L and 130.11 mcg/L respectively. Urinary iodine levels were significantly higher in schoolchildren as compared to other age groups (161.52μg/L vs 109.33μg/L in subjects older than 65 years). Forty-three percent of the population had urinary iodine levels less than 100μg/L, and 68% of women of childbearing age had levels less than 150μg/L. Iodine nutritional status appears to be adequate, but the proportion of the population with urinary iodine levels less than 100μg/L is still very high, and iodized salt consumption is much less common than recommended by the WHO. Copyright © 2015 SEEN. Published by Elsevier España, S.L.U. All rights reserved.

Relationship between plasma levels of cardiac natriuretic peptides and soluble Fas: plasma soluble Fas as a prognostic predictor in patients with congestive heart failure.

PubMed

Tsutamoto, T; Wada, A; Maeda, K; Mabuchi, N; Hayashi, M; Tsutsui, T; Ohnishi, M; Fujii, M; Matsumoto, T; Yamamoto, T; Takayama, T; Kinoshita, M

2001-12-01

Cardiac natriuretic peptides may induce apoptosis in myocytes; however, the relationship between plasma levels of cardiac natriuretic peptides and those of soluble Fas (sFas) and tumor necrosis factor (TNF)-alpha remains unknown in patients with congestive heart failure (CHF). We measured plasma levels of sFas and TNF-alpha and those of atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), norepinephrine, and endothelin 1 in 96 patients with CHF (ejection fraction < 45%). The patients were monitored for 3 years. Plasma levels of sFas and TNF-alpha increased with the severity of CHF. There was no significant correlation between sFas plasma levels and those of ANP and BNP. Cox proportional hazard analysis showed that high levels of sFas (P = .009) and BNP (P < .0001) and a low ejection fraction (P = .019) were independent significant prognostic predictors. There is no significant correlation between cardiac natriuretic peptide and sFas levels in plasma. Plasma sFas is a useful prognostic marker independent of neurohumoral factors, suggesting that immune activation and/or apoptosis play a significant role in the pathogenesis of CHF.

Effect of indapamide on urinary calcium excretion in patients with and without urinary stone disease.

PubMed

Ceylan, Kadir; Topal, Cevat; Erkoc, Reha; Sayarlioglu, Hayriye; Can, Saban; Yilmaz, Yuksel; Dogan, Ekrem; Algun, Ekrem; Gonulalan, Hasan

2005-06-01

Indapamide is an antihypertensive agent similar to thiazides, but with some different effects. Thiazide and thiazide-like diuretics are useful in preventing recurrent urinary stone formation due to their hypocalciuric effects. To determine the hypocalciuric and other effects on certain laboratory parameters of indapamide 1.5 mg in different patient groups. Four groups of patients recruited from urology and nephrology outpatient departments were experiencing non-hypercalciuric urinary stone disease (group 1), idiopathic hypercalciuria (group 2), urinary stone disease with hypercalciuria (group 3), and essential hypertension (group 4). In all patients, fasting serum uric acid, calcium, sodium, potassium, cholesterol, triglyceride, parathyroid hormone (PTH) values, and morning second-spot urine calcium and creatinine levels were assessed before and 8 weeks after treatment with indapamide. Urinary calcium excretion was reduced significantly in all groups: group 1 from 0.10 +/- 0.02 to 0.07 +/- 0.03 (mean +/-SD; 30% reduction; p < 0.001), group 2 from 0.30 +/- 0.15 to 0.15 +/- 0.10 (50% reduction; p < 0.001), group 3 from 0.35 +/- 0.15 to 0.20 +/- 0.10 (43% reduction; p < 0.001), and group 4 from 0.10 +/- 0.03 to 0.08 +/- 0.02 (20% reduction; p < 0.0010). These results should be interpreted with caution since no control group was included in this study. Mean serum uric acid and triglyceride levels were significantly increased, and mean PTH and potassium levels and diastolic and systolic blood pressure were significantly decreased in all groups. Few temporary adverse effects, such as dizziness and fatigue, were noticed and none of them caused discontinuation of treatment. Indapamide 1.5 mg/day is effective in decreasing calciuria in patients with non-hypercalciuric urinary stone disease, idiopathic hypercalciuria, urinary stone disease with hypercalciuria, and essential hypertension. This could be achieved with few adverse effects similar to those of thiazides and indapamide 2.5 mg. Indapamide decreased the PTH levels in all groups. Long-term clinical benefits of these effects should be evaluated prospectively with further randomized studies.

Biochemical and clinical studies in Libyan Jewish cystinuria patients and their relatives.

PubMed

Pras, E; Kochba, I; Lubetzky, A; Pras, M; Sidi, Y; Kastner, D L

1998-11-02

Cystinuria is a hereditary disorder manifested by the development of kidney stones. Three subtypes of the disease have been described, based on urinary excretion of cystine and the dibasic amino acids in heterozygotes, and oral loading tests in homozygotes. Cystinuria is very common among Libyan Jews living in Israel. Recently, we mapped the disease-causing gene in Libyan Jews to 19q, and have shown a very strong founder effect. In this report we present the results of biochemical and clinical studies performed on Libyan Jewish cystinuria patients and members of their families. High levels of cystine and the dibasic amino acids in heterozygotes support previous data that cystinuria in Libyan Jews is a non-type I disease. Oral loading tests performed with lysine showed some degree of intestinal absorption, but less than in normal controls. Previous criteria for determining the disease type, based solely on urinary amino acid levels, proved useless due to a very wide range of cystine and the dibasic amino acids excreted by the heterozygotes. Urinary cystine levels were useful in distinguishing between unaffected relatives and heterozygotes, but were unhelpful in differentiating between heterozygotes and homozygotes. Urinary levels of ornithine or arginine, and the sum of urinary cystine and the dibasic amino acids, could distinguish between the last two groups. Among stone formers, 90% were homozygotes and 10% were heterozygotes; 15% of the homozygotes were asymptomatic.

The Critical Importance of Urinary Concentrating Ability in the Generation of Urinary Carbon Dioxide Tension

PubMed Central

Arruda, Jose A. L.; Nascimento, Luiz; Mehta, Pradeep K.; Rademacher, Donald R.; Sehy, John T.; Westenfelder, Christof; Kurtzman, Neil A.

1977-01-01

Measurement of urine to blood (U-B) carbon dioxide tension (PCO2) gradient during alkalinization of the urine has been suggested to assess distal H+ secretion. A fact that has not been considered in previous studies dealing with urinary PCO2 is that dissolution of HCO3 in water results in elevation of PCO2 which is directly proportional to the HCO3 concentration. To investigate the interrelationship of urinary HCO3 and urinary acidification, we measured U-B PCO2 in (a) the presence of enhanced H+ secretion and decreased concentrating ability i.e., chronic renal failure (CRF), (b) animals with normal H+ secretion and decreased concentrating ability, Brattleboro (BB) rats, and (c) the presence of both impaired H+ secretion and concentrating ability (LiCl treatment and after release of unilateral ureteral obstruction). At moderately elevated plasma HCO3 levels (30-40 meq/liter), normal rats achieved a highly alkaline urine (urine pH > 7.8) and raised urine HCO3 concentration and U-B PCO2. At similar plasma HCO3 levels, BB rats had a much higher fractional water excretion and failed to raise urine pH, urine HCO3 concentration, and U-B PCO2 normally. At a very high plasma HCO3 (>50 meq/liter), BB rats raised urine pH, urine HCO3 concentration, and U-B PCO2 to the same levels seen in normals. CRF rats failed to raise urine pH, urine HCO3, and U-B PCO2 normally at moderately elevated plasma HCO3 levels; at very high plasma HCO3 levels, CRF rats achieved a highly alkaline urine but failed to raise U-B PCO2. Dogs and patients with CRF were also unable to raise urine pH, urine HCO3 concentration, and U-B PCO2 normally at moderately elevated plasma HCO3 levels. In rats, dogs, and man, U-B PCO2 was directly related to urine HCO3 concentration and inversely related to fractional water excretion. At moderately elevated plasma HCO3 levels, animals with a distal acidification defect failed to raise U-B PCO2; increasing the plasma HCO3 to very high levels resulted in a significant increase in urine HCO3 concentration and U-B PCO2. The observed urinary PCO2 was very close to the PCO2 which would be expected by simple dissolution of a comparable amount of HCO3 in water. These data demonstrate that, in highly alkaline urine, urinary PCO2 is largely determined by concentration of urinary HCO3 and cannot be used as solely indicating distal H+ secretion. PMID:893680

Reduction of cooking oil fume exposure following an engineering intervention in Chinese restaurants.

PubMed

Pan, Chih-Hong; Shih, Tung-Sheng; Chen, Chiou-Jong; Hsu, Jin-Huei; Wang, Shun-Chih; Huang, Chien-Ping; Kuo, Ching-Tang; Wu, Kuen-Yuh; Hu, Howard; Chan, Chang-Chuan

2011-01-01

A new engineering intervention measure, an embracing air curtain device (EACD), was used to increase the capture efficiency of cooker hoods and reduce cooking oil fume (COF) exposure in Chinese restaurants. An EACD was installed in six Chinese restaurants where the cooks complained of COF exposure. Before- and after-installation measurements were taken to compare changes in particulate matter (PM) and polycyclic aromatic hydrocarbons (PAHs) in kitchen air, and changes in levels of urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG) and malondialdehyde (MDA). The association between PM and PAHs in air and 8-OHdG and MDA in urine was evaluated by linear mixed-effects regression analysis. Results showed that geometric mean kitchen air levels of PM(10), PM(2.5), PM(1.0) and total particulate PAHs were significantly reduced after the EACDs were introduced. Urinary levels of 8-OHdG and MDA in cooks were also significantly lower after EACD instalment. PM(2.5), PM(1.0) and benzo(a)pyrene (BaP) levels were positively associated with urinary 8-OHdG levels after adjusting for key personal covariates. Urinary MDA levels in cooks were also positively associated with BaP levels after adjusting for key personal covariates. This study demonstrates that the EACD is effective for reducing COF and oxidative stress levels in cooks working in Chinese kitchens.

Farmworker and nonfarmworker Latino immigrant men in North Carolina have high levels of specific pesticide urinary metabolites.

PubMed

Arcury, Thomas A; Chen, Haiying; Laurienti, Paul J; Howard, Timothy D; Barr, Dana Boyd; Mora, Dana C; Quandt, Sara A

2017-06-16

This article compares detections and concentrations of specific organophosphate (OP), bis-dithiocarbamate, and pyrethroid pesticide urinary metabolites among Latino male farmworkers and nonfarmworkers in North Carolina. Data are from interviews and urine samples collected in 2012 and 2013. Farmworkers and nonfarmworkers frequently had detections for OP and pyrethroid pesticide urinary metabolites. Detection of bis-dithiocarbamate urinary metabolites was less frequent, but substantial among the nonfarmworkers. The concentrations of organophosphate, bis-dithiocarbamate, and pyrethroid pesticide urinary metabolites were high for farmworkers and nonfarmworkers compared to National Health and Nutrition Examination Survey results. Pesticide urinary metabolite detection was not associated with occupation in nonfarmworkers. Research for reducing pesticide exposure among farmworkers remains important; research is also needed to determine pesticide exposure pathways among Latino nonfarmworkers.

Changes in cat urinary glycosaminoglycans with age and in feline urologic syndrome.

PubMed

Pereira, Daionety A; Aguiar, Jair A K; Hagiwara, Mitika K; Michelacci, Yara M

2004-04-07

The aim of the present study was to characterize the urinary excretion of glycosaminoglycans in kittens and adult healthy cats, as well as in cats with a low urinary tract disease, the feline urologic syndrome (FUS). The main urinary glycosaminoglycan in cats was found to be chondroitin sulfate, with smaller amounts of dermatan sulfate and heparan sulfate. There was no difference in the urinary glycosaminoglycan concentration with sex, but a marked decrease occurred with age, due to chondroitin sulfate. Trace amounts of keratan sulfate were also detected in the urine of kittens, but not of healthy adult cats. Dermatan sulfate and heparan sulfate were the only glycosaminoglycans found in the urinary tract and kidney, and chondroitin sulfate was the only glycosaminoglycan found in the plasma. These data suggest that the main urinary glycosaminoglycan chondroitin sulfate is of systemic origin and filtered in the kidney, while the minor components dermatan sulfate and heparan sulfate may come from the urinary tract. The urinary glycosaminoglycan concentration was greatly decreased in animals with FUS, as compared to normal adults. We hypothesize that these low glycosaminoglycan levels reflect a damage to the bladder surface, resulting in absorption and/or degradation of the endogenous urinary glycosaminoglycans.

Concentrations of the urinary pyrethroid metabolite 3-phenoxybenzoic acid in farm worker families in the MICASA study

DOE Office of Scientific and Technical Information (OSTI.GOV)

Trunnelle, Kelly J., E-mail: kjtrunnelle@ucdavis.edu; Bennett, Deborah H.; Ahn, Ki Chang

Indoor pesticide exposure is a growing concern, particularly from pyrethroids, a commonly used class of pesticides. Pyrethroid concentrations may be especially high in homes of immigrant farm worker families who often live in close proximity to agricultural fields, and are faced with poor housing conditions, causing higher pest infestation and more pesticide use. We investigate exposure of farm worker families to pyrethroids in a study of mothers and children living in Mendota, CA within the population-based Mexican Immigration to California: Agricultural Safety and Acculturation (MICASA) Study. We present pyrethroid exposure based on an ELISA analysis of urinary metabolite 3-phenoxybenzoic acidmore » (3PBA) levels among 105 women and 103 children. The median urinary 3PBA levels (children=2.56 ug/g creatinine, mothers=1.46 ug/g creatinine) were higher than those reported in population based studies for the United States general population, but similar to or lower than studies with known high levels of pyrethroid exposure. A positive association was evident between poor housing conditions and the urinary metabolite levels, showing that poor housing conditions are a contributing factor to the higher levels of 3PBA seen in the urine of these farm worker families. Further research is warranted to fully investigate sources of exposure. - Highlights: • We investigate exposure of farm worker families to pyrethroids. • We present pyrethroid exposure based on an ELISA analysis of urinary 3PBA levels. • 3PBA levels were higher than those reported for the U.S. general population. • Poor housing conditions may be associated with pyrethroid exposure.« less

Does endogenous GLP-1 affect resting energy expenditure and fuel selection in overweight and obese adults?

PubMed

Poggiogalle, E; Donini, L M; Chiesa, C; Pacifico, L; Lenzi, A; Perna, S; Faliva, M; Naso, M; Rondanelli, M

2018-04-01

To investigate the association between fasting glucagon-like peptide 1 (GLP-1) levels and resting energy expenditure (REE), and respiratory quotient (RQ) in overweight and obese adults. Study participants were enrolled at the Dietetic and Metabolic Unit, University of Pavia, Italy. Inclusion criteria were age ≥ 25 and ≤ 45 years, and body mass index (BMI) ≥ 25 and ≤ 35 kg/m 2 . Diabetic subjects were excluded. Body composition was measured by dual-energy X-ray absorptiometry. REE was evaluated using indirect calorimetry, and RQ was calculated from respiratory gas exchanges. Fasting GLP-1, glucose, insulin and free fatty acid (FFA) levels, and 24-h norepinephrine urinary excretion were measured. Homeostasis model assessments of insulin resistance (HOMA-IR) and beta-cell function (HOMA-β) were calculated. Thirty-seven participants were included (age 43.4 ± 1.6 years; BMI 30.6 ± 0.5 kg/m 2 ). REE was not associated with fasting GLP-1 levels (p = 0.98) after adjustment for age, sex, fat-free mass (FFM), and fat mass (FM). Similarly, no association was observed between RQ and GLP-1 levels (p = 0.95), after adjustment for age, sex, and body fat. In adults subjects with increased adiposity fasting, GLP-1 levels do not seem to play a role in the regulation of energy metabolism and in fuel selection.

Biomarkers of oxidative stress and its association with the urinary reducing capacity in bus maintenance workers.

PubMed

Sauvain, Jean-Jacques; Setyan, Ari; Wild, Pascal; Tacchini, Philippe; Lagger, Grégoire; Storti, Ferdinand; Deslarzes, Simon; Guillemin, Michel; Rossi, Michel J; Riediker, Michael

2011-05-30

Exposure to particles (PM) induces adverse health effects (cancer, cardiovascular and pulmonary diseases). A key-role in these adverse effects seems to be played by oxidative stress, which is an excess of reactive oxygen species relative to the amount of reducing species (including antioxidants), the first line of defense against reactive oxygen species. The aim of this study was to document the oxidative stress caused by exposure to respirable particles in vivo, and to test whether exposed workers presented changes in their urinary levels for reducing species. Bus depot workers (n = 32) exposed to particles and pollutants (respirable PM4, organic and elemental carbon, particulate metal content, polycyclic aromatic hydrocarbons, NOx, O3) were surveyed over two consecutive days. We collected urine samples before and after each shift, and quantified an oxidative stress biomarker (8-hydroxy-2'-deoxyguanosine), the reducing capacity and a biomarker of PAH exposure (1-hydroxypyrene). We used a linear mixed model to test for associations between the oxidative stress status of the workers and their particle exposure as well as with their urinary level of reducing species. Workers were exposed to low levels of respirable PM4 (range 25-71 μg/m3). However, urinary levels of 8-hydroxy-2'-deoxyguanosine increased significantly within each shift and between both days for non-smokers. The between-day increase was significantly correlated (p < 0.001) with the concentrations of organic carbon, NOx, and the particulate copper content. The within-shift increase in 8OHdG was highly correlated to an increase of the urinary reducing capacity (Spearman ρ = 0.59, p < 0.0001). These findings confirm that exposure to components associated to respirable particulate matter causes a systemic oxidative stress, as measured with the urinary 8OHdG. The strong association observed between urinary 8OHdG with the reducing capacity is suggestive of protective or other mechanisms, including circadian effects. Additional investigations should be performed to understand these observations.

Direct radioimmunoassay of urinary estrogen and pregnanediol glucuronides during the menstrual cycle

DOE Office of Scientific and Technical Information (OSTI.GOV)

Stanczyk, F.Z.; Miyakawa, I.; Goebelsmann, U.

Assays measuring immunoreactive estrone glucuronide (E/sub 1/G), estradiol-3-glucuronide (E/sub 2/-3G), estradiol-17..beta..-glucuronide (E/sub 2/-17G), estriol-3-glucuronide (E/sub 3/-3G), estriol-16..cap alpha..-glucuronide (E/sub 3/-16G), and pregnanediol-3..cap alpha..-glucuronide (Pd-3G) directly in diluted urine were developed and validated. These estrogen and pregnanediol glucuronide fractions were measured in aliquots of 24-hour and overnight samples of urine collected daily from seven women for one menstrual cycle. Urinary hormone excretion was correlated with daily serum estradiol (E/sub 2/), progesterone (P), and lutenizing hormonee (LH) levels. A sharp midcycle LH peak preceded by a preovulatory rise in serum E/sub 2/ and followed by luteal phase serum P levels were notedmore » in each of the seven apparently ovulatory cycles. Twenty-four-hour and overnight urinary excretion patterns of estrogen glucuronides were similar to those of serum E/sub 2/. Of the five estrogen glucuronide fractions tested, excretion of E/sub 2/-17G exhibited the earliest and steepest ascending slope of the preovulatory estrogen surge and correlated best with serum E/sub 2/ levels. Urinary excretion of E/sub 1/-G, E/sub 2/-3G, and E/sub 3/-16G also showed an early and steep preovulatory rise and preceded that of E/sub 3/-3G, whereas urinary excretion of E/sub 3/-3G exhibited the poorest correlation with serum E/sub 2/ concentrations. The urinary excretion of Pd-3G rose parallel to serum P levels and was markedly elevated 2 to 3 days after the midcycle LH peak in both 24-hour and overnight collections of urine. These results indicate that among the urinary estrogen conjugate fractions tested, E/sub 2/-17G is the one that most suitably predicts ovulation.« less

Serum levels of natriuretic peptides in children with various types of loading conditions.

PubMed

Eerola, Anneli; Jokinen, Eero; Pihkala, Jaana I

2009-06-01

To evaluate the influence of volume overload of the left (LV) and right ventricle (RV) and pressure overload of LV and restrictive physiology on levels of N-terminal proatriopeptide (ANPN) and N-terminal pro-brain natriuretic peptide (NT-proBNP). We studied 41 children with atrial septal defect (ASD), 35 with patent ductus arteriosus (PDA), 27 with coarctation of the aorta (CoA), 25 with restrictive physiology caused by Mulibrey nanism, and 64 control children. We measured serum concentrations of natriuretic peptides and evaluated ventricular size and function with echocardiography. In patients with ASD, PDA, and Mulibrey nanism, levels of both ANPN and NT-proBNP were higher than in controls but in children with CoA, only ANPN levels were higher. ANPN levels correlated with RV size in ASD and NT-proBNP levels with LV size in PDA. In patients with restriction, NT-proBNP levels correlated negatively with LV size. Correlation between echo measurements and levels of natriuretic peptides varied according to loading condition. Measurement of natriuretic peptide levels provides a supplemental method for non-invasive haemodynamic evaluation of children's heart disease.

Quantification of VGF- and pro-SAAS-derived peptides in endocrine tissues and the brain, and their regulation by diet and cold stress.

PubMed

Chakraborty, Tandra R; Tkalych, Oleg; Nanno, Daniela; Garcia, Angelo L; Devi, Lakshmi A; Salton, Stephen R J

2006-05-17

Two novel granin-like polypeptides, VGF and pro-SAAS, which are stored in and released from secretory vesicles and are expressed widely in nervous, endocrine, and neuroendocrine tissues, play roles in the regulation of body weight, feeding, and energy expenditure. Both VGF and pro-SAAS are cleaved into peptide fragments, several of which are biologically active. We utilized a highly sensitive and specific radioimmunoassay (RIA) to immunoreactive, pro-SAAS-derived PEN peptides, developed another against immunoreactive, VGF-derived AQEE30 peptides, and quantified these peptides in various mouse tissues and brain regions. Immunoreactive AQEE30 was most abundant in the pituitary, while brain levels were highest in hypothalamus, striatum, and frontal cortex. Immunoreactive PEN levels were highest in the pancreas and spinal cord, and in brain, PEN was most abundant in striatum, hippocampus, pons and medulla, and cortex. Since both peptides were expressed in hypothalamus, a region of the brain that controls feeding and energy expenditure, double label immunofluorescence studies were employed. These demonstrated that 42% of hypothalamic arcuate neurons coexpress VGF and SAAS peptides, and that the intracellular distributions of these peptides in arcuate neurons differed. By RIA, cold stress increased immunoreactive AQEE30 and PEN peptide levels in female but not male hypothalamus, while a high fat diet increased AQEE30 and PEN peptide levels in female but not male hippocampus. VGF and SAAS-derived peptides are therefore widely expressed in endocrine, neuroendocrine, and neural tissues, can be accurately quantified by RIA, and are differentially regulated in the brain by diet and cold stress.

