Sample records for kidney tissue samples

  1. Validation of an LC-MS/MS method to measure tacrolimus in rat kidney and liver tissue and its application to human kidney biopsies.

    PubMed

    Noll, Benjamin D; Coller, Janet K; Somogyi, Andrew A; Morris, Raymond G; Russ, Graeme R; Hesselink, Dennis A; Van Gelder, Teun; Sallustio, Benedetta C

    2013-10-01

    Tacrolimus (TAC) has a narrow therapeutic index and high interindividual and intraindividual pharmacokinetic variability, necessitating therapeutic drug monitoring to individualize dosage. Recent evidence suggests that intragraft TAC concentrations may better predict transplant outcomes. This study aimed to develop a method for the quantification of TAC in small biopsy-sized samples of rat kidney and liver tissue, which could be applied to clinical biopsy samples from kidney transplant recipients. Kidneys and livers were harvested from Mrp2-deficient TR- Wistar rats administered TAC (4 mg·kg·d for 14 days, n = 8) or vehicle (n = 10). Tissue samples (0.20-1.00 mg of dry weight) were solubilized enzymatically and underwent liquid-liquid extraction before analysis by liquid chromatography tandem mass spectrometry method. TAC-free tissue was used in the calibrator and quality control samples. Analyte detection was accomplished using positive electrospray ionization (TAC: m/z 821.5 → 768.6; internal standard ascomycin m/z 809.3 → 756.4). Calibration curves (0.04-2.6 μg/L) were linear (R > 0.99, n = 10), with interday and intraday calibrator coefficients of variation and bias <17% at the lower limit of quantification and <15% at all other concentrations (n = 6-10). Extraction efficiencies for TAC and ascomycin were approximately 70%, and matrix effects were minimal. Rat kidney TAC concentrations were higher (range 109-190 pg/mg tissue) than those in the liver (range 22-53 pg/mg of tissue), with median tissue/blood concentrations ratios of 72.0 and 17.6, respectively. In 2 transplant patients, kidney TAC concentrations ranged from 119 to 285 pg/mg of tissue and were approximately 20 times higher than whole blood trough TAC concentrations. The method displayed precision and accuracy suitable for application to TAC measurement in human kidney biopsy tissue.

  2. Investigation of zoonotic disease pathogens (Aeromonas hydrophila, Pseudomonas fluorescens, Streptococcus iniae) seen in carp farms in the Northern Iraq-Erbil region by molecular methods

    NASA Astrophysics Data System (ADS)

    Ibraheem, Azad Saber; Önalan, Şükrü; Arabacı, Muhammed

    2017-04-01

    The aim of this study was to determine the zoonotic bacteria in carp farms in the Northern Iraq-Erbil region. Carp is the main fish species cultured in Erbil region. The most common zoonotic bacteria generally seen in carp farms are Aeromonas hydrophila, Pseudomonas fluorescens and Streptococcus iniae. Samples were collected from 25 carp farms in the Northern Iraq-Erbil region. Six carp samples were collected from each carp farm. Head kidney and intestine tissue samples were collected from each carp sample. Then head kidney and intestine tissue samples were pooled separately from each carp farm. Total bacterial DNA had been extracted from the 25 pooled head kidney and 25 intestinal tissue samples. The pathogen Primers were originally designed from 16S RNA gene region. Zoonotic bacteria were scanned in all tissue samples with absent/present analysis by RT-PCR. Furthermore, the capillary gel electrophoresis bands were used for confirmation of amplicon size which was planned during primer designing stage. As a result, thirteen carp farms were positive in the respect to Aeromonas hydrophila, eight carp farms were positive from head kidney and six carp farms were positive from the intestine, only one carp farm was positive from both head kidney and the intestine tissue samples. In the respect to Streptococcus iniae, four carp farms were positive from head kidney and two carp farms were positive from the intestine. Only one carp farm was positive in the respect to Pseudomonas fluorescens from the intestine. Totally, 9 of 25 carp farms were cleared (negative) the zoonotic bacteria. In conclusion, the zoonotic bacteria were high (64 %) in carp farms in the Northern Iraq-Erbil region.

  3. Insight into mechanism of oxidative DNA damage in angiomyolipomas from TSC patients

    PubMed Central

    Habib, Samy L

    2009-01-01

    Background The tuberous sclerosis complex (TSC) is caused by defects in one of two tumor suppressor genes, TSC-1 or TSC-2. TSC-2 gene encodes tuberin, a protein involved in the pathogenesis of kidney tumors, both angiomyolipomas and renal cell carcinomas. Loss of heterozygosity at the 8-oxoG-DNA glycosylase (OGG1) allele is found in human kidney clear cell carcinoma identifying loss of OGG1 function as a possible contributor to tumorigenesis in the kidney. Tuberin regulates OGG1 through the transcription factor NF-YA in cultured cells. The purpose of this study is to determine the effect of tuberin-deficiency on OGG1 protein and mRNA levels as well as on 8-oxodG levels in kidney tumors from patients with TSC. In addition we evaluated the phophorylation level of downstream targets of mTOR, phospho-S70K, in kidney tumor tissue from TSC patients. Results Kidney angiomyolipoma tissue from TSC patients expresses significant levels of phopho-tuberin and low levels of tuberin compared to control kidney tissue. The increase in tuberin phosphorylation and the decrease tuberin expression are associated with decrease in OGG1 protein and mRNA levels in tumor samples compared to normal kidney samples. The decrease OGG1 expression is also associated with significant decrease in the transcription factor, NF-YA, expression in tumor samples compared to normal tissues. In addition, the levels of 8-oxodG are 4-fold higher in tumors compared to control samples. The significant increase of phospho-tuberin expression is associated with increase phosphorylation of S6K in tumor samples compared to controls. Cyclin D1 expression is also 3-fold higher in increase in the tumor tissues compared to normal kidney tissues. Conclusion These data indicate that tuberin deficiency in angiomyolipoma enhances mTOR activation by phosphorylation of S6K and downregulation of protein and mRNA expression of OGG1 resulted in accumulation of oxidized DNA in patients with TSC. These data suggest that tuberin and OGG1 are important proteins in the pathogenesis of angiomyolipoma in TSC patients. PMID:19265534

  4. Effects of Re-heating Tissue Samples to Core Body Temperature on High-Velocity Ballistic Projectile-tissue Interactions.

    PubMed

    Humphrey, Caitlin; Henneberg, Maciej; Wachsberger, Christian; Maiden, Nicholas; Kumaratilake, Jaliya

    2017-11-01

    Damage produced by high-speed projectiles on organic tissue will depend on the physical properties of the tissues. Conditioning organic tissue samples to human core body temperature (37°C) prior to conducting ballistic experiments enables their behavior to closely mimic that of living tissues. To minimize autolytic changes after death, the tissues are refrigerated soon after their removal from the body and re-heated to 37°C prior to testing. This research investigates whether heating 50-mm-cube samples of porcine liver, kidney, and heart to 37°C for varying durations (maximum 7 h) can affect the penetration response of a high-speed, steel sphere projectile. Longer conditioning times for heart and liver resulted in a slight loss of velocity/energy of the projectile, but the reverse effect occurred for the kidney. Possible reasons for these trends include autolytic changes causing softening (heart and liver) and dehydration causing an increase in density (kidney). © 2017 American Academy of Forensic Sciences.

  5. Rapid intra-operative diagnosis of kidney cancer by attenuated total reflection infrared spectroscopy of tissue smears.

    PubMed

    Pucetaite, Milda; Velicka, Martynas; Urboniene, Vidita; Ceponkus, Justinas; Bandzeviciute, Rimante; Jankevicius, Feliksas; Zelvys, Arunas; Sablinskas, Valdas; Steiner, Gerald

    2018-05-01

    Herein, a technique to analyze air-dried kidney tissue impression smears by means of attenuated total reflection infrared (ATR-IR) spectroscopy is presented. Spectral tumor markers-absorption bands of glycogen-are identified in the ATR-IR spectra of the kidney tissue smear samples. Thin kidney tissue cryo-sections currently used for IR spectroscopic analysis lack such spectral markers as the sample preparation causes irreversible molecular changes in the tissue. In particular, freeze-thaw cycle results in degradation of the glycogen and reduction or complete dissolution of its content. Supervised spectral classification was applied to the recorded spectra of the smears and the test spectra were classified with a high accuracy of 92% for normal tissue and 94% for tumor tissue, respectively. For further development, we propose that combination of the method with optical fiber ATR probes could potentially be used for rapid real-time intra-operative tissue analysis without interfering with either the established protocols of pathological examination or the ordinary workflow of operating surgeon. Such approach could ensure easier transition of the method to clinical applications where it may complement the results of gold standard histopathology examination and aid in more precise resection of kidney tumors. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  6. A probe-based quantitative PCR assay for detecting Tetracapsuloides bryosalmonae in fish tissue and environmental DNA water samples

    USGS Publications Warehouse

    Hutchins, Patrick; Sepulveda, Adam; Martin, Renee; Hopper, Lacey

    2017-01-01

    A probe-based quantitative real-time PCR assay was developed to detect Tetracapsuloides bryosalmonae, which causes proliferative kidney disease in salmonid fish, in kidney tissue and environmental DNA (eDNA) water samples. The limits of detection and quantification were 7 and 100 DNA copies for calibration standards and T. bryosalmonae was reliably detected down to 100 copies in tissue and eDNA samples. The assay presented here is a highly sensitive and quantitative tool for detecting T. bryosalmonae with potential applications for tissue diagnostics and environmental detection.

  7. Tissue Distribution of Enrofloxacin in African Clawed Frogs (Xenopus laevis) after Intramuscular and Subcutaneous Administration

    PubMed Central

    Felt, Stephen; Papich, Mark G; Howard, Antwain; Long, Tyler; McKeon, Gabriel; Torreilles, Stéphanie; Green, Sherril

    2013-01-01

    As part of an enrofloxacin pharmacokinetic study, concentrations of enrofloxacin and ciprofloxacin (metabolite) were measured in various tissues (brain, heart, kidney, liver, lung, and spleen) collected from treated (subcutaneous delivery, n = 3; intramuscular delivery, n = 3; untreated controls, n = 2) adult female Xenopus laevis by using HPLC. Enrofloxacin was rapidly absorbed after administration by either route and readily diffused into all sampled tissues. Enrofloxacin and ciprofloxacin were present in the tissue samples collected at 8 h. The highest average tissue concentrations for enrofloxacin were found in kidney, with the lowest concentrations in liver. Ciprofloxacin tissue concentrations paralleled but were always lower than those of enrofloxacin for all time points and tissues except brain and kidney. These results, together with previously published pharmacokinetic data and known minimal inhibitory concentrations of common pathogenic bacteria, provide a strong evidence-based rationale for choosing enrofloxacin to treat infectious diseases in X. laevis. PMID:23562103

  8. Tissue distribution of enrofloxacin in African clawed frogs (Xenopus laevis) after intramuscular and subcutaneous administration.

    PubMed

    Felt, Stephen; Papich, Mark G; Howard, Antwain; Long, Tyler; McKeon, Gabriel; Torreilles, Stéphanie; Green, Sherril

    2013-03-01

    As part of an enrofloxacin pharmacokinetic study, concentrations of enrofloxacin and ciprofloxacin (metabolite) were measured in various tissues (brain, heart, kidney, liver, lung, and spleen) collected from treated (subcutaneous delivery, n = 3; intramuscular delivery, n = 3; untreated controls, n = 2) adult female Xenopus laevis by using HPLC. Enrofloxacin was rapidly absorbed after administration by either route and readily diffused into all sampled tissues. Enrofloxacin and ciprofloxacin were present in the tissue samples collected at 8 h. The highest average tissue concentrations for enrofloxacin were found in kidney, with the lowest concentrations in liver. Ciprofloxacin tissue concentrations paralleled but were always lower than those of enrofloxacin for all time points and tissues except brain and kidney. These results, together with previously published pharmacokinetic data and known minimal inhibitory concentrations of common pathogenic bacteria, provide a strong evidence-based rationale for choosing enrofloxacin to treat infectious diseases in X. laevis.

  9. Norfloxacin penetration into human renal and prostatic tissues.

    PubMed Central

    Bergeron, M G; Thabet, M; Roy, R; Lessard, C; Foucault, P

    1985-01-01

    Concurrent norfloxacin concentrations in serum, kidney, and prostatic tissue were determined in 14 patients. Mean ratios of norfloxacin concentration in tissue over concentration in serum were 6.6 +/- 2.8 for the kidney and 1.7 +/- 0.2 for the prostate samples. The levels were above the MICs of most urinary pathogens. PMID:3834837

  10. Comparison of polymerase chain reaction and Warthin-Starry techniques to detect Leptospira spp. in kidneys of slaughtered cattle.

    PubMed

    Azizi, Shahrzad; Kheirandish, Reza; Rahimi, Elham

    2014-11-12

    Leptospirosis is a worldwide zoonotic disease that is caused by Gram-negative spirochaetes, Leptospira species. Affected animals excrete the organism in the urine into the environment and act as a source of infection. Cattle are maintenance hosts for some serovars of leptospirosis and are important in the transmission of the infection to humans. At post mortem examination, affected cattle show white spots in their kidneys but these are not specific for leptospirosis. Sometimes it is necessary that leptospirosis be diagnosed in the carcass. Different direct methods, including polymerase chain reaction (PCR), Warthin-Starry silver stain (WS), immunofluorescence (IF) and immunohistochemistry (IHC) can be used in order to diagnose leptospirosis in the affected tissues, such as kidney. The main advantage of the WS technique is direct visualisation of the bacteria in the tissue samples. Silver staining is useful for retrospective studies on formalin-fixed and paraffin-embedded samples but little information is available on the sensitivity and specificity of the technique. The present study aimed to find a simple and inexpensive method that can be used in any laboratory and that also, if clinical samples are not available, can detect Leptospira in tissue samples post mortem. This study was performed on 19 paraffin-embedded kidneys of slaughtered cows that grossly had focal to multifocal white spots. Leptospirosis was confirmed in these samples with PCR based on the LipL32 gene. Out of 19 PCR positive kidneys, Leptospira was identified in 13 stained samples by WS. The kidneys revealed different grades of interstitial nephritis. No relationship was found between severity of lesions and presence of leptospires in the kidneys. The PCR results on the urine and blood were consistent with matching WS stained kidneys. Out of 13 kidneys that were positive with silver staining, 7 matching blood and 10 matching urine samples were confirmed positive for leptospirosis with PCR. In this study, the WS technique provided fewer positive results than PCR. This may be as a result of a low burden of Leptospira in the kidney, but the sensitivity of WS staining needs more investigation.

  11. Systemic effect of mineral aggregate-based cements: histopathological analysis in rats.

    PubMed

    Garcia, Lucas da Fonseca Roberti; Huck, Claudia; Magalhães, Fernando Augusto Cintra; Souza, Pedro Paulo Chaves de; Souza Costa, Carlos Alberto de

    2017-01-01

    Several studies reported the local tissue reaction caused by mineral aggregate-based cements. However, few studies have investigated the systemic effects promoted by these cements on liver and kidney when directly applied to connective tissue. The purpose of this in vivo study was to investigate the systemic effect of mineral aggregate-based cements on the livers and kidneys of rats. Samples of Mineral Trioxide Aggregate (MTA) and a calcium aluminate-based cement (EndoBinder) containing different radiopacifiers were implanted into the dorsum of 40 rats. After 7 and 30 d, samples of subcutaneous, liver and kidney tissues were submitted to histopathological analysis. A score (0-3) was used to grade the inflammatory reaction. Blood samples were collected to evaluate changes in hepatic and renal functions of animals. The moderate inflammatory reaction (2) observed for 7 d in the subcutaneous tissue decreased with time for all cements. The thickness of inflammatory capsules also presented a significant decrease with time (P<.05). Systemically, all cements caused adverse inflammatory reactions in the liver and kidney, being more evident for MTA, persisting until the end of the analysis. Liver functions increased significantly for MTA during 30 d (P<.05). The different cements induced to a locally limited inflammatory reaction. However, from the systemic point of view, the cements promoted significant inflammatory reactions in the liver and kidney. For MTA, the reactions were more accentuated.

  12. Extraintestinal Complications: Kidney Disorders

    MedlinePlus

    ... the ureters, bladder, and urethra for the passage, storage, and voiding of urine. Serious kidney complications associated with IBD are rare, ... Proteinuria, an elevated level of protein in the urine, is one sign of amyloidosis. A biopsy (tissue sample) of the kidney can confirm the diagnosis. Various ...

  13. Biomarkers in Tissue Samples From Patients With High-Risk Wilms Tumor

    ClinicalTrials.gov

    2016-05-17

    Clear Cell Sarcoma of the Kidney; Recurrent Wilms Tumor and Other Childhood Kidney Tumors; Rhabdoid Tumor of the Kidney; Stage I Wilms Tumor; Stage II Wilms Tumor; Stage III Wilms Tumor; Stage IV Wilms Tumor; Stage V Wilms Tumor

  14. Interventional Vitamin C A Strategy for Attenuation of Coagulopathy and Inflammation in Hemorrhagic Trauma and Shock

    DTIC Science & Technology

    2016-10-01

    evident in liver and kidney sections. Treatment with VitC (200mg/kg) was associated with a lower degree of histological tissue injury and a...significantly reduced ALI score. Treatment with VitC also reduced the expression of pro-inflammatory mediators in lungs, liver and kidneys . In addition, VitC...Euthasol IV  Tissue samples (lung, liver and kidney ) obtained for histology and molecular characterization Definitive trial conducted: Eight (8

  15. Printing metal-spiked inks for LA-ICP-MS bioimaging internal standardization: comparison of the different nephrotoxic behavior of cisplatin, carboplatin, and oxaliplatin.

    PubMed

    Moraleja, Irene; Esteban-Fernández, Diego; Lázaro, Alberto; Humanes, Blanca; Neumann, Boris; Tejedor, Alberto; Luz Mena, M; Jakubowski, Norbert; Gómez-Gómez, M Milagros

    2016-03-01

    The study of the distribution of the cytostatic drugs cisplatin, carboplatin, and oxaliplatin along the kidney may help to understand their different nephrotoxic behavior. Laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) allows the acquisition of trace element images in biological tissues. However, results obtained are affected by several variations concerning the sample matrix and instrumental drifts. In this work, an internal standardization method based on printing an Ir-spiked ink onto the surface of the sample has been developed to evaluate the different distributions and accumulation levels of the aforementioned drugs along the kidney of a rat model. A conventional ink-jet printer was used to print fresh sagittal kidney tissue slices of 4 μm. A reproducible and homogenous deposition of the ink along the tissue was observed. The ink was partially absorbed on top of the tissue. Thus, this approach provides a pseudo-internal standardization, due to the fact that the ablation sample and internal standard take place subsequently and not simultaneously. A satisfactory normalization of LA-ICP-MS bioimages and therefore a reliable comparison of the kidney treated with different Pt-based drugs were achieved even for tissues analyzed on different days. Due to the complete ablation of the sample, the transport of the ablated internal standard and tissue to the inductively coupled plasma-mass spectrometry (ICP-MS) is practically taking place at the same time. Pt accumulation in the kidney was observed in accordance to the dosages administered for each drug. Although the accumulation rate of cisplatin and oxaliplatin is high in both cases, their Pt distributions differ. The strong nephrotoxicity observed for cisplatin and the absence of such side effect in the case of oxaliplatin could explain these distribution differences. The homogeneous distribution of oxaliplatin in the cortical and medullar areas could be related with its higher affinity for cellular transporters such as MATE2-k.

  16. Investigation for zoonotic disease pathogens (Aeromonas hydrophila, Pseudomonas fluorescens, Streptococcus iniae) seen in carp farms in Duhok region of Northern Iraq by molecular methods

    NASA Astrophysics Data System (ADS)

    Mohammed, Kamiran Abdulrahman; Arabacı, Muhammed; Önalan, Şükrü

    2017-04-01

    The aim of this study was to determine the zoonotic bacteria in carp farms in Duhok region of the Northern Iraq. Carp is the main fish species cultured in the Duhok region. The most common zoonotic bacteria generally seen in carp farms are Aeromonas hydrophila, Pseudomonas fluorescens and Streptococcus iniae. Samples were collected from 20 carp farms in the Duhok Region of the Northern Iraq. Six carp samples were collected from each carp farm. Head kidney tissue samples and intestine tissue samples were collected from each carp sample. Than head kidney and intestine tissue samples were pooled. The total bacterial DNA extraction from the pooled each 20 head kidney tissue samples and pooled each 20 intestinal tissue samples. Primers for pathogens were originally designed from 16S Ribosomal gene region. Zoonotic bacteria were scanned in all tissue samples by absent / present analysis in the RT-PCR. After RT-PCR, Capillary gel electrophoresis bands were used for the confirmation of the size of amplicon which was planned during primer designing stage. As a result, one sample was positive in respect to Aeromonas hydrophila, from intestine and one carp farm was positive in respect to Pseudomonas fluorescens from intestine and two carp farms were positive in respect to Streptococcus iniae. Totally 17 of 20 carp farms were negative in respect to the zoonotic bacteria. In conclusion the zoonotic bacteria were very low (15 %) in carp farms from the Duhok Region in the Northern Iraq. Only in one Carp farms, both Aeromonas hydrophila and Pseudomonas fluorescens were positive. Also Streptococcus inia were positive in two carp farms.

  17. Oxidative stress in juvenile chinook salmon, Oncorhynchus tshawytscha (Walbaum)

    USGS Publications Warehouse

    Welker, T.L.; Congleton, J.L.

    2004-01-01

    Juvenile chinook salmon, Oncorhynchus tshawytscha (Walbaum), were held in 8-11??C freshwater, starved for 3 days and subjected to a low-water stressor to determine the relationship between the general stress response and oxidative stress. Lipid peroxidation (LPO) levels (lipid hydroperoxides) were measured in kidney, liver and brain samples taken at the beginning of the experiment (0-h unstressed controls) and at 6, 24 and 48 h after application of a continuous low-water stressor. Tissue samples were also taken at 48 h from fish that had not been exposed to the stressor (48-h unstressed controls). Exposure to the low-water stressor affected LPO in kidney and brain tissues. In kidney, LPO decreased 6 h after imposition of the stressor; similar but less pronounced decreases also occurred in the liver and brain. At 48 h, LPO increased (in comparison with 6-h stressed tissues) in the kidney and brain. In comparison with 48-h unstressed controls, LPO levels were higher in the kidney and brain of stressed fish. Although preliminary, results suggest that stress can cause oxidative tissue damage in juvenile chinook salmon. Measures of oxidative stress have shown similar responses to stress in mammals; however, further research is needed to determine the extent of the stress-oxidative stress relationship and the underlying physiological mechanisms in fish.

  18. Systemic effect of mineral aggregate-based cements: histopathological analysis in rats

    PubMed Central

    Garcia, Lucas da Fonseca Roberti; Huck, Claudia; Magalhães, Fernando Augusto Cintra; de Souza, Pedro Paulo Chaves; de Souza Costa, Carlos Alberto

    2017-01-01

    Abstract Objective: Several studies reported the local tissue reaction caused by mineral aggregate-based cements. However, few studies have investigated the systemic effects promoted by these cements on liver and kidney when directly applied to connective tissue. The purpose of this in vivo study was to investigate the systemic effect of mineral aggregate-based cements on the livers and kidneys of rats. Material and Methods: Samples of Mineral Trioxide Aggregate (MTA) and a calcium aluminate-based cement (EndoBinder) containing different radiopacifiers were implanted into the dorsum of 40 rats. After 7 and 30 d, samples of subcutaneous, liver and kidney tissues were submitted to histopathological analysis. A score (0-3) was used to grade the inflammatory reaction. Blood samples were collected to evaluate changes in hepatic and renal functions of animals. Results: The moderate inflammatory reaction (2) observed for 7 d in the subcutaneous tissue decreased with time for all cements. The thickness of inflammatory capsules also presented a significant decrease with time (P<.05). Systemically, all cements caused adverse inflammatory reactions in the liver and kidney, being more evident for MTA, persisting until the end of the analysis. Liver functions increased significantly for MTA during 30 d (P<.05). Conclusion: The different cements induced to a locally limited inflammatory reaction. However, from the systemic point of view, the cements promoted significant inflammatory reactions in the liver and kidney. For MTA, the reactions were more accentuated. PMID:29211283

  19. GC-MS/MS Analyses of Biological Samples in Support of Developmental Toxic Effects on Percutaneous Exposure of Rats to VX

    DTIC Science & Technology

    2016-07-01

    of blood, tissues, and organs (heart, lung, liver, kidney , brain, eye, diaphragm, and skin) that were obtained from rats (postnatal days 42 and 70...of blood, tissues, and organs (heart, lung, liver, kidney , brain, eye, and diaphragm) that were used to quantify the amounts of free and regenerated...Biosamples (brain, diaphragm, eye, heart, lung, liver, and kidney ) were collected at time of death or 48 h post-exposure for survivors. All

  20. Determination of the phenoxyacid herbicides MCPA, mecoprop and 2,4-D in kidney tissue using liquid chromatography with electrospray tandem mass spectrometry.

    PubMed

    Charlton, Andrew J A; Stuckey, Vicki; Sykes, Mark D

    2009-06-01

    An analytical method was developed to determine the phenoxyacid herbicides 2,4-D, MCPA and mecoprop in kidney tissue from animals where poisoning is suspected. Samples were Soxhlet extracted using diethyl ether and the extracts cleaned-up using anion exchange solid phase extraction cartridges. Analysis was performed using liquid chromatography with negative-ion electrospray tandem mass spectrometry (LC-MS/MS). The method was evaluated by analysing control kidney samples fortified at 1 and 5 mg/kg. Mean recoveries ranged from 82 to 93% with relative standard deviations from 3.2 to 19%. The limit of detection was estimated to be 0.02 mg/kg.

  1. Depth-section imaging of swine kidney by spectrally encoded microscopy

    NASA Astrophysics Data System (ADS)

    Liao, Jiuling; Gao, Wanrong

    2016-10-01

    The kidneys are essential regulatory organs whose main function is to regulate the balance of electrolytes in the blood, along with maintaining pH homeostasis. The study of the microscopic structure of the kidney will help identify kidney diseases associated with specific renal histology change. Spectrally encoded microscopy (SEM) is a new reflectance microscopic imaging technique in which a grating is used to illuminate different positions along a line on the sample with different wavelengths, reducing the size of system and imaging time. In this paper, a SEM device is described which is based on a super luminescent diode source and a home-built spectrometer. The lateral resolution was measured by imaging the USAF resolution target. The axial response curve was obtained as a reflect mirror was scanned through the focal plane axially. In order to test the feasibility of using SEM for depth-section imaging of an excised swine kidney tissue, the images of the samples were acquired by scanning the sample at 10 μm per step along the depth direction. Architectural features of the kidney tissue could be clearly visualized in the SEM images, including glomeruli and blood vessels. Results from this study suggest that SEM may be useful for locating regions with probabilities of kidney disease or cancer.

  2. Observation of tissues in open aqueous solution by atmospheric scanning electron microscopy: applicability to intraoperative cancer diagnosis.

    PubMed

    Memtily, Nassirhadjy; Okada, Tomoko; Ebihara, Tatsuhiko; Sato, Mari; Kurabayashi, Atsushi; Furihata, Mutsuo; Suga, Mitsuo; Nishiyama, Hidetoshi; Mio, Kazuhiro; Sato, Chikara

    2015-05-01

    In the atmospheric scanning electron microscope (ASEM), a 2- to 3-µm layer of the sample resting on a silicon nitride-film window in the base of an open sample dish is imaged, in liquid, at atmospheric pressure, from below by an inverted SEM. Thus, the time-consuming pretreatments generally required for biological samples to withstand the vacuum of a standard electron microscope are avoided. In the present study, various mouse tissues (brain, spinal cord, muscle, heart, lung, liver, kidney, spleen and stomach) were fixed, stained with heavy metals, and visualized in radical scavenger D-glucose solution using the ASEM. While some stains made the nuclei of cells very prominent (platinum-blue, phosphotungstic acid), others also emphasized cell organelles and membranous structures (uranium acetate or the NCMIR method). Notably, symbiotic bacteria were sometimes observed on stomach mucosa. Furthermore, kidney tissue could be stained and successfully imaged in <30 min. Lung and spinal cord tissue from normal mice and mice metastasized with breast cancer cells was also examined. Cancer cells present in lung alveoli and in parts of the spine tissue clearly had larger nuclei than normal cells. The results indicate that the ASEM has the potential to accelerate intraoperative cancer diagnosis, the diagnosis of kidney diseases and pathogen detection. Importantly, in the course of the present study it was possible to increase the observable tissue area by using a new multi-windowed ASEM sample dish and sliding the tissue across its eight windows.

  3. Extraction efficiency and implications for absolute quantitation of propranolol in mouse brain, liver and kidney thin tissue sections using droplet-based liquid microjunction surface sampling-HPLC ESI-MS/MS

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

    Kertesz, Vilmos; Weiskittel, Taylor M.; Vavek, Marissa

    Currently, absolute quantitation aspects of droplet-based surface sampling for thin tissue analysis using a fully automated autosampler/HPLC-ESI-MS/MS system are not fully evaluated. Knowledge of extraction efficiency and its reproducibility is required to judge the potential of the method for absolute quantitation of analytes from thin tissue sections. Methods: Adjacent thin tissue sections of propranolol dosed mouse brain (10- μm-thick), kidney (10- μm-thick) and liver (8-, 10-, 16- and 24- μm-thick) were obtained. Absolute concentration of propranolol was determined in tissue punches from serial sections using standard bulk tissue extraction protocols and subsequent HPLC separations and tandem mass spectrometric analysis. Thesemore » values were used to determine propranolol extraction efficiency from the tissues with the droplet-based surface sampling approach. Results: Extraction efficiency of propranolol using 10- μm-thick brain, kidney and liver thin tissues using droplet-based surface sampling varied between ~45-63%. Extraction efficiency decreased from ~65% to ~36% with liver thickness increasing from 8 μm to 24 μm. Randomly selecting half of the samples as standards, precision and accuracy of propranolol concentrations obtained for the other half of samples as quality control metrics were determined. Resulting precision ( ±15%) and accuracy ( ±3%) values, respectively, were within acceptable limits. In conclusion, comparative quantitation of adjacent mouse thin tissue sections of different organs and of various thicknesses by droplet-based surface sampling and by bulk extraction of tissue punches showed that extraction efficiency was incomplete using the former method, and that it depended on the organ and tissue thickness. However, once extraction efficiency was determined and applied, the droplet-based approach provided the required quantitation accuracy and precision for assay validations. Furthermore, this means that once the extraction efficiency was calibrated for a given tissue type and drug, the droplet-based approach provides a non-labor intensive and high-throughput means to acquire spatially resolved quantitative analysis of multiple samples of the same type.« less

  4. Extraction efficiency and implications for absolute quantitation of propranolol in mouse brain, liver and kidney thin tissue sections using droplet-based liquid microjunction surface sampling-HPLC ESI-MS/MS

    DOE PAGES

    Kertesz, Vilmos; Weiskittel, Taylor M.; Vavek, Marissa; ...

    2016-06-22

    Currently, absolute quantitation aspects of droplet-based surface sampling for thin tissue analysis using a fully automated autosampler/HPLC-ESI-MS/MS system are not fully evaluated. Knowledge of extraction efficiency and its reproducibility is required to judge the potential of the method for absolute quantitation of analytes from thin tissue sections. Methods: Adjacent thin tissue sections of propranolol dosed mouse brain (10- μm-thick), kidney (10- μm-thick) and liver (8-, 10-, 16- and 24- μm-thick) were obtained. Absolute concentration of propranolol was determined in tissue punches from serial sections using standard bulk tissue extraction protocols and subsequent HPLC separations and tandem mass spectrometric analysis. Thesemore » values were used to determine propranolol extraction efficiency from the tissues with the droplet-based surface sampling approach. Results: Extraction efficiency of propranolol using 10- μm-thick brain, kidney and liver thin tissues using droplet-based surface sampling varied between ~45-63%. Extraction efficiency decreased from ~65% to ~36% with liver thickness increasing from 8 μm to 24 μm. Randomly selecting half of the samples as standards, precision and accuracy of propranolol concentrations obtained for the other half of samples as quality control metrics were determined. Resulting precision ( ±15%) and accuracy ( ±3%) values, respectively, were within acceptable limits. In conclusion, comparative quantitation of adjacent mouse thin tissue sections of different organs and of various thicknesses by droplet-based surface sampling and by bulk extraction of tissue punches showed that extraction efficiency was incomplete using the former method, and that it depended on the organ and tissue thickness. However, once extraction efficiency was determined and applied, the droplet-based approach provided the required quantitation accuracy and precision for assay validations. Furthermore, this means that once the extraction efficiency was calibrated for a given tissue type and drug, the droplet-based approach provides a non-labor intensive and high-throughput means to acquire spatially resolved quantitative analysis of multiple samples of the same type.« less

  5. Precision Medicine Approaches to Diabetic Kidney Disease: Tissue as an Issue.

    PubMed

    Gluck, Caroline; Ko, Yi-An; Susztak, Katalin

    2017-05-01

    Precision medicine approaches, that tailor medications to specific individuals has made paradigm-shifting improvements for patients with certain cancer types. Such approaches, however, have not been implemented for patients with diabetic kidney disease. Precision medicine could offer new avenues for novel diagnostic, prognostic and targeted therapeutics development. Genetic studies associated with multiscalar omics datasets from tissue and cell types of interest of well-characterized cohorts are needed to change the current paradigm. In this review, we will discuss precision medicine approaches that the nephrology community can take to analyze tissue samples to develop new therapeutics for patients with diabetic kidney disease.

  6. Typeability of PowerPlex Y (Promega) profiles in selected tissue samples incubated in various environments.

    PubMed

    Niemcunowicz-Janica, Anna; Pepiński, Witold; Janica, Jacek Robert; Janica, Jerzy; Skawrońska, Małgorzata; Koc-Zórawska, Ewa

    2007-01-01

    In cases of decomposed bodies, Y chromosomal STR markers may be useful in identification of a male relative. The authors assessed typeability of PowerPlex Y (Promega) loci in post mortem tissue material stored in various environments. Kidney, spleen and pancreas specimens were collected during autopsies of five persons aged 20-30 years, whose time of death was determined within the limit of 14 hours. Tissue material was incubated at 21 degrees C and 4 degrees C in various environmental conditions. DNA was extracted by the organic method from tissue samples collected in 7-day intervals and subsequently typed using the PowerPlexY-STR kit and ABI 310. A fast decrease in the typeability rate was seen in specimens incubated in peat soil and in sand. Kidney tissue samples were typeable in all PowerPlexY-STR loci within 63 days of incubation at 4 degrees C. Faster DNA degradation was recorded in spleen and pancreas specimens. In samples with negative genotyping results, no DNA was found by fluorometric quantitation. Decomposed soft tissues are a potential material for DNA typing.

  7. Testing the use of juvenile Salmo trutta L. as biomonitors of heavy metal pollution in freshwater.

    PubMed

    Lamas, S; Fernández, J A; Aboal, J R; Carballeira, A

    2007-02-01

    Individual specimens of Salmo trutta were captured, from four sampling sites in Galician rivers (NW Spain) affected by different types of contamination: diffuse urban waste, run-off from an unrestored dump at a copper mine and waste from a fish farm. The ages of the captured trouts were established and only those belonging to the 1+ age class were selected for study. The liver and kidney were removed from each fish and analysed to determine the tissue concentrations of Cu, Fe and Zn. The results obtained showed that: (i) the use of 1+ individuals allowed differentiation of contamination scenarios on the basis of the tissue concentrations of metal; (ii) the use of 1+ individuals allowed standardization of the time of exposure, which was sufficiently long for differential uptake to have taken place; (iii) liver tissue provided the best results as, less effort was required than for processing kidney tissue, and significant differences between sampling sites were detected because the intrapopulational variability in metal levels was lower than for kidney, and (iv) the levels of elements detected were not affected by basal tissue concentrations or residual concentrations due to past contamination, which older trouts may have been exposed to. In addition, the use of 1+ trout may provide better results in annual environmental sampling surveys.

  8. Evaluation of kidney injury biomarkers in rat amniotic fluid after gestational exposure to cadmium.

    PubMed

    Jacobo-Estrada, Tania; Cardenas-Gonzalez, Mariana; Santoyo-Sánchez, Mitzi; Parada-Cruz, Benjamín; Uria-Galicia, Esther; Arreola-Mendoza, Laura; Barbier, Olivier

    2016-09-01

    Cadmium is a well-characterized nephrotoxic agent that is also capable of accumulating and diffusing across the placenta; however, only a few studies have addressed its effects over fetal kidneys and none of them has used a panel of sensitive and specific biomarkers for the detection of kidney injury. The goal of this study was to determine cadmium renal effects in rat fetuses by the quantification of early kidney injury biomarkers. Pregnant Wistar rats were exposed by inhalation to an isotonic saline solution or to CdCl2 solution (DDel =1.48 mg Cd kg(-1) day(-1) ) during gestational days (GD) 8-20. On GD 21, dams were euthanized and samples obtained. Kidney injury biomarkers were quantified in amniotic fluid samples and fetal kidneys were microscopically evaluated to search for histological alterations. Our results showed that cadmium exposure significantly raised albumin, osteopontin, vascular endothelial growth factor and tissue inhibitor of metalloproteinases-1 levels in amniotic fluid, whereas it decreased creatinine. Clusterin, calbindin and IFN-inducible protein 10 did not show any change. Accordingly, histological findings showed tubular damage and precipitations in the renal pelvis. In conclusion, gestational exposure to cadmium induces structural alterations in fetal renal tissue that can be detected by some kidney injury biomarkers in amniotic fluid samples. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

  9. Consistency of signal intensity and T2* in frozen ex vivo heart muscle, kidney, and liver tissue.

    PubMed

    Kaye, Elena A; Josan, Sonal; Lu, Aiming; Rosenberg, Jarrett; Daniel, Bruce L; Pauly, Kim Butts

    2010-03-01

    To investigate tissue dependence of the MRI-based thermometry in frozen tissue by quantification and comparison of signal intensity and T2* of ex vivo frozen tissue of three different types: heart muscle, kidney, and liver. Tissue samples were frozen and imaged on a 0.5 Tesla MRI scanner with ultrashort echo time (UTE) sequence. Signal intensity and T2* were determined as the temperature of the tissue samples was decreased from room temperature to approximately -40 degrees C. Statistical analysis was performed for (-20 degrees C, -5 degrees C) temperature interval. The findings of this study demonstrate that signal intensity and T2* are consistent across three types of tissue for (-20 degrees C, -5 degrees C) temperature interval. Both parameters can be used to calculate a single temperature calibration curve for all three types of tissue and potentially in the future serve as a foundation for tissue-independent MRI-based thermometry.

  10. Food safety aspects of primary environmental contaminants in the edible tissues of roe deer (Capreolus capreolus).

    PubMed

    Lehel, József; Zwillinger, Dóra; Bartha, András; Lányi, Katalin; Laczay, Péter

    2017-11-01

    The muscle, liver, kidney and fat samples of 20 roe deer of both sexes originating from a hunting area in central Hungary were investigated for the presence of heavy metals such as As, Cd, Hg and Pb, and their contents were evaluated for possible health risk to consumers. Both As and Hg were found at a level below the limit of detection (< 0.5 mg/kg wet weight) in all samples. The median of the measured Cd concentrations was significantly higher in both the kidney and the liver (p = 0.0011) of bucks than of does. In bucks, Cd levels exceeded the respective maximum limits laid down in the European legislation in four kidney and three muscle samples, whereas in does, the measured concentrations were below the respective limits in all samples. The detected amounts of Pb exceeded the maximum limits in the kidney of one buck and eight does, in the liver of two bucks and six does, in the muscle of six bucks and nine does, whereas in all fat tissues of both bucks and does. The concentration of Pb (p = 0.02) was significantly greater in the kidney of does compared to roebucks. Based on data obtained from the present study, the consumption of organs and tissues of the investigated roe deer could be objectionable from food-toxicological point of view and may pose risk to the high consumers of wild game due to their cadmium and lead contents.

  11. Multilaboratory trial for determination of ceftiofur residues in bovine and swine kidney and muscle, and bovine milk.

    PubMed

    Hornish, Rex E; Hamlow, Philip J; Brown, Scott A

    2003-01-01

    A multilaboratory trial for determining ceftiofur-related residues in bovine and swine kidney and muscle, and bovine milk was conducted following regulatory guidelines of the U.S. Food and Drug Administration, Center for Veterinary Medicine. The methods convert all desfuroylceftiofur-related residues containing the intact beta-lactam ring to desfuroylceftiofur acetamide to establish ceftiofur residues in tissues. Four laboratories analyzed 5 sets of samples for each tissue. Each sample set consisted of a control/blank sample and 3 control samples fortified with ceftiofur at 0.5 Rm, Rm, and 2 Rm, respectively, where Rm is the U.S. tolerance assigned for ceftiofur residue in each tissue/matrix: 0.100 microg/mL for milk, 8.0 microg/g for kidney (both species), 1.0 microg/g for bovine muscle, and 2.0 microg/g for swine muscle. Each sample set also contained 2 samples of incurred-residue tissues (one > Rm and one < Rm) from animals treated with ceftiofur hydrochloride. All laboratories completed the method trial after a familiarization phase and test of system suitability in which they demonstrated > 80% recovery in pretrial fortified test samples. Results showed that the methods met all acceptable performance criteria for recovery, accuracy, and precision. Although sample preparation was easy, solid-phase extraction cartridge performance must be carefully evaluated before samples are processed. The liquid chromatography detection system was easily set up; however, the elution profile may require slight modifications. The procedures could clearly differentiate between violative (> Rm) and nonviolative (< Rm) ceftiofur residues. Participating laboratories found the procedures suitable for ceftiofur residue determination.

  12. Multiple high-intensity focused ultrasound probes for kidney-tissue ablation.

    PubMed

    Häcker, Axel; Chauhan, Sunita; Peters, Kristina; Hildenbrand, Ralf; Marlinghaus, Ernst; Alken, Peter; Michel, Maurice Stephan

    2005-10-01

    To investigate kidney-tissue ablation by high-intensity focused ultrasound (HIFU) using multiple and single probes. Ultrasound beams (1.75 MHz) produced by a piezoceramic element (focal distance 80 mm) were focused at the center of renal parenchyma. One of the three probes (mounted on a jig) could also be used for comparison with a single probe at comparable power ratings. Lesion dimensions were examined in perfused and unperfused ex vivo porcine kidneys at different power levels (40, 60, and 80 W) and treatment times (4, 6, and 8 seconds). At identical power levels, the lesions induced by multiple probes were larger than those induced by a single probe. Lesion size increased with increasing pulse duration and generator power. The sizes and shapes of the lesions were predictably repeatable in all samples. Lesions in perfused kidneys were smaller than those in unperfused kidneys. Ex vivo, kidney-tissue ablation by means of multiple HIFU probes offers significant advantages over single HIFU probes in respect of lesion size and formation. These advantages need to be confirmed by tests in vivo at higher energy levels.

  13. Genetic stock assessment of spawning arctic cisco (Coregonus autumnalis) populations by flow cytometric determination of DNA content.

    PubMed

    Lockwood, S F; Bickham, J W

    1991-01-01

    Intraspecific variation in cellular DNA content was measured in five Coregonus autumnalis spawning populations from the Mackenzie River drainage, Canada, using flow cytometry. The rivers assayed were the Peel, Arctic Red, Mountain, Carcajou, and Liard rivers. DNA content was determined from whole blood preparations of fish from all rivers except the Carcajou, for which kidney tissue was used. DNA content measurements of kidney and blood preparations of the same fish from the Mountain River revealed statistically indistinguishable results. Mosaicism was found in blood preparations from the Peel, Arctic Red, Mountain, and Liard rivers, but was not observed in kidney tissue preparations from the Mountain or Carcajou rivers. The Liard River sample had significantly elevated mean DNA content relative to the other four samples; all other samples were statistically indistinguishable. Significant differences in mean DNA content among spawning stocks of a single species reinforces the need for adequate sample sizes of both individuals and populations when reporting "C" values for a particular species.

  14. Evaluation of contralateral kidney, liver and lung after extracorporeal shock wave lithotripsy in rabbits.

    PubMed

    Senyucel, M F; Boybeyi, O; Ayva, S; Aslan, M K; Soyer, T; Demet, A I; Kısa, U; Basar, M; Cakmak, M A

    2013-10-01

    An experimental study was carried out to evaluate the effects of extracorporeal shock wave lithotripsy (ESWL) on contralateral kidney, liver and lung by histopathological and biochemical methods. Twelve New Zealand rabbits were allocated to two groups (n = 6). Tissues of control group (CG, n = 6) were harvested without any intervention. In ESWL group (EG), right kidneys were exposed to 3,000 shock waves at 14 kV energy using electro-hydraulic type ESWL device three times every other day. Both kidneys, liver, and right lobe of lung tissues in EG were harvested on seventh day. Kidneys were examined histopathologically for presence of glomerular and tubular injury, interstitial edema, congestion, inflammation and fibrosis. Livers were examined for hepatocyte vacuolization, congestion, portal inflammation and fibrosis. Lung tissues were examined for loss of normal structure, emphysema, interstitial congestion-edema, prominent alveolar septal vessels, interstitial inflammation, intra-alveolar hemorrhage, intraluminal hemorrhage, peribronchial edema, congestion, inflammation in bronchial wall and epithelial desquamation. Biochemical analysis of tissue samples was performed for oxidative injury markers. Histopathological evaluations revealed that tubular injury was found in both shocked and contralateral kidneys (p < 0.05). EG showed higher grades of portal fibrosis in liver and higher grades of peribronchial congestion in lung when compared to CG (p < 0.05). Biochemical evaluations of both kidneys showed that malondialdehyde levels were higher in EG than in CG (p < 0.05). ESWL causes histopathologic alterations both in shocked and contralateral kidneys. Extrarenal tissues such as liver and lung can be affected by shock waves histopathologically and oxidative injury of contralateral kidney may occur acutely after ESWL.

  15. Intra-operative on-line discrimination of kidney cancer from normal tissue by IR ATR spectroscopy of extracellular fluid

    NASA Astrophysics Data System (ADS)

    Urboniene, V.; Velicka, M.; Ceponkus, J.; Pucetaite, M.; Jankevicius, F.; Sablinskas, V.; Steiner, G.

    2016-03-01

    Determination of cancerous and normal kidney tissues during partial, simple or radical nephrectomy surgery was performed by using differences in the IR absorption spectra of extracellular fluid taken from the corresponding tissue areas. The samples were prepared by stamping of the kidney tissue on ATR diamond crystal. The spectral measurements were performed directly in the OR during surgery for 58 patients. It was found that intensities of characteristic spectral bands of glycogen (880-1200 cm-1) in extracellular fluid are sensitive to the type of the tissue and can be used as spectral markers of tumours. Characteristic spectral band of lactic acid (1730 cm-1) - product of the anaerobic glycolysis, taking place in the cancer cells is not suitable for use as a spectral marker of cancerous tissue, since it overlaps with the band of carbonyl stretch in phospholipids and fatty acids. Results of hierarchical cluster analysis of the spectra show that the spectra of healthy and tumour tissue films can be reliably separated into two groups. On the other hand, possibility to differentiate between tumours of different types and grades remains in question. While the fluid from highly malignant G3 tumour tissue contains highly pronounced glycogen spectral bands and can be well separated from benign and G1 tumours by principal component analysis, the variations between spectra from sample to sample prevent from obtaining conclusive results about the grouping between different tumour types and grades. The proposed method is instant and can be used in situ and even in vivo.

  16. Kidney and urinary tract polyomavirus infection and distribution: molecular biology investigation of 10 consecutive autopsies.

    PubMed

    Boldorini, Renzo; Veggiani, Claudia; Barco, Diana; Monga, Guido

    2005-01-01

    Distinct human polyomavirus genotypes cause different diseases in patients with renal transplants: BK virus (BKV) causes tubulointerstitial nephritis and ureteral stenosis, whereas both JC virus (JCV) and BKV are responsible for hemorrhagic cystitis. These findings could result from a selective infection of kidney and urinary tract segments by JCV or BKV. To verify this hypothesis, 10 complete, unselected, consecutive autopsies from 9 immunocompetent patients and 1 patient affected by acquired immunodeficiency syndrome were investigated. Samples from kidneys (n = 80), renal pelvis (n = 20), ureter (n = 40), and urinary bladder (n = 30) obtained from 10 consecutive autopsies were investigated by means of multiplex nested polymerase chain reaction to detect polyomavirus DNA and to distinguish different species of the Polyomavirus genus. In situ hybridization and immunohistochemistry were also carried out to define the viral status of the infected tissues. Polyomavirus DNA was detected in all of the subjects (positive samples ranging from 2 to 7 samples), for a total of 43 of 170 samples (25.3%), distributed as follows: urinary bladder (10/30, 33%), renal pelvis (6/20, 30%), ureter (10/40, 25%), and kidney tissue (17/80, 21%). We found that JCV was most frequently detected overall (23/43 samples, 53.5%) and was also detected most frequently within the kidney (8/17 positive samples, 47%), the renal pelvis (5/6 positive samples, 70%), and the ureter (7/10 positive samples, 70%), whereas BKV was found in 14 samples (32.5%), and it was the prevailing genotype in urinary bladder (6/10 positive samples, 60%). Coinfection of BKV-JCV was found in 6 samples (14%). Immunohistochemistry and in situ hybridization returned negative results. The viruses JCV and BKV latently persist randomly in kidney and urinary tract. Distinct diseases induced by them could be related more closely to molecular viral rearrangements than to the topographic distribution of latent viruses.

  17. Health implications of radionuclide levels in cattle raised near U mining and milling facilities in Ambrosia Lake, New Mexico

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

    Lapham, S.C.; Millard, J.B.; Samet, J.M.

    1989-03-01

    This study was conducted to determine radionuclide tissue levels in cattle raised near U mining and milling facilities. Ambrosia Lake, New Mexico, has been the site of extensive U mining for 30 y and contains several underground U mines, a processing mill, and two large U tailings piles. Ten cows were purchased from two grazing areas in Ambrosia Lake and ten control animals were purchased from Crownpoint, New Mexico. Muscle, liver, kidney, and bone tissue taken from these animals, and environmental samples, including water, grasses and soil collected from the animals' grazing areas, were analyzed for /sup 238/U, /sup 234/U,more » /sup 230/Th, /sup 226/Ra, /sup 210/Pb, and /sup 210/Po. Mean radionuclide levels in cattle tissue and environmental samples from Ambrosia Lake were higher in almost every comparison than those found in respective controls. Liver and kidney tissues were particularly elevated in /sup 226/Ra and /sup 210/Po. Radiation dose commitments from eating cattle tissue with these radionuclide concentrations were calculated. We concluded that the health risk to the public from eating exposed cattle is minimal, unless large amounts of this tissue, especially liver and kidney, are ingested.« less

  18. Expression of bone morphogenetic proteins 4, 6 and 7 is downregulated in kidney allografts with interstitial fibrosis and tubular atrophy.

    PubMed

    Furic-Cunko, Vesna; Kes, Petar; Coric, Marijana; Hudolin, Tvrtko; Kastelan, Zeljko; Basic-Jukic, Nikolina

    2015-07-01

    Bone morphogenetic proteins (BMPs) are pleiotropic growth factors. This paper investigates the connection between the expression pattern of BMPs in kidney allograft tissue versus the cause of allograft dysfunction. The expression pattern of BMP2, BMP4, BMP6 and BMP7 in 50 kidney allografts obtained by transplant nephrectomy is investigated. Immunohistochemical staining is semiquantitatively evaluated for intensity to identify the expression pattern of BMPs in normal and allograft kidney tissues. The expression of BMP4 is unique between different tubular cell types in grafts without signs of fibrosis. This effect is not found in specimens with high grades of interstitial fibrosis and tubular atrophy (IFTA). In samples with IFTA grades II and III, the BMP7 expression is reduced in a significant fraction of specimens relative to those without signs of IFTA. The expression pattern of BMP6 indicates that its activation may be triggered by the act of transplantation and subsequent reperfusion injury. The expression of BMP2 is strong in all types of tubular epithelial cells and does not differ between the compared allografts and control kidney specimens. The intensity and expression pattern of BMP4, BMP6 and BMP7 in transplanted kidney tissue are found to be dependent upon the length of the transplanted period, the clinical indication for transplant nephrectomy and signs of IFTA in kidney tissue.

  19. The Study of Pentoxifylline Drug Effects on Renal Apoptosis and BCL-2 Gene Expression Changes Following Ischemic Reperfusion Injury in Rat

    PubMed Central

    Hashemi, Mehrdad

    2014-01-01

    Ischemia Reperfusion injury is the tissue damage caused when blood supply returns to the tissue after a period of ischemia or lack of oxygen. In this study, the effect of pentoxyfylline on BCL-2 gene expression changes and cell injury in kidney of rat following Ischemia Reperfusion were evaluated. In this experimental study, 20 male wistar rats with average weight of 250-300 g were selected and then were accidently divided them on two tenth group of control and treatment groups. In the control group, celiotomy was performed by ventral midline incision. The left kidney was isolated, and then both the renal artery and vein were obstructed. After 60 minutes of warm ischemia, vessel obstruction resolved and the right kidney was removed. 72 hours after reperfusion, tissue samples were taken from left kidney for Tunel assay. We used quantitative real time PCR for detection of BCL-2 gene expression in treated groups and then compared them to control samples. In the treatment group, the cell death changes, showed lower level than the control group. The results also showed the BCL-2 gene expression was declined in ischemia group as campared to PNT drug group. The pentoxyfylline might have a role in control of apoptosis result from Ischemia- reperfusion and quantitative real-time PCR can be used as a direct method for detection BCL-2 gene expression in tested samples and normal samples. PMID:24734070

  20. Development of a nested polymerase chain reaction for amplification of a sequence of the p57 gene of Renibacterium salmoninarum that provides a highly sensitive method for detection of the bacterium in salmonid kidney

    USGS Publications Warehouse

    Chase, D.M.; Pascho, R.J.

    1998-01-01

    Nucleic acid-based assays have shown promise for diagnosing Renibacterium salmoninarum in tissues and body fluids of salmonids. DeVelopment of a nested polymerase chain reaction (PCR) method to detect a 320 bp DNA segment of the gene encoding the p57 protein of R. salmoninarum is described. Whereas a conventional PCR for a 383 bp segment of the p57 gene reliably detected 1000 R. salmoninarum cells per reaction in kidney tissue, the nested PCR detected as few as 10 R. salmoninarum per reaction in kidney tissue. Two DNA extraction methods for the nested PCR were compared and the correlation between replicate samples was generally higher in samples extracted by the QIAamp system compared with those extracted by the phenol/chloroform method. The specificity of the nested PCR was confirmed by testing DNA extracts of common bacterial fish pathogens and a panel of bacterial species reported to cause false-positive reactions in the enzyme-linked immunosorbent assay (ELISA) and the fluorescent antibody test (FAT) for R. salmoninarum. Kidney samples from 74 naturally infected chinook Salmon were examined by the nested PCR, the ELISA, and the FAT, and the detected prevalences of R. salmoninarum were 61, 47, and 43%, respectively.

  1. HPLC determination of strychnine and brucine in rat tissues and the distribution study of processed semen strychni.

    PubMed

    Chen, Jun; Hou, Ting; Fang, Yun; Chen, Zhi-peng; Liu, Xiao; Cai, Hao; Lu, Tu-lin; Yan, Guo-jun; Cai, Bao-chang

    2011-01-01

    A simple and low-cost HPLC method with UV absorbance detection was developed and validated to simultaneously determine strychnine and brucine, the most abundant alkaloids in the processed Semen Strychni, in rat tissues (kidney, liver, spleen, lung, heart, stomach, small intestine, brain and plasma). The tissue samples were treated with a simple liquid-liquid extraction prior to HPLC. The LOQs were in the range of 0.039-0.050 µg/ml for different tissue or plasma samples. The extraction recoveries varied from 71.63 to 98.79%. The linear range was 0.05-2 µg/ml with correlation coefficient of over 0.991. The intra- and inter-day precision was less than 15%. Then the method was used to measure the tissue distribution of strychnine and brucine after intravenous administration of 1 mg/kg crude alkaloids fraction (CAF) extracted from the processed Semen Strychni. The results revealed that strychnine and brucine possessed similar tissue distribution characterization. The highest level was observed in kidney, while the lowest level was found in brain. It was indicated that kidney might be the primary excretion organ of prototype strychnine and brucine. It was also deduced that strychnine and brucine had difficulty in crossing the blood-brain barrier. Furthermore, no long-term accumulation of strychnine and brucine was found in rat tissues.

  2. Evaluating nephrotoxicity of high-molecular-weight organic compounds in drinking water from lignite aquifers

    USGS Publications Warehouse

    Bunnell, J.E.; Tatu, C.A.; Lerch, H.E.; Orem, W.H.; Pavlovic, N.

    2007-01-01

    High-molecular-weight organic compounds such as humic acids and/or fulvic acids that are naturally mobilized from lignite beds into untreated drinking-water supplies were suggested as one possible cause of Balkan endemic nephropathy (BEN) and cancer of the renal pelvis. A lab investigation was undertaken in order to assess the nephrotoxic potential of such organic compounds using an in vitro tissue culture model. Because of the infeasibility of exposing kidney tissue to low concentrations of organics for years in the lab, tangential flow ultrafiltration was employed to hyperconcentrate samples suitable for discerning effects in the short time frames necessitated by tissue culture systems. Effects on HK-2 kidney cells were measured using two different cell proliferation assays (MTT and alamarBlue). Results demonstrated that exposure of kidney tissue to high-molecular-weight organics produced excess cell death or proliferation depending on concentration and duration of exposure. Copyright ?? Taylor & Francis Group, LLC.

  3. Morphology of certain viruses of Salmonid fishes. II. In vivo studies of infectious Hematopoietic Necrosis Virus

    USGS Publications Warehouse

    Amend, Donald F.; Chambers, Velma C.

    1970-01-01

    Juvenile sockeye salmon (Oncorhynchus nerka) were injected with the infectious hematopoietic necrosis (IHN) virus, and tissue samples from the anterior kidney, spleen, liver, intestine, and pyloric caeca of moribund fish were prepared for electron microscopy. Bullet-shaped virus particles measuring 158 × 90 mμ were observed in the hematopoietic tissues of the anterior kidney and spleen. Virus particles were also observed in the outer connective tissues of the pancreas or pyloric caeca, or both. No virus was found in the intestine or liver. The healthy appearance of erythrocytes, reticular cells, and endothelial cells in necrotic areas of the spleen and anterior kidney, and the absence of lymphocytes in these areas, suggested that lymphocytes might be one source of the virus.

  4. Basics of kidney biopsy: A nephrologist's perspective

    PubMed Central

    Agarwal, S. K.; Sethi, S.; Dinda, A. K.

    2013-01-01

    The introduction of the kidney biopsy is one of the major events in the history of nephrology. Primary indications of kidney biopsy are glomerular hematuria/proteinuria with or without renal dysfunction and unexplained renal failure. Kidney biopsy is usually performed in prone position but in certain situations, supine and lateral positions may be required. Biopsy needles have changed with times from Vim–Silverman needle to Tru-cut needle to spring-loaded automatic gun. The procedure has also changed from blind bedside kidney biopsy to ultrasound marking to real-time ultrasound guidance to rarely computerized tomography guidance and laparoscopic and open biopsy. In very specific situations, transjugular kidney biopsy may be required. Most of the centers do kidney biopsy on short 1-day admission, whereas some take it as an outdoor procedure. For critical interpretation of kidney biopsy, adequate sample and clinical information are mandatory. Tissue needs to be stained with multiple stains for delineation of various components of kidney tissue. Many consider that electron microscopy (EM) is a must for all kidney biopsies, but facilities for EM are limited even in big centers. Sophisticated tests such as immunohistochemistry and in-situ hybridization are useful adjuncts for definitive diagnosis in certain situations. PMID:23960337

  5. Protective effect of Malva sylvestris L. extract in ischemia-reperfusion induced acute kidney and remote liver injury

    PubMed Central

    Najafi, Houshang; Mohamadi Yarijani, Zeynab; Changizi-Ashtiyani, Saeed; Mansouri, Kamran; Modarresi, Masoud; Madani, Seyed Hamid

    2017-01-01

    Mallow (Malva sylvestris L.) has had medicinal and therapeutic uses in addition to its oral consumption. The present study was conducted to examine the protective effect of Malva sylvestris L. extract on ischemia-reperfusion-induced kidney injury and remote organ injuries in the liver. Before ischemia-reperfusion, rats in the different groups received intraperitoneal normal saline or mallow extract at the doses of 200, 400 or 600 mg/kg of body weight. After 30-minutes of bilateral renal ischemia followed by 24-hours of reperfusion, tissue damage in the kidney and liver samples were determined through studying H&E-stained slides under a light microscope. The degree of leukocyte infiltration and tissue mRNA expressions of TNF- and ICAM-1 were then measured to examine the degree of renal inflammation. The renal tissue MDA and FRAP levels were measured for determining the amount of oxidative stress. Plasma concentrations of creatinine, urea, ALT and ALP were also measured. Ischemia-reperfusion led to a significant increase in plasma concentrations of creatinine, urea, ALT and ALP, and renal tissue MDA, and a significant decrease in renal tissue FRAP. The expression of pro-inflammatory factors in the kidney tissue, the level of leukocyte infiltration and the amount of tissue damage in the kidney and liver also increased. Pretreatment by mallow extract led to a significant improvement in all the variables measured. The 200- and 400-mg doses yielded better results in most parameters compared to the 600-mg dose. The findings showed that mallow extract protects the kidney against ischemia-reperfusion and reduces remote organ injury in the liver. PMID:29155898

  6. Enzyme activities in plasma, kidney, liver, and muscle of five avian species

    USGS Publications Warehouse

    Franson, J.C.; Murray, H.C.; Bunck, C.

    1985-01-01

    Activities of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), creatine phosphokinase (CPK), and lactate dehydrogenase (LDH) were determined in plasma, kidney, liver, and muscle from five species of captive birds. Few differences occurred in plasma activities between sexes but considerable differences occurred between species. All five enzymes were detected in each of the tissues sampled. Relative enzyme activities in liver, kidney, and muscle were similar for each species. CPK activity was much higher in muscle than in liver or kidney and, of the five enzymes studied, may be the best indicator of muscle damage. Most of the other enzymes were more evenly distributed among the three tissues, and no organ-specific enzyme could be identified for liver or kidney. Because of interspecific variations in plasma enzyme activities, it is important to establish baseline values for each species to ensure accurate interpretation of results.

  7. Spectroscopic photoacoustics for assessing ischemic kidney damage

    NASA Astrophysics Data System (ADS)

    Berndl, Elizabeth S. L.; He, Xiaolin; Yuen, Darren A.; Kolios, Michael C.