Therapeutic efficacy of the non-peptide AVP antagonist OPC-31260 in cirrhotic rats.

PubMed

Tsuboi, Y; Ishikawa, S; Fujisawa, G; Okada, K; Saito, T

1994-07-01

The present study was undertaken to determine whether a non-peptide arginine vasopressin (AVP) antagonist [5-dimethylamino-1-(4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetra hydro-1H- benzazepine] (OPC-31260) improves the impaired water excretion in rats with experimental liver cirrhosis. Male Wistar rats weighing 200 to 250 g were injected in an equal volume (4 ml/kg) of carbon tetrachloride and olive oil at an interval of seven days for three months, causing liver cirrhosis with ascites. Control rats were injected with only olive oil. Body weight (body wt) and hematocrit (Hct) were lower in the cirrhotic rats than the control rats (body wt 360.7 vs. 238.5 g, P < 0.01; Hct 46.3 vs. 39.2%, P < 0.01). A water loading test (30 ml/kg) was carried out and 20-minute urine collections were made for three hours. The percent of water load excreted was 62.5% in the cirrhotic rats, a value significantly less than that of 102.1% in the control rats. However, its percent increased to 215.1% after the oral administration of 5 mg/kg OPC-31260 (P < 0.01). Minimal urinary osmolality (UOsm) was 185.5 mOsm/kg H2O in the cirrhotic rats receiving the vehicle, a value greater than the control rats of 125.5 mOsm/kg H2O (P < 0.01). The oral administration of 5 mg/kg OPC-31260 reduced minimal UOsm to 85.2 mOsm/kg H2O in the cirrhotic rats (P < 0.01). Urinary excretion of sodium was lower in the cirrhotic rats than the control rats (87.1 vs. 312.4 microEq/3 hr, P < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Studies on absorption and elimination of dietary maillard reaction products.

PubMed

Förster, Anke; Kühne, Yvonne; Henle, Thomas

2005-06-01

A nine-day dietary study involving 18 healthy volunteers was performed in order to investigate the influence of nutrition on the urinary excretion of the Maillard reaction products (MRPs) fructoselysine, pyrraline, and pentosidine. From day two through day eight, most types of Maillard product-containing food had to be avoided. On day five, participants were divided into four groups, three of them receiving a test meal (pretzel sticks, brewed coffee, or custard) containing defined amounts of MRPs. The fourth group served as a control. Urine samples taken over a 24-h period were analyzed for MRPs using chromatographic means. As a result of the MRP-free diet, urinary excretion of free pyrraline and fructoselysine, which was calculated from furosine analysis, were lowered about 90%. Excretion of pentosidine decreased about 40%. Consumption of pretzel sticks and coffee on day five resulted in increased amounts of pyrraline and pentosidine in urine samples on days five to seven. Related to the supplied amounts of pyrraline, about 50% were recovered in the urine samples after ingestion of the pretzel sticks. For pentosidine, 60% of the ingested free derivative from coffee brew and 2% of the peptide-bound amino acid ingested with the bakery product were recovered in the urine samples, indicating a better bioavailability for free pentosidine compared to the protein-bound form. For peptide-bound Amadori products, no influence on the excretion was observed after ingestion of the test foods, indicating degradation in the intestine or plasma to yet-unknown metabolites. In conclusion, differences concerning the excretion rate of individual MRPs point to individual resorption and metabolic pathways. These results are of importance for the discussion of a possible (patho)physiological role of dietary advanced glycation end products (AGEs).

Polymorphisms in α-Defensin–Encoding DEFA1A3 Associate with Urinary Tract Infection Risk in Children with Vesicoureteral Reflux

PubMed Central

Schwaderer, Andrew L.; Wang, Huanyu; Kim, SungHwan; Kline, Jennifer M.; Liang, Dong; Brophy, Pat D.; McHugh, Kirk M.; Tseng, George C.; Saxena, Vijay; Barr-Beare, Evan; Pierce, Keith R.; Shaikh, Nader; Manak, J. Robert; Cohen, Daniel M.; Becknell, Brian; Spencer, John D.; Baker, Peter B.; Yu, Chack-Yung

2016-01-01

The contribution of genetic variation to urinary tract infection (UTI) risk in children with vesicoureteral reflux is largely unknown. The innate immune system, which includes antimicrobial peptides, such as the α-defensins, encoded by DEFA1A3, is important in preventing UTIs but has not been investigated in the vesicoureteral reflux population. We used quantitative real–time PCR to determine DEFA1A3 DNA copy numbers in 298 individuals with confirmed UTIs and vesicoureteral reflux from the Randomized Intervention for Children with Vesicoureteral Reflux (RIVUR) Study and 295 controls, and we correlated copy numbers with outcomes. Outcomes studied included reflux grade, UTIs during the study on placebo or antibiotics, bowel and bladder dysfunction, and renal scarring. Overall, 29% of patients and 16% of controls had less than or equal to five copies of DEFA1A3 (odds ratio, 2.09; 95% confidence interval, 1.40 to 3.11; P<0.001). For each additional copy of DEFA1A3, the odds of recurrent UTI in patients receiving antibiotic prophylaxis decreased by 47% when adjusting for vesicoureteral reflux grade and bowel and bladder dysfunction. In patients receiving placebo, DEFA1A3 copy number did not associate with risk of recurrent UTI. Notably, we found that DEFA1A3 is expressed in renal epithelium and not restricted to myeloid-derived cells, such as neutrophils. In conclusion, low DEFA1A3 copy number associated with recurrent UTIs in subjects in the RIVUR Study randomized to prophylactic antibiotics, providing evidence that copy number polymorphisms in an antimicrobial peptide associate with UTI risk. PMID:26940096

Prediction of the severity of acute pancreatitis on admission by urinary trypsinogen activation peptide: A meta-analysis

PubMed Central

Huang, Wei; Altaf, Kiran; Jin, Tao; Xiong, Jun-Jie; Wen, Li; Javed, Muhammad A; Johnstone, Marianne; Xue, Ping; Halloran, Christopher M; Xia, Qing

2013-01-01

AIM: To undertake a meta-analysis on the value of urinary trypsinogen activation peptide (uTAP) in predicting severity of acute pancreatitis on admission. METHODS: Major databases including Medline, Embase, Science Citation Index Expanded and the Cochrane Central Register of Controlled Trials in the Cochrane Library were searched to identify all relevant studies from January 1990 to January 2013. Pooled sensitivity, specificity and the diagnostic odds ratios (DORs) with 95%CI were calculated for each study and were compared to other systems/biomarkers if mentioned within the same study. Summary receiver-operating curves were conducted and the area under the curve (AUC) was evaluated. RESULTS: In total, six studies of uTAP with a cut-off value of 35 nmol/L were included in this meta-analysis. Overall, the pooled sensitivity and specificity of uTAP for predicting severity of acute pancreatitis, at time of admission, was 71% and 75%, respectively (AUC = 0.83, DOR = 8.67, 95%CI: 3.70-20.33). When uTAP was compared with plasma C-reactive protein, the pooled sensitivity, specificity, AUC and DOR were 0.64 vs 0.67, 0.77 vs 0.75, 0.82 vs 0.79 and 6.27 vs 6.32, respectively. Similarly, the pooled sensitivity, specificity, AUC and DOR of uTAP vs Acute Physiology and Chronic Health Evaluation II within the first 48 h of admission were found to be 0.64 vs 0.69, 0.77 vs 0.61, 0.82 vs 0.73 and 6.27 vs 4.61, respectively. CONCLUSION: uTAP has the potential to act as a stratification marker on admission for differentiating disease severity of acute pancreatitis. PMID:23901239

Use of urinary biomarkers to characterize occupational exposure to BTEX in healthcare waste autoclave operators.

PubMed

Rafiee, Ata; Delgado-Saborit, Juana Maria; Gordi, Elham; Quémerais, Bernadette; Kazemi Moghadam, Vahid; Lu, Wenjing; Hashemi, Fallah; Hoseini, Mohammad

2018-08-01

Urinary benzene, toluene, ethylbenzene, and xylenes (BTEX) can be used as a reliable biomarker of exposure to these pollutants. This study was aimed to investigate the urinary BTEX concentration in operators of healthcare waste (HCW) autoclaves. This cross-sectional study was conducted in selected hospitals in Tehran, Iran between April and June 2017. Twenty operators (as the case group) and twenty control subjects were enrolled in the study. Personal urine samples were collected at the beginning and end of the work shift. Urinary BTEX were measured by a headspace gas chromatography-mass spectrometry (GC/MS). A detailed questionnaire was used to gather information from subjects. Results showed that the median of urinary benzene, toluene, ethylbenzene, m-p xylene, and o-xylene levels in the exposed group were 3.26, 3.36, 0.84, 3.94 and 4.48 μg/L, respectively. With the exception of ethylbenzene, subjects in the exposed group had significantly higher urinary BTEX levels than control group (p < 0.05). Urinary BTEX concentrations in the exposed case group were 2.5-fold higher than in the control group. There was a significant relationship between the amount of generated waste per day and the urinary BTEX in the exposed group. Smoking status and type of autoclave used were also identified as predictors of urinary BTEX concentrations. The healthcare waste treatment autoclaves can be considered as a significant BTEX exposure source for operators working with these treatment facilities. The appropriate personal protection equipment and control measures capable in reducing BTEX exposure should be provided to HCW workers to reduce their exposures to BTEX. Copyright © 2018 Elsevier B.V. All rights reserved.

Harnessing the Power of Cruciferous Vegetables: Developing a Biomarker for Brassica Vegetable Consumption Using Urinary 3,3'-Diindolylmethane.

PubMed

Fujioka, Naomi; Ransom, Benjamin W; Carmella, Steven G; Upadhyaya, Pramod; Lindgren, Bruce R; Roper-Batker, Astia; Hatsukami, Dorothy K; Fritz, Vincent A; Rohwer, Charles; Hecht, Stephen S

2016-10-01

Glucobrassicin in Brassica vegetables gives rise to indole-3-carbinol (I3C), a compound with potent anticancer effects in preclinical models. We previously showed that the urinary metabolite 3,3'-diindolylmethane (DIM) could discriminate between volunteers fed high and low doses of Brassica vegetables. However, the quantitative relationship between glucobrassicin exposure and urinary DIM level is unclear. We conducted a clinical trial to examine the hypotheses that a range of glucobrassicin exposure from Brassica vegetables is reflected in urinary DIM and that this effect plateaus. Forty-five subjects consumed vegetables, a mixture of brussels sprouts and/or cabbage, at one of seven discrete dose levels of glucobrassicin ranging from 25 to 500 μmol, once daily for 2 consecutive days. All urine was collected for 24 hours after each vegetable-eating session. Urinary DIM was measured using our published liquid chromatography-electrospray ionization-tandem mass spectrometry-selected reaction monitoring (LC/ESI-MS/MS-SRM) method. Urinary DIM excretion increased predictably with increasing glucobrassicin dose and plateaued between 200 and 300 μmol of glucobrassicin. The association between glucobrassicin dose and urinary DIM was strong and positive (R 2 = 0.68). The majority of DIM was excreted in the first 12 hours after vegetable consumption. We conclude that urinary DIM is a reliable biomarker of glucobrassicin exposure and I3C uptake and that feeding glucobrassicin beyond 200 μmol did not consistently lead to more urinary DIM, suggesting a plateau in potential chemopreventive benefit. Cancer Prev Res; 9(10); 788-93. ©2016 AACR. ©2016 American Association for Cancer Research.

Association between maternal urinary chromium and premature rupture of membranes in the Healthy Baby Cohort study in China.

PubMed

Huang, Sha; Xia, Wei; Li, Yuanyuan; Zhang, Bin; Zhou, Aifen; Zheng, Tongzhang; Qian, Zhengmin; Huang, Zheng; Lu, Shi; Chen, Zhong; Wang, Youjie; Pan, Xinyun; Huo, Wenqian; Jin, Shuna; Jiang, Yangqian; Xu, Shunqing

2017-11-01

Chromium exposure from increasing industrial releases has become a threat for pregnant women due to the potential health effects on vulnerable embryos. Previous studies have suggested that maternal chromium exposure is associated with adverse birth outcomes, but no epidemiological research has been conducted to examine the relationship between chromium exposure and premature rupture of membranes (PROM). This study aimed at investigating the association of maternal urinary chromium exposure levels with PROM and was performed with 5408 pregnant women recruited from 2012 to 2014 in the city of Wuhan, China. Maternal urinary chromium collected before labor was adjusted with creatinine, and its association with PROM was evaluated using logistic regression. Each one unit increase in the natural logarithm transformed maternal urinary chromium concentration (μg/g creatinine), an odds ratio (OR) of 1.47 [95% confidence interval (CI): 1.36, 1.58] for PROM was observed. Compared to the lowest tertile of maternal urinary chromium, PROM was positively correlated with increased urinary levels of chromium (adjusted OR = 1.42; 95% CI: 1.09, 1.84 for the medium tertile; adjusted OR = 2.77; 95% CI: 2.18, 3.52 for the highest tertile). Additionally, the association of chromium with PROM appeared to be more significant among male infants (adjusted OR = 3.52; 95% CI: 2.51, 4.94 for the highest tertile) than female infants (adjusted OR = 2.16; 95% CI: 1.52, 3.06 for the highest tertile) (p for interaction = 0.05). Our large birth cohort showed an association between maternal urinary chromium levels and PROM, and the association may differ by infant gender. Further studies from different populations are needed to confirm the observed association. Copyright © 2017 Elsevier Ltd. All rights reserved.

Circadian characteristics of urinary leukotriene E(4) in healthy subjects and nocturnal asthmatic patients.

PubMed

Kurokawa, K; Tanaka, H; Tanaka, S; Abe, S

2001-12-01

Circadian rhythmicity of cysteinyl leukotrienes (LTs) and thromboxane (TX)-A(2) in healthy subjects and nocturnal asthmatic patients remains a subject of controversy. The aim of this study was to investigate the contribution of these mediators to the pathogenesis of nocturnal asthma. We measured peak expiratory flow rate, urinary concentration of LTE(4), 11-dehydro-TXB(2), and creatinine eight times every 3 h in three groups: healthy control subjects (n = 5, group A), nocturnal asthmatic patients (n = 9, group B), and nonnocturnal asthmatic subjects (n = 9, group C). To evaluate the reproducibility of the measurement of urinary LTE(4), we measured urinary LTE(4) in group A for 3 separate days. The urinary LTE(4) concentrations from 3 to 6 AM were significantly (p < 0.05) higher than from 3 to 6 PM in both group A and group B, but not in group C. The mean levels of LTE(4) in group B and group C were significantly higher (p < 0.05) than those in group A. In group B, another small peak was observed from 6 to 9 PM. No significant day-to-day variation was observed in group A. Urinary 11-dehydro-TXB(2) values from 3 to 6 AM were significantly (p < 0.001) higher than those levels from 3 to 6 PM in all groups, and the mean levels in group B and group C were significantly higher than those in group A (p < 0.05). Circadian rhythmicity of urinary LTE(4) with a morning peak was found in healthy control subjects and nocturnal asthmatic subjects, but not in nonnocturnal asthmatic patients. It was suggested that cysteinyl LTs rather than TXA(2) might contribute to the nocturnal worsening of asthma.

Urinary level of nickel and acute leukaemia in Chinese children.

PubMed

Yang, Y; Jin, X M; Yan, C H; Tian, Y; Tang, J Y; Shen, X M

2008-10-01

The 8-hydroxy-2'-deoxyguanosine (8-OHdG), an oxidized nucleoside of DNA, not only is a widely used biomarker for the measurement of endogenous oxidative DNA damage but might also be a risk factor for many diseases including cancer. Metal exposure may play an important role in oxidative DNA damage among children. However, few studies on urinary 8-OHdG and metals have been conducted in children with acute leukemia. In the present study, urinary Ni and 8-OHdG were examined in 116 children with acute leukaemia (94 acute lymphoid leukaemia [ALL] and 22 acute myeloid leukaemia [AML]) and 51 healthy child controls. Our result showed that urinary Ni in acute leukaemia patients (ALL: 68.40 +/- 133.98, AML: 41.48 +/- 76.31 ng/mg creatinine) was significantly higher than that in controls (62.47 +/- 124.90 vs 17.63 +/- 46.17 ng/mg creatinine, P < 0.05). Similarly, the pretherapy level of urinary 8-OHdG in patients (ALL: 11.83 +/- 16.23, AML: 12.36 +/- 11.36 ng/mg creatinine) was significantly elevated compared with controls (11.92 +/- 15.42 vs 4.03 +/- 4.70 ng/mg creatinine, P < 0.05). Moreover, urinary 8-OHdG and urinary Ni showed a weak but significant association with increased risk of childhood leukaemia. The present study suggests that Ni may be an etiologic factor for childhood acute leukaemia by oxidative DNA damage.

Detection of occupational lead nephropathy using early renal markers.

PubMed

Kumar, B D; Krishnaswamy, K

1995-01-01

Automotive use of leaded gasoline continues to be an important source of occupational exposure to lead in India and other countries. The present study assessed the renal function and markers of early renal damage of 22 mechanics at three automobile garages. Urinary N-acetyl-3-D-glucosaminidase activity and beta-2-microglobulin levels were significantly increased in auto garage mechanics with blood leads of 30-69 micrograms/dL. A significant correlation was observed between blood lead levels and urinary N-acetyl-3-D-glucosaminidase activity but not with urine beta-2-microglobulin levels. A marginal impairment in creatinine clearance was not statistically significant. Urinary N-acetyl-3-D-glucosaminidase activity offers a sensitive monitor of blood lead and renal tubular injury.

Work Environment Factors and Their Influence on Urinary Chromium Levels in Informal Electroplating Workers

NASA Astrophysics Data System (ADS)

Setyaningsih, Yuliani; Husodo, Adi Heru; Astuti, Indwiani

2018-02-01

One of the informal sector which absorbs labor was electroplating business. This sector uses chromium as coating material because it was strong, corrosion resistant and strong. Nonetheless hexavalent chromium is highly toxic if inhaled, swallowed and contact with skin. Poor hygiene, the lack of work environment factors and sanitation conditions can increase the levels of chromium in the body. This aimed of this study was to analyze the association between work environment factors and levels of urinary chromium in informal electroplating worker. A Purposive study was conducted in Tegal Central Java. The research subjects were 66 male workers. Chi Square analysis was used to establish an association between work environment factors and level of urinary chromium. There is a relationship between heat stress and wind direction to the chromium levels in urine (p <0.05), but there is no relationship between humidity and levels of chromium in the urine (p> 0.05). This explains that work environment factors can increase chromium levels in the urine of informal electroplating workers.

Lime powder treatment reduces urinary excretion of total protein and transferrin but increases uromodulin excretion in patients with urolithiasis.

PubMed

Tosukhowong, Piyaratana; Kulpradit, Pimsuda; Chaiyarit, Sakdithep; Ungjareonwattana, Wattanachai; Kalpongnukul, Nuttiya; Ratchanon, Supoj; Thongboonkerd, Visith

2018-06-01

Our previous study has shown that lime powder (LP) had an inhibitory effect against calcium oxalate stone formation. However, the precise mechanisms underlying such beneficial effect remained unclear. Our present study thus aimed to address the effect of LP on excretory level and compositions of urinary proteins using a proteomics approach. From a total of 80 calcium oxalate stone formers recruited into our 2-year randomized clinical trial of LP effect, 10 patients with comparable age and clinical parameters were selected for this proteomic study. 24-h urine specimens were collected from all subjects, at baseline (before) and after LP treatment for 6 months, and then subjected to quantitative proteomics analysis and subsequent validation by ELISA. Total urinary protein excretion was significantly decreased by LP treatment, but unaffected by placebo. Nanoflow liquid chromatography coupled to tandem mass spectrometry (nanoLC-MS/MS) followed by quantitative analysis revealed 17 proteins whose levels were significantly altered (16 decreased and 1 increased) exclusively by LP treatment. Among these, the decrease of transferrin and increase of uromodulin were validated by ELISA. Moreover, there was a significant correlation between microalbuminuria and urinary transferrin level by Pearson's correlation test. In summary, LP treatment caused significant reduction in total urinary protein excretion and changes in urinary protein compositions that could be linked to stone inhibitory effects and might be relevant mechanisms responsible for the beneficial effects of LP to prevent kidney stone formation and recurrence.

Exploring relationships of catheter-associated urinary tract infection and blockage in people with long-term indwelling urinary catheters.

PubMed

Wilde, Mary H; McMahon, James M; Crean, Hugh F; Brasch, Judith

2017-09-01

To describe and explore relationships among catheter problems in long-term indwelling urinary catheter users, including excess healthcare use for treating catheter problems. Long-term urinary catheter users experience repeated problems with catheter-related urinary tract infection and blockage of the device, yet little has been reported of the patterns and relationships among relevant catheter variables. Secondary data analysis was conducted from a sample in a randomised clinical trial, using data from the entire sample of 202 persons over 12 months' participation. Descriptive statistics were used to characterise the sample over time. Zero-inflated negative binomial models were employed for logistic regressions to evaluate predictor variables of the presence/absence and frequencies of catheter-related urinary tract infection and blockage. Catheter-related urinary tract infection was marginally associated with catheter blockage. Problems reported at least once per person in the 12 months were as follows: catheter-related urinary tract infection 57%, blockage 34%, accidental dislodgment 28%, sediment 87%, leakage (bypassing) 67%, bladder spasms 59%, kinks/twists 42% and catheter pain 49%. Regression analysis demonstrated that bladder spasms were significantly related to catheter-related urinary tract infection and sediment amount, and catheter leakages were marginally significantly and positively related to catheter-related urinary tract infection. Frequencies of higher levels of sediment and catheter leakage were significantly associated with higher levels of blockage, and being female was associated with fewer blockages. Persons who need help with eating (more disabled) were also more likely to have blockages. Catheter-related urinary tract infection and blockage appear to be related and both are associated with additional healthcare expenditures. More research is needed to better understand how to prevent adverse catheter outcomes and patterns of problems in subgroups. Nurses can develop care management strategies to identify catheter blockage prior to its occurrence by tracking the amount of sediment and frequency of leakage. Bladder spasms could be an early warning of catheter-related urinary tract infection. © 2016 John Wiley & Sons Ltd.

111In-labeled lactam bridge-cyclized alpha-melanocyte stimulating hormone peptide analogues for melanoma imaging.

PubMed

Miao, Yubin; Gallazzi, Fabio; Guo, Haixun; Quinn, Thomas P

2008-02-01

The purpose of this study was to examine the influence of the lactam bridge cyclization on melanoma targeting and biodistribution properties of the radiolabeled conjugates. Two novel lactam bridge-cyclized alpha-MSH peptide analogues, DOTA-CycMSH (1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid-c[Lys-Nle-Glu-His-DPhe-Arg-Trp-Gly-Arg-Pro-Val-Asp]) and DOTA-GlyGlu-CycMSH (DOTA-Gly-Glu-c[Lys-Nle-Glu-His-DPhe-Arg-Trp-Gly-Arg-Pro-Val-Asp]), were synthesized and radiolabeled with (111)In. The internalization and efflux of (111)In-labeled CycMSH peptides were examined in B16/F1 melanoma cells. The melanoma targeting properties, pharmacokinetics, and SPECT/CT imaging of (111)In-labeled CycMSH peptides were determined in B16/F1 melanoma-bearing C57 mice. Both (111)In-DOTA-CycMSH and (111)In-DOTA-GlyGlu-CycMSH exhibited fast internalization and extended retention in B16/F1 cells. The tumor uptake values of (111)In-DOTA-CycMSH and (111)In-DOTA-GlyGlu-CycMSH were 9.53+/-1.41% injected dose/gram (% ID/g) and 10.40+/-1.40% ID/g at 2 h postinjection, respectively. Flank melanoma tumors were clearly visualized with (111)In-DOTA-CycMSH and (111)In-DOTA-GlyGlu-CycMSH by SPECT/CT images at 2 h postinjection. Whole-body clearance of the peptides was fast, with greater than 90% of the radioactivities cleared through urinary system by 2 h postinjection. There was low radioactivity (<0.8% ID/g) accumulated in blood and normal organs except kidneys at all time points investigated. Introduction of a negatively charged linker (-Gly-Glu-) into the peptide sequence decreased the renal uptake by 44% without affecting the tumor uptake at 4 h postinjection. High receptor-mediated melanoma uptakes coupled with fast whole-body clearance in B16/F1 melanoma-bearing C57 mice demonstrated the feasibility of using (111)In-labeled lactam bridge-cyclized alpha-MSH peptide analogues as a novel class of imaging probes for receptor-targeting melanoma imaging.

Nursing students' knowledge and attitudes toward urinary incontinence: A cross-sectional survey.

PubMed

Luo, Yan; Parry, Monica; Huang, Yan-Jin; Wang, Xiu-Hua; He, Guo-Ping

2016-05-01

Nurses must have adequate knowledge to manage the complexities of urinary incontinence. Nursing students are the nurses of the future, yet little is known about urinary incontinence education in undergraduate nursing programs. The aim of this study was (a) to assess the knowledge and attitudes of urinary incontinence held by undergraduate nursing students in China and (b) to explore the relationship between knowledge, attitudes and socio-demographic characteristics. A cross-sectional survey using cluster random sampling. Undergraduate departments of Nursing within the Faculty of Health Sciences at six Universities, located in different areas of China. A random selection of 6 faculties with a total of 1313 full time undergraduate nursing students completed the survey. Self-reported data were collected using two validated questionnaires, the Urinary Incontinence Knowledge Scale and the Urinary Incontinence Attitude Scale, to access students' knowledge and attitudes toward urinary incontinence. Overall urinary incontinence knowledge was poor (49.9%, 15.0/30) and attitudes about urinary incontinence were generally positive (71.7%, 43.0/60). A high level of interest in learning more about urinary incontinence was found. There was a weak correlation between urinary incontinence knowledge and attitudes (r=0.135, p<0.01). There was also a significant positive correlation between urinary incontinence knowledge and attitudes and nursing students' year of study, urinary incontinence education and training, and formal clinical practicum experience in urology (p<0.05). Chinese nursing students showed poor urinary incontinence knowledge but generally positive attitudes toward urinary incontinence. This study suggests there is a need to examine urinary incontinence content throughout undergraduate nursing curricula in China. Copyright © 2016 Elsevier Ltd. All rights reserved.

Microplate magnetic chemiluminescence immunoassay for detecting urinary survivin in bladder cancer.

PubMed

Chang, Yanli; Xu, Jianjun; Zhang, Qingyun

2017-10-01

Survivin is a tumor marker for bladder cancer; however the role of urinary survivin levels has not been fully elucidated due to the limitations of current detection methods. Based on two survivin-specific monoclonal antibodies (McAbs) already confirmed through enzyme linked immunosorbent assays, the present study aimed to establish a microplate magnetic chemiluminescence immunoassay (CLIA) for the detection of urinary survivin levels and evaluate its application for the diagnosis of patients with bladder cancer. Horseradish peroxidase and biotin conjugates were used to label two different anti-survivin McAbs, respectively. The labeled antibodies combined with survivin to form a sandwiched immune complex. The streptavidin magnetic particles (MPs) served as the solid phase and the separator. The relevant parameters involved in the immunoassay, including the immunoassay reagents used and the physicochemical parameters were optimized. Then, urine samples from 130 patients with bladder cancer and 113 healthy controls were detected, and analyzed using the established method. The method was linear to 1,000 ng/ml survivin with a detection limit of 0.83 ng/ml. The intra- and inter-assay coefficients of variation were <8, and <11%, respectively. The concentration of diluted survivin and the dilution ratios gave a linear correlation of 0.9989. The results demonstrated that the urinary survivin levels in patients with bladder cancer were significantly higher (P<0.001) compared with that in healthy controls. At a survivin concentration of 2.0884 ng/ml, the sensitivity and specificity were 86.9 and 61.9%, respectively. Furthermore, the urinary survivin levels were positively correlated with metastatic stage, histological stage and recurrence (P<0.01). In conclusion, the present study preliminarily proposed a microplate magnetic CLIA for survivin detection and further evaluated the value of urinary survivin as a diagnostic marker for bladder cancer.

Microplate magnetic chemiluminescence immunoassay for detecting urinary survivin in bladder cancer

PubMed Central

Chang, Yanli; Xu, Jianjun; Zhang, Qingyun

2017-01-01

Survivin is a tumor marker for bladder cancer; however the role of urinary survivin levels has not been fully elucidated due to the limitations of current detection methods. Based on two survivin-specific monoclonal antibodies (McAbs) already confirmed through enzyme linked immunosorbent assays, the present study aimed to establish a microplate magnetic chemiluminescence immunoassay (CLIA) for the detection of urinary survivin levels and evaluate its application for the diagnosis of patients with bladder cancer. Horseradish peroxidase and biotin conjugates were used to label two different anti-survivin McAbs, respectively. The labeled antibodies combined with survivin to form a sandwiched immune complex. The streptavidin magnetic particles (MPs) served as the solid phase and the separator. The relevant parameters involved in the immunoassay, including the immunoassay reagents used and the physicochemical parameters were optimized. Then, urine samples from 130 patients with bladder cancer and 113 healthy controls were detected, and analyzed using the established method. The method was linear to 1,000 ng/ml survivin with a detection limit of 0.83 ng/ml. The intra- and inter-assay coefficients of variation were <8, and <11%, respectively. The concentration of diluted survivin and the dilution ratios gave a linear correlation of 0.9989. The results demonstrated that the urinary survivin levels in patients with bladder cancer were significantly higher (P<0.001) compared with that in healthy controls. At a survivin concentration of 2.0884 ng/ml, the sensitivity and specificity were 86.9 and 61.9%, respectively. Furthermore, the urinary survivin levels were positively correlated with metastatic stage, histological stage and recurrence (P<0.01). In conclusion, the present study preliminarily proposed a microplate magnetic CLIA for survivin detection and further evaluated the value of urinary survivin as a diagnostic marker for bladder cancer. PMID:28943911

Smoking modify the effects of polycyclic aromatic hydrocarbons exposure on oxidative damage to DNA in coke oven workers.

PubMed

Yang, Jin; Zhang, Hongjie; Zhang, Huitao; Wang, Wubin; Liu, Yanli; Fan, Yanfeng

2017-07-01

Coke oven emissions containing polycyclic aromatic hydrocarbons (PAHs) are predominant toxic constituents of particulate air pollution that have been linked to increased risk of lung cancer. Numerous epidemiological studies have suggested that oxidative DNA damage may play a pivotal role in the carcinogenic mechanism of lung cancer. Little is known about the effect of interaction between PAHs exposure and lifestyle on DNA oxidative damage. The study population is composed by coke oven workers (365) and water treatment workers (144), and their urinary levels of four PAH metabolites and 8-hydroxydeoxyguanosine (8-OHdG) were determined. Airborne samples of exposed sites (4) and control sites (3) were collected, and eight carcinogenic PAHs were detected by high-performance liquid chromatography. The median values of the sum of eight carcinogenic PAHs and BaP in exposed sites were significantly higher than control sites (P < 0.01). The study found that the urinary PAH metabolites were significantly elevated in coke oven workers (P < 0.01). Multivariate logistic regression analysis revealed that the risk of high levels of urinary 8-OHdG will increase with increasing age, cigarette consumption, and levels of urinary 1-hydroxypyrene, and P for trend were all <0.05. Smoking can significantly modify the effects of urinary 1-hydroxypyrene on high concentrations urinary 8-OHdG, during co-exposure to both light or heavy smoking and high 1-hydroxypyrene levels (OR 4.28, 95% CI 1.32-13.86 and OR 5.05, 95% CI 1.63-15.67, respectively). Our findings quantitatively demonstrate that workers exposed to coke oven fumes and smoking will cause more serious DNA oxidative damage.

Urinary arsenic, pesticides, heavy metals, phthalates, polyaromatic hydrocarbons, and polyfluoroalkyl compounds are associated with sleep troubles in adults: USA NHANES, 2005-2006.

PubMed

Shiue, Ivy

2017-01-01

Links between environmental chemicals and human health have emerged, but the effects on sleep health were less studied. Therefore, the aim of the present study was to investigate the relationships of different sets of environmental chemicals and common sleep troubles in a national and population-based setting. Data were retrieved from the United States National Health and Nutrition Examination Surveys, 2005-2006 including demographics, serum measurements, lifestyle factors, self-reported sleep troubles, and urinary environmental chemical concentrations. Statistical analyses including descriptive statistics, t-test, chi-square test, and survey-weighted logistic regression models were performed. Of all 5563 Americans aged 18-85, 2331 (42.0%) had wake-up at night, 2914 (52.5%) felt unrested during the day, 740 (13.4%) had leg jerks while sleeping, and 1059 (19.1%) had leg cramps for 2+ times a month. Higher levels of urinary arsenic, phthalates, and polyfluoroalkyl compounds were associated with wake-up at night. Higher levels of urinary 4-tert-octylphenol and polyfluoroalkyl compounds were associated with being unrested during the day. Higher levels of urinary arsenic, polyaromatic hydrocarbons, and polyfluoroalkyl compounds were associated with leg jerks while sleeping. Higher levels of urinary pesticides, heavy metals, phthalates, and polyaromatic hydrocarbons were associated with leg cramps while sleeping. However, there were no significant associations with other environmental chemicals such as parabens, bisphenol A, benzophenone-3, triclosan, perchlorate, nitrate, or thiocyanate. Eliminating arsenic, heavy metals, phthalate, pesticides, polyaromatic hydrocarbons, and polyfluoroalkyl compounds to improve sleep health might be considered while understanding the biological pathway with a longitudinal or experimental approach in future research would be suggested.

Estimating 24-Hour Urinary Sodium Excretion From Casual Urinary Sodium Concentrations in Western Populations

PubMed Central

Brown, Ian J.; Dyer, Alan R.; Chan, Queenie; Cogswell, Mary E.; Ueshima, Hirotsugu; Stamler, Jeremiah; Elliott, Paul

2013-01-01

High intakes of dietary sodium are associated with elevated blood pressure levels and an increased risk of cardiovascular disease. National and international guidelines recommend reduced sodium intake in the general population, which necessitates population-wide surveillance. We assessed the utility of casual (spot) urine specimens in estimating 24-hour urinary sodium excretion as a marker of sodium intake in the International Cooperative Study on Salt, Other Factors, and Blood Pressure. There were 5,693 participants recruited in 1984–1987 at the ages of 20–59 years from 29 North American and European samples. Participants were randomly assigned to test or validation data sets. Equations derived from casual urinary sodium concentration and other variables in the test data were applied to the validation data set. Correlations between observed and estimated 24-hour sodium excretion were 0.50 for individual men and 0.51 for individual women; the values were 0.79 and 0.71, respectively, for population samples. Bias in mean values (observed minus estimated) was small; for men and women, the values were −1.6 mmol per 24 hours and 2.3 mmol per 24 hours, respectively, at the individual level and −1.8 mmol per 24 hours and 2.2 mmol per 24 hours, respectively, at the population level. Proportions of individuals with urinary 24-hour sodium excretion above the recommended levels were slightly overestimated by the models. Casual urine specimens may be a useful, low-burden, low-cost alternative to 24-hour urine collections for estimation of population sodium intakes; ongoing calibration with study-specific 24-hour urinary collections is recommended to increase validity. PMID:23673246

Increase in urinary purines and pyrimidines in patients with methylmalonic aciduria combined with homocystinuria.

PubMed

Porcu, Simona; Corda, Marcella; Lilliu, Franco; Contini, Liliana; Era, Benedetta; Traldi, Pietro; Fais, Antonella

2010-06-03

Methylmalonic aciduria combined with homocystinuria (MMA-HC) is the biochemical trait of a metabolic disorder resulting from impaired conversion of dietary cobalamin (cbl, or vitamin B12) to its two metabolically active forms. Effects on urinary purine and pyrimidine levels have not been described for this condition. Urine samples were collected from three patients with methylmalonic aciduria combined with homocystinuria and from 70 healthy subjects. Urinary purine and pyrimidine levels were quantitated by the use of LC/UV-Vis and LC/ESI/MS. Higher urine levels of pyrimidines were detected with both methods in patients compared to controls. Methylmalonic aciduria with homocystinuria is due to deficiency of the enzyme, cobalamin reductase. The enzyme defect leads to altered hepatic metabolism, which appears to modify circulating pyrimidine levels. Copyright 2010 Elsevier B.V. All rights reserved.

Induced resistance to the antimicrobial peptide lactoferricin B in Staphylococcus aureus.

PubMed

Samuelsen, Orjan; Haukland, Hanne H; Jenssen, Håvard; Krämer, Manuela; Sandvik, Kjersti; Ulvatne, Hilde; Vorland, Lars H

2005-06-20

This study was designed to investigate inducible intrinsic resistance against lactoferricin B in Staphylococcus aureus. Serial passage of seven S. aureus strains in medium with increasing concentrations of peptide resulted in an induced resistance at various levels in all strains. The induced resistance was unstable and decreased relatively rapidly during passages in peptide free medium but the minimum inhibitory concentration remained elevated after thirty passages. Cross-resistance to penicillin G and low-level cross-resistance to the antimicrobial peptides indolicidin and Ala(8,13,18)-magainin-II amide [corrected] was observed. No cross-resistance was observed to the human cathelicidin LL-37. In conclusion, this study shows that S. aureus has intrinsic resistance mechanisms against antimicrobial peptides that can be induced upon exposure, and that this may confer low-level cross-resistance to other antimicrobial peptides.

The presence of food-derived collagen peptides in human body-structure and biological activity.

PubMed

Sato, Kenji

2017-12-13

It has been demonstrated that the ingestion of some protein hydrolysates exerts health-promoting effects. For understanding the underlying mechanisms responsible for these effects, the identification of bioactive peptides in the target organ is crucial. For this purpose, in vitro activity-guided fractionation for peptides in the protein hydrolysate has been performed. However, the peptides in the hydrolysate may be further degraded during digestion. The concentration of the active peptides, which were identified by in vitro activity-guided fractionation, in human blood is frequently very low (nanomolar levels). In contrast, micromolar levels of food-derived collagen peptides are present in human blood. Pro-Hyp, one of the major food-derived collagen peptides, enhances the growth of fibroblasts and synthesis of hyaluronic acid. These observations partially explain the beneficial effects of collagen hydrolysate ingestion on the enhancement of wound healing and improvement in the skin condition. The recent advancement involving liquid chromatography and mass spectrometry coupled with a pre-column derivatization technique has enabled the identification of food-derived peptides at nanomolar levels in the body post-ingestion of protein hydrolysates. Thus, this technique can be used for the identification of bioactive food-derived peptides in the body.

Effects of sodium intake and diet on racial differences in urinary potassium excretion: results from the Dietary Approaches to Stop Hypertension (DASH)-Sodium trial.

PubMed

Turban, Sharon; Thompson, Carol B; Parekh, Rulan S; Appel, Lawrence J

2013-01-01

We previously showed that African Americans excreted less urinary potassium than whites, even while consuming similar diets in the Dietary Approaches to Stop Hypertension (DASH) trial. We hypothesized that a low-sodium diet may eliminate these differences. Data from the DASH-Sodium randomized controlled feeding trial were analyzed. 412 adults with prehypertension or stage 1 hypertension. Random assignment to either a typical American "control" diet (1.7 g [43 mEq] potassium/2,100 kcal/d) or the DASH diet (4.1 g [105 mEq] potassium/2,100 kcal/d). Within each diet, participants received 3 levels of sodium intake in random order for 30 days. 24-hour urine samples were analyzed at the end of each period. The primary outcome was urinary potassium excretion. On the DASH diet, African Americans consistently excreted significantly less urinary potassium (mean 24-hour urinary potassium excretion, 2,594 ± 961 mg [66 ± 25 mEq]) than whites (3,412 ± 1,016 mg [87 ± 26 mEq]) at the highest sodium level; adjusted (P < 0.001); this difference was not altered by sodium level (P = 0.6 comparing white to African American difference in urinary potassium excretion on high- vs low-sodium diet). In contrast, there was a smaller but significant white-African American difference in mean daily urinary potassium excretion in participants fed the control/high-sodium diet that was not present in the control/low-sodium diet (adjusted differences of 281 mg [7 mEq]/d vs 20 mg [0.5 mEq]/d, respectively; P = 0.007). Significant interactions were found between race and diet (P < 0.001) and between race and sodium (P = 0.02). Single rather than multiple urine collections were available at each time. Lack of stool potassium and sweat potassium values. Racial differences in urinary potassium excretion depend on sodium intake and diet. Our results may help explain the previously documented large variability in urinary potassium excretion. Copyright © 2012 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

Comparison of Urinary Biomarkers of Exposure in Humans Using Electronic Cigarettes, Combustible Cigarettes, and Smokeless Tobacco.

PubMed

Lorkiewicz, Pawel; Riggs, Daniel W; Keith, Rachel J; Conklin, Daniel J; Xie, Zhengzhi; Sutaria, Saurin; Lynch, Blake; Srivastava, Sanjay; Bhatnagar, Aruni

2018-06-02

Cigarette smoking is associated with an increase in cardiovascular disease risk, attributable in part to reactive volatile organic chemicals (VOCs). However, little is known about the extent of VOC exposure due to the use of other tobacco products. We recruited 48 healthy, tobacco users in four groups: cigarette, smokeless tobacco, occasional users of first generation e-cigarette and e-cigarette menthol and 12 healthy nontobacco users. After abstaining for 48 h, tobacco users used an assigned product. Urine was collected at baseline followed by five collections over a 3-h period to measure urinary metabolites of VOCs, nicotine, and tobacco alkaloids. Urinary levels of nicotine were ≃2-fold lower in occasional e-cigarette and smokeless tobacco users than in the cigarette smokers; cotinine and 3-hydroxycotinine levels were similar in all groups. Compared with nontobacco users, e-cigarette users had higher levels of urinary metabolites of xylene, cyanide, styrene, ethylbenzene, and benzene at baseline and elevated urinary levels of metabolites of xylene, N,N-dimethylformamide, and acrylonitrile after e-cigarette use. Metabolites of acrolein, crotonaldehyde, and 1,3-butadiene were significantly higher in smokers than in users of other products or nontobacco users. VOC metabolite levels in smokeless tobacco group were comparable to those found in nonusers with the exception of xylene metabolite-2-methylhippuric acid (2MHA), which was almost three fold higher than in nontobacco users. Smoking results in exposure to a range of VOCs at concentrations higher than those observed with other products, and first generation e-cigarette use is associated with elevated levels of N,N-dimethylformamide and xylene metabolites. This study shows that occasional users of first generation e-cigarettes have lower levels of nicotine exposure than the users of combustible cigarettes. Compared with combustible cigarettes, e-cigarettes, and smokeless tobacco products deliver lower levels of most VOCs, with the exception of xylene, N,N-dimethylformamide, and acrylonitrile, whose metabolite levels were higher in the urine of e-cigarette users than nontobacco users. Absence of anatabine in the urine of e-cigarette users suggests that measuring urinary levels of this alkaloid may be useful in distinguishing between users of e-cigarettes and combustible cigarettes. However, these results have to be validated in a larger cohortcomprised of users of e-cigarettes of multiple brands.

Effects of Transdermal Testosterone on Natriuretic Peptide Levels in Women: A Randomized Placebo-Controlled Pilot Study

PubMed Central

Lin, Eleanor; McCabe, Elizabeth; Newton-Cheh, Christopher; Bloch, Kenneth; Buys, Emmanuel; Wang, Thomas; Miller, Karen K.