    2018-02-01

    Ischemic reperfusion injuries (IRIs) are caused by return of blood to a tissue or organ after a period without oxygen or nutrients. Damage in the microvasculature causes an inflammatory response and heterogeneous scarring, which is associated with an increase in collagen in the extracellular matrix. Although most often associated with heart attacks and strokes, IRI also occurs when blood reperfuses a transplanted organ. Currently, monitoring for IRI is limited to biopsies, which are invasive and sample a limited area. In this work, we explored photoacoustic (PA) biomarkers of scarring. IRI events were induced in mice (n=2) by clamping the left renal artery, then re-establishing flow. At 53 days post-surgery, kidneys were saline perfused and cut in half laterally. One half was immediately imaged with a VevoX system (Fujifilm-VisualSonics, Toronto) in two near infrared ranges - 680 to 970 nm (NIR), and 1200 to 1350 nm (NIR II). The other half was decellularized and then imaged at NIR and NIR II. Regions of interest were manually identified and analyzed for each kidney. For both cellularized and decellularized samples, the PA signal ratio based on irradiation wavelengths of 715:930 nm was higher in damaged kidneys than for undamaged kidneys (p < 0.0001 for both). Damaged kidneys had ROIs with spectra indicating the presence of collagen in the NIR II range, while healthy kidneys did not. Collagen rich spectra were more apparent in decellularized kidneys, suggesting that in the cellularized samples, other components may be contributing to the signal. PA imaging using spectral ratios associated with collagen signatures may provide a non-invasive tool to determine areas of tissue damage due to IRIs.

  8. Histopathology Image Analysis in Two Long-Term Animal Experiments with Helical Flow Total Artificial Heart.

    PubMed

    Wotke, Jiri; Homolka, Pavel; Vasku, Jaromír; Dobsak, Petr; Palanova, Petra; Mrkvicova, Veronika; Konecny, Petr; Soska, Vladimir; Pohanka, Michal; Novakova, Marie; Yurimoto, Terumi; Saito, Itsuro; Inoue, Yusuke; Isoyama, Takashi; Abe, Yusuke

    2016-12-01

    Histopathological analysis can provide important information in long-term experiments with total artificial heart (TAH). Recently, a new type of blood pump, the helical flow total artificial heart (HF-TAH) was developed. This study aimed to investigate the changes in selected vital organs in animal experiments with implanted HF-TAH. Samples from lung, liver, and kidneys from two female goats (No. 1301 and No. 1304) with implanted HF-TAH were analyzed. Tissue samples were fixed in 10% formaldehyde and 4 µm thick transverse sections were stained with hematoxylin-eosin (HE). Additional staining was done for detection of connective tissue (Masson-Goldner stain) and for detection of iron (hemosiderin) deposits (Perls stain). Sections were scanned at 100× and 500× magnification with a light microscope. Experiment no. 1301 survived 100 days (cause of termination was heavy damage of the right pump); experimental goat no.1304 survived 68 days and was sacrificed due to severe right hydrodynamic bearing malfunction. Histopathological analysis of liver samples proved signs of chronic venostasis with limited focal necrotic zones. Dilated tubules, proteinaceous material in tubular lumen, and hemosiderin deposits were detected in kidney samples. Contamination of the organs by embolized micro-particles was suspected at the autopsy after discovery of visible damage (scratches) of the pump impeller surface (made from titanium alloy) in both experiments. Sporadic deposits of foreign micro-particles (presumably titanium) were observed in most of the analyzed parenchymal organs. However, the described deposits were not in direct connection with inflammatory reactions in the analyzed tissues. Histopathological analysis showed the presence of minimal contamination of the lung, kidney, and liver tissue samples by foreign material (titanium very likely). The analysis showed only limited pathological changes, especially in liver and kidneys, which might be attributed to the influence of artificial perfusion often observed in chronic TAH experiments. © 2016 Wiley Periodicals, Inc. and International Center for Artificial Organs and Transplantation.

  9. Marine Mammal Necropsy: An Introductory Guide for Stranding Responders and Field Biologists

    DTIC Science & Technology

    2007-09-01

    the researcher or lab for required tissues and proper sample storage protocols (chill, fix, freeze and/or place in viral transport media). The most...tissues and fluids such as: liver, kidney, serum, aqueous humor, stom- ach contents, intestinal contents, feces, and urine . Tissue samples can be stored...refer to the Figure (2-1) for further explanation on frozen sample storage . The first label is written in black Sharpie on a 1 - 2 square inch piece of

  10. Heavy metal concentrations in bovine tissues (muscle, liver and kidney) and their relationship with heavy metal contents in consumed feed.

    PubMed

    Hashemi, Majid

    2018-06-15

    Toxic (lead, cadmium and mercury) and essential trace (copper and zinc) metals were measured in muscle, liver and kidney samples of bovine and their relationships with heavy metal concentrations in consumed feed were studied. A total of 216 tissue samples from 72 cows and 216 feed samples from 18 farms were collected during four seasons and analyzed for heavy metals by inductively coupled plasma-optical emission spectrometry after wet digestion. The arithmetic mean concentrations (mg/Kg wet weight) of lead (Pb), cadmium (Cd) and mercury were respectively, 0.221, 0.028 and 0.003 in muscle, 0.273, 0.047 and 0.002 in liver and 0.244, 0.114 and 0.003 in kidney. All measured concentrations (with the exception of Pb in muscle) were below the European Union maximum residual limits (MRL). The Cd contents of the kidney were significantly higher than which observed in other tissues. Although, copper (Cu) and zinc (Zn) levels in all of samples were below MRL, but results showed that many cattles may be suffering from Cu and/or Zn deficiency. Significant and positive correlations between Pb (p < 0.05, r = 0.163) and Cd (p < 0.01, r = 0.303) concentrations in feed and studied organs were observed. As a considerable amount of metals above MRL were noticed in our study, continuous monitoring of these metals is recommended to avoid hazardous transfer to human through the food of animal origin. Copyright © 2018 Elsevier Inc. All rights reserved.

  11. Leptospira spp. infection in sheep herds in southeast Brazil

    PubMed Central

    2014-01-01

    Background With the aim of studying Leptospira spp. infection in sheep herds, blood samples and respective kidney and liver fragments were collected from 100 animals from twenty different properties during slaughter at a meat company in the Sorocaba region, São Paulo state, southeast Brazil. The microscopic agglutination test (MAT) was performed with 29 strains of Leptospira spp. To identify the agent in the liver and kidney, 100 samples of each tissue were submitted to culture in Fletcher medium and analyzed by the polymerase chain reaction (PCR) for Leptospira spp. Results MAT detected 23 samples serologically positive for one or more Leptospira spp. serovars and significantly more for Autumnalis. Eight (4%) samples were positive in culture (four kidneys and four livers), corresponding to five animals with positive serology (one animal simultaneously positive for both kidney and liver) and two negatives. PCR detected Leptospira spp. in 14 samples (seven kidneys and seven livers) corresponding to 12 positive animals (two animals simultaneously positive for kidney and liver), of which ten were serologically positive and two negative. Conclusions PCR was faster, more practical and more sensitive than culture for detecting leptospires. The results reinforce the importance of sheep in the epidemiological context of leptospirosis. PMID:24822059

  12. Determination of tilmicosin residues in chicken, cattle, swine, and sheep tissues by liquid chromatography.

    PubMed

    Stobba-Wiley, C M; Chang, J P; Elsbury, D T; Moran, J W; Turner, J M; Readnour, R S; Stobba-Wiley, C M; Chang, J P; Elsbury, D T; Moran, J W; Turner, J M; Readnour, R S

    2000-01-01

    A method was developed and validated for determination and quantitation of tilmicosin residues in swine, cattle, and sheep edible tissues, as well as chicken fat, skin, and muscle over a concentration range of 0.025 microg/g-20 microg/g. For chicken kidney and liver, the method was validated over a range of 0.060 microg/g-20 microg/g. The tissue sample was extracted with methanol and a C18 cartridge was used for solid-phase extraction cleanup. A reversed-phase gradient liquid chromatographic method with detection at 280 nm was used to separate the tilmicosin from matrix components in 30 min run time. The limit of quantitation (LOQ) of the method was 0.025 microg/g for all tested tissues except chicken kidney and liver, for which the LOQ was 0.06 microg/g. Average recoveries for tissue samples ranged from 73 to 98%. Relative standard deviation values ranged from 0.6 to 14.7%.

  13. Biochemical and pathological changes in the male rat kidney and bladder following exposure to continuous 900-MHz electromagnetic field on postnatal days 22-59.

    PubMed

    Türedi, Sibel; Kerimoğlu, Gökçen; Mercantepe, Tolga; Odacı, Ersan

    2017-09-01

    To investigate the effect on male rat kidney and bladder tissues of exposure to 900-megahertz (MHz) electromagnetic field (EMF) applied on postnatal days 22-59, inclusive. Twenty-four male Sprague Dawley rats, aged 21 days, were used. These were divided equally into one of three groups, control (CG), sham (SG) or EMF (EMFG). CG was not exposed to any procedure. SG rats were kept inside a cage, without being exposed to the effect of EMF, for 1 h a day on postnatal days 22-59, inclusive. EMFG rats were exposed to continuous 900-MHz EMF for 1 h a day under the same conditions as those for the SG rats. Rats were sacrificed on postnatal day 60, and the kidney and bladder tissues were removed. Tissues were stained with hematoxylin and eosin (H&E) and Masson trichrome for histomorphological evaluation. The TUNEL method was used to assess apoptosis. Transmission electron microscopy (TEM) was also used for the kidney tissue. Oxidant/antioxidant parameters were studied in terms of biochemical values. The findings showed that tissue malondialdehyde increased in EMFG compared to CG and SG in both kidney (p = 0.004 and p = 0.004, respectively) and bladder tissue (p = 0.004, p = 0.006, respectively), while catalase and glutathione levels decreased compared to CG (p = 0.004; p = 0.004, respectively) and SG (p = 0.004; p = 0.004, respectively). In the EMF group, pathologies such as dilatation and vacuolization in the distal and proximal tubules, degeneration in glomeruli and an increase in cells tending to apoptosis were observed in kidney tissue. In bladder tissue, degeneration in the transitional epithelium and stromal irregularity and an increase in cells tending to apoptosis were observed in EMFG. Additionally, EMFG samples exhibited glomerular capillary degeneration with capillary basement membranes under TEM. We conclude that continuous exposure to the effect of 900-MHz EMF for 1 h a day on postnatal days 22-59, inclusive, causes an increase in oxidative stress and various pathological changes in male rat kidney and bladder tissues.

  14. Glutamine Provides Effective Protection against Deltamethrin-Induced Acute Hepatotoxicity in Rats But Not Against Nephrotoxicity

    PubMed Central

    Gündüz, Ercan; Ülger, Burak Veli; İbiloğlu, İbrahim; Ekinci, Aysun; Dursun, Recep; Zengin, Yılmaz; İçer, Mustafa; Uslukaya, Ömer; Ekinci, Cenap; Güloğlu, Cahfer

    2015-01-01

    Background The aim of this study was to investigate the protective effects of L-glutamine (GLN) against liver and kidney injury caused by acute toxicity of deltamethrin (DLM). Material/Methods Thirty-two rats were indiscriminately separated into 4 groups with 8 rats each: control group (distilled water; 10 ml/kg, perorally [p.o.]), DLM group (35 mg/kg p.o. one dose.), GLN group (1.5 gr/kg, p.o. single dose.) and DLM (35 mg/kg p.o. one dose.) + GLN group (1.5 gr/kg, p.o. one dose after 4 hours.). Testing for total antioxidant status (TAS), total oxidant status (TOS), interleukin-1 beta (IL-1β), tumor necrosis factor-alpha (TNF-α), and interleukin-6 (IL-6) analyses were performed on tissue samples, and alanine aminotransferase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase (LDH), urea, and creatinine were analyzed on serum samples. Liver and kidney samples were histopathologically analyzed. Results The TOS level in liver was significantly higher in the DLM group than in the control group, and the level in DLM+GLN group was considerably lower than in the DLM group. The TAS level in the DLM+GLN group was considerably higher than in the control and DLM groups. The TAS level in kidney tissues was considerably lower in the DLM group than in controls, but was similar to other groups. Histopathological analyses of liver tissues established a significant difference between DLM and DLM+GLN groups in terms of grade 2 hepatic injury. However, no significant difference was found between DLM and DLM+GLN groups in terms of kidney injury. Conclusions Glutamine leads to significant improvement in deltamethrin-induced acute hepatotoxicity in terms of histopathologic results, tissue oxidative stress parameters, and serum liver function marker enzymes. PMID:25890620

  15. The clinical relevance of plasma CD147/basigin in biopsy-proven kidney diseases.

    PubMed

    Mori, Yoshiko; Masuda, Tomohiro; Kosugi, Tomoki; Yoshioka, Tomoki; Hori, Mayuko; Nagaya, Hiroshi; Maeda, Kayaho; Sato, Yuka; Kojima, Hiroshi; Kato, Noritoshi; Ishimoto, Takuji; Katsuno, Takayuki; Yuzawa, Yukio; Kadomatsu, Kenji; Maruyama, Shoichi

    2017-12-12

    Precise understanding of kidney disease activity is needed to design therapeutic strategies. CD147/basigin is involved in the pathogenesis of acute kidney injury and renal fibrosis through inflammatory cell infiltration. The present study examined the clinical relevance of CD147 in biopsy-proven kidney diseases that lead to the progression of chronic kidney disease. Kidney biopsy specimens and plasma and urine samples were obtained from patients with kidney diseases, including IgA nephropathy (IgAN), Henoch-Schönlein purpura nephritis (HSPN), diabetic kidney disease (DKD), focal segmental glomerulosclerosis (FSGS), and membranous nephropathy (MN), who underwent renal biopsy between 2011 and 2014. Plasma and urinary CD147 levels were measured and evaluated for their ability to reflect histological features. Disease activity of IgAN tissues was evaluated according to the Oxford classification and the Japanese histological grading system. In biopsy tissues, CD147 induction was detected in injured lesions representing renal inflammation. Plasma CD147 values correlated with eGFR in patients with inflammation-related kidney diseases such as IgAN, HSPN, and DKD. Particularly in IgAN patients, plasma CD147 levels were correlated with injured regions comprising more than 50% of glomeruli or with tubular atrophy/interstitial injury in biopsy tissues. Proteinuria showed a closer correlation with urinary values of CD147 and L-FABP. Of note, plasma and urinary CD147 levels showed a strong correlation with eGFR or proteinuria, respectively, only in DKD patients. Evaluation of plasma and urinary CD147 levels might provide key insights for the understanding of the activity of various kidney diseases.

  16. Effects of propolis, caffeic acid phenethyl ester, and pollen on renal injury in hypertensive rat: An experimental and theoretical approach.

    PubMed

    Salmas, Ramin Ekhteiari; Gulhan, Mehmet Fuat; Durdagi, Serdar; Sahna, Engin; Abdullah, Huda I; Selamoglu, Zeliha

    2017-08-01

    The objective of this study was to evaluate the antioxidant effects of propolis, caffeic acid phenethyl ester (CAPE; active compound in propolis), and pollen on biochemical oxidative stress biomarkers in rat kidney tissue inhibited by N ω -nitro-L-arginine methyl ester (L-NAME). The biomarkers evaluated were paraoxonase (PON1), oxidative stress index (OSI), total antioxidant status (TAS), total oxidant status (TOS), asymmetric dimethylarginine (ADMA), and nuclear factor kappa B (NF-κB). TAS levels and PON1 activity were significantly decreased in kidney tissue samples in the L-NAME-treated group (P < 0.05). The levels of TAS and PONI were higher in the L-NAME plus propolis, CAPE, and pollen groups compared with the L-NAME-treated group. TOS, ADMA, and NF-κB levels were significantly increased in the kidney tissue samples of the L-NAME-treated group (P < 0.05). However, these parameters were significantly lower in the L-NAME plus propolis, CAPE, and pollen groups (P < 0.05) compared with rats administered L-NAME alone (P < 0.05). Furthermore, the binding energy of CAPE within catalytic domain of glutathione reductase (GR) enzyme as well as its inhibitory mechanism was determined using molecular modeling approaches. In conclusion, experimental and theoretical data suggested that oxidative alterations occurring in the kidney tissue of chronic hypertensive rats may be prevented via active compound of propolis, CAPE administration. Copyright © 2017 John Wiley & Sons, Ltd.

  17. Quantitative determination of selenium and mercury, and an ICP-MS semi-quantitative scan of other elements in samples of eagle tissues collected from the Pacific Northwest--Summer 2011

    USGS Publications Warehouse

    May, Thomas; Walther, Mike; Brumbaugh, William

    2013-01-01

    Eagle tissues from dead eagle carcasses were collected by U.S. Fish and Wildlife Service personnel at various locations in the Pacific Northwest as part of a study to document the occurrence of metal and metalloid contaminants. A group of 182 eagle tissue samples, consisting of liver, kidney, brain, talon, feather, femur, humerus, and stomach contents, were quantitatively analyzed for concentrations of selenium and mercury by atomic absorption techniques, and for other elements by semi-quantitative scan with an inductively coupled plasma-mass spectrometer. For the various tissue matrices analyzed by an ICP-MS semiquantitative scan, some elemental concentrations (micrograms per gram dry weight) were quite variable within a particular matrix; notable observations were as follows: lead concentrations ranged from 0.2 to 31 in femurs, 0.1 to 29 in humeri, 0.1 to 54 in talons, less than (<) 0.05 to 120 in livers, <0.05 to 34 in kidneys, and 0.05 to 8 in brains; copper concentrations ranged from 5 to 9 in feathers, 8 to 47 in livers, 7 to 43 in kidneys, and 7 to 28 in brains; cadmium concentrations ranged from 0.1 to 10 in kidneys. In stomach contents, concentrations of vanadium ranged from 0.08 to 5, chromium 2 to 34, manganese 1 to 57, copper 2 to 69, arsenic <0.05 to 6, rubidium 1 to 13, and barium <0.5 to 18. Selenium concentrations from highest to lowest based on the matrix mean were as follows: kidney, liver, feather, brain, stomach content, talon, femur, and humerus. For mercury, the highest to lowest concentrations were feather, liver, talon, brain, stomach content, femur, and humerus.

  18. [Histology of gill, liver and kidney in juvenile fish Colossoma macropomum exposed to three temperatures].

    PubMed

    Rojas, Luz-Marina; Mata, Claunis; Oliveros, Aridays; Salazar-Lugo, Raquel

    2013-06-01

    Abstract: Histology of gill, liver and kidney in juvenile fish Colossoma macropomum exposed to three temperatures. Water temperature is an important factor that affects growth and antioxidant enzyme activities in fish, and when adverse, it may trigger diseases in fish populations. C. macropomum is a freshwater neotropical fish widely distributed in South America and abundant in river basins as the Amazon and Orinoco. It is highly used for intensive aquaculture development and is a very important product for the local riverside economy in Venezuela. The purpose of our study was to examine the water temperature effect on gills, liver and kidneys of juvenile fishes of C macropomum. Eighteen juveniles with biometrical index of 17.87 +/- 7.88 cm and 87.69 +/- 34.23 g were respectively exposed to three culture temperatures (T18, T29 and T35 degrees C) during a period of 21 days. Histological analyses on gills, liver and kidney were made according to standard methodologies. Our results showed that these tissues exhibited normal citoarchitecture at T29. On the contrary, T18-gills displayed brachiallipid droplets inside brachial epithelium; and disorganization in the brachial tissue was observed at T35. Furthermore, we observed two kinds of hepatocytes (dark and light) on T180 degrees C-liver. The T35-liver samples showed cytoplasmatic granulation and damages in cytoplasmatic membrane. Kidney samples from T18 observed alterations in the cellular distribution of the hematopoietic tissue; while, at T35, the most important feature observed was the disorganization of the glomerular structure. We concluded that T18 and T35 are respectively critical and severe temperatures to C. macropomum; besides, the most sensible tissues to changes induced by temperature in this species were the liver and gills.

  19. Survey of antibiotic residues in Canadian slaughter animals.

    PubMed Central

    Tittiger, F; Kingscote, B; Meldrum, B; Prior, M

    1975-01-01

    Kidneys and urine of cattle, swine, sheep and chickens were tested for bacterial growth inhibitors using Bacillus subtilis and Sarcina lutea as test organisms. Results were as follows: 211 beef kidneys four positive, 611 swine kidneys five positive, 27 sheep and 120 chicken kidneys all negative, 2108 beef urine 76 positive, 2409 swine urine 186 positive, 176 sheep urine 17 positive. Strongest reactions were obtained with B. subtilis on phosphate buffered pH 6.0 plates. Larger zones were produced by urine from injected animals than by tissue samples. PMID:236082

  20. Detecting Renibacterium salmoninarum in wild brown trout by use of multiple organ samples and diagnostic methods

    USGS Publications Warehouse

    Guomundsdottir, S.; Applegate, Lynn M.; Arnason, I.O.; Kristmundsson, A.; Purcell, Maureen K.; Elliott, Diane G.

    2017-01-01

    Renibacterium salmoninarum, the causative agent of salmonid bacterial kidney disease (BKD), is endemic in many wild trout species in northerly regions. The aim of the present study was to determine the optimal R. salmoninarum sampling/testing strategy for wild brown trout (Salmo trutta L.) populations in Iceland. Fish were netted in a lake and multiple organs—kidney, spleen, gills, oesophagus and mid-gut—were sampled and subjected to five detection tests i.e. culture, polyclonal enzyme-linked immunosorbent assay (pELISA) and three different PCR tests. The results showed that each fish had encountered R. salmoninarum but there were marked differences between results obtained depending on organ and test. The bacterium was not cultured from any kidney sample while all kidney samples were positive by pELISA. At least one organ from 92.9% of the fish tested positive by PCR. The results demonstrated that the choice of tissue and diagnostic method can dramatically influence the outcome of R. salmoninarum surveys.

  1. Tylosin depletion from edible pig tissues.

    PubMed

    Prats, C; El Korchi, G; Francesch, R; Arboix, M; Pérez, B

    2002-12-01

    The depletion of tylosin from edible pig tissues was studied following 5 days of intramuscular (i.m.) administration of 10 mg/kg of tylosin to 16 crossbreed pigs. Animals were slaughtered at intervals after treatment and samples of muscle, kidney, liver, skin+fat, and injection site were collected and analysed by high-performance liquid chromatography (HPLC). Seven days after the completion of treatment, the concentration of tylosin in kidney, skin+fat, and at the injection site was higher than the European Union maximal residue limit (MRL) of 100 microg/kg. Tylosin residues in all tissues were below the quantification limit (50 microg/kg) at 10 and 14 days post-treatment.

  2. Determination of sulfonamide residues in the tissues of food animals using automated precolumn derivatization and liquid chromatography with fluorescence detection.

    PubMed

    Salisbury, Craig D C; Sweet, Jason C; Munro, Roger

    2004-01-01

    A liquid chromatographic method for the determination of sulfachloropyridazine, sulfadiazine, sulfadimethoxine, sulfadoxine, sulfaethoxypyridazine, sulfamethazine, sulfaquinoxaline, and sulfathiazole residues in the muscle, liver, and kidney of food animals using sulfapyridine as internal standard is reported. Tissues are extracted using a modified version of AOAC Official Method 983.31 (Sulfonamide Residues in Animal Tissues). The sample extract is reconstituted in pH 3.0 buffer-acetonitrile (60 + 40) and filtered into an autosampler vial. Using a programmable autosampler of a liquid chromatograph, a portion of the sample is derivatized precolumn with fluorescamine. The sulfonamide derivatives are separated by liquid chromatography using a C18 column with a mobile phase of 0.02M phosphoric acid-acetonitrile (60.5 + 39.5) and detected by fluorescence (excitation, 405 nm; emission, 495 nm). The method was applied to swine and cattle muscle, liver, and kidney; sheep and horse muscle and kidney; and chicken muscle and liver. The mean values for samples fortified with sulfonamides at levels between 0.05 and 0.2 microg/g agreed within 96-99% of spiked levels, with coefficients of variation ranging from 4-10%. The limit of detection (LOD) for all sulfonamides was 0.01 microg/g, with the exception of sulfaquinoxaline, for which the LOD was 0.015 microg/g.

  3. Neuropeptide Levels as well as Neprilysin Activity Decrease in Renal Cell Carcinoma.

    PubMed

    Erin, Nuray; İpekçi, Tümay; Akkaya, Bahar; Özbudak, İrem Hicran; Baykara, Mehmet

    2016-12-01

    Calcitonin Gene-related Peptide (CGRP), Vasoactive Intestinal Peptide (VIP) and Substance P (SP) are sensory neuropeptides which may alter cancer growth through modulation of chronic inflammation. We recently reported that SP suppresses breast cancer growth and metastasis through neuroimmune modulation. These neuropeptides are hydrolyzed by Neprilysin (NEP) to bioactive fragments. Decreased activity of NEP was reported in clear cell and chromophobe type renal cell carcinoma (RCC). It is however not known how the levels of neuropeptides hydrolyzed with NEP changes in RCC. Decrease activity of SP and CGRP containing sensory nerve endings was previously reported to increase cancer metastasis in animal models. It is however not known how peptidergic nerve endings are altered in RCC. Hence we here evaluated the levels of neuronal and non-neuronal neuropeptides and NEP activity in RCC including papillary type as well as neighboring uninvolved kidney. A cross-sectional study was conducted in 57 patients undergoing radical nephrectomy and diagnosed with RCC. NEP activity, levels and expression were determined using flourogenic substrate, western blot and qPCR respectively in freshly-frozen tissues. Immunohistochemical analyses were also performed. Neuronal and non-neuronal levels of CGRP, SP and VIP levels were determined using two-step acetic acid extraction. Levels and activity of NEP were markedly decreased in RCC regardless of subtype. Similar levels of VIP were detected in first and second extractions. VIP levels were higher in clear cell and papillary RCC compared to nearby kidney tissue. VIP levels of neighboring kidney tissue of papillary type RCC was significantly lower compared to kidney samples from clear cell RCC. CGRP levels were higher in second extraction. Similar to VIP levels, CGRP levels of neighboring kidney tissue from clear cell and chromophobe type RCC was significantly lower compared to corresponding tumor samples, an effect observed in the second extraction. VIP and CGRP levels of nearby kidney tissue varied subtype dependently demonstrating that different subtypes of RCC alter their local environment differently. Furthermore NEP-induce hydrolysis of VIP creates selective VPAC-1 receptor agonist which has anti-proliferative and anti-inflammatory effects. Hence loss of NEP activity may prevent anti-tumoral effects of VIP on RCC.

  4. Accumulation of polonium 210Po in tissues and organs of deer carvidae from Northern Poland.

    PubMed

    Skwarzec, Bogdan; Prucnal, Malgorzata

    2007-01-01

    This study was undertaken to provide information on accumulation of polonium in tissues and organs of deer carvidae in order to assess the potential transport of this element via food-chain to game meat consumers. Livers, kidneys and muscles of large herbivorous animals belonging to three species: roe deer (Capreolus capreolus), red deer (Cervus elaphus) and fallow deer (Dama dama), collected in Northern Poland, were the subject of the present investigation. Activities of (210)Po were determined by means of alpha spectrometry along with relevant radiochemical procedures. The concentration of (210)Po in analyzed animals decreased in the order kidney > liver > muscle tissue. The average activity concentrations of (210)Po ranged between 0.02 +/- 0.01 Bq. kg(- 1) w.w. in muscles and 7.15 +/- 0.12 Bq. kg(- 1) w.w. in kidneys. Levels of polonium were not influenced by sampling location, sex, age and species of animals.

  5. New approaches in renal microscopy: volumetric imaging and superresolution microscopy.

    PubMed

    Kim, Alfred H J; Suleiman, Hani; Shaw, Andrey S

    2016-05-01

    Histologic and electron microscopic analysis of the kidney has provided tremendous insight into structures such as the glomerulus and nephron. Recent advances in imaging, such as deep volumetric approaches and superresolution microscopy, have the capacity to dramatically enhance our current understanding of the structure and function of the kidney. Volumetric imaging can generate images millimeters below the surface of the intact kidney. Superresolution microscopy breaks the diffraction barrier inherent in traditional light microscopy, enabling the visualization of fine structures. Here, we describe new approaches to deep volumetric and superresolution microscopy of the kidney. Rapid advances in lasers, microscopic objectives, and tissue preparation have transformed our ability to deep volumetric image the kidney. Innovations in sample preparation have allowed for superresolution imaging with electron microscopy correlation, providing unprecedented insight into the structures within the glomerulus. Technological advances in imaging have revolutionized our capacity to image both large volumes of tissue and the finest structural details of a cell. These new advances have the potential to provide additional profound observations into the normal and pathologic functions of the kidney.

  6. The Histopathologic Reliability of Tissue Taken from Cadavers within the Gross Anatomy Laboratory

    ERIC Educational Resources Information Center

    Rae, Guenevere; Newman, William P., III; McGoey, Robin; Donthamsetty, Supriya; Karpinski, Aryn C.; Green, Jeffrey

    2018-01-01

    The purpose of this study was to examine the histopathologic reliability of embalmed cadaveric tissue taken from the gross anatomy laboratory. Tissue samples from hearts, livers, lungs, and kidneys were collected after the medical students' dissection course was completed. All of the cadavers were embalmed in a formalin-based fixative solution.…

  7. The protective effect of pomegranate extract against cisplatin toxicity in rat liver and kidney tissue.

    PubMed

    Bakır, Salih; Yazgan, Ümit Can; İbiloğlu, İbrahim; Elbey, Bilal; Kızıl, Murat; Kelle, Mustafa

    2015-01-01

    The purpose of this study was to perform a histopathological investigation, at the light microscopy level, of the protective effects of pomegranate extract in cisplatin-induced liver and kidney damage in rats. Twenty-eight adult male Wistar albino rats were randomly divided into four groups of seven animals: Group 1: Control; Group 2: Treated for 10 consecutive days by gavage with pomegranate juice (2 ml/kg/day); Group 3: Injected intraperitoneally with cisplatin (8 mg/kg body weight, single dose) onset of the day 5, and Group 4: Treated by gavage with pomegranate juice 10 days before and after a single injection of cisplatin onset of the day 5. After 10 days, the animals were sacrificed and their kidneys and liver tissue samples were removed from each animal after experimental procedures. Cisplatin-induced renal and hepatic toxicity and the effect of pomegranate juice were evaluated by histopatological examinations. In the kidney tissue, pomegranate juice significantly ameliorated cisplatin-induced structural alterations when compared with the cisplatin alone group. But in the liver tissue, although pomegranate juice attenuated the cisplatin-induced toxicity only in two rats, significant improvement was not observed. In conclusion, these results demonstrate that the anti-oxidant pomegranate juice might have a protective effect against cisplatin-induced toxicity in rat kidney, but not in liver. Pomegranate juice could be beneficial as a dietary supplement in patients receiving chemotherapy medications.

  8. Macro- and microelements in the rat liver, kidneys, and brain tissues; sex differences and effect of blood removal by perfusion in vivo.

    PubMed

    Orct, Tatjana; Jurasović, Jasna; Micek, Vedran; Karaica, Dean; Sabolić, Ivan

    2017-03-01

    Concentrations of macro- and microelements in animal organs indicate the animal health status and represent reference data for animal experiments. Their levels in blood and tissues could be different between sexes, and could be different with and without blood in tissues. To test these hypotheses, in adult female and male rats the concentrations of various elements were measured in whole blood, blood plasma, and tissues from blood-containing (nonperfused) and blood-free liver, kidneys, and brain (perfused in vivo with an elements-free buffer). In these samples, 6 macroelements (Na, Mg, P, S, K, Ca) and 14 microelements (Fe, Mn, Co, Cu, Zn, Se, I, As, Cd, Hg, Pb, Li, B, Sr) were determined by inductively coupled plasma mass spectrometry following nitric acid digestion. In blood and plasma, female- or male-dominant sex differences were observed for 6 and 5 elements, respectively. In nonperfused organs, sex differences were observed for 3 (liver, brain) or 9 (kidneys) elements, whereas in perfused organs, similar differences were detected for 9 elements in the liver, 5 in the kidneys, and none in the brain. In females, perfused organs had significantly lower concentrations of 4, 5, and 2, and higher concentrations of 10, 4, and 7 elements, respectively, in the liver, kidneys, and brain. In males, perfusion caused lower concentrations of 4, 7, and 2, and higher concentrations of 1, 1, and 7 elements, respectively, in the liver, kidneys, and brain. Therefore, the residual blood in organs can significantly influence tissue concentrations of various elements and their sex-dependency. Copyright © 2017 Elsevier GmbH. All rights reserved.

  9. Evaluation of Nucleic Acid Preservation Cards for West Nile Virus Testing in Dead Birds

    PubMed Central

    Foss, Leslie; Reisen, William K.; Fang, Ying; Kramer, Vicki; Padgett, Kerry

    2016-01-01

    The California West Nile virus (WNV) Dead Bird Surveillance Program (DBSP) is an important component of WNV surveillance in the state. We evaluated FTA™ and RNASound™ cards as an alternative method for sampling dead birds for WNV molecular testing as these cards allow for more cost effective, rapid, and safer diagnostic sampling than the shipment of bird carcasses. To evaluate accuracy of results among avian sampling regimes, Reverse-Transcription Polymerase Chain Reaction (RT-PCR) results from FTA™ and RNASound™ cards were compared with results from kidney tissue, brain tissue, or oral swabs in lysis buffer in 2012–2013. In addition, RT-PCR results were compared with results from oral swabs tested by rapid antigen tests (RAMP™ and VecTOR™). While test results from the cards were not as sensitive as kidney tissue testing, they were more likely to provide accurate results than rapid antigen tests, and detected WNV in corvids as well as in other passerines, raptors, and waterfowl. Overall, WNV RT-PCR cycle threshold (Ct) scores from the cards were higher than those from tissue testing, but both card products displayed high sensitivity and specificity. American Crow samples provided the highest sensitivity. The cards also proved to be easier and more convenient vehicles for collecting and shipping samples, and in 2014 our program launched use of RNASound™ cards in the DBSP. Both FTA™ and RNASound™ products displayed 96% agreement with tissue results and are an adequate alternative sampling method for WNV dead bird testing. PMID:27341492

  10. Cadmium contamination of tissues and organs of delphinids species (Stenella attenuata)--influence of biological and ecological factors

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

    Andre, J.M.; Amiard, J.C.; Amiard-Triquet, C.

    1990-12-01

    Based on a sample of 27 dolphins (Stenella attenuata) captured in the Eastern tropical zone of the Pacific Ocean, this study was carried out to analyze the cadmium accumulation levels and distribution in 12 organs or tissue samples. The average cadmium concentrations were between 0.2 mg Cd.kg-1 in the brain and muscle and 48 mg Cd.kg-1 in the kidneys. For most of organs and tissues the average values were between 1 and 5 mg Cd.kg-1. Kidneys, liver, muscle, and intestine contained almost 85% of the total cadmium burden of all tissues considered in this study. Most of the biological andmore » ecological factors taken into account (age, sex, total weight, and length of the dolphins, weight of the organs, place and date of capture) interacted with the cadmium concentrations and burdens in the collected organs or tissues. Three factors appear to be of prime importance: age, body weight, and geographical location of the area of capture.« less

  11. Research of human kidney thermal properties for the purpose of cryosurgery

    NASA Astrophysics Data System (ADS)

    Ponomarev, D. E.; Pushkarev, A. V.

    2017-11-01

    Calculation of the heat transfer is required to correctly predict the results of cryosurgery, cryopreservation, etc. One of the important initial parameters are the thermophysical properties of biological tissues. In the present study, the values of the heat capacity, cryoscopic temperature and enthalpy of the phase transition of the kidney samples in vitro were obtained by differential scanning calorimetry.

  12. Comparison of conventional PCR, quantitative PCR, bacteriological culture and the Warthin Starry technique to detect Leptospira spp. in kidney and liver samples from naturally infected sheep from Brazil.

    PubMed

    Fornazari, Felipe; da Silva, Rodrigo Costa; Richini-Pereira, Virginia Bodelão; Beserra, Hugo Enrique Orsini; Luvizotto, Maria Cecília Rui; Langoni, Helio

    2012-09-01

    Leptospirosis is an infectious disease of worldwide importance. The development of diagnostic techniques allows sick animals to be identified, reservoirs to be eliminated and the disease prevented and controlled. The present study aimed to compare different techniques for diagnosing leptospirosis in sheep. Samples of kidney, liver and blood were collected from 465 animals that originated from a slaughterhouse. The sera were analyzed by the Microscopic Agglutination Test (MAT), and kidney and liver samples of seropositive animals were analyzed using four techniques: bacteriological culture, the Warthin Starry (WS) technique, conventional PCR (cPCR), and quantitative PCR (qPCR). With the MAT, 21 animals were positive (4.5%) to serovars Hardjo (n=12), Hebdomadis (n=5), Sentot (n=2), Wolfii (n=1) and Shermani (n=1). Titers were 100 (n=10), 200 (n=2), 400 (n=6) and 1600 (n=3). No animal was positive by bacteriological culture; four animals were positive by the WS technique in kidney samples; six animals were positive by cPCR in kidney samples; and 11 animals were positive by qPCR, eight of which in kidney samples and three in liver. The bacterial quantification revealed a median of 4.3 bacteria/μL in liver samples and 36.6 bacteria/μL in kidney samples. qPCR presented the highest sensitivity among the techniques, followed by cPCR, the WS technique and bacteriological culture. These results indicate that sheep can carry leptospires of the Sejroe serogroup, and demonstrate the efficiency of quantitative PCR to detect Leptospira spp. in tissue samples. Published by Elsevier B.V.

  13. Liquid microjunction surface sampling coupled with high-pressure liquid chromatography-electrospray ionization-mass spectrometry for analysis of drugs and metabolites in whole-body thin tissue sections.

    PubMed

    Kertesz, Vilmos; Van Berkel, Gary J

    2010-07-15

    In this work, a commercially available autosampler was adapted to perform direct liquid microjunction (LMJ) surface sampling followed by a high-pressure liquid chromatography (HPLC) separation of the extract components and detection with electrospray ionization mass spectrometry (ESI-MS). To illustrate the utility of coupling a separation with this direct liquid extraction based surface sampling approach, four different organs (brain, lung, kidney, and liver) from whole-body thin tissue sections of propranolol dosed and control mice were examined. The parent drug was observed in the chromatograms of the surface sampling extracts from all the organs of the dosed mouse examined. In addition, two isomeric phase II metabolites of propranolol (an aliphatic and an aromatic hydroxypropranolol glucuronide) were observed in the chromatograms of the extracts from lung, kidney, and liver. Confirming the presence of one or the other or both of these glucuronides in the extract from the various organs was not possible without the separation. These drug and metabolite data obtained using the LMJ surface sampling/HPLC-MS method and the results achieved by analyzing similar samples by conventional extraction of the tissues and subsequent HPLC-MS analysis were consistent. The ability to directly and efficiently sample from thin tissue sections via a liquid extraction and then perform a subsequent liquid phase separation increases the utility of this liquid extraction surface sampling approach.

  14. Testing of candidate non-lethal sampling methods for detection of Renibacterium salmoninarum in juvenile Chinook salmon Oncorhynchus tshawytscha

    USGS Publications Warehouse

    Elliott, Diane G.; McKibben, Constance L.; Conway, Carla M.; Purcell, Maureen K.; Chase, Dorothy M.; Applegate, Lynn M.

    2015-01-01

    Non-lethal pathogen testing can be a useful tool for fish disease research and management. Our research objectives were to determine if (1) fin clips, gill snips, surface mucus scrapings, blood draws, or kidney biopsies could be obtained non-lethally from 3 to 15 g Chinook salmon Oncorhynchus tshawytscha, (2) non-lethal samples could accurately discriminate between fish exposed to the bacterial kidney disease agent Renibacterium salmoninarum and non-exposed fish, and (3) non-lethal samples could serve as proxies for lethal kidney samples to assess infection intensity. Blood draws and kidney biopsies caused ≥5% post-sampling mortality (Objective 1) and may be appropriate only for larger fish, but the other sample types were non-lethal. Sampling was performed over 21 wk following R. salmoninarum immersion challenge of fish from 2 stocks (Objectives 2 and 3), and nested PCR (nPCR) and real-time quantitative PCR (qPCR) results from candidate non-lethal samples were compared with kidney tissue analysis by nPCR, qPCR, bacteriological culture, enzyme-linked immunosorbent assay (ELISA), fluorescent antibody test (FAT) and histopathology/immunohistochemistry. R. salmoninarum was detected by PCR in >50% of fin, gill, and mucus samples from challenged fish. Mucus qPCR was the only non-lethal assay exhibiting both diagnostic sensitivity and specificity estimates >90% for distinguishing between R. salmoninarum-exposed and non-exposed fish and was the best candidate for use as an alternative to lethal kidney sample testing. Mucus qPCR R. salmoninarum quantity estimates reflected changes in kidney bacterial load estimates, as evidenced by significant positive correlations with kidney R. salmoninaruminfection intensity scores at all sample times and in both fish stocks, and were not significantly impacted by environmentalR. salmoninarum concentrations.

  15. Kidney tissue targeted metabolic profiling of glucocorticoid-induced osteoporosis and the proposed therapeutic effects of Rhizoma Drynariae studied using UHPLC/MS/MS.

    PubMed

    Huang, Yue; Liu, Xinyu; Zhao, Longshan; Li, Famei; Xiong, Zhili

    2014-06-01

    Traditional Chinese medicine and modern science have indicated that there is a close relationship between bone and kidney. In light of this, this project was designed to study the metabolic profiling by UHPLC/MS/MS of glucocorticoid-induced osteoporosis in kidney tissue and the possible therapeutic effects of Rhizoma Drynariae (RD), a classic traditional Chinese medicine, in improving the kidney function and strengthening bone. Twenty-one Wistar rats were divided into three groups: control group (rats before prednisolone inducing), a model group (prednisolone-induced group) and a treatment group (prednisolone-induced rats that were then administered RD ethanol extracts). By using pattern recognition analysis, a significant change in the metabolic profile of kidney tissue samples was observed in the model group and restoration of the profile was observed after the administration of RD ethanol extracts. Some significantly changed biomarkers related to osteoporosis such as sphingolipids (C16 dihydrosphingosine, C18 dihydrosphingosine, C18 phytosphingosine, C20 phytosphingosine), lysophosphatidycholines (C16:0 LPC, C18:0 LPC) and phenylalanine were identified. As a complement to the metabolic profiling of RD in plasma, these biomarkers suggest that kidney damage, cell cytotoxicity and apoptosis exist in osteoporosis rats, which is helpful in further understanding the underlying process of glucocorticoid-induced osetoporosis and the suggested therapeutic effects of RD. The method shows that tissue target metabonomics might provide a powerful tool to further understand the process of disease and the mechanism of therapeutic effect of Chinese medicines. Copyright © 2014 John Wiley & Sons, Ltd.

  16. Human exposure to metals: levels in autopsy tissues of individuals living near a hazardous waste incinerator.

    PubMed

    Mari, Montse; Nadal, Martí; Schuhmacher, Marta; Barbería, Eneko; García, Francisco; Domingo, José L

    2014-06-01

    The concentrations of a number of metals were determined in the brain, bone, kidney, liver, and lung of 20 autopsied subjects who had lived, at least 10 years, in the neighborhood of a hazardous waste incinerator (HWI) in Tarragona (Catalonia, Spain). Results were compared with those obtained in 1998 (baseline survey) and previous surveys (2003 and 2007). Arsenic, Be, Ni, Tl, and V showed concentrations below the corresponding detection limits in all tissues. Cadmium showed the highest levels in the kidney, with a mean value of 21.15 μg/g. However, Cd was found below the detection limit in the brain and bone. Chromium showed similar concentrations in the kidney, brain, and lung (range of mean values, 0.57-0.66 μg/g) and higher in the bone (1.38 μg/g). In turn, Hg was below the detection limit in all tissues with the exception of the kidney, where the mean concentration was 0.15 μg/g (range, <0.05-0.58 μg/g). On the other hand, Mn could be detected in all tissues showing the highest levels in the liver and kidney (1.45 and 1.09 μg/g, respectively). Moreover, Pb showed the highest concentrations in bone (mean, 1.39 μg/g; range, <0.025-4.88 μg/g). Finally, Sn could be detected only in some tissue samples, reaching the highest values in the bone (0.17 μg/g). The current metal levels in human tissues from individuals living near the HWI of Tarragona are comparable and of a similar magnitude to previously reported results corresponding to general populations, as well as those of our previous surveys.

  17. Transplacental transfer of persistent organic pollutants in La Plata dolphins (Pontoporia blainvillei; Cetartiodactyla, Pontoporiidae).

    PubMed

    Barbosa, Ana Paula Moreno; Méndez-Fernandez, Paula; Dias, Patrick Simões; Santos, Marcos César Oliveira; Taniguchi, Satie; Montone, Rosalinda Carmela

    2018-08-01

    Persistent organic pollutants (POPs) accumulate in the fat tissue of living organisms and are found in relatively high concentrations in animals at the top of the food chain, such as dolphins. The ability of these compounds to interact with the endocrine system of marine mammals constitutes a risk for the reproduction and conservation of species. The La Plata dolphin, Pontoporia blainvillei, is exclusive to the southwestern Atlantic Ocean and is classified on the IUCN red list as a vulnerable species. Blubber, liver, kidney and muscle samples from four P. blainvillei mother-fetus pairs were analyzed to evaluate the transfer of POPs to fetal tissues through the placenta. The presence of POPs in fetal tissues indicates the maternal transfer of compounds. In the pregnant females, blubber was the tissue with POP highest concentration, followed by the liver, kidneys and muscles. In the fetuses, POP accumulation mainly occurred in the blubber followed by the muscles, liver and kidneys. Polychlorinated biphenyls (PCBs) and dichlorodiphenyltrichloroethane (DDTs) were found in all tissues analyzed and had the highest concentrations among all compounds. The main PCB congeners in the fetal samples had five to seven chlorine atoms. The only polybrominated diphenyl ether (PBDE) in the fetal samples was 47 and was found only in blubber. The main DDT metabolite in the fetuses was p,p'-DDE. POP transfer via the placenta occurs in the first months of gestation and increases with fetal development, according to fetus/mother (F/M) ratio: HCB>DDT>PCB>PBDE>Mirex, which may follow the order of the octanol/water partition coefficient (K ow ) values. Copyright © 2018 Elsevier B.V. All rights reserved.

  18. Expression pattern of aquaporins in patients with primary nephrotic syndrome with edema

    PubMed Central

    WANG, YU; BU, JIMEI; ZHANG, QING; CHEN, KAI; ZHANG, JIHONG; BAO, XIAORONG

    2015-01-01

    The association between the expression of aquaporins (AQPs) in kidney tissues and the occurrence of edema in nephrotic syndrome (NS) remains unclear. The current study aimed to investigate this association. A total of 54 patients with primary glomerular disease, diagnosed by renal biopsy, were divided into three groups: Control, NS without edema and NS with edema. The expression of AQP1, AQP2, AQP3 and AQP4 in kidney tissues from these patients was assessed using immunohistochemistry, and urinary AQP concentrations were quantified by ELISA. Comparison of the three groups was conducted using one way analysis of variance, independent samples t-test or the Chi-square test. AQP1 was strongly expressed in the proximal tubules. The proportion of the AQP1-positive area in kidney tissues from patients with NS with edema was significantly reduced, in comparison with the other two groups. By contrast, the proportion of the AQP2-positive area in the NS with edema group was significantly higher than that of the other two groups; significant differences were also observed between the control and NS without edema groups for this parameter. Urinary AQP2 concentrations in patients with NS (with and without edema) were significantly higher than that of the control group, and exhibited a significant positive correlation with kidney tissue AQP2 concentrations. The present study demonstrated the abnormal expression pattern of AQP1-AQP4 in the kidney tissues of patients with NS, providing a basis for an improved understanding of the role of AQP in the pathogenesis of NS. PMID:26261083

  19. Tissue-associated self-antigens containing exosomes: Role in allograft rejection.

    PubMed

    Sharma, Monal; Ravichandran, Ranjithkumar; Bansal, Sandhya; Bremner, Ross M; Smith, Michael A; Mohanakumar, T

    2018-06-15

    Exosomes are extracellular vesicles that express self-antigens (SAgs) and donor human leukocyte antigens. Tissue-specific exosomes can be detected in the circulation following lung, heart, kidney and islet cell transplantations. We collected serum samples from patients who had undergone lung (n = 30), heart (n = 8), or kidney (n = 15) transplantations to isolate circulating exosomes. Exosome purity was analyzed by Western blot, using CD9 exosome-specific markers. Tissue-associated lung SAgs, collagen V (Col-V) and K-alpha 1 tubulin (Kα1T), heart SAgs, myosin and vimentin, and kidney SAgs, fibronectin and collagen IV (Col-IV), were identified using western blot. Lung transplant recipients diagnosed with bronchiolitis obliterans syndrome had exosomes with higher expression of Col-V (4.2-fold) and Kα1T (37.1-fold) than stable. Exosomes isolated from heart transplant recipients diagnosed with coronary artery vasculopathy had a 3.9-fold increase in myosin and a 4.7-fold increase in vimentin compared with stable. Further, Kidney transplant recipients diagnosed with transplant glomerulopathy had circulating exosomes with a 2-fold increased expression of fibronectin and 2.5-fold increase in Col-IV compared with stable. We conclude that circulating exosomes with tissue associated SAgs have the potential to be a noninvasive biomarker for allograft rejection. Copyright © 2018. Published by Elsevier Inc.

  20. Investigation of enrofloxacin residues in broiler tissues using ELISA and LC-MS/MS.

    PubMed

    Panzenhagen, Pedro Henrique N; Aguiar, Waldemir S; Gouvêa, Raquel; de Oliveira, Andréa M G; Barreto, Fabiano; Pereira, Virgínia L A; Aquino, Maria Helena C

    2016-01-01

    This study investigated the efficiency of an enrofloxacin ELISA test kit to detect the presence of enrofloxacin residues in broiler tissues compared with LC-MS/MS. Broiler tissues from 72 samples consisting of 60 breast muscle, six pools of livers (500 g each) and six pools of kidneys (500 g each) were obtained from six different slaughterhouses. Breast muscle from 10 carcasses and pools of livers and kidneys from approximately 200 carcasses of the same flock were collected from each slaughterhouse. ELISA and HPLC were used to identify and quantify the contamination of the samples with enrofloxacin. A total of 72% of the analysed samples contained enrofloxacin residues detected by the ELISA and 22.2% were detected by LC-MS/MS. The mean values of enrofloxacin contamination found in chicken breast by ELISA and HPLC were 8.63 and 12.25 μg kg(-1), respectively. None of the samples exceeded the maximum limit of 100 μg kg(-1) by both methods set by the European Union as well as the Brazilian Agriculture Ministry. All positive samples for enrofloxacin residues detected by LC-MS/MS were also positive by ELISA. These data confirm the efficiency of the ELISA test, and suggest its use as a screening method for enrofloxacin residues in poultry tissues due to its quick results, low price and ease of applicability.

  1. Effect of pomegranate (Punica granatum L.) juice on kidney, liver, heart and testis histopathological changes, and the tissues lipid peroxidation and antioxidant status in lead acetate-treated rats.

    PubMed

    Aksu, D S; Sağlam, Y S; Yildirim, S; Aksu, T

    2017-10-31

    Pomegranate juice (PJ) contains relevant amounts of active biological compounds which alleviate the detrimental effects of chronic heavy metal exposure. This study investigated the protective potential of PJ against lead-induced oxidative stress. A total of forty adult male Sprague Dawley rats were divided into four experimental groups. The animals were fed a standard pellet diet and tap water ad libitum. The rats were divided into four groups (n=10 for each group): control, lead asetat (2000 ppm), low-treated PJ- a daily dose of 2.000 ppm lead plus 30µl pomegranate juice (included 1.050 µmol total polyphenols, gallic acid equivalent), and high-treated PJ- a daily dose of 2.000 ppm lead plus 60µl pomegranate juice (included 2.100 µmol total polyphenols, gallic acid equivalent). The treatments were delivered for 5 weeks. After the treatment period, the tissues samples (kidney, liver, heart and testis) were collected. Tissue lead (Pb) and mineral amounts (copper, zinc, and iron), tissues lipid peroxidation level and antioxidant status, and tissues histopathological changes were determined. The results showed that the highest rate lead loading was in the kidney and the testis. Pomegranate juice was decreased the lead levels of soft tissues examined; increased Zn amounts in tissues of which the lead accumulation was higher (kidney and the testis); decreased the copper, zinc and the iron levels of the liver and heart tissues, without creating a weakness in antioxidant capacity of these tissues, restricted the oxidative stress by decreasing lipid peroxidation, improved both of the activities of antioxidant enzymes such as superoxide dismutase (SOD) and catalaz (CAT), and the level of glutathione (GSH) in all the tissues examined in lead-treated groups. As histopathological findings, the cellular damage induced by lead in the tissues of the kidney, liver and the heart were observed to have been partially prevented by PJ treatment. The protective effect of PJ was more pronounced in the testis compared to those others.

  2. Liquid Microjunction Surface Sampling Coupled with High-Pressure Liquid Chromatography-Electrospray Ionization-Mass Spectrometry for Analysis of Drugs and Metabolites in Whole-Body Thin Tissue Sections

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

    Kertesz, Vilmos; Van Berkel, Gary J

    2010-01-01

    In this work, a commercially available autosampler was adapted to perform direct liquid microjunction (LMJ) surface sampling followed by a high-pressure liquid chromatography (HPLC) separation of the extract components and detection with electrospray ionization mass spectrometry (ESI-MS). To illustrate the utility of coupling a separation with this direct liquid extraction based surface sampling approach, four different organs (brain, lung, kidney, and liver) from whole-body thin tissue sections of propranolol dosed and control mice were examined. The parent drug was observed in the chromatograms of the surface sampling extracts from all the organs of the dosed mouse examined. In addition, twomore » isomeric phase II metabolites of propranolol (an aliphatic and an aromatic hydroxypropranolol glucuronide) were observed in the chromatograms of the extracts from lung, kidney, and liver. Confirming the presence of one or the other or both of these glucuronides in the extract from the various organs was not possible without the separation. These drug and metabolite data obtained using the LMJ surface sampling/HPLC-MS method and the results achieved by analyzing similar samples by conventional extraction of the tissues and subsequent HPLC-MS analysis were consistent.« less

  3. Role of Magnetic Resonance Elastography as a Noninvasive Measurement Tool of Fibrosis in a Renal Allograft: A Case Report.

    PubMed

    Kim, J K; Yuen, D A; Leung, G; Jothy, S; Zaltzman, J; Ramesh Prasad, G V; Prabhudesai, V; Mnatzakanian, G; Kirpalani, A

    2017-09-01

    A major reason for poor long-term kidney transplant outcomes is the development of chronic allograft injury, characterized by interstitial fibrosis and tubular atrophy. Currently, an invasive biopsy that samples only <1% of the kidney is the gold standard for detecting kidney allograft fibrosis. We report the use of magnetic resonance elastography (MRE) to quantify tissue stiffness as a noninvasive and whole-kidney measurement tool of allograft fibrosis in a kidney transplant patient at 2 time points. The MRE whole-kidney stiffness values reflected the changes in fibrosis of the kidney allograft as assessed by histologic examination. To our knowledge, this technique is the first observation of change over time in MRE-derived whole-kidney stiffness in an allograft that is consistent with changes in histology-derived fibrosis scores in a single patient. Copyright © 2017 Elsevier Inc. All rights reserved.

  4. Advantages of tandem LC-MS for the rapid assessment of tissue-specific metabolic complexity using a pentafluorophenylpropyl stationary phase

    PubMed Central

    Lv, Haitao; Palacios, Gustavo; Hartil, Kirsten; Kurland, Irwin J.

    2014-01-01

    In this study a UPLC-tandem (Waters Xevo TQ) MRM based MS method was developed for rapid, broad profiling of hydrophilic metabolites from biological samples, in either positive or negative ion modes without the need for an ion pairing reagent, using a reversed-phase pentafluorophenylpropyl (PFPP) column. The developed method was successfully applied to analyze various biological samples from C57BL/6 mice; including urine, duodenum, liver, plasma, kidney, heart, and skeletal muscle. As result, a total 112 of hydrophilic metabolites were detected within 8 min of running time to obtain a metabolite profile of the biological samples. The analysis of this number of hydrophilic metabolites is significantly faster than previous studies. Classification separation for metabolites from different tissues was globally analyzed by PCA, PLS-DA and HCA biostatistical methods. Overall, most of the hydrophilic metabolites were found to have a “fingerprint” characteristic of tissue dependency. In general, a higher level of most metabolites was found in urine, duodenum and kidney. Altogether, these results suggest that this method has potential application for targeted metabolomic analyzes of hydrophilic metabolites in a wide ranges of biological samples. PMID:21322650

  5. Advantages of tandem LC-MS for the rapid assessment of tissue-specific metabolic complexity using a pentafluorophenylpropyl stationary phase.

    PubMed

    Lv, Haitao; Palacios, Gustavo; Hartil, Kirsten; Kurland, Irwin J

    2011-04-01

    In this study, a tandem LC-MS (Waters Xevo TQ) MRM-based MS method was developed for rapid, broad profiling of hydrophilic metabolites from biological samples, in either positive or negative ion modes without the need for an ion pairing reagent, using a reversed-phase pentafluorophenylpropyl (PFPP) column. The developed method was successfully applied to analyze various biological samples from C57BL/6 mice, including urine, duodenum, liver, plasma, kidney, heart, and skeletal muscle. As result, a total 112 of hydrophilic metabolites were detected within 8 min of running time to obtain a metabolite profile of the biological samples. The analysis of this number of hydrophilic metabolites is significantly faster than previous studies. Classification separation for metabolites from different tissues was globally analyzed by PCA, PLS-DA and HCA biostatistical methods. Overall, most of the hydrophilic metabolites were found to have a "fingerprint" characteristic of tissue dependency. In general, a higher level of most metabolites was found in urine, duodenum, and kidney. Altogether, these results suggest that this method has potential application for targeted metabolomic analyzes of hydrophilic metabolites in a wide ranges of biological samples.

  6. Targeting Increased Polyamine Transport of Resistant Melanomas

    DTIC Science & Technology

    2017-08-01

    rapid clearance of AP (Me44Nap44Me) from the blood after 1 h, with likely clearance through the kidneys (see UCF consortium report). To develop a... Kidney 4.20 ± 0.85 11.11 ± 1.84 0.91 ± 0.16 0.01 0.04 ± 0.01 a errors expressed as the standard deviation around the reported mean. b only observed...various tissues. Since all four of the kidney samples contained trace quantities of AP (Me44Nap44Me), we suspect that this water-soluble compound

  7. Effect of sex on histological and histochemical structures of different parts of the kidney in Japanese quail.

    PubMed

    Mobini, Behzad; Abdollahi, MohammadHossein

    2016-09-01

    The aim of the present study was to investigate the effect of gender on the histological and histochemical structures of different anatomical regions of the kidney in Japanese quail (Coturnix japonica). Tissue samples from cranial, middle and caudal divisions of each kidney were obtained from 20 male and 20 female adult, healthy Japanese quail. The sections stained with hematoxylin & eosin ( H & E: ), Masson's trichrome, Verhoeff's, Alcian blue (pH 2.5), Periodic acid-Schiff, and Gomori's method for reticulum. Unusual findings of the kidney in Japanese quail were the presence of three types of nephrons, all the connective tissue fibers in capsule and interlobular septa and AB-reactions of the proximal convoluted cells. No significant sex-based differences were found. The various histological structures of the kidney showed no significant differences among different divisions of the left and right kidneys. It is concluded that the general histological and histochemical properties of the kidney in Japanese quail were similar to those of chickens and some other species, but that there were also some differences. One of the major differences was brush border of interdigitating microvilli on luminal surface of collecting ducts in Japanese quail. © 2016 Poultry Science Association Inc.

  8. Proteomic analysis of formalin-fixed paraffin-embedded renal tissue samples by label-free MS: assessment of overall technical variability and the impact of block age.

    PubMed

    Craven, Rachel A; Cairns, David A; Zougman, Alexandre; Harnden, Patricia; Selby, Peter J; Banks, Rosamonde E

    2013-04-01

    Protein profiling of formalin-fixed paraffin-embedded (FFPE) tissues has enormous potential for the discovery and validation of disease biomarkers. The aim of this study was to systematically characterize the effect of length of time of storage of such tissue blocks in pathology archives on the quality of data produced using label-free MS. Normal kidney and clear cell renal cell carcinoma tissues routinely collected up to 10 years prior to analysis were profiled using LC-MS/MS and the data analyzed using MaxQuant. Protein identities and quantification data were analyzed to examine differences between tissue blocks of different ages and assess the impact of technical and biological variability. An average of over 2000 proteins was seen in each sample with good reproducibility in terms of proteins identified and quantification for normal kidney tissue, with no significant effect of block age. Greater biological variability was apparent in the renal cell carcinoma tissue, possibly reflecting disease heterogeneity, but again there was good correlation between technical replicates and no significant effect of block age. These results indicate that archival storage time does not have a detrimental effect on protein profiling of FFPE tissues, supporting the use of such tissues in biomarker discovery studies. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  9. Effects of pregnancy on the solubility of halogenated volatile anaesthetics in rat blood and tissues.

    PubMed

    Rao, Y; Wang, Y L; Li, H; Zhang, W; Liu, J

    2008-11-01

    This study was designed to evaluate the effects of pregnancy on the solubility of halogenated volatile anaesthetics in rat blood and tissues. Tissue samples from 10 pregnant and 10 non-pregnant adult female Sprague Dawley rats, including the heart, liver, kidney and brain, were obtained and made into respective homogenates. Blood/gas and tissue/gas partition coefficients for halothane, sevoflurane and isoflurane were determined by the method of two-stage headspace equilibration by gas chromatography with each of the homogenates. Values were analysed by t-test or one-way analysis of variance. The solubility within blood and brain for halothane in the pregnant group (2.90 +/- 0.44, 5.55 +/- 0.73) was significantly lower than that of the non-pregnant group (3.42 +/- 023, 6.33 +/- 0.64; P < 0.05). However, there were no significant differences between the two groups for liver, kidney or heart solubility. For sevoflurane and isoflurane, there were no significant differences in solubility between the two groups. In conclusion, pregnancy decreased the solubility of halothane within the blood and brain, whereas the solubility of halothane in other tissues including the liver, kidney and heart showed no significant alteration. Pregnancy did not affect the solubility ofsevoflurane or isoflurane within blood or the other tissues studied.

  10. Contrast Enhanced Diagnostic Ultrasound Causes Renal Tissue Damage in a Porcine Model

    PubMed Central

    Miller, Douglas L.; Dou, Chunyan; Wiggins, Roger C.