2011-01-01

Objective To investigate whether testosterone administration alters natriuretic peptide levels in women. Design Three-month, double-blind, randomized, placebo-controlled study. Setting Clinical research center. Patients 51 women with hypoandrogenemia due to hypopituitarism. Intervention Transdermal testosterone (300 mcg daily) or placebo patch. Main Outcome Measure N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels. Results NT-proBNP levels decreased in the transdermal testosterone group compared with placebo over three months (p = 0.009). The difference between groups remained significant after controlling for baseline age, systolic blood pressure, body mass index, and homeostasis model of assessment-insulin resistance (p = 0.008). Change in NT-proBNP over three months was inversely associated with change in free testosterone levels (ρ = −0.41, p = 0.01). Conclusions Testosterone administration to women results in decreased natriuretic peptide levels, suggesting that testosterone may be an inverse regulator of the natriuretic peptide system. Clinical Trials Registration Number NCT00027430 PMID:22137497

Calcitriol Reduces Albuminuria and Urinary Angiotensinogen Level in Renal Transplant Recipients.

PubMed

Tiryaki, O; Usalan, C; Tarakcioglu, M; Coban, S

2018-06-01

Although nonhuman animal models have strongly suggested that vitamin D suppresses the renin-angiotensin system (RAS) and albuminuria, human data are largely lacking. The aim of this study was to examine the relationship between 25-hydroxyvitamin D [25-(OH)D] level and albuminuria and urinary angiotensinogen (UAGT) level in renal transplant recipients (RTRs). We also planned to investigate the effect of calcitriol treatment on albuminuria and UAGT level in these patients. A total of 124 nondiabetic RTRs participated in this study. UAGT level was positively correlated with the urinary albumin-creatinine ratio (UACR) in all patients (r = 0.855; P < .001). The mean UACR (P = .036) and UAGT/urinary creatinine (UCr) level (P = .02) were significantly higher in RTRs with low 25-(OH)D than in RTRs with normal 25-(OH)D level. RTRs with low 25-(OH)D level were randomized to receive either 0.25 μg/d calcitriol (n = 40) or placebo (n = 40). All of the parameters were assessed again 12 months later in both groups. The mean UACR (P = .014) and UAGT/UCr level (P = .012) were significantly lower in the calcitriol group than in the placebo group at the end of the study. Low 25-(OH)D status may be related to the elevation in albuminuria and UAGT, and calcitriol may have a beneficial effect on albuminuria through the inhibition of intrarenal RAS in RTRs. Copyright © 2018 Elsevier Inc. All rights reserved.

Association between urinary sodium excretion and uric acid, and its interaction on the risk of prehypertension among Chinese young adults.

PubMed

Wang, Yang; Hu, Jia-Wen; Qu, Peng-Fei; Wang, Ke-Ke; Yan, Yu; Chu, Chao; Zheng, Wen-Ling; Xu, Xian-Jing; Lv, Yong-Bo; Ma, Qiong; Gao, Ke; Yuan, Yue; Li, Hao; Yuan, Zu-Yi; Mu, Jian-Jun

2018-05-17

High uric acid (UA) level and high salt intake are reportedly associated with cardiovascular disease. This study investigated the association between UA and urinary sodium excretion, as well as its interaction on the risk of prehypertension. A total of 1869 participants without hypertension were recruited from a previously established cohort in Shaanxi Province, China. The participants were classified as normotensive or prehypertensive on the basis of their blood pressure. Increasing quartiles of sodium excretion were associated with high urinary UA/creatinine levels in prehypertensive participants. Estimated sodium excretion positively correlated with urinary UA/creatinine excretions in the prehypertensive group. In addition, the multivariate-adjusted odds ratios for prehypertension compared with normotension were 1.68 (1.27-2.22) for sodium excretion and 1.71 (1.21-2.42) for serum UA. Increasing sodium excretion and serum UA were associated with higher risk of prehypertension. Compared with the lowest quartiles, the highest sodium excretion and serum UA quartiles entailed 3.48 times greater risk of prehypertension. Sodium excretion is associated with urinary UA excretion in prehypertensive participants. The present study shows that high levels of salt intake and serum UA simultaneously are associated with a higher risk of prehypertension.

Copper Is a Host Effector Mobilized to Urine during Urinary Tract Infection To Impair Bacterial Colonization

PubMed Central

Hyre, Amanda N.; Kavanagh, Kylie; Kock, Nancy D.; Donati, George L.

2016-01-01

ABSTRACT Urinary tract infection (UTI) is a major global infectious disease affecting millions of people annually. Human urinary copper (Cu) content is elevated during UTI caused by uropathogenic Escherichia coli (UPEC). UPEC upregulates the expression of Cu efflux genes during clinical UTI in patients as an adaptive response to host-derived Cu. Whether Cu is mobilized to urine as a host response to UTI and its role in protection against UTI remain unresolved. To address these questions, we tested the hypothesis that Cu is a host effector mobilized to urine during UTI to limit bacterial growth. Our results reveal that Cu is mobilized to urine during UTI caused by the major uropathogens Proteus mirabilis and Klebsiella pneumoniae, in addition to UPEC, in humans. Ceruloplasmin, a Cu-containing ferroxidase, is found at higher levels in UTI urine than in healthy control urine and serves as the molecular source of urinary Cu during UTI. Our results demonstrate that ceruloplasmin decreases the bioavailability of iron in urine by a transferrin-dependent mechanism. Experimental UTI with UPEC in nonhuman primates recapitulates the increased urinary Cu content observed during clinical UTI. Furthermore, Cu-deficient mice are highly colonized by UPEC, indicating that Cu is involved in the limiting of bacterial growth within the urinary tract. Collectively, our results indicate that Cu is a host effector that is involved in protection against pathogen colonization of the urinary tract. Because urinary Cu levels are amenable to modulation, augmentation of the Cu-based host defense against UTI represents a novel approach to limiting bacterial colonization during UTI. PMID:28031261

Progress in cadmium-related health effects in persons with high environmental exposure in northwestern Thailand: A five-year follow-up

DOE Office of Scientific and Technical Information (OSTI.GOV)

Swaddiwudhipong, Witaya, E-mail: swaddi@hotmail.com; Limpatanachote, Pisit; Mahasakpan, Pranee

Food-borne cadmium was the principal source of exposure for persons living in the 12 cadmium-contaminated villages in Mae Sot District, Tak Province, northwestern Thailand. This report presents progress in cadmium-related health effects among persons with high cadmium exposure. The study included 436 persons who had urinary cadmium levels {>=}5 {mu}g/g creatinine and were screened for urinary cadmium, renal function, hypertension, diabetes and urinary stones in 2005 (baseline) and 2010 (5-year follow-up). Study renal biomarkers included urinary excretion of {beta}{sub 2}-microglobulin ({beta}{sub 2}-MG), total protein and calcium, serum creatinine and glomerular filtration rate (GFR). The geometric mean level of urinary cadmiummore » statistically significantly reduced from 9.5{+-}1.6 {mu}g/g creatinine in 2005 to 8.8{+-}1.6 {mu}g/g creatinine in 2010. Compared to baseline, the follow-up examination revealed significant increases in urinary {beta}{sub 2}-MG (tubular effect), urinary total protein and serum creatinine, and a decrease in GFR (glomerular effects). Progressive renal dysfunctions were similarly observed in persons both with and without reduction in cadmium intake. Significant increases in prevalence of hypertension, diabetes and urinary stones were also detected at follow-up. These three disorders were found to markedly impair renal functions in the study persons. Our study indicates that in persons with prolonged excessive cadmium exposure, toxic health effects may progress even after exposure reduction. Renal damage from cadmium can be due to its direct nephrotoxic effect and also through the related disorders causing nephropathy.« less

The relationship between sodium intake and some bone minerals and osteoporosis risk assessment instrument in postmenopausal women.

PubMed

Vafa, Mohammadreza; Soltani, Sepideh; Zayeri, Farid; Niroomand, Mahtab; Najarzadeh, Azadeh

2016-01-01

The results of the studies on the effects of sodium on bone metabolism have been inconsistent. There is no definitive answer to the question of whether sodium restriction can be associated with a lower incidence of osteoporosis. What reinforces the necessity of designing this study is the lack of findings with the approach of examining the effects of sodium on bone in our country. This was a cross-sectional study conducted on 185 retired female teachers aged 45 to 70. Sodium intake was evaluated using two methods: A 24-hour recall and a 12-hour urine sample. To assess bone health, ORAI index was calculated for each individual. Urinary calcium, phosphorus, potassium and serum vitamin D and PTH were measured as laboratory variables. To compare the general characteristics of the participants across tertiles of urinary sodium, the analysis of variance (ANOVA) was used for quantitative variables and the Chi-square test for categorical variables. Phosphorous, calcium and potassium urinary excretion rate increased with the increase in urinary sodium (p<0.05). However, the changes in serum vitamin D, and PTH levels across tertiles of urinary sodium were not significant. Changes in urinary sodium levels were not significant (p=0.933) in ORAI groups (sorted by rating). The relationship between urinary calcium and sodium was apparent in low calcium intake (r=0.415, p<0.001), but not in higher calcium intake (r=0.144, p=0.177). Although urinary calcium and potassium increased with the increase in sodium intake, no relationship was found between sodium and ORAI.

Secondary pseudohypoaldosteronism caused by urinary tract infection associated with urinary tract anomalies: case reports.

PubMed

Torun-Bayram, Meral; Soylu, Alper; Kasap-Demir, Belde; Alaygut, Demet; Türkmen, Mehmet; Kavukçu, Salih

2012-01-01

Secondary pseudohypoaldosteronism type 1 develops due to transient aldosterone resistance in renal tubules and is characterized by renal sodium loss, hyponatremia, hyperkalemia and high plasma aldosterone levels. Although many reasons are described, urinary tract infections and/or urinary tract anomalies are the most common causes. Although the cause of the tubular resistance is not known exactly, renal scar development due to obstruction and reduced sensitivity of mineralocorticoid receptors due to cytokines such as transforming growth factor (TGF)-beta are the possible mechanisms. It is seen especially within the first three months of life and the frequency decreases with age. The treatment is usually elimination of the underlying cause. In this article, we present four patients with several urinary tract anomalies and concomitant urinary tract infection who developed transient secondary pseudohypoaldosteronism.

Demographic, dietary, and urinary factors and 24-h urinary calcium excretion.

PubMed

Taylor, Eric N; Curhan, Gary C

2009-12-01

Higher urinary calcium is a risk factor for nephrolithiasis. This study delineated associations between demographic, dietary, and urinary factors and 24-h urinary calcium. Cross-sectional studies were conducted of 2201 stone formers (SF) and 1167 nonstone formers (NSF) in the Health Professionals Follow-up Study (men) and Nurses' Health Studies I and II (older and younger women). Median urinary calcium was 182 mg/d in men, 182 mg/d in older women, and 192 mg/d in younger women. Compared with NSF, urinary calcium as a fraction of calcium intake was 33 to 38% higher in SF (P values < or =0.01). In regression analyses, participants were combined because associations with urinary calcium were similar in each cohort and in SF and NSF. After multivariate adjustment, participants in the highest quartile of calcium intake excreted 18 mg/d more urinary calcium than those in the lowest (P trend =0.01). Caffeine and family history of nephrolithiasis were positively associated, whereas urinary potassium, thiazides, gout, and age were inversely associated, with urinary calcium. After multivariate adjustment, participants in the highest quartiles of urinary magnesium, sodium, sulfate, citrate, phosphorus, and volume excreted 71 mg/d, 37 mg/d, 44 mg/d, 61 mg/d, 37 mg/d, and 24 mg/d more urinary calcium, respectively, than participants in the lowest (P values trend < or =0.01). Intestinal calcium absorption and/or negative calcium balance is greater in SF than NSF. Higher calcium intakes at levels typically observed in free-living individuals are associated with only small increases in urinary calcium.

Urinary concentrations of organophosphate and carbamate pesticides in residents of a vegetarian community.

PubMed

Berman, T; Göen, T; Novack, L; Beacher, L; Grinshpan, L; Segev, D; Tordjman, K

2016-11-01

Few population studies have measured urinary levels of pesticides in individuals with vegan, vegetarian, or organic diets. The objectives of this study were to evaluate whether a vegan/vegetarian diet was associated with increased exposure to organophosphate and carbamate pesticides, and to evaluate the impact of organic consumption on pesticide exposure in vegans and vegetarians. In the current pilot study conducted in 2013-2014, we collected spot urine samples and detailed 24h recall dietary data in 42 adult residents of Amirim, a vegetarian community in Northern Israel. We measured urinary levels of non-specific organophosphate pesticide metabolites (dialkylphosphates, (DAPs)) and specific metabolites of the current-use pesticides chlorpyrifos (3,5,6-trichloro-2-pyridinol (TCPy)), propoxur (-isopropoxyphenol (IPPX)), and carbaryl (1-naphthol). Six DAP metabolites were detected in between 67 and 100% of urine samples, with highest geometric mean concentrations for dimethylphosphate (19.2μg/g). Creatinine-adjusted median concentrations of total DAPs and of TCPy were significantly higher in Amirim residents compared to the general Jewish population in Israel (0.29μmol/g compared to 0.16, p<0.05 for DAPs and 4.32μg/g compared to 2.34μg/g, p<0.05 for TCPy). Within Amirim residents, we observed a positive association between vegetable intake and urinary TCPy levels (rho=0.47, p<0.05) and lower median total dimethyl phosphate levels in individuals reporting that >25% of the produce they consume is organic (0.065μmol/L compared to 0.22, p<0.05). Results from this pilot study indicate relatively high levels of urinary organophosphate pesticide metabolite concentrations in residents of a vegetarian community, a positive association between vegetable intake and urinary levels of a chlorpyrifos specific metabolite, and lower levels of total dimethyl phosphate in individuals reporting higher intake of organic produce. Results suggest that consumption of organic produce may offer some protection from increased exposure to organophosphate pesticide residues in vegetarians. Copyright © 2016 Elsevier Ltd. All rights reserved.

Urinary Triclosan Concentrations Are Inversely Associated with Body Mass Index and Waist Circumference in the US General Population: Experience in NHANES 2003-2010

PubMed Central

Li, Shengxu; Zhao, Jinying; Wang, Guangdi; Zhu, Yun; Rabito, Felicia; Krousel-Wood, Marie; Chen, Wei; Whelton, Paul K

2015-01-01

Background Humans are extensively exposed to triclosan, an antibacterial and antifungal agent. Triclosan’s effects on human health, however, have not been carefully investigated. Objective To examine whether triclosan exposure is associated with obesity traits. Methods This study included 2,898 children (6-19 years old) and 5,066 adults (20 years or older) who participated in the National Health and Nutrition Examination Surveys (NHANES) 2003-2010 and had a detectable level of urinary triclosan. Multiple linear regression models were used to examine the association between urinary triclosan and both body mass index (BMI) and waist circumference. Results Each standard deviation increase in urinary triclosan was associated with a 0.34 (95% confidence interval, CI: 0.05, 0.64) kg/m2 lower level of BMI (p=0.02) and 0.92 (95% CI: 0.09, 1.74) cm smaller waist circumference (p=0.03) in boys, and a 0.62 (95% CI: 0.31, 0.94) kg/m2 lower level of BMI (p=0.0002) and 1.32 (95% CI: 0.54, 2.09) cm smaller waist circumference in girls (P=0.001); a 0.42 (95% CI: 0.06, 0.77) kg/m2 lower level of BMI (P=0.02) and 1.35 (95% CI: 0.48, 2.22) cm smaller waist circumference (P=0.003) in men, and a 0.71 (95% CI: 0.34, 1.07) kg/m2 lower level of BMI (P=0.0002) and 1.68 (95% CI: 0.86, 2.50) cm smaller waist circumference (P=0.0001) in women. In both children and adults, there was a consistent trend for lower levels of BMI and smaller waist circumference with increasing levels of urinary triclosan, from the lowest to the highest quartile of urinary triclosan (P≤0.001 in all cases). Conclusion Triclosan exposure is inversely associated with BMI and waist circumference. The biological mechanisms linking triclosan exposure to obesity await further investigation. PMID:25823951

Maternal Urinary Triclosan Concentration in Relation to Maternal and Neonatal Thyroid Hormone Levels: A Prospective Study.

PubMed

Wang, Xu; Ouyang, Fengxiu; Feng, Liping; Wang, Xia; Liu, Zhiwei; Zhang, Jun

2017-06-27

Triclosan (TCS) is a synthetic antibacterial chemical widely used in personal care products. TCS exposure has been associated with decreased thyroid hormone levels in animals, but human studies are scarce and controversial. We evaluated the association between maternal TCS exposure and thyroid hormone levels of mothers and newborns. TCS was measured by high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) in urine samples collected during gestational weeks 38.8±1.1 from 398 pregnant women in a prospective birth cohort enrolled in 2012-2013 in Shanghai, China. Maternal serum levels of free thyroxine (FT 4 ), thyroid-stimulating hormone (TSH), and thyroid peroxidase antibody (TPOAb) were obtained from medical records. Cord blood levels of free triiodothyronine (FT 3 ), FT 4 , TSH, and TPOAb were measured. Multiple linear and logistic regression models were used to examine the relationship between maternal urinary TCS and thyroid hormone levels. TCS was detectable (≥0.1 ng/mL) in 98.24% of maternal urine samples with tertile of urinary TCS levels: low (>0.1-2.75 μg/g.Cr), medium (2.75–9.78 μg/g.Cr), and high (9.78–427.38 μg/g.Cr). With adjustment for potential confounders, cord blood log(FT 3 )pmol/L concentration was 0.11 lower in newborns of mothers with medium and high urinary TCS levels compared with those with low levels. At third trimester, the high TCS concentration was associated with 0.03 [95% confidence interval (CI) −0.08, −0.02] lower maternal serum log(FT 4 )pmol/L, whereas the medium TCS concentration was associated with 0.15 (95% CI: −0.28, −0.03) lower serum log(TSH)mIU/L with adjustment for covariates. Our results suggest significant inverse associations between maternal urinary TCS and cord blood FT 3 as well as maternal blood FT 4 concentrations at third trimester. https://doi.org/10.1289/EHP500.

Urinary ATP May Be a Dynamic Biomarker of Detrusor Overactivity in Women with Overactive Bladder Syndrome

PubMed Central

Oliveira, Olga; Ferreira, Sónia; Reis, Maria Júlia; Oliveira, José Carlos; Correia-de-Sá, Paulo

2013-01-01

Background Nowadays, there is a considerable bulk of evidence showing that ATP has a prominent role in the regulation of human urinary bladder function and in the pathophysiology of detrusor overactivity. ATP mediates nonadrenergic-noncholinergic detrusor contractions in overactive bladders. In vitro studies have demonstrated that uroepithelial cells and cholinergic nerves from overactive human bladder samples (OAB) release more ATP than controls. Here, we compared the urinary ATP concentration in samples collected non-invasively from OAB women with detrusor overactivity and age-matched controls. Methods Patients with neurologic diseases, history of malignancy, urinary tract infections or renal impairment (creatinine clearance <70 ml/min) were excluded. All patients completed a 3-day voiding diary, a 24 h urine collection and blood sampling to evaluate creatinine clearance. Urine samples collected during voluntary voids were immediately freeze-preserved for ATP determination by the luciferin-luciferase bioluminescence assay; for comparison purposes, samples were also tested for urinary nerve growth factor (NGF) by ELISA. Results The urinary content of ATP, but not of NGF, normalized to patients’ urine creatinine levels (ATP/Cr) or urinary volume (ATP.Vol) were significantly (P<0.05) higher in OAB women with detrusor overactivity (n = 34) than in healthy controls (n = 30). Significant differences between the two groups were still observed by boosting urinary ATP/Cr content after water intake, but these were not detected for NGF/Cr. In OAB patients, urinary ATP/Cr levels correlated inversely with mean voided volumes determined in a 3-day voiding diary. Conclusion A high area under the receiver operator characteristics (ROC) curve (0.741; 95% CI 0.62–0.86; P<0.001) is consistent with urinary ATP/Cr being a highly sensitive dynamic biomarker for assessing detrusor overactivity in women with OAB syndrome. PMID:23741373

Combined effects of DNA methyltransferase 1 and 3A polymorphisms and urinary total arsenic levels on the risk for clear cell renal cell carcinoma

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yang, Shu-Mei

Our previous study showed that high urinary total arsenic levels were associated with higher odds ratio (OR) for renal cell carcinoma (RCC). Single nucleotide polymorphisms (SNPs) of DNA methyltransferases (DNMTs) might influence DNMT enzyme activity associated with tumorigenesis. In this study, we investigated the association of five SNPs from DNMT1 (rs8101626 and rs2228611), DNMT3A (rs34048824 and rs1550117), and DNMT3B (rs1569686) with the risk of clear cell renal cell carcinoma (ccRCC). We also examined the combined effects of DNMT genotypes and urinary arsenic levels on ccRCC risk. We conducted a hospital-based case-control study, which included 293 subjects with ccRCC and 293more » age- and gender-matched controls. The urinary arsenic species were determined by a high performance liquid chromatography-linked hydride generator and atomic absorption spectrometry. Genotypes were investigated using polymerase chain reaction and restriction fragment length polymorphism analyses. We observed that the DNMT1 rs8101626 G/G genotype was significantly associated with reduced odds ratio (OR) of ccRCC [OR = 0.38, 95% confidence interval (CI) 0.14–0.99]. Subjects with concurrent DNMT1 rs8101626 A/A + A/G and DNMT3A rs34048824 T/T + T/C genotypes had significantly higher OR for ccRCC [OR = 2.88, 95% CI 1.44–5.77]. Participants with the high-risk genotype of DNMT1 rs8101626 and DNMT3A rs34048824 with concurrently high urinary total arsenic levels had even higher OR of ccRCC in a dose-response manner. This is the first study to evaluate variant DNMT1 rs8101626 and DNMT3A rs34048824 genotypes that modify the arsenic-related ccRCC risk in a geographic area without significant arsenic exposure in Taiwan. - Highlights: • High urinary total arsenic level or polymorphism of DNMT1 increased the OR of ccRCC. • High risk genotypes of combination of DNMT1 and DNMT3A increased the OR of ccRCC. • A joint effect of urinary total arsenic level and DNMTs genotypes may affect ccRCC.« less

Endocrine relationships during human spaceflight

NASA Technical Reports Server (NTRS)

Stein, T. P.; Schluter, M. D.; Moldawer, L. L.

1999-01-01

Human spaceflight is associated with a chronic loss of protein from muscle. The objective of this study was to determine whether changes in urinary hormone excretion could identify a hormonal role for this loss. Urine samples were collected from the crews of two Life Sciences Space Shuttle missions before and during spaceflight. Data are means +/- SE with the number of subjects in parentheses. The first value is the mean preflight measurement, and the second value is the mean inflight measurement. Adrenocorticotropic hormone (ACTH) [27.7 +/- 4.4 (9) vs. 25.1 +/- 3.4 (9) ng/day], growth hormone [724 +/- 251 (9) vs. 710 +/- 206 (9) ng/day], insulin-like growth factor I [6.81 +/- 0.62 vs. 6.04 +/- 0.51 (8) nM/day], and C-peptide [44.9 +/- 8.3 (9) vs. 50.7 +/- 10.3 (9) micrograms/day] were unchanged with spaceflight. In contrast, free 3,5,3'-triiodothyronine [791 +/- 159 (9) vs. 371 +/- 41 (9) pg/day, P < 0.05], prostaglandin E2 (PGE2) [1, 064 +/- 391 (8) vs. 465 +/- 146 (8) ng/day, P < 0.05], and its metabolite PGE-M [1,015 +/- 98 (9) vs. 678 +/- 105 (9) ng/day, P < 0. 05] were decreased inflight. The urinary excretion of most hormones returned to their preflight levels during the postflight period, with the exception of ACTH [47.5 +/- 10.3 (9) ng/day], PGE2 [1,433 +/- 327 (8) ng/day], PGF2alpha, [2,786 +/- 313 (8) ng/day], and its metabolite PGF-M [4,814 +/- 402 (9) ng/day], which were all increased compared with the preflight measurement (P < 0.05). There was a trend for urinary cortisol to be elevated inflight [55.3 +/- 5. 9 (9) vs. 72.5 +/- 11.1 micrograms/day, P = 0.27] and postflight [82.7 +/- 8.6 (8) micrograms/day, P = 0.13]. The inflight human data support ground-based in vitro work showing that prostaglandins have a major role in modulating the changes in muscle protein content in response to tension or the lack thereof.

Impact of pesticide exposure misclassification on estimates of relative risks in the Agricultural Health Study.

PubMed

Blair, Aaron; Thomas, Kent; Coble, Joseph; Sandler, Dale P; Hines, Cynthia J; Lynch, Charles F; Knott, Charles; Purdue, Mark P; Zahm, Shelia Hoar; Alavanja, Michael C R; Dosemeci, Mustafa; Kamel, Freya; Hoppin, Jane A; Freeman, Laura Beane; Lubin, Jay H

2011-07-01

The Agricultural Health Study (AHS) is a prospective study of licensed pesticide applicators and their spouses in Iowa and North Carolina. We evaluate the impact of occupational pesticide exposure misclassification on relative risks using data from the cohort and the AHS Pesticide Exposure Study (AHS/PES). We assessed the impact of exposure misclassification on relative risks using the range of correlation coefficients observed between measured post-application urinary levels of 2,4-dichlorophenoxyacetic acid (2,4-D) and a chlorpyrifos metabolite and exposure estimates based on an algorithm from 83 AHS pesticide applications. Correlations between urinary levels of 2,4-D and a chlorpyrifos metabolite and algorithm estimated intensity scores were about 0.4 for 2,4-D (n=64), 0.8 for liquid chlorpyrifos (n=4) and 0.6 for granular chlorpyrifos (n=12). Correlations of urinary levels with kilograms of active ingredient used, duration of application, or number of acres treated were lower and ranged from -0.36 to 0.19. These findings indicate that a priori expert-derived algorithm scores were more closely related to measured urinary levels than individual exposure determinants evaluated here. Estimates of potential bias in relative risks based on the correlations from the AHS/PES indicate that non-differential misclassification of exposure using the algorithm would bias estimates towards the null, but less than that from individual exposure determinants. Although correlations between algorithm scores and urinary levels were quite good (ie, correlations between 0.4 and 0.8), exposure misclassification would still bias relative risk estimates in the AHS towards the null and diminish study power.

Bisphenol A exposure through receipt handling and its association with insulin resistance among female cashiers.

PubMed

Lee, Inae; Kim, Sunmi; Kim, Ki-Tae; Kim, Sungkyoon; Park, Suhyun; Lee, Hyojin; Jeong, Yunsun; Lim, Jae-Eun; Moon, Hyo-Bang; Choi, Kyungho

2018-05-16

Bisphenol A (BPA) is one of the most widely used chemicals in various consumer products. In thermal papers such as receipts and tickets, BPA is used as a heat-activated developer. Cashiers are therefore suspected to be a vulnerable group of exposure to BPA, but neither contribution of receipt handling to the total body burden of BPA among cashiers, nor related health effects are well characterized. Female cashiers (n = 54) were recruited from seven retail shops of a major supermarket chain in Korea, and urinary levels of BPA and metabolic syndrome (MetS) related biomarkers were measured. In order to estimate the contribution of receipt handling to the body burden of BPA, an intervention was designed on the use of gloves: the subjects were asked not to wear gloves during the work for one week, and in the following week, to wear gloves. Urine samples were collected at pre-shift and post-shift for the first two consecutive days in each week, and urinary BPA concentrations were measured. In cashiers without gloves, about a two-fold increase in urinary BPA concentrations was observed after work-shift. When the cashiers wore gloves, however, urinary BPA levels showed no changes. Higher urinary BPA concentrations were associated with greater levels of fasting insulin and insulin resistance. Our observation shows that receipt handling among the cashiers could double the BPA exposure levels at post-shift compared to those at pre-shift, and use of simple protective equipment such as gloves could effectively reduce the BPA exposure levels. Copyright © 2018 Elsevier Ltd. All rights reserved.

Alterations of type IV collagen alpha chains in patients with chronic acquired glomerulopathies: mRNA levels, protein expression and urinary loss.

PubMed

Sanna-Cherchi, Simone; Carnevali, Maria Luisa; Martorana, Davide; Cravedi, Paolo; Maggiore, Umberto; Alinovi, Rossella; Bovino, Achiropita; Mattei, Silvia; Orlandini, Guido; Gatti, Rita; Savi, Mario; Sado, Yoshikazu; Neri, Tauro M; Allegri, Landino

2007-01-01

Type IV collagen is a major structural component of the normal kidney glomerulus. However, its role in chronic acquired glomerulopathies has been only partially elucidated. Urinary levels of col(IV)alpha1, col(IV)alpha3 and col(IV)alpha5 collagen chains were analyzed in 107 patients with chronic acquired glomerulopathies. In a subgroup of 33 patients, tissue mRNA levels, protein expression and urinary excretion were evaluated for all col(IV)alpha chains, from col(IV)alpha1 to col(IV)alpha5. The renal specimens were examined to get a semiquantitative score of the acute and chronic activity of the histological lesions. Urines obtained from 13 healthy subjects and 10 normal renal tissue samples were used as controls. Urinary levels of col(IV)alpha1, col(IV)alpha3, col(IV)alpha5 chains were significantly higher in patients than in controls [p < 0.01 for all], while only col(IV)alpha1 and col(IV)alpha3 urinary excretion correlated with the degree of chronic histological damage [col(IV)alpha1 R = 0.44, p < 0.001; col(IV)alpha3: R = 0.47, p < 0.001]. Compared with controls, patients showed a renal expression of mRNA for col(IV)alpha5 chain significantly higher [p = 0.001], while having a significantly lower protein expression of col(IV)alpha3, col(IV)alpha4 and col(IV)alpha5 chains [p < 0.01 for all]. Patients with chronic acquired glomerulopathies show important alterations in the col(IV)alpha chain network mimicking some molecular features of the X-linked Alport's syndrome. Further studies are needed to show whether urinary levels of the col(IV)alpha chains may be used as markers for monitoring renal injury. Copyright 2007 S. Karger AG, Basel.

Health Risk Assessment of Dietary Cadmium Intake: Do Current Guidelines Indicate How Much is Safe?

PubMed

Satarug, Soisungwan; Vesey, David A; Gobe, Glenda C

2017-03-01

Cadmium (Cd), a food-chain contaminant, is a significant health hazard. The kidney is one of the primary sites of injury after chronic Cd exposure. Kidney-based risk assessment establishes the urinary Cd threshold at 5.24 μg/g creatinine, and tolerable dietary intake of Cd at 62 μg/day per 70-kg person. However, cohort studies show that dietary Cd intake below a threshold limit and that tolerable levels may increase the risk of death from cancer, cardiovascular disease, and Alzheimer's disease. We evaluated if the current tolerable dietary Cd intake guideline and urinary Cd threshold limit provide sufficient health protection. Staple foods constitute 40-60% of total dietary Cd intake by average consumers. Diets high in shellfish, crustaceans, mollusks, spinach, and offal add to dietary Cd sources. Modeling studies predict the current tolerable dietary intake corresponding to urinary Cd of 0.70-1.85 μg/g creatinine in men and 0.95-3.07 μg/g creatinine in women. Urinary Cd levels of < 1 μg/g creatinine were associated with progressive kidney dysfunction and peripheral vascular disease. A urinary Cd of 0.37 μg/g creatinine was associated with breast cancer, whereas dietary Cd of 16-31.5 μg/day was associated with 25-94% increase in risk of estrogen receptor-positive breast cancer. Modeling shows that dietary intake levels for Cd exceed the levels associated with kidney damage and many other adverse outcomes. Thus, the threshold level of urinary Cd should be re-evaluated. A more restrictive dietary intake guideline would afford enhanced health protection from this pervasive toxic metal. Citation: Satarug S, Vesey DA, Gobe GC. 2017. Health risk assessment of dietary cadmium intake: do current guidelines indicate how much is safe? Environ Health Perspect 125:284-288; http://dx.doi.org/10.1289/EHP108.

Effect of Hygrophila spinosa in ethylene glycol induced nephrolithiasis in rats.

PubMed

Ingale, Kundan G; Thakurdesai, Prasad A; Vyawahare, Neeraj S

2012-01-01

Hygrophila spinosa (Acanthaceae) is traditionally used to treat urinary calculi. The present study aimed to evaluate the antiurolithiatic activity of methanolic extract of Hygrophila spinosa (Acanthaceae) in ethylene glycol induced nephrolithiasic rats. Methanolic extract of Hygrophila spinosa (HSME) (250 and 500 mg/ kg body weight) was administered orally to male Wistar albino rats. Ethylene glycol (EG) was used to induce nephrolithiasis. The parameters studied included water intake, urinary volume, urinary pH, urinary and kidney oxalate and calcium, urinary magnesium and serum uric acid. Ethylene glycol feeding resulted in hyperoxaluria as well as increased renal excretion of calcium and serum uric acid along with decreased excretion of urinary magnesium. Treatment with HSME significantly reduced the elevated urinary oxalate, urinary calcium and serum uric acid with increase in reduced urinary magnesium. Ethylene glycol feeding also resulted in increased levels of calcium and oxalate in kidney which was decreased after the treatment with HSME. The increased deposition of stone forming constituents in the kidneys of ethylene glycol treated rats was significantly lowered by treatment with HSME. The results indicate that the aerial parts of Hygrophila spinosa are endowed with antiurolithiatic activity, thereby justifying its traditional claim.

α-Intercalated cells defend the urinary system from bacterial infection.

PubMed

Paragas, Neal; Kulkarni, Ritwij; Werth, Max; Schmidt-Ott, Kai M; Forster, Catherine; Deng, Rong; Zhang, Qingyin; Singer, Eugenia; Klose, Alexander D; Shen, Tian Huai; Francis, Kevin P; Ray, Sunetra; Vijayakumar, Soundarapandian; Seward, Samuel; Bovino, Mary E; Xu, Katherine; Takabe, Yared; Amaral, Fábio E; Mohan, Sumit; Wax, Rebecca; Corbin, Kaitlyn; Sanna-Cherchi, Simone; Mori, Kiyoshi; Johnson, Lynne; Nickolas, Thomas; D'Agati, Vivette; Lin, Chyuan-Sheng; Qiu, Andong; Al-Awqati, Qais; Ratner, Adam J; Barasch, Jonathan

2014-07-01

α-Intercalated cells (A-ICs) within the collecting duct of the kidney are critical for acid-base homeostasis. Here, we have shown that A-ICs also serve as both sentinels and effectors in the defense against urinary infections. In a murine urinary tract infection model, A-ICs bound uropathogenic E. coli and responded by acidifying the urine and secreting the bacteriostatic protein lipocalin 2 (LCN2; also known as NGAL). A-IC-dependent LCN2 secretion required TLR4, as mice expressing an LPS-insensitive form of TLR4 expressed reduced levels of LCN2. The presence of LCN2 in urine was both necessary and sufficient to control the urinary tract infection through iron sequestration, even in the harsh condition of urine acidification. In mice lacking A-ICs, both urinary LCN2 and urinary acidification were reduced, and consequently bacterial clearance was limited. Together these results indicate that A-ICs, which are known to regulate acid-base metabolism, are also critical for urinary defense against pathogenic bacteria. They respond to both cystitis and pyelonephritis by delivering bacteriostatic chemical agents to the lower urinary system.

α–Intercalated cells defend the urinary system from bacterial infection

PubMed Central

Paragas, Neal; Kulkarni, Ritwij; Werth, Max; Schmidt-Ott, Kai M.; Forster, Catherine; Deng, Rong; Zhang, Qingyin; Singer, Eugenia; Klose, Alexander D.; Shen, Tian Huai; Francis, Kevin P.; Ray, Sunetra; Vijayakumar, Soundarapandian; Seward, Samuel; Bovino, Mary E.; Xu, Katherine; Takabe, Yared; Amaral, Fábio E.; Mohan, Sumit; Wax, Rebecca; Corbin, Kaitlyn; Sanna-Cherchi, Simone; Mori, Kiyoshi; Johnson, Lynne; Nickolas, Thomas; D’Agati, Vivette; Lin, Chyuan-Sheng; Qiu, Andong; Al-Awqati, Qais; Ratner, Adam J.; Barasch, Jonathan

2014-01-01

α–Intercalated cells (A-ICs) within the collecting duct of the kidney are critical for acid-base homeostasis. Here, we have shown that A-ICs also serve as both sentinels and effectors in the defense against urinary infections. In a murine urinary tract infection model, A-ICs bound uropathogenic E. coli and responded by acidifying the urine and secreting the bacteriostatic protein lipocalin 2 (LCN2; also known as NGAL). A-IC–dependent LCN2 secretion required TLR4, as mice expressing an LPS-insensitive form of TLR4 expressed reduced levels of LCN2. The presence of LCN2 in urine was both necessary and sufficient to control the urinary tract infection through iron sequestration, even in the harsh condition of urine acidification. In mice lacking A-ICs, both urinary LCN2 and urinary acidification were reduced, and consequently bacterial clearance was limited. Together these results indicate that A-ICs, which are known to regulate acid-base metabolism, are also critical for urinary defense against pathogenic bacteria. They respond to both cystitis and pyelonephritis by delivering bacteriostatic chemical agents to the lower urinary system. PMID:24937428

Obesity-Induced Diabetes and Lower Urinary Tract Fibrosis Promote Urinary Voiding Dysfunction in a Mouse Model

PubMed Central

Gharaee-Kermani, Mehrnaz; Rodriguez-Nieves, Jose A.; Mehra, Rohit; Vezina, Chad A.; Sarma, Aruna V.; Macoska, Jill A.

2017-01-01

BACKGROUND Progressive aging- and inflammation-associated fibrosis effectively remodels the extracellular matrix (ECM) to increase prostate tissue stiffness and reduce urethral flexibility, resulting in urinary flow obstruction and lower urinary tract symptoms (LUTS). In the current study, we sought to test whether senescence-accelerated mouse prone (SAMP)6 mice, which were reported to develop prostatic fibrosis, would also develop LUTS, and whether these symptoms would be exacerbated by diet-induced obesity and concurrent Type 2 Diabetes Mellitus (T2DM). METHODS To accomplish this, SAMP6 and AKR/J background strain mice were fed regular mouse chow, low fat diet chow, or high fat diet chow for 8 months, then subjected to glucose tolerance tests, assessed for plasma insulin levels, evaluated for urinary voiding function, and assessed for lower urinary tract fibrosis. RESULTS The results of these studies show that SAMP6 mice and AKR/J background strain mice develop diet-induced obesity and T2DM concurrent with urinary voiding dysfunction. Moreover, urinary voiding dysfunction was more severe in SAMP6 than AKR/J mice and was associated with pronounced prostatic and urethral tissue fibrosis. CONCLUSIONS Taken together, these studies suggest that obesity, T2DM, lower urinary tract fibrosis, and urinary voiding dysfunction are inextricably and biologically linked. Prostate. PMID:23532836

Urinary bisphenol A and hypertension in a multiethnic sample of US adults.

PubMed

Shankar, Anoop; Teppala, Srinivas

2012-01-01

Bisphenol A (BPA) is a common chemical used in the manufacture of polycarbonate plastics and epoxy resins, with >93% of US adults having detectable BPA levels in urine. Recent animal studies have suggested that BPA exposure may have a role in several mechanisms involved in the development of hypertension, including weight gain, insulin resistance, thyroid dysfunction, endothelial dysfunction, and oxidative stress. However, no previous human study has examined the association between markers of BPA exposure and hypertension. We examined urinary BPA levels in 1380 subjects from the National Health and Nutritional Examination Survey 2003-2004. Main outcome-of-interest was hypertension, defined as blood pressure-reducing medication use and/or blood pressures >140/90 mm of Hg (n = 580). We observed a positive association between increasing levels of urinary BPA and hypertension independent of confounding factors such as age, gender, race/ethnicity, smoking, body mass index (BMI), diabetes mellitus and total serum cholesterol levels. Compared to tertile 1 (referent), the multivariate-adjusted odds ratio (95% confidence interval) of hypertension associated with tertile 3 was 1.50 (1.12-2.00); P-trend = 0.007. The association was consistently present in subgroup analyses by race/ethnicity, smoking status, BMI, and diabetes mellitus. Urinary BPA levels are associated with hypertension, independent of traditional risk factors.

Genetic and Epigenetic Biomarkers for Recurrent Prostate Cancer After Radiotherapy

DTIC Science & Technology

2013-05-01

prostatectomy are urinary incontinence , erectile dysfunction, and typical post-operative complications. Radiation therapy (RT) shows several distinct...includes a low risk of urinary incontinence . Major disadvantage of external beam RT include a treatment course of 8-9 weeks. -50% of patients have some...this treatment include the risk of acute urinary retention. Currently, the level of PSA, clinical stage and the Gleason score are used to

Matrix Metalloproteinase-7 Is a Urinary Biomarker and Pathogenic Mediator of Kidney Fibrosis

PubMed Central

Zhou, Dong; Tian, Yuan; Sun, Ling; Zhou, Lili; Xiao, Liangxiang; Tan, Roderick J.; Tian, Jianwei; Fu, Haiyan

2017-01-01

Matrix metalloproteinase-7 (MMP-7), a secreted zinc– and calcium–dependent endopeptidase, is a transcriptional target of canonical Wnt/β-catenin signaling. Because Wnt/β-catenin is activated in diseased kidney, we hypothesized that urinary MMP-7 level may be used as a noninvasive surrogate biomarker for fibrotic lesions. To test this hypothesis, we conducted a cross-sectional study, measuring urinary MMP-7 levels in a cohort of 102 patients with CKD. Compared with normal subjects, patients with various kidney disorders had markedly elevated urinary levels of MMP-7. Furthermore, urinary MMP-7 levels closely correlated with renal fibrosis scores in patients. In mice, knockout of MMP-7 ameliorated the fibrotic lesions and expression of matrix genes induced by obstructive injury. Genetic ablation of MMP-7 also preserved E-cadherin protein expression and substantially reduced the expression of total and dephosphorylated β-catenin and the de novo expression of vimentin and fibroblast-specific protein 1 in renal tubules of obstructed kidneys. In vitro, MMP-7 proteolytically degraded E-cadherin in proximal tubular cells, leading to β-catenin liberation and nuclear translocation and induction of β-catenin target genes by a mechanism independent of Wnt ligands. Finally, pharmacologic inhibition of MMP-7 immediately after obstructive injury reduced renal fibrosis in vivo. These results suggest that MMP-7 not only can serve as a noninvasive biomarker but also is an important pathogenic mediator of kidney fibrosis. PMID:27624489

Urinary leukotriene E4, obesity, and adenotonsillar hypertrophy in Chinese children with sleep disordered breathing.

PubMed

Shen, Yuelin; Xu, Zhifei; Shen, Kunling

2011-08-01

Sleep disordered breathing (SDB) has been associated with increased inflammatory responses. Changes in the level of pro-inflammatory leukotrienes (LTs) may initiate or exacerbate pediatric SDB and may play a major role in end-organ morbidity. The objective of the study was to investigate the relationship of LT productions with severity of SDB, obesity, and adenotonsillar hypertrophy in children. Prospective, observational study that included standard questionnaires, physical examinations, overnight polysomnography (PSG), and urinary leukotriene E(4) (LTE(4)) assay. Sleep Center and Laboratory of Nutriology. 282 children with SDB and 94 healthy control subjects were recruited. Urinary LTE(4) levels were elevated in children with SDB compared to the controls, and LTE(4) productions emerged disease severity- and obesity-dependent increases. In stepwise multiple regression analysis, the independent predictors of the apnea-hypopnea index (AHI) included LTE(4) level and adenotonsillar-size sum score (P < 0.001 respectively; adjusted R(2)=0.318). A positive relationship between LTE(4) urinary level and adenotonsillar-size sum scores was present in the underweight/normal weight SDB subjects (r=0.276; P < 0.001), but not in the overweight/obese children (P > 0.05). Systemic inflammation mediated by LTs participates in the pathophysiological mechanisms of SDB in children. The magnitude of inflammation as reflected by urinary LTE(4) is significantly related to the severity of SDB and obesity. However, a correlation between LTE(4) concentration and adenotonsillar size is present only among nonobese children.

Inflammatory C-reactive protein and cytokine levels in asymptomatic people with chronic spinal cord injury.