    2010-01-01

    Objective Glomerular capillary hemorrhage (GCH) has been reported and confirmed as a consequence of contrast-enhanced diagnostic ultrasound (CEDUS) of rat kidney. This study assessed renal tissue injury in the larger porcine model. Methods The right kidneys of anesthetized pigs were imaged in 8 groups of 4 pigs. A Vingmed System Five (General Electric Co. Cincinnati OH) was used at 1.5 MHz in B-mode to intermittently scan the kidney at 4 s intervals. A Sequoia 512 (Acuson, Mountain View CA) was used in the 1.5 MHz Cadence CPS mode with intermittent agent-clearance bursts at 4 s intervals. Kidneys were scanned transabdominally, or after laparotomy through a saline standoff. The Sequoia 512 probe was placed in contact with the kidney for one group. Definity (Lantheus Medical Imaging, N. Billerica, MA) was infused at 4 μl/kg/min (diluted 33:1 in saline) for 4 min during scanning. Results Blood-filled urinary tubules were evident on the kidney surface for all groups, except for the group with the probe in contact with the kidney. GCH was found by histology in 31.7 % ± 9.8 % of glomeruli in the center of the scan plane for 1.7 MPa transabdominal scanning and 1.5 % ± 2.9 % of glomeruli in sham samples (P<0.05). In addition, hematuria was detected after scanning, and tubular obstruction occurred in some nephrons. Conclusion Renal tissue damage was induced by CEDUS in the porcine model. This result, together with previous studies in rats, support an hypothesis that GCH would occur in humans from similar CEDUS. PMID:20876892

  11. Stromal cells in tissue homeostasis: balancing regeneration and fibrosis.

    PubMed

    Rabelink, Ton J; Little, Melissa H

    2013-12-01

    The ageing population and the increasing prevalence of noncommunicable diseases such as diabetes and hypertension have led to an increased prevalence of chronic kidney disease. The generation of de novo kidney tissue from embryonic tissue and stem cells using tissue engineering approaches is being explored as an alternative to renal replacement therapy for treating the disease. It is, however, becoming clear that resident cells can not only induce fibrotic repair, but can also restore damaged kidney tissue. Mobilizing this innate capacity of the kidney to regenerate is of particular interest in the prevention of irreversible kidney failure. A novel concept is that the interaction of interstitial stromal cells with the local immune system may regulate tissue homeostasis and the balance between tissue repair and fibrosis. Mesenchymal stromal cells (MSCs), in particular, may enhance the intrinsic reparative capabilities of the kidney. This Perspectives article considers the innate regenerative potential of the kidney in the context of ongoing studies of MSC therapy.

  12. A fluorogenic near-infrared imaging agent for quantifying plasma and local tissue renin activity in vivo and ex vivo

    PubMed Central

    Zhang, Jun; Preda, Dorin V.; Vasquez, Kristine O.; Morin, Jeff; Delaney, Jeannine; Bao, Bagna; Percival, M. David; Xu, Daigen; McKay, Dan; Klimas, Michael; Bednar, Bohumil; Sur, Cyrille; Gao, David Z.; Madden, Karen; Yared, Wael; Rajopadhye, Milind

    2012-01-01

    The renin-angiotensin system (RAS) is well studied for its regulation of blood pressure and fluid homeostasis, as well as for increased activity associated with a variety of diseases and conditions, including cardiovascular disease, diabetes, and kidney disease. The enzyme renin cleaves angiotensinogen to form angiotensin I (ANG I), which is further cleaved by angiotensin-converting enzyme to produce ANG II. Although ANG II is the main effector molecule of the RAS, renin is the rate-limiting enzyme, thus playing a pivotal role in regulating RAS activity in hypertension and organ injury processes. Our objective was to develop a near-infrared fluorescent (NIRF) renin-imaging agent for noninvasive in vivo detection of renin activity as a measure of tissue RAS and in vitro plasma renin activity. We synthesized a renin-activatable agent, ReninSense 680 FAST (ReninSense), using a NIRF-quenched substrate derived from angiotensinogen that is cleaved specifically by purified mouse and rat renin enzymes to generate a fluorescent signal. This agent was assessed in vitro, in vivo, and ex vivo to detect and quantify increases in plasma and kidney renin activity in sodium-sensitive inbred C57BL/6 mice maintained on a low dietary sodium and diuretic regimen. Noninvasive in vivo fluorescence molecular tomographic imaging of the ReninSense signal in the kidney detected increased renin activity in the kidneys of hyperreninemic C57BL/6 mice. The agent also effectively detected renin activity in ex vivo kidneys, kidney tissue sections, and plasma samples. This approach could provide a new tool for assessing disorders linked to altered tissue and plasma renin activity and to monitor the efficacy of therapeutic treatments. PMID:22674025

  13. Effects of Electromagnetic Radiation Use on Oxidant/Antioxidant Status and DNA Turn-over Enzyme Activities in Erythrocytes and Heart, Kidney, Liver, and Ovary Tissues From Rats: Possible Protective Role of Vitamin C.

    PubMed

    Devrim, Erdinç; Ergüder, Imge B; Kılıçoğlu, Bülent; Yaykaşlı, Emine; Cetin, Recep; Durak, Ilker

    2008-01-01

    ABSTRACT In this study, the aim was to investigate possible effects of Electromagnetic Radiation (EMR) use on oxidant and antioxidant status in erythrocytes and kidney, heart, liver, and ovary tissues from rats, and possible protective role of vitamin C. For this aim, 40 Wistar albino female rats were used throughout the study. The treatment group was exposed to EMR in a frequency of 900 MHz, the EMR plus vitamin C group was exposed to the same EMR frequency and given vitamin C (250 mg/kg/day) orally for 4 weeks. There were 10 animals in each group including control and vitamin C groups. At the end of the study period, blood samples were obtained from the animals to get erythrocyte sediments. Then the animals were sacrificed and heart, kidney, liver, and ovary tissues were removed. Malondialdehyde (MDA) levels and superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px), xanthine oxidase (XO), and adenosine deaminase (ADA) enzyme activities were measured in the tissues and erythrocytes. It was observed that MDA level, XO, and GSH-Px activities significantly increased in the EMR group as compared with those of the control group in the erythrocytes. In the kidney tissues, it was found that MDA level and CAT activity significantly increased, whereas XO and ADA activities decreased in the cellular phone group as compared with those of the control group. However, in the heart tissues it was observed that MDA level, ADA, and XO activities significantly decreased in the cellular phone group as compared with those of the control group. The results suggest that EMR at the frequency generated by a cell phone causes oxidative stress and peroxidation in the erythrocytes and kidney tissues from rats. In the erythrocytes, vitamin C seems to make partial protection against the oxidant stress.

  14. Interpreting dual ELISA and qPCR data for bacterial kidney disease of salmonids.

    PubMed

    Nance, Shelly L; Riederer, Michael; Zubkowski, Tyler; Trudel, Marc; Rhodes, Linda D

    2010-09-02

    Although there are a variety of methods available for the detection of Renibacterium salmoninarum, the causative agent of bacterial kidney disease in salmon and trout, the enzyme-linked immunosorbent assay (ELISA) is probably the most widely used method. However, ELISA measures bacterial antigen, which does not necessarily reflect the number of cells present. We hypothesized that dual analysis of kidney tissue by ELISA and a quantitative real-time polymerase chain reaction assay (qPCR) would provide complementary information about antigen level and the number of bacterial genomes. We found that DNA extracted from the insoluble fraction of the ELISA tissue preparation produced the same qPCR result as DNA extracted directly from frozen tissue, permitting true dual analysis of the same tissue sample. We examined kidney tissue in this manner from individual free-ranging juvenile Chinook salmon and antibiotic-treated captive subadult Chinook salmon and observed 3 different patterns of results. Among the majority of fish, there was a strong correlation between the ELISA value and the qPCR value. However, subsets of fish exhibited either low ELISA values with elevated qPCR values or higher ELISA values with very low qPCR values. These observations suggest a conceptual model that allows inferences about the state of infection of individual fish based on dual ELISA/qPCR results. Although this model requires further assessment through experimental infections and treatments, it may have utility in broodstock selection programs that currently apply egg-culling practices based on ELISA alone.

  15. A quantitative method for residues of macrolide antibiotics in porcine kidney by liquid chromatography/tandem mass spectrometry.

    PubMed

    Dickson, Leslie C; O'Byrne, Collin; Chan, Wayne

    2012-01-01

    An LC/MS/MS-based multiresidue quantitative method was developed for the macrolides erythromycin A, neospiramycin I, oleandomycin, spiramycin I, tilmicosin, and tylosin A in porcine kidney tissues. The Canadian Food Inspection Agency (CFIA) had as part of its analytical scope an LC/UV method for quantification of residues of two macrolide antibiotics, tilmicosin and tylosin A, in the kidney, liver, and muscle of cattle, swine, and poultry. The method could not reliably detect concentrations below 10 microg/kg. To increase the scope of the CFIA's analytical capabilities, a sensitive multiresidue quantitative method for macrolide residues in food animal tissues was required. Porcine kidney samples were extracted with acetonitrile and alkaline buffer and cleaned-up using silica-based C18 SPE cartridges. Sample extracts were analyzed using LC/MS/MS with positive electrospray ionization. Fitness for purpose was verified in a single-laboratory validation study using a second analyst. The working analytical range was 5 to 50 microg/kg. LOD and LOQ were 0.5 to 0.6 microg/kg and 1.5 to 3.0 microg/kg, respectively. Limits of identification were 0.5 to 2.0 microg/kg. Relative intermediate precisions were 8 to 17%. Average absolute recoveries were 68 to 76%.

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

    Hofmann, R.; Hartung, R.; Geissdoerfer, K.A.

    Laser energy of a Nd-YAG laser (1064 nm. wave length, 8 nsec pulse duration) was directed against various tissue cultures and the urothelium of the ureter, bladder and kidney parenchyma in pigs. Single pulse energy was 50 to 120 mJ with a repetition rate of 20 Hz. Urothelium and kidney parenchyma were irradiated in seven pigs. Tissue samples were examined histologically and electron microscopically directly, two, four, eight and 12 days after irradiation. No macroscopic lesion could be found. Maximum energy caused a small rupture cone of 40 micron. depth. No thermic effects or necrosis resulted, so that no harmmore » is to be expected with unintentional irradiation during laser stone disintegration.« less

  17. Inorganic elements in green sea turtles (Chelonia mydas): relationships among external and internal tissues

    USGS Publications Warehouse

    Faust, Derek R.; Hooper, Michael J.; Cobb, George P.; Barnes, Melanie; Shaver, Donna; Ertolacci, Shauna; Smith, Philip N.

    2014-01-01

    Inorganic elements from anthropogenic sources have entered marine environments worldwide and are detectable in marine organisms, including sea turtles. Threatened and endangered classifications of sea turtles have heretofore made assessments of contaminant concentrations difficult because of regulatory restrictions on obtaining samples using nonlethal techniques. In the present study, claw and skin biopsy samples were examined as potential indicators of internal tissue burdens in green sea turtles (Chelonia mydas). Significant relationships were observed between claw and liver, and claw and muscle concentrations of mercury, nickel, arsenic, and selenium (p < 0.05). Similarly, significant relationships were observed between skin biopsy concentrations and those in liver, kidney, and muscle tissues for mercury, arsenic, selenium, and vanadium (p < 0.05). Concentrations of arsenic, barium, chromium, nickel, strontium, vanadium, and zinc in claws and skin biopsies were substantially elevated when compared with all other tissues, indicating that these highly keratinized tissues may represent sequestration or excretion pathways. Correlations between standard carapace length and cobalt, lead, and manganese concentrations were observed (p < 0.05), indicating that tissue concentrations of these elements may be related to age and size. Results suggest that claws may indeed be useful indicators of mercury and nickel concentrations in liver and muscle tissues, whereas skin biopsy inorganic element concentrations may be better suited as indicators of mercury, selenium, and vanadium concentrations in liver, kidney, and muscle tissues of green sea turtles.

  18. Assignment of vibrational spectral bands of kidney tissue by means of low temperature SERS spectroscopy

    NASA Astrophysics Data System (ADS)

    Velicka, M.; Radzvilaite, M.; Ceponkus, J.; Urboniene, V.; Pucetaite, M.; Jankevicius, F.; Steiner, G.; Sablinskas, V.

    2017-02-01

    Surface enhanced Raman scattering (SERS) spectroscopy is a useful method for detection of trace amounts of molecules. It has already been successfully implemented for detection of explosives, food additives, biomarkers in blood or urine, etc. In the last decade, SERS spectroscopy was introduced into the field of health sciences and has been especially focused on early disease detection. In the recent years, application of SERS spectroscopy for detection of various types of human cancerous tissues emerged. Furthermore, SERS spectroscopy of extracellular fluid shows great potential for the differentiation of normal and cancerous tissues; however, due to high variety of molecules present in such biological samples, the experimental spectrum is a combination of many different overlapping vibrational spectral bands. Thus, precise assignment of these bands to the corresponding molecular vibrations is a difficult task. In most cases, researchers try to avoid this task satisfying just with tentative assignment. In this study, low temperature SERS measurements of extracellular fluid of cancerous and healthy kidney tissue samples were carried out in order to get a deeper understanding of the nature of vibrational spectral bands present in the experimental spectrum. The SERS spectra were measured in temperature range from 300 K down to 100 K. SERS method was implemented using silver nanoparticle colloidal solution. The results of the low temperature SERS experiment were analysed and compared with the results of theoretical calculations. The analysis showed that the SERS spectrum of extracellular fluid of kidney tissue is highly influenced by the vibrational bands of adenine and Lcystine molecules.

  19. Azithromycin metabolite identification in plasma, bile, and tissues of the ball python (Python regius).

    PubMed

    Hunter, R P; Koch, D E; Coke, R L; Goatley, M A; Isaza, R

    2003-04-01

    Azithromycin is the first of a class of antibiotics classified as azalides. Six ball pythons (Python regius) were given a single dose of azithromycin at 10 mg/kg p.o. and i.v. in a crossover design. Serial blood samples were collected for unchanged azithromycin and to determine, if possible, the structure and number of circulating azithromycin metabolites. After a 4-month wash-out period, the snakes were given azithromycin p.o. as a single dose of 10 mg/kg for the study of azithromycin metabolism and metabolite tissue distribution. Bile, liver, lung, kidney, and skin samples were analyzed for the metabolites identified from the first experiment. Unchanged azithromycin accounted for 80, 68, and 60% of the total material at 12, 24, and 48 h postadministration in plasma, independent of route of administration. At both 24 and 72 h postadministration, azithromycin accounted for 70% of total azithromycin- associated material in bile. In liver and kidney, unchanged azithromycin accounted for 40% of the total azithromycin-associated material; this doubled in lung and skin. Fifteen metabolites were positively or tentatively identified in plasma, bile, or tissues of all snakes. Four of these possible metabolites: 3'-desamine-3-ene-azithromycin, descladinose dehydroxy-2-ene-azithromycin, 3'-desamine-3-ene descladinose-azithromycin, and 3'-N-nitroso,9a-N-desmethyl-azithromycin are unique to this species. Descladinose-azithromycin, 3'-N-desmethyl,9a-N-desmethyl-azithromycin, and 3'-N-desmethyl, 3'-O-desmethyl-azithromycin were the only metabolites identified in skin. Kidney tissue contained a greater number of metabolites than liver tissue, with 3'-N-didesmethyl-azithromycin being identified only in the kidney. Compared with the dog and cat, a greater number of metabolites were identified in ball python plasma. The percentage of unchanged azithromycin in bile is not different between the three species.

  20. Angiogenin Mediates Cell-Autonomous Translational Control under Endoplasmic Reticulum Stress and Attenuates Kidney Injury

    PubMed Central

    Mami, Iadh; Bouvier, Nicolas; El Karoui, Khalil; Gallazzini, Morgan; Rabant, Marion; Laurent-Puig, Pierre; Li, Shuping; Tharaux, Pierre-Louis; Beaune, Philippe; Thervet, Eric; Chevet, Eric; Hu, Guo-Fu

    2016-01-01

    Endoplasmic reticulum (ER) stress is involved in the pathophysiology of kidney disease and aging, but the molecular bases underlying the biologic outcomes on the evolution of renal disease remain mostly unknown. Angiogenin (ANG) is a ribonuclease that promotes cellular adaptation under stress but its contribution to ER stress signaling remains elusive. In this study, we investigated the ANG-mediated contribution to the signaling and biologic outcomes of ER stress in kidney injury. ANG expression was significantly higher in samples from injured human kidneys than in samples from normal human kidneys, and in mouse and rat kidneys, ANG expression was specifically induced under ER stress. In human renal epithelial cells, ER stress induced ANG expression in a manner dependent on the activity of transcription factor XBP1, and ANG promoted cellular adaptation to ER stress through induction of stress granules and inhibition of translation. Moreover, the severity of renal lesions induced by ER stress was dramatically greater in ANG knockout mice (Ang−/−) mice than in wild-type mice. These results indicate that ANG is a critical mediator of tissue adaptation to kidney injury and reveal a physiologically relevant ER stress-mediated adaptive translational control mechanism. PMID:26195817

  1. Relationships of mercury concentrations across tissue types, muscle regions and fins for two shark species.

    PubMed

    O'Bryhim, Jason R; Adams, Douglas H; Spaet, Julia L Y; Mills, Gary; Lance, Stacey L

    2017-04-01

    Mercury (Hg) exposure poses a threat to both fish and human health. Sharks are known to bioaccumulate Hg, however, little is known regarding how Hg is distributed between different tissue groups (e.g. muscle regions, organs). Here we evaluated total mercury (THg) concentrations from eight muscle regions, four fins (first dorsal, left and right pectorals, caudal-from both the inner core and trailing margin of each fin), and five internal organs (liver, kidney, spleen, heart, epigonal organ) from two different shark species, bonnethead (Sphyrna tiburo) and silky shark (Carcharhinus falciformis) to determine the relationships of THg concentrations between and within tissue groups. Total Hg concentrations were highest in the eight muscle regions with no significant differences in THg concentrations between the different muscle regions and muscle types (red and white). Results from tissue collected from any muscle region would be representative of all muscle sample locations. Total Hg concentrations were lowest in samples taken from the fin inner core of the first dorsal, pectoral, and caudal (lower lobe) fins. Mercury concentrations for samples taken from the trailing margin of the dorsal, pectoral, and caudal fins (upper and lower lobe) were also not significantly different from each other for both species. Significant relationships were found between THg concentrations in dorsal axial muscle tissue and the fin inner core, liver, kidney, spleen and heart for both species as well as the THg concentrations between the dorsal fin trailing margin and the heart for the silky shark and all other sampled tissue types for the bonnethead shark. Our results suggest that biopsy sampling of dorsal muscle can provide data that can effectively estimate THg concentrations in specific organs without using more invasive, or lethal methods. Copyright © 2017 Elsevier Ltd. All rights reserved.

  2. In situ detection of cancerous kidney tissue by means of fiber ATR-FTIR spectroscopy

    NASA Astrophysics Data System (ADS)

    Sablinskas, Valdas; Velicka, Martynas; Pucetaite, Milda; Urboniene, Vidita; Ceponkus, Justinas; Bandzeviciute, Rimante; Jankevicius, Feliksas; Sakharova, Tatiana; Bibikova, Olga; Steiner, Gerald

    2018-02-01

    The crucial goal of kidney-sparing surgical resection of a malignant tumor is complete removal of the cancerous tissue. The exact border between the cancerous and normal tissues is not always possible to identify by naked eye, therefore, a supplementary intraoperative diagnosis is needed. Unfortunately, intraoperative pathology methods used nowadays are time consuming and of inadequate quality rendering not definitive diagnosis. It has recently been shown that ATR-FTIR spectroscopy can be used for fast discrimination between cancerous and normal kidney tissues by analyzing the collected spectra of the tissue touch imprint smears. Most prominent differences are obtained in the wavenumber region from 950 cm-1 to 1250 cm-1, where the spectral bands due to the molecular vibrations of glycogen arise in the spectra of cancerous tissue smears. Such method of detection of cancerous tissue is limited by requirement to transfer the suspected tissue from the body to the FTIR instrument and stamp it on an ATR crystal of the spectrometer. We propose a spectroscopic tool which exploits the same principle of detection of cancerous cells as mentioned above, but does not require the tissue to be transferred from the body to the spectrometer. The portable spectrometer used in this design is equipped with fiber ATR probe and a sensitive liquid nitrogen cooled MCT detector. The design of the fiber probe allows the ATR tip to be changed easily in order to use only new sterilized tips for each measurement point of the tissue. It also enables sampling multiple areas of the suspected tissue with high lateral resolution which, in turn, increases accuracy with which the marginal regions between normal and cancerous tissues can be identified. Due to the loss of optical signal in the fiber probe the spectra have lower signal-to-noise ratio than in the case of standard ATR sampling setup. However, software for the spectral analysis used with the fiber probe design is still able to distinguish between cancerous and normal tissues with high accuracy.

  3. Real-time PCR for quantification of viable Renibacterium salmoninarum in chum salmon Oncorhynchus keta.

    PubMed

    Suzuki, Kunio; Sakai, D K

    2007-03-13

    Quantification of msa gene mRNA of Renibacterium salmoninarum, the causative agent of bacterial kidney disease (BKD), was investigated using reverse transcription followed by real-time PCR assay on R. salmoninarum in culture, and in experimentally challenged chum salmon Oncorhynchus keta fry kidney tissues (total of 70 samples) after intraperitoneal (i.p.) injection and bath infection. Correlations of msa gene mRNA concentrations with culturable cell concentrations (as colony forming units [CFU]), determined by drop-plate culture method on selective kidney disease medium (SKDM) agar through a 12 wk incubation time, and msa gene DNA concentrations by real-time PCR assay were examined. Furthermore, ovarian fluid samples from wild chum salmon adults with no clinical signs of disease were collected from 8 rivers and from clinically infected kokanee 0. nerka and masu salmon O. masou that were reared in 1 and 2 hatcheries, respectively (total of 414 samples). All samples were examined by nested PCR assay. Then, positive samples were examined by real-time PCR assays for mRNA and DNA; mRNA was detectable at 8 log units (5.0 x 101 to 5.0 x 10(9) copies p11(-1)) with high correlation (R2 = 0.999). The mRNA concentration correlated with CFU in kidney tissue from fish infected by i.p. injection (R2 = 0.924), by bath infection (R2 = 0.502) and in culture (R2 = 0.888). R. salmoninarum was detected and quantified by real-time PCR assay for mRNA in ovarian fluid samples in both subclinically infected chum salmon adults and clinically infected kokanee and masu salmon adults; detection rates ranged from 0 to 44.4% and concentrations ranged from 9.7 x 10(2) to 5.6 x 10(5) copies pl(-1). These results indicate that real-time PCR assay for the mRNA is a rapid, sensitive and reliable method to detect and quantify the viability of R. salmoninarum in kidney and ovarian fluid samples of salmonid fishes with both clinical and subclinical infection of the pathogen.

  4. Ontogeny and nutritional programming of mitochondrial proteins in the ovine kidney, liver and lung.

    PubMed

    Yakubu, D P; Mostyn, A; Hyatt, M A; Kurlak, L O; Budge, H; Stephenson, T; Symonds, M E

    2007-12-01

    This study investigated the developmental and nutritional programming of two important mitochondrial proteins, namely voltage-dependent anion channel (VDAC) and cytochrome c, in the sheep kidney, liver and lung. The effect of maternal nutrient restriction between early and mid-gestation (i.e. 28- to 80-day gestation, the period of maximal placental growth) on the abundance of these proteins was also examined in fetal and juvenile offspring. Fetuses were sampled at 80 and 140 days of gestation (term approximately 147 days), and postnatal animals at 1 and 30 days and 6 months of age. The abundance of VDAC peaked at 140 days of gestation in the lung, compared with 1 day after birth in the kidney and liver, whereas cytochrome c abundance was greatest at 140 days of gestation in the liver, 1 day after birth in the kidney and 6 months of age in lungs. This differential ontogeny in mitochondrial protein abundance between tissues was accompanied with very different tissue-specific responses to changes in maternal food intake. In the liver, maternal nutrient restriction only increased mitochondrial protein abundance at 80 days of gestation, compared with no effect in the kidney. In contrast, in the lung mitochondrial protein, abundance was raised near to term, whereas VDAC abundance was decreased by 6 months of age. These findings demonstrate the tissue-specific nature of mitochondrial protein development that reflects differences in functional adaptation after birth. The divergence in mitochondrial response between tissues to maternal nutrient restriction early in pregnancy further reflects these differential ontogenies.

  5. Tissue distribution of metals in white-fronted geese and spot-billed ducks from Korea.

    PubMed

    Kim, Jungsoo; Oh, Jong-Min

    2013-07-01

    This study presents concentrations of Fe, Zn, Mn, Cu, Pb and Cd in livers, kidneys, muscles and bones of white-fronted geese Anser albifrons (geese) and spot-billed ducks Anas poecilorhyncha (ducks). Iron in livers, kidneys and muscles, Zn in muscles, Mn and Cd in every tissue, Cu in livers, muscles and bones and Pb in bones differed between species, and there were significant differences among tissues in both species. Essential elements such as Fe, Zn, Mn and Cu concentrations were within the background levels. Lead concentrations in livers of 7 of 14 geese and 7 of 19 ducks and in bones of 4 of 19 ducks exceeded background concentrations for waterfowl (5 μg/g dw for the liver, 10 μg/g dw for the bone). Almost all samples of both species had the background Cd concentrations in the liver (33 of 33 geese and ducks) and kidney (14 geese and 18 ducks). Tissue concentrations of Cd were greater in geese than ducks. In contrast, tissue concentrations of Pb in bones were greater in ducks than in geese. These different trends for Cd and Pb reflect a short and/or long term difference in exposure and degree of accumulation of these metals.

  6. Examining the occurrence of residues of flunixin meglumine in cull dairy cows by use of the flunixin cull cow survey.

    PubMed

    Deyrup, Cynthia L; Southern, Kristal J; Cornett, Julie A; Shultz, Craig E; Cera, Deborah A

    2012-07-15

    To determine whether cull dairy cows with signs of certain clinical conditions, termed suspect, are more likely than healthy-appearing cull dairy cows to have violative concentrations of flunixin meglumine in their tissues at slaughter. Cross-sectional study. 961 cull dairy cows. Suspect cull dairy cows were selected from 21 beef slaughter establishments with a high production volume of dairy cows, and kidney and liver tissues were collected for screening. Kidney tissues were screened for antibiotics and sulfonamides with the fast antimicrobial screening test (FAST). Liver tissues were screened for flunixin meglumine with an ELISA, and quantitative analysis of ELISA-positive samples was performed with high-performance liquid chromatography. During the same time period, liver tissues from 251 healthy-appearing cull dairy cows were collected for the Food Safety and Inspection Service National Residue Program Scheduled Sampling Plan, but were screened only for flunixin meglumine. Of 710 suspect cull dairy cows, 50 (7.04%) had liver tissue flunixin concentrations higher than the flunixin tolerance concentration (0.125 ppm). Thirty-one of 168 (18.45%) FAST-positive and 19 of 542 (3.51%) FAST-negative suspect cull dairy cows had violative tissue flunixin concentrations. Two of the 251 (0.80%) healthy-appearing cull dairy cows had violative tissue flunixin concentrations. Suspect cull dairy cows, especially those that were also FAST positive, had a significantly higher incidence of violative tissue flunixin concentrations than healthy-appearing cull dairy cows at slaughter. Targeted sampling plans for flunixin meglumine in suspect dairy cows can help to support more efficient use of resources and further safeguard the nation's food supply.

  7. Flow-cytometric determination of genotoxic effects of exposure to petroleum in mink and sea otters

    USGS Publications Warehouse

    Bickham, J.W.; Mazet, J.A.; Blake, J.; Smolen, M.J.; Lou, Y.; Ballachey, Brenda E.

    1998-01-01

    Three experiments were conducted to investigate the genotoxic effects of crude oil on mink and sea otters, In the first experiment, the effects on mink of chronic exposure to weathered Prudhoe Bay crude oil were studied, Female mink were fed a diet that included weathered crude oil for a period of 3 weeks prior to mating, during pregnancy and until weaning. Kits were exposed through lactation and by diet after weaning until 4 months of age. Kidney and liver tissues of the kits were examined using flow cytometry (FCM) and it was found that the genome size was increased in kidney samples from the experimental group compared to the control group. This effect was probably due to some type of DNA amplification and it could have been inherited from the exposed mothers or have been a somatic response to oil exposure in the pups, No evidence of clastogenic effects, as measured by the coefficient of variation (CV) of the G(1) peak, was found in kidney or liver tissue. In the second experiment, yearling female mink were exposed either by diet or externally to crude oil or bunker C fuel oil. Evidence for clastogenic damage was found in spleen tissue for the exposure groups, but not in kidney tissue. No evidence of increased genome size was observed. In the third experiment, blood was obtained from wild-caught sea otters in Prince William Sound. The sea otters represented two populations: one from western Prince William Sound that was potentially exposed to oil from the Exxon Valdez oil spill and a reference population from eastern Prince William Sound that did not receive oil from the spill. The spill had occurred 1.5 years prior to obtaining the blood samples. Although the mean CVs did not differ between the populations, the exposed population had a significantly higher variance of CV measurements and five out of 15 animals from the exposed population had CVs higher than the 95% confidence limits of the reference population, It is concluded that FCM is a sensitive indicator of the clastogenic effects of oil exposure and that haematopoietic tissues and blood are best for detecting clastogenic damage. Moreover, the observed differences in the genome size of the kidney cells mere possibly heritable effects, but this needs further investigation. Lastly, sea otters exposed to spilled oil 1.5 years earlier showed evidence of clastogenic damage in one-third of the individuals sampled.

  8. Counting glomeruli and podocytes: rationale and methodologies

    PubMed Central

    Puelles, Victor G.; Bertram, John F.

    2015-01-01

    Purpose of review There is currently much interest in the numbers of both glomeruli and podocytes. This interest stems from greater understanding of the effects of suboptimal fetal events on nephron endowment, the associations between low nephron number and chronic cardiovascular and kidney disease in adults, and the emergence of the podocyte depletion hypothesis. Recent findings Obtaining accurate and precise estimates of glomerular and podocyte number has proven surprisingly difficult. When whole kidneys or large tissue samples are available, design-based stereological methods are considered gold-standard because they are based on principles that negate systematic bias. However, these methods are often tedious and time-consuming, and oftentimes inapplicable when dealing with small samples such as biopsies. Therefore, novel methods suitable for small tissue samples, and innovative approaches to facilitate high through put measurements, such as magnetic resonance imaging (MRI) to estimate glomerular number and flow cytometry to estimate podocyte number, have recently been described. Summary This review describes current gold-standard methods for estimating glomerular and podocyte number, as well as methods developed in the past 3 years. We are now better placed than ever before to accurately and precisely estimate glomerular and podocyte number, and to examine relationships between these measurements and kidney health and disease. PMID:25887899

  9. The histopathologic reliability of tissue taken from cadavers within the gross anatomy laboratory.

    PubMed

    Rae, Guenevere; Newman, William P; McGoey, Robin; Donthamsetty, Supriya; Karpinski, Aryn C; Green, Jeffrey

    2018-03-01

    The purpose of this study was to examine the histopathologic reliability of embalmed cadaveric tissue taken from the gross anatomy laboratory. Tissue samples from hearts, livers, lungs, and kidneys were collected after the medical students' dissection course was completed. All of the cadavers were embalmed in a formalin-based fixative solution. The tissue was processed, embedded in paraffin, sectioned at six micrometers, and stained with H&E. The microscope slides were evaluated by a board certified pathologist to determine whether the cellular components of the tissues were preserved at a high enough quality to allow for histopathologic diagnosis. There was a statistically significant relationship between ratings and organ groups. Across all organs, there was a smaller proportion of "poor" ratings. The lung group had the highest percentage of "poor" ratings (23.1%). The heart group had the least "poor" ratings (0.0%). The largest percentage of "satisfactory" ratings were in the lung group (52.8%), and the heart group contained the highest percentage of "good" ratings (58.5%) The lung group had the lowest percentage of "good" ratings (24.2%). These results indicate that heart tissue is more reliable than lung, kidney, or liver tissue when utilizing tissue from the gross anatomy laboratory for research and/or educational purposes. This information advises educators and researchers about the quality and histopathologic reliability of tissue samples obtained from the gross anatomy laboratory. Anat Sci Educ 11: 207-214. © 2017 American Association of Anatomists. © 2017 American Association of Anatomists.

  10. Tissue microarrays and digital image analysis.

    PubMed

    Ryan, Denise; Mulrane, Laoighse; Rexhepaj, Elton; Gallagher, William M

    2011-01-01

    Tissue microarrays (TMAs) have recently emerged as very valuable tools for high-throughput pathological assessment, especially in the cancer research arena. This important technology, however, has yet to fully penetrate into the area of toxicology. Here, we describe the creation of TMAs representative of samples produced from conventional toxicology studies within a large-scale, multi-institutional pan-European project, PredTox. PredTox, short for Predictive Toxicology, formed part of an EU FP6 Integrated Project, Innovative Medicines for Europe (InnoMed), and aimed to study pre-clinically 16 compounds of known liver and/or kidney toxicity. In more detail, TMAs were constructed from materials corresponding to the full face sections of liver and kidney from rats treated with different drug candidates by members of the consortium. We also describe the process of digital slide scanning of kidney and liver sections, in the context of creating an online resource of histopathological data.

  11. Dyspepsia treatment with Al compounds widely used in clinical practice — an animal model approach

    NASA Astrophysics Data System (ADS)

    Pinheiro, T.; Canena, J.; Reis, J.; Santos, A. M.; Pinto, A. S.; Quina, M. G.; Reis, M. A.; Alves, L. C.

    1996-04-01

    The potential toxic effects of Al to organs and tissues used in drugs commonly applied in dyspepsia as therapeutic, have been studied. Brain, liver, kidney and serum samples obtained from Wistar rats treated with two commercial Al complexes were studied and compared with equivalent samples collected from healthy animals receiving a placebo. The major alterations found, connected with the persistent intake of medicaments based on Al compounds, are relative to the accumulation of Al in liver and kidney. Also, the Al levels increase in brain and serum of rats supplemented with one of the Al complexes used. In the liver and kidney samples analyzed alterations in the Cu and Zn content levels were observed. Furthermore, a tendency to the decrease of Fe content in kidney and an increase of the Mn levels in brain is observed. The elemental alterations found are probably related to the intake of the drugs tested and are dependent on the type of the Al complex administered. The results obtained suggest that the long term use of these medicaments in the clinical practice should be thought over.

  12. Mycotoxin-Containing Diet Causes Oxidative Stress in the Mouse

    PubMed Central

    Hou, Yan-Jun; Zhao, Yong-Yan; Xiong, Bo; Cui, Xiang-Shun; Kim, Nam-Hyung; Xu, Yin-Xue; Sun, Shao-Chen

    2013-01-01

    Mycotoxins which mainly consist of Aflatoxin (AF), Zearalenone (ZEN) and Deoxynivalenol (DON) are commonly found in many food commodities. Although each component has been shown to cause liver toxicity and oxidative stress in several species, there is no evidence regarding the effect of naturally contained multiple mycotoxins on tissue toxicity and oxidative stress in vivo. In the present study, mycotoxins-contaminated maize (AF 597 µg/kg, ZEN 729 µg/kg, DON 3.1 mg/kg maize) was incorporated into the diet at three different doses (0, 5 and 20%) to feed the mice, and blood and tissue samples were collected to examine the oxidative stress related indexes. The results showed that the indexes of liver, kidney and spleen were all increased and the liver and kidney morphologies changed in the mycotoxin-treated mice. Also, the treatment resulted in the elevated glutathione peroxidase (GPx) activity and malondialdehyde (MDA) level in the serum and liver, indicating the presence of the oxidative stress. Moreover, the decrease of catalase (CAT) activity in the serum, liver and kidney as well as superoxide dismutase (SOD) activity in the liver and kidney tissue further confirmed the occurrence of oxidative stress. In conclusion, our data indicate that the naturally contained mycotoxins are toxic in vivo and able to induce the oxidant stress in the mouse. PMID:23555961

  13. Carbendazim-induced haematological, biochemical and histopathological changes to the liver and kidney of male rats.

    PubMed

    Selmanoglu, G; Barlas, N; Songür, S; Koçkaya, E A

    2001-12-01

    Carbendazim is a systemic broad-spectrum fungicide controlling a wide range of pathogens. It is also used as a preservative in paint, textile, papermaking and leather industry, as well as a preservative of fruits. In the present study, carbendazim was administered at 0, 150, 300 and 600 mg/kg per day doses orally to male rats (Rattus rattus) for 15 weeks. At the end of the experiment, blood samples, liver and kidney tissues of each animal were taken. Serum enzyme activities, and haematological and biochemical parameters were analysed. In toxicological tests, 600 mg/kg per day doses of carbendazim caused an increase of albumin, glucose, creatinine and cholesterol levels. Also, at the same doses, white blood cell and lymphocyte counts decreased. However, mean cell hemoglobin and mean cell hemoglobin concentrations increased. Histopathological examinations revealed congestion, an enlargement of the sinusoids, an increase in the number of Kupffer cells, mononuclear cell infiltration and hydropic degeneration in the liver. At the highest doses, congestion, mononuclear cell infiltration, tubular degeneration and fibrosis were observed in the kidney tissue. These results indicate that 300 and 600 mg/kg per day carbendazim affected the liver and kidney tissue and caused some changes on haematological and biochemical parameters of rats.

  14. Mercury in alligators (Alligator mississippiensis) in the southeastern United States

    USGS Publications Warehouse

    Jagoe, C.H.; Arnold-Hill, B.; Yanochko, G.M.; Winger, P.V.; Brisbin, I.L.

    1998-01-01

    Mercury methylation may be enhanced in wetlands and humic-rich, blackwater systems that crocodiles and alligators typically inhabit. Given their high trophic level and long life-spans, crocodilians could accumulate significant burdens of Hg. Our objectives were to survey Hg concentrations in alligators from several areas in the southeastern United States to test their utility as sentinels of Hg contamination, to examine relationships among Hg concentrations in various tissues and to look for any differences in tissue Hg concentrations among locations. We measured total Hg concentrations in alligators collected in the Florida Everglades (n = 18), the Okefenokee National Wildlife Refuge, Georgia (n = 9), the Savannah River Site (SRS), South Carolina (n = 49) and various locations in central Florida ( n = 21), sampling tissues including blood, brain, liver, kidney, muscle, bone, fat, spleen, claws and dermal scutes. Alligators from the Everglades were mostly juvenile, but Hg concentrations in tissues were high (means: liver 41.0, kidney 36.4, muscle 5.6 mg Hg/kg dry wt.). Concentrations in alligators from other locations in Florida were lower (means: liver 14.6, kidney 12.6, muscle 1.8 mg Hg/kg dry wt.), although they tended to be larger adults. Alligators from the Okefenokee were smallest and had the lowest Hg concentrations (means: liver 4.3, kidney 4.8, muscle 0.8 mg Hg/kg dry wt.). At some locations, alligator length was correlated with Hg concentrations in some internal organs. However, at three of the four locations, muscle Hg was not related to length. Tissue Hg concentrations were correlated at most locations; however, claw or dermal scute Hg explained less than 74% of the variation of Hg in muscle or organs, suggesting readily-obtained tissues, such as scutes or claws, have limited value for nondestructive screening of Hg in alligator populations.

  15. Some aspects of pathogenesis of infectious hematopoietic necrosis (IHN)

    USGS Publications Warehouse

    Yasutake, William T.; Amend, Donald F.

    1972-01-01

    The histopathogenesis of infectious haematopoietic necrosis (IHN) virus infection was studied by exposing juvenile sockeye salmon (Oncorhynchus nerka) to the IHN virus. Fish samples were taken every 24 h for histological examination and for determination of virus concentration. A close correlation was found between histopathological changes and virus concentration. The most significant changes occurred 4 days after exposure. The haematopocitic tissue of the kidney was the most extensively involved but minor degenerative changes were seen in the liver, pancreas, and in the granular cells of the digestive tract. On the 4th day, maximum tissue concentration of virus was reached and the mortality increased. By the 5th day, 90% of the samples showed extensive pathological changes in the kidney, together with variable changes in spleen, liver, pancreas, and gut. Similarities in the histopathogenesis of IHN, Oregon sockeye disease (OSD), Sacramento River chinook disease (SRCD) and viral haemorrhagic septicaemia (VHS), are discussed.

  16. Ghrelin clearance is reduced at the late stage of polymicrobial sepsis.

    PubMed

    Wu, Rongqian; Zhou, Mian; Cui, Xiaoxuan; Simms, H Hank; Wang, Ping

    2003-11-01

    The cardiovascular response to sepsis is characterized by an early, hyperdynamic phase followed by a late, hypodynamic phase. Ghrelin, a newly-identified endogenous ligand for growth hormone secretagogue receptor (i.e., ghrelin receptor), was recently demonstrated to be a potent vasoactive peptide in addition to its effects on growth hormone release and energy homeostasis. We have shown that ghrelin (via its receptor) may play an important role in regulating cardiovascular responses in the progression of polymicrobial sepsis. However, it remains unknown whether the clearance of this peptide is altered in sepsis. To determine this, male adult rats were injected with 125I-ghrelin through the jugular vein at 5 or 20 h after cecal ligation and puncture (CLP, i.e., sepsis model) or sham operation. The blood sample was collected every 2 min for 30 min for determining half-life (t1/2). Tissue samples (i.e., kidneys, liver, brain, heart, lungs, spleen, stomach, small intestine, large intestine, skin and muscle) were then harvested. The radioactivities of samples were counted. The results indicate that 125I-ghrelin's t1/2 and its distribution were not significantly altered in early sepsis (5 h after CLP). However, the t1/2 increased significantly in late sepsis (20 h after CLP). Tissue distribution of 125I-ghrelin was far greater in the kidneys than in any other tissues tested in both sham and septic animals. Moreover, the kidneys and liver had significantly less radioactive uptake at 20 h after CLP, but the radioactivity in blood was much higher at the same time point. There were no significant changes in 125I-ghrelin distribution in other organs at the late stage of sepsis. These results indicate that the kidneys are the primary site of ghrelin clearance, which is significantly diminished in late sepsis. In addition, the liver also plays a role in the clearance of ghrelin, which was also reduced in late sepsis. The decreased clearance of ghrelin by the kidneys and liver may be due to renal and hepatic dysfunctions under such conditions.

  17. Molecular identification and histopathological study of natural Streptococcus agalactiae infection in hybrid tilapia (Oreochromis niloticus).

    PubMed

    Laith, A A; Ambak, Mohd Azmi; Hassan, Marina; Sheriff, Shahreza Md; Nadirah, Musa; Draman, Ahmad Shuhaimi; Wahab, Wahidah; Ibrahim, Wan Nurhafizah Wan; Aznan, Alia Syafiqah; Jabar, Amina; Najiah, Musa

    2017-01-01

    The main objective of this study was to emphasize on histopathological examinations and molecular identification of Streptococcus agalactiae isolated from natural infections in hybrid tilapia ( Oreochromis niloticus ) in Temerloh Pahang, Malaysia, as well as to determine the susceptibility of the pathogen strains to various currently available antimicrobial agents. The diseased fishes were observed for variable clinical signs including fin hemorrhages, alterations in behavior associated with erratic swimming, exophthalmia, and mortality. Tissue samples from the eyes, brain, kidney, liver, and spleen were taken for bacterial isolation. Identification of S. agalactiae was screened by biochemical methods and confirmed by VITEK 2 and 16S rRNA gene sequencing. The antibiogram profiling of the isolate was tested against 18 standard antibiotics included nitrofurantoin, flumequine, florfenicol, amoxylin, doxycycline, oleandomycin, tetracycline, ampicillin, lincomycin, colistin sulfate, oxolinic acid, novobiocin, spiramycin, erythromycin, fosfomycin, neomycin, gentamycin, and polymyxin B. The histopathological analysis of eyes, brain, liver, kidney, and spleen was observed for abnormalities related to S. agalactiae infection. The suspected colonies of S. agalactiae identified by biochemical methods was observed as Gram-positive chained cocci, β-hemolytic, and non-motile. The isolate was confirmed as S. agalactiae by VITEK 2 (99% similarity), reconfirmed by 16S rRNA gene sequencing (99% similarity) and deposited in GenBank with accession no. KT869025. The isolate was observed to be resistance to neomycin and gentamicin. The most consistent gross findings were marked hemorrhages, erosions of caudal fin, and exophthalmos. Microscopic examination confirmed the presence of marked congestion and infiltration of inflammatory cell in the eye, brain, kidney, liver, and spleen. Eye samples showed damage of the lens capsule, hyperemic and hemorrhagic choroid tissue, and retina hyperplasia accompanied with edema. Brain samples showed perivascular and pericellular edema and hemorrhages of the meninges. Kidney samples showed hemorrhage and thrombosis in the glomeruli and tubules along with atrophy in hematopoietic tissue. Liver samples showed congestion of the sinusoids and blood vessel, thrombosis of portal blood vessel, and vacuolar (fatty) degeneration of hepatocytes. Spleen samples showed large thrombus in the splenic blood vessel, multifocal hemosiderin deposition, congestion of blood vessels, and multifocal infiltration of macrophages. Therefore, it can be concluded that pathological changes in tissues and organs of fish occur proportionally to the pathogen invasion, and because of their high resistance, neomycin and gentamicin utilization in the prophylaxis or treatment of S. agalactiae infection should be avoided.

  18. Molecular identification and histopathological study of natural Streptococcus agalactiae infection in hybrid tilapia (Oreochromis niloticus)

    PubMed Central

    Laith, AA; Ambak, Mohd Azmi; Hassan, Marina; Sheriff, Shahreza Md.; Nadirah, Musa; Draman, Ahmad Shuhaimi; Wahab, Wahidah; Ibrahim, Wan Nurhafizah Wan; Aznan, Alia Syafiqah; Jabar, Amina; Najiah, Musa

    2017-01-01

    Aim: The main objective of this study was to emphasize on histopathological examinations and molecular identification of Streptococcus agalactiae isolated from natural infections in hybrid tilapia (Oreochromis niloticus) in Temerloh Pahang, Malaysia, as well as to determine the susceptibility of the pathogen strains to various currently available antimicrobial agents. Materials and Methods: The diseased fishes were observed for variable clinical signs including fin hemorrhages, alterations in behavior associated with erratic swimming, exophthalmia, and mortality. Tissue samples from the eyes, brain, kidney, liver, and spleen were taken for bacterial isolation. Identification of S. agalactiae was screened by biochemical methods and confirmed by VITEK 2 and 16S rRNA gene sequencing. The antibiogram profiling of the isolate was tested against 18 standard antibiotics included nitrofurantoin, flumequine, florfenicol, amoxylin, doxycycline, oleandomycin, tetracycline, ampicillin, lincomycin, colistin sulfate, oxolinic acid, novobiocin, spiramycin, erythromycin, fosfomycin, neomycin, gentamycin, and polymyxin B. The histopathological analysis of eyes, brain, liver, kidney, and spleen was observed for abnormalities related to S. agalactiae infection. Results: The suspected colonies of S. agalactiae identified by biochemical methods was observed as Gram-positive chained cocci, β-hemolytic, and non-motile. The isolate was confirmed as S. agalactiae by VITEK 2 (99% similarity), reconfirmed by 16S rRNA gene sequencing (99% similarity) and deposited in GenBank with accession no. KT869025. The isolate was observed to be resistance to neomycin and gentamicin. The most consistent gross findings were marked hemorrhages, erosions of caudal fin, and exophthalmos. Microscopic examination confirmed the presence of marked congestion and infiltration of inflammatory cell in the eye, brain, kidney, liver, and spleen. Eye samples showed damage of the lens capsule, hyperemic and hemorrhagic choroid tissue, and retina hyperplasia accompanied with edema. Brain samples showed perivascular and pericellular edema and hemorrhages of the meninges. Kidney samples showed hemorrhage and thrombosis in the glomeruli and tubules along with atrophy in hematopoietic tissue. Liver samples showed congestion of the sinusoids and blood vessel, thrombosis of portal blood vessel, and vacuolar (fatty) degeneration of hepatocytes. Spleen samples showed large thrombus in the splenic blood vessel, multifocal hemosiderin deposition, congestion of blood vessels, and multifocal infiltration of macrophages. Conclusion: Therefore, it can be concluded that pathological changes in tissues and organs of fish occur proportionally to the pathogen invasion, and because of their high resistance, neomycin and gentamicin utilization in the prophylaxis or treatment of S. agalactiae infection should be avoided. PMID:28246454

  19. Inorganic elements in green sea turtles (Chelonia mydas): relationships among external and internal tissues.

    PubMed

    Faust, Derek R; Hooper, Michael J; Cobb, George P; Barnes, Melanie; Shaver, Donna; Ertolacci, Shauna; Smith, Philip N

    2014-09-01

    Inorganic elements from anthropogenic sources have entered marine environments worldwide and are detectable in marine organisms, including sea turtles. Threatened and endangered classifications of sea turtles have heretofore made assessments of contaminant concentrations difficult because of regulatory restrictions on obtaining samples using nonlethal techniques. In the present study, claw and skin biopsy samples were examined as potential indicators of internal tissue burdens in green sea turtles (Chelonia mydas). Significant relationships were observed between claw and liver, and claw and muscle concentrations of mercury, nickel, arsenic, and selenium (p < 0.05). Similarly, significant relationships were observed between skin biopsy concentrations and those in liver, kidney, and muscle tissues for mercury, arsenic, selenium, and vanadium (p < 0.05). Concentrations of arsenic, barium, chromium, nickel, strontium, vanadium, and zinc in claws and skin biopsies were substantially elevated when compared with all other tissues, indicating that these highly keratinized tissues may represent sequestration or excretion pathways. Correlations between standard carapace length and cobalt, lead, and manganese concentrations were observed (p < 0.05), indicating that tissue concentrations of these elements may be related to age and size. Results suggest that claws may indeed be useful indicators of mercury and nickel concentrations in liver and muscle tissues, whereas skin biopsy inorganic element concentrations may be better suited as indicators of mercury, selenium, and vanadium concentrations in liver, kidney, and muscle tissues of green sea turtles. © 2014 SETAC.

  20. Renal coccidiosis in interior Canada geese, Branta canadensis interior Todd, of the Mississippi Valley population

    USGS Publications Warehouse

    Tuggle, Benjamin N.; Crites, John L.

    1984-01-01

    Kidneys from 309 Interior Canada geese from three locations in the Mississippi Flyway were examined for renal coccidia. Oocysts and/or young zygotes of Eimeria sp. were found in 6.8% of goose kidneys sampled. Only one type of renal coccidian oocyst was observed. Significantly more immature geese were infected than adults; however, there was no significant difference observed between the prevalences of infection in male and female birds. A host cellular response to zygotes and oocysts was noted in the majority of infected adult geese. Heavily infected kidneys were hypertrophic with minute foci on the surface of the organ. Histological examinations showed large numbers of unsporulated oocysts accumulated in distended collecting tubules, resulting in pressure necrosis to adjacent tissue and urate retention. Zygotes were observed in the cytoplasm of tubule cells and extracellularly in interstitial tissue. Infected tubule cells were characterized by the peripheral location of the nuclei, cytoplasmic basophilia, and cellular hypertrophy. This is the first report of an Eimeria sp. in the kidneys of Canada geese of the Mississippi Valley population.

  1. Bioaccumulation and Subchronic Toxicity of 14 nm Gold Nanoparticles in Rats.

    PubMed

    Rambanapasi, Clinton; Zeevaart, Jan Rijn; Buntting, Hylton; Bester, Cornelius; Kotze, Deon; Hayeshi, Rose; Grobler, Anne

    2016-06-10

    Colloidal suspensions of 14 nm gold nanoparticles (AuNPs) were repeatedly administered intravenously at three dose levels (0.9, 9 and 90 µg) to male Sprague Dawley rats weekly for 7 weeks, followed by a 14-day washout period. After sacrificing, the amount of gold was quantified in the liver, lungs, spleen, skeleton and carcass using neutron activation analysis (NAA). During the study, pre- and post (24 h) administration blood samples were collected from both the test and control groups, the latter which received an equal injection volume of normal saline. General health indicators were monitored together with markers of kidney and liver damage for acute and subchronic toxicity assessment. Histopathological assessments were done on the heart, kidneys, liver, lungs and spleen to assess any morphological changes as a result of the exposure to AuNPs. The mass measurements of all the groups showed a steady increase with no signs of overt toxicity. The liver had the highest amount of gold (µg) per gram of tissue after 56 days followed by the spleen, lungs, skeleton and carcass. Markers of kidney and liver damage showed similar trends between the pre and post samples within each group and across groups. The histopathological examination also showed no hepatotoxicity and nephrotoxicity. There was accumulation of Au in tissues after repeated dosing, albeit with no observable overt toxicity, kidney or liver damage.

  2. Caffeic acid phenethyl ester protects kidneys against acetylsalicylic acid toxicity in rats.

    PubMed

    Bozkurt, Yasar; Bozkurt, Mehtap; Turkçu, Gul; Sancaktutar, Ahmet Ali; Soylemez, Haluk; Penbegul, Necmettin; Atar, Murat; Bodakcı, Mehmet Nuri; Hatipoglu, Namık Kemal; Yuksel, Hatice; Kıbrıslı, Erkan; Yavuz, Celal

    2012-01-01

    The aim of this study was to investigate the protective effect of caffeic acid phenethyl ester (CAPE) on acetylsalicylic acid (ASA)-induced renal damage in rats. A total of 40 rats were randomly divided into five groups, with eight rats in each group-group 1: control, not receiving any medication; group 2: ASA (50 mg/kg/day); group 3: ASA (50 mg/kg/day) + CAPE (20 μg/kg/day); group 4: ASA (100 mg/kg/day); and group 5: ASA (100 mg/kg/day) + CAPE (20 μg/kg/day). ASA and CAPE were given via orogastric gavage for 5 days. The total oxidant status (TOS), total antioxidant capacity (TAC), and paraoxonase-1 (PON-1) activity of the blood samples and kidney tissues were determined. Histopathological examinations of the kidneys were performed using light microscopic methods. The TOS level in the serum of rats and kidney tissues given ASA (groups 2 and 4) significantly increased, but the levels of TAC and PON-1 in these tissues significantly decreased in group 4 when compared with the control rats (p < 0.05). The levels of TAC and PON-1 in the kidney tissues increased and the levels of TOS decreased in the CAPE treatment groups (groups 3 and 5) when compared with the rats in the no CAPE treatment groups (groups 2 and 4). The PON-1, TAC, and TOS values reverted to normal levels in group 5 when compared to group 4 (p < 0.05). These results were supported by histopathological observation. Oxidative stress plays an important role in ASA-induced nephrotoxicity, and CAPE may protect against ASA-induced nephrotoxicity in rats.

  3. MALDI Orbitrap Mass Spectrometry Profiling of Dysregulated Sulfoglycosphingolipids in Renal Cell Carcinoma Tissues

    NASA Astrophysics Data System (ADS)

    Jirásko, Robert; Holčapek, Michal; Khalikova, Maria; Vrána, David; Študent, Vladimír; Prouzová, Zuzana; Melichar, Bohuslav

    2017-08-01

    Matrix-assisted laser desorption/ionization coupled with Orbitrap mass spectrometry (MALDI-Orbitrap-MS) is used for the clinical study of patients with renal cell carcinoma (RCC), as the most common type of kidney cancer. Significant changes in sulfoglycosphingolipid abundances between tumor and autologous normal kidney tissues are observed. First, sulfoglycosphingolipid species in studied RCC samples are identified using high mass accuracy full scan and tandem mass spectra. Subsequently, optimization, method validation, and statistical evaluation of MALDI-MS data for 158 tissues of 80 patients are discussed. More than 120 sulfoglycosphingolipids containing one to five hexosyl units are identified in human RCC samples based on the systematic study of their fragmentation behavior. Many of them are recorded here for the first time. Multivariate data analysis (MDA) methods, i.e., unsupervised principal component analysis (PCA) and supervised orthogonal partial least square discriminant analysis (OPLS-DA), are used for the visualization of differences between normal and tumor samples to reveal the most up- and downregulated lipids in tumor tissues. Obtained results are closely correlated with MALDI mass spectrometry imaging (MSI) and histologic staining. Important steps of the present MALDI-Orbitrap-MS approach are also discussed, such as the selection of best matrix, correct normalization, validation for semiquantitative study, and problems with possible isobaric interferences on closed masses in full scan mass spectra.

  4. Histopathology of Middle East respiratory syndrome coronovirus (MERS-CoV) infection - clinicopathological and ultrastructural study.

    PubMed

    Alsaad, Khaled O; Hajeer, Ali H; Al Balwi, Mohammed; Al Moaiqel, Mohammed; Al Oudah, Nourah; Al Ajlan, Abdulaziz; AlJohani, Sameera; Alsolamy, Sami; Gmati, Giamal E; Balkhy, Hanan; Al-Jahdali, Hamdan H; Baharoon, Salim A; Arabi, Yaseen M

    2018-02-01

    The pathogenesis, viral localization and histopathological features of Middle East respiratory syndrome - coronavirus (MERS-CoV) in humans are not described sufficiently. The aims of this study were to explore and define the spectrum of histological and ultrastructural pathological changes affecting various organs in a patient with MERS-CoV infection and represent a base of MERS-CoV histopathology. We analysed the post-mortem histopathological findings and investigated localisation of viral particles in the pulmonary and extrapulmonary tissue by transmission electron microscopic examination in a 33-year-old male patient of T cell lymphoma, who acquired MERS-CoV infection. Tissue needle biopsies were obtained from brain, heart, lung, liver, kidney and skeletal muscle. All samples were collected within 45 min from death to reduce tissue decomposition and artefact. Histopathological examination showed necrotising pneumonia, pulmonary diffuse alveolar damage, acute kidney injury, portal and lobular hepatitis and myositis with muscle atrophic changes. The brain and heart were histologically unremarkable. Ultrastructurally, viral particles were localised in the pneumocytes, pulmonary macrophages, renal proximal tubular epithelial cells and macrophages infiltrating the skeletal muscles. The results highlight the pulmonary and extrapulmonary pathological changes of MERS-CoV infection and provide the first evidence of the viral presence in human renal tissue, which suggests tissue trophism for MERS-CoV in kidney. © 2017 John Wiley & Sons Ltd.

  5. Non-destructive pollution exposure assessment in the European hedgehog (Erinaceus europaeus): II. Hair and spines as indicators of endogenous metal and As concentrations.

    PubMed

    D'Havé, Helga; Scheirs, Jan; Mubiana, Valentine Kayawe; Verhagen, Ron; Blust, Ronny; De Coen, Wim

    2006-08-01

    The role of hair and spines of the European hedgehog as non-destructive monitoring tools of metal (Ag, Al, Cd, Co, Cr, Cu, Fe, Ni, Pb, Zn) and As pollution in terrestrial ecosystems was investigated. Our results showed that mean pollution levels of a random sample of hedgehogs in Flanders are low to moderate. Yet, individual hedgehogs may be at risk for metal toxicity. Tissue distribution analyses (hair, spines, liver, kidney, muscle and fat tissue) indicated that metals and As may reach considerable concentrations in external tissues, such as hair and spines. Positive relationships were observed between concentrations in hair and those in liver, kidney and muscle for Al, Co, Cr, Cu, and Pb (0.43 < r < 0.85). Spine concentrations were positively related to liver, kidney and muscle concentrations for Cd, Co, Cr, Cu and Pb (0.37 < r < 0.62). Hair Ag, As, Fe and Zn and spine Ag, Al, As and Fe were related to metal concentrations in one or two of the investigated internal tissues (0.31 < r < 0.45). The regression models presented here may be used to predict metal and As concentrations in internal tissues of hedgehogs when concentrations in hair or spines are available. The present study demonstrated the possibility of using hair and spines for non-destructive monitoring of metal and As pollution in hedgehogs.

  6. Effects of kefir on ischemia-reperfusion injury.

    PubMed

    Yener, A U; Sehitoglu, M H; Ozkan, M T A; Bekler, A; Ekin, A; Cokkalender, O; Deniz, M; Sacar, M; Karaca, T; Ozcan, S; Kurt, T

    2015-01-01

    We aimed to investigate the effect of kefir on Ischemia-Reperfusion (I/R) injury on rats. 24 male Sprague-Dawley rats between 250-350 g were selected. Rats were divided into three groups, and there were eight rats in each group. Rats were fed for 60 days. All of the rats were fed with the same diet for the first 30 days. In the second thirty days, kefir [10 cc/kg/day body weight (2 x 109 cfu/kg/day)] was added to the diet of the study group by gavage method. In all groups, lung and kidney tissues were removed after the procedure and rats were sacrificed. The biochemical and histopathological changes were observed in the lung and kidney within the samples. Serum urea, creatinine and tumor necrosis factor (TNF-α) were determined. Kefir + I/R groups was compared with I/R groups, a significant decrease (p < 0.05) was seen in Lipid peroxidation (MDA) levels of lung and renal tissues. Superoxide dismutase (SOD), Catalase (CAT) and Glutathione peroxidase (GSH-Px) activities of lung and kidney tissues decreased in I/R groups (p < 0.05). The enzyme activities in Kefir + I/R groups of renal tissues were significantly (p < 0.05) higher than I/R, not significantly different in lung tissues (p < 0.05). Kefir reduced the levels of serum urea, creatinine and TNF-α significantly.   This would be useful in this model against ischemia/reperfusion, and shows the protective effect of kefir in tissue and serum functions.

  7. Distribution of the anticancer drugs doxorubicin, mitoxantrone and topotecan in tumors and normal tissues.

    PubMed

    Patel, Krupa J; Trédan, Olivier; Tannock, Ian F

    2013-07-01

    Pharmacokinetic analyses estimate the mean concentration of drug within a given tissue as a function of time, but do not give information about the spatial distribution of drugs within that tissue. Here, we compare the time-dependent spatial distribution of three anticancer drugs within tumors, heart, kidney, liver and brain. Mice bearing various xenografts were treated with doxorubicin, mitoxantrone or topotecan. At various times after injection, tumors and samples of heart, kidney, liver and brain were excised. Within solid tumors, the distribution of doxorubicin, mitoxantrone and topotecan was limited to perivascular regions at 10 min after administration and the distance from blood vessels at which drug intensity fell to half was ~25-75 μm. Although drug distribution improved after 3 and 24 h, there remained a significant decrease in drug fluorescence with increasing distance from tumor blood vessels. Drug distribution was relatively uniform in the heart, kidney and liver with substantially greater perivascular drug uptake than in tumors. There was significantly higher total drug fluorescence in the liver than in tumors after 10 min, 3 and 24 h. Little to no drug fluorescence was observed in the brain. There are marked differences in the spatial distributions of three anticancer drugs within tumor tissue and normal tissues over time, with greater exposure to most normal tissues and limited drug distribution to many cells in tumors. Studies of the spatial distribution of drugs are required to complement pharmacokinetic data in order to better understand and predict drug effects and toxicities.

  8. Stem cells in kidney regeneration.

    PubMed

    Yokote, Shinya; Yokoo, Takashi

    2012-01-01

    Currently many efforts are being made to apply regenerative medicine to kidney diseases using several types of stem/progenitor cells, such as mesenchymal stem cells, renal stem/progenitor cells, embryonic stem cells and induced pluripotent stem cells. Stem cells have the ability to repair injured organs and ameliorate damaged function. The strategy for kidney tissue repair is the recruitment of stem cells and soluble reparative factors to the kidney to elicit tissue repair and the induction of dedifferentiation of resident renal cells. On the other hand, where renal structure is totally disrupted, absolute kidney organ regeneration is needed to rebuild a whole functional kidney. In this review, we describe current advances in stem cell research for kidney tissue repair and de novo organ regeneration.