PubMed

Frost, Frederick; Roach, Mary Jo; Kushner, Irving; Schreiber, Peter

2005-02-01

To determine the relation between serologic markers of information and clinical characteristics of people with chronic spinal cord injury (SCI). Cross-sectional study. Academic medical center SCI outpatient clinic. Convenience sample of 37 men with chronic SCI and 10 healthy control subjects. Not applicable. Serum levels of interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), and C-reactive protein (CRP). The following results achieved statistical significance at P less than .05. Asymptomatic chronic SCI patients differed from referent controls with respect to serum CRP levels but not IL-6 or TNF-alpha. In SCI patients, higher levels of CRP correlated negatively with hemoglobin and albumin levels. A longer time since injury correlated with lower TNF-alpha values, whereas higher TNF-alpha levels correlated with higher serum albumin. Pressure ulcers and indwelling urinary catheters were associated with higher mean levels of CRP but not of the cytokines TNF-alpha and IL-6. Intermittent urinary catheterization was associated with lower levels of CRP when compared with other methods of bladder management. Asymptomatic people with long-term SCI, especially those with indwelling urinary catheters, showed serologic evidence of a systemic inflammatory state. There was no evidence of an elevation in proinflammatory cytokines. Detection of an ongoing systemic inflammatory response in apparently healthy people with indwelling urinary catheters and small skin ulcers further supports the aggressive pursuit of catheter-free voiding options and pressure ulcer healing.

Environmental tobacco smoke and canine urinary cotinine level

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bertone-Johnson, Elizabeth R.; Department of Clinical Sciences, Cummings School of Veterinary Medicine, Tufts University, North Grafton, MA; Procter-Gray, Elizabeth

Epidemiologic studies of companion animals such as dogs have been established as models for the relationship between exposure to environmental tobacco smoke (ETS) and cancer risk in humans. While results from these studies are provocative, pet owner report of a dog's ETS exposure has not yet been validated. We have evaluated the relationship between dog owner's report of household smoking by questionnaire and dog's urinary cotinine level. Between January and October 2005, dog owners presenting their pet for non-emergency veterinary care at the Foster Hospital for Small Animals at Cummings School of Veterinary Medicine, Tufts University, were asked to completemore » a 10-page questionnaire measuring exposure to household ETS in the previous 24 h and other factors. A free-catch urine sample was also collected from dogs. Urinary cotinine level was assayed for 63 dogs, including 30 whose owners reported household smoking and 33 unexposed dogs matched on age and month of enrollment. Urinary cotinine level was significantly higher in dogs exposed to household smoking in the 24 h before urine collection compared to unexposed dogs (14.6 ng/ml vs. 7.4 ng/ml; P=0.02). After adjustment for other factors, cotinine level increased linearly with number of cigarettes smoked by all household members (P=0.004). Other canine characteristics including age, body composition and nose length were also associated with cotinine level. Findings from our study suggest that household smoking levels as assessed by questionnaire are significantly associated with canine cotinine levels.« less

Cardiovascular abnormalities with normal blood pressure in tissue kallikrein-deficient mice

NASA Astrophysics Data System (ADS)

Meneton, Pierre; Bloch-Faure, May; Hagege, Albert A.; Ruetten, Hartmut; Huang, Wei; Bergaya, Sonia; Ceiler, Debbie; Gehring, Doris; Martins, Isabelle; Salmon, Georges; Boulanger, Chantal M.; Nussberger, Jürg; Crozatier, Bertrand; Gasc, Jean-Marie; Heudes, Didier; Bruneval, Patrick; Doetschman, Tom; Ménard, Joël; Alhenc-Gelas, François

2001-02-01

Tissue kallikrein is a serine protease thought to be involved in the generation of bioactive peptide kinins in many organs like the kidneys, colon, salivary glands, pancreas, and blood vessels. Low renal synthesis and urinary excretion of tissue kallikrein have been repeatedly linked to hypertension in animals and humans, but the exact role of the protease in cardiovascular function has not been established largely because of the lack of specific inhibitors. This study demonstrates that mice lacking tissue kallikrein are unable to generate significant levels of kinins in most tissues and develop cardiovascular abnormalities early in adulthood despite normal blood pressure. The heart exhibits septum and posterior wall thinning and a tendency to dilatation resulting in reduced left ventricular mass. Cardiac function estimated in vivo and in vitro is decreased both under basal conditions and in response to βadrenergic stimulation. Furthermore, flow-induced vasodilatation is impaired in isolated perfused carotid arteries, which express, like the heart, low levels of the protease. These data show that tissue kallikrein is the main kinin-generating enzyme in vivo and that a functional kallikrein-kinin system is necessary for normal cardiac and arterial function in the mouse. They suggest that the kallikrein-kinin system could be involved in the development or progression of cardiovascular diseases.

The greatest taboo: urinary incontinence as a source of shame and embarrassment.

PubMed

Elenskaia, Ksenia; Haidvogel, Karin; Heidinger, Christine; Doerfler, Daniela; Umek, Wolfgang; Hanzal, Engelbert

2011-10-01

While urinary incontinence is often labeled as a taboo in the literature, we found no scientific data addressing this issue exclusively. The aim of our study was to measure the perception of urinary incontinence as a taboo and how this compares to other medical conditions that may be embarrassing. 150 test persons completed a self-administered 13-item questionnaire about perception and knowledge of urinary incontinence. Data were analysed with the SPSS 10.0.5 software package using the U-test, Chi-square-test, Yates-correction, Fisher's exact test and Kolmogorov-Smirnov test. Eighty-six (60.6%) of 142 respondents thought that urinary incontinence constituted a taboo in Austria. To be incontinent was considered significantly more embarrassing than depression or cancer, respectively (p = 0.001). Despite its high prevalence, urinary incontinence is still considered a taboo in up to 60% of our Austrian test persons. The level of shame and embarrassment of urinary incontinence is significantly higher than that of depression and cancer.

Lipid and Creatinine Adjustment to Evaluate Health Effects of Environmental Exposures.

PubMed

O'Brien, Katie M; Upson, Kristen; Buckley, Jessie P

2017-03-01

Urine- and serum-based biomarkers are useful for assessing individuals' exposure to environmental factors. However, variations in urinary creatinine (a measure of dilution) or serum lipid levels, if not adequately corrected for, can directly impact biomarker concentrations and bias exposure-disease association measures. Recent methodological literature has considered the complex relationships between creatinine or serum lipid levels, exposure biomarkers, outcomes, and other potentially relevant factors using directed acyclic graphs and simulation studies. The optimal measures of urinary dilution and serum lipids have also been investigated. Existing evidence supports the use of covariate-adjusted standardization plus creatinine adjustment for urinary biomarkers and standardization plus serum lipid adjustment for lipophilic, serum-based biomarkers. It is unclear which urinary dilution measure is best, but all serum lipid measures performed similarly. Future research should assess methods for pooled biomarkers and for studying diseases and exposures that affect creatinine or serum lipids directly.

Urinary fluoride as a monitoring tool for assessing successful intervention in the provision of safe drinking water supply in five fluoride-affected villages in Dhar district, Madhya Pradesh, India.

PubMed

Srikanth, R; Gautam, Anil; Jaiswal, Suresh Chandra; Singh, Pavitra

2013-03-01

Endemic fluorosis was detected in 31 villages in the Dhar district of Madhya Pradesh, Central India. Out of the 109 drinking water sources that were analyzed, about 67 % were found to contain high concentration of fluoride above the permissible level of 1.0 mg/l. Dental fluorosis among the primary school children in the age between 8 and 15 served as primary indicator for fluoride intoxication among the children. Urinary fluoride levels among the adults were found to be correlated with drinking water fluoride in 10 villages affected by fluoride. Intervention in the form of alternate safe water supply in five villages showed significant reduction in the urinary fluoride concentration when compared to the control village. Urinary fluoride serves as an excellent marker for assessing the effectiveness of intervention program in the fluoride-affected villages.

Lipid and Creatinine Adjustment to Evaluate Health Effects of Environmental Exposures

PubMed Central

O’Brien, Katie M.; Upson, Kristen; Buckley, Jessie P.

2017-01-01

Purpose of review Urine- and serum-based biomarkers are useful for assessing individuals’ exposure to environmental factors. However, variations in urinary creatinine (a measure of dilution) or serum lipid levels, if not adequately corrected for, can directly impact biomarker concentrations and bias exposure-disease association measures. Recent findings Recent methodological literature has considered the complex relationships between creatinine or serum lipid levels, exposure biomarkers, outcomes, and other potentially relevant factors using directed acyclic graphs and simulation studies. The optimal measures of urinary dilution and serum lipids have also been investigated. Summary Existing evidence supports the use of covariate-adjusted standardization plus creatinine adjustment for urinary biomarkers and standardization plus serum lipid adjustment for lipophilic, serum-based biomarkers. It is unclear which urinary dilution measure is best, but all serum lipid measures performed similarly. Future research should assess methods for pooled biomarkers and for studying diseases and exposures that affect creatinine or serum lipids directly. PMID:28097619

Significance of urinary hippuric acid determination as an index of toluene exposure

PubMed Central

Ikeda, Masayuki; Ohtsuji, Hatsue

1969-01-01

Ikeda, Masayuki, and Ohtsuji, Hatsue (1969).Brit. J. industr. Med.,26, 244-246. Significance of urinary hippuric acid determination as an index of toluene exposure. Urine samples from 118 male workers in photogravure printing factories were analysed for hippuric acid. The urinary levels of hippuric acid were proportional to the environmental concentrations of toluene, although within wide variations. The urinary concentration of hippuric acid corresponding to 200 p.p.m. of toluene was 3·5 g./litre (specific gravity 1·016) or 4·3 g./g. creatinine. PMID:5794951

Laparoscopic insertion of artificial periprostatic urinary sphincter.

PubMed

Gamé, Xavier; Bram, Raphael; Abu Anz, Sami; Doumerc, Nicolas; Guillotreau, Julien; Malavaud, Bernard; Rischmann, Pascal

2009-02-01

The objective of this case report is to describe the laparoscopic insertion of an artificial periprostatic urinary sphincter. We report the case of a paraplegic patient in whom an artificial urinary sphincter was inserted in a periprostatic position by way of laparoscopy to treat stress urinary incontinence. In addition to laparoscopy being minimally invasive, its advantages include the excellent quality of retroprostatic dissection and the perfect visualization it gives at the level of cuff positioning with respect to the anatomic landmarks. It is more appropriate to be able to cleave the interprostatorectal space to ensure passage of the cuff under perfectly safe conditions.

The mediating effect of 'bothersome' urinary incontinence on help-seeking intentions among community-dwelling women.

PubMed

Xu, Dongjuan; Wang, Xiaojuan; Li, Jingjing; Wang, Kefang

2015-02-01

To explore the mediating effect of bother of urinary incontinence between urinary incontinence severity and help-seeking intentions and detect whether the International Consultation on Incontinence Questionnaire-UI Short Form could be a valid measure to delineate bothersome urinary incontinence. Urinary incontinence is a common condition among women, which has a profound adverse effect on quality of life. However, many of them experiencing significant clinical symptoms do not seek medical help. A cross-sectional survey design. Women with urinary incontinence (N = 620) from three randomized selected community health service centres from May-October 2011 participated in the study. Data were collected using a pencil-and-paper questionnaire. Multivariate regression models were used to test the role of bother as a mediator in the relation between urinary incontinence severity and help-seeking intentions. Receiver operating characteristic analysis was used to find the best cut-off International Consultation on Incontinence Questionnaire-UI Short Form score (range: 0-21) to delineate the bother of urinary incontinence. Bothersome urinary incontinence mediated the relationship between urinary incontinence severity and help-seeking intentions. Age and duration of urine leakage had a negative association on help-seeking intentions, while educational level and previous help-seeking behaviours had a positive association. Bother was a mediator in the relation between urinary incontinence severity and help-seeking intentions. The International Consultation on Incontinence Questionnaire-UI Short Form was a discriminative measure to delineate the bothersome urinary incontinence. © 2014 John Wiley & Sons Ltd.

GSTO and AS3MT genetic polymorphisms and differences in urinary arsenic concentrations among residents in Bangladesh.

PubMed

Rodrigues, Ema G; Kile, Molly; Hoffman, Elaine; Quamruzzaman, Quazi; Rahman, Mahmuder; Mahiuddin, Golam; Hsueh, Yumei; Christiani, David C

2012-05-01

We determined whether single nucleotide polymorphisms (SNPs) in the glutathione S-transferase omega (GSTO) and arsenic(III)methyltransferase (AS3MT) genes were associated with concentrations of urinary arsenic metabolites among 900 individuals without skin lesions in Bangladesh. Four SNPs were assessed in these genes. A pathway analysis evaluated the association between urinary arsenic metabolites and SNPs. GSTO1 rs4925 homozygous wild type was significantly associated with higher monomethylarsonic acid (MMA) and dimethylarsinic acid urinary concentrations, whereas wild-type AS3MT rs11191439 had significantly lower levels of As(III) and MMA. Genetic polymorphisms GSTO and As3MT modify arsenic metabolism as evidenced by altered urinary arsenic excretion.

The influence of obesity, constitution and physical work on the phenomenon of urinary incontinence in women.

PubMed

Sustersic, O; Kralj, B

1998-01-01

Urinary incontinence in women is a common and complex problem which can be defined and classified as stress, urge and mixed incontinence. Three of the eight most common risk factors are obesity, constitution and physical work, in addition to age, length of menstrual cycle, number of pregnancies, education and level of health awareness. Women with the diagnosis of urinary incontinence were invited to respond to questionnaires on a voluntary basis. The three factors found to be associated with urinary incontinence are increased body weight, strong osteomuscular structure and hard physical work. These indicate that the work of a health team must take a holistic approach to women even before the phenomenon of urinary incontinence occurs.

Hydrogen atom scrambling in selectively labeled anionic peptides upon collisional activation by MALDI tandem time-of-flight mass spectrometry.

PubMed

Bache, Nicolai; Rand, Kasper D; Roepstorff, Peter; Ploug, Michael; Jørgensen, Thomas J D

2008-12-01

We have previously shown that peptide amide hydrogens undergo extensive intramolecular migration (i.e., complete hydrogen scrambling) upon collisional activation of protonated peptides (Jørgensen et al. J. Am. Chem. Soc. 2005, 127, 2785-2793). The occurrence of hydrogen scrambling enforces severe limitations on the application of gas-phase fragmentation as a convenient method to obtain information about the site-specific deuterium uptake for proteins and peptides in solution. To investigate whether deprotonated peptides exhibit a lower level of scrambling relative to their protonated counterparts, we have now measured the level of hydrogen scrambling in a deprotonated, selectively labeled peptide using MALDI tandem time-of-flight mass spectrometry. Our results conclusively show that hydrogen scrambling is prevalent in the deprotonated peptide upon collisional activation. The amide hydrogens ((1)H/(2)H) have migrated extensively in the anionic peptide, thereby erasing the original regioselective deuteration pattern obtained in solution.

THE METABOLISM OF SILICON IN THE RAT AND ITS RELATION TO THE FORMATION OF ARTIFICIAL SILICEOUS CALCULI

PubMed Central

Keeler, Richard F.; Lovelace, Stuart A.

1959-01-01

The urinary excretion of silicon in the rat was found to be enhanced beyond normal levels by the administration of various chemical forms of silicon. The excretion was enhanced to a much greater degree by the administration of ethyl silicate than by magnesium trisilicate, sodium metasilicate, or water glass. The tolerance level of rats to sustained daily doses of ethyl silicate fed via stomach tube was approximately 15 to 30 mg. of silicon per rat per day. Urinary silicon excretion was found to be a straight line function of the concentration of ethyl silicate administered, via stomach tube, with approximately 18 per cent of the administered silicon appearing in the urine at all levels tested. Using sustained dietary additions of ethyl silicate as a means of enhancing urine silicon levels, artificial siliceous urinary calculi were consistently produced on zinc pellets implanted in the bladders of rats. PMID:13654631

Relationship of urinary isoprostanes to prostate cancer occurrence.

PubMed

Brys, Magdalena; Morel, Agnieszka; Forma, Ewa; Krzeslak, Anna; Wilkosz, Jacek; Rozanski, Waldemar; Olas, Beata

2013-01-01

To estimate the oxidative stress in patients with prostate cancer and in a control group, we used the biomarker of lipid peroxidation-isoprostanes (8-isoPGF(2)) and the level of selected antioxidants (glucose and uric acid [UA]). The level of urinary isoprostanes was determined in patients and controls using an immunoassay kit according to the manufacturer's instruction. The levels of UA and glucose were also determined in serum by the use of UA Assay Kit and Glucose Assay Kit. We observed a statistically increased the level of isoprostanes in urine of patients with prostate cancer in compared with a control group. The concentration of tested antioxidants in blood from patients with prostate cancer was also higher than in healthy subjects. Moreover, our experiments indicate that the correlation between the increased amount of UA and the lipid peroxidation exists in prostate cancer patients (in all tested groups). Prostate cancer risk by urinary isoprostanes level was analyzed, and a positive association was found (relative risk for highest vs. lowest quartile of urinary isoprostanes = 1.6; 95 % confidence interval 1.2-2.4; p for trend = 0.03). We suggest that reactive oxygen species induce peroxidation of unsaturated fatty acid in patients with prostate cancer, and the level of isoprostanes may be used as a non-invasive marker for determination of oxidative stress. We also propose that UA may enhance the oxidative stress in patients with prostate cancer.

Low Serum Testosterone Levels Are Associated with Elevated Urinary Mandelic Acid, and Strontium Levels in Adult Men According to the US 2011–2012 National Health and Nutrition Examination Survey

PubMed Central

Liu, Hui; Héroux, Paul; Zhang, Qunwei; Jiang, Zhao-Yan; Gu, Aihua

2015-01-01

Background Little is known regarding the effects of environmental exposure of chemicals on androgenic system in the general population. We studied 5,107 subjects included in the National Health and Nutrition Examination Survey (2011–2012). Methods Urinary, serum, and blood levels of 15 subclasses comprising 110 individual chemicals were analyzed for their association with serum testosterone levels. The subjects were divided into high and low testosterone groups according to the median testosterone concentration (374.51 ng/dL). Odds ratios (ORs) of individual chemicals in association with testosterone were estimated using logistic regression after adjusting for age, ethnicity, cotinine, body mass index, creatinine, alcohol, and the poverty income ratio. Results Adjusted ORs for the highest versus lowest quartiles of exposure were 2.12 (95% CI: 1.07, 4.21; Ptrend = 0.044), 1.84 (95% CI: 1.02, 3.34; Ptrend = 0.018) for the association between urinary mandelic acid, and strontium quartiles with low testosterone concentrations in adult men, respectively. However, no association was observed for the remaining chemicals with testosterone. Conclusions The National Health and Nutrition Examination Survey data suggest that elevations in urinary mandelic acid, and strontium levels are negatively related to low serum testosterone levels in adult men. PMID:25996772

Association of Urinary Calcium Excretion with Serum Calcium and Vitamin D Levels

PubMed Central

Rathod, Anita; Bonny, Olivier; Guessous, Idris; Suter, Paolo M.; Conen, David; Erne, Paul; Binet, Isabelle; Gabutti, Luca; Gallino, Augusto; Muggli, Franco; Hayoz, Daniel; Péchère-Bertschi, Antoinette; Paccaud, Fred

2015-01-01

Background and objectives Population-based data on urinary calcium excretion are scarce. The association of serum calcium and circulating levels of vitamin D [25(OH)D2 or D3] with urinary calcium excretion in men and women from a population-based study was explored. Design, settings, participants, & measurements Multivariable linear regression was used to explore factors associated with square root–transformed 24-hour urinary calcium excretion (milligrams per 24 hours) taken as the dependent variable with a focus on month-specific vitamin D tertiles and serum calcium in the Swiss Survey on Salt Study. Results In total, 624 men and 669 women were studied with mean ages of 49.2 and 47.0 years, respectively (age range=15–95 years). Mean urinary calcium excretion was higher in men than in women (183.05 versus 144.60 mg/24 h; P<0.001). In adjusted models, the association (95% confidence interval) of square root urinary calcium excretion with protein–corrected serum calcium was 1.78 (95% confidence interval, 1.21 to 2.34) mg/24 h per milligram per deciliter in women and 0.59 (95% confidence interval, −0.11 to 1.29) mg/24 h per milligram per deciliter in men. Men in the third 25(OH)D3 tertile had higher square root urinary calcium excretion than men in the first tertile (0.99; 95% confidence interval, 0.36 to 1.63 mg/24 h per nanogram per milliliter), and the corresponding association was 0.32 (95% confidence interval, −0.22 to 0.85) mg/24 h per nanogram per milliliter in women. These sex differences were more marked under conditions of high urinary sodium or urea excretions. Conclusions There was a positive association of serum calcium with urinary calcium excretion in women but not men. Vitamin 25(OH)D3 was associated with urinary calcium excretion in men but not women. These results suggest important sex differences in the hormonal and dietary control of urinary calcium excretion. PMID:25518946

Tissue accumulation and urinary excretion of chromium in rats fed diets containing graded levels of chromium chloride or chromium picolinate.

PubMed

Yoshida, Munehiro; Hatakeyama, Erika; Hosomi, Ryota; Kanda, Seiji; Nishiyama, Toshimasa; Fukunaga, Kenji

2010-08-01

To attempt a risk assessment of the excess intake of trivalent chromium (Cr), tissue Cr accumulation and urinary Cr excretion were examined in weanling rats fed experimental diets containing graded levels of Cr chloride (CrCl3) or Cr picolinate (CrPic). Thirty-six male weanling 4-weeks-old Wistar rats were divided into six groups and fed a casein-based semi-purified diet (Cr content: <0.02 microg/g) supplemented with 1, 10, or 100 microg Cr/g as CrCl3 or CrPic for 28 days. Among the experimental groups, no significant difference was observed in body weight; however, supplementation of 100 microg Cr/g to the diets caused a significant low liver weight irrespective of the chemical species of Cr. Activities of serum aspartate aminotransferase and alanine aminotransferase were significantly elevated in rats given CrPic at 100 microg Cr/g. In the liver, kidney and femur, Cr accumulation increased with elevation of the dietary Cr level. No influence of the difference in the chemical species of supplemented Cr was observed in the liver and kidney, but CrCl3 caused significantly higher Cr accumulation than CrPic in the femur of rats given 100 microg Cr/g. Daily urinary Cr excretion elevated with the increase of the dietary Cr level. Rats given CrPic showed significantly higher daily urinary Cr excretion than those given CrCl3, particularly at a dietary Cr level of 100 microg/g. The rate of urinary Cr excretion in rats given CrPic was constant, irrespective of the dietary Cr level, but that of rats given CrCl3 fell with the increase of the dietary Cr level. These results indicate that the lowest adverse effect level of dietary Cr is less than 100 microg/g, irrespective of the chemical species of Cr.

Urinary concentrations of benzophenone-type ultra violet light filters and reproductive parameters in young men.

PubMed

Adoamnei, Evdochia; Mendiola, Jaime; Moñino-García, Miriam; Vela-Soria, Fernando; Iribarne-Durán, Luz M; Fernández, Mariana F; Olea, Nicolás; Jørgensen, Niels; Swan, Shanna H; Torres-Cantero, Alberto M

2018-04-01

Benzophenone (BP)-type ultraviolet (UV) light filters are chemicals frequently added to personal care products, insect repellents, sunscreens, and beverage and food packaging to diminish the harmful effects of UV sunlight on human skin or foodstuffs. BP-type UV filters have shown negative effects on male reproduction function in in vitro and animal models, but human epidemiologic studies are limited. The goal of this study was to examine associations between urinary concentrations of BP-type UV filters and semen quality and reproductive hormone levels. This is a cross-sectional study with 215 young university students (18-23 years old) recruited between 2010 and 2011 in Southern Spain (Murcia Region). All men provided a urine, blood and semen sample on a single day. Urinary concentrations of 2,4-dihydroxybenzophenone (BP-1); 2,2',4,4'-tetrahydroxybenzophenone (BP-2); 2-hydroxy-4-methoxybenzophenone (BP-3); 2,2'-dihydroxy-4-methoxybenzophenone (BP-8) and 4-hydroxybenzophenone (4OH-BP) were measured by dispersive liquid-liquid microextraction and ultra-high performance liquid chromatography with tandem mass spectrometry detection. Semen quality was evaluated by measuring volume, sperm counts, motility and morphology. Serum samples were analyzed for reproductive hormones, including follicle-stimulating hormone (FSH), luteinizing hormone (LH), testosterone (T), inhibin B and estradiol (E2). Associations between urinary concentrations of BP-type UV filters and semen quality parameters and reproductive hormone levels were examined using linear regression, adjusting for potential confounders. Ninety-seven percent of the men had detectable urinary concentrations of at least one of the five BP-type UV filters quantified. After adjustment for important covariates (body mass index, smoking status and time of blood sample collection), there was a significant positive association between urinary BP-1 and BP-3 concentrations and serum FSH levels (β = 0.08, 95%CI: 0.009; 0.15 and β = 0.04, 95%CI: 0.0002; 0.08, respectively). Urinary BP-1 concentration was also significantly positively associated with T/E2 (β = 0.04, 95%CI: 0.002; 0.07) and negatively with inhibin b/FSH (β = -0.11, 95%CI: -0.21; -0.006) ratio. No significant associations were found between other urinary BP-type UV filters and other reproductive hormone levels or between any semen parameters and any of the urinary BP-type UV filters quantified. Our results suggest that, in young men, urinary BP-type UV filters may be associated with a modest alteration of some reproductive hormones, but the effects we report on reproductive function are likely to be small, and of unclear clinical significance. Further research is needed to replicate these findings in other male populations. Copyright © 2018 Elsevier GmbH. All rights reserved.

Development of In Vitro-In Vivo Correlation for Potassium Chloride Extended Release Tablet Formulation Using Urinary Pharmacokinetic Data.

PubMed

Mittapalli, Rajendar K; Marroum, Patrick; Qiu, Yihong; Apfelbaum, Kathleen; Xiong, Hao

2017-07-01

To develop and validate a Level A in vitro-in vivo correlation (IVIVC) for potassium chloride extended-release (ER) formulations. Three prototype ER formulations of potassium chloride with different in vitro release rates were developed and their urinary pharmacokinetic profiles were evaluated in healthy subjects. A mathematical model between in vitro dissolution and in vivo urinary excretion, a surrogate for measuring in vivo absorption, was developed using time-scale and time-shift parameters. The IVIVC model was then validated based on internal and external predictability. With the established IVIVC model, there was a good correlation between the observed fraction of dose excreted in urine and the time-scaled and time-shifted fraction of the drug dissolved, and between the in vitro dissolution time and the in vivo urinary excretion time for the ER formulations. The percent prediction error (%PE) on cumulative urinary excretion over the 24 h interval (A e0-24h ) and maximum urinary excretion rate (R max ) was less than 15% for the individual formulations and less than 10% for the average of the two formulations used to develop the model. Further, the %PE values using external predictability were below 10%. A novel Level A IVIVC was successfully developed and validated for the new potassium chloride ER formulations using urinary pharmacokinetic data. This successful IVIVC may facilitate future development or manufacturing changes to the potassium chloride ER formulation.

Correlations of urinary cadmium with hypertension and diabetes in persons living in cadmium-contaminated villages in northwestern Thailand: A population study

DOE Office of Scientific and Technical Information (OSTI.GOV)

Swaddiwudhipong, Witaya, E-mail: swaddi@hotmail.com; Mahasakpan, Pranee; Limpatanachote, Pisit

Risk for hypertension and diabetes has not been conclusively found to be a result of cadmium exposure. A population-based study was conducted in 2009 to examine the correlations of urinary cadmium, a good biomarker of long-term cadmium exposure, with hypertension and diabetes in persons aged 35 years and older who lived in the 12 cadmium-contaminated rural villages in northwestern Thailand. A total of 5273 persons were interviewed and screened for urinary cadmium, hypertension, and diabetes. The geometric mean level of urinary cadmium for women (2.4{+-}2.3 {mu}g/g creatinine) was significantly greater than that for men (2.0{+-}2.2 {mu}g/g creatinine). Hypertension was presentedmore » in 29.8% of the study population and diabetes was detected in 6.6%. The prevalence of hypertension significantly increased from 25.0% among persons in the lowest tertile of urinary cadmium to 35.0% in the highest tertile. In women, the rate of hypertension significantly increased with increasing urinary cadmium levels in both ever and never smokers, after adjusting for age, alcohol consumption, body mass index, and diabetes. In men, such association was less significantly found in never smokers. The study revealed no significant association between urinary cadmium and diabetes in either gender. Our study supports the hypothesis that environmental exposure to cadmium may increase the risk of hypertension. Risk for diabetes in relation to cadmium exposure remains uncertain in this exposed population.« less

MGMT hypomethylation is associated with DNA damage in workers exposed to low-dose benzene.

PubMed

Li, Jie; Zhang, Xinjie; He, Zhini; Sun, Qing; Qin, Fei; Huang, Zhenlie; Zhang, Xiao; Sun, Xin; Liu, Linhua; Chen, Liping; Gao, Chen; Wang, Shan; Wang, Fangping; Li, Daochuan; Zeng, Xiaowen; Deng, Qifei; Wang, Qing; Zhang, Bo; Tang, Huanwen; Chen, Wen; Xiao, Yongmei

2017-07-01

This study aims to assess the effects of low-dose benzene on DNA damage and O 6 -methylguanine-DNA methyltransferase (MGMT) methylation in occupational workers. We recruited 96 nonsmoking male petrochemical industry workers exposed to low-dose benzene and 100 matched control workers. Urinary S-phenylmercapturic acid (SPMA) and S-benzylmercapturic acid (SBMA) were measured for indicating internal exposure of benzene and toluene. The degree of DNA damage was determined by the Comet assay. The levels of MGMT methylation were detected quantitatively by bisulphite-PCR pyrosequencing assay. The benzene-exposed workers had significantly higher levels of urinary SPMA, degree of DNA damage but decreased MGMT methylation than the controls (all p < 0.05). In contrast, the level of urinary SBMA does not differ between benzene-exposed workers and the controls. In all participants, MGMT methylation was negatively associated with the urinary SPMA and the degree of DNA damage, indicating that epigenetic regulation might be involved in response to low-dose benzene exposure-induced genetic damage. MGMT methylation could be a potent biomarker associated with low-dose benzene exposure and benzene-induced DNA damage.

Urinary CD80 as a Replacement for Renal Biopsy for Diagnosis of Pediatric Minimal Change Disease.

PubMed

Ahmed, Heba Mostafa; Ezzat, Dina Ahmed; Doudar, Noha A; Adel, Mai

2018-03-01

Early diagnosis of minimal change disease (MCD) is challenging in nephrotic children. CD80 is a protein expressed on the surface of podocytes associated with nephrotic syndrome and it is implicated in the induction of proteinuria. This study aimed to investigate the use of urinary CD80 for the diagnosis of MCD. Urinary CD80 levels were evaluated in 36 children with nephrotic syndrome and normal glomerular filtration rate. They were divided into three groups of MCD (n = 21), focal segmental glomerulosclerosis (n = 9), and other glomerulopathies (n = 6). The MCD group was subdivided into 2 of those with remission (n = 11) and those in the active stage (n = 10). Forty healthy children were included as controls. The urinary CD80 level was significantly higher in the MCD group (3.5 ± 2.1 ng/mg creatinine) than in the focal segmental glomerulosclerosis group (1.2 ± 0.5 ng/mg creatinine, P < .001), the other glomerulopathies group (1.4 ± 0.7 ng/mg creatinine, P < .001), and the control group (0.7 ± 0.2 ng/mg creatinine, P < .001), while it showed no significant difference among the non-MCD groups. There was no significant difference between MCD in remission and MCD in relapse, either. A urinary CD80 cutoff value of 1.5 ng/gm creatinine showed a sensitivity of 100% and a specificity of 86% for diagnosis of MCD. Urinary CD80 levels were significantly higher in the children with MCD than in the controls and patients with other causes of nephrotic syndrome.

[Effects of excess nicotinic acid on growth and the urinary excretion of B-group vitamins and the metabolism of tryptophan in weaning rats].

PubMed

Fukuwatari, Tsutomu; Kurata, Kaori; Shibata, Katsumi

2009-04-01

To determine the tolerable upper intake level of nicotinic acid in humans, we investigated the effects of excess nicotinic acid administration on body weight gain, food intake, and urinary excretion of water-soluble vitamins and the metabolism of tryptophan in weaning rats. The weaning rats were freely fed a niacin-free 20% casein diet (control diet) or the same diet with 0.1%, 0.3% or 0.5% nicotinic acid for 23 days. The excess nicotinic acid intake did not affect body weight gain, food intake, serotonin contents in the brain, stomach and small intestine, or the urinary excretions of water-soluble vitamins. Although excess nicotinic acid did not affect the upper part of the tryptophan-nicotinamide pathway, 0.5% nicotinic acid diet increased the urinary excretion of quinolinic acid. The diet containing more than 0.3% nicotinic acid also increased the urinary excretion of nicotinic acid, which is usually below the limit of detection. As determined from the results of body weight gain and food intake as indices for apparent adverse effects, the no-observed-adverse-effect-level (NOAEL) for nicotinic acid was 0.5% in diet, corresponding to 450 mg/kg body weight/day. As judged from in increase of urinary quinolinic acid and nicotinic acid as indices of metabolic change, NOAEL was 0.1% in diet, corresponding to 90 mg/kg body weight/day, and the lowest-observed-adverse-effect-level (LOAEL) was 0.3% in diet, corresponding to 270 mg/kg body weight/day.

Levels of prostaglandin E metabolite and leukotriene E(4) are increased in the urine of smokers: evidence that celecoxib shunts arachidonic acid into the 5-lipoxygenase pathway.

PubMed

Duffield-Lillico, Anna J; Boyle, Jay O; Zhou, Xi Kathy; Ghosh, Aradhana; Butala, Geera S; Subbaramaiah, Kotha; Newman, Robert A; Morrow, Jason D; Milne, Ginger L; Dannenberg, Andrew J

2009-04-01

Cyclooxygenase-2 (COX-2) and 5-lipoxygenase (5-LO) play a role in inflammation and carcinogenesis. Biomarkers that reflect tobacco smoke-induced tissue injury are needed. In this study, levels of urinary prostaglandin E metabolite (PGE-M) and leukotriene E(4) (LTE(4)), biomarkers of the COX and 5-LO pathways, were compared in never smokers, former smokers, and current smokers. The effects of celecoxib, a selective COX-2 inhibitor, on levels of PGE-M and LTE(4) were determined. Baseline levels of PGE-M and LTE(4) were positively associated with smoking status; levels of PGE-M and LTE(4) were higher in current versus never smokers. Treatment with 200 mg celecoxib twice daily for 6 +/- 1 days led to a reduction in urinary PGE-M levels in all groups but exhibited the greatest effect among subjects with high baseline PGE-M levels. Thus, high baseline PGE-M levels in smokers reflected increased COX-2 activity. In individuals with high baseline PGE-M levels, treatment with celecoxib led to a significant increase in levels of urinary LTE(4), an effect that was not found in individuals with low baseline PGE-M levels. In conclusion, increased levels of urinary PGE-M and LTE(4) were found in human smokers, a result that may reflect subclinical lung inflammation. In individuals with high baseline levels of PGE-M (elevated COX-2 activity), celecoxib administration shunted arachidonic acid into the proinflammatory 5-LO pathway. Because 5-LO activity and LTE(4) have been suggested to play a role in cardiovascular disease, these results may help to explain the link between use of COX-2 inhibitors and cardiovascular complications.

Urinary heavy metals in Hispanics 40–85 years old in Doña Ana County, New Mexico

PubMed Central

Adams, Scott V.; Barrick, Brian; Freney, Emily P.; Shafer, Martin M.; Song, Xiaoling; Vilchis, Hugo; Newcomb, Polly A.; Ulery, April

2017-01-01

As, Cd, Pb, and U exposure among older Hispanic adults residing in underserved communities in southern New Mexico was investigated. Personal information was obtained by standardized interview from 188 adults age 40–85y. Urinary metal concentrations were measured and compared to results from the National Health and Nutritional Examination Survey (NHANES). Urinary As and U in study participants significantly (P<0.05) exceeded NHANES reference values. Elevated urinary As concentration was significantly associated with older age, Latin American birthplace, clinic site, private well drinking water, higher self-rated health, and diabetes. Higher urinary Cd was significantly associated with older age, clinic site, female sex, agricultural work, and current cigarette smoking. No personal characteristics were significantly associated with urinary Pb or U. Our results suggest elevated levels of As and U in this population. PMID:26666397

Correlation between increased urinary sodium excretion and decreased left ventricular diastolic function in patients with type 2 diabetes mellitus.

PubMed

Kagiyama, Shuntaro; Koga, Tokushi; Kaseda, Shigeru; Ishihara, Shiro; Kawazoe, Nobuyuki; Sadoshima, Seizo; Matsumura, Kiyoshi; Takata, Yutaka; Tsuchihashi, Takuya; Iida, Mitsuo

2009-10-01

Increased salt intake may induce hypertension, lead to cardiac hypertrophy, and exacerbate heart failure. When elderly patients develop heart failure, diastolic dysfunction is often observed, although the ejection fraction has decreased. Diabetes mellitus (DM) is an established risk factor for heart failure. However, little is known about the relationship between cardiac function and urinary sodium excretion (U-Na) in patients with DM. We measured 24-hour U-Na; cardiac function was evaluated directly during coronary catheterization in type 2 DM (n = 46) or non-DM (n = 55) patients with preserved cardiac systolic function (ejection fraction > or = 60%). Cardiac diastolic and systolic function was evaluated as - dp/dt and + dp/dt, respectively. The average of U-Na was 166.6 +/- 61.2 mEq/24 hour (mean +/- SD). In all patients, stepwise multivariate regression analysis revealed that - dp/dt had a negative correlation with serum B-type natriuretic peptide (BNP; beta = - 0.23, P = .021) and U-Na (beta = - 0.24, P = .013). On the other hand, + dp/dt negatively correlated with BNP (beta = - 0.30, P < .001), but did not relate to U-Na. In the DM-patients, stepwise multivariate regression analysis showed that - dp/dt still had a negative correlation with U-Na (beta = - 0.33, P = .025). The results indicated that increased urinary sodium excretion is associated with an impairment of cardiac diastolic function, especially in patients with DM, suggesting that a reduction of salt intake may improve cardiac diastolic function.

Urine protein profiling identified alpha-1-microglobulin and haptoglobin as biomarkers for early diagnosis of acute allograft rejection following kidney transplantation.

PubMed

Stubendorff, Beatrice; Finke, Stephanie; Walter, Martina; Kniemeyer, Olaf; von Eggeling, Ferdinand; Gruschwitz, Torsten; Steiner, Thomas; Ott, Undine; Wolf, Gunter; Wunderlich, Heiko; Junker, Kerstin

2014-12-01

Early diagnosis of acute rejection and effective immunosuppressive therapy lead to improvement in graft survival following kidney transplantation. In this study, we aimed to establish a urinary protein profile suitable to distinguish between patients with rejection and stable graft function and to predict acute rejection based on postoperatively collected urine samples. A further objective was to identify candidate proteins for the use as biomarkers in clinical practice. Urine samples of 116 kidney recipients were included. Rejection was proven by biopsy (n = 58), and stable transplant function was monitored for at least 2 years (n = 58). Postoperative urine samples were collected between 3rd and 10th day following transplantation. Urinary protein profiles were obtained by surface-enhanced laser desorption/ionization time-of-flight mass spectrometry. Protein identification and validation were performed using multiplex fluorescence 2DE, peptide mass fingerprinting and enzyme-linked immunosorbent assay. A protein profile including four mass peaks differentiated acute rejection from stable transplants at the time point of rejection and at the postoperative state with 73 % sensitivity and 88 % specificity. Alpha-1-microglobulin (A1MG) and Haptoglobin (Hp) were identified as putative rejection biomarkers. Protein levels were significantly higher in postoperative urine from patients with rejection (A1MG 29.13 vs. 22.06 μg/ml, p = 0.001; Hp 628.34 vs. 248.57 ng/ml, p = 0.003). The combination of both proteins enabled the diagnosis of early rejection with 85 % sensitivity and 80 % specificity. Protein profiling using mass spectrometry is suitable for noninvasive detection of rejection-specific changes following kidney transplantation. A specific protein profile enables the prediction of early acute allograft rejection in the immediate postoperative period. A1MG and Hp appear to be reliable rejection biomarkers.

Urinary podocyte-associated mRNA levels correlate with proximal tubule dysfunction in early diabetic nephropathy of type 2 diabetes mellitus.

PubMed

Petrica, Ligia; Ursoniu, Sorin; Gadalean, Florica; Vlad, Adrian; Gluhovschi, Gheorghe; Dumitrascu, Victor; Vlad, Daliborca; Gluhovschi, Cristina; Velciov, Silvia; Bob, Flaviu; Matusz, Petru; Milas, Oana; Secara, Alina; Simulescu, Anca; Popescu, Roxana

2017-01-01

The study assessed mRNA expression of podocyte-associated molecules in urinary sediments of patients with type 2 diabetes mellitus (DM) in relation to urinary podocytes, biomarkers of podocyte injury and of proximal tubule (PT) dysfunction. A total of 76 patients with type 2 DM and 20 healthy subjects were enrolled in a cross-sectional study, and assessed concerning urinary podocytes, urinary mRNA of podocyte-associated genes, urinary biomarkers of podocyte damage and of PT dysfunction. We found significant differences between urinary mRNA of podocyte-associated molecules in relation with albuminuria stage. In multivariable regression analysis, urinary mRNA of nephrin, podocin, alpha-actinin-4, CD2-associated protein, glomerular epithelial protein 1 (GLEPP1), ADAM 10, and NFκB correlated directly with urinary podocytes, albuminuria, urinary alpha 1 -microglobulin, urinary kidney-injury molecule-1, nephrinuria, urinary vascular endothelial growth factor, urinary advanced glycation end-products (AGE), and indirectly with eGFR (p < 0.0001, R 2  = 0.808; p < 0.0001, R 2  = 0.825; p < 0.0001, R 2  = 0.805; p < 0.0001, R 2  = 0.663; p < 0.0001, R 2  = 0.726; p < 0.0001, R 2  = 0.720; p < 0.0001, R 2  = 0.724). In patients with type 2 DM there is an association between urinary mRNA of podocyte-associated molecules, biomarkers of podocyte damage, and of PT dysfunction. GLEPP1, ADAM10, and NFκB may be considered additional candidate molecules indicative of early diabetic nephropathy. AGE could be involved in this association.

Demographic, Dietary, and Urinary Factors and 24-h Urinary Calcium Excretion

PubMed Central

Curhan, Gary C.

2009-01-01

Background and objectives: Higher urinary calcium is a risk factor for nephrolithiasis. This study delineated associations between demographic, dietary, and urinary factors and 24-h urinary calcium. Design, setting, participants, & measurements: Cross-sectional studies were conducted of 2201 stone formers (SF) and 1167 nonstone formers (NSF) in the Health Professionals Follow-up Study (men) and Nurses' Health Studies I and II (older and younger women). Results: Median urinary calcium was 182 mg/d in men, 182 mg/d in older women, and 192 mg/d in younger women. Compared with NSF, urinary calcium as a fraction of calcium intake was 33 to 38% higher in SF (P values ≤0.01). In regression analyses, participants were combined because associations with urinary calcium were similar in each cohort and in SF and NSF. After multivariate adjustment, participants in the highest quartile of calcium intake excreted 18 mg/d more urinary calcium than those in the lowest (P trend =0.01). Caffeine and family history of nephrolithiasis were positively associated, whereas urinary potassium, thiazides, gout, and age were inversely associated, with urinary calcium. After multivariate adjustment, participants in the highest quartiles of urinary magnesium, sodium, sulfate, citrate, phosphorus, and volume excreted 71 mg/d, 37 mg/d, 44 mg/d, 61 mg/d, 37 mg/d, and 24 mg/d more urinary calcium, respectively, than participants in the lowest (P values trend ≤0.01). Conclusions: Intestinal calcium absorption and/or negative calcium balance is greater in SF than NSF. Higher calcium intakes at levels typically observed in free-living individuals are associated with only small increases in urinary calcium. PMID:19820135

Passive exposures of children to volatile trihalomethanes during domestic cleaning activities of their parents

DOE Office of Scientific and Technical Information (OSTI.GOV)

Andra, Syam S.; Harvard-Cyprus Program, Department of Environmental Health, Harvard School of Public Health, Boston, MA; Charisiadis, Pantelis

Domestic cleaning has been proposed as a determinant of trihalomethanes (THMs) exposure in adult females. We hypothesized that parental housekeeping activities could influence children's passive exposures to THMs from their mere physical presence during domestic cleaning. In a recent cross-sectional study (n=382) in Cyprus [41 children (<18y) and 341 adults (≥18y)], we identified 29 children who met the study's inclusion criteria. Linear regression models were applied to understand the association between children sociodemographic variables, their individual practices influencing ingestion and noningestion exposures to ΣTHMs, and their urinary THMs levels. Among the children-specific variables, age alone showed a statistically significant inversemore » association with their creatinine-adjusted urinary ΣTHMs (r{sub S}=−0.59, p<0.001). A positive correlation was observed between urinary ΣTHMs (ng g{sup −1}) of children and matched-mothers (r{sub S}=0.52, p=0.014), but this was not the case for their matched-fathers (r{sub S}=0.39, p=0.112). Time spent daily by the matched-mothers for domestic mopping, toilet and other cleaning activities using chlorine-based cleaning products was associated with their children's urinary THMs levels (r{sub S}=0.56, p=0.007). This trend was not observed between children and their matched-fathers urinary ΣTHMs levels, because of minimum amount of time spent by the latter in performing domestic cleaning. The proportion of variance of creatinine-unadjusted and adjusted urinary ΣTHMs levels in children that was explained by the matched-mothers covariates was 76% and 74% (p<0.001), respectively. A physiologically-based pharmacokinetic model adequately predicted urinary chloroform excretion estimates, being consistent with the corresponding measured levels. Our findings highlighted the influence of mothers' domestic cleaning activities towards enhancing passive THMs exposures of their children. The duration of such activities could be further tested as a valid indicator of children's THMs body burden. - Highlights: • First report on THMs exposure assessment in matched parents and children. • Duration of domestic cleaning by mothers influenced passive exposure to THMs in children. • Matched-fathers did little cleaning and thereby no contribution to passive exposure to THMs in children. • Reverse dosimetry showed a good agreement between predicted and observed urinary chloroform. • Passive exposures to THMs require new attention in survey questionnaires and epidemiology.« less

Serial urinary IL-2, IL-6, IL-8, TNFalpha, UBC, CYFRA 21-1 and NMP22 during follow-up of patients with bladder cancer receiving intravesical BCG.