  9. Fatal Transplant-Associated West Nile Virus Encephalitis and Public Health Investigation—California, 2010

    PubMed Central

    Rabe, Ingrid B.; Schwartz, Brian S.; Farnon, Eileen C.; Josephson, S. Andrew; Webber, Allison B.; Roberts, John Paul; de Mattos, Angelo M.; Gallay, Brian J.; van Slyck, Sean; Messenger, Sharon L.; Yen, Cynthia J.; Bloch, Evan M.; Drew, Clifton P.; Fischer, Marc; Glaser, Carol A.

    2017-01-01

    Background In December 2010, a case of West Nile virus (WNV) encephalitis occurring in a kidney recipient shortly after organ transplantation was identified. Methods A public health investigation was initiated to determine the likely route of transmission, detect potential WNV infections among recipients from the same organ donor, and remove any potentially infected blood products or tissues. Available serum, cerebrospinal fluid, and urine samples from the organ donor and recipients were tested for WNV infection by nucleic acid testing and serology. Results Two additional recipients from the same organ donor were identified, their clinical and exposure histories were reviewed, and samples were obtained. WNV RNA was retrospectively detected in the organ donor’s serum. After transplantation, the left kidney recipient had serologic and molecular evidence of WNV infection and the right kidney recipient had prolonged but clinically inapparent WNV viremia. The liver recipient showed no clinical signs of infection but had flavivirus IgG antibodies; however, insufficient samples were available to determine the timing of infection. No remaining infectious products or tissues were identified. Conclusions Clinicians should suspect WNV as a cause of encephalitis in organ transplant recipients and report cases to public health departments for prompt investigation of the source of infection. Increased use of molecular testing and retaining pretransplantation sera may improve the ability to detect and diagnose transplant-associated WNV infection in organ transplant recipients. PMID:23823653

  10. Selenium and 17 other largely essential and toxic metals in muscle and organ meats of Red Deer (Cervus elaphus)--consequences to human health.

    PubMed

    Jarzyńska, Grażyna; Falandysz, Jerzy

    2011-07-01

    Concentrations, composition and interrelationships of selenium and metallic elements (Ag, Ba, Cd, Co, Cr, Cs, Cu, Ga, Mn, Mo, Pb, Rb, Sb, Sr, Tl, V and Zn) have been examined in muscle and organ meats of Red Deer hunted in Poland. The analytical data obtained were also discussed in terms of Se supplementation and deficit to Deer as well as the benefits and risk to humans associated with the essential and toxic metals intake resulting from consumption of Deer meat and products. These elements were determined in 20 adult animals of both sexes that were obtained in the 2000/2001 hunting season from Warmia and Mazury in the north-eastern part of Poland. The whole kidneys contained Ba, Cd, Cr, Ga, Pb, Se, Sr and Tl at statistically greater concentrations than liver or muscle tissue from the same animal. Liver showed statistically greater concentrations of Ag, Co, Cu, Mn and Mo than kidneys or muscle tissue, and muscle tissue was richer in Zn, when compared to the kidneys or liver. Cs and Rb were similarly distributed between all three tissue types, while V was less abundant in liver than kidneys or muscle tissue. There were significant associations between some metallic elements retained in Red Deer demonstrated by Principal Component Analysis (PCA) of the data set. In organ and muscle meats (kidneys, liver and muscle tissue considered together) the first principal component (PC1) was strongly influenced by positively correlated variables describing Se, Ba and Cd and negatively correlated variables describing Ag, Co, Cs, Mn, Pb, Tl and V; PC2, respectively, by Cu, Mn and Mo (+) and Zn (-); PC3 by Ga (+) and PC4 by Sb (+). Selenium occurred in muscle tissue, liver and kidneys at median concentrations of 0.13, 0.19 and 4.0mg/g dry weight, respectively. These values can be defined as marginally deficient (< 0.6mg Se/kg liver dw) or satisfactory (≤ 3.0mg Se/kg kidneys dw) for the amount required to maintain the Deer's body condition and health, depending on the criterion for supplementation used. In terms of human nutritional needs, a relatively high selenium content of kidneys can be beneficial. The muscle meat, liver and kidneys of Red Deer can be considered as a very good source of essential Co, Cr, Cu, Mo, Mn, Se and Zn in the human diet. Lead is generally considered as toxic, and the concentrations found in Red Deer (via the food chain intake) were well below the European Union tolerance limit. Pb from the lead bullets can always create food hygienic problem, if not well recognized during sanitary inspection, and this was noted for one muscle meat sample in this study (5% surveyed). There is no tolerance limit of Cd in game animal meats. The median values of Cd noted in fresh muscle tissue, liver and whole kidneys were 0.07, 0.18, and 3.3mg/kg wet weight, respectively. Cd exists as a chemical element present at trace levels in plants and mushrooms in Deer's food chain in background (uncontaminated) areas. When these are consumed by the Deer, the amount of Cd sequestered with metallothioneins and retained in the organ and muscle meat in this study is low enough to be considered safe for human consumption. Copyright © 2011 Elsevier Ltd. All rights reserved.

  11. The effects of kefir, koumiss, yogurt and commercial probiotic formulations on PPARα and PPAR-β/δ expressions in mouse kidney.

    PubMed

    Sari, E K; Bakir, B; Aydin, B D; Sozmen, M

    2014-05-01

    Commercial probiotic capsules that contain probiotic bacteria, kefir, koumiss and yogurt contain beneficial microorganisms that affect cholesterol levels and immune response, and are used for treatment of some diseases. We investigated using immunohistochemistry the effects of kefir, koumiss, yogurt and a commercial probiotic formulation on the expression levels of peroxisome proliferator-activated receptor-α (PPARα) and peroxisome proliferator-activated receptor-β/δ (PPAR-β/δ), which are members of the nuclear steroid hormone receptor superfamily in mouse kidney. Mice were assigned to five groups: group 1, commercial probiotic capsules; group 2, kefir; group 3, koumiss; group 4, yogurt; group 5, control. After oral administration for 15 days, body weights were recorded and kidney tissue samples were obtained. Hematoxylin & eosin staining and the streptavidin-biotin peroxidase complex (ABC) method were applied to tissue sections to examine histology and to determine the localization of PPARα and PPAR-β/δ in the kidneys. We found that the weights of the mice in the kefir, koumiss, yogurt and commercial probiotic capsules groups were increased compared to controls. No differences in kidney histology were observed in any of the experimental groups. Kefir, koumiss, yogurt and the commercial probiotic preparation increased PPARα and PPAR-β/δ expressions.

  12. Bioaccumulation of selected heavy metals and histopathological and hematobiochemical alterations in backyard chickens reared in an industrial area, India.

    PubMed

    Kar, Indrajit; Mukhopadhayay, Sunit Kumar; Patra, Amlan Kumar; Pradhan, Saktipada

    2018-02-01

    This study was carried out to determine the concentrations of four heavy metals, cadmium (Cd), lead (Pb), copper (Cu), and cobalt (Co), and histopathological lesions in tissues of chickens reared in an industrial area of West Bengal, India. In particular, Mejhia Block was selected as a heavy metal-exposed area and Vatar Block (120 km away from industrially polluted areas) as a reference site. Samples were collected from the backyard chickens in these areas. Concentrations of heavy metals in soil, water, feedstuffs, tissues (liver, kidney, spleen, lung, and muscle), and droppings were greater (p < 0.05) in the polluted site than in the reference site. The greatest tissue concentrations of Cd and Pb were noted in the kidney, followed by the liver, lung, spleen, and muscle, whereas Cu and Co concentrations accumulated in these tissues resulted in the following: liver > kidney > lung > spleen > muscle. Heavy metal concentrations were greater in older chickens (> 1 year) than in young chickens (< 1 year). Packed cell volume, total erythrocyte counts, hemoglobin, total protein, and total leucocyte counts were significantly (p < 0.01) lower in the blood picture of chickens in the exposed area. Different serum enzymes and biochemical profiles were altered due to heavy metal exposure. Histological changes revealed necrotic lesions and tubulitis in the kidney, degeneration and necrosis in liver parenchyma, and periarteriolitis, peribronchiolitis, and presence of hemosiderin pigment in the lung of chickens in the exposed site. Results indicated that backyard chickens in heavy metal-exposed site may show pathological lesions in different tissues due to accumulation of heavy metals, and thus, the consumption of chicken meat from the industrially exposed site may pose a potential health risk to local residents of polluted sites.

  13. Direct tissue analysis by matrix-assisted laser desorption ionization mass spectrometry: application to kidney biology.

    PubMed

    Herring, Kristen D; Oppenheimer, Stacey R; Caprioli, Richard M

    2007-11-01

    Direct tissue analysis using matrix-assisted laser desorption ionization mass spectrometry (MALDI MS) provides in situ molecular analysis of a wide variety of biological molecules including xenobiotics. This technology allows measurement of these species in their native biological environment without the use of target-specific reagents such as antibodies. It can be used to profile discrete cellular regions and obtain region-specific images, providing information on the relative abundance and spatial distribution of proteins, peptides, lipids, and drugs. In this article, we report the sample preparation, MS data acquisition and analysis, and protein identification methodologies used in our laboratory for profiling/imaging MS and how this has been applied to kidney disease and toxicity.

  14. Histological change and heat shock protein 70 expression in different tissues of Japanese flounder Paralichthys olivaceus in response to elevated temperature

    NASA Astrophysics Data System (ADS)

    Liu, Yifan; Ma, Daoyuan; Xiao, Zhizhong; Xu, Shihong; Wang, Yanfeng; Wang, Yufu; Xiao, Yongshuang; Song, Zongcheng; Teng, Zhaojun; Liu, Qinghua; Li, Jun

    2015-01-01

    High temperature influences the homeostasis of fish. We investigated the effects of elevated temperature on tissues of Japanese flounder ( Paralichthys olivaceus) by analyzing the histology and heat shock protein 70 ( hsp70) expression of fish reared in warm conditions. In this study, temperature was increased at 1±0.5°C/day starting at 24±0.5°C, and was kept at that temperature for 5 days before the next rise. After raising temperature at the rate up to 32±0.5°C, tissue samples from midgut, spleen, stomach, liver, muscle, gill, heart, trunk kidney and brain were collected for histological analysis and mRNA assay. Almost all the tissues showed changes in morphological structure and hsp70 level at 32±0.5°C. Histological assessment of the tissues indicated that the gill had the most serious damage, including highly severe epithelial lifting and edema, curved tips and hyperemia at the ending of the lamellars, desquamation and necrosis. The next most severe damage was found in liver and kidney. The hsp70 levels in all the tissues first increased and then decreased. The gut, stomach, muscle, heart, and brain had the highest expressions in 6 h, whereas the spleen, liver, gill and kidney had the highest expressions in 2 h. Therefore, tissues with the most significant lesions (especially gill and liver) responded much earlier (2 h) in hsp70 expression than other tissues, and these tissues demonstrated the most marked histological disruption and elevated mRNA levels, making them ideal candidates for further studies on the thermal physiology of this species.

  15. [Determination of trace Cs, Th and U in ten kinds of human autopsy tissues by ICP-MS].

    PubMed

    Wang, Jing-yu; Zhu, Hong-da; Ouyang, Li; Liu, Ya-qiong; Wang, Xiao-yan; Huang, Zhuo; Wang, Nai-fen; Liu, Hu-sheng

    2004-09-01

    This paper studied the trace elements Cs, Th and U in ten kinds of human autopsy tissues by ICP-MS. The instrumental operating conditions were optimized for the measurement of Cs, Th and U. Rhodium (Rh) was used as an internal standard element to compensate matrix effect. Detection limits for Th, U and Cs were 5.7-17.8 pg x mL(-1). The recoveries for spiking liver samples were 96%-107%, and their RSDs were 4.8%-8.9%. Reference materials of NIST SRM 8414 Bovine and NIST SRM 1486 Bone Meal were analyzed by the described method, and the analytical results agreed well with the reference values. Human autopsy tissues samples were digested by mixed acid (HNO3 + HClO4). The determination of Cs, Th and U in lung, liver, bone, heart, stomach, spleen, muscle, kidney, thyroid gland and intestinum tenue was performed by ICP-MS without separation and enrichment procedures. The obtained results indicated that this method is rapid, sensitive and accurate; the distribution of the three elements is different from one to another human organ sample; the main organ targets for Th and U are lungs and kidneys; and a coordinated variation of Cs, Th and U concentration in lungs was found in the samples collected from Hebei and Sichuan provinces.

  16. Renal Gene Expression Database (RGED): a relational database of gene expression profiles in kidney disease

    PubMed Central

    Zhang, Qingzhou; Yang, Bo; Chen, Xujiao; Xu, Jing; Mei, Changlin; Mao, Zhiguo

    2014-01-01

    We present a bioinformatics database named Renal Gene Expression Database (RGED), which contains comprehensive gene expression data sets from renal disease research. The web-based interface of RGED allows users to query the gene expression profiles in various kidney-related samples, including renal cell lines, human kidney tissues and murine model kidneys. Researchers can explore certain gene profiles, the relationships between genes of interests and identify biomarkers or even drug targets in kidney diseases. The aim of this work is to provide a user-friendly utility for the renal disease research community to query expression profiles of genes of their own interest without the requirement of advanced computational skills. Availability and implementation: Website is implemented in PHP, R, MySQL and Nginx and freely available from http://rged.wall-eva.net. Database URL: http://rged.wall-eva.net PMID:25252782

  17. Renal Gene Expression Database (RGED): a relational database of gene expression profiles in kidney disease.

    PubMed

    Zhang, Qingzhou; Yang, Bo; Chen, Xujiao; Xu, Jing; Mei, Changlin; Mao, Zhiguo

    2014-01-01

    We present a bioinformatics database named Renal Gene Expression Database (RGED), which contains comprehensive gene expression data sets from renal disease research. The web-based interface of RGED allows users to query the gene expression profiles in various kidney-related samples, including renal cell lines, human kidney tissues and murine model kidneys. Researchers can explore certain gene profiles, the relationships between genes of interests and identify biomarkers or even drug targets in kidney diseases. The aim of this work is to provide a user-friendly utility for the renal disease research community to query expression profiles of genes of their own interest without the requirement of advanced computational skills. Website is implemented in PHP, R, MySQL and Nginx and freely available from http://rged.wall-eva.net. http://rged.wall-eva.net. © The Author(s) 2014. Published by Oxford University Press.

  18. Biological monitoring of heavy metal contaminations using owls.

    PubMed

    Kim, Jungsoo; Oh, Jong-Min

    2012-03-01

    Iron, manganese, copper, lead and cadmium were measured in the livers, muscles, kidneys and bones of Eurasian Eagle Owls (Bubo bubo), Brown Hawk Owls (Nixos scutulata) and Collared Scops Owls (Otus lempiji) from Korea. Iron concentrations by tissue within species did not differ, but there were significant differences among tissues across all species. Manganese and copper concentrations in muscles, kidneys and bones, but not livers, differed among species and also differed among tissues in the three owl species. We suggest that manganese and copper concentrations from this study were far below the level associated with their toxicity. Lead concentrations significantly differed among all species for livers and bones, and among tissues for each species. Cadmium concentrations were significantly different among species for all tissues and among tissues in Eurasian Eagle Owls and Collared Scops Owls. For most samples, lead concentrations in livers and bones, and cadmium in livers and kidneys, were within the background levels for wild birds. For some Eurasian Eagle Owls and Collared Scops Owls, lead concentrations were at an acute exposure level, whilst lead concentrations were at a chronic exposure level in Brown Hawk Owls. Cadmium concentrations were at a chronic exposure level in all three owl species. Acute and chronic poisoning was significantly correlated between indicator tissues. We suggest that lead and cadmium contamination in Eurasian Eagle Owls may reflect a Korean source, Brown Hawk Owls may reflect Korean and wintering sites, and Collared Scops Owls may reflect breeding and/or wintering sites. This journal is © The Royal Society of Chemistry 2012

  19. (Re)Building a Kidney

    PubMed Central

    Carroll, Thomas J.; Cleaver, Ondine; Gossett, Daniel R.; Hoshizaki, Deborah K.; Hubbell, Jeffrey A.; Humphreys, Benjamin D.; Jain, Sanjay; Jensen, Jan; Kaplan, David L.; Kesselman, Carl; Ketchum, Christian J.; Little, Melissa H.; McMahon, Andrew P.; Shankland, Stuart J.; Spence, Jason R.; Valerius, M. Todd; Wertheim, Jason A.; Wessely, Oliver; Zheng, Ying; Drummond, Iain A.

    2017-01-01

    (Re)Building a Kidney is a National Institute of Diabetes and Digestive and Kidney Diseases-led consortium to optimize approaches for the isolation, expansion, and differentiation of appropriate kidney cell types and the integration of these cells into complex structures that replicate human kidney function. The ultimate goals of the consortium are two-fold: to develop and implement strategies for in vitro engineering of replacement kidney tissue, and to devise strategies to stimulate regeneration of nephrons in situ to restore failing kidney function. Projects within the consortium will answer fundamental questions regarding human gene expression in the developing kidney, essential signaling crosstalk between distinct cell types of the developing kidney, how to derive the many cell types of the kidney through directed differentiation of human pluripotent stem cells, which bioengineering or scaffolding strategies have the most potential for kidney tissue formation, and basic parameters of the regenerative response to injury. As these projects progress, the consortium will incorporate systematic investigations in physiologic function of in vitro and in vivo differentiated kidney tissue, strategies for engraftment in experimental animals, and development of therapeutic approaches to activate innate reparative responses. PMID:28096308

  20. Reconstruction and Analysis of Human Kidney-Specific Metabolic Network Based on Omics Data

    PubMed Central

    Zhang, Ai-Di; Dai, Shao-Xing; Huang, Jing-Fei

    2013-01-01

    With the advent of the high-throughput data production, recent studies of tissue-specific metabolic networks have largely advanced our understanding of the metabolic basis of various physiological and pathological processes. However, for kidney, which plays an essential role in the body, the available kidney-specific model remains incomplete. This paper reports the reconstruction and characterization of the human kidney metabolic network based on transcriptome and proteome data. In silico simulations revealed that house-keeping genes were more essential than kidney-specific genes in maintaining kidney metabolism. Importantly, a total of 267 potential metabolic biomarkers for kidney-related diseases were successfully explored using this model. Furthermore, we found that the discrepancies in metabolic processes of different tissues are directly corresponding to tissue's functions. Finally, the phenotypes of the differentially expressed genes in diabetic kidney disease were characterized, suggesting that these genes may affect disease development through altering kidney metabolism. Thus, the human kidney-specific model constructed in this study may provide valuable information for the metabolism of kidney and offer excellent insights into complex kidney diseases. PMID:24222897

  1. Automated Morphological and Morphometric Analysis of Mass Spectrometry Imaging Data: Application to Biomarker Discovery

    NASA Astrophysics Data System (ADS)

    Picard de Muller, Gaël; Ait-Belkacem, Rima; Bonnel, David; Longuespée, Rémi; Stauber, Jonathan

    2017-12-01

    Mass spectrometry imaging datasets are mostly analyzed in terms of average intensity in regions of interest. However, biological tissues have different morphologies with several sizes, shapes, and structures. The important biological information, contained in this highly heterogeneous cellular organization, could be hidden by analyzing the average intensities. Finding an analytical process of morphology would help to find such information, describe tissue model, and support identification of biomarkers. This study describes an informatics approach for the extraction and identification of mass spectrometry image features and its application to sample analysis and modeling. For the proof of concept, two different tissue types (healthy kidney and CT-26 xenograft tumor tissues) were imaged and analyzed. A mouse kidney model and tumor model were generated using morphometric - number of objects and total surface - information. The morphometric information was used to identify m/z that have a heterogeneous distribution. It seems to be a worthwhile pursuit as clonal heterogeneity in a tumor is of clinical relevance. This study provides a new approach to find biomarker or support tissue classification with more information. [Figure not available: see fulltext.

  2. Characterization of the Reproductive Toxicity of Depleted Uranium

    DTIC Science & Technology

    2005-06-01

    thymus, kidney, liver, skeletal muscle, uterus, ovaries, testes, bone marrow. Requested tissues were identified, embedded in paraffin and trimmed...located (all but 2-females), a cross section of the uterus was processed for evaluation. Each sample of skeletal muscle was bread-loafed in an attempt...correlation with the formation of soft tissue sarcomas . In contrast, none of these three animal’s implant sites showed evidence of a proliferative or

  3. Lead content in soft tissues of white-tailed deer

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

    Khan, A.T.

    1995-12-31

    The white-tailed deer is one of the North America`s most abundant game animals and can be used to monitor the quality of the environment. During the 1994 and 1995 hunting seasons, twenty-nine white-tailed deer were harvested with the permission of the Game Biologist of the Alabama Cooperative Deer Management Assistance Program and their liver and kidney samples were analyzed for lead levels. The lead levels in the livers and kidneys, were 0.35 and 0.37 ppm, respectively. The lead levels in the livers and kidneys did not show any significant difference. The lead levels in the livers of males and femalesmore » were 0.49 and 0.28 ppm and in the kidneys of males and females were 0.36 and 0.38 ppm, respectively. The lead levels in the livers and kidneys of males and females also did not show any significant difference. Likewise, the lead level neither in the livers nor in the kidneys of young and old deer showed any significant difference.« less

  4. Establishment of a protocol for the gene expression analysis of laser microdissected rat kidney samples with affymetrix genechips

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

    Stemmer, Kerstin; Ellinger-Ziegelbauer, Heidrun; Lotz, Kerstin

    2006-11-15

    Laser microdissection in conjunction with microarray technology allows selective isolation and analysis of specific cell populations, e.g., preneoplastic renal lesions. To date, only limited information is available on sample preparation and preservation techniques that result in both optimal histomorphological preservation of sections and high-quality RNA for microarray analysis. Furthermore, amplification of minute amounts of RNA from microdissected renal samples allowing analysis with genechips has only scantily been addressed to date. The objective of this study was therefore to establish a reliable and reproducible protocol for laser microdissection in conjunction with microarray technology using kidney tissue from Eker rats p.o. treatedmore » for 7 days and 6 months with 10 and 1 mg Aristolochic acid/kg bw, respectively. Kidney tissues were preserved in RNAlater or snap frozen. Cryosections were cut and stained with either H and E or cresyl violet for subsequent morphological and RNA quality assessment and laser microdissection. RNA quality was comparable in snap frozen and RNAlater-preserved samples, however, the histomorphological preservation of renal sections was much better following cryopreservation. Moreover, the different staining techniques in combination with sample processing time at room temperature can have an influence on RNA quality. Different RNA amplification protocols were shown to have an impact on gene expression profiles as demonstrated with Affymetrix Rat Genome 230{sub 2}.0 arrays. Considering all the parameters analyzed in this study, a protocol for RNA isolation from laser microdissected samples with subsequent Affymetrix chip hybridization was established that was also successfully applied to preneoplastic lesions laser microdissected from Aristolochic acid-treated rats.« less

  5. Use of a tissue sectioner to expose internal structures of biological samples for scanning electron microscopy.

    PubMed

    Brown, M F; Brotzman, H G; Kinden, D A

    1976-09-01

    A procedure yielding sections of unembedded biological samples for observation by scanning electron microscopy is described. Sections of samples, fixed and hardened in OsO4, were obtained in quantity with a tissue sectioner. Subsequent treatments to osmium-coat cut surfaces were employed prior to critical point drying. The procedure yields cleanly cut surfaces through cells and cytoplasmic organelles which are retained in their normal position. Sections of apple leaf and mouse kidney are illustrated. Sections can be readily cut in a desired plane with less structural damage than is typically encountered by other sectioning or dissection techniques.

  6. Integrating UHPLC-MS/MS quantification and DAS analysis to investigate the effects of wine-processing on the tissue distributions of bioactive constituents of herbs in rats: Exemplarily shown for Dipsacus asper.

    PubMed

    Tao, Yi; Du, Yingshan; Li, Weidong; Cai, Baochang; Di, Liuqing; Shi, Liyun; Hu, Lihong

    2017-06-15

    Wine-processing, which is sauteing with rice wine, will change the inclination and direction of herbs' actions. After being wine-processed, the effects of nourishing liver and kidney of Dipsacus asper will be strengthened. However, the underlying mechanism remains elusive. The following study is to establish and validate an UHPLC-MS/MS approach to determine six bioactive constituents in tissue samples, including loganin, loganic acid, chlorogenic acid, 3,5-dicaffeoylquinic acid, 4-caffeoylquinic acid and asperosaponin VI and apply the approach to a comparative tissue distribution study of raw and wine-processed Dipsacus asper in rats. A Shimadzu UHPLC system coupled with triple quadrupole mass spectrometer was employed for analysis of the six analytes using multiple reaction monitoring (MRM) mode. A one-step protein precipitation by methanol was employed to extract the six analytes from tissues. Chloramphenicol and glycyrrhetinic acid were selected as internal standards. The proposed approach was fully validated in terms of linearity, sensitivity, precision, repeatability as well as recovery. Our results revealed that all of the calibration curves displayed good linear regression (r 2 >0.9991). Intra- and inter-assay variability for all analytes ranged from -4.62 to 4.93% and from -4.98 to 4.92%, respectively. The recovery rates for each analytes were determined to be 88.3-100.1%. All the samples showed satisfactory precision and accuracy after various stability tests, including storage at 25°C for 4h, -80°C for 30days, three-freeze-thaw cycles, and 4°C for 24h. Tissue pharmacokinetic parameters including AUC 0-t , t 1/2 , T max and C max were calculated. Collectively, the parameters of C max and AUC 0-t of the six analytes in wine-processed group were remarkably elevated (p<0.05) in the rat liver and kidney as compared with those of the raw group. But in the rat heart and spleen, the C max and AUC 0-t of asperosaponin VI was decreased as compared with those of the raw group. The accumulation of bioactive constituents in liver and kidney tissues after wine-processing will contribute to the enhancement of liver and kidney nourishing effects. Copyright © 2017 Elsevier B.V. All rights reserved.

  7. Quantitative Enzymatic and Immunologic Histophotometry of Diseased Human Kid-Ney Tissues Using Tv-Camera and Computer Assisted Image Processing Systems.

    NASA Astrophysics Data System (ADS)

    Heinert, G.; Mondorf, W.

    1982-11-01

    High speed image processing was used to analyse morphologic and metabolic characteristics of clinically relevant kidney tissue alterations.Qualitative computer-assisted histophotometry was performed to measure alterations in levels of the enzymes alkaline phosphatase (Ap),alanine aminopeptidase (AAP),g-glutamyltranspepti-dase (GGTP) and A-glucuronidase (B-G1) and AAP and GGTP immunologically determined in prepared renal and cancer tissue sections. A "Mioro-Videomat 2" image analysis system with a "Tessovar" macroscope,a computer-assisted "Axiomat" photomicroscope and an "Interactive Image Analysis System (IBAS)" were employed for analysing changes in enzyme activities determined by changes in absorbance or transmission.Diseased kidney as well as renal neoplastic tissues could be distinguished by significantly (wilcoxon test,p<0,05) decreased enzyme concentrations as compared to those found in normal human kidney tissues.This image analysis techniques might be of potential use in diagnostic and prognostic evaluation of renal cancer and diseased kidney tissues.

  8. Kidney damage in extracorporeal shock wave lithotripsy: a numerical approach for different shock profiles.

    PubMed

    Weinberg, Kerstin; Ortiz, Michael

    2009-08-01

    In shock-wave lithotripsy--a medical procedure to fragment kidney stones--the patient is subjected to hypersonic waves focused at the kidney stone. Although this procedure is widely applied, the physics behind this medical treatment, in particular the question of how the injuries to the surrounding kidney tissue arise, is still under investigation. To contribute to the solution of this problem, two- and three-dimensional numerical simulations of a human kidney under shock-wave loading are presented. For this purpose a constitutive model of the bio-mechanical system kidney is introduced, which is able to map large visco-elastic deformations and, in particular, material damage. The specific phenomena of cavitation induced oscillating bubbles is modeled here as an evolution of spherical pores within the soft kidney tissue. By means of large scale finite element simulations, we study the shock-wave propagation into the kidney tissue, adapt unknown material parameters and analyze the resulting stress states. The simulations predict localized damage in the human kidney in the same regions as observed in animal experiments. Furthermore, the numerical results suggest that in first instance the pressure amplitude of the shock wave impulse (and not so much its exact time-pressure profile) is responsible for damaging the kidney tissue.

  9. Kidney biopsy

    MedlinePlus

    ... normal structure. What Abnormal Results Mean An abnormal result means there are changes in the kidney tissue. This may be due to: Infection Poor blood flow through the kidney Connective tissue diseases such as systemic lupus erythematosus Other diseases that may be affecting the ...

  10. Probing metabolic stability of CdSe nanoparticles: alkaline extraction of free cadmium from liver and kidney samples of rats exposed to CdSe nanoparticles

    PubMed Central

    Arslan, Zikri; Ates, Mehmet; McDuffy, Wanaki; Agachan, M. Sabri; Farah, Ibrahim O.; Yu, W. William; Bednar, Anthony J.

    2011-01-01

    Cadmium selenide nanoparticles (CdSe NPs) exhibit novel optoelectronic properties for potential biomedical applications. However, their metabolic stability is not fully understood because of the difficulties in measurement of free Cd from biological tissues of exposed individuals. In this study, alkaline dissolution with tetramethylammonium hydroxide (TMAH) is demonstrated for selective determination of free Cd and intact NPs from liver and kidney samples of animals that were exposed to thiol-capped CdSe NPs. Aqueous suspensions of CdSe NPs (3.2 nm) were used to optimize the conditions for extracting free Cd without affecting NPs. Nanoparticles were found to aggregate when heated in TMAH without releasing any significant Cd to solution. Performance of the method in discriminating free Cd and intact NPs were verified by Dogfish Liver (DOLT-4) certified reference material. The samples from the animals were digested in 4 mL TMAH at 70 °C to extract free Cd followed by analysis of aqueous phase by ICP-MS. Both liver and kidney contained significant levels of free Cd. Total Cd was higher in the liver, while kidney accumulated mostly free Cd such that up to 47.9% of total Cd in the kidney was free Cd when NPs were exposed to UV-light before injection. PMID:21700388

  11. The Tissue Distribution and Urinary Excretion Study of Gallic Acid and Protocatechuic Acid after Oral Administration of Polygonum Capitatum Extract in Rats.

    PubMed

    Ma, Feng-Wei; Deng, Qing-Fang; Zhou, Xin; Gong, Xiao-Jian; Zhao, Yang; Chen, Hua-Guo; Zhao, Chao

    2016-03-24

    In the present study, we investigated the tissue distribution and urinary excretion of gallic acid (GA) and protocatechuic acid (PCA) after rat oral administration of aqueous extract of Polygonum capitatum (P. capitatum, named Herba Polygoni Capitati in China). An UHPLC-MS/MS analytical method was developed and adopted for quantification of GA and PCA in different tissue homogenate and urine samples. Interestingly, we found that GA and PCA showed a relatively targeted distribution in kidney tissue after dosing 60 mg/kg P. capitatum extract (equivalent to 12 mg/kg of GA and 0.9 mg/kg of PCA). The concentrations of GA and PCA in the kidney tissue reached 1218.62 ng/g and 43.98 ng/g, respectively, at one hour after oral administration. The results helped explain the empirical use of P. capitatum for kidney diseases in folk medicine. Further studies on urinary excretion of P. capitatum extract indicated that GA and PCA followed a concentrated elimination over a 4-h period. The predominant metabolites were putatively identified to be 4-methylgallic acid (4-OMeGA) and 4-methylprotocatechuic acid (4-OMePCA) by analyzing their precursor ions and characteristic fragment ions using tandem mass spectrometry. However, the amount of unchanged GA and PCA that survived the metabolism were about 14.60% and 15.72% of the total intake, respectively, which is reported for the first time in this study.

  12. Amyloidosis and Kidney Disease

    MedlinePlus

    ... Solitary Kidney Your Kidneys & How They Work Amyloidosis & Kidney Disease What is amyloidosis? Amyloidosis is a rare ... the organs and tissues affected. What are the kidneys and what do they do? The kidneys are ...

  13. Impact of the Di(2-Ethylhexyl) Phthalate Administration on Trace Element and Mineral Levels in Relation of Kidney and Liver Damage in Rats.

    PubMed

    Aydemir, Duygu; Karabulut, Gözde; Şimşek, Gülsu; Gok, Muslum; Barlas, Nurhayat; Ulusu, Nuriye Nuray

    2018-04-13

    Di(2-ethylhexyl) phthalate (DEHP) is a widely used synthetic polymer in the industry. DEHP may induce reproductive and developmental toxicity, obesity, carcinogenesis and cause abnormal endocrine function in both human and wildlife. The aim of this study was to investigate trace element and mineral levels in relation of kidney and liver damage in DEHP-administered rats. Therefore, prepubertal male rats were dosed with 0, 100, 200, and 400 mg/kg/day of DEHP. At the end of the experiment, trace element and mineral levels, glucose-6-phosphate dehydrogenase (G6PD), 6-phosphogluconate dehydrogenase (6-PGD), glutathione reductase (GR) and glutathione S-transferase (GST) enzyme activities were evaluated in the serum, liver, and kidney samples of rats. Furthermore, serum clinical biochemistry parameters, organ/body weight ratios and histological changes were investigated to evaluate impact of DEHP more detailed. Our data indicated that sodium (Na), calcium (Ca), potassium (K), lithium (Li), rubidium (Rb) and cesium (Cs) levels significantly decreased, however iron (Fe) and selenium (Se) concentrations significantly increased in DEHP-administered groups compared to the control in the serum samples. On the other hand, upon DEHP administration, selenium concentration, G6PD and GR activities were significantly elevated, however 6-PGD activity significantly decreased compared to the control group in the kidney samples. Decreased G6PD activity was the only significant change between anti-oxidant enzyme activities in the liver samples. Upon DEHP administration, aberrant serum biochemical parameters have arisen and abnormal histological changes were observed in the kidney and liver tissue. In conclusion, DEHP may induce liver and kidney damage, also result abnormalities in the trace element and mineral levels.

  14. Protective Effect of Hydroalcoholic Extract of Tribulus Terrestris on Cisplatin Induced Renal Tissue Damage in Male Mice

    PubMed Central

    Raoofi, Amir; Khazaei, Mozafar; Ghanbari, Ali

    2015-01-01

    Background: According beneficial effects of Tribulus terrestris (TT) extract on tissue damage, the present study investigated the influence of hydroalcoholic extract of TT plant on cisplatin (CIS) (EBEWE Pharma, Unterach, Austria) induced renal tissue damage in male mice. Methods: Thirty mice were divided into five groups (n = 6). The first group (control) was treated with normal saline (0.9% NaCl) and experimental groups with CIS (E1), CIS + 100 mg/kg extract of TT (E2), CIS + 300 mg/kg extract of TT (E3), CIS + 500 mg/kg extract of TT (E4) intraperitoneally. The kidneys were removed after 4 days of injections, and histological evaluations were performed. Results: The data were analyzed using one-way analysis of variance followed by Tukey's post-hoc test, paired-sample t-test, Kruskal–Wallis and Mann–Whitney tests. In the CIS treated group, the whole kidney tissue showed an increased dilatation of Bowman's capsule, medullar congestion, and dilatation of collecting tubules and a decreased in the body weight and kidney weight. These parameters reached to the normal range after administration of fruit extracts of TT for 4 days. Conclusions: The results suggested that the oral administration of TT fruit extract at dose 100, 300 and 500 mg/kg body weight provided protection against the CIS induced toxicity in the mice. PMID:25789143

  15. Observation of human tissue with phase-contrast x-ray computed tomography

    NASA Astrophysics Data System (ADS)

    Momose, Atsushi; Takeda, Tohoru; Itai, Yuji; Tu, Jinhong; Hirano, Keiichi

    1999-05-01

    Human tissues obtained from cancerous kidneys fixed in formalin were observed with phase-contrast X-ray computed tomography (CT) using 17.7-keV synchrotron X-rays. By measuring the distributions of the X-ray phase shift caused by samples using an X-ray interferometer, sectional images that map the distribution of the refractive index were reconstructed. Because of the high sensitivity of phase- contrast X-ray CT, a cancerous lesion was differentiated from normal tissue and a variety of other structures were revealed without the need for staining.

  16. Scanning ion conductance microscopy for visualizing the three-dimensional surface topography of cells and tissues.

    PubMed

    Nakajima, Masato; Mizutani, Yusuke; Iwata, Futoshi; Ushiki, Tatsuo

    2018-01-01

    Scanning ion conductance microscopy (SICM), which belongs to the family of scanning probe microscopy, regulates the tip-sample distance by monitoring the ion current through the use of an electrolyte-filled nanopipette as the probing tip. Thus, SICM enables "contact-free" imaging of cell surface topography in liquid conditions. In this paper, we applied hopping mode SICM for obtaining topographical images of convoluted tissue samples such as trachea and kidney in phosphate buffered saline. Some of the SICM images were compared with the images obtained by scanning electron microscopy (SEM) after drying the same samples. We showed that the imaging quality of hopping mode SICM was excellent enough for investigating the three-dimensional surface structure of the soft tissue samples. Thus, SICM is expected to be used for imaging a wide variety of cells and tissues - either fixed or alive- at high resolution under physiologically relevant liquid conditions. Copyright © 2017 Elsevier Ltd. All rights reserved.

  17. A comparative study: Difference in omega-6/omega-3 balance and saturated fat in diets for Atlantic salmon (Salmo salar) affect immune-, fat metabolism-, oxidative and apoptotic-gene expression, and eicosanoid secretion in head kidney leukocytes.

    PubMed

    Holen, Elisabeth; Araujo, Pedro; Sissener, Nini H; Rosenlund, Grethe; Waagbø, Rune

    2018-01-01

    The aim of this study was to compare how different dietary vegetable oil n-6/n-3 ratios affect gene responses involved in inflammation, signaling pathways, fatty acid synthesis and oxidation, oxidation and apoptosis as well as eicosanoid production in salmon head kidney tissues and isolated head kidney leukocytes. Salmon smolts (200 g) were fed four different diets where the main lipid components were palm oil (n-6/n-3 ratio = 0.7), rapeseed oil (n-6/n-3 ratio = 0.9), and soybean oil (n-6/n-3 ratio = 2.4) and a high soybean oil diet with an n-6/n-3 ratio = 4. Both head kidney tissue and leukocytes isolated from head kidneys were sampled from the four diets, but from different fish. Leukocytes isolated from the head kidneys were seeded into culture wells and added lipopolysaccharide (LPS) to induce inflammatory responses. Controls without LPS were included. Head kidney leukocytes and the tissues should have the same phenotype reflecting the different diets. Interleukin 1β (IL-1β) transcription was elevated in head kidney tissue and especially in LPS treated leukocytes isolated from soybean oil (n-6/n-3 = 2.4) fed salmon, which confirmed the suitability of the in vitro model in this experiment. Leukocytes, treated with LPS, and isolated from salmon fed the soybean oil diet (n-6/n-3 = 2.4) also upregulated tumor necrosis factor alpha (tnf-α), cyclooxygenase (cox2), prostaglandin D and E synthase (ptgds, ptges), fatty acyl synthase (fas), 5 and 6 desaturases (5des, 6 des) and a fatty acid translocase protein (cd36) when compared to the other diets. The results suggest that diets with a specific n-6/n-3 ratio influence the transcription of pro-inflammatory genes and may be cross-linked to transcription of selected fatty acid metabolism genes. Salmon fed the palm oil diet (n-6/n-3 = 0.7) showed a lower expression of inflammatory genes. Instead, peroxisome proliferator activated receptor β1 (pparβ1), acyl coenzyme A (aco), apoptosis regulator (bax) and superoxide dismutase (sod) were upregulated in leukocytes in vitro, while head kidney tissue transcription of a dendritic marker (cd83) was lower than measured in tissues from fish fed the other diets. The concentration of LTB4 (10-20 ng/mL) were relatively constant in leukocyte supernatants, all diets. Head kidney leukocytes from soybean oil (n-6/n-3 = 2.4) fed fish produced LPS induced PGE2 (mean 0.5 ng/mL) while leukocytes isolated from palm oil diet (n-6/n-3 = 0.7) secreted very high amounts of LTB5 (50-70 ng/mL). In addition, equal amounts of LPS induced PGE2 and PGE3 (mean 0, 5 ng/mL) were produced, indicating that the n-6/n-3 ratio of this saturated fatty acid may have a specific impact on eicosanoid production in the head kidney of salmon. Copyright © 2017 Elsevier Ltd. All rights reserved.

  18. Distribution and elimination of [14C] sarafloxacin hydrochloride from tissues of juvenile channel catfish (Ictalurus punctatus)

    USGS Publications Warehouse

    Gingerich, W.H.; Meinertz, J.R.; Dawson, V.K.; Gofus, J.E.; Delaney, L.J.; Bunnell, P.R.

    1995-01-01

    The distribution and loss of radioactivity from tissues were determined in 60 juvenile channel catfish (Ictalurus punctatus) following oral dosing with the candidate fish therapeutant Sarafin® ([14C] sarafloxacin hydrochloride) at 10 mg/kg for 5 consecutive days. Twelve groups of 5 fish each were sampled at selected times ranging from 3 to 240 h after the last dose was administered, The concentration and content of sarafloxacin-equivalent activity was determined in liver, gallbladder, kidney, skin, and skinless fillet by sample oxidation and liquid scintillation counting; content of sarafloxacin-equivalent activity was determined in stomach and anterior and posterior intestines, Skinless fillet tissues were also analyzed for sarafloxacin and for potential metabolites by gradient-elution high-performance liquid chromatography (HPLC) with in-line radiometric and fluorescence detection, Loss of radioactivity from the whole body conformed to a bimodal elimination pattern with a rapid initial phase (t1/2=11 h) and a slower secondary phase (t1/2=222 h). Tissue and contents of the gastrointestinal tract (i.e. stomach and anterior and posterior intestines) were a principal depot of activity during the first four sample times (3, 6, 12, and 24 h); the combined head, skeleton, and fins (i.e. residual carcass) were the principal depot of activity in samples taken after 24 h. Of those tissues sampled 3 h after the last dose, relative sarafloxacin concentration was greatest in the liver (4.06 μg equivalents/g) and least in the residual carcass (1.13 μg equivalents/g), Intermediate concentrations were found in the kidney (2.04 μg equivalents/g), skinless fillet (1.71 μg equivalents/ g), and the skin (1.51 μg equivalents/g). Concentrations of sarafloxacin-equivalent residues in edible skinless fillet were consistently among the lowest of all tissues examined. The highest mean concentration of parent-equivalent material in the fillet tissue was found 12 h after administration of the last dose (2.27 μg equivalents/g) and declined thereafter, Sarafloxacin constituted between 80 and 90% of the extractable radioactive residues from the fillet homogenates. No other peaks were resolved in any of the fillet tissue samples analyzed by HPLC with in-line radiometric detection.

  19. The characteristics of placental transfer and tissue concentrations of nickel in late gestational rats and fetuses.

    PubMed

    Hou, Y-P; Gu, J-Y; Shao, Y-F; Song, Y-F; Jing, Y-H; Wu, W-S; Pu, S

    2011-03-01

    The dynamics of nickel (Ni) uptake, transfer, retention and clearance in fetuses and late gestational rats were investigated by assessing its distributions in placenta, maternal and fetal organs and tissues during the 24 h period after a single dose of (63)Ni intraperitoneal injection on gestational day 20. Peak (63)Ni radioactivity was detected at 0.5 h in maternal blood, at 3 h in placenta, fetal membranes, fetal blood, fetal heart, maternal kidney, lung, stomach, liver and brain, at 9 h in fetal kidney, stomach, liver and brain, and lastly at 24 h in fetal lung and amniotic fluid. The maximal (63)Ni radioactivity among all samples was detected consistently in the fetal membranes and placenta. The (63)Ni radioactivity in fetal blood was higher than that in maternal blood from 3 to 24 h. The fetal liver, heart, stomach and brain exhibited higher (63)Ni radioactivity than the corresponding maternal organs from 6 to 24 h. However, maternal kidney consistently exhibited significantly higher (63)Ni radioactivity than the fetal kidney. The (63)Ni in fetal lung and amniotic fluid increased throughout the period of experimental observation. These observations corroborated previous finding that nickel is actively transferred across the blood-placenta-barrier into fetus, but hardly from fetus to mother. Moreover, these results suggest that the placenta has a high affinity for nickel and its barrier does not protect the fetus from nickel exposure. The fact that nickel concentrations are higher in most fetal organs and tissues than in corresponding maternal organs and tissues in late gestation indicates that, unlike the dam, fetuses lack effective means for getting rid of excessive nickel due to its confined environment and relatively weak kidney functions. The situation is exacerbated by mother-to-fetus unidirectional transfer. Consequently, the fetuses are particularly vulnerable to the damaging effects of nickel. Copyright © 2010 Elsevier Ltd. All rights reserved.

  20. Phase-Contrast Hounsfield Units of Fixated and Non-Fixated Soft-Tissue Samples

    PubMed Central

    Willner, Marian; Fior, Gabriel; Marschner, Mathias; Birnbacher, Lorenz; Schock, Jonathan; Braun, Christian; Fingerle, Alexander A.; Noël, Peter B.; Rummeny, Ernst J.; Pfeiffer, Franz; Herzen, Julia

    2015-01-01

    X-ray phase-contrast imaging is a novel technology that achieves high soft-tissue contrast. Although its clinical impact is still under investigation, the technique may potentially improve clinical diagnostics. In conventional attenuation-based X-ray computed tomography, radiological diagnostics are quantified by Hounsfield units. Corresponding Hounsfield units for phase-contrast imaging have been recently introduced, enabling a setup-independent comparison and standardized interpretation of imaging results. Thus far, the experimental values of few tissue types have been reported; these values have been determined from fixated tissue samples. This study presents phase-contrast Hounsfield units for various types of non-fixated human soft tissues. A large variety of tissue specimens ranging from adipose, muscle and connective tissues to liver, kidney and pancreas tissues were imaged by a grating interferometer with a rotating-anode X-ray tube and a photon-counting detector. Furthermore, we investigated the effects of formalin fixation on the quantitative phase-contrast imaging results. PMID:26322638

  1. Automated classification of tissue by type using real-time spectroscopy

    NASA Astrophysics Data System (ADS)

    Benaron, David A.; Cheong, Wai-Fung; Duckworth, Joshua L.; Noles, Kenneth; Nezhat, Camran; Seidman, Daniel; Hintz, Susan R.; Levinson, Carl J.; Murphy, Aileen L.; Price, John W., Jr.; Liu, Frank W.; Stevenson, David K.; Kermit, Eben L.

    1997-12-01

    Each tissue type has a unique spectral signature (e.g. liver looks distinct from bowel due to differences in both absorbance and in the way the tissue scatters light). While differentiation between normal tissues and tumors is not trivial, automated discrimination among normal tissue types (e.g. nerve, artery, vein, muscle) is feasible and clinically important, as many medical errors in medicine involve the misidentification of normal tissues. In this study, we have found that spectroscopic differentiation of tissues can be successfully applied to tissue samples (kidney and uterus) and model systems (fruit). Such optical techniques may usher in use of optical tissue diagnosis, leading to automated and portable diagnostic devices which can identify tissues, and guide use of medical instruments, such as during ablation or biopsy.

  2. Expression of p53/HGF/c-met/STAT3 signal in fetuses with neural tube defects.

    PubMed

    Trovato, Maria; D'Armiento, Maria; Lavra, Luca; Ulivieri, Alessandra; Dominici, Roberto; Vitarelli, Enrica; Grosso, Maddalena; Vecchione, Raffaella; Barresi, Gaetano; Sciacchitano, Salvatore

    2007-02-01

    Neural tube defects (NTD) are morphogenetic alterations due to a defective closure of neural tube. Hepatocyte growth factor (HGF)/c-met system plays a role in morphogenesis of nervous system, lung, and kidney. HGF/c-met morphogenetic effects are mediated by signal transducers and activators of transcription (STAT)3 and both HGF and c-met genes are regulated from p53. The aim of our study was to analyze mRNA and protein expressions of p53, HGF, c-met, and STAT3 in fetuses with NTD. By reverse transcriptase-polymerase chain reaction and immunohistochemistry, we analyzed neural tissues from four NTD fetuses and the corresponding non-malformed lungs, kidneys and placentas. We found a reduced mRNA expression of HGF/c-met/STAT3 pathway, in the malformed nervous systems and placentas. The reduced expression of this pathway correlated with the absence of p53 in all these samples. On the contrary, detectable expression levels of p53, HGF, c-met, and STAT3 were observed in non-malformed lungs and kidneys obtained from the same fetuses. Comparable results were obtained by immunohistochemistry, with the exception of p53, which was undetected in all fetal tissues. In conclusion, in NTD fetuses, both the defective neural tube tissue and the placenta have a reduction in all components of the p53/HGF/c-met/STAT3 cascade. This raises the possibility of using the suppression of these genes for early diagnosis of NTD especially on chorionic villus sampling.

  3. Freezing/Thawing without Cryoprotectant Damages Native but not Decellularized Porcine Renal Tissue

    PubMed Central

    Poornejad, Nafiseh; Frost, Timothy S; Scott, Daniel R; Elton, Brinden B; Reynolds, Paul R; Roeder, Beverly L; Cook, Alonzo D

    2015-01-01

    abstract Whole organ decellularization of porcine renal tissue and recellularization with a patient's own cells would potentially overcome immunorejection, which is one of the most significant problems with allogeneic kidney transplantation. However, there are obstacles to achieving this goal, including preservation of the decellularized extracellular matrix (ECM), identifying the proper cell types, and repopulating the ECM before transplantation. Freezing biological tissue is the best option to avoid spoilage; however, it may damage the structure of the tissue or disrupt cellular membranes through ice crystal formation. Cryoprotectants have been used to repress ice formation during freezing, although cell toxicity can still occur. The effect of freezing/thawing on native (n = 10) and decellularized (n = 10) whole porcine kidneys was studied without using cryoprotectants. Results showed that the elastic modulus of native kidneys was reduced by a factor of 22 (P < 0.0001) by freezing/thawing or decellularization, while the elastic modulus for decellularized ECM was essentially unchanged by the freezing/thawing process (p = 0.0636). Arterial pressure, representative of structural integrity, was also reduced by a factor of 52 (P < 0.0001) after freezing/thawing for native kidneys, compared to a factor of 43 (P < 0.0001) for decellularization and a factor of 4 (P < 0.0001) for freezing/thawing decellularized structures. Both freezing/thawing and decellularization reduced stiffness, but the reductions were not additive. Investigation of the microstructure of frozen/thawed native and decellularized renal tissues showed increased porosity due to cell removal and ice crystal formation. Orcein and Sirius staining showed partial damage to elastic and collagen fibers after freezing/thawing. It was concluded that cellular damage and removal was more responsible for reducing stiffness than fibril destruction. Cell viability and growth were demonstrated on decellularized frozen/thawed and non-frozen samples using human renal cortical tubular epithelial (RCTE) cells over 12 d. No adverse effect on the ability to recellularize after freezing/thawing was observed. It is recommended that porcine kidneys be frozen prior to decellularization to prevent contamination, and after decellularization to prevent protein denaturation. Cryoprotectants may still be necessary, however, during storage and transportation after recellularization. PMID:25730294

  4. A survey of spontaneous occurrence of ochratoxin A residues in chicken tissues and concurrence with histopathological changes in liver and kidneys

    USGS Publications Warehouse

    Milicevic, Dragan; Jovanovic, Milijan; Matekalosverak, Vesna; Radicevic, Tatjana; Petrovic, Milan M.; Lilic, Slobodan

    2011-01-01

    Toxicological and histopathological investigations of tissues of commercially slaughtered chickens were carried out to provide a preliminary evaluation of the incidence of occurrence of ochratoxin A (OTA) in chicken sold in Serbian retail market. In addition, the etiology of nephropathies of these chickens was elucidated. The majority of these tissue samples were not found to contain measurable amounts of OTA. Moreover, the OTA levels found in analyzed tissues were generally low and there was no positive correlation between the presence of OTA and the frequency of histopathological changes. Histopathological changes such as degenerative changes in the kidneys and liver differed from the classical description of the mycotoxic nephropathy, indicating that the chicken nephropathy observed in Serbia may have a multitoxic etiology with possible synergistic effect between microorganisms and natural toxins, usually present in low concentrations. The low OTA results also suggested that chicken meat available in the retail market in Serbia are unlikely to pose any significant adverse health risk to the consumers with respect to OTA toxicity.

  5. Generation of a Three-Dimensional Kidney Structure from Pluripotent Stem Cells.

    PubMed

    Yoshimura, Yasuhiro; Taguchi, Atsuhiro; Nishinakamura, Ryuichi

    2017-01-01

    The kidney is a vital organ that has an important role in the maintenance of homeostasis by fluid volume regulation and waste product excretion. This role cannot be performed without the three-dimensional (3D) structure of the kidney. Therefore, it is important to generate the 3D structure of the kidney when inducing functional kidney tissue or the whole organ from pluripotent stem cells. In this chapter, we describe the detailed methods to induce kidney progenitor cells from pluripotent stem cells, which are based on embryological development. We also provide a method to generate 3D kidney tissue with vascularized glomeruli upon transplantation.

  6. Interferon-γ production by tubulointerstitial human CD56bright natural killer cells contributes to renal fibrosis and chronic kidney disease progression.

    PubMed

    Law, Becker M P; Wilkinson, Ray; Wang, Xiangju; Kildey, Katrina; Lindner, Mae; Rist, Melissa J; Beagley, Kenneth; Healy, Helen; Kassianos, Andrew J

    2017-07-01

    Natural killer (NK) cells are a population of lymphoid cells that play a significant role in mediating innate immune responses. Studies in mice suggest a pathological role for NK cells in models of kidney disease. In this study, we characterized the NK cell subsets present in native kidneys of patients with tubulointerstitial fibrosis, the pathological hallmark of chronic kidney disease. Significantly higher numbers of total NK cells (CD3 - CD56 + ) were detected in renal biopsies with tubulointerstitial fibrosis compared with diseased biopsies without fibrosis and healthy kidney tissue using multi-color flow cytometry. At a subset level, both the CD56 dim NK cell subset and particularly the CD56 bright NK cell subset were elevated in fibrotic kidney tissue. However, only CD56 bright NK cells significantly correlated with the loss of kidney function. Expression of the tissue-retention and -activation molecule CD69 on CD56 bright NK cells was significantly increased in fibrotic biopsy specimens compared with non-fibrotic kidney tissue, indicative of a pathogenic phenotype. Further flow cytometric phenotyping revealed selective co-expression of activating receptor CD335 (NKp46) and differentiation marker CD117 (c-kit) on CD56 bright NK cells. Multi-color immunofluorescent staining of fibrotic kidney tissue localized the accumulation of NK cells within the tubulointerstitium, with CD56 bright NK cells (NKp46 + CD117 + ) identified as the source of pro-inflammatory cytokine interferon-γ within the NK cell compartment. Thus, activated interferon-γ-producing CD56 bright NK cells are positioned to play a key role in the fibrotic process and progression to chronic kidney disease. Crown Copyright © 2017. Published by Elsevier Inc. All rights reserved.

  7. Stereological study of developing glomerular forms during human fetal kidney development.

    PubMed

    Dakovic Bjelakovic, Marija; Vlajkovic, Slobodan; Petrovic, Aleksandar; Bjelakovic, Marko; Antic, Milorad

    2018-05-01

    Human fetal kidney development is a complex and stepwise process. The number, shape, size and distribution of glomeruli provide important information on kidney organization. The aim of this study was to quantify glomerular developing forms during human fetal kidney development using stereological methods. Kidney tissue specimens of 40 human fetuses with gestational ages ranging from 9 to 40 weeks were analyzed. Specimens were divided into eight groups based on gestational age, each corresponding to 1 lunar month. Stereological methods were used at the light microscopy level to estimate volume, surface and numerical density of the glomerular developing forms. During gestation, nephrogenesis continually advanced, and the number of nephrons increased. Volume, surface and numerical densities of vesicular forms and S-shaped bodies decreased gradually in parallel with gradual increases in estimated stereological parameters for vascularized glomeruli. Volume density and surface density of vascularized glomeruli increased gradually during fetal kidney development, and numerical density increased until the seventh lunar month. A relative decrease in vascularized glomeruli per unit volume of cortex occurred during the last 3 lunar months. Nephrogenesis began to taper off by 32 weeks and was completed by 36 weeks of gestation. The last sample in which we observed vesicles was from a fetus aged 32 weeks, and the last sample with S-shaped bodies was from a fetus aged 36 weeks. The present study is one of few quantitative studies conducted on human kidney development. Knowledge of normal human kidney morphogenesis during development could be important for future medical practice. Events occurring during fetal life may have significant consequences later in life.

  8. A strain-hardening bi-power law for the nonlinear behaviour of biological soft tissues.

    PubMed

    Nicolle, S; Vezin, P; Palierne, J-F

    2010-03-22

    Biological soft tissues exhibit a strongly nonlinear viscoelastic behaviour. Among parenchymous tissues, kidney and liver remain less studied than brain, and a first goal of this study is to report additional material properties of kidney and liver tissues in oscillatory shear and constant shear rate tests. Results show that the liver tissue is more compliant but more strain hardening than kidney. A wealth of multi-parameter mathematical models has been proposed for describing the mechanical behaviour of soft tissues. A second purpose of this work is to develop a new constitutive law capable of predicting our experimental data in the both linear and nonlinear viscoelastic regime with as few parameters as possible. We propose a nonlinear strain-hardening fractional derivative model in which six parameters allow fitting the viscoelastic behaviour of kidney and liver tissues for strains ranging from 0.01 to 1 and strain rates from 0.0151 s(-1) to 0.7s(-1). Copyright (c) 2009 Elsevier Ltd. All rights reserved.

  9. De Novo Kidney Regeneration with Stem Cells

    PubMed Central

    Yokote, Shinya; Yamanaka, Shuichiro; Yokoo, Takashi

    2012-01-01

    Recent studies have reported on techniques to mobilize and activate endogenous stem-cells in injured kidneys or to introduce exogenous stem cells for tissue repair. Despite many recent advantages in renal regenerative therapy, chronic kidney disease (CKD) remains a major cause of morbidity and mortality and the number of CKD patients has been increasing. When the sophisticated structure of the kidneys is totally disrupted by end stage renal disease (ESRD), traditional stem cell-based therapy is unable to completely regenerate the damaged tissue. This suggests that whole organ regeneration may be a promising therapeutic approach to alleviate patients with uncured CKD. We summarize here the potential of stem-cell-based therapy for injured tissue repair and de novo whole kidney regeneration. In addition, we describe the hurdles that must be overcome and possible applications of this approach in kidney regeneration. PMID:23251079

  10. Analytical determination of virginiamycin drug residues in edible porcine tissues by LC-MS with confirmation by LC-MS/MS.

    PubMed

    Boison, Joe; Lee, Stephen; Gedir, Ron

    2009-01-01

    A liquid chromatographic-mass spectrometric (LC-MS) method was developed and validated for the determination and confirmation of virginiamycin (VMY) M1 residues in porcine liver, kidney, and muscle tissues at concentrations > or =2 ng/g. Porcine liver, kidney, or muscle tissue is homogenized with methanol-acetonitrile. After centrifugation, the supernatant is diluted with phosphate buffer and cleaned up on a C18 solid-phase extraction cartridge. VMY in the eluate is partitioned into chloroform and the aqueous upper layer is removed by aspiration. After evaporating the chloroform in the residual mixture to dryness, the dried extract is reconstituted in mobile phase and VMY is quantified by LC-MS. Any samples eliciting quantifiable levels of VMY M1 (i.e., at concentrations > or =2 ng/g) are subjected to confirmatory analysis by LC-MSIMS. VMY S1, a minor component of the VMY complex, is monitored but not quantified or confirmed.

  11. Concentrations of mercury in tissues of striped dolphins suggest decline of pollution in Mediterranean open waters.

    PubMed

    Borrell, A; Aguilar, A; Tornero, V; Drago, M

    2014-07-01

    The Mediterranean is a semi-enclosed sea subject to high mercury (Hg) pollution from both natural and anthropogenic sources. With the objective of discerning temporal changes in marine Hg pollution in the oceanic waters of the northwestern Mediterranean Sea, we analysed liver and kidney from striped dolphins (Stenella coeruleoalba) collected during 2007-2009 and compared them with previous results from a similar sample from 1990-1993. The effect of body length and sex on tissue Hg concentrations was investigated to ensure an unbiased comparison between the periods. The Hg concentrations did not show significant sex-related differences in any tissue or period but were correlated positively with body length. Using body length as a covariate, Hg concentrations in liver and kidney were higher in 1990-1993 than in 2007-2009. This result suggests that measures to reduce emissions in Western European countries have been effective in reducing mercury pollution in Mediterranean open waters. Copyright © 2014 Elsevier Ltd. All rights reserved.

  12. Phase-contrast Hounsfield units of fixated and non-fixated soft-tissue samples

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

    Willner, Marian; Fior, Gabriel; Marschner, Mathias

    X-ray phase-contrast imaging is a novel technology that achieves high soft-tissue contrast. Although its clinical impact is still under investigation, the technique may potentially improve clinical diagnostics. In conventional attenuation-based X-ray computed tomography, radiological diagnostics are quantified by Hounsfield units. Corresponding Hounsfield units for phase-contrast imaging have been recently introduced, enabling a setup-independent comparison and standardized interpretation of imaging results. Thus far, the experimental values of few tissue types have been reported; these values have been determined from fixated tissue samples. This study presents phase-contrast Hounsfield units for various types of non-fixated human soft tissues. A large variety of tissuemore » specimens ranging from adipose, muscle and connective tissues to liver, kidney and pancreas tissues were imaged by a grating interferometer with a rotating-anode X-ray tube and a photon-counting detector. In addition, we investigated the effects of formalin fixation on the quantitative phase-contrast imaging results.« less

  13. Phase-contrast Hounsfield units of fixated and non-fixated soft-tissue samples

    DOE PAGES

    Willner, Marian; Fior, Gabriel; Marschner, Mathias; ...

    2015-08-31

    X-ray phase-contrast imaging is a novel technology that achieves high soft-tissue contrast. Although its clinical impact is still under investigation, the technique may potentially improve clinical diagnostics. In conventional attenuation-based X-ray computed tomography, radiological diagnostics are quantified by Hounsfield units. Corresponding Hounsfield units for phase-contrast imaging have been recently introduced, enabling a setup-independent comparison and standardized interpretation of imaging results. Thus far, the experimental values of few tissue types have been reported; these values have been determined from fixated tissue samples. This study presents phase-contrast Hounsfield units for various types of non-fixated human soft tissues. A large variety of tissuemore » specimens ranging from adipose, muscle and connective tissues to liver, kidney and pancreas tissues were imaged by a grating interferometer with a rotating-anode X-ray tube and a photon-counting detector. In addition, we investigated the effects of formalin fixation on the quantitative phase-contrast imaging results.« less

  14. Quantitation of repaglinide and metabolites in mouse whole-body thin tissue sections using droplet-based liquid microjunction surface sampling-high-performance liquid chromatography-electrospray ionization tandem mass spectrometry.

    PubMed

    Chen, Weiqi; Wang, Lifei; Van Berkel, Gary J; Kertesz, Vilmos; Gan, Jinping

    2016-03-25

    Herein, quantitation aspects of a fully automated autosampler/HPLC-MS/MS system applied for unattended droplet-based surface sampling of repaglinide dosed thin tissue sections with subsequent HPLC separation and mass spectrometric analysis of parent drug and various drug metabolites were studied. Major organs (brain, lung, liver, kidney and muscle) from whole-body thin tissue sections and corresponding organ homogenates prepared from repaglinide dosed mice were sampled by surface sampling and by bulk extraction, respectively, and analyzed by HPLC-MS/MS. A semi-quantitative agreement between data obtained by surface sampling and that by employing organ homogenate extraction was observed. Drug concentrations obtained by the two methods followed the same patterns for post-dose time points (0.25, 0.5, 1 and 2 h). Drug amounts determined in the specific tissues was typically higher when analyzing extracts from the organ homogenates. In addition, relative comparison of the levels of individual metabolites between the two analytical methods also revealed good semi-quantitative agreement. Copyright © 2015 Elsevier B.V. All rights reserved.

  15. Quantitation of repaglinide and metabolites in mouse whole-body thin tissue sections using droplet-based liquid microjunction surface sampling-high-performance liquid chromatography-electrospray ionization tandem mass spectrometry

    DOE PAGES

    Chen, Weiqi; Wang, Lifei; Van Berkel, Gary J.; ...

    2015-11-03

    Herein, quantitation aspects of a fully automated autosampler/HPLC-MS/MS system applied for unattended droplet-based surface sampling of repaglinide dosed thin tissue sections with subsequent HPLC separation and mass spectrometric analysis of parent drug and various drug metabolites was studied. Major organs (brain, lung, liver, kidney, muscle) from whole-body thin tissue sections and corresponding organ homogenates prepared from repaglinide dosed mice were sampled by surface sampling and by bulk extraction, respectively, and analyzed by HPLC-MS/MS. A semi-quantitative agreement between data obtained by surface sampling and that by employing organ homogenate extraction was observed. Drug concentrations obtained by the two methods followed themore » same patterns for post-dose time points (0.25, 0.5, 1 and 2 h). Drug amounts determined in the specific tissues was typically higher when analyzing extracts from the organ homogenates. Furthermore, relative comparison of the levels of individual metabolites between the two analytical methods also revealed good semi-quantitative agreement.« less

  16. Quantitation of repaglinide and metabolites in mouse whole-body thin tissue sections using droplet-based liquid microjunction surface sampling-high-performance liquid chromatography-electrospray ionization tandem mass spectrometry

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

    Chen, Weiqi; Wang, Lifei; Van Berkel, Gary J.

    Herein, quantitation aspects of a fully automated autosampler/HPLC-MS/MS system applied for unattended droplet-based surface sampling of repaglinide dosed thin tissue sections with subsequent HPLC separation and mass spectrometric analysis of parent drug and various drug metabolites was studied. Major organs (brain, lung, liver, kidney, muscle) from whole-body thin tissue sections and corresponding organ homogenates prepared from repaglinide dosed mice were sampled by surface sampling and by bulk extraction, respectively, and analyzed by HPLC-MS/MS. A semi-quantitative agreement between data obtained by surface sampling and that by employing organ homogenate extraction was observed. Drug concentrations obtained by the two methods followed themore » same patterns for post-dose time points (0.25, 0.5, 1 and 2 h). Drug amounts determined in the specific tissues was typically higher when analyzing extracts from the organ homogenates. Furthermore, relative comparison of the levels of individual metabolites between the two analytical methods also revealed good semi-quantitative agreement.« less

  17. Microsomal and Cytosolic Scaling Factors in Dog and Human Kidney Cortex and Application for In Vitro-In Vivo Extrapolation of Renal Metabolic Clearance

    PubMed Central

    Scotcher, Daniel; Billington, Sarah; Brown, Jay; Jones, Christopher R.; Brown, Colin D. A.; Rostami-Hodjegan, Amin

    2017-01-01

    In vitro-in vivo extrapolation of drug metabolism data obtained in enriched preparations of subcellular fractions rely on robust estimates of physiologically relevant scaling factors for the prediction of clearance in vivo. The purpose of the current study was to measure the microsomal and cytosolic protein per gram of kidney (MPPGK and CPPGK) in dog and human kidney cortex using appropriate protein recovery marker and evaluate functional activity of human cortex microsomes. Cytochrome P450 (CYP) content and glucose-6-phosphatase (G6Pase) activity were used as microsomal protein markers, whereas glutathione-S-transferase activity was a cytosolic marker. Functional activity of human microsomal samples was assessed by measuring mycophenolic acid glucuronidation. MPPGK was 33.9 and 44.0 mg/g in dog kidney cortex, and 41.1 and 63.6 mg/g in dog liver (n = 17), using P450 content and G6Pase activity, respectively. No trends were noted between kidney, liver, and intestinal scalars from the same animals. Species differences were evident, as human MPPGK and CPPGK were 26.2 and 53.3 mg/g in kidney cortex (n = 38), respectively. MPPGK was 2-fold greater than the commonly used in vitro-in vivo extrapolation scalar; this difference was attributed mainly to tissue source (mixed kidney regions versus cortex). Robust human MPPGK and CPPGK scalars were measured for the first time. The work emphasized the importance of regional differences (cortex versus whole kidney–specific MPPGK, tissue weight, and blood flow) and a need to account for these to improve assessment of renal metabolic clearance and its extrapolation to in vivo. PMID:28270564

  18. Characterization of the mechanical properties of resected porcine organ tissue using optical fiber photoelastic polarimetry.

    PubMed

    Hudnut, Alexa W; Babaei, Behzad; Liu, Sonya; Larson, Brent K; Mumenthaler, Shannon M; Armani, Andrea M

    2017-10-01

    Characterizing the mechanical behavior of living tissue presents an interesting challenge because the elasticity varies by eight orders of magnitude, from 50Pa to 5GPa. In the present work, a non-destructive optical fiber photoelastic polarimetry system is used to analyze the mechanical properties of resected samples from porcine liver, kidney, and pancreas. Using a quasi-linear viscoelastic fit, the elastic modulus values of the different organ systems are determined. They are in agreement with previous work. In addition, a histological assessment of compressed and uncompressed tissues confirms that the tissue is not damaged during testing.

  19. Metallothionein as potential biomarker of cadmium exposure in Persian sturgeon (Acipenser persicus).

    PubMed

    Shariati, Fatemeh; Esaili Sari, Abbas; Mashinchian, Ali; Pourkazemi, Mohammad

    2011-10-01

    Metallothionein (MT) concentration in gills, liver, and kidney tissues of Persian sturgeon (Acipenser persicus) were determined following exposure to sublethal levels of waterborne cadmium (Cd) (50, 400, and 1,000 μg l(-1)) after 1, 2, 4, and 14 days. The increases of MT from background levels were 4.6-, 3-, and 2.8-fold for kidney, liver, and gills, respectively. The results showed that MT level change in the kidney is time and concentration dependent. Also, cortisol measurement revealed elevation at the day 1 of exposure and followed by MT increase in the liver. Cd concentrations in the cytosol of experimental tissues were measured, and the results indicated that Cd levels in the cytosol of liver, kidney, and gills increased 240.71-, 32.05-, and 40.16-fold, respectively, 14 days after exposure to 1,000 μg l(-1) Cd. The accumulation of Cd in cytosol of tissues is in the order of liver > gills > kidney. Pearson correlation coefficients showed that the MT content in kidney is correlated with Cd concentration, the value of which is more than in liver and gills. Thus, kidney can be considered as a tissue indicator in A. persicus for waterborne Cd contamination.

  20. Molecular cloning of the myo-inositol oxygenase gene from the kidney of baboons

    PubMed Central

    González-Álvarez, Rafael; Pérez-Ibave, Diana Cristina; Garza-Rodríguez, María Lourdes; Lugo-Trampe, Ángel; Delgado-Enciso, Iván; Tejero-Barrera, María Elizabeth; Martínez-De-Villarreal, Laura Elia; Garza-Guajardo, Raquel; Sánchez-Chaparro, María Marisela; Ruiz-Ayma, Gabriel; Barboza-Quintana, Oralia; Barrera-Saldaña, Hugo Alberto; Rocha-Pizaña, María Del Refugio; Rodríguez-Sánchez, Irám Pablo

    2017-01-01

    The enzyme myo-Inositol oxygenase (MIOX) is also termed ALDRL6. It is a kidney-specific member of the aldo-keto reductase family. MIOX catalyzes the first reaction involved in the myo-inositol metabolism signaling pathway and is fully expressed in mammalian tissues. MIOX catalyzes the oxidative cleavage of myo-Inositol and its epimer, D-chiro-Inositol to D-glucuronate. The dioxygen-dependent cleavage of the C6 and C1 bond in myo-Inositol is achieved by utilizing the Fe2+/Fe3+ binuclear iron center of MIOX. This enzyme has also been implicated in the complications of diabetes, including diabetic nephropathy. The MIOX gene was amplified with reverse transcription-polymerase chain reaction from baboon tissue samples, and the product was cloned and sequenced. MIOX expression in the baboon kidney is described in the present study. The percentages of nucleotide and amino acid similarities between baboons and humans were 95 and 96%, respectively. The MIOX protein of the baboon may be structurally identical to that of humans. Furthermore, the evolutionary changes, which have affected these sequences, have resulted from purifying forces. PMID:29085625

  1. Molecular cloning of the myo-inositol oxygenase gene from the kidney of baboons.

    PubMed

    González-Álvarez, Rafael; Pérez-Ibave, Diana Cristina; Garza-Rodríguez, María Lourdes; Lugo-Trampe, Ángel; Delgado-Enciso, Iván; Tejero-Barrera, María Elizabeth; Martínez-De-Villarreal, Laura Elia; Garza-Guajardo, Raquel; Sánchez-Chaparro, María Marisela; Ruiz-Ayma, Gabriel; Barboza-Quintana, Oralia; Barrera-Saldaña, Hugo Alberto; Rocha-Pizaña, María Del Refugio; Rodríguez-Sánchez, Irám Pablo

    2017-10-01

    The enzyme myo-Inositol oxygenase (MIOX) is also termed ALDRL6. It is a kidney-specific member of the aldo-keto reductase family. MIOX catalyzes the first reaction involved in the myo-inositol metabolism signaling pathway and is fully expressed in mammalian tissues. MIOX catalyzes the oxidative cleavage of myo-Inositol and its epimer, D-chiro-Inositol to D-glucuronate. The dioxygen-dependent cleavage of the C6 and C1 bond in myo-Inositol is achieved by utilizing the Fe 2+ /Fe 3+ binuclear iron center of MIOX. This enzyme has also been implicated in the complications of diabetes, including diabetic nephropathy. The MIOX gene was amplified with reverse transcription-polymerase chain reaction from baboon tissue samples, and the product was cloned and sequenced. MIOX expression in the baboon kidney is described in the present study. The percentages of nucleotide and amino acid similarities between baboons and humans were 95 and 96%, respectively. The MIOX protein of the baboon may be structurally identical to that of humans. Furthermore, the evolutionary changes, which have affected these sequences, have resulted from purifying forces.

  2. Tylosin depletion in edible tissues of turkeys.

    PubMed

    Montesissa, C; De Liguoro, M; Santi, A; Capolongo, F; Biancotto, G

    1999-10-01

    The depletion of tylosin residues in edible turkey tissues was followed after 3 days of administration of tylosin tartrate at 500 mg l-1 in drinking water, to 30 turkeys. Immediately after the end of the treatment (day 0) and at day 1, 3, 5 and 10 of withdrawal, six turkeys (three males and three females) per time were sacrificed and samples of edible tissues were collected. Tissue homogenates were extracted, purified and analysed by HPLC according to a method previously published for the analysis of tylosin residues in pig tissues. In all tissues, tylosin residues were already below the detection limits of 50 micrograms kg-1 at time zero. However, in several samples of tissues (skin + fat, liver, kidney, muscle), from the six turkeys sacrificed at that time, one peak corresponding to an unknown tylosin equivalent was detected at measurable concentrations. The identification of this unknown compound was performed by LC-MS/MS analysis of the extracts from incurred samples. The mass fragmentation of the compound was consistent with the structure of tylosin D (the alcoholic derivative of tylosin A), the major metabolite of tylosin previously recovered and identified in tissues and/or excreta from treated chickens, cattle and pigs.

  3. Studying Kidney Disease Using Tissue and Genome Engineering in Human Pluripotent Stem Cells.

    PubMed

    Garreta, Elena; González, Federico; Montserrat, Núria

    2018-01-01

    Kidney morphogenesis and patterning have been extensively studied in animal models such as the mouse and zebrafish. These seminal studies have been key to define the molecular mechanisms underlying this complex multistep process. Based on this knowledge, the last 3 years have witnessed the development of a cohort of protocols allowing efficient differentiation of human pluripotent stem cells (hPSCs) towards defined kidney progenitor populations using two-dimensional (2D) culture systems or through generating organoids. Kidney organoids are three-dimensional (3D) kidney-like tissues, which are able to partially recapitulate kidney structure and function in vitro. The current possibility to combine state-of-the art tissue engineering with clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated systems 9 (Cas9)-mediated genome engineering provides an unprecedented opportunity for studying kidney disease with hPSCs. Recently, hPSCs with genetic mutations introduced through CRISPR/Cas9-mediated genome engineering have shown to produce kidney organoids able to recapitulate phenotypes of polycystic kidney disease and glomerulopathies. This mini review provides an overview of the most recent advances in differentiation of hPSCs into kidney lineages, and the latest implementation of the CRISPR/Cas9 technology in the organoid setting, as promising platforms to study human kidney development and disease. © 2017 S. Karger AG, Basel.

  4. Evidence of Nonuniformity in Urothelium Barrier Function between the Upper Urinary Tract and Bladder.

    PubMed

    Williams, Nicholas A; Barnard, Luke; Allender, Chris J; Bowen, Jenna L; Gumbleton, Mark; Harrah, Tim; Raja, Aditya; Joshi, Hrishi B

    2016-03-01

    We compared the relative permeability of upper urinary tract and bladder urothelium to mitomycin C. Ex vivo porcine bladder, ureters and kidneys were dissected out and filled with 1 mg ml(-1) mitomycin C. At 60 minutes the organs were emptied and excised tissue samples were sectioned parallel to the urothelium. Sectioned tissue was homogenized and extracted mitomycin C was quantified. Transurothelial permeation across the different urothelia was calculated by normalizing the total amount of drug extracted to the surface area of the tissue sample. Average mitomycin C concentrations at different tissue depths (concentration-depth profiles) were calculated by dividing the total amount of drug recovered by the total weight of tissue. Mitomycin C permeation across the ureteral urothelium was significantly greater than across the bladder and renal pelvis urothelium (9.07 vs 0.94 and 3.61 μg cm(-2), respectively). Concentrations of mitomycin C in the ureter and kidney were markedly higher than those achieved in the bladder at all tissue depths. Average urothelial mitomycin C concentrations were greater than 6.5-fold higher in the ureter and renal pelvis than in the bladder. To our knowledge we report for the first time that the upper urinary tract and bladder show differing permeability to a single drug. Ex vivo porcine ureter is significantly more permeable to mitomycin C than bladder urothelium and consequently higher mitomycin C tissue concentrations can be achieved after topical application. Data in this study correlate with the theory that mammalian upper tract urothelium represents a different cell lineage than that of the bladder and it is innately more permeable to mitomycin C. Copyright © 2016 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

  5. Comparison of microbial growth inhibition screening assays with high-pressure liquid chromatography for detection of experimentally incurred penicillin G residues in calves.

    PubMed

    Musser, Jeffrey M B; Anderson, Kevin L; Boison, Joe O

    2002-01-01

    Twelve calves were fed milk replacer containing 3.33 ppm penicillin G for one feeding, and 12 calves were fed the medicated milk replacer once daily at a rate of 12% of their body weight for 14 days. Two calves served as controls. Calves were slaughtered 4 to 13 hours after being fed. Kidney, liver, muscle, and urine samples were assayed for penicillin by high-pressure liquid chromatography (HPLC). Penicillin G was not detected in any muscle samples and concentrations of penicillin exceeded the tolerance level (0.05 microg/g) in kidney or liver tissue from 13 of 24 treated-calf carcasses examined by HPLC. The Live Animal Swab Test identified all 13 carcasses with violative drug residues. Using kidney as the test matrix, the Swab Test on Premises identified 10 of 13 carcasses with violative drug residues, while the Calf Antibiotic Sulfa Test identified seven of 13 carcasses with violative residues.

  6. Trace and major element levels in rats after oral administration of diesel and biodiesel derived from opium poppy (Papaver somniferum L.) seeds.

    PubMed

    Aksoy, Laçine; Sözbilir, Nalan Bayşu

    2015-10-01

    The study investigated the toxic effects of diesel and biodiesel derived from opium poppy (Papaver somniferum L.) oil seeds on the trace and major elements in kidney, lung, liver, and serum of rats. By the end of 21 days, trace and major element concentrations in kidney, lung, and liver tissues and the serum were measured using inductively coupled plasma-optical emission spectroscopy. We observed that trace and major element levels in kidney, lung, and liver tissues and the serum changed. Especially, important differences were detected in trace and major element concentrations in kidney and lung tissues. In kidney tissue, the concentration differences of calcium, sodium, and zinc (Zn) were found between diesel and biodiesel groups. In lung tissue, the concentration differences of cadmium, lithium, magnesium, manganese, and Zn were found between diesel and biodiesel groups. Among the significant findings, Zn concentration in serum and liver tissue of diesel and biodiesel were different from control (p < 0.05). However, the metal levels of biodiesel group were similar to control group. Due to lesser toxicity of biodiesel, it could be considered as an alternate fuel. © The Author(s) 2013.

  7. Genetic associations at 53 loci highlight cell types and biological pathways relevant for kidney function.

    PubMed

    Pattaro, Cristian; Teumer, Alexander; Gorski, Mathias; Chu, Audrey Y; Li, Man; Mijatovic, Vladan; Garnaas, Maija; Tin, Adrienne; Sorice, Rossella; Li, Yong; Taliun, Daniel; Olden, Matthias; Foster, Meredith; Yang, Qiong; Chen, Ming-Huei; Pers, Tune H; Johnson, Andrew D; Ko, Yi-An; Fuchsberger, Christian; Tayo, Bamidele; Nalls, Michael; Feitosa, Mary F; Isaacs, Aaron; Dehghan, Abbas; d'Adamo, Pio; Adeyemo, Adebowale; Dieffenbach, Aida Karina; Zonderman, Alan B; Nolte, Ilja M; van der Most, Peter J; Wright, Alan F; Shuldiner, Alan R; Morrison, Alanna C; Hofman, Albert; Smith, Albert V; Dreisbach, Albert W; Franke, Andre; Uitterlinden, Andre G; Metspalu, Andres; Tonjes, Anke; Lupo, Antonio; Robino, Antonietta; Johansson, Åsa; Demirkan, Ayse; Kollerits, Barbara; Freedman, Barry I; Ponte, Belen; Oostra, Ben A; Paulweber, Bernhard; Krämer, Bernhard K; Mitchell, Braxton D; Buckley, Brendan M; Peralta, Carmen A; Hayward, Caroline; Helmer, Catherine; Rotimi, Charles N; Shaffer, Christian M; Müller, Christian; Sala, Cinzia; van Duijn, Cornelia M; Saint-Pierre, Aude; Ackermann, Daniel; Shriner, Daniel; Ruggiero, Daniela; Toniolo, Daniela; Lu, Yingchang; Cusi, Daniele; Czamara, Darina; Ellinghaus, David; Siscovick, David S; Ruderfer, Douglas; Gieger, Christian; Grallert, Harald; Rochtchina, Elena; Atkinson, Elizabeth J; Holliday, Elizabeth G; Boerwinkle, Eric; Salvi, Erika; Bottinger, Erwin P; Murgia, Federico; Rivadeneira, Fernando; Ernst, Florian; Kronenberg, Florian; Hu, Frank B; Navis, Gerjan J; Curhan, Gary C; Ehret, George B; Homuth, Georg; Coassin, Stefan; Thun, Gian-Andri; Pistis, Giorgio; Gambaro, Giovanni; Malerba, Giovanni; Montgomery, Grant W; Eiriksdottir, Gudny; Jacobs, Gunnar; Li, Guo; Wichmann, H-Erich; Campbell, Harry; Schmidt, Helena; Wallaschofski, Henri; Völzke, Henry; Brenner, Hermann; Kroemer, Heyo K; Kramer, Holly; Lin, Honghuang; Leach, I Mateo; Ford, Ian; Guessous, Idris; Rudan, Igor; Prokopenko, Inga; Borecki, Ingrid; Heid, Iris M; Kolcic, Ivana; Persico, Ivana; Jukema, J Wouter; Wilson, James F; Felix, Janine F; Divers, Jasmin; Lambert, Jean-Charles; Stafford, Jeanette M; Gaspoz, Jean-Michel; Smith, Jennifer A; Faul, Jessica D; Wang, Jie Jin; Ding, Jingzhong; Hirschhorn, Joel N; Attia, John; Whitfield, John B; Chalmers, John; Viikari, Jorma; Coresh, Josef; Denny, Joshua C; Karjalainen, Juha; Fernandes, Jyotika K; Endlich, Karlhans; Butterbach, Katja; Keene, Keith L; Lohman, Kurt; Portas, Laura; Launer, Lenore J; Lyytikäinen, Leo-Pekka; Yengo, Loic; Franke, Lude; Ferrucci, Luigi; Rose, Lynda M; Kedenko, Lyudmyla; Rao, Madhumathi; Struchalin, Maksim; Kleber, Marcus E; Cavalieri, Margherita; Haun, Margot; Cornelis, Marilyn C; Ciullo, Marina; Pirastu, Mario; de Andrade, Mariza; McEvoy, Mark A; Woodward, Mark; Adam, Martin; Cocca, Massimiliano; Nauck, Matthias; Imboden, Medea; Waldenberger, Melanie; Pruijm, Menno; Metzger, Marie; Stumvoll, Michael; Evans, Michele K; Sale, Michele M; Kähönen, Mika; Boban, Mladen; Bochud, Murielle; Rheinberger, Myriam; Verweij, Niek; Bouatia-Naji, Nabila; Martin, Nicholas G; Hastie, Nick; Probst-Hensch, Nicole; Soranzo, Nicole; Devuyst, Olivier; Raitakari, Olli; Gottesman, Omri; Franco, Oscar H; Polasek, Ozren; Gasparini, Paolo; Munroe, Patricia B; Ridker, Paul M; Mitchell, Paul; Muntner, Paul; Meisinger, Christa; Smit, Johannes H; Kovacs, Peter; Wild, Philipp S; Froguel, Philippe; Rettig, Rainer; Mägi, Reedik; Biffar, Reiner; Schmidt, Reinhold; Middelberg, Rita P S; Carroll, Robert J; Penninx, Brenda W; Scott, Rodney J; Katz, Ronit; Sedaghat, Sanaz; Wild, Sarah H; Kardia, Sharon L R; Ulivi, Sheila; Hwang, Shih-Jen; Enroth, Stefan; Kloiber, Stefan; Trompet, Stella; Stengel, Benedicte; Hancock, Stephen J; Turner, Stephen T; Rosas, Sylvia E; Stracke, Sylvia; Harris, Tamara B; Zeller, Tanja; Zemunik, Tatijana; Lehtimäki, Terho; Illig, Thomas; Aspelund, Thor; Nikopensius, Tiit; Esko, Tonu; Tanaka, Toshiko; Gyllensten, Ulf; Völker, Uwe; Emilsson, Valur; Vitart, Veronique; Aalto, Ville; Gudnason, Vilmundur; Chouraki, Vincent; Chen, Wei-Min; Igl, Wilmar; März, Winfried; Koenig, Wolfgang; Lieb, Wolfgang; Loos, Ruth J F; Liu, Yongmei; Snieder, Harold; Pramstaller, Peter P; Parsa, Afshin; O'Connell, Jeffrey R; Susztak, Katalin; Hamet, Pavel; Tremblay, Johanne; de Boer, Ian H; Böger, Carsten A; Goessling, Wolfram; Chasman, Daniel I; Köttgen, Anna; Kao, W H Linda; Fox, Caroline S

    2016-01-21

    Reduced glomerular filtration rate defines chronic kidney disease and is associated with cardiovascular and all-cause mortality. We conducted a meta-analysis of genome-wide association studies for estimated glomerular filtration rate (eGFR), combining data across 133,413 individuals with replication in up to 42,166 individuals. We identify 24 new and confirm 29 previously identified loci. Of these 53 loci, 19 associate with eGFR among individuals with diabetes. Using bioinformatics, we show that identified genes at eGFR loci are enriched for expression in kidney tissues and in pathways relevant for kidney development and transmembrane transporter activity, kidney structure, and regulation of glucose metabolism. Chromatin state mapping and DNase I hypersensitivity analyses across adult tissues demonstrate preferential mapping of associated variants to regulatory regions in kidney but not extra-renal tissues. These findings suggest that genetic determinants of eGFR are mediated largely through direct effects within the kidney and highlight important cell types and biological pathways.

  8. Genetic associations at 53 loci highlight cell types and biological pathways relevant for kidney function

    PubMed Central

    Pattaro, Cristian; Teumer, Alexander; Gorski, Mathias; Chu, Audrey Y.; Li, Man; Mijatovic, Vladan; Garnaas, Maija; Tin, Adrienne; Sorice, Rossella; Li, Yong; Taliun, Daniel; Olden, Matthias; Foster, Meredith; Yang, Qiong; Chen, Ming-Huei; Pers, Tune H.; Johnson, Andrew D.; Ko, Yi-An; Fuchsberger, Christian; Tayo, Bamidele; Nalls, Michael; Feitosa, Mary F.; Isaacs, Aaron; Dehghan, Abbas; d'Adamo, Pio; Adeyemo, Adebowale; Dieffenbach, Aida Karina; Zonderman, Alan B.; Nolte, Ilja M.; van der Most, Peter J.; Wright, Alan F.; Shuldiner, Alan R.; Morrison, Alanna C.; Hofman, Albert; Smith, Albert V.; Dreisbach, Albert W.; Franke, Andre; Uitterlinden, Andre G.; Metspalu, Andres; Tonjes, Anke; Lupo, Antonio; Robino, Antonietta; Johansson, Åsa; Demirkan, Ayse; Kollerits, Barbara; Freedman, Barry I.; Ponte, Belen; Oostra, Ben A.; Paulweber, Bernhard; Krämer, Bernhard K.; Mitchell, Braxton D.; Buckley, Brendan M.; Peralta, Carmen A.; Hayward, Caroline; Helmer, Catherine; Rotimi, Charles N.; Shaffer, Christian M.; Müller, Christian; Sala, Cinzia; van Duijn, Cornelia M.; Saint-Pierre, Aude; Ackermann, Daniel; Shriner, Daniel; Ruggiero, Daniela; Toniolo, Daniela; Lu, Yingchang; Cusi, Daniele; Czamara, Darina; Ellinghaus, David; Siscovick, David S.; Ruderfer, Douglas; Gieger, Christian; Grallert, Harald; Rochtchina, Elena; Atkinson, Elizabeth J.; Holliday, Elizabeth G.; Boerwinkle, Eric; Salvi, Erika; Bottinger, Erwin P.; Murgia, Federico; Rivadeneira, Fernando; Ernst, Florian; Kronenberg, Florian; Hu, Frank B.; Navis, Gerjan J.; Curhan, Gary C.; Ehret, George B.; Homuth, Georg; Coassin, Stefan; Thun, Gian-Andri; Pistis, Giorgio; Gambaro, Giovanni; Malerba, Giovanni; Montgomery, Grant W.; Eiriksdottir, Gudny; Jacobs, Gunnar; Li, Guo; Wichmann, H-Erich; Campbell, Harry; Schmidt, Helena; Wallaschofski, Henri; Völzke, Henry; Brenner, Hermann; Kroemer, Heyo K.; Kramer, Holly; Lin, Honghuang; Leach, I. Mateo; Ford, Ian; Guessous, Idris; Rudan, Igor; Prokopenko, Inga; Borecki, Ingrid; Heid, Iris M.; Kolcic, Ivana; Persico, Ivana; Jukema, J. Wouter; Wilson, James F.; Felix, Janine F.; Divers, Jasmin; Lambert, Jean-Charles; Stafford, Jeanette M.; Gaspoz, Jean-Michel; Smith, Jennifer A.; Faul, Jessica D.; Wang, Jie Jin; Ding, Jingzhong; Hirschhorn, Joel N.; Attia, John; Whitfield, John B.; Chalmers, John; Viikari, Jorma; Coresh, Josef; Denny, Joshua C.; Karjalainen, Juha; Fernandes, Jyotika K.; Endlich, Karlhans; Butterbach, Katja; Keene, Keith L.; Lohman, Kurt; Portas, Laura; Launer, Lenore J.; Lyytikäinen, Leo-Pekka; Yengo, Loic; Franke, Lude; Ferrucci, Luigi; Rose, Lynda M.; Kedenko, Lyudmyla; Rao, Madhumathi; Struchalin, Maksim; Kleber, Marcus E.; Cavalieri, Margherita; Haun, Margot; Cornelis, Marilyn C.; Ciullo, Marina; Pirastu, Mario; de Andrade, Mariza; McEvoy, Mark A.; Woodward, Mark; Adam, Martin; Cocca, Massimiliano; Nauck, Matthias; Imboden, Medea; Waldenberger, Melanie; Pruijm, Menno; Metzger, Marie; Stumvoll, Michael; Evans, Michele K.; Sale, Michele M.; Kähönen, Mika; Boban, Mladen; Bochud, Murielle; Rheinberger, Myriam; Verweij, Niek; Bouatia-Naji, Nabila; Martin, Nicholas G.; Hastie, Nick; Probst-Hensch, Nicole; Soranzo, Nicole; Devuyst, Olivier; Raitakari, Olli; Gottesman, Omri; Franco, Oscar H.; Polasek, Ozren; Gasparini, Paolo; Munroe, Patricia B.; Ridker, Paul M.; Mitchell, Paul; Muntner, Paul; Meisinger, Christa; Smit, Johannes H.; Abecasis, Goncalo R.; Adair, Linda S.; Alexander, Myriam; Altshuler, David; Amin, Najaf; Arking, Dan E.; Arora, Pankaj; Aulchenko, Yurii; Bakker, Stephan J. L.; Bandinelli, Stefania; Barroso, Ines; Beckmann, Jacques S.; Beilby, John P.; Bergman, Richard N.; Bergmann, Sven; Bis, Joshua C.; Boehnke, Michael; Bonnycastle, Lori L.; Bornstein, Stefan R.; Bots, Michiel L.; Bragg-Gresham, Jennifer L.; Brand, Stefan-Martin; Brand, Eva; Braund, Peter S.; Brown, Morris J.; Burton, Paul R.; Casas, Juan P.; Caulfield, Mark J.; Chakravarti, Aravinda; Chambers, John C.; Chandak, Giriraj R.; Chang, Yen-Pei C.; Charchar, Fadi J.; Chaturvedi, Nish; Shin Cho, Yoon; Clarke, Robert; Collins, Francis S.; Collins, Rory; Connell, John M.; Cooper, Jackie A.; Cooper, Matthew N.; Cooper, Richard S.; Corsi, Anna Maria; Dörr, Marcus; Dahgam, Santosh; Danesh, John; Smith, George Davey; Day, Ian N. M.; Deloukas, Panos; Denniff, Matthew; Dominiczak, Anna F.; Dong, Yanbin; Doumatey, Ayo; Elliott, Paul; Elosua, Roberto; Erdmann, Jeanette; Eyheramendy, Susana; Farrall, Martin; Fava, Cristiano; Forrester, Terrence; Fowkes, F. Gerald R.; Fox, Ervin R.; Frayling, Timothy M.; Galan, Pilar; Ganesh, Santhi K.; Garcia, Melissa; Gaunt, Tom R.; Glazer, Nicole L.; Go, Min Jin; Goel, Anuj; Grässler, Jürgen; Grobbee, Diederick E.; Groop, Leif; Guarrera, Simonetta; Guo, Xiuqing; Hadley, David; Hamsten, Anders; Han, Bok-Ghee; Hardy, Rebecca; Hartikainen, Anna-Liisa; Heath, Simon; Heckbert, Susan R.; Hedblad, Bo; Hercberg, Serge; Hernandez, Dena; Hicks, Andrew A.; Hilton, Gina; Hingorani, Aroon D.; Bolton, Judith A Hoffman; Hopewell, Jemma C.; Howard, Philip; Humphries, Steve E.; Hunt, Steven C.; Hveem, Kristian; Ikram, M. Arfan; Islam, Muhammad; Iwai, Naoharu; Jarvelin, Marjo-Riitta; Jackson, Anne U.; Jafar, Tazeen H.; Janipalli, Charles S.; Johnson, Toby; Kathiresan, Sekar; Khaw, Kay-Tee; Kim, Hyung-Lae; Kinra, Sanjay; Kita, Yoshikuni; Kivimaki, Mika; Kooner, Jaspal S.; Kumar, M. J. Kranthi; Kuh, Diana; Kulkarni, Smita R.; Kumari, Meena; Kuusisto, Johanna; Kuznetsova, Tatiana; Laakso, Markku; Laan, Maris; Laitinen, Jaana; Lakatta, Edward G.; Langefeld, Carl D.; Larson, Martin G.; Lathrop, Mark; Lawlor, Debbie A.; Lawrence, Robert W.; Lee, Jong-Young; Lee, Nanette R.; Levy, Daniel; Li, Yali; Longstreth, Will T.; Luan, Jian'an; Lucas, Gavin; Ludwig, Barbara; Mangino, Massimo; Mani, K. Radha; Marmot, Michael G.; Mattace-Raso, Francesco U. S.; Matullo, Giuseppe; McArdle, Wendy L.; McKenzie, Colin A.; Meitinger, Thomas; Melander, Olle; Meneton, Pierre; Meschia, James F.; Miki, Tetsuro; Milaneschi, Yuri; Mohlke, Karen L.; Mooser, Vincent; Morken, Mario A.; Morris, Richard W.; Mosley, Thomas H.; Najjar, Samer; Narisu, Narisu; Newton-Cheh, Christopher; Nguyen, Khanh-Dung Hoang; Nilsson, Peter; Nyberg, Fredrik; O'Donnell, Christopher J.; Ogihara, Toshio; Ohkubo, Takayoshi; Okamura, Tomonori; Ong, RickTwee-Hee; Ongen, Halit; Onland-Moret, N. Charlotte; O'Reilly, Paul F.; Org, Elin; Orru, Marco; Palmas, Walter; Palmen, Jutta; Palmer, Lyle J.; Palmer, Nicholette D.; Parker, Alex N.; Peden, John F.; Peltonen, Leena; Perola, Markus; Pihur, Vasyl; Platou, Carl G. P.; Plump, Andrew; Prabhakaran, Dorairajan; Psaty, Bruce M.; Raffel, Leslie J.; Rao, Dabeeru C.; Rasheed, Asif; Ricceri, Fulvio; Rice, Kenneth M.; Rosengren, Annika; Rotter, Jerome I.; Rudock, Megan E.; Sõber, Siim; Salako, Tunde; Saleheen, Danish; Salomaa, Veikko; Samani, Nilesh J.; Schwartz, Steven M.; Schwarz, Peter E. H.; Scott, Laura J.; Scott, James; Scuteri, Angelo; Sehmi, Joban S.; Seielstad, Mark; Seshadri, Sudha; Sharma, Pankaj; Shaw-Hawkins, Sue; Shi, Gang; Shrine, Nick R. G.; Sijbrands, Eric J. G.; Sim, Xueling; Singleton, Andrew; Sjögren, Marketa; Smith, Nicholas L.; Artigas, Maria Soler; Spector, Tim D.; Staessen, Jan A.; Stancakova, Alena; Steinle, Nanette I.; Strachan, David P.; Stringham, Heather M.; Sun, Yan V.; Swift, Amy J.; Tabara, Yasuharu; Tai, E-Shyong; Talmud, Philippa J.; Taylor, Andrew; Terzic, Janos; Thelle, Dag S.; Tobin, Martin D.; Tomaszewski, Maciej; Tripathy, Vikal; Tuomilehto, Jaakko; Tzoulaki, Ioanna; Uda, Manuela; Ueshima, Hirotsugu; Uiterwaal, Cuno S. P. M.; Umemura, Satoshi; van der Harst, Pim; van der Schouw, Yvonne T.; van Gilst, Wiek H.; Vartiainen, Erkki; Vasan, Ramachandran S.; Veldre, Gudrun; Verwoert, Germaine C.; Viigimaa, Margus; Vinay, D. G.; Vineis, Paolo; Voight, Benjamin F.; Vollenweider, Peter; Wagenknecht, Lynne E.; Wain, Louise V.; Wang, Xiaoling; Wang, Thomas J.; Wareham, Nicholas J.; Watkins, Hugh; Weder, Alan B.; Whincup, Peter H.; Wiggins, Kerri L.; Witteman, Jacqueline C. M.; Wong, Andrew; Wu, Ying; Yajnik, Chittaranjan S.; Yao, Jie; Young, J. H.; Zelenika, Diana; Zhai, Guangju; Zhang, Weihua; Zhang, Feng; Zhao, Jing Hua; Zhu, Haidong; Zhu, Xiaofeng; Zitting, Paavo; Zukowska-Szczechowska, Ewa; Okada, Yukinori; Wu, Jer-Yuarn; Gu, Dongfeng; Takeuchi, Fumihiko; Takahashi, Atsushi; Maeda, Shiro; Tsunoda, Tatsuhiko; Chen, Peng; Lim, Su-Chi; Wong, Tien-Yin; Liu, Jianjun; Young, Terri L.; Aung, Tin; Teo, Yik-Ying; Kim, Young Jin; Kang, Daehee; Chen, Chien-Hsiun; Tsai, Fuu-Jen; Chang, Li-Ching; Fann, S. -J. Cathy; Mei, Hao; Hixson, James E.; Chen, Shufeng; Katsuya, Tomohiro; Isono, Masato; Albrecht, Eva; Yamamoto, Kazuhiko; Kubo, Michiaki; Nakamura, Yusuke; Kamatani, Naoyuki; Kato, Norihiro; He, Jiang; Chen, Yuan-Tsong; Tanaka, Toshihiro; Reilly, Muredach P; Schunkert, Heribert; Assimes, Themistocles L.; Hall, Alistair; Hengstenberg, Christian; König, Inke R.; Laaksonen, Reijo; McPherson, Ruth; Thompson, John R.; Thorsteinsdottir, Unnur; Ziegler, Andreas; Absher, Devin; Chen, Li; Cupples13, L. Adrienne; Halperin, Eran; Li, Mingyao; Musunuru, Kiran; Preuss, Michael; Schillert, Arne; Thorleifsson, Gudmar; Wells, George A.; Holm, Hilma; Roberts, Robert; Stewart, Alexandre F. R.; Fortmann, Stephen; Go, Alan; Hlatky, Mark; Iribarren, Carlos; Knowles, Joshua; Myers, Richard; Quertermous, Thomas; Sidney, Steven; Risch, Neil; Tang, Hua; Blankenberg, Stefan; Schnabel, Renate; Sinning, Christoph; Lackner, Karl J.; Tiret, Laurence; Nicaud, Viviane; Cambien, Francois; Bickel, Christoph; Rupprecht, Hans J.; Perret, Claire; Proust, Carole; Münzel, Thomas F.; Barbalic, Maja; Chen, Ida Yii-Der; Demissie-Banjaw, Serkalem; Folsom, Aaron; Lumley, Thomas; Marciante, Kristin; Taylor, Kent D.; Volcik, Kelly; Gretarsdottir, Solveig; Gulcher, Jeffrey R.; Kong, Augustine; Stefansson, Kari; Thorgeirsson, Gudmundur; Andersen, Karl; Fischer, Marcus; Grosshennig, Anika; Linsel-Nitschke, Patrick; Stark, Klaus; Schreiber, Stefan; Aherrahrou, Zouhair; Bruse, Petra; Doering, Angela; Klopp, Norman; Diemert, Patrick; Loley, Christina; Medack, Anja; Nahrstedt, Janja; Peters, Annette; Wagner, Arnika K.; Willenborg, Christina; Böhm, Bernhard O.; Dobnig, Harald; Grammer, Tanja B.; Hoffmann, Michael M.; Meinitzer, Andreas; Winkelmann, Bernhard R.; Pilz, Stefan; Renner, Wilfried; Scharnagl, Hubert; Stojakovic, Tatjana; Tomaschitz, Andreas; Winkler, Karl; Guiducci, Candace; Burtt, Noel; Gabriel, Stacey B.; Dandona, Sonny; Jarinova, Olga; Qu, Liming; Wilensky, Robert; Matthai, William; Hakonarson, Hakon H.; Devaney, Joe; Burnett, Mary Susan; Pichard, Augusto D.; Kent, Kenneth M.; Satler, Lowell; Lindsay, Joseph M.; Waksman, Ron; Knouff, Christopher W.; Waterworth, Dawn M.; Walker, Max C.; Epstein, Stephen E.; Rader, Daniel J.; Nelson, Christopher P.; Wright, Benjamin J.; Balmforth, Anthony J.; Ball, Stephen G.; Loehr, Laura R.; Rosamond, Wayne D.; Benjamin, Emelia; Haritunians, Talin; Couper, David; Murabito, Joanne; Wang, Ying A.; Stricker, Bruno H.; Chang, Patricia P.; Willerson, James T.; Felix, Stephan B.; Watzinger, Norbert; Aragam, Jayashri; Zweiker, Robert; Lind, Lars; Rodeheffer, Richard J.; Greiser, Karin Halina; Deckers, Jaap W.; Stritzke, Jan; Ingelsson, Erik; Kullo, Iftikhar; Haerting, Johannes; Reffelmann, Thorsten; Redfield, Margaret M.; Werdan, Karl; Mitchell, Gary F.; Arnett, Donna K.; Gottdiener, John S.; Blettner, Maria; Friedrich, Nele; Kovacs, Peter; Wild, Philipp S.; Froguel, Philippe; Rettig, Rainer; Mägi, Reedik; Biffar, Reiner; Schmidt, Reinhold; Middelberg, Rita P. S.; Carroll, Robert J.; Penninx, Brenda W.; Scott, Rodney J.; Katz, Ronit; Sedaghat, Sanaz; Wild, Sarah H.; Kardia, Sharon L. R.; Ulivi, Sheila; Hwang, Shih-Jen; Enroth, Stefan; Kloiber, Stefan; Trompet, Stella; Stengel, Benedicte; Hancock, Stephen J.; Turner, Stephen T.; Rosas, Sylvia E.; Stracke, Sylvia; Harris, Tamara B.; Zeller, Tanja; Zemunik, Tatijana; Lehtimäki, Terho; Illig, Thomas; Aspelund, Thor; Nikopensius, Tiit; Esko, Tonu; Tanaka, Toshiko; Gyllensten, Ulf; Völker, Uwe; Emilsson, Valur; Vitart, Veronique; Aalto, Ville; Gudnason, Vilmundur; Chouraki, Vincent; Chen, Wei-Min; Igl, Wilmar; März, Winfried; Koenig, Wolfgang; Lieb, Wolfgang; Loos, Ruth J. F.; Liu, Yongmei; Snieder, Harold; Pramstaller, Peter P.; Parsa, Afshin; O'Connell, Jeffrey R.; Susztak, Katalin; Hamet, Pavel; Tremblay, Johanne; de Boer, Ian H.; Böger, Carsten A.; Goessling, Wolfram; Chasman, Daniel I.; Köttgen, Anna; Kao, W. H. Linda; Fox, Caroline S.

    2016-01-01

    Reduced glomerular filtration rate defines chronic kidney disease and is associated with cardiovascular and all-cause mortality. We conducted a meta-analysis of genome-wide association studies for estimated glomerular filtration rate (eGFR), combining data across 133,413 individuals with replication in up to 42,166 individuals. We identify 24 new and confirm 29 previously identified loci. Of these 53 loci, 19 associate with eGFR among individuals with diabetes. Using bioinformatics, we show that identified genes at eGFR loci are enriched for expression in kidney tissues and in pathways relevant for kidney development and transmembrane transporter activity, kidney structure, and regulation of glucose metabolism. Chromatin state mapping and DNase I hypersensitivity analyses across adult tissues demonstrate preferential mapping of associated variants to regulatory regions in kidney but not extra-renal tissues. These findings suggest that genetic determinants of eGFR are mediated largely through direct effects within the kidney and highlight important cell types and biological pathways. PMID:26831199

  9. Lesions in mink (Mustela vison) infected with giant kidney worm (Dioctophyma renale).

    PubMed

    Mace, T F

    1976-01-01

    Adult Dioctophyma renale occupied the enlarged renal pelvis of the right kidney of naturally infected mink. Lesions in the kidney parenchyma consisted of connective tissue proliferation in the interstitial tissue, tubular atrophy and fibrosis, and periglomerular fibrosis. The luminal surface of the renal pelvis wall was formed of numerous papillae covered with transitional epithelium. The nematodes in the lumen were bathed in an albuminous fluid containing red blood cells, epithelial cells and D. renale eggs. The left (uninfected) kidney was 60% larger than the left kidney of normal mink.

  10. Characterization and localization of /sup 3/H-arginine8-vasopressin binding to rat kidney and brain tissue

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

    Dorsa, D.M.; Majumdar, L.A.; Petracca, F.M.

    Anatomic, behavioral and pharmacologic evidence suggests that arginine8-vasopressin (AVP) serves as a CNS neurotransmitter or neuromodulator. AVP binding to membrane and tissue slice preparations from brain and kidney was characterized, and the anatomical distribution of these binding sites was examined. Conditions for the binding assay were optimized using kidney medullary tissue. Binding of /sup 3/H-AVP (S.A. . 30-51 Ci/mmol, NEN) to brain and kidney membranes and tissue slices was saturable, temperature dependent, linearly related to protein concentration (or number of tissue slices), reversible, and specific since the ability of cold AVP to displace /sup 3/H-AVP from binding was greater thanmore » oxytocin and other related peptide fragments. Autoradiographic localization of /sup 3/H-AVP binding was restricted to kidney medullary tissue. In brain tissue, /sup 3/H-AVP binding was found to occur in concentrated foci. Brainstem areas such as the nucleus tractus solitarius (NTS) showed a high density of AVP binding sites. Since local injections of AVP into the NTS have been shown to influence blood pressure, the present study presents the first anatomical evidence for the presence of AVP specific binding sites which might mediate this effect.« less

  11. Expression of transforming growth factor alpha and epidermal growth factor receptor messenger RNA in neoplastic and nonneoplastic human kidney tissue.

    PubMed

    Mydlo, J H; Michaeli, J; Cordon-Cardo, C; Goldenberg, A S; Heston, W D; Fair, W R

    1989-06-15

    Using Northern blot analysis, we have demonstrated that mRNA for transforming growth factor alpha (TGF-alpha) was expressed in five malignant kidney tissue specimens but was not detected in their autologous nonneoplastic homologues. In addition, the expression of epidermal growth factor (EGF) receptor mRNA in these malignant tissues was 2- to 3-fold greater than in nontransformed tissues. In two cases examined using immunohistochemistry, we were able to correlate the increased expression of the mRNA with an increase in protein expression. Since TGF-alpha is known to bind to the EGF receptor, the finding of an increased expression of both TGF-alpha and EGF receptor mRNA in kidney tumor tissue suggests that interaction between TGF-alpha and the EGF receptor may play a role in promoting transformation and/or proliferation of kidney neoplasms, perhaps by an autocrine mechanism.

  12. [Gene expression analyses of kidney biopsies: the European renal cDNA bank--Kröner-Fresenius biopsy bank].

    PubMed

    Cohen, C D; Kretzler, M

    2009-03-01

    Histological analysis of kidney biopsies is an essential part of our current diagnostic workup of patients with renal disease. Besides the already established diagnostic tools, new methods allow extensive analysis of the sample tissue's gene expression. Using results from a European multicenter study on gene expression analysis of renal biopsies, in this review we demonstrate that this novel approach not only expands the scope of so-called basic research but also might supplement future biopsy diagnostics. The goals are improved diagnosis and more specific therapy choice and prognosis estimates.

  13. Peptide Regulation of Cells Renewal Processes in Kidney Tissue Cultures from Young and Old Animals.

    PubMed

    Chalisova, N I; Lin'kova, N S; Nichik, T E; Ryzhak, A P; Dudkov, A V; Ryzhak, G A

    2015-05-01

    Polypeptide complex isolated from calf kidneys stimulates the processes of cell renewal in organotypic kidney tissue cultures from young and old rats. The polypeptide complex enhances expression of proliferation marker Ki-67 and reduces expression of proapoptotic peptide p53 in kidney explants obtained from young and old animals. Short peptides T-31 (AED) and T-35 (EDL) also stimulate proliferation and reduce apoptosis of the kidney cells, but to a lesser degree than the polypeptide complex. The results provide the basis for further investigation of the polypeptide complex as a preparation for the therapy of kidney diseases, including age-related pathologies.

  14. Cyanobacteria and cyanotoxins in fishponds and their effects on fish tissue.

    PubMed

    Drobac, Damjana; Tokodi, Nada; Lujić, Jelena; Marinović, Zoran; Subakov-Simić, Gordana; Dulić, Tamara; Važić, Tamara; Nybom, Sonja; Meriluoto, Jussi; Codd, Geoffrey A; Svirčev, Zorica

    2016-05-01

    Cyanobacteria can produce toxic metabolites known as cyanotoxins. Common and frequently investigated cyanotoxins include microcystins (MCs), nodularin (NOD) and saxitoxins (STXs). During the summer of 2011 extensive cyanobacterial growth was found in several fishponds in Serbia. Sampling of the water and fish (common carp, Cyprinus carpio) was performed. Water samples from 13 fishponds were found to contain saxitoxin, microcystin, and/or nodularin. LC-MS/MS showed that MC-RR was present in samples of fish muscle tissue. Histopathological analyses of fish grown in fishponds with cyanotoxin production showed histopathological damage to liver, kidney, gills, intestines and muscle tissues. This study is among the first so far to report severe hyperplasia of intestinal epithelium and severe degeneration of muscle tissue of fish after cyanobacterial exposure. These findings emphasize the importance of cyanobacterial and cyanotoxin monitoring in fishponds in order to recognize cyanotoxins and their potential effects on fish used for human consumption and, further, on human health. Copyright © 2016 Elsevier B.V. All rights reserved.

  15. Thalidomide Ameliorates Inflammation and Vascular Injury but Aggravates Tubular Damage in the Irradiated Mouse Kidney

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

    Scharpfenecker, Marion, E-mail: m.scharpfenecker@nki.nl; Floot, Ben; Russell, Nicola S.

    Purpose: The late side effects of kidney irradiation include vascular damage and fibrosis, which are promoted by an irradiation-induced inflammatory response. We therefore treated kidney-irradiated mice with the anti-inflammatory and angiogenesis-modulating drug thalidomide in an attempt to prevent the development of late normal tissue damage and radiation nephropathy in the mouse kidney. Methods and Materials: Kidneys of C57Bl/6 mice were irradiated with a single dose of 14 Gy. Starting from week 16 after irradiation, the mice were fed with thalidomide-containing chow (100 mg/kg body weight/day). Gene expression and kidney histology were analyzed at 40 weeks and blood samples at 10, 20, 30, andmore » 40 weeks after irradiation. Results: Thalidomide improved the vascular structure and vessel perfusion after irradiation, associated with a normalization of pericyte coverage. The drug also reduced infiltration of inflammatory cells but could not suppress the development of fibrosis. Irradiation-induced changes in hematocrit and blood urea nitrogen levels were not rescued by thalidomide. Moreover, thalidomide worsened tubular damage after irradiation and also negatively affected basal tubular function. Conclusions: Thalidomide improved the inflammatory and vascular side effects of kidney irradiation but could not reverse tubular toxicity, which probably prevented preservation of kidney function.« less

  16. Pathological analysis, detection of antigens, FasL expression analysis and leucocytes survival analysis in tilapia (Oreochromis niloticus) after infection with green fluorescent protein labeled Streptococcus agalactiae.

    PubMed

    Wang, Jingyuan; Wu, Jinying; Yi, Liyuan; Hou, Zengxin; Li, Wensheng

    2017-03-01

    The pathogenesis of Streptococcus agalactiae infection in tilapia has not been fully described. To understand this, we investigated the clinic-pathological features of acute experimental septicemia in tilapia (Oreochromis niloticus) after receiving an intra-peritoneal injection with S. agalactiae THN-1901GFP. Immunohistochemistry and sections of pathological tissues were used to estimate the level of damage in the head-kidney, liver, spleen and trunk-kidney. The expression of FasL was analyzed by western blotting in these samples based on their damage levels. Leucocytes were isolated from the head-kidney and incubated with S. agalactiae THN-1901GFP. Then, phagocytosis, programmed cell death and the expression of FasL were analyzed. The infected tissues showed varying degrees of necrosis and histolysis. The serous membrane of the intestine was dissolved by S. agalactiae THN-1901GFP. Antigens of S. agalactiae THN-1901GFP accumulated in different parts of the infected organs. In the head-kidney and spleen, the expression of FasL was up-regulated in parallel with increased tissue damage. After being incubated with S. agalactiae THN-1901GFP, the phagocytic capacity and ability were both very high and the expression of FasL remained high in leucocytes. S. agalactiae THN-1901GFP was able to survive for a long period of time after being engulfed by phagocytic cells. These findings offer insight into the pathogenesis of S. agalactiae infection in tilapia. Copyright © 2017 Elsevier Ltd. All rights reserved.

  17. Predilection sites for Toxoplasma gondii in sheep tissues revealed by magnetic capture and real-time PCR detection.

    PubMed

    Juránková, Jana; Basso, Walter; Neumayerová, Helena; Frencová, Anita; Baláž, Vojtech; Deplazes, Peter; Koudela, Břetislav

    2015-12-01

    Undercooked lamb and mutton are common sources of Toxoplasma gondii infection for humans. A sequence specific magnetic capture technique in combination with quantitative real-time PCR targeting the 529 bp repeat element of T. gondii was used for estimation of the parasite burdens in various sheep tissues (n = 6) three months after peroral experimental inoculation with 10,000 T. gondii oocysts. Brain was the most frequently affected organ (positive in all 6 sheep) and showed the highest estimated parasite loads (0.5-30,913 parasites/g tissue). Lung samples were positive in three sheep, with load estimates of 36.3 to <1 parasite/g tissue. Heart tissue was positive in three sheep and kidney only in one animal with low parasite loads (<1 parasite/g tissue). Only few skeletal muscle samples in 2 animals showed positive results, with very low parasite burdens, while samples from further internal organs (i.e. liver and spleen) were negative in all animals. This study identified the brain as the most important predilection site and therefore the most appropriate tissue for T. gondii detection. Copyright © 2015 Elsevier Ltd. All rights reserved.

  18. Automatic 3D kidney segmentation based on shape constrained GC-OAAM

    NASA Astrophysics Data System (ADS)

    Chen, Xinjian; Summers, Ronald M.; Yao, Jianhua

    2011-03-01

    The kidney can be classified into three main tissue types: renal cortex, renal medulla and renal pelvis (or collecting system). Dysfunction of different renal tissue types may cause different kidney diseases. Therefore, accurate and efficient segmentation of kidney into different tissue types plays a very important role in clinical research. In this paper, we propose an automatic 3D kidney segmentation method which segments the kidney into the three different tissue types: renal cortex, medulla and pelvis. The proposed method synergistically combines active appearance model (AAM), live wire (LW) and graph cut (GC) methods, GC-OAAM for short. Our method consists of two main steps. First, a pseudo 3D segmentation method is employed for kidney initialization in which the segmentation is performed slice-by-slice via a multi-object oriented active appearance model (OAAM) method. An improved iterative model refinement algorithm is proposed for the AAM optimization, which synergistically combines the AAM and LW method. Multi-object strategy is applied to help the object initialization. The 3D model constraints are applied to the initialization result. Second, the object shape information generated from the initialization step is integrated into the GC cost computation. A multi-label GC method is used to segment the kidney into cortex, medulla and pelvis. The proposed method was tested on 19 clinical arterial phase CT data sets. The preliminary results showed the feasibility and efficiency of the proposed method.

  19. Growing kidney tissue from stem cells: how far from ‘party trick’ to medical application?

    PubMed Central

    Little, Melissa H

    2016-01-01

    The successful generation of kidney-like structures from human pluripotent stem cells, although slower to come than other tissue types, brings the hope of new therapies. While the demand for alternative treatments for kidney failure is acute, huge challenges remain to move these exciting but preliminary results towards clinical use. PMID:27257757

  20. Distribution of lead and mercury in tissues of raccoons

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

    Khan, A.T.; Thompson, S.J.; Mielke, H.W.

    1994-12-31

    Liver and kidney tissues of raccoons from Tuskegee, Alabama, were analyzed for Hg and Pb contents. The mean levels of Hg and Pb were 0.41 and 3.24 ppm in livers and 0.24 and 4.95 ppm in kidneys, respectively. These metal levels showed no significant differences between livers and kidneys or between males and females.

  1. 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

  2. Thermal Effect of J-Plasma® Energy in a Porcine Tissue Model: Implications for Minimally Invasive Surgery.

    PubMed

    Pedroso, Jasmine D; Gutierrez, Melissa M; Volker, K Warren; Howard, David L

    2017-07-25

    To evaluate tissue effect of J-Plasma® (Bovie Medical Corporation, Clearwater, Florida) in porcine liver, kidney, muscle, ovarian, and uterine tissue blocks. Prospective study utilizing porcine tissue blocks to evaluate the thermal spread of J-Plasma® device on liver, kidney, muscle, ovarian, and uterine tissue at various power settings, gas flow, and exposure times. J-Plasma® helium was used in porcine liver, kidney, and muscle tissue at 20%, 50%, and 100% power, and 1 L/min, 3 L/min, and 5 L/min gas flow at one, five, and 10-second intervals. J-Plasma® was then used in ovarian and uterine tissue at maximum power and gas flow settings in intervals of one, five, 10, and 30 seconds. Histologic evaluation of each tissue was then performed to measure thermal spread. Regardless of tissue type, increased power setting, gas flow rate, and exposure time correlated with greater depth of thermal spread in liver, kidney, and muscle tissue. J-Plasma® did not exceed 2 mm thermal spread on liver, kidney, muscle, ovarian, and uterine tissue, even at a maximum setting of 100% power and 5 L/min gas flow after five seconds. Prolonged exposure to J-Plasma® of up to 30 seconds resulted in increased length and width of thermal spread of up to 12 mm, but did not result in significantly increased depth at 2.84 mm. The J-Plasma® helium device has minimal lateral and depth of thermal spread in a variety of tissue types and can likely be used for a multitude of gynecologic surgical procedures. However, further studies are needed to demonstrate device safety in a clinical setting.

  3. Confirmatory and quantitative analysis of beta-lactam antibiotics in bovine kidney tissue by dispersive solid-phase extraction and liquid chromatography-tandem mass spectrometry.

    PubMed

    Fagerquist, Clifton K; Lightfield, Alan R; Lehotay, Steven J

    2005-03-01

    A simple, rapid, rugged, sensitive, and specific method for the confirmation and quantitation of 10 beta-lactam antibiotics in fortified and incurred bovine kidney tissue has been developed. The method uses a simple solvent extraction, dispersive solid-phase extraction (dispersive-SPE) cleanup, and liquid chromatography-tandem mass spectrometry (LC/MS/MS) for confirmation and quantitation. Dispersive-SPE greatly simplifies and accelerates sample cleanup and improves overall recoveries compared with conventional SPE cleanup. The beta-lactam antibiotics tested were as follows: deacetylcephapirin (an antimicrobial metabolite of cephapirin), amoxicillin, desfuroylceftiofur cysteine disulfide (DCCD, an antimicrobial metabolite of ceftiofur), ampicillin, cefazolin, penicillin G, oxacillin, cloxacillin, naficillin, and dicloxacillin. Average recoveries of fortified samples were 70% or better for all beta-lactams except DCCD, which had an average recovery of 58%. The LC/MS/MS method was able to demonstrate quantitative recoveries at established tolerance levels and provide confirmatory data for unambiguous analyte identification. The method was also tested on 30 incurred bovine kidney samples obtained from the USDA Food Safety and Inspection Service, which had previously tested the samples using the approved semiquantitative microbial assay. The results from the quantitative LC/MS/MS analysis were in general agreement with the microbial assay for 23 samples although the LC/MS/MS method was superior in that it could specifically identify which beta-lactam was present and quantitate its concentration, whereas the microbial assay could only identify the type of beta-lactam present and report a concentration with respect to the microbial inhibition of a penicillin G standard. In addition, for 6 of the 23 samples, LC/MS/MS analysis detected a penicillin and a cephalosporin beta-lactam, whereas the microbial assay detected only a penicillin beta-lactam. For samples that do not fall into the "general agreement" category, the most serious discrepancy involves two samples where the LC/MS/MS method detected a violative level of a cephalosporin beta-lactam (deacetylcephapirin) in the first sample and a possibly violative level of desfuroylceftiofur in the second, whereas the microbial assay identified the two samples as having only violative levels of a penicillin beta-lactam.

  4. Liquid microjunction surface sampling of acetaminophen, terfenadine and their metabolites in thin tissue sections

    DOE PAGES

    Kertesz, Vilmos; Paranthaman, Nithya; Moench, Paul; ...

    2014-10-01

    The aim of this paper was to evaluate the analytical performance of a fully automated droplet-based surface-sampling system for determining the distribution of the drugs acetaminophen and terfenadine, and their metabolites, in rat thin tissue sections. The following are the results: The rank order of acetaminophen concentration observed in tissues was stomach > small intestine > liver, while the concentrations of its glucuronide and sulfate metabolites were greatest in the liver and small intestine. Terfenadine was most concentrated in the liver and kidney, while its major metabolite, fexofenadine, was found in the liver and small intestine. In conclusion, the spatialmore » distributions of both drugs and their respective metabolites observed in this work were consistent with previous studies using radiolabeled drugs.« less

  5. [Morphological characteristics of kidneys connective tissue of mature fetuses and newborns from mothers, whose pregnancy was complicated by preeclampsia of varying degrees of severity].