PubMed

Sanchez-Carbayo, M; Urrutia, M; Romani, R; Herrero, M; Gonzalez de Buitrago, J M; Navajo, J A

2001-01-01

We evaluated the potential role of serial preinstillation levels of several interleukins, TNFalpha and urinary tumor markers to monitor patients with bladder cancer receiving intravesical BCG. 121 urine samples were collected from: patients with bladder cancer treated with BCG (group 1); patients with bladder cancer receiving other intravesical treatment (group 2) and patients with urinary tract infections (group 3). Cytokines [IL-2, IL6 and [L8] and TNFalpha and urinary tumor markers [UBC, CYFRA 21-1 and NMP22] were measured by immunoassays. In 3 out of 15 BCG non-responders that recurred over the period of the study, no cytokine peak for IL-2, IL-6 or TNFa were detected. Urinary tumor markers increased in 2 out of 3 of these patients earlier than scheduled cystoscopies. Cytokine measurement was heterogeneous among 12 out of 15 BCG-responding patients: there were low levels of IL-6 and TNFalpha and peaks of IL-2 and IL-8 in 10 out of 12 and 4 out of 12 patients, respectively. During responding patients' follow-up we observed false-positive results in 7 out of 65 urine samples for UBC, 8 out of 65 for CYFRA 21-1 and 20 out of 65 for NMP22. Urinary tract infections were the main factor associated with non-specific elevations of IL-6 and IL-8 and urinary tumor markers in all groups of patients. Although larger series are required to confirn our preliminary observations, our data argue for a potential predictive role for IL-2 of favourable response to BCG therapy. Monitoring BCG with urinary tumor markers could early detect recurrence in non-responding patients.

Copper Is a Host Effector Mobilized to Urine during Urinary Tract Infection To Impair Bacterial Colonization.

PubMed

Hyre, Amanda N; Kavanagh, Kylie; Kock, Nancy D; Donati, George L; Subashchandrabose, Sargurunathan

2017-03-01

Urinary tract infection (UTI) is a major global infectious disease affecting millions of people annually. Human urinary copper (Cu) content is elevated during UTI caused by uropathogenic Escherichia coli (UPEC). UPEC upregulates the expression of Cu efflux genes during clinical UTI in patients as an adaptive response to host-derived Cu. Whether Cu is mobilized to urine as a host response to UTI and its role in protection against UTI remain unresolved. To address these questions, we tested the hypothesis that Cu is a host effector mobilized to urine during UTI to limit bacterial growth. Our results reveal that Cu is mobilized to urine during UTI caused by the major uropathogens Proteus mirabilis and Klebsiella pneumoniae , in addition to UPEC, in humans. Ceruloplasmin, a Cu-containing ferroxidase, is found at higher levels in UTI urine than in healthy control urine and serves as the molecular source of urinary Cu during UTI. Our results demonstrate that ceruloplasmin decreases the bioavailability of iron in urine by a transferrin-dependent mechanism. Experimental UTI with UPEC in nonhuman primates recapitulates the increased urinary Cu content observed during clinical UTI. Furthermore, Cu-deficient mice are highly colonized by UPEC, indicating that Cu is involved in the limiting of bacterial growth within the urinary tract. Collectively, our results indicate that Cu is a host effector that is involved in protection against pathogen colonization of the urinary tract. Because urinary Cu levels are amenable to modulation, augmentation of the Cu-based host defense against UTI represents a novel approach to limiting bacterial colonization during UTI. Copyright © 2017 American Society for Microbiology.

Fermented whey-based product improves the quality of life of males with moderate lower urinary tract symptoms: A randomized double-blind study.

PubMed

Ausmees, Kristo; Ehrlich-Peets, Kersti; Vallas, Mirjam; Veskioja, Andre; Rammul, Kadi; Rehema, Aune; Zilmer, Mihkel; Songisepp, Epp; Kullisaar, Tiiu

2018-01-01

The purpose of this research was to evaluate the effect of a specific fermented whey product on lower urinary tract symptoms, main prostate related indices and oxidative stress/inflammatory markers in urine and seminal plasma in men with moderate dysuric symptoms. An additional purpose was to clarify associations between different parameters with special emphasis on pain. This was a prospective randomized double-blind 4-weeks study on men with moderate lower urinary tract symptoms who underwent the evaluation for quality of life at the baseline and at the end of the study. The symptoms were characterized by International Prostate Symptom Score (I-PSS) and National Institutes of Health Chronic Prostatitis Symptom Index (NIH-PSI), the maximum urinary flow and the main prostate-related indices. In order to obtain more comprehensive information about the effects of fermented whey product on systemic oxidative stress marker 8-EPI and seminal plasma inflammatory markers (interleukin-6 and interleukin-8) were also measured. After 4 weeks consumption of fermented whey product there was a statistically significant decrease of prostate-specific antigen level in serum and systemic stress marker 8-EPI in urine compared to control group. Maximum urinary flow and NIH-PSI all studied scores and sub-scores had also significant improvement. In addition, seminal plasma interleukin-8 level substantially decreased. The consumption of special fermented whey product improved urinary function, reduced lower urinary tract symptoms, systemic oxidative stress marker and seminal plasma inflammatory status. Thus it contributed to an improvement of the quality of life in men with moderate lower urinary tract symptoms.

Progress in cadmium-related health effects in persons with high environmental exposure in northwestern Thailand: a five-year follow-up.

PubMed

Swaddiwudhipong, Witaya; Limpatanachote, Pisit; Mahasakpan, Pranee; Krintratun, Somyot; Punta, Boonyarat; Funkhiew, Thippawan

2012-01-01

Food-borne cadmium was the principal source of exposure for persons living in the 12 cadmium-contaminated villages in Mae Sot District, Tak Province, northwestern Thailand. This report presents progress in cadmium-related health effects among persons with high cadmium exposure. The study included 436 persons who had urinary cadmium levels ≥5 μg/g creatinine and were screened for urinary cadmium, renal function, hypertension, diabetes and urinary stones in 2005 (baseline) and 2010 (5-year follow-up). Study renal biomarkers included urinary excretion of β(2)-microglobulin (β(2)-MG), total protein and calcium, serum creatinine and glomerular filtration rate (GFR). The geometric mean level of urinary cadmium statistically significantly reduced from 9.5±1.6 μg/g creatinine in 2005 to 8.8±1.6 μg/g creatinine in 2010. Compared to baseline, the follow-up examination revealed significant increases in urinary β(2)-MG (tubular effect), urinary total protein and serum creatinine, and a decrease in GFR (glomerular effects). Progressive renal dysfunctions were similarly observed in persons both with and without reduction in cadmium intake. Significant increases in prevalence of hypertension, diabetes and urinary stones were also detected at follow-up. These three disorders were found to markedly impair renal functions in the study persons. Our study indicates that in persons with prolonged excessive cadmium exposure, toxic health effects may progress even after exposure reduction. Renal damage from cadmium can be due to its direct nephrotoxic effect and also through the related disorders causing nephropathy. Copyright © 2011 Elsevier Inc. All rights reserved.

A receiver operated curve-based evaluation of change in sensitivity and specificity of cotinine urinalysis for detecting active tobacco use.

PubMed

Balhara, Yatan Pal Singh; Jain, Raka

2013-01-01

Tobacco use has been associated with various carcinomas including lung, esophagus, larynx, mouth, throat, kidney, bladder, pancreas, stomach, and cervix. Biomarkers such as concentration of cotinine in the blood, urine, or saliva have been used as objective measures to distinguish nonusers and users of tobacco products. A change in the cut-off value of urinary cotinine to detect active tobacco use is associated with a change in sensitivity and sensitivity of detection. The current study aimed at assessing the impact of using different cut-off thresholds of urinary cotinine on sensitivity and specificity of detection of smoking and smokeless tobacco product use among psychiatric patients. All the male subjects attending the psychiatry out-patient department of the tertiary care multispecialty teaching hospital constituted the sample frame for the current study in a cross-sectionally. Quantitative urinary cotinine assay was done by using ELISA kits of Calbiotech. Inc., USA. We used the receiver operating characteristic (ROC) curve to assess the sensitivity and specificity of various cut-off values of urinary cotinine to identify active smokers and users of smokeless tobacco products. ROC analysis of urinary cotinine levels in detection of self-reported smoking provided the area under curve (AUC) of 0.434. Similarly, the ROC analysis of urinary cotinine levels in detection of self-reported smoking revealed AUC of 0.44. The highest sensitivity and specificity of 100% for smoking were detected at the urinary cut-off value greater than or equal to 2.47 ng/ml. The choice of cut-off value of urinary cotinine used to distinguish nonusers form active users of tobacco products impacts the sensitivity as well as specificity of detection.

[Values of combination of urinary L-FABP and NGAL in early diagnosis of acute kidney injury after cardiac surgery in children].

PubMed

Tang, Rong; Ao, Xiang; Zhong, Yong; Wang, Rui-Ling; Zhou, Qiao-Ling

2017-07-01

To investigate the values of combination of urinary liver-type fatty acid-binding protein (L-FABP) and neutrophil gelatinase-associated lipocalin (NGAL) in early diagnosis of acute kidney injury (AKI) after cardiac surgery in children. A total of 97 children with congenital heart disease undergoing cardiopulmonary bypass surgery were enrolled. Serum and urine samples were collected before and after surgery. Levels of serum creatinine (Scr), urinary L-FABP, and urinary NGAL from AKI group (n=18) and non-AKI group (n=79) were measured, and the postoperative dynamic changes in these markers were compared between the two groups. The receiver operating characteristic (ROC) curve and the area under ROC curve (AUC) were used to assess the values of these markers alone or in combination in the prediction of postoperative AKI. The levels of urinary L-FABP and NGAL in the AKI group were significantly higher than those in the non-AKI group at 2 and 6 hours after surgery, and the changes in their concentrations were earlier than Scr. The AUCs of urinary L-FABP alone in predicting AKI at 2 and 6 hours after surgery were 0.921 and 0.896 respectively, and those of urinary NGAL alone were 0.908 and 0.928 respectively. Those of their combination were 0.942 and 0.929 respectively. Urinary L-FABP and NGAL significantly increase in the early stage of AKI after cardiac surgery in children, which are significantly earlier than the changes in Scr. They can be used to predict the occurrence of AKI in the early stage. A combination of the two biomarkers can further improve the accuracy of diagnosis.

Changes of urinary angiotensinogen concentration and its association with urinary proteins in diabetic rats

PubMed Central

Zhuang, Zhen; Bai, Qiong; A, Lata; Liang, Yaoxian; Zheng, Danxia; Wang, Yue

2015-01-01

Objective: It had been reported that angiotensinogen might be a marker for activation of renin-angiotensin system, which was associated with the development of diabetic nephropathy. The purpose of this study was to investigate the functional roles of AGT in DN in vitro. Methods: Diabetic rat models were built by single intraperitoneal injection of streptozotocin. The diabetic rats were divided into three groups, two of the three groups were treated with different doses of losartan, the other diabetic group was as control and normal rats acted as healthy control. In a 12-week investigation, we detected the changes of AGT in all rats’ blood and urine and the association between AGT concentration and RAS activation and urinary proteins were analyzed in this study. Results: The serum AGT of rats had no significant differences (P>0.05 for all). The urinary AGT of the diabetic rats was significantly different from the control group, moreover, the urinary AGT of the diabetic rats under different treatments was also obviously different (P<0.05 for all). Besides, the results of immunohistochemical assay indicated that AGT expression level was correlated with renal tissues damage. The level of AGT was positively associated with urinary protein (r=0.493, P<0.01) and negatively correlated with CCr (r=-0.474, P=0.007) and the dose of ARB (r=-0.575, P=0.001). Moreover, the dose of ARB was independently associated with urinary AGT (B=-2.963, P=0.024) in diabetic rats. Conclusion: Urinary AGT may be a marker for the activation of local RAS in kidney and independently associated with ARB. PMID:26722381

Association between exposures to brominated trihalomethanes, hepatic injury and type II diabetes mellitus.

PubMed

Makris, Konstantinos C; Andrianou, Xanthi D; Charisiadis, Pantelis; Burch, James B; Seth, Ratanesh K; Ioannou, Androniki; Picolos, Michael; Christophi, Costas A; Chatterjee, Saurabh

2016-01-01

Non-alcoholic fatty liver disease (NAFLD) is considered the most common liver disorder in the Western world, commonly diagnosed in the majority of obese patients with type 2 diabetes mellitus (T2DM). Metabolic disrupting chemicals with short half-lives, such as those of halogenated structure (trihalomethanes, THM) have been linked with hepatic insulin resistance phenomena in animal studies. However, human studies evaluating the role of THM exposure on liver pathogenesis and T2DM disease process are scarce. The objectives of this study were to: i) determine the association of urinary brominated THM (BrTHM) levels and T2DM disease status, and ii) investigate the association between urinary BrTHM levels and serum alanine aminotransferase (ALT) concentrations, often used as surrogate markers of NAFLD. A pilot case-control study was conducted in Nicosia, Cyprus (n=95). Cases were physician-diagnosed T2DM patients and controls were healthy individuals. Liver enzymes, leptin and TNF-α were measured in sera, while urinary THM levels were measured using tandem mass spectrometry. Diabetics had higher levels of serum leptin, body mass index and ALT than the controls. Among all study participants those with serum ALT levels above the median (17IU/L) had higher mean tribromomethane (TBM) concentrations compared to those with serum ALT below 17IU/L. A significant increase in the odds of having above the median serum ALT levels [OR 6.38, 95% CI: 1.11, 42.84 (p=0.044)] was observed for each unit increase in creatinine-unadjusted urinary TBM levels, along with BMI and past smoking, after adjusting for possible confounders, such as urinary creatinine, age, sex, and leptin; no other THM compound showed a significant association with serum ALT. Logistic regression models for T2DM using the urinary BrTHM as exposure variables did not reach the predetermined level of significance. The interplay between exposures to BrTHM and the initiation of key pathophysiological events relating to hepatic injury (ALT) and inflammation (leptin) was recognized via the use of selected biomarkers of effect. Our evidence that THM could act as hepatic toxins with a further initiation of diabetogenic effects call for additional studies to help us better understand the disease process of the two co-morbidities (NAFLD and T2DM). Copyright © 2016 Elsevier Ltd. All rights reserved.

A 12-month phase 3 study of pasireotide in Cushing's disease.

PubMed

Colao, Annamaria; Petersenn, Stephan; Newell-Price, John; Findling, James W; Gu, Feng; Maldonado, Mario; Schoenherr, Ulrike; Mills, David; Salgado, Luiz Roberto; Biller, Beverly M K

2012-03-08

Cushing's disease is associated with high morbidity and mortality. Pasireotide, a potential therapy, has a unique, broad somatostatin-receptor-binding profile, with high binding affinity for somatostatin-receptor subtype 5. In this double-blind, phase 3 study, we randomly assigned 162 adults with Cushing's disease and a urinary free cortisol level of at least 1.5 times the upper limit of the normal range to receive subcutaneous pasireotide at a dose of 600 μg (82 patients) or 900 μg (80 patients) twice daily. Patients with urinary free cortisol not exceeding 2 times the upper limit of the normal range and not exceeding the baseline level at month 3 continued to receive their randomly assigned dose; all others received an additional 300 μg twice daily. The primary end point was a urinary free cortisol level at or below the upper limit of the normal range at month 6 without an increased dose. Open-label treatment continued through month 12. Twelve of the 82 patients in the 600-μg group and 21 of the 80 patients in the 900-μg group met the primary end point. The median urinary free cortisol level decreased by approximately 50% by month 2 and remained stable in both groups. A normal urinary free cortisol level was achieved more frequently in patients with baseline levels not exceeding 5 times the upper limit of the normal range than in patients with higher baseline levels. Serum and salivary cortisol and plasma corticotropin levels decreased, and clinical signs and symptoms of Cushing's disease diminished. Pasireotide was associated with hyperglycemia-related adverse events in 118 of 162 patients; other adverse events were similar to those associated with other somatostatin analogues. Despite declines in cortisol levels, blood glucose and glycated hemoglobin levels increased soon after treatment initiation and then stabilized; treatment with a glucose-lowering medication was initiated in 74 of 162 patients. The significant decrease in cortisol levels in patients with Cushing's disease who received pasireotide supports its potential use as a targeted treatment for corticotropin-secreting pituitary adenomas. (Funded by Novartis Pharma; ClinicalTrials.gov number, NCT00434148.).

Hair mercury and urinary cadmium levels in Belgian children and their mothers within the framework of the COPHES/DEMOCOPHES projects.

PubMed

Pirard, Catherine; Koppen, Gudrun; De Cremer, Koen; Van Overmeire, Ilse; Govarts, Eva; Dewolf, Marie-Christine; Van De Mieroop, Els; Aerts, Dominique; Biot, Pierre; Casteleyn, Ludwine; Kolossa-Gehring, Marike; Schwedler, Gerda; Angerer, Jürgen; Koch, Holger M; Schindler, Birgit K; Castaño, Argelia; Esteban, Marta; Schoeters, Greet; Den Hond, Elly; Sepai, Ovnair; Exley, Karen; Horvat, Milena; Bloemen, Louis; Knudsen, Lisbeth E; Joas, Reinhard; Joas, Anke; Van Loco, Joris; Charlier, Corinne

2014-02-15

A harmonized human biomonitoring pilot study was set up within the frame of the European projects DEMOCOPHES and COPHES. In 17 European countries, biomarkers of some environmental pollutants, including urinary cadmium and hair mercury, were measured in children and their mothers in order to obtain European-wide comparison values on these chemicals. The Belgian participant population consisted in 129 school children (6-11 years) and their mothers (≤ 45 years) living in urban or rural areas of Belgium. The geometric mean levels for mercury in hair were 0.383 μg/g and 0.204 μg/g for respectively mothers and children. Cadmium in mother's and children's urine was detected at a geometric mean concentration of respectively 0.21 and 0.04 μg/l. For both biomarkers, levels measured in the mothers and their child were correlated. While the urinary cadmium levels increased with age, no trend was found for hair mercury content, except the fact that mothers hold higher levels than children. The hair mercury content increased significantly with the number of dental amalgam fillings, explaining partially the higher levels in the mothers by their higher presence rate of these amalgams compared to children. Fish or seafood consumption was the other main parameter determining the mercury levels in hair. No relationship was found between smoking status and cadmium or mercury levels, but the studied population included very few smokers. Urinary cadmium levels were higher in both mothers and children living in urban areas, while for mercury this difference was only significant for children. Our small population showed urinary cadmium and hair mercury levels lower than the health based guidelines suggested by the WHO or the JECFA (Joint FAO/WHO Expert Committee on Food Additives). Only 1% had cadmium level slightly higher than the German HBM-I value (1 μg/l for adults), and 9% exceeded the 1 μg mercury/g hair suggested by the US EPA. Copyright © 2013 Elsevier B.V. All rights reserved.

The effect of dietary factors on nitrosoproline levels in human urine.

PubMed

Stich, H F; Hornby, A P; Dunn, B P

1984-05-15

The effect of dietary components on the levels of nitrosoproline ( NPRO ) excreted over a 24 h period in the urine was examined in volunteers ingesting known amounts of various food products. The ingestion of nitrite-preserved meats (85-170 g per meal), including canned, rolled or Yunnan ham, cured pork, luncheon meat, and various Chinese and European-style sausages, led to urinary NPRO excretion levels ranging from 2.5 to 78.5 micrograms/24 h, whereas the consumption of non-preserved meat and fish products, including chicken, herring, salmon, shrimp, ground beef (hamburger), pork chops and beef liver, led to relatively low NPRO excretion levels, ranging from 0.0 to 0.8 micrograms/24 h. The urinary NPRO levels of 22 vegetarians and 14 lacto-vegetarians averaged 0.8 and 1.4 micrograms/24 h, respectively. A change from a nitrite-preserved meat diet to a vegetarian diet was accompanied by an approximately six-fold reduction in urinary NPRO levels; however, these remained above control levels for at least 3 days following the dietary change. The relatively high NPRO levels following the ingestion of nitrite-preserved meats could not be reduced by nitrite-trapping chemicals, including ascorbic acid, ferulic acid, caffeic acid, or phenolic-containing mixtures such as coffee and tea, which were effective in suppressing endogenous NPRO formation following the intake of nitrate and proline. The high urinary NPRO levels after ingestion of preserved meat products appear to be due to the consumption of preformed NPRO . An understanding of the relative contribution of preformed and endogenously formed nitrosamines appears to be essential when designing dietary intervention programmes.