    PubMed

    Sorokina, Iryna V; Myroshnychenko, Mykhailo S; Kapustnyk, Nataliia V; Khramova, Tetyana O; Dehtiarova, Oksana V; Danylchenko, Svitlana I

    2018-01-01

    Introduction: The kidneys connective tissue condition in the antenatal period affects the formation of tissues and it changes with the development of various general pathological processes in this organ. The aim of the study was to identify the morphological features of kidneys connective tissue of fetuses and newborns from mothers whose pregnancy was complicated by preeclampsia of varying degrees of severity. Materials and methods: The material of the study was the tissue of kidneys of mature fetuses and newborns from mothers with physiological pregnancy (28 cases), as well as from mothers whose pregnancy was complicated by preeclampsia of varying degrees of severity (78 cases). Immunohistochemical study was performed by an indirect Coons method according to M. Brosman's technique using monoclonal antibodies to collagen type I, III and IV. Results: The kidneys connective tissue of fetuses and newborns developing under the maternal preeclampsia conditions is characterized by the qualitative and quantitative changes that indicate the development of sclerotic processes in this organ, the severity of which increase with the age and with the increase of the maternal preeclampsia severity. Qualitative changes are characterized by an increase of the fibrous component, thickening of the bundles of connective tissue fibers, and a decrease in the distance between them. Quantitative changes are characterized by a pronounced predominance of collagen fibers over elastic fibers, almost total absence in some field of view elastic fibers and the violation of the content of collagen type I, III and IV. Conclusion: Maternal preeclampsia underlies the development of qualitative and quantitative changes in kidneys connective tissue of fetuses and newborns, which as a result will lead to disruption of the functions of these organs in such children.

  6. Bioimaging of isosteric osmium and ruthenium anticancer agents by LA-ICP-MS.

    PubMed

    Klose, Matthias H M; Theiner, Sarah; Kornauth, Christoph; Meier-Menches, Samuel M; Heffeter, Petra; Berger, Walter; Koellensperger, Gunda; Keppler, Bernhard K

    2018-03-01

    Laser ablation-inductively coupled plasma-mass spectrometry (LA-ICP-MS) was used to study the spatial distribution of two metallodrugs with anticancer activities in vivo, namely the organoruthenium plecstatin-1 (1) and its isosteric osmium analogue (2), in liver, kidneys, muscles and tumours of treated mice bearing a CT-26 tumour after single-dose i.p. administration. To the best of our knowledge, this is the first time that the spatial distribution of an osmium drug candidate has been investigated using LA-ICP-MS in tissues. Independent measurements of the average ruthenium and osmium concentration via microwave digestion and ICP-MS in organs and tumours were in good agreement with the LA-ICP-MS results. Matrix-matched standards (MMS) ranging from 1 to 30 μg g -1 were prepared to quantify the spatial distributions of the metals and the average metal content of the MMS samples was additionally quantified by ICP-MS after microwave digestion. The recoveries for osmium and ruthenium in the MMS were 105% and 101% on average, respectively, validating the sample preparation procedure of the MMS. Preparation of MMS was carried out under an argon atmosphere to prevent oxidation of osmium-species to the volatile OsO 4 . The highest metal concentrations were found in the liver, followed by kidney, lung and tumour tissues, while muscles displayed only very low quantities of the respective metal. Both metallodrugs accumulated in the cortex of the kidneys more strongly compared to the medulla. Interestingly, osmium from 2 was largely located at the periphery and tissue edges, whereas ruthenium from 1 was observed to penetrate deeper into the organs and tumours.

  7. Resveratrol influences platinum pharmacokinetics: A novel mechanism in protection against cisplatin-induced nephrotoxicity.

    PubMed

    Darwish, Mostafa A; Abo-Youssef, Amira M; Khalaf, Marwa M; Abo-Saif, Ali A; Saleh, Ibrahim G; Abdelghany, Tamer M

    2018-06-15

    Cisplatin (CP) is a widely used drug in treatment of solid tumors. However, the use of CP was hampered by its serious side effects especially nephrotoxicity. This study aims to investigate the effect of resveratrol (RES) on CP-induced nephrotoxicity, particularly, the effect of RES on CP pharmacokinetics (PKs). Male white albino rats were divided to four group's six rats each. The first group received (1%) tween 80 in normal saline and served as control. The second group received RES (30 mg kg -1 ) per day for 14 consecutive day's i.p. The third and fourth groups were given a single i.p. injection of CP (6 mg kg -1 ) with or without pre-treatment of RES (30 mg kg -1 per day for 14 consecutive days), respectively. Following administration of CP, plasma, urine and kidney platinum concentration were monitored to study PKs of CP. Five days after the CP injection, rats were killed; blood samples were collected; kidneys were dissected; and biochemical, immunohistochemical, and histological examinations were performed. Our results revealed that CP treatment significantly deteriorated kidney functions with subsequent alteration in redox balance of the kidney. On the other hand, RES successfully ameliorated CP-induced kidney injury and recovered normal kidney tissue redox status. Importantly, while RES pre-treatment did not significantly alter the plasma CP level, it dramatically decreased the urine concentration of CP and lowered its accumulation into the kidneys. Moreover, it increased CP plasma half-life (t 1/2 ) with subsequent decrease in its elimination rate constant, indicating an important role of PKs modulation in RES protection against CP-induced renal damage. Taken together, RES may protect the kidney tissue from the deleterious effects of CP through constringe of CP renal accumulation and enhancement of CP-induced oxidative stress. Copyright © 2018 Elsevier B.V. All rights reserved.

  8. Tissue distribution, metabolism, and residue depletion study in Atlantic salmon following oral administration of [3H]emamectin benzoate.

    PubMed

    Kim-Kang, Heasook; Bova, Alice; Crouch, Louis S; Wislocki, Peter G; Robinson, Robert A; Wu, Jinn

    2004-04-07

    Atlantic salmon (approximately 1.3 kg) maintained in tanks of seawater at 5 +/- 1 degrees C were dosed with [3H]emamectin B1 benzoate in feed at a nominal rate of 50 microg of emamectin benzoate/kg/day for 7 consecutive days. Tissues, blood, and bile were collected from 10 fish each at 3 and 12 h and at 1, 3, 7, 15, 30, 45, 60, and 90 days post final dose. Feces were collected daily from the tanks beginning just prior to dosing to 90 days post final dose. The total radioactive residues (TRR) of the daily feces samples during dosing were 0.25 ppm maximal, and >97% of the TRR in pooled feces covering the dosing period was emamectin B1a. Feces TRR then rapidly declined to approximately 0.05 ppm by 1 day post final dose. The ranges of mean TRR for tissues over the 90 days post dose period were as follows: kidney, 1.4-3 ppm; liver, 1.0-2.3 ppm; skin, 0.04-0.09 ppm; muscle, 0.02-0.06 ppm; and bone, <0.01 ppm. The residue components of liver, kidney, muscle, and skin samples pooled by post dose interval were emamectin B1a (81-100% TRR) and desmethylemamectin B1a (0-17% TRR) with N-formylemamectin B1a seen in trace amounts (<2%) in some muscle samples. The marker residue selected for regulatory surveillance of emamectin residues was emamectin B1a. The emamectin B1a level was quantified in individual samples of skin and muscle using HPLC-fluorometry and was below 85 ppb in all samples analyzed (3 h to 30 days post dose).

  9. A method for direct assessment of tissue-nonspecific alkaline phosphatase (TNAP) inhibitors in blood samples.

    PubMed

    Sergienko, Eduard A; Sun, Qing; Ma, Chen-Ting

    2013-01-01

    Tissue nonspecific alkaline phosphatase (TNAP) is one of four human alkaline phosphatases (AP), a family of exocytic enzymes that catalyze hydrolysis of phospho-monoesters in bone, liver, kidney, and various other tissues. Overexpression of TNAP gives rise to excessive bone and soft tissue mineralization, including blood vessel calcification. Our prior screening campaigns have found several leads against this attractive therapeutic target using in vitro assay with a recombinant enzyme; these compounds were further optimized using medicinal chemistry approaches. To prioritize compounds for their use in animal models, we have designed and developed a biomarker assay for in situ detection of TNAP activity within human and mouse blood samples at physiological pH. This assay is suitable for screening compounds in 1,536-well plates using blood plasma from different mammalian species. The user may choose from two different substrates based on the need for greater assay simplicity or sensitivity.

  10. Comparison of liquid chromatographic and bioassay procedures for determining depletion of intramuscularly injected tylosin.

    PubMed

    Moats, W A; Harris, E W; Steele, N C

    1985-01-01

    Crossbred pigs weighing 80-110 kg were injected intramuscularly in the ham with 8.8 mg/kg tylosin. Animals were slaughtered in groups of 3 at intervals of 4 h, and 1, 2, 4, and 8 days after injection, and samples of blood, injected muscle, uninjected muscle, liver, and kidney were analyzed by liquid chromatography (LC) and by bioassay using Sarcina lutea as the test organism. The LC method was far more sensitive with a detection limit of less than 0.1 ppm, while the detection limit by bioassay was about 0.5 ppm in tissue. Results by bioassay and LC sometimes differed considerably for tissue samples. Residues in all tissues were below the tolerance limit of 0.2 ppm at 24 h, except in the injected muscle in one animal. Residues were not detected in any tissue of any animal at 48 h after treatment.

  11. Development of a quantitative assay to measure expression of transforming growth factor ß (TGF-ß) in Lost River sucker (Deltistes luxatus) and shortnose sucker (Chasmistes brevirostris) and evaluation of potential pitfalls in use with field-collected samples

    USGS Publications Warehouse

    Robertson, Laura S.; Ottinger, Christopher A.; Burdick, Summer M.; VanderKooi, Scott P.

    2012-01-01

    The Nature Conservancy is in the process of restoring the Williamson River Delta in an attempt to recreate important juvenile habitat for the endangered shortnose sucker Chasmistes brevirostris and the endangered Lost River sucker Deltistes luxatus. Measurement of TGF-β mRNA expression level was one of the indicators chosen to evaluate juvenile sucker health during the restoration process. TGF-β mRNA expression level has been correlated with disease status in several laboratory studies and TGF-β mRNA expression level has been used as a species-specific indicator of immune status in field-based fish health assessments. We describe here the identification of TGF-β and a possible splice variant from shortnose sucker and from Lost River sucker. The performance of a quantitative RT-PCR assay to measure TGF-β mRNA expression level was evaluated in field-collected spleen and kidney tissue samples. The quality of extracted RNA was higher in tissues harvested in September compared to July and higher in tissues harvested at lower temperature compared to higher temperature. In addition, the expression level of both TGF-β and 18S as assessed by qRT-PCR was higher in samples with higher quality RNA. TGF-β mRNA expression was lower in kidney than in spleen in both Lost River sucker and shortnose sucker.

  12. Comparative Sensitivity of Tissue Cultures to Rubella Virus: Use of Guinea Pig Cells for Virus Titration

    PubMed Central

    Horta-Barbosa, L.; Warren, Joel

    1969-01-01

    A series of 19 different primary and serial tissue cultures were investigated for their sensitivity to virulent or attenuated rubella virus (RV). Primary guinea pig tissues, a serial passage of baby hamster kidney, and primary human amnion were comparable to African green monkey kidney tissue cultures in their sensitivity. In general, primary human tissues were relatively insusceptible to the Gilchrist strain of RV. RV interfered with the growth of vesicular stomatitis virus. Based on this finding, it was possible to develop an assay method in guinea pig tissue cultures by using VSV as the challenge virus. This system appeared to be comparable in sensitivity to the use of primary monkey kidney tissue cultures for the detection of small amounts of RV and offers the advantages of economy, rapidity, and safety. PMID:4979943

  13. Tissue-Engineering Approaches to Restore Kidney Function.

    PubMed

    Katari, Ravi; Edgar, Lauren; Wong, Theresa; Boey, Angela; Mancone, Sarah; Igel, Daniel; Callese, Tyler; Voigt, Marcia; Tamburrini, Riccardo; Zambon, Joao Paulo; Perin, Laura; Orlando, Giuseppe

    2015-10-01

    Kidney transplantation for the treatment of chronic kidney disease has established outcome and quality of life. However, its implementation is severely limited by a chronic shortage of donor organs; consequently, most candidates remain on dialysis and on the waiting list while accruing further morbidity and mortality. Furthermore, those patients that do receive kidney transplants are committed to a life-long regimen of immunosuppressive drugs that also carry significant adverse risk profiles. The disciplines of tissue engineering and regenerative medicine have the potential to produce alternative therapies which circumvent the obstacles posed by organ shortage and immunorejection. This review paper describes some of the most promising tissue-engineering solutions currently under investigation for the treatment of acute and chronic kidney diseases. The various stem cell therapies, whole embryo transplantation, and bioengineering with ECM scaffolds are outlined and summarized.

  14. Online, absolute quantitation of propranolol from spatially distinct 20-μm and 40-μm dissections of brain, liver, and kidney thin tissue sections by laser microdissection – liquid vortex capture – mass spectrometry

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

    Kertesz, Vilmos; Vavrek, Marissa; Freddo, Carol

    Here, spatial resolved quantitation of chemical species in thin tissue sections by mass spectrometric methods has been constrained by the need for matrix-matched standards or other arduous calibration protocols and procedures to mitigate matrix effects (e.g., spatially varying ionization suppression). Reported here is the use of laser cut and drop sampling with a laser microdissection-liquid vortex capture electrospray ionization tandem mass spectrometry (LMD-LVC/ESI-MS/MS) system for online and absolute quantitation of propranolol in mouse brain, kidney, and liver thin tissue sections of mice administered with the drug at a 7.5 mg/kg dose, intravenously. In this procedure either 20 μm x 20more » μm or 40 μm x 40 μm tissue microdissections were cut and dropped into the flowing solvent of the capture probe. During transport to the ESI source drug related material was completely extracted from the tissue into the solvent, which contained a known concentration of propranolol-d 7 as an internal standard. This allowed absolute quantitation to be achieved with an external calibration curve generated from standards containing the same fixed concentration of propranolold-d 7 and varied concentrations of propranolol. Average propranolol concentrations determined with the laser cut and drop sampling method closely agreed with concentration values obtained from 2.3 mm diameter tissue punches from serial sections that were extracted and quantified by HPLC/ESI-MS/MS measurements. In addition, the relative abundance of hydroxypropranolol glucuronide metabolites were recorded and found to be consistent with previous findings.« less

  15. Online, absolute quantitation of propranolol from spatially distinct 20-μm and 40-μm dissections of brain, liver, and kidney thin tissue sections by laser microdissection – liquid vortex capture – mass spectrometry

    DOE PAGES

    Kertesz, Vilmos; Vavrek, Marissa; Freddo, Carol; ...

    2016-05-23

    Here, spatial resolved quantitation of chemical species in thin tissue sections by mass spectrometric methods has been constrained by the need for matrix-matched standards or other arduous calibration protocols and procedures to mitigate matrix effects (e.g., spatially varying ionization suppression). Reported here is the use of laser cut and drop sampling with a laser microdissection-liquid vortex capture electrospray ionization tandem mass spectrometry (LMD-LVC/ESI-MS/MS) system for online and absolute quantitation of propranolol in mouse brain, kidney, and liver thin tissue sections of mice administered with the drug at a 7.5 mg/kg dose, intravenously. In this procedure either 20 μm x 20more » μm or 40 μm x 40 μm tissue microdissections were cut and dropped into the flowing solvent of the capture probe. During transport to the ESI source drug related material was completely extracted from the tissue into the solvent, which contained a known concentration of propranolol-d 7 as an internal standard. This allowed absolute quantitation to be achieved with an external calibration curve generated from standards containing the same fixed concentration of propranolold-d 7 and varied concentrations of propranolol. Average propranolol concentrations determined with the laser cut and drop sampling method closely agreed with concentration values obtained from 2.3 mm diameter tissue punches from serial sections that were extracted and quantified by HPLC/ESI-MS/MS measurements. In addition, the relative abundance of hydroxypropranolol glucuronide metabolites were recorded and found to be consistent with previous findings.« less

  16. Novel mechanism of regulation of fibrosis in kidney tumor with tuberous sclerosis

    PubMed Central

    2013-01-01

    Background Deficiency in tuberin results in activation the mTOR pathway and leads to accumulation of cell matrix proteins. The mechanisms by which tuberin regulates fibrosis in kidney angiomyolipomas (AMLs) of tuberous sclerosis patients are not fully known. Method In the present study, we investigated the potential role of tuberin/mTOR pathway in the regulation of cell fibrosis in AML cells and kidney tumor tissue from tuberous sclerosis complex (TSC) patients. Results AML cells treated with rapamycin shows a significant decrease in mRNA and protein expression as well as in promoter transcriptional activity of alpha-smooth muscle actin (α-SMA) compared to untreated cells. In addition, cells treated with rapamycin significantly decreased the protein expression of the transcription factor YY1. Rapamycin treatment also results in the redistribution of YY1 from the nucleus to cytoplasm in AML cells. Moreover, cells treated with rapamycin resulted in a significant reduce of binding of YY1 to the αSMA promoter element in nuclear extracts of AML cells. Kidney angiomyolipoma tissues from TSC patients showed lower levels of tuberin and higher levels of phospho-p70S6K that resulted in higher levels of mRNA and protein of αSMA expression compared to control kidney tissues. In addition, most of the α-SMA staining was identified in the smooth muscle cells of AML tissues. YY1 was also significantly increased in tumor tissue of AMLs compared to control kidney tissue suggesting that YY1 plays a major role in the regulation of αSMA. Conclusions These data comprise the first report to provide one mechanism whereby rapamycin might inhibit the cell fibrosis in kidney tumor of TSC patients. PMID:23705901

  17. Deleterious effects of incense smoke exposure on kidney function and architecture in male albino rats.

    PubMed

    Hussain, Tajamul; Al-Attas, Omar S; Alrokayan, Salman A; Ahmed, Mukhtar; Al-Daghri, Nasser M; Al-Ameri, Salman; Pervez, Shamsh; Dewangan, Shippi; Mohammed, Arif; Gambhir, Dikshit; Sumague, Terrance S

    2016-07-01

    Previous studies, including ours, have shown adverse effects of incense smoke on human health. However, the effect of incense smoke on kidney function and structure remains unknown. To evaluate possible adverse effects of incense smoke on kidney function and architecture in albino rats after chronic exposure to Arabian incense. Emission characteristics including particle size distribution, volatile organic compounds (VOCs) and polycyclic aromatic hydrocarbons (PAHs) were determined by gravimetric and GCMS analyses. Kidney functional markers, oxidative stress and inflammatory markers were measured by standard or ELISA based procedures. Ultrastructural changes in kidney were examined by transmission electron microscope (TEM) and the gene expression of xenobiotic metabolizing enzymes including cytochrome P-450-1A1 (CYP1A1) and CYP1A2 were studied by real time PCR. Rats exposed to incense smoke demonstrated a significant increase in serum creatinine, uric acid, blood urea nitrogen (BUN), tissue malondialdehyde (MDA), tumor necrosis factor-alpha (TNF-α) and interleukin-4 (IL-4) levels and a significant decline in tissue reduced glutathione (GSH) and catalase activity. Incense smoke exposed rats also displayed marked ultrastructural changes in kidney tissue. Further, a significant increase in tissue gene expression of both CYP1A1 and CYP1A2 was noted in exposed rats. Changes to kidney functional markers and architecture appear to be mediated through augmented oxidative stress and inflammation. Long-term exposure to incense smoke may have deleterious effects on kidney function and architecture. Though, inhalation is the rout of exposure, findings of this study underscore that incense smoke may also have an effect on non-pulmonary tissues.

  18. Potential Noncutaneous Sites of Chelonid Herpesvirus 5 Persistence and Shedding in Green Sea Turtles Chelonia mydas.

    PubMed

    Page-Karjian, Annie; Gottdenker, Nicole L; Whitfield, Jordyn; Herbst, Lawrence; Norton, Terry M; Ritchie, Branson

    2017-09-01

    Chelonid herpesvirus 5 (ChHV5), the likely etiologic agent of sea turtle fibropapillomatosis (FP), is predicted to be unevenly distributed within an infected turtle, in which productive virus replication and virion shedding occurs in cutaneous tumor keratinocytes. In this study, we measured and compared ChHV5 DNA quantities in tumors, skin, urine, major organs, and nervous tissue samples from green turtles Chelonia mydas. These samples were taken from the carcasses of 10 juvenile green turtles with and without clinical signs of FP that stranded in Florida during 2014. Quantitative PCR for ChHV5 UL30 was used to identify ChHV5 DNA in tumors, skin, heart, kidney, nerves, and urine sampled from five out of five FP-positive and three out of five FP-free turtles. The most frequently co-occurring sites were cutaneous tumor and kidney (n = 4). Novel data presented here include the identification of ChHV5 DNA in kidney, heart, and nerve samples from three FP-free turtles. These data support candidate nontumored anatomic sites of ChHV5 DNA localization and mobilization during two different disease states that may be involved in the ChHV5 infection cycle. Received September 8, 2016; accepted April 17, 2017.

  19. 21 CFR 556.50 - Amprolium.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... edible tissues and in eggs of chickens and turkeys: (1) 1 part per million in uncooked liver and kidney... in uncooked fat. (2) 0.5 part per million in uncooked muscle tissue, liver, and kidney. (c) In the...

  20. 21 CFR 556.50 - Amprolium.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... edible tissues and in eggs of chickens and turkeys: (1) 1 part per million in uncooked liver and kidney... in uncooked fat. (2) 0.5 part per million in uncooked muscle tissue, liver, and kidney. (c) In the...

  1. Beneficial Effect of Bis(Hinokitiolato)Zn Complex on High-fat Diet-induced Lipid Accumulation in Mouse Liver and Kidney.

    PubMed

    Naito, Yuki; Yoshikawa, Yutaka; Yoshizawa, Katsuhiko; Takenouchi, Akiko; Yasui, Hiroyuki

    2017-01-01

    Metabolic syndrome-induced lifestyle-related diseases include diabetes mellitus (DM) and hypertension, and Zn-based compounds have effects on DM. We aimed to investigate the ameliorating effects of bis(hinokitiolato)Zn, [Zn(hkt) 2 ] on lipid metabolism in the liver and kidney, histopathologically. We used a high-fat diet (HFD)-fed C57BL/6J mouse model and administered a diet containing 10-20 mg Zn/kg body weight (BW) or 20 mg pioglitazone/kg BW as the positive control. After the treatments, we collected blood, liver, and kidney samples and morphologically evaluated the mouse organs for fat accumulation. After a 4-month HFD administration, ectopic fat deposition was detected in the liver and kidney. Furthermore, Zn accumulation in the liver and kidney increased following [Zn(hkt) 2 ] treatment, that reduced lipid accumulations and lipid toxicity in these tissues. The results of this study suggest that [Zn(hkt) 2 ] could be a novel anti-dyslipidaemia compound for treating diet-induced obesity. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

  2. Immunohistochemical examination of effects of kefir, koumiss and commercial probiotic capsules on platelet derived growth factor-c and platelet derived growth factor receptor-alpha expression in mouse liver and kidney.

    PubMed

    Bakir, B; Sari, E K; Aydin, B D; Yildiz, S E

    2015-04-01

    We investigated using immunohistochemistry the effects of kefir, koumiss and commercial probiotic capsules on the expression of platelet derived growth factor-c (PDGF-C) and platelet derived growth factor receptor-alpha (PDGFR-α) in mouse liver and kidney. Mice were assigned to four groups: group 1 was given commercial probiotic capsules, group 2 was given kefir, group 3 was given koumiss and group 4 was untreated. After oral administration for 15 days, body weights were recorded and liver and kidney tissue samples were obtained. Hematoxylin and eosin staining was used to examine histology. PDGF-C and PDGFR-α in liver and kidney were localized using the streptavidin-biotin peroxidase complex method (ABC). We found that the weights of the mice in the kefir, koumiss and commercial probiotic capsules groups increased compared to the control group. No differences in liver and kidney histology were observed in any of the experimental groups. Kefir, koumiss and the commercial probiotic preparation increased PDGF-C and PDGFR-α expression.

  3. Measuring water contents in animal organ tissues using terahertz spectroscopic imaging.

    PubMed

    Lee, Kyumin; Jeoung, Kiyong; Kim, Sang Hoon; Ji, Young-Bin; Son, Hyeyoung; Choi, Yuna; Huh, Young-Min; Suh, Jin-Suck; Oh, Seung Jae

    2018-04-01

    We investigated the water contents in several organ tissues such as the liver, spleen, kidney, and brain tissue of rats using the terahertz spectroscopic imaging technique. The water contents of the tissues were determined by using a simple equation containing the absorption coefficients of fresh and lyophilized tissues and water. We compared the measured water contents with the difference in mass of tissues before and after lyophilization. All results showed a good match except for the kidney, which has several Bowman's capsules.

  4. Imaging Prostate Cancer with Positron Emission Tomography

    DTIC Science & Technology

    2016-07-01

    pool. Radioactivity was retained in kidney tissue and suggests that this is the primary route of excretion. Tumor targeting was inefficient.    15...radioactivity in hepatic tissue. Elevated levels of radioactivity were observed in kidney tissue suggesting that these radiotracers are excreted...20, 21], and its Blood 0 10 20 30 0.00 0.05 0.10 0.15 0.20 Time (h) % ID /g Liver 0 10 20 30 0.0 0.5 1.0 1.5 2.0 Time (h) % ID /g Kidney 0 10 20 30

  5. Ambient ionization mass spectrometric analysis of human surgical specimens to distinguish renal cell carcinoma from healthy renal tissue.

    PubMed

    Alfaro, Clint M; Jarmusch, Alan K; Pirro, Valentina; Kerian, Kevin S; Masterson, Timothy A; Cheng, Liang; Cooks, R Graham

    2016-08-01

    Touch spray-mass spectrometry (TS-MS) is an ambient ionization technique (ionization of unprocessed samples in the open air) that may find intraoperative applications in quickly identifying the disease state of cancerous tissues and in defining surgical margins. In this study, TS-MS was performed on fresh kidney tissue (∼1-5 cm(3)), within 1 h of resection, from 21 human subjects afflicted by renal cell carcinoma (RCC). The preliminary diagnostic value of TS-MS data taken from freshly resected tissue was evaluated. Principal component analysis (PCA) of the negative ion mode (m/z 700-1000) data provided the separation between RCC (16 samples) and healthy renal tissue (13 samples). Linear discriminant analysis (LDA) on the PCA-compressed data estimated sensitivity (true positive rate) and specificity (true negative rate) of 98 and 95 %, respectively, based on histopathological evaluation. The results indicate that TS-MS might provide rapid diagnostic information in spite of the complexity of unprocessed kidney tissue and the presence of interferences such as urine and blood. Desorption electrospray ionization-MS imaging (DESI-MSI) in the negative ionization mode was performed on the tissue specimens after TS-MS analysis as a reference method. The DESI imaging experiments provided phospholipid profiles (m/z 700-1000) that also separated RCC and healthy tissue in the PCA space, with PCA-LDA sensitivity and specificity of 100 and 89 %, respectively. The TS and DESI loading plots indicated that different ions contributed most to the separation of RCC from healthy renal tissue (m/z 794 [PC 34:1 + Cl](-) and 844 [PC 38:4 + Cl](-) for TS vs. m/z 788 [PS 36:1 - H](-) and 810 [PS 38:4 - H](-) for DESI), while m/z 885 ([PI 38:4 - H](-)) was important in both TS and DESI. The prospect, remaining hurdles, and future work required for translating TS-MS into a method of intraoperative tissue diagnosis are discussed. Graphical abstract Touch spray-mass spectrometry used for lipid profiling of fresh human renal cell carcinoma. Left) Photograph of the touch spray probe pointed at the MS inlet. Right) Average mass spectra of healthy renal tissue (blue) and RCC (red).

  6. Quantitative PCR analysis of CYP1A induction in Atlantic salmon (Salmo salar)

    USGS Publications Warehouse

    Rees, C.B.; McCormick, S.D.; Vanden, Heuvel J.P.; Li, W.

    2003-01-01

    Environmental pollutants are hypothesized to be one of the causes of recent declines in wild populations of Atlantic salmon (Salmo salar) across Eastern Canada and the United States. Some of these pollutants, such as polychlorinated biphenyls and dioxins, are known to induce expression of the CYP1A subfamily of genes. We applied a highly sensitive technique, quantitative reverse transcription-polymerase chain reaction (RT-PCR), for measuring the levels of CYP1A induction in Atlantic salmon. This assay was used to detect patterns of CYP1A mRNA levels, a direct measure of CYP1A expression, in Atlantic salmon exposed to pollutants under both laboratory and field conditions. Two groups of salmon were acclimated to 11 and 17??C, respectively. Each subject then received an intraperitoneal injection (50 mg kg-1) of either ??-naphthoflavone (BNF) in corn oil (10 mg BNF ml-1 corn oil) or corn oil alone. After 48 h, salmon gill, kidney, liver, and brain were collected for RNA isolation and analysis. All tissues showed induction of CYP1A by BNF. The highest base level of CYP1A expression (2.56??1010 molecules/??g RNA) was found in gill tissue. Kidney had the highest mean induction at five orders of magnitude while gill tissue showed the lowest mean induction at two orders of magnitude. The quantitative RT-PCR was also applied to salmon sampled from two streams in Massachusetts, USA. Salmon liver and gill tissue sampled from Millers River (South Royalston, Worcester County), known to contain polychlorinated biphenyls (PCBs), showed on average a two orders of magnitude induction over those collected from a stream with no known contamination (Fourmile Brook, Northfield, Franklin County). Overall, the data show CYP1A exists and is inducible in Atlantic salmon gill, brain, kidney, and liver tissue. In addition, the results obtained demonstrate that quantitative PCR analysis of CYP1A expression is useful in studying ecotoxicity in populations of Atlantic salmon in the wild. ?? 2003 Elsevier Science B.V. All rights reserved.

  7. Transport of organic anions and cations in murine embryonic kidney development and in serially-reaggregated engineered kidneys

    PubMed Central

    Lawrence, Melanie L.; Chang, C-Hong; Davies, Jamie A.

    2015-01-01

    Recent advances in renal tissue engineering have shown that dissociated, early renogenic tissue from the developing embryo can self-assemble into morphologically accurate kidney-like organs arranged around a central collecting duct tree. In order for such self-assembled kidneys to be useful therapeutically or as models for drug screening, it is necessary to demonstrate that they are functional. One of the main functional characteristics of mature kidneys is transport of organic anions and cations into and out of the proximal tubule. Here, we show that the transport function of embryonic kidneys allowed to develop in culture follows a developmental time-course that is comparable to embryonic kidney development in vivo. We also demonstrate that serially-reaggregated engineered kidneys can transport organic anions and cations through specific uptake and efflux channels. These results support the physiological relevance of kidneys grown in culture, a commonly used model for kidney development and research, and suggest that serially-reaggregated kidneys self-assembled from separated cells have some functional characteristics of intact kidneys. PMID:25766625

  8. Reproducible Tissue Homogenization and Protein Extraction for Quantitative Proteomics Using MicroPestle-Assisted Pressure-Cycling Technology.

    PubMed

    Shao, Shiying; Guo, Tiannan; Gross, Vera; Lazarev, Alexander; Koh, Ching Chiek; Gillessen, Silke; Joerger, Markus; Jochum, Wolfram; Aebersold, Ruedi

    2016-06-03

    The reproducible and efficient extraction of proteins from biopsy samples for quantitative analysis is a critical step in biomarker and translational research. Recently, we described a method consisting of pressure-cycling technology (PCT) and sequential windowed acquisition of all theoretical fragment ions-mass spectrometry (SWATH-MS) for the rapid quantification of thousands of proteins from biopsy-size tissue samples. As an improvement of the method, we have incorporated the PCT-MicroPestle into the PCT-SWATH workflow. The PCT-MicroPestle is a novel, miniaturized, disposable mechanical tissue homogenizer that fits directly into the microTube sample container. We optimized the pressure-cycling conditions for tissue lysis with the PCT-MicroPestle and benchmarked the performance of the system against the conventional PCT-MicroCap method using mouse liver, heart, brain, and human kidney tissues as test samples. The data indicate that the digestion of the PCT-MicroPestle-extracted proteins yielded 20-40% more MS-ready peptide mass from all tissues tested with a comparable reproducibility when compared to the conventional PCT method. Subsequent SWATH-MS analysis identified a higher number of biologically informative proteins from a given sample. In conclusion, we have developed a new device that can be seamlessly integrated into the PCT-SWATH workflow, leading to increased sample throughput and improved reproducibility at both the protein extraction and proteomic analysis levels when applied to the quantitative proteomic analysis of biopsy-level samples.

  9. Epizootiology and histopathology of Parvicapsula sp. in coho salmon Oncorhynchus kisutch

    USGS Publications Warehouse

    Yasutake, William T.; Elliott, Diane G.

    2003-01-01

    The epizootiology and histopathology of the myxosporean Parvicapsula sp. was studied during monthly health surveys of 4 groups of coho salmon Oncorhynchus kisutch at a commercial farm in Puget Sound, Washington, USA, from 1984 to 1986. No Parvicapsula sp. was detected in histological samples taken from juvenile fish in fresh water, but the parasite was detected in fish from all groups 2 to 8 mo after transfer to seawater net pens. Groups placed in seawater net pens in November and December had a higher prevalence of infection, and a longer period of continuous detected infection, than those introduced into net pens in May. For the groups transferred to seawater in November and December, the highest infection prevalence (45 to 90%) was detected during the following March and April. Among 13 tissues examined histologically, only the pseudobranch and kidney were positive for Parvicapsula sp., with 26 (62%) of 42 positive fish showing infections only in the pseudobranch, 5 (12%) showing infections only in the kidney, and 11 (26%) showing infections in both organs. Both the pseudobranch and kidney were apparent primary infection sites, but pseudobranch infections appeared to persist longer in a population. Pseudobranch infections were frequently heavy and associated with extensive inflammation and necrosis of filament and lamellar tissues. The kidney had been the only infection site reported for Parvicapsula sp. in previous studies of coho salmon.

  10. Constructing kidney-like tissues from cells based on programs for organ development: toward a method of in vitro tissue engineering of the kidney.

    PubMed

    Rosines, Eran; Johkura, Kohei; Zhang, Xing; Schmidt, Heidi J; Decambre, Marvalyn; Bush, Kevin T; Nigam, Sanjay K

    2010-08-01

    The plausibility of constructing vascularized three-dimensional (3D) kidney tissue from cells was investigated. The kidney develops from mutual inductive interactions between cells of the ureteric bud (UB), derived from the Wolffian duct (WD), and the metanephric mesenchyme (MM). We found that isolated MMs were capable of inducing branching morphogenesis of the WD (an epithelial tube) in recombination cultures; suggesting that the isolated MM retains inductive capacity for WD-derived epithelial tubule cells other than those from the UB. Hanging drop aggregates of embryonic and adult renal epithelial cells from UB and mouse inner medullary collecting duct cell (IMCD) lines, which are ultimately of WD origin, were capable of inducing MM epithelialization and tubulogenesis with apparent connections (UB cells) and collecting duct-like tubules with lumens (IMCD). This supports the view that the collecting system can be constructed from certain epithelial cells (those ultimately of WD origin) when stimulated by MM. Although the functions of the MM could not be replaced by cultured mesenchymal cells, primary MM cells and one MM-derived cell line (BSN) produced factors that stimulate UB branching morphogenesis, whereas another, rat inducible metanephric mesenchyme (RIMM-18), supported WD budding as a feeder layer. This indicates that some MM functions can be recapitulated by cells. Although engineering of a kidney-like tissue from cultured cells alone remains to be achieved, these results suggest the feasibility of such an approach following the normal developmental progression of the UB and MM. Consistent with this notion, implants of kidney-like tissues constructed in vitro from recombinations of the UB and MM survived for over 5 weeks and achieved an apparently host-derived glomerular vasculature. Lastly, we addressed the issue of optimal macro- and micro-patterning of kidney-like tissue, which might be necessary for function of an organ assembled using a tissue engineering approach. To identify suitable conditions, 3D reconstructions of HoxB7-green fluorescent protein mouse rudiments (E12) cultured on a filter or suspended in a collagen gel (type I or type IV) revealed that type IV collagen 3D culture supports the deepest tissue growth (600 +/- 8 microm) and the largest kidney volume (0.22 +/- 0.02 mm(3)), and enabled the development of an umbrella-shaped collecting system such as occurs in vivo. Taken together with prior work (Rosines et al., 2007; Steer et al., 2002), these results support the plausibility of a developmental strategy for constructing and propagating vascularized 3D kidney-like tissues from recombinations of cultured renal progenitor cells and/or primordial tissue.

  11. Glycerol dehydration of native and diabetic animal tissues studied by THz-TDS and NMR methods

    PubMed Central

    Smolyanskaya, O. A.; Schelkanova, I. J.; Kulya, M. S.; Odlyanitskiy, E. L.; Goryachev, I. S.; Tcypkin, A. N.; Grachev, Ya. V.; Toropova, Ya. G.; Tuchin, V. V.

    2018-01-01

    The optical clearing method has been widely used for different spectral ranges where it provides tissue transparency. In this work, we observed the enhanced penetration of the terahertz waves inside biological samples (skin, kidney, and cornea) treated with glycerol solutions inducing changes of optical and dielectric properties. It was supported by the observed trend of free-to-bound water ratio measured by the nuclear magnetic resonance (NMR) method. The terahertz clearing efficiency was found to be less for diabetic samples than for normal ones. Results of the numerical simulation proved that pulse deformation is due to bigger penetration depth caused by the reduction of absorption and refraction at optical clearing. PMID:29541513

  12. Expression of adropin in rat brain, cerebellum, kidneys, heart, liver, and pancreas in streptozotocin-induced diabetes.

    PubMed

    Aydin, Suleyman; Kuloglu, Tuncay; Aydin, Suna; Eren, Mehmet Nesimi; Yilmaz, Musa; Kalayci, Mehmet; Sahin, Ibrahim; Kocaman, Nevin; Citil, Cihan; Kendir, Yalcin

    2013-08-01

    We have investigated how diabetes affects the expression of adropin (ADR) in rat brain, cerebellum, kidneys, heart, liver, and pancreas tissues. The rats in the diabetic group were administered an intraperitoneal (i.p.) injection of a single dose of 60 mg/kg streptozotocin (STZ) dissolved in a 0.1 M phosphate-citrate buffer (pH 4.5). The rats were maintained in standard laboratory conditions in a temperature between 21 and 23 °C and a relative humidity of 70 %, under a 12-h light/dark cycle. The animals were fed a standard commercial pellet diet. After 10 weeks, the animals were sacrified. ADR concentrations in the serum and tissue supernatants were measured by ELISA, and immunohistochemical staining was used to follow the expression of the hormones in the brain, cerebellum, kidneys, heart, liver, and pancreas tissues. The quantities were then compared. Increased ADR immunoreaction was seen in the brain, cerebellum, kidneys, heart, liver, and pancreas in the diabetes-induced rats compared to control subjects. ADR was detected in the brain (vascular area, pia mater, neuroglial cell, and neurons), cerebellum (neuroglial cells, Purkinje cells, vascular areas, and granular layer), kidneys (glomerulus, peritubular interstitial cells, and peritubular capillary endothelial cells), heart (endocardium, myocardium, and epicardium), liver (sinusoidal cells), and pancreas (serous acini). Its concentrations (based on mg/wet weight tissues) in these tissues were measured by using ELISA showed that the levels of ADR were higher in the diabetic rats compared to the control rats. Tissue ADR levels based on mg/wet weight tissues were as follows: Pancreas > liver > kidney > heart > brain > cerebellar tissues. Evidence is presented that shows ADR is expressed in various tissues in the rats and its levels increased in STZ-induced diabetes; however, this effect on the pathophysiology of the disorder remains to be understood.

  13. Effect of transportation stress on heat shock protein 70 concentration and mRNA expression in heart and kidney tissues and serum enzyme activities and hormone concentrations of pigs.

    PubMed

    Yu, Hong; Bao, En-Dong; Zhao, Ru-Qian; Lv, Qiong-Xia

    2007-11-01

    To determine the enzymatic and hormonal responses, heat shock protein 70 (Hsp70) production, and Hsp70 mRNA expression in heart and kidney tissues of transport-stressed pigs. 24 pigs (mean weight, 20 +/- 1 kg). Pigs were randomly placed into groups of 12 each. One group was transported for 2 hours. The other group was kept under normal conditions and used as control pigs. Sera were used to detect triiodothyronine, thyroxine, and cortisol concentrations and alanine aminotransferase, aspartate aminotransferase, and creatine kinase activities. The heart and kidneys of anesthetized pigs were harvested and frozen in liquid nitrogen for quantification of Hsp70 and Hsp70 mRNA. No significant differences were detected in serum alanine aminotransferase activity and triiodothyronine and cortisol concentrations between groups; however, the serum creatine kinase and aspartate aminotransferase activities and thyroxine concentrations were higher in transported pigs. Densitometric readings of western blots revealed that the amount of Hsp70 in heart and kidney tissues was significantly higher in transported pigs, compared with control pigs. Results of fluorescence quantitative real-time PCR assay revealed that the Hsp70 mRNA transcription in heart tissue, but not kidney tissue, was significantly higher in transported pigs, compared with control pigs. Transportation imposed a severe stress on pigs that was manifested as increased serum activities of aspartate aminotransferase and creatine kinase and increased amounts of Hsp70 and Hsp70 mRNA expression in heart and kidney tissues. Changes in serum enzyme activities were related to the tissue damage of transport-stressed pigs.

  14. Effects of Supplemental Acerola Juice on the Mineral Concentrations in Liver and Kidney Tissue Samples of Mice Fed with Cafeteria Diet.

    PubMed

    Leffa, Daniela Dimer; dos Santos, Carla Eliete Iochims; Daumann, Francine; Longaretti, Luiza Martins; Amaral, Livio; Dias, Johnny Ferraz; da Silva, Juliana; Andrade, Vanessa Moraes

    2015-09-01

    We evaluated the impact of a supplemental acerola juice (unripe, ripe, and industrial) and its main pharmaceutically active components on the concentrations of minerals in the liver and kidney of mice fed with cafeteria diet. Swiss male mice were fed with a cafeteria (CAF) diet for 13 weeks. The CAF consisted of a variety of supermarket products with high energy content. Subsequently, animals received one of the following food supplements for 1 month: water, unripe acerola juice, ripe acerola juice, industrial acerola juice, vitamin C, or rutin. Mineral concentrations of the tissues were determined by particle-induced X-ray emission (PIXE). Our study suggests that the simultaneous intake of acerola juices, vitamin C, or rutin in association with a hypercaloric and hyperlipidic diet provides change in the mineral composition of organisms in the conditions of this study, which plays an important role in the antioxidant defenses of the body. This may help to reduce the metabolism of the fat tissue or even to reduce the oxidative stress.

  15. Novel surgical techniques, regenerative medicine, tissue engineering and innovative immunosuppression in kidney transplantation.

    PubMed

    Nowacki, Maciej; Nazarewski, Łukasz; Kloskowski, Tomasz; Tyloch, Dominik; Pokrywczyńska, Marta; Pietkun, Katarzyna; Jundziłł, Arkadiusz; Tyloch, Janusz; Habib, Samy L; Drewa, Tomasz

    2016-10-01

    On the 60 th anniversary of the first successfully performed renal transplantation, we summarize the historical, current and potential future status of kidney transplantation. We discuss three different aspects with a potential significant influence on kidney transplantation progress: the development of surgical techniques, the influence of regenerative medicine and tissue engineering, and changes in immunosuppression. We evaluate the standard open surgical procedures with modern techniques and compare them to less invasive videoscopic as well as robotic techniques. The role of tissue engineering and regenerative medicine as a potential method for future kidney regeneration or replacement and the interesting search for novel solutions in the field of immunosuppression will be discussed. After 60 years since the first successfully performed kidney transplantation, we can conclude that the greatest achievements are associated with the development of surgical techniques and with planned systemic immunosuppression.

  16. Novel surgical techniques, regenerative medicine, tissue engineering and innovative immunosuppression in kidney transplantation

    PubMed Central

    Nowacki, Maciej; Nazarewski, Łukasz; Tyloch, Dominik; Pokrywczyńska, Marta; Pietkun, Katarzyna; Jundziłł, Arkadiusz; Tyloch, Janusz; Habib, Samy L.; Drewa, Tomasz

    2016-01-01

    On the 60th anniversary of the first successfully performed renal transplantation, we summarize the historical, current and potential future status of kidney transplantation. We discuss three different aspects with a potential significant influence on kidney transplantation progress: the development of surgical techniques, the influence of regenerative medicine and tissue engineering, and changes in immunosuppression. We evaluate the standard open surgical procedures with modern techniques and compare them to less invasive videoscopic as well as robotic techniques. The role of tissue engineering and regenerative medicine as a potential method for future kidney regeneration or replacement and the interesting search for novel solutions in the field of immunosuppression will be discussed. After 60 years since the first successfully performed kidney transplantation, we can conclude that the greatest achievements are associated with the development of surgical techniques and with planned systemic immunosuppression. PMID:27695507

  17. An improved method of renal tissue engineering, by combining renal dissociation and reaggregation with a low-volume culture technique, results in development of engineered kidneys complete with loops of Henle.

    PubMed

    Chang, C-Hong; Davies, Jamie A

    2012-01-01

    Tissue engineering of functional kidney tissue is an important goal for clinical restoration of renal function in patients damaged by infectious, toxicological, or genetic disease. One promising approach is the use of the self-organizing abilities of embryonic kidney cells to arrange themselves, from a simply reaggregated cell suspension, into engineered organs similar to fetal kidneys. The previous state-of-the-art method for this results in the formation of a branched collecting duct tree, immature nephrons (S-shaped bodies) beside and connected to it, and supportive stroma. It does not, though, result in the significant formation of morphologically detectable loops of Henle - anatomical features of the nephron that are critical to physiological function. We have combined the best existing technique for renal tissue engineering from cell suspensions with a low-volume culture technique that allows intact kidney rudiments to make loops of Henle to test whether engineered kidneys can produce these loops. The result is the formation of loops of Henle in engineered cultured 'fetal kidneys', very similar in both morphology and in number to those formed by intact organ rudiments. This brings the engineering technique one important step closer to production of a fully realistic organ. Copyright © 2012 S. Karger AG, Basel.

  18. Microgravity

    NASA Image and Video Library

    1996-06-01

    The NASA Bioreactor provides a low turbulence culture environment which promotes the formation of large, three-dimensional cell clusters. Due to their high level of cellular organization and specialization, samples constructed in the bioreactor more closely resemble the original tumor or tissue found in the body. NASA-sponsored bioreactor research has been instrumental in helping scientists to better understand normal and cancerous tissue development. In cooperation with the medical community, the bioreactor design is being used to prepare better models of human colon, prostate, breast and ovarian tumors. Cartilage, bone marrow, heart muscle, skeletal muscle, pancreatic islet cells, liver and kidney are just a few of the normal tissues currently being cultured in rotating bioreactors by investigators

  19. Microgravity

    NASA Image and Video Library

    1988-07-14

    The NASA Bioreactor provides a low turbulence culture environment which promotes the formation of large, three-dimensional cell clusters. Due to their high level of cellular organization and specialization, samples constructed in the bioreactor more closely resemble the original tumor or tissue found in the body. NASA-sponsored bioreactor research has been instrumental in helping scientists to better understand normal and cancerous tissue development. In cooperation with the medical community, the bioreactor design is being used to prepare better models of human colon, prostate, breast and ovarian tumors. Cartilage, bone marrow, heart muscle, skeletal muscle, pancreatic islet cells, liver and kidney are just a few of the normal tissues currently being cultured in rotating bioreactors by investigators.

  20. Bioreactor

    NASA Technical Reports Server (NTRS)

    1996-01-01

    The NASA Bioreactor provides a low turbulence culture environment which promotes the formation of large, three-dimensional cell clusters. Due to their high level of cellular organization and specialization, samples constructed in the bioreactor more closely resemble the original tumor or tissue found in the body. NASA-sponsored bioreactor research has been instrumental in helping scientists to better understand normal and cancerous tissue development. In cooperation with the medical community, the bioreactor design is being used to prepare better models of human colon, prostate, breast and ovarian tumors. Cartilage, bone marrow, heart muscle, skeletal muscle, pancreatic islet cells, liver and kidney are just a few of the normal tissues currently being cultured in rotating bioreactors by investigators

  1. Rotating Bioreactor

    NASA Technical Reports Server (NTRS)

    1988-01-01

    The NASA Bioreactor provides a low turbulence culture environment which promotes the formation of large, three-dimensional cell clusters. Due to their high level of cellular organization and specialization, samples constructed in the bioreactor more closely resemble the original tumor or tissue found in the body. NASA-sponsored bioreactor research has been instrumental in helping scientists to better understand normal and cancerous tissue development. In cooperation with the medical community, the bioreactor design is being used to prepare better models of human colon, prostate, breast and ovarian tumors. Cartilage, bone marrow, heart muscle, skeletal muscle, pancreatic islet cells, liver and kidney are just a few of the normal tissues currently being cultured in rotating bioreactors by investigators.

  2. Could MRI Be Used To Image Kidney Fibrosis? A Review of Recent Advances and Remaining Barriers.

    PubMed

    Leung, General; Kirpalani, Anish; Szeto, Stephen G; Deeb, Maya; Foltz, Warren; Simmons, Craig A; Yuen, Darren A

    2017-06-07

    A key contributor to the progression of nearly all forms of CKD is fibrosis, a largely irreversible process that drives further kidney injury. Despite its importance, clinicians currently have no means of noninvasively assessing renal scar, and thus have historically relied on percutaneous renal biopsy to assess fibrotic burden. Although helpful in the initial diagnostic assessment, renal biopsy remains an imperfect test for fibrosis measurement, limited not only by its invasiveness, but also, because of the small amounts of tissue analyzed, its susceptibility to sampling bias. These concerns have limited not only the prognostic utility of biopsy analysis and its ability to guide therapeutic decisions, but also the clinical translation of experimental antifibrotic agents. Recent advances in imaging technology have raised the exciting possibility of magnetic resonance imaging (MRI)-based renal scar analysis, by capitalizing on the differing physical features of fibrotic and nonfibrotic tissue. In this review, we describe two key fibrosis-induced pathologic changes (capillary loss and kidney stiffening) that can be imaged by MRI techniques, and the potential for these new MRI-based technologies to noninvasively image renal scar. Copyright © 2017 by the American Society of Nephrology.

  3. Could MRI Be Used To Image Kidney Fibrosis? A Review of Recent Advances and Remaining Barriers

    PubMed Central

    Leung, General; Kirpalani, Anish; Szeto, Stephen G.; Deeb, Maya; Foltz, Warren; Simmons, Craig A.

    2017-01-01

    A key contributor to the progression of nearly all forms of CKD is fibrosis, a largely irreversible process that drives further kidney injury. Despite its importance, clinicians currently have no means of noninvasively assessing renal scar, and thus have historically relied on percutaneous renal biopsy to assess fibrotic burden. Although helpful in the initial diagnostic assessment, renal biopsy remains an imperfect test for fibrosis measurement, limited not only by its invasiveness, but also, because of the small amounts of tissue analyzed, its susceptibility to sampling bias. These concerns have limited not only the prognostic utility of biopsy analysis and its ability to guide therapeutic decisions, but also the clinical translation of experimental antifibrotic agents. Recent advances in imaging technology have raised the exciting possibility of magnetic resonance imaging (MRI)–based renal scar analysis, by capitalizing on the differing physical features of fibrotic and nonfibrotic tissue. In this review, we describe two key fibrosis-induced pathologic changes (capillary loss and kidney stiffening) that can be imaged by MRI techniques, and the potential for these new MRI-based technologies to noninvasively image renal scar. PMID:28298435

  4. Cadmium in tissues of green turtles (Chelonia mydas): A global perspective for marine biota.

    PubMed

    Fraga, Nairana Santos; Martins, Agnaldo Silva; Faust, Derek R; Sakai, Haruya; Bianchini, Adalto; da Silva, Cinthia Carneiro; Aguirre, A Alonso

    2018-05-09

    Cadmium (Cd) is a metal of toxicological interest because of its potential high toxicity to organisms and ability to biomagnify. Evaluating concentrations of Cd in organisms on a large spatial scale can provide insights to its global distribution. This study examined Cd concentrations in kidney and liver tissues of 137 specimens of green turtles (Chelonia mydas) collected in Australia, Brazil, Hawaii, Japan, and the continental United States (Gulf of Mexico). We used comparative analyses of kidney and liver of 35 individuals, of which seven turtles from each locality belong to the same size class for comparison purposes between their ocean of origin. Cd was detected in all samples, with the highest bioconcentration in kidneys. Specimens originating from the Pacific Ocean had significantly higher mean Cd levels in liver (13.24 μg/g) and kidney (34.17 μg/g) than the specimens collected in the Atlantic Ocean with lower mean values in liver (1.00 μg/g) and kidney (4.04 μg/g). Furthermore, Cd concentrations in turtle tissues were generally greater than concentrations found in other marine organisms, for example dolphins. This result was unexpected because dolphins occupy a higher trophic level than green turtles which are only herbivorous. A possible explanation is a change in feeding habits of green turtles, in which juveniles feed in near shore habitats, potentially resulting in greater Cd accumulation in juveniles compared to adults. This global distribution trend has also been observed in other marine organisms (e.g., insects, birds, and mammals) and indicates that global factors may be more important than regional factors in determining Cd concentrations of marine organisms. Global factors are more relevant than local factors in the distribution of cadmium in biota, using green turtle as a sentinel species. Copyright © 2018. Published by Elsevier B.V.

  5. Isotonicity of liver and of kidney tissue in solutions of electrolytes.

    PubMed

    OPIE, E L

    1959-07-01

    Solutions of a wide variety of electrolytes, isotonic with liver or with kidney tissue, have approximately the same osmotic pressure as solutions of sodium chloride isotonic with tissues of the two organs respectively; that is, with solutions approximately twice as concentrated as the sodium chloride of mammalian blood plasma. The molar concentration of various electrolytes isotonic with liver or with kidney tissue immediately after its removal from the body is determined by the molecular weight, valency, and ion-dissociation of these electrolytes in accordance with the well known conditions of osmosis. The plasma membranes of liver and of kidney cells are imperfectly semipermeable to electrolytes, and those that enter the cell, though retarded in so doing, bring about injury which increases permeability to water. The osmotic activity of cells of mammalian liver and kidney immediately after their removal from the body resembles that of plant cells, egg cells of marine invertebrates, and mammalian red blood corpuscles and presumably represents a basic property of living cells by which osmotic pressure may be adjusted to functional need.

  6. ISOTONICITY OF LIVER AND OF KIDNEY TISSUE IN SOLUTIONS OF ELECTROLYTES

    PubMed Central

    Opie, Eugene L.

    1959-01-01

    Solutions of a wide variety of electrolytes, isotonic with liver or with kidney tissue, have approximately the same osmotic pressure as solutions of sodium chloride isotonic with tissues of the two organs respectively; that is, with solutions approximately twice as concentrated as the sodium chloride of mammalian blood plasma. The molar concentration of various electrolytes isotonic with liver or with kidney tissue immediately after its removal from the body is determined by the molecular weight, valency, and ion-dissociation of these electrolytes in accordance with the well known conditions of osmosis. The plasma membranes of liver and of kidney cells are imperfectly semipermeable to electrolytes, and those that enter the cell, though retarded in so doing, bring about injury which increases permeability to water. The osmotic activity of cells of mammalian liver and kidney immediately after their removal from the body resembles that of plant cells, egg cells of marine invertebrates, and mammalian red blood corpuscles and presumably represents a basic property of living cells by which osmotic pressure may be adjusted to functional need. PMID:13664872

  7. The E2F3—Oncomir 1 axis is activated in Wilms Tumor

    PubMed Central

    Kort, Eric J.; Farber, Leslie; Tretiakova, Maria; Petillo, David; Furge, Kyle A.; Yang, Ximing J.; Cornelius, Albert; Teh, Bin T.

    2008-01-01

    Oncomir-1 is an oncogenic cluster of microRNAs located on chromosome 13. Previous in vitro studies demonstrated that it is transcriptionally regulated by the transcription factor E2F3. In this report we combine expression profiling of both messenger RNA (mRNA) and micro RNAs (miRNA) in Wilms tumor (WT) samples to provide the first evidence that the E2F3—Oncomir 1 axis, previously identified in cell culture, is deregulated in primary human tumors. Analysis of RNA expression signatures demonstrated that an E2F3 gene signature was activated in all Wilms tumor samples analyzed, in contrast to other kidney tumors. This finding was validated by immunohistochemistry (IHC) on the protein level. Expression of E2F3 was lowest in early stage tumors, and highest in metastatic tissue. Expression profiling of miRNAs in WT showed that expression of each measured member of the Oncomir-1 family was highest in WT relative to other kidney tumor subtypes. Quantitative polymerase chain reaction (PCR) confirmed that these microRNAs were overexpressed in Wilms tumor relative to normal kidney tissue. These results suggest that the E2F3—Oncomir-1 axis is activated in Wilms tumor. Our study also demonstrates the utility of integrated genomics combining gene signature analysis with miRNA expression profiling to identify protein-miRNA interactions that are perturbed in disease states. PMID:18519660

  8. Cold preservation with hyperbranched polyglycerol-based solution improves kidney functional recovery with less injury at reperfusion in rats

    PubMed Central

    Li, Shadan; Liu, Bin; Guan, Qiunong; Chafeeva, Irina; Brooks, Donald E; Nguan, Christopher YC; Kizhakkedathu, Jayachandran N; Du, Caigan

    2017-01-01

    Minimizing donor organ injury during cold preservation (including cold perfusion and storage) is the first step to prevent transplant failure. We recently reported the advantages of hyperbranched polyglycerol (HPG) as a novel substitute for hydroxyethyl starch in UW solution for both cold heart preservation and cold kidney perfusion. This study evaluated the functional recovery of the kidney at reperfusion after cold preservation with HPG solution. The impact of HPG solution compared to conventional UW and HTK solutions on tissue weight and cell survival at 4°C was examined using rat kidney tissues and cultured human umbilical vein endothelial cells (HUVECs), respectively. The kidney protection by HPG solution was tested in a rat model of cold kidney ischemia-reperfusion injury, and was evaluated by histology and kidney function. Here, we showed that preservation with HPG solution prevented cell death in cultured HUVECs and edema formation in kidney tissues at 4°C similar to UW solution, whereas HTK solution was less effective. In rat model of cold ischemia-reperfusion injury, the kidneys perfused and subsequently stored 1-hour with cold HPG solution showed less leukocyte infiltration, less tubular damage and better kidney function (lower levels of serum creatinine and blood urea nitrogen) at 48 h of reperfusion than those treated with UW or HTK solution. In conclusion, our data show the superiority of HPG solution to UW or HTK solution in the cold perfusion and storage of rat kidneys, suggesting that the HPG solution may be a promising candidate for improved donor kidney preservation prior to transplantation. PMID:28337272

  9. Effect of trichloroethylene (TCE) toxicity on the enzymes of carbohydrate metabolism, brush border membrane and oxidative stress in kidney and other rat tissues.

    PubMed

    Khan, Sheeba; Priyamvada, Shubha; Khan, Sara A; Khan, Wasim; Farooq, Neelam; Khan, Farah; Yusufi, A N K

    2009-07-01

    Trichloroethylene (TCE), an industrial solvent, is a major environmental contaminant. Histopathological examinations revealed that TCE caused liver and kidney toxicity and carcinogenicity. However, biochemical mechanism and tissue response to toxic insult are not completely elucidated. We hypothesized that TCE induces oxidative stress to various rat tissues and alters their metabolic functions. Male Wistar rats were given TCE (1000 mg/kg/day) in corn oil orally for 25 d. Blood and tissues were collected and analyzed for various biochemical and enzymatic parameters. TCE administration increased blood urea nitrogen, serum creatinine, cholesterol and alkaline phosphatase but decreased serum glucose, inorganic phosphate and phospholipids indicating kidney and liver toxicity. Activity of hexokinase, lactate dehydrogenase increased in the intestine and liver whereas decreased in renal tissues. Malate dehydrogenase and glucose-6-phosphatase and fructose-1, 6-bisphosphatase decreased in all tissues whereas increased in medulla. Glucose-6-phosphate dehydrogenase increased but NADP-malic enzyme decreased in all tissues except in medulla. The activity of BBM enzymes decreased but renal Na/Pi transport increased. Superoxide dismutase and catalase activities variably declined whereas lipid peroxidation significantly enhanced in all tissues. The present results indicate that TCE caused severe damage to kidney, intestine, liver and brain; altered carbohydrate metabolism and suppressed antioxidant defense system.

  10. Introduction of a new laser-scalpel for partial kidney resection based on 1.94 micrometer fiber laser system: initial in vivo-data

    NASA Astrophysics Data System (ADS)

    Tedsen, Sönke; Theisen-Kunde, Dirk; Doehn, Christian; Kausch, Ingo; Jocham, Dieter

    2009-02-01

    The technique of nephron sparing surgery has matured significantly over the past decade and is emerging as an oncologically sound procedure for the management of renal tumors. Methods of tumor excision as well as parenchymal reconstruction in a hemostaticallly controlled field have evolved to make this procedure safer. In an attempt to find an improoved hemostatic cutting instrument we developed a 1.94 micrometer Laser-Scalpel system in a porcine model. We evaluated data for partial porcine kidney resection performed by a 1.94 micrometer Laser-Scalpel and compared the data to those of a standard HF- (High- Frequency) dissection device. In 12 pigs general anesthesia and a median laparotomy was performed to expose both kidneys. In each pig one kidney was partially resected with the Laser-Scalpel and the other side with the HF-dissection device. The first 6 pigs were euthanized immediately after the procedure. The following 6 pigs were allowed to recover and underwent 2-3 weeks later euthanasia. The final evaluation data included total resection time, blood loss, mass of dissected tissue, total ischemic time and histological examination. Mean resected kidney tissue mass was 4.75 g with the laser system and 5.57 g for the HF-dissector, respectively. Mean estimated blood loss was 22 ml for the Laser- Scalpel and 78.2 ml for the HF-dissection device. Resection time was 9.45 min for the Laser-scalpel compared to 10.16 min. No complications, specifically no postoperative bleeding, occured in any of the animals. Histological evaluation with H&E staining showed a carbonized zone of about 0.57 mm directly at the dissected edge followed by a thermal damaged zone of about 1.25 mm in width. Thereafter healthy tissue was found in all histological samples. Partial kidney resection was easily and fast performed by the use of a 1.94 micrometer Laser-Scalpel system. Hemostasis was highly sufficient, so blood loss was minimal compared to conventional HF-dissection device. Therefore the 1.94 micrometer Laser-Scalpel system is a very promising dissection device for urological surgery.

  11. Intermediate Volume on Computed Tomography Imaging Defines a Fibrotic Compartment that Predicts Glomerular Filtration Rate Decline in Autosomal Dominant Polycystic Kidney Disease Patients

    PubMed Central

    Caroli, Anna; Antiga, Luca; Conti, Sara; Sonzogni, Aurelio; Fasolini, Giorgio; Ondei, Patrizia; Perico, Norberto; Remuzzi, Giuseppe; Remuzzi, Andrea

    2011-01-01

    Total kidney and cyst volumes have been used to quantify disease progression in autosomal dominant polycystic kidney disease (ADPKD), but a causal relationship with progression to renal failure has not been demonstrated. Advanced image processing recently allowed to quantify extracystic tissue, and to identify an additional tissue component named “intermediate,” appearing hypoenhanced on contrast-enhanced computed tomography (CT). The aim of this study is to provide a histological characterization of intermediate volume, investigate its relation with renal function, and provide preliminary evidence of its role in long-term prediction of functional loss. Three ADPKD patients underwent contrast-enhanced CT scans before nephrectomy. Histological samples of intermediate volume were drawn from the excised kidneys, and stained with hematoxylin and eosin and with saturated picrosirius solution for histological analysis. Intermediate volume showed major structural changes, characterized by tubular dilation and atrophy, microcysts, inflammatory cell infiltrate, vascular sclerosis, and extended peritubular interstitial fibrosis. A significant correlation (r = −0.69, P < 0.001) between relative intermediate volume and baseline renal function was found in 21 ADPKD patients. Long-term prediction of renal functional loss was investigated in an independent cohort of 13 ADPKD patients, followed for 3 to 8 years. Intermediate volume, but not total kidney or cyst volume, significantly correlated with glomerular filtration rate decline (r = −0.79, P < 0.005). These findings suggest that intermediate volume may represent a suitable surrogate marker of ADPKD progression and a novel therapeutic target. PMID:21683674

  12. Assessing risk of mercury exposure and nutritional benefits of consumption of caribou (Rangifer tarandus) in the Vuntut Gwitchin First Nation community of Old Crow, Yukon, Canada.

    PubMed

    Schuster, Roseanne C; Gamberg, Mary; Dickson, Cindy; Chan, Hing Man

    2011-08-01

    The contamination of traditional foods with chemical pollutants is a challenge to the food security of Aboriginal Peoples. Mercury levels are generally low in terrestrial animals; however renal mercury levels have been shown to change over time in the Porcupine Caribou Herd, the principal food source for the Vuntut Gwitchin First Nation of Old Crow in Yukon, Canada. Seventy-five Porcupine Caribou muscle, sixty-three kidney and three liver samples were analyzed for total mercury. Average concentrations were 0.003, 0.360 and 0.120mg/kg wet weight total mercury for muscle, kidney and liver, respectively. Consumption data of caribou muscle, kidney and liver were collected from twenty-six adults in Vuntut Gwitchin households. Women of child-bearing age (n=5) consumed a median of 71.5g/person/day of caribou muscle and 0.0g/person/day kidney but consumed no liver; median consumptions for all other adults (women aged 40+ and all men, n=21) were 75.8, 3.2 and 2.5g/person/day for meat, kidney and liver, respectively. Median dietary exposures to total mercury from caribou tissues were estimated to be 0.138μg/kg body weight for women of child-bearing age and 0.223μg/kg body weight for other adults. Caribou tissues were found to contribute high levels of important nutrients to the diet and pose minimal health risk from mercury exposure. Copyright © 2011 Elsevier Inc. All rights reserved.

  13. Perspectives on using a multiplex human kidney safety biomarker panel to detect cisplatin-induced tubular toxicity in male and female Cynomolgus monkeys.

    PubMed

    Chen, Yafei; Dale Thurman, J; Kinter, Lewis B; Bialecki, Russell; Eric McDuffie, J

    2017-12-01

    Multiplex biomarker panel assays would enable early de-risking of discovery compound related kidney safety liabilities. The objective of this study was to evaluate the usefulness of the Myriad RBM Human KidneyMAP (Multi-Analyte Profile)® v.1.0 panel to detect experimental nephrotoxicity in Cynomolgus monkeys following a single intravenous administration of cisplatin (2.5mg/kg). Urine samples were collected at baseline on day -2; at approximately 4hr post-dose on day 1; and on days 4, 9, 15 and/or 20. Blood samples were collected at predose on day -2; at 4hr post-dose on day 1; and on days 2, 5, 10 and/or 21. Changes in toxicokinetic and biochemistry parameters in plasma, qualitative/quantitative urinalysis parameters, and urinary kidney safety biomarkers were assessed. Kidney tissues were collected on days 2, 5, 10 and 21 for routine microscopy. Cisplatin-induced tubular alterations were characterized by acute and progressive cortical tubular degeneration/necrosis, regeneration, tubular dilation and proteinaceous cast in the absence of statistically significant changes in traditional plasma biochemistry and urinalysis parameters. When normalized to urinary creatinine, cisplatin-induced significant increases in urinary levels of kidney injury molecule 1 (females on day 4), increases in calbindin D28k (males and females on day 4), decreases in Tamm-Horsfall glycoprotein (males on days 1, 4 and 9), and increases in clusterin (females and males on days 15 and 20, respectively), when compared to concurrent controls. This study revealed the usefulness of the Human KidneyMAP® multiplex panel when measuring changes in urine-based biomarkers to reliably detect cisplatin-induced acute/progressive cortical tubular injury in male and female Cynomolgus monkeys. Copyright © 2017 Elsevier Inc. All rights reserved.

  14. SWIR dispersive Raman spectroscopy for discrimination of normal and malignant kidney tissue (Conference Presentation)

    NASA Astrophysics Data System (ADS)

    Haifler, Miki; Pence, Isaac J.; Zisman, Amnon; Uzzo, Robert G.; Greenberg, Richard; Kutikov, Alexander; Smaldone, Marc; Chen, David; Viterbo, Rosalia; Ristau, Benjamin; Mahadevan-Jansen, Anita; Dumont, Alexander; Patil, Chetan A.

    2017-02-01

    Kidney cancer affects 65,000 new patients every. As computerized tomography became ubiquitous, the number of small, incidentally detected renal masses increased. About 6,000 benign cases are misclassified radiographically as malignant and removed surgically. Raman spectroscopy (RS) has been widely demonstrated for disease discrimination, however intense near-infrared auto-fluorescence of certain tissues (e.g kidney) can present serious challenges to bulk tissue diagnosis. A 1064nm excitation dispersive detection RS system demonstrated the ability to collect spectra with superior quality in tissues with strong auto-fluorescence. Our objective is to develop a 1064 nm dispersive detection RS system capable of differentiating normal and malignant renal tissue. We will report on the design and development of a clinical system for use in nephron sparing surgeries. We will present pilot data that has been collected from normal and malignant ex vivo kidney specimens using a benchtop RS system. A total of 93 measurements were collected from 12 specimens (6 Renal Cell Carcinoma, 6 Normal ). Spectral classification was performed using sparse multinomial logistic regression (SMLR). Correct classification by SMLR was obtained in 78% of the trials with sensitivity and specificity of 82% and 75% respectively. We will present the association of spectral features with biological indicators of healthy and diseased kidney tissue. Our findings indicate that 1064nm RS is a promising technique for differentiation of normal and malignant renal tissue. This indicates the potential for accurately separating healthy and cancerous tissues and suggests implications for utilizing RS for optical biopsy and surgical guidance in nephron sparing surgery.

  15. The use of feather as an indicator for heavy metal contamination in house crow (Corvus splendens) in the Klang area, Selangor, Malaysia.

    PubMed

    Janaydeh, Mohammed; Ismail, Ahmad; Zulkifli, Syaizwan Zahmir; Bejo, Mohd Hair; Aziz, Nor Azwady Abd; Taneenah, Ayat

    2016-11-01

    The Klang area of Peninsular Malaysia has experienced rapid industrial growth with intense activities, which can increase the concentration of pollutants in the environment that significantly impact on habitats and the human health. The purpose of this study was to determine the levels of selected heavy metals (Cu, Zn, Ni, Fe, and Pb) in the heart, lung, brain, liver, kidney, muscle tissues, and feathers of house crow, Corvus splendens, in Klang, Peninsular Malaysia. House crow samples were collected from the Klang area through the Department of Public Health at Majlis Perbandaran Klang. Quantitative determination of heavy metals was carried out using atomic absorption spectrophotometer (AAS). The result shows the presence of heavy metals in all biological samples of house crows. For heavy metals in all the house crow tissues analyzed, Fe concentrations were the highest, followed by those of Zn, Cu, Pb, and Ni. The feathers and kidney accumulated high concentrations of Pb, whereas the liver accumulated high concentrations of essential heavy metals (Fe > Zn > Cu > Ni). Significant variations were also detected in the concentrations of Pb among adult and juvenile and male and female bird samples. The results also revealed significant positive correlations between Pb metal concentration in the breast feathers and all internal organs. Accumulation of toxic heavy metals in feathers reflected storing and elimination processes, while the accumulation of toxic heavy metals in the kidney can be consequential to chronic exposure. The present study clearly shows the usefulness of house crow breast feather as a suitable indicator for heavy metal accumulation in the internal organs of house crows in the Klang area.

  16. Occurrence of organochlorines in the green sea turtle (Chelonia mydas) on the northern coast of the state of São Paulo, Brazil.

    PubMed

    da Silva, Josilene; Taniguchi, Satie; Becker, José Henrique; Werneck, Max Rondon; Montone, Rosalinda Carmela

    2016-11-15

    Organochlorines (OCs), such as pesticides and polychlorinated biphenyls (PCBs), are persistent, toxic and widely distributed through atmospheric transport and ocean currents. Few studies have been conducted on OCs in sea turtles, especially on the coast of Brazil. Chelonia mydas is the largest hard-shell sea turtle and is found tropical and subtropical regions in all oceans. The aim of the present study was to determine the occurrence of OCs in the green sea turtle (C. mydas). Fat, liver, kidney and muscle samples were collected from 27 juveniles found on the beach of the city of Ubatuba on the northern coast of the state of São Paulo, Brazil. OCs were extracted with organic solvents and the extract was purified with concentrated acid. Gas chromatography-mass spectrometry and electron capture detection were used for the identification and quantification of PCBs and pesticides, respectively. No organochlorine pesticides were detected in any of the samples. Concentrations of total PCBs in wet weight were <1.6 to 48.9ng/g in fat tissue, <1.6 to 17.4ng/g in liver tissue and <1.6 to 37.7ng/g in kidney tissue. The low levels found are mainly related to diet, as the green sea turtle is basically herbivorous and lower PCB contamination compared to other regions. Copyright © 2016 Elsevier Ltd. All rights reserved.

  17. Determination of oxytetracycline residues in cattle meat marketed in the Kilosa district, Tanzania.

    PubMed

    Kimera, Zuhura I; Mdegela, Robinson H; Mhaiki, Consolatha J N; Karimuribo, Esron D; Mabiki, Faith; Nonga, Hezron E; Mwesongo, James

    2015-11-27

    Oxytetracycline is used to treat various diseases in cattle. However, its use may be associated with unacceptable residue levels in food. Oxytetracycline residues in tissues from indigenous cattle were determined in a cross-sectional study conducted in the Kilosa district, Tanzania, between November 2012 and April 2013. A total of 60 tissue samples, including muscle, liver and kidney, were collected from slaughterhouses and butchers and analysed for oxytetracycline using high-performance liquid chromatography. Oxytetracycline residues were found in 71.1% of the samples, of which 68.3% were above acceptable regulatory levels. The mean concentration of oxytetracycline across tissues was 3401.1 μg/kg ± 879.3 μg/kg; concentrations in muscle, liver and kidney were 2604.1 μg/kg ± 703.7 μg/kg, 3434.4 μg/kg ± 606.4 μg/kg and 3533.1 μg/kg ± 803.6 μg/kg, respectively. High levels of oxytetracycline residue in meat from indigenous cattle may pose a health threat to consumers in Kilosa. The findings possibly reflect a general lack of implementation of recommended withdrawal periods, ignorance about drug use and lack of extension services. Strict regulation of the use of antimicrobial drugs in the livestock industry and associated testing of animal-derived food sources prior to marketing are required.

  18. Comparison of the Ovary and Kidney as Sites for Islet Transplantation in Diabetic Rats.

    PubMed

    Karakose, M; Pinarli, F A; Arslan, M S; Boyuk, G; Boztok, B; Albayrak, A; Ulus, A T; Cakal, E; Delibasi, T

    2016-01-01

    Currently, the most commonly used site for clinical islet transplantation is the liver although it is far from being an ideal site. Low oxygen tension and the induction of an inflammatory response impair islet implantation and lead to significant early loss of islet. The present study aimed to investigate and compare the efficacy of islet transplantation to the ovary and kidney subcapsule in diabetic rats. The study was performed with 3 groups of rats (control, ovary, and kidney subcapsule) including 6 Sprague female rats each. Diabetes model was created with the use of streptozotocin, and blood glucose levels of the rats were measured after 72 hours. Thirty days after the transplantation, blood samples were obtained from the rats, and then pancreas, kidney, and ovary specimens were fixed in 10% formaldehyde and the experiment completed. After staining with hematoxylin and eosin, the tissue samples were morphologically evaluated by a specialist histopathologist. Changes in mean blood glucose and C-peptide levels were statistically significant in the ovary and kidney subcapsule groups. Histologic examination revealed that granulosus insulin-bearing cells were detected in the islet grafts of both ovary and kidney subcapsule groups. The renal subcapsule group had inflammation signs on histologic examination. The islet cells of both ovary and renal subcapsule groups had no vacuolization. We showed that the ovary might be a new site for islet transplantation. Further research should be done on whether the initial results of this study can be reproduced in larger numbers of animal models and eventually in humans. Copyright © 2016 Elsevier Inc. All rights reserved.

  19. Dual-Purpose Bioreactors to Monitor Noninvasive Physical and Biochemical Markers of Kidney and Liver Scaffold Recellularization

    PubMed Central

    Uzarski, Joseph S.; Bijonowski, Brent M.; Wang, Bo; Ward, Heather H.; Wandinger-Ness, Angela

    2015-01-01

    Analysis of perfusion-based bioreactors for organ engineering and a detailed evaluation of physical and biochemical parameters that measure dynamic changes within maturing cell-laden scaffolds are critical components of ex vivo tissue development that remain understudied topics in the tissue and organ engineering literature. Intricately designed bioreactors that house developing tissue are critical to properly recapitulate the in vivo environment, deliver nutrients within perfused media, and monitor physiological parameters of tissue development. Herein, we provide an in-depth description and analysis of two dual-purpose perfusion bioreactors that improve upon current bioreactor designs and enable comparative analyses of ex vivo scaffold recellularization strategies and cell growth performance during long-term maintenance culture of engineered kidney or liver tissues. Both bioreactors are effective at maximizing cell seeding of small-animal organ scaffolds and maintaining cell survival in extended culture. We further demonstrate noninvasive monitoring capabilities for tracking dynamic changes within scaffolds as the native cellular component is removed during decellularization and model human cells are introduced into the scaffold during recellularization and proliferate in maintenance culture. We found that hydrodynamic pressure drop (ΔP) across the retained scaffold vasculature is a noninvasive measurement of scaffold integrity. We further show that ΔP, and thus resistance to fluid flow through the scaffold, decreases with cell loss during decellularization and correspondingly increases to near normal values for whole organs following recellularization of the kidney or liver scaffolds. Perfused media may be further sampled in real time to measure soluble biomarkers (e.g., resazurin, albumin, or kidney injury molecule-1) that indicate degree of cellular metabolic activity, synthetic function, or engraftment into the scaffold. Cell growth within bioreactors is validated for primary and immortalized cells, and the design of each bioreactor is scalable to accommodate any three-dimensional scaffold (e.g., synthetic or naturally derived matrix) that contains conduits for nutrient perfusion to deliver media to growing cells and monitor noninvasive parameters during scaffold repopulation, broadening the applicability of these bioreactor systems. PMID:25929317

  20. Dual-Purpose Bioreactors to Monitor Noninvasive Physical and Biochemical Markers of Kidney and Liver Scaffold Recellularization.

    PubMed

    Uzarski, Joseph S; Bijonowski, Brent M; Wang, Bo; Ward, Heather H; Wandinger-Ness, Angela; Miller, William M; Wertheim, Jason A

    2015-10-01

    Analysis of perfusion-based bioreactors for organ engineering and a detailed evaluation of physical and biochemical parameters that measure dynamic changes within maturing cell-laden scaffolds are critical components of ex vivo tissue development that remain understudied topics in the tissue and organ engineering literature. Intricately designed bioreactors that house developing tissue are critical to properly recapitulate the in vivo environment, deliver nutrients within perfused media, and monitor physiological parameters of tissue development. Herein, we provide an in-depth description and analysis of two dual-purpose perfusion bioreactors that improve upon current bioreactor designs and enable comparative analyses of ex vivo scaffold recellularization strategies and cell growth performance during long-term maintenance culture of engineered kidney or liver tissues. Both bioreactors are effective at maximizing cell seeding of small-animal organ scaffolds and maintaining cell survival in extended culture. We further demonstrate noninvasive monitoring capabilities for tracking dynamic changes within scaffolds as the native cellular component is removed during decellularization and model human cells are introduced into the scaffold during recellularization and proliferate in maintenance culture. We found that hydrodynamic pressure drop (ΔP) across the retained scaffold vasculature is a noninvasive measurement of scaffold integrity. We further show that ΔP, and thus resistance to fluid flow through the scaffold, decreases with cell loss during decellularization and correspondingly increases to near normal values for whole organs following recellularization of the kidney or liver scaffolds. Perfused media may be further sampled in real time to measure soluble biomarkers (e.g., resazurin, albumin, or kidney injury molecule-1) that indicate degree of cellular metabolic activity, synthetic function, or engraftment into the scaffold. Cell growth within bioreactors is validated for primary and immortalized cells, and the design of each bioreactor is scalable to accommodate any three-dimensional scaffold (e.g., synthetic or naturally derived matrix) that contains conduits for nutrient perfusion to deliver media to growing cells and monitor noninvasive parameters during scaffold repopulation, broadening the applicability of these bioreactor systems.

  1. Molecular glycopathology by capillary electrophoresis: Analysis of the N-glycome of formalin-fixed paraffin-embedded mouse tissue samples.

    PubMed

    Donczo, Boglarka; Szarka, Mate; Tovari, Jozsef; Ostoros, Gyorgyi; Csanky, Eszter; Guttman, Andras

    2017-06-01

    Capillary electrophoresis with laser-induced fluorescence (CE-LIF) detection was used to analyze endoglycosidase released and fluorophore-labeled N-glycans from formalin-fixed paraffin-embedded (FFPE) mouse tissue samples of lung, brain, heart, spleen, liver, kidney and intestine. The FFPE samples were first deparaffinized followed by solubilization and glycoprotein retrieval. PNGase F mediated release of the N-linked oligosaccharides was followed by labeling with aminopyrene trisulfonate. After CE-LIF glycoprofiling of the FFPE mouse tissues, the N-glycan pool of the lung specimen was subject to further investigation by exoglycosidase array based carbohydrate sequencing. Structural assignment of the oligosaccharides was accomplished by the help of the GUcal software and the associated database, based on the mobility shifts after treatments with the corresponding exoglycosidase reaction mixtures. Sixteen major N-linked carbohydrate structures were sequenced from the mouse lung FFPE tissue glycome and identified, as high mannose (3) neutral biantennary (3) sialylated monoantennary (1) and sialylated bianennary (9) oligosaccharides. Two of these latter ones also possessed alpha(1-3) linked galactose residues. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  2. Concise Review: Kidney Stem/Progenitor Cells: Differentiate, Sort Out, or Reprogram?

    PubMed Central

    Pleniceanu, Oren; Harari-Steinberg, Orit; Dekel, Benjamin

    2010-01-01

    End-stage renal disease (ESRD) is defined as the inability of the kidneys to remove waste products and excess fluid from the blood. ESRD progresses from earlier stages of chronic kidney disease (CKD) and occurs when the glomerular filtration rate (GFR) is below 15 ml/minute/1.73 m2. CKD and ESRD are dramatically rising due to increasing aging population, population demographics, and the growing rate of diabetes and hypertension. Identification of multipotential stem/progenitor populations in mammalian tissues is important for therapeutic applications and for understanding developmental processes and tissue homeostasis. Progenitor populations are ideal targets for gene therapy, cell transplantation, and tissue engineering. The demand for kidney progenitors is increasing due to severe shortage of donor organs. Because dialysis and transplantation are currently the only successful therapies for ESRD, cell therapy offers an alternative approach for kidney diseases. However, this approach may be relevant only in earlier stages of CKD, when kidney function and histology are still preserved, allowing for the integration of cells and/or for their paracrine effects, but not when small and fibrotic end-stage kidneys develop. Although blood- and bone marrow-derived stem cells hold a therapeutic promise, they are devoid of nephrogenic potential, emphasizing the need to seek kidney stem cells beyond known extrarenal sources. Moreover, controversies regarding the existence of a true adult kidney stem cell highlight the importance of studying cell-based therapies using pluripotent cells, progenitor cells from fetal kidney, or dedifferentiated/reprogrammed adult kidney cells. Stem Cells 2010; 28:1649–1660. PMID:20652959

  3. Relationship between Pb and Cd accumulations in house crow, their habitat, and food content from Klang area, Peninsular Malaysia.

    PubMed

    Janaydeh, Mohammed; Ismail, Ahmad; Omar, Hishamuddin; Zulkifli, Syaizwan Zahmir; Bejo, Mohd Hair; Aziz, Nor Azwady Abd

    2017-12-27

    Heavy metal pollution has become a global concern due to accumulation in tissue and transferable effects to humans via the food chain. This study focused on monitoring the accumulation of cadmium (Cd) and lead (Pb) in surface soil and body content: bone, heart, brain, liver, lung, muscle, kidney, feathers, feces, and gizzard contents of house crow Corvus splendens in the Klang region, Malaysia. The results revealed the occurrence of Pb and Cd in all biological samples from house crows, food contents, and surface soil samples. Heart and kidney accrued high amounts of Cd, while high amounts of Pb were found to accumulate in bones and feathers. Major discrepancies were also discovered in the concentrations of metals between juvenile and adults, as well as female and male bird samples. Concentrations of Pb and Cd in house crow internal tissues correlated significantly with that of bird feathers, but none could be established with that of surface soil. In addition, a significant correlation was observed between Pb concentration in the internal tissues to that of the feces, but the same was not the case when compared with the surface soil concentration. Metal accrual in the house crows feathers and feces may be through a long-term transmission via the food chain, which are eliminated from feathers via molting. This may suggest the utility of molted breast feathers of house crow in the bio-monitoring of Cd and Pb contamination, whereas feces of house crow appear only to be suitable for the bio-monitoring of Pb contamination.

  4. Antioxidant effect of Arabic gum against mercuric chloride-induced nephrotoxicity.

    PubMed

    Gado, Ali M; Aldahmash, Badr A

    2013-01-01

    The effects of Arabic gum (AG) against nephrotoxicity of mercury (Hg), an oxidative-stress inducing substance, in rats were investigated. A single dose of mercuric chloride (5 mg/kg intraperitoneal injection) induced renal toxicity, manifested biochemically by a significant increase in serum creatinine, blood urea nitrogen, thiobarbituric acid reactive substances, and total nitrate/nitrite production in kidney tissues. In addition, reduced glutathione, glutathione peroxidase, and catalase enzymes in renal tissues were significantly decreased. Pretreatment of rats with AG (7.5 g/kg/day per oral administration), starting 5 days before mercuric chloride injection and continuing through the experimental period, resulted in a complete reversal of Hg-induced increase in creatinine, blood urea nitrogen, thiobarbituric acid reactive substances, and total nitrate/nitrite to control values. Histopathologic examination of kidney tissues confirmed the biochemical data; pretreatment of AG prevented Hg-induced degenerative changes of kidney tissues. These results indicate that AG is an efficient cytoprotective agent against Hg-induced nephrotoxicity by a mechanism related at least in part to its ability to decrease oxidative and nitrosative stress and preserve the activity of antioxidant enzymes in kidney tissues.

  5. The role of myoglobin degradation in nephrotoxicity after rhabdomyolysis.

    PubMed

    Zorova, Ljubava D; Pevzner, Irina B; Chupyrkina, Anastasia A; Zorov, Savva D; Silachev, Denis N; Plotnikov, Egor Y; Zorov, Dmitry B

    2016-08-25

    The fate of myoglobin in renal cells was explored in an animal model of rhabdomyolysis known as the pathology highly related to oxidative stress resulting in impairment of renal functioning. The working hypothesis was that the proper degradation of myoglobin in rhabdomyolytic kidney can activate the reparative processes in the tissue. We found that incubation of myoglobin with kidney cells causes its accumulation in the cytoplasm. In rhabdomyolytic rats, the level of heme and free iron in cytoplasm and mitochondria of kidney cells is remarkably increased while inhibition of proteolysis results in further elevation of myoglobin content in the renal tissue. Heme oxygenase and ferritin levels were found to be increased in the kidney tissue at rhabdomyolysis and simulating conditions performed by i/v injection of myoglobin. In addition, the level of peroxidized lipids was high in rhabdomyolytic kidney and became even higher after inhibition of proteolysis by aprotinin. Elevated levels of carbonylated proteins were also observed after rhabdomyolysis, however, if prior to induction of rhabdomyolysis the injection of myoglobin was done, the level of carbonylated proteins dropped versus unprimed kidney tissue thus affording protection to the kidney against oxidative stress. Injection of myoglobin to the rat results in impairment of renal functioning and inhibition of myoglobin degradation in the rhabdomyolytic animal aggravates acute renal failure, demonstrating that degradation of myoglobin is somehow beneficial although it may result in undesired release of free iron which can participate in toxic redox cycling. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  6. Detection of Nanophyetus salmincola in water, snails, and fish tissues by quantitative polymerase chain reaction

    USGS Publications Warehouse

    Purcell, Maureen K.; Powers, Rachel L.; Besijn, Bonnie; Hershberger, Paul K.

    2017-01-01

    We report the development and validation of two quantitative PCR (qPCR) assays to detect Nanophyetus salmincola DNA in water samples and in fish and snail tissues. Analytical and diagnostic validation demonstrated good sensitivity, specificity, and repeatability of both qPCR assays. The N. salmincola DNA copy number in kidney tissue was significantly correlated with metacercaria counts based on microscopy. Extraction methods were optimized for the sensitive qPCR detection of N. salmincola DNA in settled water samples. Artificially spiked samples suggested that the 1-cercaria/L threshold corresponded to an estimated log10 copies per liter ≥ 6.0. Significant correlation of DNA copy number per liter and microscopic counts indicated that the estimated qPCR copy number was a good predictor of the number of waterborne cercariae. However, the detection of real-world samples below the estimated 1-cercaria/L threshold suggests that the assays may also detect other N. salmincola life stages, nonintact cercariae, or free DNA that settles with the debris. In summary, the qPCR assays reported here are suitable for identifying and quantifying all life stages of N. salmincola that occur in fish tissues, snail tissues, and water.

  7. Ractopamine analysis in pig kidney, liver and lungs: A validation of the method scope extension using QuEChERS as a sample preparation step.

    PubMed

    Feddern, Vivian; Aroeira, Carolina Naves; Molognoni, Luciano; Gressler, Vanessa; Daguer, Heitor; Dalla Costa, Osmar Antonio; Castillo, Carmen Josefina Contreras; de Lima, Gustavo Julio Mello Monteiro

    2018-05-23

    Ractopamine has been allowed by some countries as a repartitioning additive in pig diet, since it promotes protein synthesis and fat lipolysis. Most regulatory agencies only propose the ractopamine assessment in meat, kidney, liver and fat. Aiming at contributing to the scarcity data regarding this analyte in pig lungs, we extended the scope of a LC-MS method to evaluate pig offals. Homogenized tissue samples were extracted by a QuEChERS procedure; following by clean up steps and further tandem mass spectrometry determination. Method performance was evaluated through specificity, recovery, linearity, reproducibility, repeatability, decision limit (CC α ), and detection capability (CC β ), in accordance to the Commission Decision 2002/657/EC. Regression coefficients (R 2 ) between 0.994 and 0.999 were achieved for kidney, liver and lungs. Recoveries ranged from 92.0 to 127%. CC α and CC β values ranged from 3.65 to 4.86 μg kg -1 , and from 6.27 to 7.21 μg kg -1 , respectively. These values were under the maximum residue limits suggested by Codex Alimentarius, which are 90 and 40 μg kg -1 for kidney and liver, respectively. When applied to real samples up to 22.5, 92 and 1003 μg kg -1 of ractopamine residues were detected in pig liver, kidney and lungs, respectively. The results allowed concluding that the proposed analytical method is capable to detect ractopamine residues in all evaluated matrices. Therefore, it can be successfully applied and used as a routine method in laboratories of residue analysis. Copyright © 2018. Published by Elsevier B.V.

  8. A rabbit model of non-typhoidal Salmonella bacteremia.

    PubMed

    Panda, Aruna; Tatarov, Ivan; Masek, Billie Jo; Hardick, Justin; Crusan, Annabelle; Wakefield, Teresa; Carroll, Karen; Yang, Samuel; Hsieh, Yu-Hsiang; Lipsky, Michael M; McLeod, Charles G; Levine, Myron M; Rothman, Richard E; Gaydos, Charlotte A; DeTolla, Louis J

    2014-09-01

    Bacteremia is an important cause of morbidity and mortality in humans. In this study, we focused on the development of an animal model of bacteremia induced by non-typhoidal Salmonella. New Zealand White rabbits were inoculated with a human isolate of non-typhoidal Salmonella strain CVD J73 via the intra-peritoneal route. Blood samples were collected at specific time points and at euthanasia from infected rabbits. Additionally, tissue samples from the heart, lungs, spleen, gastrointestinal tract, liver and kidneys were obtained at euthanasia. All experimentally infected rabbits displayed clinical signs of disease (fever, dehydration, weight loss and lethargy). Tissues collected at necropsy from the animals exhibited histopathological changes indicative of bacteremia. Non-typhoidal Salmonella bacteria were detected in the blood and tissue samples of infected rabbits by microbiological culture and real-time PCR assays. The development of this animal model of bacteremia could prove to be a useful tool for studying how non-typhoidal Salmonella infections disseminate and spread in humans. Copyright © 2014 Elsevier Ltd. All rights reserved.

  9. Uranium hexafluoride public risk

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

    Fisher, D.R.; Hui, T.E.; Yurconic, M.

    1994-08-01

    The limiting value for uranium toxicity in a human being should be based on the concentration of uranium (U) in the kidneys. The threshold for nephrotoxicity appears to lie very near 3 {mu}g U per gram kidney tissue. There does not appear to be strong scientific support for any other improved estimate, either higher or lower than this, of the threshold for uranium nephrotoxicity in a human being. The value 3 {mu}g U per gram kidney is the concentration that results from a single intake of about 30 mg soluble uranium by inhalation (assuming the metabolism of a standard person).more » The concentration of uranium continues to increase in the kidneys after long-term, continuous (or chronic) exposure. After chronic intakes of soluble uranium by workers at the rate of 10 mg U per week, the concentration of uranium in the kidneys approaches and may even exceed the nephrotoxic limit of 3 {mu}g U per gram kidney tissue. Precise values of the kidney concentration depend on the biokinetic model and model parameters assumed for such a calculation. Since it is possible for the concentration of uranium in the kidneys to exceed 3 {mu}g per gram tissue at an intake rate of 10 mg U per week over long periods of time, we believe that the kidneys are protected from injury when intakes of soluble uranium at the rate of 10 mg U per week do not continue for more than two consecutive weeks. For long-term, continuous occupational exposure to low-level, soluble uranium, we recommend a reduced weekly intake limit of 5 mg uranium to prevent nephrotoxicity in workers. Our analysis shows that the nephrotoxic limit of 3 {mu}g U per gram kidney tissues is not exceeded after long-term, continuous uranium intake at the intake rate of 5 mg soluble uranium per week.« less

  10. Modulation of metallothionein and metal partitioning in liver and kidney of Solea senegalensis after long-term acclimation to two environmental temperatures

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

    Siscar, R.; Torreblanca, A.; Ramo, J. del

    Juveniles of Solea senegalensis were fed with commercial pellets under controlled conditions at two environmental Mediterranean temperatures (15 and 20 °C) for two months. After this period, the accumulation of essential and non-essential metals and metallothionein (MT) levels was measured in liver and kidney by inductively coupled plasma mass spectrometry (ICP-MS) and pulse polarography, respectively. The bioaccumulation factor (BAF) for selected metals in both tissues was calculated in relation to levels present in the feed. Tissue partitioning (liver/kidney) and molar ratios, considering the metal protective mechanisms: MT and Selenium (Se), were included for evaluating the detoxification capacity of each tissue.more » Ag, Cd, Cu and Mn were preferentially accumulated in the liver whereas Co, Fe, Hg, Se and Zn were found in larger concentrations in the kidney, and higher temperature enhanced the accumulation of some of them, but not all. MT content in liver, but not in kidney, was also influenced by temperature changes and by length of exposure. The BAF revealed that Cu was taken up mainly by the liver whereas Se was efficiently taken up by both tissues. The high molar ratios of MT and most metals denoted the kidney's remarkable spare capacity for metal detoxification through MT binding. Moreover, the potential protective role of Se was also more evident in kidney as a higher Se:Cd and Se:Ag molar ratios were reached in this organ. In contrast to other fish, the storage of Cd in kidney was particularly low. - Highlights: • Long-term increases in temperature entailed changes in MT and metal content in liver. • The liver is the preferred storage organ for most metals. • Se assimilation from feed results in a high BAF in the liver and kidney. • MT/metal and Se/metal are higher in kidney than in liver for most metals, except Cd.« less

  11. Molecular evidence of simian virus 40 infections in children

    NASA Technical Reports Server (NTRS)

    Butel, J. S.; Arrington, A. S.; Wong, C.; Lednicky, J. A.; Finegold, M. J.

    1999-01-01

    Recent studies have detected simian virus 40 (SV40) DNA in certain human tumors and normal tissues. The significance of human infections by SV40, which was first discovered as a contaminant of poliovirus vaccines used between 1955 and 1963, remains unknown. The occurrence of SV40 infections in unselected hospitalized children was evaluated. Polymerase chain reaction and DNA sequence analyses were done on archival tissue specimens from patients positive for SV40 neutralizing antibody. SV40 DNA was identified in samples from 4 of 20 children (1 Wilms' tumor, 3 transplanted kidney samples). Sequence variation among SV40 regulatory regions ruled out laboratory contamination of specimens. This study shows the presence of SV40 infections in pediatric patients born after 1982.

  12. Carotid Catheterization and Automated Blood Sampling Induce Systemic IL-6 Secretion and Local Tissue Damage and Inflammation in the Heart, Kidneys, Liver and Salivary Glands in NMRI Mice.

    PubMed

    Teilmann, Anne Charlotte; Rozell, Björn; Kalliokoski, Otto; Hau, Jann; Abelson, Klas S P

    2016-01-01

    Automated blood sampling through a vascular catheter is a frequently utilized technique in laboratory mice. The potential immunological and physiological implications associated with this technique have, however, not been investigated in detail. The present study compared plasma levels of the cytokines IL-1β, IL-2, IL-6, IL-10, IL-17A, GM-CSF, IFN-γ and TNF-α in male NMRI mice that had been subjected to carotid artery catheterization and subsequent automated blood sampling with age-matched control mice. Body weight and histopathological changes in the surgical area, including the salivary glands, the heart, brain, spleen, liver, kidneys and lungs were compared. Catheterized mice had higher levels of IL-6 than did control mice, but other cytokine levels did not differ between the groups. No significant difference in body weight was found. The histology revealed inflammatory and regenerative (healing) changes at surgical sites of all catheterized mice, with mild inflammatory changes extending into the salivary glands. Several catheterized mice had multifocal degenerative to necrotic changes with inflammation in the heart, kidneys and livers, suggesting that thrombi had detached from the catheter tip and embolized to distant sites. Thus, catheterization and subsequent automated blood sampling may have physiological impact. Possible confounding effects of visceral damage should be assessed and considered, when using catheterized mouse models.

  13. Experimental verification of stopping-power prediction from single- and dual-energy computed tomography in biological tissues

    NASA Astrophysics Data System (ADS)

    Möhler, Christian; Russ, Tom; Wohlfahrt, Patrick; Elter, Alina; Runz, Armin; Richter, Christian; Greilich, Steffen

    2018-01-01

    An experimental setup for consecutive measurement of ion and x-ray absorption in tissue or other materials is introduced. With this setup using a 3D-printed sample container, the reference stopping-power ratio (SPR) of materials can be measured with an uncertainty of below 0.1%. A total of 65 porcine and bovine tissue samples were prepared for measurement, comprising five samples each of 13 tissue types representing about 80% of the total body mass (three different muscle and fatty tissues, liver, kidney, brain, heart, blood, lung and bone). Using a standard stoichiometric calibration for single-energy CT (SECT) as well as a state-of-the-art dual-energy CT (DECT) approach, SPR was predicted for all tissues and then compared to the measured reference. With the SECT approach, the SPRs of all tissues were predicted with a mean error of (-0.84  ±  0.12)% and a mean absolute error of (1.27  ±  0.12)%. In contrast, the DECT-based SPR predictions were overall consistent with the measured reference with a mean error of (-0.02  ±  0.15)% and a mean absolute error of (0.10  ±  0.15)%. Thus, in this study, the potential of DECT to decrease range uncertainty could be confirmed in biological tissue.

  14. [Induction of hypoxia-inducible factor-1alpha in two kinds of rats asphyxiation death models].

    PubMed

    Zhang, Bei-lei; Yang, Zhi-hui; Ran, Peng; Liang, Wei-bo; Zhou, Bin; Zhang, Geng-qian; Lu, Mei-li; Zhang, Lin

    2007-02-15

    To investigate the expression of hypoxia-inducible factor 1-alpha (HIF1-alpha) in the heart, lung, liver and kidney in rats died of two typical models of asphyxia. Two asphyxia models were made and tissue samples of the dead rats were collected from different groups at various postmortem duration. The expression and the changes of HIF1-alpha in various tissues were examined by immunohistochemistry and image analysis techniques. Results Significant expression of HIF1-alpha was observed in the myocardial fibers, kidney cells, liver cells and lung cells in both asphyxia models, but not in the control group. The expression of HIF1-alpha in various tissues in the rat died of nitrogen gas breathing was found in the nuclei at 0 hour and the expression level decreased gradually thereafter. The HIF1-alpha expression level and duration in various tissues of the rat died of hanging were higher and longer than that of the former group, with a peak of the expression level observed 6 hours after death, and then started to decline in all tissues except the heart where the expression still showed an increase 24 hours after death. The control groups showed a steady expression in the cytoplasm but not in the nuclei. HIF1-alpha appears to be a valuable biomarker in the diagnosis of asphyxia within 24 hours after death.

  15. Heavy metal accumulation in lizards living near a phosphate treatment plant: possible transfer of contaminants from aquatic to terrestrial food webs.

    PubMed

    Nasri, Intissar; Hammouda, Abdessalam; Hamza, Foued; Zrig, Ahlem; Selmi, Slaheddine

    2017-05-01

    We investigated the accumulation of heavy metals in Bosk's fringe-toed lizards (Acanthodactylus boskianus) living in Gabès region (southeastern Tunisia), in relation to habitat, diet, and distance from the Gabès-Ghannouche factory complex of phosphate treatment. More specifically, we compared the concentrations of cadmium, lead, and zinc in the stomach contents and samples of the liver, kidney, and tail from lizards living in four sites corresponding to different combinations of habitat (coastal dunes vs backshore) and distance from the factory complex (<500 vs 20 km). Examination of stomach contents showed that lizards living on the coastal dunes mainly feed on littoral amphipods, while those living in the backshore feed exclusively on terrestrial invertebrates. The concentrations of heavy metals in lizard tissues were overall positively correlated with those in the preys they ingested. Moreover, there was a general tendency towards increased concentrations of cadmium, lead, and zinc in the samples from lizards living on coastal dunes compared to those from the other sites, although some differences still lacked statistical significance. These results suggest that the highest contamination of lizards living on coastal dunes was probably related to the ingestion of contaminated amphipods. Thus, amphipods and Bosk's fringe-toed lizards seem to provide an important link between the marine and terrestrial food webs, with higher concentrations appearing to accumulate from materials released into the sea rather than the terrestrial environment. With regard to metal distribution among tissues, our results were overall in agreement with previous findings in other reptiles. In particular, cadmium was most concentrated in the liver samples, stressing once more the role of the liver as a storage organ of Cd. Moreover, high concentrations of the three assessed metals were found in the kidney samples, showing the role of the kidney as an active site of heavy metal accumulation.

  16. A taxonomy of epithelial human cancer and their metastases

    PubMed Central

    2009-01-01

    Background Microarray technology has allowed to molecularly characterize many different cancer sites. This technology has the potential to individualize therapy and to discover new drug targets. However, due to technological differences and issues in standardized sample collection no study has evaluated the molecular profile of epithelial human cancer in a large number of samples and tissues. Additionally, it has not yet been extensively investigated whether metastases resemble their tissue of origin or tissue of destination. Methods We studied the expression profiles of a series of 1566 primary and 178 metastases by unsupervised hierarchical clustering. The clustering profile was subsequently investigated and correlated with clinico-pathological data. Statistical enrichment of clinico-pathological annotations of groups of samples was investigated using Fisher exact test. Gene set enrichment analysis (GSEA) and DAVID functional enrichment analysis were used to investigate the molecular pathways. Kaplan-Meier survival analysis and log-rank tests were used to investigate prognostic significance of gene signatures. Results Large clusters corresponding to breast, gastrointestinal, ovarian and kidney primary tissues emerged from the data. Chromophobe renal cell carcinoma clustered together with follicular differentiated thyroid carcinoma, which supports recent morphological descriptions of thyroid follicular carcinoma-like tumors in the kidney and suggests that they represent a subtype of chromophobe carcinoma. We also found an expression signature identifying primary tumors of squamous cell histology in multiple tissues. Next, a subset of ovarian tumors enriched with endometrioid histology clustered together with endometrium tumors, confirming that they share their etiopathogenesis, which strongly differs from serous ovarian tumors. In addition, the clustering of colon and breast tumors correlated with clinico-pathological characteristics. Moreover, a signature was developed based on our unsupervised clustering of breast tumors and this was predictive for disease-specific survival in three independent studies. Next, the metastases from ovarian, breast, lung and vulva cluster with their tissue of origin while metastases from colon showed a bimodal distribution. A significant part clusters with tissue of origin while the remaining tumors cluster with the tissue of destination. Conclusion Our molecular taxonomy of epithelial human cancer indicates surprising correlations over tissues. This may have a significant impact on the classification of many cancer sites and may guide pathologists, both in research and daily practice. Moreover, these results based on unsupervised analysis yielded a signature predictive of clinical outcome in breast cancer. Additionally, we hypothesize that metastases from gastrointestinal origin either remember their tissue of origin or adapt to the tissue of destination. More specifically, colon metastases in the liver show strong evidence for such a bimodal tissue specific profile. PMID:20017941

  17. Triglycerides in the human kidney cortex: relationship with body size.

    PubMed

    Bobulescu, Ion Alexandru; Lotan, Yair; Zhang, Jianning; Rosenthal, Tara R; Rogers, John T; Adams-Huet, Beverley; Sakhaee, Khashayar; Moe, Orson W

    2014-01-01

    Obesity is associated with increased risk for kidney disease and uric acid nephrolithiasis, but the pathophysiological mechanisms underpinning these associations are incompletely understood. Animal experiments have suggested that renal lipid accumulation and lipotoxicity may play a role, but whether lipid accumulation occurs in humans with increasing body mass index (BMI) is unknown. The association between obesity and abnormal triglyceride accumulation in non-adipose tissues (steatosis) has been described in the liver, heart, skeletal muscle and pancreas, but not in the human kidney. We used a quantitative biochemical assay to quantify triglyceride in normal kidney cortex samples from 54 patients undergoing nephrectomy for localized renal cell carcinoma. In subsets of the study population we evaluated the localization of lipid droplets by Oil Red O staining and measured 16 common ceramide species by mass spectrometry. There was a positive correlation between kidney cortex trigyceride content and BMI (Spearman R = 0.27, P = 0.04). Lipid droplets detectable by optical microscopy had a sporadic distribution but were generally more prevalent in individuals with higher BMI, with predominant localization in proximal tubule cells and to a lesser extent in glomeruli. Total ceramide content was inversely correlated with triglycerides. We postulate that obesity is associated with abnormal triglyceride accumulation (steatosis) in the human kidney. In turn, steatosis and lipotoxicity may contribute to the pathogenesis of obesity-associated kidney disease and nephrolithiasis.

  18. Physiological and biochemical effects of nickel on rainbow trout (Oncorhynchus mykiss) tissues: Assessment of nuclear factor kappa B activation, oxidative stress and histopathological changes.

    PubMed

    Topal, Ahmet; Atamanalp, Muhammed; Oruç, Ertan; Erol, Hüseyin Serkan

    2017-01-01

    We investigated changes in nuclear factor kappa B (NFkB) activity, antioxidant responses and histopathological effects in the liver, gill and kidney tissues of rainbow trout exposed to nickel chloride (Ni). Two different concentrations (1 mg/L and 2 mg/L) were administrated to fish for 21 days. Tissues were taken from all fish for NFkB activity, histopathological examination and determination of superoxide dismutase (SOD), catalase (CAT) enzyme activity and of lipid peroxidation (LPO), and glutathione (GSH) levels. The findings of this study indicated that Ni exposure led to a significant increase in LPO indicating peroxidative damage and antioxidant enzymes SOD and CAT activity in tissues (p < 0.05), but 2 mg/Ni concentration caused a significant decrease in CAT activity in kidney tissues (p < 0.05). One of mechanism in the antioxidant defense system seems to be GSH, which increased in gill and kidney tissues of fish exposed to Ni (p < 0.05). NFkB immunopositivity was detected in all tissues. Ni exposure caused lamellar thickening, cellular infiltration in gill tissues, hydropic degeneration of hepatocytes in liver tissues, hyalinous accumulation within the glomeruli and tubular degeneration in kidney tissues. Our results suggested that Ni toxicity may disturb the biochemical and physiological functions of fish by causing changes in NFkB activity and oxidative and histopathological damage in the tissues of rainbow trout. This study can provide useful information for understanding of Ni-induced toxicity. Copyright © 2016 Elsevier Ltd. All rights reserved.

  19. Determination of 240Pu/239Pu isotopic ratios in human tissues collected from areas around the Semipalatinsk Nuclear Test Site by sector-field high resolution ICP-MS.

    PubMed

    Yamamoto, M; Oikawa, S; Sakaguchi, A; Tomita, J; Hoshi, M; Apsalikov, K N

    2008-09-01

    Information on the 240Pu/239Pu isotope ratios in human tissues for people living around the Semipalatinsk Nuclear Test Site (SNTS) was deduced from 9 sets of soft tissues and bones, and 23 other bone samples obtained by autopsy. Plutonium was radiochemically separated and purified, and plutonium isotopes (239Pu and 240Pu) were determined by sector-field high resolution inductively coupled plasma-mass spectrometry. For most of the tissue samples from the former nine subjects, low 240Pu/239Pu isotope ratios were determined: bone, 0.125 +/- 0.018 (0.113-0.145, n = 4); lungs, 0.063 +/- 0.010 (0.051-0.078, n = 5); and liver, 0.148 +/- 0.026 (0.104-0.189, n = 9). Only 239Pu was detected in the kidney samples; the amount of 240Pu was too small to be measured, probably due to the small size of samples analyzed. The mean 240Pu/239Pu isotope ratio for bone samples from the latter 23 subjects was 0.152 +/- 0.034, ranging from 0.088 to 0.207. A significant difference (a two-tailed Student's t test; 95% significant level, alpha = 0.05) between mean 240Pu/239Pu isotope ratios for the tissue samples and for the global fallout value (0.178 +/- 0.014) indicated that weapons-grade plutonium from the atomic bombs has been incorporated into the human tissues, especially lungs, in the residents living around the SNTS. The present 239,240Pu concentrations in bone, lung, and liver samples were, however, not much different from ranges found for human tissues from other countries that were due solely to global fallout during the 1970's-1980's.

  20. Comparison of Tissue Injury from Focused Ultrasonic Propulsion of Kidney Stones Versus Extracorporeal Shock Wave Lithotripsy

    PubMed Central

    Connors, Bret A.; Evan, Andrew P.; Blomgren, Philip M.; Hsi, Ryan S.; Harper, Jonathan D.; Sorensen, Mathew D.; Wang, Yak-Nam; Simon, Julianna C.; Paun, Marla; Starr, Frank; Cunitz, Bryan W.; Bailey, Michael R.; Lingeman, James E.

    2013-01-01

    Purpose Focused ultrasonic propulsion is a new non-invasive technique designed to move kidney stones and stone fragments out of the urinary collecting system. However, the extent of tissue injury associated with this technique is not known. As such, we quantitated the amount of tissue injury produced by focused ultrasonic propulsion under simulated clinical treatment conditions, and under conditions of higher power or continuous duty cycles, and compared those results to SWL injury. Materials and Methods A human calcium oxalate monohydrate stone and/or nickel beads were implanted (with ureteroscopy) into 3 kidneys of live pigs (45–55 kg) and repositioned using focused ultrasonic propulsion. Additional pig kidneys were exposed to SWL level pulse intensities or continuous ultrasound exposure of 10 minutes duration (ultrasound probe either transcutaneous or on the kidney). These kidneys were compared to 6 kidneys treated with an unmodified Dornier HM3 Lithotripter (2400 shocks, 120 SWs/min and 24 kV). Histological analysis was performed to assess the volume of hemorrhagic tissue injury created by each technique (% functional renal volume, FRV). Results SWL produced a lesion of 1.56±0.45% FRV. Ultrasonic propulsion produced no detectable lesion with the simulated clinical treatment. A lesion of 0.46±0.37% FRV or 1.15±0.49% FRV could be produced if excessive treatment parameters were used while the ultrasound probe was placed on the kidney. Conclusions Focused ultrasonic propulsion produced no detectable morphological injury to the renal parenchyma when using clinical treatment parameters and produced injury comparable in size to SWL when using excessive treatment parameters. PMID:23917165

  1. Epizootiology and histopathology of Parvicapsula sp. in coho salmon Oncorhynchus kisutch

    USGS Publications Warehouse

    Yasutake, William T.; Elliott, Diane G.

    2003-01-01

    The epizootiology and histopathology of the myxosporean Parvicapsula sp. was studied during monthly health surveys of 4 groups of coho salmon Oncorhynchus kisutch at a commercial farm in Puget Sound, Washington, USA, from 1984 to 1986. No Parvicapsula sp. was detected in histological samples taken from juvenile fish in fresh water, but the parasite was detected in fish from all groups 2 to 8 mo after transfer to seawater net pens. Groups placed in seawater net pens in November and December had a higher prevalence of infection, and a longer period of continuous detected infection, than those introduced into net pens in May. For the groups transferred to seawater in November and December, the highest infection prevalence (45 to 90%) was detected during the following March and April. Among 13 tissues examined histologically, only the pseudobranch and kidney were positive for Parvicapsula sp., with 26 (62%) of 42 positive fish showing infections only in the pseudobranch, 5 (12%) showing infections only in the kidney, and 11 (26%) showing infections in both organs. Both the pseudobranch and kidney were apparent primary infection sites, but pseudobranch infections appeared to persist longer in a population. Pseudobranch infections were frequently heavy and associated with extensive inflammation and necrosis of filament and lamellar tissues. The kidney had been the only infection site reported for Parvicapsula sp. in previous studies of coho salmon.

  2. Sex, age, and tissue specific accumulation of eight metals, arsenic, and selenium in the European hedgehog (Erinaceus europaeus).

    PubMed

    Rautio, Anni; Kunnasranta, Mervi; Valtonen, Anu; Ikonen, Mirva; Hyvärinen, Heikki; Holopainen, Ismo J; Kukkonen, Jussi V K

    2010-11-01

    Many insectivores have been shown to be sensitive to heavy metals and therefore suitable for biomonitoring purposes. In Finland, the hibernation period of the European hedgehog (Erinaceus europaeus) is long, and during hibernation the stress caused by environmental toxins may be crucial. Concentrations of cadmium (Cd), copper (Cu), iron (Fe), magnesium (Mg), manganese (Mn), molybdenum (Mo), nickel (Ni), lead (Pb), arsenic (As), and selenium (Se) were measured in a population of hedgehogs in the town of Joensuu in eastern Finland during the summers of 2004 and 2005. The analyzed tissues were kidney, liver, hair, and spine. The sampled hedgehogs (n = 65) were mainly road-killed animals. As expected, the concentrations of heavy metals were low because the hedgehogs were living in a comparatively unpolluted area. Significant increases with age were found in Cd concentrations (kidney, liver, and spine) and some essential elements (Se in spine, kidney, and liver; Mo in kidney and liver; Cu in spine; Fe in liver; and Mn in spine). Age accumulation and correlations between Se and Cd and between Mo and Cd may indicate the protective roles of Se and Mo against Cd toxicity in hedgehogs, in which Cd is already at comparatively low concentrations. Sex had no significant effect on concentrations of the elements studied. In conclusion, age is an important parameter to be taken into account when studying heavy-metal concentrations in hedgehogs and other insectivores.

  3. Transcriptomic analysis on responses of the liver and kidney of finishing pigs fed cadmium contaminated rice.

    PubMed

    Xia, Yaoyao; Li, Jun; Ren, Wenkai; Feng, Zemeng; Huang, Ruilin; Yin, Yulong

    2018-06-01

    Cadmium (Cd) is a common harmful substance that has many deleterious effects on the liver and kidney. Most reports about Cd toxic studies focused on its inorganic status, whereas the toxicity of Cd in organic materials is less studied. Here, we performed RNA-seq to explore the influences of Cd contaminated rice on function of the liver and kidney of finishing pigs. The concentration of Cd in liver and kidney of pigs fed Cd contaminated rice increased by 4.00 and 2.94 times, respectively, compared to those in the control group. With transcriptomic analysis, approximately 4-6 × 10 7 clean reads were acquired. Five differently expressed genes (DEGs) were identified in the liver, and 12 DEGs in the kidney. SPHK2 was commonly down-regulated. No significantly enriched gene ontology (GO) terms were identified. By Kyoto encyclopaedia of genes and genomes (KEGG) enrichments, four pathways were identified in hepatic tissue, and five pathways in nephritic tissue. Intriguingly, two pathways (sphingolipid metabolism and VEGF signalling pathway) were altered both in the liver and kidney. Cd contaminated rice may cause liver and kidney damage and inflammation, or even lead to more severe harm to these tissues. © 2017 Society of Chemical Industry. © 2017 Society of Chemical Industry.

  4. Liquid Chromatography Electrospray Ionization Tandem Mass Spectrometric (LC/ESI-MS/MS) Study for the Identification and Characterization of In Vivo Metabolites of Cisplatin in Rat Kidney Cancer Tissues: Online Hydrogen/Deuterium (H/D) Exchange Study.

    PubMed

    Bandu, Raju; Ahn, Hyun Soo; Lee, Joon Won; Kim, Yong Woo; Choi, Seon Hee; Kim, Hak Jin; Kim, Kwang Pyo

    2015-01-01

    In vivo rat kidney tissue metabolites of an anticancer drug, cisplatin (cis-diamminedichloroplatinum [II]) (CP) which is used for the treatment of testicular, ovarian, bladder, cervical, esophageal, small cell lung, head and neck cancers, have been identified and characterized by using liquid chromatography positive ion electrospray ionization tandem mass spectrometry (LC/ESI-MS/MS) in combination with on line hydrogen/deuterium exchange (HDX) experiments. To identify in vivo metabolites, kidney tissues were collected after intravenous administration of CP to adult male Sprague-Dawley rats (n = 3 per group). The tissue samples were homogenized and extracted using newly optimized metabolite extraction procedure which involves liquid extraction with phosphate buffer containing ethyl acetate and protein precipitation with mixed solvents of methanol-water-chloroform followed by solid-phase clean-up procedure on Oasis HLB 3cc cartridges and then subjected to LC/ESI-HRMS analysis. A total of thirty one unknown in vivo metabolites have been identified and the structures of metabolites were elucidated using LC-MS/MS experiments combined with accurate mass measurements. Online HDX experiments have been used to further support the structural characterization of metabolites. The results showed that CP undergoes a series of ligand exchange biotransformation reactions with water and other nucleophiles like thio groups of methionine, cysteine, acetylcysteine, glutathione and thioether. This is the first research approach focused on the structure elucidation of biotransformation products of CP in rats, and the identification of metabolites provides essential information for further pharmacological and clinical studies of CP, and may also be useful to develop various effective new anticancer agents.

  5. Distribution of OV-TL 3 and MOv18 in normal and malignant ovarian tissue.

    PubMed

    Buist, M R; Molthoff, C F; Kenemans, P; Meijer, C J

    1995-07-01

    To analyse the distribution of OV-TL 3 and MOv18 in normal ovarian tissue to determine which antibody is most suitable for (radio)immunotherapy of ovarian carcinoma. The distribution of OV-TL 3 and MOv18 was determined using immunohistochemistry and flow cytometry. Epithelial and other cells in many tissues, and leucocytes in peripheral blood, bone marrow and spleen stained positively with OV-TL 3. The staining pattern of MOv18 in normal tissues was more restricted and was confined to epithelial cells in the lung, kidney, pancreas, salivary gland, ovary, Fallopian tubes, and cervix. Reactivity was also observed with pneumocytes in the lung, tubuli in the kidney, acinar cells in the salivary gland and pancreas, in the placenta, and with Kupffer cells in the liver. The staining pattern of chimeric MOv18 was identical with the murine form. OV-TL 3 and MOv18 reacted with 100% and 98% (45/46) of the 46 tested epithelial ovarian cancers, respectively. In ovarian carcinoma tissue homogeneous staining of epithelial cells was observed with OV-TL 3 and more heterogeneous staining with MOv18. In 12 and nine patients, respectively, a difference in staining intensity for OV-TL 3 and MOv18 was observed between various tumour samples from the same patient. MOv18 has greater therapeutic potential because of its restricted reactivity with normal tissues and especially, in contrast to OV-TL 3, its lack of reactivity with haematopoietic cells.

  6. Micro-polarimetry for pre-clinical diagnostics of pathological changes in human tissues

    NASA Astrophysics Data System (ADS)

    Golnik, Andrzej; Golnik, Natalia; Pałko, Tadeusz; Sołtysiński, Tomasz

    2008-05-01

    The paper presents a practical study of several methods of image analysis applied to polarimetric images of regular and malignant human tissues. The images of physiological and pathologically changed tissues from body and cervix of uterus, intestine, kidneys and breast were recorded in transmitted light of different polarization state. The set up of the conventional optical microscope with CCD camera and rotating polarizer's were used for analysis of the polarization state of the light transmitted through the tissue slice for each pixel of the camera image. The set of images corresponding to the different coefficients of the Stockes vectors, a 3×3 subset of the Mueller matrix as well as the maps of the magnitude and in-plane direction of the birefringent components in the sample were calculated. Then, the statistical analysis and the Fourier transform as well as the autocorrelation methods were used to analyze spatial distribution of birefringent elements in the tissue samples. For better recognition of tissue state we proposed a novel method that takes advantage of multiscale image data decomposition The results were used for selection of the optical characteristics with significantly different values for regular and malignant tissues.

  7. Lead and cadmium in wild birds in southeastern Spain

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

    Garcia-Fernandez, A.J.; Sanchez-Garcia, J.A.; Luna, A.

    1995-12-01

    The main purpose of this study was to monitor exposure to lead and cadmium in wild birds in Murcia, a southeastern region of Spain on the Mediterranean coast. This region lies on one of the African-European flyways. Samples of liver, kidney, brain, bone, and whole blood from several species of wild birds were obtained during 1993. The authors found a clear relationship between cadmium and lead concentrations in birds and their feedings habits. Vultures (Gyps fulvus) had the highest concentrations of lead (mean 40 {micro}g/dl in blood), and seagulls (Larus argentatus and Larus ridibundus) the highest concentrations of cadmium (meanmore » 4.43 {micro}g/g in kidney). Insectivores had high concentrations of both metals, and diurnal and nocturnal raptors showed the lowest tissue concentrations. The findings that tissue and blood concentrations were generally not elevated suggests environmental (rather than acute) exposure. Birds from more industrialized areas of the region studied here had higher concentrations of both lead and cadmium.« less

  8. Nephron sparing by partial median nephrectomy for treatment of renal hemangioma in a dog.

    PubMed

    Mott, J C; McAnulty, J F; Darien, D L; Steinberg, H

    1996-04-15

    A 6-year-old neutered male Golden Retriever was admitted for evaluation of intermittent hematuria of 2 months' duration. A 3-cm heterogeneous mass causing distortion of the caudomedial aspect of the left kidney was detected via ultrasonography. Histologic examination of a renal tissue sample obtained by ultrasound-guided biopsy revealed a telangiectatic vascular plexus of unknown origin. Low glomerular filtration rate was identified by a modified exogenous creatinine clearance test. Excretory urography revealed a filling defect in the medial aspect of the caudal pole of the kidney, near the hilus. Because total renal function was low, a decision was made to perform nephron-sparing surgery involving resection of centrally located renal parenchymal and pelvic tissue by en bloc resection in the median plane, instead of radical nephrectomy. After surgery, the hematuria resolved and further decrease in renal function was not evident. Nephron-sparing surgery is a viable option for dogs with compromised renal function when there is concern that radical nephrectomy may precipitate uremia.

  9. Diabetes mellitus reduces activity of human UDP-glucuronosyltransferase 2B7 in liver and kidney leading to decreased formation of mycophenolic acid acyl-glucuronide metabolite.

    PubMed

    Dostalek, Miroslav; Court, Michael H; Hazarika, Suwagmani; Akhlaghi, Fatemeh

    2011-03-01

    Mycophenolic acid (MPA) is an immunosuppressive agent commonly used after organ transplantation. Altered concentrations of MPA metabolites have been reported in diabetic kidney transplant recipients, although the reason for this difference is unknown. We aimed to compare MPA biotransformation and UDP-glucuronosyltransferase (UGT) expression and activity between liver (n = 16) and kidney (n = 8) from diabetic and nondiabetic donors. Glucuronidation of MPA, as well as the expression and probe substrate activity of UGTs primarily responsible for MPA phenol glucuronide (MPAG) formation (UGT1A1 and UGT1A9), and MPA acyl glucuronide (AcMPAG) formation (UGT2B7), was characterized. We have found that both diabetic and nondiabetic human liver microsomes and kidney microsomes formed MPAG with similar efficiency; however, AcMPAG formation was significantly lower in diabetic samples. This finding is supported by markedly lower glucuronidation of the UGT2B7 probe zidovudine, UGT2B7 protein, and UGT2B7 mRNA in diabetic tissues. UGT genetic polymorphism did not explain this difference because UGT2B7*2 or *1c genotype were not associated with altered microsomal UGT2B7 protein levels or AcMPAG formation. Furthermore, mRNA expression and probe activities for UGT1A1 or UGT1A9, both forming MPAG but not AcMPAG, were comparable between diabetic and nondiabetic tissues, suggesting the effect may be specific to UGT2B7-mediated AcMPAG formation. These findings suggest that diabetes mellitus is associated with significantly reduced UGT2B7 mRNA expression, protein level, and enzymatic activity of human liver and kidney, explaining in part the relatively low circulating concentrations of AcMPAG in diabetic patients.

  10. Reno-protective effects of TAK-242 on acute kidney injury in a rat model.

    PubMed

    Mohammad, Bassim I; Raheem, Abdulla K; Hadi, Najah R; Jamil, Dina A; Al-Aubaidy, Hayder A

    2018-06-13

    Acute kidney inschemia/reperfusion (I/R) injury is characterized by an abrupt loss of kidney function, resulting in the retention of urea and other nitrogenous waste products and in the dysregulation of extracellular volume and electrolytes. Despite the advances in therapeutic techniques, the mortality and morbidity of patients remain high and have not appreciably improved. This study aims to evaluate the potential protective effect of TAK-242 on renal ischemia/reperfusion injury using an animal model. Thirty-five adult male Sprague-dawely rats (weighing 200-300), were assigned randomly into the following experimental groups (n = 7 in each group), Control (I/R), Sham (negative control), TAK-242 (5 mg/kg body weight), TAK-242 (10 mg/kg body weight) and Vehicle (DMSO). Rats were exposed to a 30 min of ischemia then 3 h of reperfusion. At the end of reperfusion phase, rats were sacrificed then plasma, serum and tissue samples were obtained to measure markers of kidney oxidative stress and inflammation. Plasma levels of neutrophil gelatinase-associated lipocalin (NGAL), and tissue levels of interleukin-18 (IL-18) and malondialdehyde (MDA) were significantly lower in TAK-242 pretreated groups than the vehicle group and the control group (p < 0.05). Furthermore; serum levels of urea and creatinine were significantly lower in the TAK-242 pretreated groups as compared to the control group (p < 0.05). We conclude that administration of TAK-242 can be useful preventive method in attenuating the degree of acute kidney injury during ischemic reperfusion process as shown by a significant reduction of urinary inflammatory markers as well as significant reduction of urea and creatinine levels. Copyright © 2018 Elsevier Inc. All rights reserved.

  11. The effect of hypericum perforatum on kidney ischemia/reperfusion damage.

    PubMed

    Cakir, Murat; Duzova, Halil; Baysal, Işil; Gül, Cemile Ceren; Kuşcu, Gülbahar; Kutluk, Fatma; Çakin, Hilal; Şeker, Şifanur; İlbeği, Esranur; Uslu, Seda; Avci, Umut; Demir, Samet; Akinci, Cihan; Atli, Sercan

    2017-11-01

    It has been revealed in recent studies that Hypericum Perforatum (HP) is influential on cancer, inflammatory diseases, bacterial and viral diseases, and has neuroprotective and antioxidant properties. In this study, we investigated the effect of HP, which is known to have antioxidant and anti-inflammatory effects, on kidney I/R damage. Male Sprague-Dawley rats were divided into three groups, and each of the groups had eight rats: The Control Group; the Ischemia/Reperfusion (I/R) Group; and the IR + HP Group which was treated with 50 mg/kg of HP. The right kidneys of the rats were removed, and the left kidney developed ischemia during the 45th min, and reperfusion occurred in the following 3rd h. The histopathological findings and also the level of Malondialdehyde (MDA), Glutathione (GSH) and superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-PX) enzyme activations in the renal tissues were measured. Blood Urea Nitrogen (BUN), Creatinin (Cre) from serum samples were determined. The levels of BUN, Cre, and kidney tissue MDA increased at a significant level, and the SOD, CAT, and GSH-PX enzyme activity decreased at a significant level in the I/R group, compared with the Control Group (p < 0.05). In the I/R + HP group, the levels of MDA decreased at a significant level compared to the I/R group, while the SOD, CAT, and GSH-PX activity increased (p < 0.05). In histopathological examinations, it was observed that the tubular dilatation and epithelial desquamation regressed in the IR + HP Group when compared with the I/R Group. It has been shown with the histological and biochemical results in this study that HP is protective against acute renal I/R.

  12. Protective effect of Silybum marianum and Taraxacum officinale extracts against oxidative kidney injuries induced by carbon tetrachloride in rats.

    PubMed

    Karakuş, Ali; Değer, Yeter; Yıldırım, Serkan

    2017-11-01

    The protective effect of the extracts of the plants Silybum marianum and Taraxacum officinale by carbon tetrachloride (CCl 4 ) was researched. Sixty-six female Wistar albino rats were divided into six groups: Control, Silybum marianum, Taraxacum officinale, CCl 4 , Silybum marianum+ CCl 4 , Taraxacum officinale+CCl 4 . The Silybum marianum and Taraxacum officinale extracts were administered as 100 mg/kg/day by gavage. The CCl 4 was administered as 1.5 mL/kg (i.p.). At the end of the trial period, in the serums obtained from the animals, in the CCl 4 group it was found that the MDA level increased in the kidney tissue samples as well as in the ALP and GGT enzyme activities. It was also found that the GSH level and the GST enzyme activities decreased (p<.05). The microscopic evaluations showed that the CCl 4 caused a serious hydropic degeneration, coagulation necrosis, and mono-nuclear cell infiltration in the kidney cell. In the animals where CCl 4 and Silybum marianum and Taraxacum officinale extracts were applied together, it was found that the serum ALP and GGT enzyme activities decreased and that the MDA level decreased in the kidney tissue, and that the GSH level and GST enzyme activities increased. It was observed that the histopathological changes caused by the CCl 4 toxicity were corrected by applying the extracts. Eventually, it was determined that the Silybum marianum was more effective. Silybum marianum and Taraxacum officinale extracts which were used against histopathological changes in the kidney caused by toxication showed a corrective effect, which were supported by biochemical parameters.

  13. NASA Bioreactor tissue culture

    NASA Technical Reports Server (NTRS)

    1998-01-01

    Dr. Lisa E. Freed of the Massachusetts Institute of Technology and her colleagues have reported that initially disc-like specimens tend to become spherical in space, demonstrating that tissues can grow and differentiate into distinct structures in microgravity. The Mir Increment 3 (Sept. 16, 1996 - Jan. 22, 1997) samples were smaller, more spherical, and mechanically weaker than Earth-grown control samples. These results demonstrate the feasibility of microgravity tissue engineering and may have implications for long human space voyages and for treating musculoskeletal disorders on earth. The work is sponsored by NASA's Office of Biological and Physical Research. The bioreactor is managed by the Biotechnology Cell Science Program at NASA's Johnson Space Center (JSC). NASA-sponsored bioreactor research has been instrumental in helping scientists to better understand normal and cancerous tissue development. In cooperation with the medical community, the bioreactor design is being used to prepare better models of human colon, prostate, breast and ovarian tumors. Cartilage, bone marrow, heart muscle, skeletal muscle, pancreatic islet cells, liver and kidney are just a few of the normal tissues being cultured in rotating bioreactors by investigators.

  14. Acute renal failure potentiates methylmalonate-induced oxidative stress in brain and kidney of rats.

    PubMed

    Schuck, P F; Alves, L; Pettenuzzo, L F; Felisberto, F; Rodrigues, L B; Freitas, B W; Petronilho, F; Dal-Pizzol, F; Streck, E L; Ferreira, G C

    2013-03-01

    Tissue methylmalonic acid (MMA) accumulation is the biochemical hallmark of methylmalonic acidemia. The disease is clinically characterized by progressive neurological deterioration and kidney failure, whose pathophysiology is still unclear. In the present work we investigated the effects of acute MMA administration on various parameters of oxidative stress in cerebral cortex and kidney of young rats, as well as the influence of acute renal failure on MMA-elicited effects on these parameters. Acute renal failure was induced by gentamicin, an aminoglycoside antibiotic whose utilization over prolonged periods causes nephrotoxicity. The administration of gentamicin alone increased carbonyl content and inhibited superoxide dismutase (SOD) activity in cerebral cortex, as well as increased thiobarbituric acid-reactive substances (TBA-RS) and sulfhydryl levels and diminished glutathione peroxidase activity in kidney. On the other hand, MMA administration increased TBA-RS levels in cerebral cortex and decreased SOD activity in kidney. Furthermore, the simultaneous administration of MMA and gentamicin to the rats provoked an augment in TBA-RS levels and superoxide generation in cerebral cortex and in TBA-RS, carbonyl and sulfhydryl levels in kidney, while diminished SOD activity in both studied tissues. Finally, nitrate/nitrite content, reduced glutathione levels, 2',7'-dihydrodichlorofluorescein oxidation and catalase activity were not affected by this animal treatment in either tissue. In conclusion, our present data are in line with the hypothesis that MMA acts as a toxin in brain and kidney of rats and suggest that renal injury potentiates the toxicity of MMA on oxidative stress parameters in brain and peripheral tissues.

  15. Classical Complement Pathway Activation in the Kidneys of Women With Preeclampsia.

    PubMed

    Penning, Marlies; Chua, Jamie S; van Kooten, Cees; Zandbergen, Malu; Buurma, Aletta; Schutte, Joke; Bruijn, Jan Anthonie; Khankin, Eliyahu V; Bloemenkamp, Kitty; Karumanchi, S Ananth; Baelde, Hans

    2015-07-01

    A growing body of evidence suggests that complement dysregulation plays a role in the pathogenesis of preeclampsia. The kidney is one of the major organs affected in preeclampsia. Because the kidney is highly susceptible to complement activation, we hypothesized that preeclampsia is associated with renal complement activation. We performed a nationwide search for renal autopsy material in the Netherlands using a computerized database (PALGA). Renal tissue was obtained from 11 women with preeclampsia, 25 pregnant controls, and 14 nonpregnant controls with hypertension. The samples were immunostained for C4d, C1q, mannose-binding lectin, properdin, C3d, C5b-9, IgA, IgG, and IgM. Preeclampsia was significantly associated with renal C4d-a stable marker of complement activation-and the classical pathway marker C1q. In addition, the prevalence of IgM was significantly higher in the kidneys of the preeclamptic women. No other complement markers studied differed between the groups. Our findings in human samples were validated using a soluble fms-like tyrosine kinase 1 mouse model of preeclampsia. The kidneys in the soluble fms-like tyrosine kinase 1-injected mice had significantly more C4 deposits than the control mice. The association between preeclampsia and renal C4d, C1q, and IgM levels suggests that the classical complement pathway is involved in the renal injury in preeclampsia. Moreover, our finding that soluble fms-like tyrosine kinase 1-injected mice develop excess C4 deposits indicates that angiogenic dysregulation may play a role in complement activation within the kidney. We suggest that inhibiting complement activation may be beneficial for preventing the renal manifestations of preeclampsia. © 2015 American Heart Association, Inc.

  16. Mechanisms of Chemical Carcinogenesis in the Kidneys

    PubMed Central

    Radford, Robert; Frain, Helena; Ryan, Michael P.; Slattery, Craig; McMorrow, Tara

    2013-01-01

    Chemical carcinogens are substances which induce malignant tumours, increase their incidence or decrease the time taken for tumour formation. Often, exposure to chemical carcinogens results in tissue specific patterns of tumorigenicity. The very same anatomical, biochemical and physiological specialisations which permit the kidney to perform its vital roles in maintaining tissue homeostasis may in fact increase the risk of carcinogen exposure and contribute to the organ specific carcinogenicity observed with numerous kidney carcinogens. This review will address the numerous mechanisms which play a role in the concentration, bioactivation, and uptake of substances from both the urine and blood which significantly increase the risk of cancer in the kidney. PMID:24071941

  17. Ion Imbalance Is Involved in the Mechanisms of Liver Oxidative Damage in Rats Exposed to Glyphosate

    PubMed Central

    Tang, Juan; Hu, Ping; Li, Yansen; Win-Shwe, Tin-Tin; Li, Chunmei

    2017-01-01

    Glyphosate (N-phosphonomethyl-glycine, GLP) is the most popular herbicide used worldwide. This study aimed to investigate the effects of glyphosate on rats' liver function and induction of pathological changes in ion levels and oxidative stress in hepatic tissue. Sprague-Dawley rats were treated orally with 0, 5, 50, and 500 mg/kg body weight of the GLP. After 5 weeks of treatment, blood and liver samples were analyzed for biochemical and histomorphological parameters. The various mineral elements content in the organs of the rats were also measured. Significant decreases were shown in the weights of body, liver, kidney and spleen between the control and treatment groups. Changes also happened in the histomorphology of the liver and kidney tissue of GLP-treated rats. The GLP resulted in an elevated level of glutamic-oxalacetic transaminase (GOT), glutamic-pyruvic transaminase (GPT) and IL-1β in the serum. Besides, decreased total superoxide dismutase (T-SOD) activity and increased malondialdehyde (MDA) contents in the serum, liver, and kidney indicated the presence of oxidative stress. Moreover, increase of hydrogen peroxide (H2O2) level and catalase (CAT) activity in the serum and liver and decrease of glutathione (GSH) and lutathione peroxidase (GSH-Px) activity in the kidney tissue further confirmed the occurrence of oxidative stress. The results of RT-PCR showed that the mRNA expressions of IL-1α, IL-1β, IL-6, MAPK3, NF-κB, SIRT1, TNF-α, Keap1, GPX2, and Caspase-3 were significantly increased in the GLP-treated groups compared to the control group. Furthermore, PPARα, DGAT, SREBP1c, and SCD1 mRNA expressions were also remarkably increased in the GLP-treated groups compared to the control group. In addition, aluminum (Al), iron (Fe), copper (Cu), zinc (Zn), and magnesium (Mg) levels were showed a significant difference reduction or increase in rat liver, kidney, spleen, lung, heart, muscle, brain, and fat tissues. These results suggested that glyphosate caused obvious damage to rats' liver and caused various mineral elements content imbalances in various organs of rats. Ion imbalance could weaken antioxidant capacity and involve in the mechanism of liver oxidative damage caused by GLP. PMID:29311996

  18. Determination of ochratoxin A in tissues of wild boar (Sus scrofa L.) by enzymatic digestion (ED) coupled to high-performance liquid chromatography with a fluorescence detector (HPLC-FLD).

    PubMed

    Luci, Giacomo; Intorre, Luigi; Ferruzzi, Guido; Mani, Danilo; Giuliotti, Lorella; Pretti, Carlo; Tognetti, Rosalba; Bertini, Simone; Meucci, Valentina

    2018-03-01

    Ochratoxin A (OTA) is a secondary toxic metabolite synthesized by Aspergillus or Penicillium species, which can contaminate various crops. The International Agency for Research on Cancer (IARC) classified OTA as a group 2B possible human carcinogen. The aim of the present study was to assess OTA concentrations in tissues of wild boar (Sus scrofa L.) from Tuscany (Italy). Over a period of 2 years, samples of muscle, liver, and kidney from 48 wild boars were collected and concentrations of OTA were determined by enzymatic digestion (ED) coupled to high-performance liquid chromatography with a fluorescence detector (HPLC-FLD). The highest concentrations of OTA were found in the kidneys of the 48 wild boars analyzed. No difference in concentrations was found based on years of collection and sex while a significantly higher OTA concentration was found in the kidney of the young wild boars with respect to the adult one. Monitoring the quality of meat destined for transformation is a priority in order to decrease the possibility of toxin carry-over to humans. The present study showed that contamination of wild boar meat products by OTA represents a potential emerging source of OTA.

  19. Sub-Chronic Oral Exposure to Iridium (III) Chloride Hydrate in Female Wistar Rats: Distribution and Excretion of the Metal

    PubMed Central

    Iavicoli, Ivo; Fontana, Luca; Bergamaschi, Antonio; Conti, Marcelo Enrique; Pino, Anna; Mattei, Daniela; Bocca, Beatrice; Alimonti, Alessandro

    2012-01-01

    Iridium tissue distribution and excretion in female Wistar rats following oral exposure to iridium (III) chloride hydrate in drinking water (from 1 to 1000 ng/ml) in a sub-chronic oral study were determined. Samples of urine, feces, blood and organs (kidneys, liver, lung, spleen and brain) were collected at the end of exposure. The most prominent fractions of iridium were retained in kidney and spleen; smaller amounts were found in lungs, liver and brain. Iridium brain levels were lower than those observed in other tissues but this finding can support the hypothesis of iridium capability to cross the blood brain barrier. The iridium kidney levels rose significantly with the administered dose. At the highest dose, important amounts of the metal were found in serum, urine and feces. Iridium was predominantly excreted via feces with a significant linear correlation with the ingested dose, which is likely due to low intestinal absorption of the metal. However, at the higher doses iridium was also eliminated through urine. These findings may be useful to help in the understanding of the adverse health effects, particularly on the immune system, of iridium dispersed in the environment as well as in identifying appropriate biological indices of iridium exposure. PMID:22942873

  20. Urinary Elimination of Bile Acid Glucuronides under Severe Cholestatic Situations: Contribution of Hepatic and Renal Glucuronidation Reactions.

    PubMed

    Perreault, Martin; Wunsch, Ewa; Białek, Andrzej; Trottier, Jocelyn; Verreault, Mélanie; Caron, Patrick; Poirier, Guy G; Milkiewicz, Piotr; Barbier, Olivier

    2018-01-01

    Biliary obstruction, a severe cholestatic complication, causes accumulation of toxic bile acids (BAs) in liver cells. Glucuronidation, catalyzed by UDP-glucuronosyltransferase (UGT) enzymes, detoxifies cholestatic BAs. Using liquid chromatography coupled to tandem mass spectrometry, 11 BA glucuronide (-G) species were quantified in prebiliary and postbiliary stenting serum and urine samples from 17 patients with biliary obstruction. Stenting caused glucuronide- and fluid-specific changes in BA-G levels and BA-G/BA metabolic ratios. In vitro glucuronidation assays with human liver and kidney microsomes revealed that even if renal enzymes generally displayed lower K M values, the two tissues shared similar glucuronidation capacities for BAs. By contrast, major differences between the two tissues were observed when four human BA-conjugating UGTs 1A3, 1A4, 2B4, and 2B7 were analyzed for mRNA and protein levels. Notably, the BA-24G producing UGT1A3 enzyme, abundant in the liver, was not detected in kidney microsomes. In conclusion, the circulating and urinary BA-G profiles are hugely impacted under severe cholestasis. The similar BA-glucuronidating abilities of hepatic and renal extracts suggest that both the liver and kidney may contribute to the urine BA-G pool.

  1. Urinary Elimination of Bile Acid Glucuronides under Severe Cholestatic Situations: Contribution of Hepatic and Renal Glucuronidation Reactions

    PubMed Central

    Perreault, Martin; Białek, Andrzej; Trottier, Jocelyn; Verreault, Mélanie; Caron, Patrick; Poirier, Guy G.

    2018-01-01

    Biliary obstruction, a severe cholestatic complication, causes accumulation of toxic bile acids (BAs) in liver cells. Glucuronidation, catalyzed by UDP-glucuronosyltransferase (UGT) enzymes, detoxifies cholestatic BAs. Using liquid chromatography coupled to tandem mass spectrometry, 11 BA glucuronide (-G) species were quantified in prebiliary and postbiliary stenting serum and urine samples from 17 patients with biliary obstruction. Stenting caused glucuronide- and fluid-specific changes in BA-G levels and BA-G/BA metabolic ratios. In vitro glucuronidation assays with human liver and kidney microsomes revealed that even if renal enzymes generally displayed lower KM values, the two tissues shared similar glucuronidation capacities for BAs. By contrast, major differences between the two tissues were observed when four human BA-conjugating UGTs 1A3, 1A4, 2B4, and 2B7 were analyzed for mRNA and protein levels. Notably, the BA-24G producing UGT1A3 enzyme, abundant in the liver, was not detected in kidney microsomes. In conclusion, the circulating and urinary BA-G profiles are hugely impacted under severe cholestasis. The similar BA-glucuronidating abilities of hepatic and renal extracts suggest that both the liver and kidney may contribute to the urine BA-G pool. PMID:29850459

  2. Clinical-Grade Isolated Human Kidney Perivascular Stromal Cells as an Organotypic Cell Source for Kidney Regenerative Medicine.

    PubMed

    Leuning, Daniëlle G; Reinders, Marlies E J; Li, Joan; Peired, Anna J; Lievers, Ellen; de Boer, Hetty C; Fibbe, Willem E; Romagnani, Paola; van Kooten, Cees; Little, Melissa H; Engelse, Marten A; Rabelink, Ton J

    2017-02-01

    Mesenchymal stromal cells (MSCs) are immunomodulatory and tissue homeostatic cells that have shown beneficial effects in kidney diseases and transplantation. Perivascular stromal cells (PSCs) identified within several different organs share characteristics of bone marrow-derived MSCs (BM-MSCs). These PSCs may also possess tissue-specific properties and play a role in local tissue homeostasis. We hypothesized that human kidney-derived PSCs (hkPSCs) would elicit improved kidney repair in comparison with BM-MSCs. Here we introduce a novel, clinical-grade isolation method of hkPSCs from cadaveric kidneys by enriching for the perivascular marker, NG2. hkPSCs show strong transcriptional similarities to BM-MSCs but also show organotypic expression signatures, including the HoxD10 and HoxD11 nephrogenic transcription factors. Comparable to BM-MSCs, hkPSCs showed immunosuppressive potential and, when cocultured with endothelial cells, vascular plexus formation was supported, which was specifically in the hkPSCs accompanied by an increased NG2 expression. hkPSCs did not undergo myofibroblast transformation after exposure to transforming growth factor-β, further corroborating their potential regulatory role in tissue homeostasis. This was further supported by the observation that hkPSCs induced accelerated repair in a tubular epithelial wound scratch assay, which was mediated through hepatocyte growth factor release. In vivo, in a neonatal kidney injection model, hkPSCs reintegrated and survived in the interstitial compartment, whereas BM-MSCs did not show this potential. Moreover, hkPSCs gave protection against the development of acute kidney injury in vivo in a model of rhabdomyolysis-mediated nephrotoxicity. Overall, this suggests a superior therapeutic potential for the use of hkPSCs and their secretome in the treatment of kidney diseases. Stem Cells Translational Medicine 2017;6:405-418. © 2016 The Authors Stem Cells Translational Medicine published by Wiley Periodicals, Inc. on behalf of AlphaMed Press.

  3. Accumulation profiles of parabens and their metabolites in fish, black bear, and birds, including bald eagles and albatrosses.

    PubMed

    Xue, Jingchuan; Kannan, Kurunthachalam

    2016-09-01

    Although several studies have reported the ubiquitous occurrence of parabens in human specimens and the environment, little is known about the accumulation of these estrogenic chemicals in fish and birds. In this study, accumulation profiles of six parabens and their metabolites were determined in 254 tissue (including liver, kidney, egg, and plasma) samples from 12 species of fish and seven species of birds collected from inland, coastal, and remote aquatic ecosystems. In addition, liver and kidney tissues from black bears were analyzed. Methyl paraben (MeP) was found in a majority of the tissues, with the highest concentration (796ng/g (wet weight [wet wt])) found in the liver of a bald eagle from Michigan. 4-Hydroxy benzoate (HB) was the major metabolite, found in 91% of the tissue samples analyzed at concentrations as high as 68,600ng/g, wet wt, which was found in the liver of a white-tailed sea eagle from the Baltic Sea coast. The accumulation pattern of MeP and 4-HB varied, depending on the species. The mean concentrations of MeP measured in fishes from Michigan, New York, and Florida waters were <2.01 (fillet), 152 (liver), and 32.0 (liver) ng/g, wet wt, respectively, and the corresponding 4-HB concentrations were 39.5, 10,500, and 642ng/g, wet wt. The mean hepatic and renal concentrations of 4-HB in black bears were 1,720 and 1,330ng/g, wet wt, respectively. The concentrations of MeP and 4-HB were significantly positively correlated with each other in various tissues and species, which suggested a common source of exposure to these compounds in fish and birds. Trace concentrations of MeP and 4-HB also were found in the tissues of albatrosses from Midway Atoll, Northwestern Pacific Ocean, which suggested widespread distribution of these compounds in the marine environment. Copyright © 2016 Elsevier Ltd. All rights reserved.

  4. Distribution of mercury in the environment at Almaden, Spain

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

    Hildebrand, S.G.; Huckabee, J.W.; Diaz, F.S.

    1980-10-01

    An ecological survey of the concentration and distribution of mercury in terrestrial and aquatic systems near the mercury mine at Almaden, Spain, was initiated in 1974. Field studies were completed in 1977, and chemical analyses were completed in 1979. Sample collection at Almaden followed a trophic-level approach in which certain compartments were sampled at a given instant in time (fall 1974, fall 1975, spring 1976, fall 1976, spring 1977). Mean total mercury concentration in terrestrial plants (8 taxa combined) ranged from >100 ..mu..g/g within 0.5 km of the mine to 1 ..mu..g/g 20 km distant from the mine. Different plantmore » species had different affinities for mercury, but moss species usually had higher total mercury concentration than vascular plants. Woody plants were lower in mercury concentration than forbs. Total mercury concentration in muscle, brain, kidney, and liver tissue from mice was highest at a station near the stream receiving liquid effluent from the mine (mean total mercury at this station ranging from 0.18 ..mu..g/g in muscle to 4.74 ..mu..g/g in kidney). Approximately 15 to 30% of total mercury in mouse tissue was in the methylated form. Total mercury concentration in muscle tissue from house sparrows varied inversely with distance from the mine, with highest concentrations exceeding 0.1 ..mu..g/g. Approximately 1 to 4% of total mercury in sparrow muscle was in the methylated form.« less

  5. Uptake of selenium and mercury by captive mink: Results of a controlled feeding experiment.

    PubMed

    Evans, R D; Grochowina, N M; Basu, N; O'Connor, E M; Hickie, B E; Rouvinen-Watt, K; Evans, H E; Chan, H M

    2016-02-01

    Captive, juvenile, ranch-bred, male mink (Neovison vison) were fed diets containing various concentrations of methyl-mercury (MeHg) and selenium (Se) for a period of 13 weeks and then sacrificed to determine total Hg levels in fur, blood, brain, liver and kidneys and total Se concentrations in brain tissue. As MeHg concentrations in the diet increased, concentrations of total Hg in the tissues also increased with the highest level occurring in the fur > liver = kidney > brain > blood. Concentrations of Hg in the fur were correlated (r(2) > 0.97) with liver, kidney, blood and brain concentrations. The addition of Se to the mink diet did not appear to affect most tissue concentrations of total Hg nor did it affect the partitioning of Hg between the liver:blood, kidney:blood and brain:blood; however, partitioning of Hg between fur and blood was apparently affected. Copyright © 2015 Elsevier Ltd. All rights reserved.

  6. Testing an aflatoxin B1 gene signature in rat archival tissues.

    PubMed

    Merrick, B Alex; Auerbach, Scott S; Stockton, Patricia S; Foley, Julie F; Malarkey, David E; Sills, Robert C; Irwin, Richard D; Tice, Raymond R

    2012-05-21

    Archival tissues from laboratory studies represent a unique opportunity to explore the relationship between genomic changes and agent-induced disease. In this study, we evaluated the applicability of qPCR for detecting genomic changes in formalin-fixed, paraffin-embedded (FFPE) tissues by determining if a subset of 14 genes from a 90-gene signature derived from microarray data and associated with eventual tumor development could be detected in archival liver, kidney, and lung of rats exposed to aflatoxin B1 (AFB1) for 90 days in feed at 1 ppm. These tissues originated from the same rats used in the microarray study. The 14 genes evaluated were Adam8, Cdh13, Ddit4l, Mybl2, Akr7a3, Akr7a2, Fhit, Wwox, Abcb1b, Abcc3, Cxcl1, Gsta5, Grin2c, and the C8orf46 homologue. The qPCR FFPE liver results were compared to the original liver microarray data and to qPCR results using RNA from fresh frozen liver. Archival liver paraffin blocks yielded 30 to 50 μg of degraded RNA that ranged in size from 0.1 to 4 kB. qPCR results from FFPE and fresh frozen liver samples were positively correlated (p ≤ 0.05) by regression analysis and showed good agreement in direction and proportion of change with microarray data for 11 of 14 genes. All 14 transcripts could be amplified from FFPE kidney RNA except the glutamate receptor gene Grin2c; however, only Abcb1b was significantly upregulated from control. Abundant constitutive transcripts, S18 and β-actin, could be amplified from lung FFPE samples, but the narrow RNA size range (25-500 bp length) prevented consistent detection of target transcripts. Overall, a discrete gene signature derived from prior transcript profiling and representing cell cycle progression, DNA damage response, and xenosensor and detoxication pathways was successfully applied to archival liver and kidney by qPCR and indicated that gene expression changes in response to subchronic AFB1 exposure occurred predominantly in the liver, the primary target for AFB1-induced tumors. We conclude that an evaluation of gene signatures in archival tissues can be an important toxicological tool for evaluating critical molecular events associated with chemical exposures.

  7. Oxidized LDL accumulation in experimental renal ischemia reperfusion injury model.

    PubMed

    Kulah, Eyup; Tascilar, Oge; Acikgoz, Serefden; Tekin, Ishak Ozel; Karadeniz, Guldeniz; Can, Murat; Gun, Banu; Barut, Figen; Comert, Mustafa

    2007-01-01

    The aim of this study was to identify oxidative damage of kidney during ischemia reperfusion injury (IRI) by evaluating changes in lipid peroxidation markers in tissue and blood by an experimental model. Oxidized LDL (ox-LDL) was used as an oxidative stress biomarker, whereas paraoxonase (PON-1) activity was used as an antioxidative biomarker. Sixty-three male Wistar rats were randomly assigned into three groups: renal IRI, sham, and control. In the renal IRI group, the right kidney was removed and the artery and vein of the left kidney were clamped for 90 minutes. The presence of ox-LDL in the kidney tissue sections was determined by using an immunofluorescent staining method. The plasma ox-LDL levels did not increase significantly at the 24th hour following IRI, made a peak at the 48th hour, and declined at the 72nd hour. Accumulation of ox-LDL was detected in the kidney tissue on the 24th, 48th, and 72nd hours of the renal IRI. Serum PON-1 levels have peaked on the 24th hour and then declined. This study demonstrates the accumulation of ox-LDL molecules in the renal tissues of the IRI model. Future strategies aimed to reduce the lipid peroxidation during the initial hours of renal IRI may be useful to prevent complications of ischemia.

  8. 77 FR 9671 - National Institute of Diabetes and Digestive and Kidney Diseases; Notice of Closed Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-02-17

    ... Diabetes and Digestive and Kidney Diseases; Notice of Closed Meeting Pursuant to section 10(d) of the... Diabetes and Digestive and Kidney Diseases Special Emphasis Panel; Liver Tissue and Cell Distribution... and Nutrition Research; 93.849, Kidney Diseases, Urology and Hematology Research, National Institutes...

  9. C-kit+ cells isolated from developing kidneys are a novel population of stem cells with regenerative potential

    PubMed Central

    Rangel, Erika B; Gomes, Samirah A; Dulce, Raul A; Premer, Courtney; Rodrigues, Claudia O; Kanashiro-Takeuchi, Rosemeire M; Oskouei, Behzad; Carvalho, Decio A; Ruiz, Phillip; Reiser, Jochen; Hare, Joshua M

    2013-01-01

    The presence of tissue specific precursor cells is an emerging concept in organ formation and tissue homeostasis. Several progenitors are described in the kidneys. However, their identity as a true stem cell remains elusive. Here, we identify a neonatal kidney-derived c-kit+ cell population that fulfills all of the criteria as a stem cell. These cells were found in the thick ascending limb of Henle's loop and exhibited clonogenicity, self-renewal, and multipotentiality with differentiation capacity into mesoderm and ectoderm progeny. Additionally, c-kit+ cells formed spheres in nonadherent conditions when plated at clonal density and expressed markers of stem cells, progenitors, and differentiated cells. Ex-vivo expanded c-kit+ cells integrated into several compartments of the kidney, including tubules, vessels, and glomeruli, and contributed to functional and morphological improvement of the kidney following acute ischemia-reperfusion injury in rats. Together these findings document a novel neonatal rat kidney c-kit+ stem cell population that can be isolated, expanded, cloned, differentiated, and employed for kidney repair following acute kidney injury. These cells have important biological and therapeutic implications. PMID:23733311

  10. Chronic kidney disease, severe arterial and arteriolar sclerosis and kidney neoplasia: on the spectrum of kidney involvement in MELAS syndrome

    PubMed Central

    2012-01-01

    Background MELAS syndrome (MIM ID#540000), an acronym for Mitochondrial Encephalopathy, Lactic Acidosis and Stroke-like episodes, is a genetically heterogeneous mitochondrial disorder with protean manifestations and occasional kidney involvement. Interest in the latter is rising due to the identification of cases with predominant kidney involvement and to the hypothesis of a link between mitochondrial DNA and kidney neoplasia. Case presentation We report the case of a 41-year-old male with full blown MELAS syndrome, with lactic acidosis and neurological impairment, affected by the "classic" 3243A > G mutation of mitochondrial DNA, with kidney cancer. After unilateral nephrectomy, he rapidly developed severe kidney functional impairment, with nephrotic proteinuria. Analysis of the kidney tissue at a distance from the two tumor lesions, sampled at the time of nephrectomy was performed in the context of normal blood pressure, recent onset of diabetes and before the appearance of proteinuria. The morphological examination revealed a widespread interstitial fibrosis with dense inflammatory infiltrate and tubular atrophy, mostly with thyroidization pattern. Vascular lesions were prominent: large vessels displayed marked intimal fibrosis and arterioles had hyaline deposits typical of hyaline arteriolosclerosis. These severe vascular lesions explained the different glomerular alterations including ischemic and obsolescent glomeruli, as is commonly observed in the so-called "benign" arteriolonephrosclerosis. Some rare glomeruli showed focal segmental glomerulosclerosis; as the patient subsequently developed nephrotic syndrome, these lesions suggest that silent ischemic changes may result in the development of focal segmental glomerulosclerosis secondary to nephron loss. Conclusions Nephron loss may trigger glomerular sclerosis, at least in some cases of MELAS-related nephropathy. Thus the incidence of kidney disease in the "survivors" of MELAS syndrome may increase as the support therapy of these patients improves. PMID:22353239

  11. Chronic kidney disease, severe arterial and arteriolar sclerosis and kidney neoplasia: on the spectrum of kidney involvement in MELAS syndrome.

    PubMed

    Piccoli, Giorgina Barbara; Bonino, Laura Davico; Campisi, Paola; Vigotti, Federica Neve; Ferraresi, Martina; Fassio, Federica; Brocheriou, Isabelle; Porpiglia, Francesco; Restagno, Gabriella

    2012-02-21

    MELAS syndrome (MIM ID#540000), an acronym for Mitochondrial Encephalopathy, Lactic Acidosis and Stroke-like episodes, is a genetically heterogeneous mitochondrial disorder with protean manifestations and occasional kidney involvement. Interest in the latter is rising due to the identification of cases with predominant kidney involvement and to the hypothesis of a link between mitochondrial DNA and kidney neoplasia. We report the case of a 41-year-old male with full blown MELAS syndrome, with lactic acidosis and neurological impairment, affected by the "classic" 3243A > G mutation of mitochondrial DNA, with kidney cancer. After unilateral nephrectomy, he rapidly developed severe kidney functional impairment, with nephrotic proteinuria. Analysis of the kidney tissue at a distance from the two tumor lesions, sampled at the time of nephrectomy was performed in the context of normal blood pressure, recent onset of diabetes and before the appearance of proteinuria. The morphological examination revealed a widespread interstitial fibrosis with dense inflammatory infiltrate and tubular atrophy, mostly with thyroidization pattern. Vascular lesions were prominent: large vessels displayed marked intimal fibrosis and arterioles had hyaline deposits typical of hyaline arteriolosclerosis. These severe vascular lesions explained the different glomerular alterations including ischemic and obsolescent glomeruli, as is commonly observed in the so-called "benign" arteriolonephrosclerosis. Some rare glomeruli showed focal segmental glomerulosclerosis; as the patient subsequently developed nephrotic syndrome, these lesions suggest that silent ischemic changes may result in the development of focal segmental glomerulosclerosis secondary to nephron loss. Nephron loss may trigger glomerular sclerosis, at least in some cases of MELAS-related nephropathy. Thus the incidence of kidney disease in the "survivors" of MELAS syndrome may increase as the support therapy of these patients improves.

  12. Validation and use of three complementary analytical methods (LC-FLS, LC-MS/MS and ICP-MS) to evaluate the pharmacokinetics, biodistribution and stability of motexafin gadolinium in plasma and tissues.

    PubMed

    Miles, Dale R; Mesfin, Mimi; Mody, Tarak D; Stiles, Mark; Lee, Jean; Fiene, John; Denis, Bernie; Boswell, Garry W

    2006-05-01

    Liquid chromatography-fluorescence (LC-FLS), liquid chromatography-tandem mass spectrometry (LC-MS/MS) and inductively coupled plasma-mass spectrometry (ICP-MS) methods were developed and validated for the evaluation of motexafin gadolinium (MGd, Xcytrin) pharmacokinetics and biodistribution in plasma and tissues. The LC-FLS method exhibited the greatest sensitivity (0.0057 microg mL(-1)), and was used for pharmacokinetic, biodistribution, and protein binding studies with small sample sizes or low MGd concentrations. The LC-MS/MS method, which exhibited a short run time and excellent selectivity, was used for routine clinical plasma sample analysis. The ICP-MS method, which measured total Gd, was used in conjunction with LC methods to assess MGd stability in plasma. All three methods were validated using human plasma. The LC-FLS method was also validated using plasma, liver and kidneys from mice and rats. All three methods were shown to be accurate, precise and robust for each matrix validated. For three mice, the mean (standard deviation) concentration of MGd in plasma/tissues taken 5 hr after dosing with 23 mg kg(-1) MGd was determined by LC-FLS as follows: plasma (0.025+/-0.002 microg mL(-1)), liver (2.89+/-0.45 microg g(-1)), and kidney (6.09+/-1.05 microg g(-1)). Plasma samples from a subset of patients with brain metastases from extracranial tumors were analyzed using both LC-MS/MS and ICP-MS methods. For a representative patient, > or = 90% of the total Gd in plasma was accounted for as MGd over the first hour post dosing. By 24 hr post dosing, 63% of total Gd was accounted for as MGd, indicating some metabolism of MGd.

  13. Monitoring impacts of air pollution: PIXE analysis and histopathological modalities in evaluating relative risks of elemental contamination.

    PubMed

    Ejaz, Sohail; Camer, Gerry Amor; Anwar, Khaleeq; Ashraf, Muhammad

    2014-04-01

    Environmental toxicants invariably affect all biological organisms resulting to sufferings ranging from subclinical to debilitating clinical conditions. This novel research aimed to determine the toxic burdens of increased environmental elements in some vital organs/tissues of the wild animals (starling, owl, crow and pigeon), exposed to air polluted environment were assessed using particle induced X-ray emission and histopathological approaches. The presence of significantly elevated amounts of elemental toxicants namely: Aluminum (Al), Chlorine (Cl), Iron (Fe), Potassium (K), Magnesium (Mg), Manganese (Mn), Silicon (Si) and Vanadium (V) from the skin, muscle, lungs, liver and kidney of sampled animals were in concurrence with the observed histopathological changes. The skin of sampled starling, owl, pigeon and crow spotlighted highly significant increase (P < 0.001) in Al, Cl, Mg and Si. Muscle samples with myodegenerative lesions and mineral depositions highlighted substantial augmentation (P < 0.001) in the amount of Al, Fe, Mn, Si and V. The lungs of starling, owl, and pigeon were severely intoxicated (P < 0.001) with increased amount of Al, Fe, K, Mn and Si producing pulmonary lesions of congestion, edema, pneumonitis and mineral debris depositions. Liver samples revealed that the sampled animals were laden with Cl, Fe, Mg, Mn and V with histopathological profound degenerative changes and hepatic necrosis. Kidney sections presented severe tubular degenerative and necrotic changes that may be attributed to increased amounts of Cl and Fe. These current findings implied that the environmental/elemental toxicants and the accompanying lesions that were discerned in the organs/tissues of sampled birds may as well be afflicting people living within the polluted area. Further assessment to more conclusively demonstrate correlations of current findings to those of the populace within the area is encouraged.

  14. Expression of cleaved caspase-3 in renal tubular cells in Plasmodium falciparum malaria patients.

    PubMed

    Wichapoon, Benjamas; Punsawad, Chuchard; Viriyavejakul, Parnpen

    2017-01-01

    In Plasmodium falciparum malaria, the clinical manifestation of acute kidney injury (AKI) is commonly associated with acute tubular necrosis (ATN) in the kidney tissues. Renal tubular cells often exhibit various degrees of cloudy swelling, cell degeneration, and frank necrosis. To study individual cell death, this study evaluates the degree of renal tubular necrosis in association with apoptosis in malarial kidneys. Kidney tissues from P. falciparum malaria with AKI (10 cases), and without AKI (10 cases) were evaluated for tubular pathology. Normal kidney tissues from 10 cases served as controls. Tubular necrosis was assessed quantitatively in kidney tissues infected with P. falciparum malaria, based on histopathological evaluation. In addition, the occurrence of apoptosis was investigated using cleaved caspase-3 marker. Correlation between tubular necrosis and apoptosis was analyzed. Tubular necrosis was found to be highest in P. falciparum malaria patients with AKI (36.44% ± 3.21), compared to non-AKI (15.88% ± 1.63) and control groups (2.58% ± 0.39) (all p < 0.001). In the AKI group, the distal tubules showed a significantly higher degree of tubular necrosis than the proximal tubules (p = 0.021) and collecting tubules (p = 0.033). Tubular necrosis was significantly correlated with the level of serum creatinine (r = 0.596, p = 0.006), and the occurrence of apoptosis (r = 0.681, p = 0.001). In malarial AKI, the process of apoptosis occurs in ATN. © 2016 Asian Pacific Society of Nephrology.

  15. Decellularized scaffold of cryopreserved rat kidney retains its recellularization potential.

    PubMed

    Chani, Baldeep; Puri, Veena; Sobti, Ranbir C; Jha, Vivekanand; Puri, Sanjeev

    2017-01-01

    The multi-cellular nature of renal tissue makes it the most challenging organ for regeneration. Therefore, till date whole organ transplantations remain the definitive treatment for the end stage renal disease (ESRD). The shortage of available organs for the transplantation has, thus, remained a major concern as well as an unsolved problem. In this regard generation of whole organ scaffold through decellularization followed by regeneration of the whole organ by recellularization is being viewed as a potential alternative for generating functional tissues. Despite its growing interest, the optimal processing to achieve functional organ still remains unsolved. The biggest challenge remains is the time line for obtaining kidney. Keeping these facts in mind, we have assessed the effects of cryostorage (3 months) on renal tissue architecture and its potential for decellularization and recellularization in comparison to the freshly isolated kidneys. The light microscopy exploiting different microscopic stains as well as immuno-histochemistry and Scanning electron microscopy (SEM) demonstrated that ECM framework is well retained following kidney cryopreservation. The strength of these structures was reinforced by calculating mechanical stress which confirmed the similarity between the freshly isolated and cryopreserved tissue. The recellularization of these bio-scaffolds, with mesenchymal stem cells quickly repopulated the decellularized structures irrespective of the kidneys status, i.e. freshly isolated or the cryopreserved. The growth pattern employing mesenchymal stem cells demonstrated their equivalent recellularization potential. Based on these observations, it may be concluded that cryopreserved kidneys can be exploited as scaffolds for future development of functional organ.

  16. Development and validation of an UPLC-MS/MS method for the quantification of irinotecan, SN-38 and SN-38 glucuronide in plasma, urine, feces, liver and kidney: Application to a pharmacokinetic study of irinotecan in rats.

    PubMed

    Basu, Sumit; Zeng, Min; Yin, Taijun; Gao, Song; Hu, Ming

    2016-03-15

    The objective of this research is to develop and validate a sensitive and reproducible UPLC-MS/MS method to quantify irinotecan, its active metabolite SN-38 and SN-38 glucuronide (phase II metabolite of SN-38) simultaneously in different bio-matrices (plasma, urine, feces), tissues (liver and kidney) and to use the method to investigate its pharmacokinetic behavior in rats. Irinotecan, SN-38 and SN-38 glucuronide has been resolved and separated by C18 column using acetonitrile and 0.1% formic acid in water used as the mobile phases. Triple quadruple mass spectrometer using multiple reaction monitoring (MRM) with positive scan mode were employed to perform mass analysis. The results showed that the linear response range of irinotecan and SN-38 in plasma, feces, liver and kidney is 4.88-10000 nM, 39-5000 nM, 48.8-6250 nM and 48.8-6250 nM, respectively (R(2)>0.99). In case of SN-38 glucuronide, the standard curves were linear in the concentration range of 6.25-2000 nM, 4.88-1250 nM, 9.8-1250 nM and 9.8-1250 nM in plasma, feces, liver and kidney homogenates, respectively. The lower limit of detection (LLOD) of irinotecan, SN-38 and SN-38 glucuronide was determined to be less than 25 nM in all bio-matrices as well as tissue homogenates. Recoveries of irinotecan, SN-38 and SN-38 glucuronide at three different concentrations (low, medium and high) were not less than 85% at three different concentrations in plasma and feces. The percentage matrix factors in different bio-matrices and tissues were within 20%. The UPLC-MS/MS method was validated with intra-day and inter-day precision of less than 15% in plasma, feces, liver and kidney. Owing to the high sensitivity of this method, only 20 μl of plasma, urine and homogenates of liver, kidney and feces is needed. The validated method has been successfully employed for pharmacokinetic evaluation of irinotecan in male wistar rats to quantify irinotecan, SN-38 and SN-38 glucuronide in plasma, feces, and urine samples. Published by Elsevier B.V.

  17. Development and validation of an UPLC-MS/MS method for the quantification of irinotecan, SN 38 and SN-38 glucuronide in plasma, urine, feces, liver and kidney: Application to a pharmacokinetic study of irinotecan in rats

    PubMed Central

    Basu, Sumit; Zeng, Min; Yin, Taijun; Gao, Song; Hu, Ming

    2016-01-01

    The objective of this research is to develop and validate a sensitive and reproducible UPLC-MS/MS method to quantify irinotecan, its active metabolite SN-38 and SN-38 glucuronide (phase II metabolite of SN-38) simultaneously in different bio-matrices (plasma, urine, feces), tissues (liver and kidney) and to use the method to investigate its pharmacokinetic behavior in rats. Irinotecan, SN-38 and SN-38 glucuronide has been resolved and separated by C18 column using acetonitrile and 0.1% formic acid in water used as the mobile phases. Triple quadruple mass spectrometer using multiple reaction monitoring (MRM) with positive scan mode were employed to perform mass analysis. The results showed that the linear response range of irinotecan and SN-38 in plasma, feces, liver and kidney is 4.88 –10000 nM, 39 – 5000 nM, 48.8 –6250 nM and 48.8 – 6250 nM, respectively (R2 > 0.99). In case of SN-38 glucuronide, the standard curves were linear in the concentration range of 6.25 – 2000 nM, 4.88 – 1250 nM, 9.8 – 1250 nM and 9.8 – 1250 nM in plasma, feces, liver and kidney homogenates, respectively. The lower limit of detection (LLOD) of irinotecan, SN-38 and SN-38 glucuronide was determined to be less than 25 nM in all bio-matrices as well as tissue homogenates. Recoveries of irinotecan, SN-38 and SN-38 glucuronide at three different concentrations (low, medium and high) were not less than 85% at three different concentrations in plasma and feces. The percentage matrix factors in different bio-matrices and tissues were within 20%. The UPLC-MS/MS method was validated with intra-day and inter-day precision of less than 15% in plasma, feces, liver and kidney. Owing to the high sensitivity of this method, only 20 µl of plasma, urine and homogenates of liver, kidney and feces is needed. The validated method has been successfully employed for pharmacokinetic evaluation of irinotecan in male wistar rats to quantify irinotecan, SN-38 and SN-38 glucuronide in plasma, feces, and urine samples. PMID:26894853

  18. Histological Comparison of Kidney Tissue Following Radioembolization with Yttrium-90 Resin Microspheres and Embolization with Bland Microspheres

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

    Silva, Suresh de, E-mail: suresh.desilva@unsw.edu.au; Mackie, Simon; Aslan, Peter

    BackgroundIntra-arterial brachytherapy with yttrium-90 ({sup 90}Y) resin microspheres (radioembolization) is a procedure to selectively deliver high-dose radiation to tumors. The purpose of this research was to compare the radioembolic effect of {sup 90}Y-radioembolization versus the embolic effect of bland microspheres in the porcine kidney model.MethodsIn each of six pigs, ~25–33 % of the kidney volume was embolized with {sup 90}Y resin microspheres and an equivalent number of bland microspheres in the contralateral kidney. Kidney volume was estimated visually from contrast-enhanced fluoroscopy imaging. Morphologic and histologic analysis was performed 8–9 weeks after the procedure to assess the locations of the microspheres and extentmore » of tissue necrosis from {sup 90}Y-radioembolization and bland embolization. A semi-quantified evaluation of the non-acute peri-particle and perivascular tissue reaction was conducted. All guidelines for the care and use of animals were followed.ResultsKidneys embolized with {sup 90}Y-radioembolization decreased in mass by 30–70 % versus the contralateral kidney embolized with bland microspheres. These kidneys showed significant necrosis/fibrosis, avascularization, and glomerular atrophy in the immediate vicinity of the {sup 90}Y resin microspheres. By contrast, glomerular changes were not observed, even with clusters of bland microspheres in afferent arterioles. Evidence of a foreign body reaction was recorded in some kidneys with bland microspheres, and subcapsular scarring/infarction only with the highest load (4.96 × 10{sup 6}) of bland microspheres.ConclusionThis study showed that radioembolization with {sup 90}Y resin microspheres produces localized necrosis/fibrosis and loss of kidney mass in a porcine kidney model. This result supports the study of {sup 90}Y resin microspheres for the localized treatment of kidney tumors.« less

  19. The effect of thiamine injection on upstream migration, survival, and thiamine status of putative thiamine-deficient coho salmon

    USGS Publications Warehouse

    Fitzsimons, J.D.; Williston, B.; Amcoff, P.; Balk, L.; Pecor, C.; Ketola, H.G.; Hinterkopf, J.P.; Honeyfield, D.C.

    2005-01-01

    A diet containing a high proportion of alewives Alosa pseudoharengus results in a thiamine deficiency that has been associated with high larval salmonid mortality, known as early mortality syndrome (EMS), but relatively little is known about the effects of the deficiency on adults. Using thiamine injection (50 mg thiamine/kg body weight) of ascending adult female coho salmon Oncorhynchus kisutch on the Platte River, Michigan, we investigated the effects of thiamine supplementation on migration, adult survival, and thiamine status. The thiamine concentrations of eggs, muscle (red and white), spleen, kidney (head and trunk), and liver and the transketolase activity of the liver, head kidney, and trunk kidney of fish injected with thiamine dissolved in physiological saline (PST) or physiological saline only (PS) were compared with those of uninjected fish. The injection did not affect the number of fish making the 15-km upstream migration to a collection weir but did affect survival once fish reached the upstream weir, where survival of PST-injected fish was almost twice that of controls. The egg and liver thiamine concentrations in PS fish sampled after their upstream migration were significantly lower than those of uninjected fish collected at the downstream weir, but the white muscle thiamine concentration did not differ between the two groups. At the upper weir, thiamine levels in the liver, spleen, head kidney, and trunk kidney of PS fish were indistinguishable from those of uninjected fish (called "wigglers") suffering from a severe deficiency and exhibiting reduced equilibrium, a stage that precedes total loss of equilibrium and death. For PST fish collected at the upstream weir, total thiamine levels in all tissues were significantly elevated over those of PS fish. Based on the limited number of tissues examined, thiamine status was indicated better by tissue thiamine concentration than by transketolase activity. The adult injection method we used appears to be a more effective means of increasing egg thiamine levels than immersion of eggs in a thiamine solution. ?? Copyright by the American Fisheries Society 2005.

  20. High Resolution Tissue Imaging Using the Single-probe Mass Spectrometry under Ambient Conditions

    NASA Astrophysics Data System (ADS)

    Rao, Wei; Pan, Ning; Yang, Zhibo

    2015-06-01

    Ambient mass spectrometry imaging (MSI) is an emerging field with great potential for the detailed spatial analysis of biological samples with minimal pretreatment. We have developed a miniaturized sampling and ionization device, the Single-probe, which uses in-situ surface micro-extraction to achieve high detection sensitivity and spatial resolution during MSI experiments. The Single-probe was coupled to a Thermo LTQ Orbitrap XL mass spectrometer and was able to create high spatial and high mass resolution MS images at 8 ± 2 and 8.5 μm on flat polycarbonate microscope slides and mouse kidney sections, respectively, which are among the highest resolutions available for ambient MSI techniques. Our proof-of-principle experiments indicate that the Single-probe MSI technique has the potential to obtain ambient MS images with very high spatial resolutions with minimal sample preparation, which opens the possibility for subcellular ambient tissue MSI to be performed in the future.

  1. Quantifying the motion of magnetic particles in excised tissue: Effect of particle properties and applied magnetic field

    NASA Astrophysics Data System (ADS)

    Kulkarni, Sandip; Ramaswamy, Bharath; Horton, Emily; Gangapuram, Sruthi; Nacev, Alek; Depireux, Didier; Shimoji, Mika; Shapiro, Benjamin

    2015-11-01

    This article presents a method to investigate how magnetic particle characteristics affect their motion inside tissues under the influence of an applied magnetic field. Particles are placed on top of freshly excised tissue samples, a calibrated magnetic field is applied by a magnet underneath each tissue sample, and we image and quantify particle penetration depth by quantitative metrics to assess how particle sizes, their surface coatings, and tissue resistance affect particle motion. Using this method, we tested available fluorescent particles from Chemicell of four sizes (100 nm, 300 nm, 500 nm, and 1 μm diameter) with four different coatings (starch, chitosan, lipid, and PEG/P) and quantified their motion through freshly excised rat liver, kidney, and brain tissues. In broad terms, we found that the applied magnetic field moved chitosan particles most effectively through all three tissue types (as compared to starch, lipid, and PEG/P coated particles). However, the relationship between particle properties and their resulting motion was found to be complex. Hence, it will likely require substantial further study to elucidate the nuances of transport mechanisms and to select and engineer optimal particle properties to enable the most effective transport through various tissue types under applied magnetic fields.

  2. The protective role of bee honey against the toxic effect of melamine in the male rat kidney.

    PubMed

    Al-Seeni, Madeha N; El Rabey, Haddad A; Al-Solamy, Suad M

    2015-06-01

    This study aimed to test the protective role of natural bee honey against melamine toxicity in the kidney of male albino rats. The dietary supplementation of melamine at a dose of 20,000 ppm for 28 days induced renal dysfunction, as reflected by a significant increase in kidney function parameters (urea, creatinine, and uric acid) and an increase in potassium levels. In addition, a decrease in catalase and glutathione-S-transferase and an increase in lipid peroxide in the kidney tissue homogenate were also observed. Histological changes in the melamine-treated group revealed hyperplasia and damage in kidney cells and the accumulation of melamine crystals in kidney tissues. Honey treatment for 28 days in rats concurrently administered melamine at a dose of 2.5 g/kg body weight for 28 days improved the kidney function, increased antioxidant enzymes, and decreased lipid peroxide levels. The morphology of the kidney cells of the melamine-fed rats was also improved as a result of honey treatment. In conclusion, this study revealed that natural bee honey protects the kidney against the adverse effects induced by melamine toxicity in male albino rats. © The Author(s) 2014.

  3. NMR-based metabolomics approach to study the toxicity of lambda-cyhalothrin to goldfish (Carassius auratus).

    PubMed

    Li, Minghui; Wang, Junsong; Lu, Zhaoguang; Wei, Dandan; Yang, Minghua; Kong, Lingyi

    2014-01-01

    In this study, a (1)H nuclear magnetic resonance (NMR) based metabolomics approach was applied to investigate the toxicity of lambda-cyhalothrin (LCT) in goldfish (Carassius auratus). LCT showed tissue-specific damage to gill, heart, liver and kidney tissues of goldfish. NMR profiling combined with statistical methods such as orthogonal partial least squares discriminant analysis (OPLS-DA) and two-dimensional statistical total correlation spectroscopy (2D-STOCSY) was developed to discern metabolite changes occurring after one week LCT exposure in brain, heart and kidney tissues of goldfish. LCT exposure influenced levels of many metabolites (e.g., leucine, isoleucine and valine in brain and kidney; lactate in brain, heart and kidney; alanine in brain and kidney; choline in brain, heart and kidney; taurine in brain, heart and kidney; N-acetylaspartate in brain; myo-inositol in brain; phosphocreatine in brain and heart; 2-oxoglutarate in brain; cis-aconitate in brain, and etc.), and broke the balance of neurotransmitters and osmoregulators, evoked oxidative stress, disturbed metabolisms of energy and amino acids. The implication of glutamate-glutamine-gamma-aminobutyric axis in LCT induced toxicity was demonstrated for the first time. Our findings demonstrated the applicability and potential of metabolomics approach for the elucidation of toxicological effects of pesticides and the underlying mechanisms, and the discovery of biomarkers for pesticide pollution in aquatic environment. Copyright © 2013 Elsevier B.V. All rights reserved.

  4. Nandrolone administration with or without strenuous exercise promotes overexpression of nephrin and podocin genes and induces structural and functional alterations in the kidneys of rats.

    PubMed

    Tofighi, Asghar; Ahmadi, Shima; Seyyedi, Seyyedeh Masoumeh; Shirpoor, Alireza; Kheradmand, Fatemeh; Gharalari, Farzaneh Hosseini

    2018-01-05

    Among the various adverse effects of nandrolone administration with or without strenuous exercise, kidney abnormalities, where there are associations between nandrolone decanoate consumption, have not been well defined yet. The aim of this study was to investigate the effect of nandrolone decanoate intake with or without strenuous exercise on nephrin and podocin gene expressions, cystatin C, oxidative DNA damage, and histological changes in the kidneys of rats. Thirty-two male wistar rats were assigned into four groups, namely control, nandrolone, nandrolone with strenuous exercise, and strenuous exercise groups. After six weeks of treatment, the results revealed a significant increase in the nephrin and podocin gene expression, plasma cystatin C, and the amount of 8-OHdG in the kidney tissue; as well as a decrease in creatinine clearance in nandrolone and nandrolone with strenuous exercise groups compared to the control group. Moreover, compared to the control group, the nandrolone and the nandrolone with strenuous exercise groups, showed histological changes such as fibrosis and kidney tissue cells proliferation. These findings indicate that nandrolone induces kidney abnormalities, which may in part be associated with overexpression of nephrin and podocin genes mediated by oxidative stress, which was manifested in increased 8-OHdG in kidney tissue. Copyright © 2017 Elsevier B.V. All rights reserved.

  5. Unique molecular changes in kidney allografts after simultaneous liver-kidney compared with solitary kidney transplantation.

    PubMed

    Taner, Timucin; Park, Walter D; Stegall, Mark D

    2017-05-01

    Kidney allografts transplanted simultaneously with liver allografts from the same donor are known to be immunologically privileged. This is especially evident in recipients with high levels of donor-specific anti-HLA antibodies. Here we investigated the mechanisms of liver's protective impact using gene expression in the kidney allograft. Select solitary kidney transplant or simultaneous liver-kidney transplant recipients were retrospectively reviewed and separated into four groups: 16 cross-match negative kidney transplants, 15 cross-match positive kidney transplants, 12 cross-match negative simultaneous liver-kidney transplants, and nine cross-match-positive simultaneous liver-kidney transplants. Surveillance biopsies of cross-match-positive kidney transplants had increased expression of genes associated with donor-specific antigens, inflammation, and endothelial cell activation compared to cross-match-negative kidney transplants. These changes were not found in cross-match-positive simultaneous liver-kidney transplant biopsies when compared to cross-match-negative simultaneous liver-kidney transplants. In addition, simultaneously transplanting a liver markedly increased renal expression of genes associated with tissue integrity/metabolism, regardless of the cross-match status. While the expression of inflammatory gene sets in cross-match-positive simultaneous liver-kidney transplants was not completely reduced to the level of cross-match-negative kidney transplants, the downstream effects of donor-specific anti-HLA antibodies were blocked. Thus, simultaneous liver-kidney transplants can have a profound impact on the kidney allograft, not only by decreasing inflammation and avoiding endothelial cell activation in cross-match-positive recipients, but also by increasing processes associated with tissue integrity/metabolism by unknown mechanisms. Copyright © 2017 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

  6. Low dose X -ray effects on catalase activity in animal tissue

    NASA Astrophysics Data System (ADS)

    Focea, R.; Nadejde, C.; Creanga, D.; Luchian, T.

    2012-12-01

    This study was intended to investigate the effect of low-dose X ray-irradiation upon the activity of catalase (CAT) in freshly excised chicken tissues (liver, kidney, brain, muscle). The tissue samples were irradiated with 0.5Gy and 2Gy respectively, in a 6 MV photon beam produced by a clinical linear accelerator (VARIAN CLINAC 2100SC). The dose rate was of 260.88cGy/min. at 100 cm source to sample distance. The catalase level was assayed spectrophotometrically, based on reaction kinetics, using a catalase UV assay kit (SIGMA). Catalase increased activity in various tissue samples exposed to the studied X ray doses (for example with 24 % in the liver cells, p<0.05) suggested the stimulation of the antioxidant enzyme biosynthesis within several hours after exposure at doses of 0.5 Gy and 2 Gy; the putative enzyme inactivation could also occur (due to the injuries on the hydrogen bonds that ensure the specificity of CAT active site) but the resulted balance of the two concurrent processes indicates the cell ability of decomposing the hydrogen peroxide-with benefits for the cell physiology restoration for the chosen low dose radiation.

  7. Histological Evaluation of Selected Organs of the Eurasian Beavers (Castor fiber) Inhabiting Poland.

    PubMed

    Dolka, I; Giżejewska, A; Giżejewski, Z; Kluciński, W; Kołodziejska, J

    2015-10-01

    There is a general scarcity of data on the histological structure of major organs in the Eurasian beaver (Castor fiber). This study presents the histological characteristics of beaver organs such as the liver, spleen, cardiac muscle, lungs and kidneys. Tissue samples were collected from 21 beavers and analysed. Selected samples of tail tissue were additionally examined. Tissue samples were placed in neutral buffered formalin and embedded in paraffin. 4-μm-thick sections were stained with haematoxylin and eosin, and other staining techniques were also used. Scant amounts of inter-lobular connective tissue were found in the liver. Ion or copper deposition was not observed, but scattered cytoplasmic glycogen deposits were present in hepatocytes. Our results suggest that beavers have defensive rather than storage spleens. Interestingly, the presence of melanin in splenic red pulp was noted. The histological structure of the examined organs closely resembled that of other rodent species. According to our knowledge, this is the first study evaluating the histological structure of beaver organs. Nevertheless, precise characterization of the evaluated organs requires further work with the involvement of accurate and reliable techniques, such as molecular biology or electron microscopy methods. © 2014 Blackwell Verlag GmbH.

  8. Detection and Clinical Patterns of Nephron Hypertrophy and Nephrosclerosis Among Apparently Healthy Adults.

    PubMed

    Denic, Aleksandar; Alexander, Mariam P; Kaushik, Vidhu; Lerman, Lilach O; Lieske, John C; Stegall, Mark D; Larson, Joseph J; Kremers, Walter K; Vrtiska, Terri J; Chakkera, Harini A; Poggio, Emilio D; Rule, Andrew D

    2016-07-01

    Even among ostensibly healthy adults, there is often mild pathology in the kidney. The detection of kidney microstructural variation and pathology by imaging and the clinical pattern associated with these structural findings is unclear. Cross-sectional (clinical-pathologic correlation). Living kidney donors at Mayo Clinic (Minnesota and Arizona sites) and Cleveland Clinic 2000 to 2011. Predonation kidney function, risk factors, and contrast computed tomographic scan of the kidneys. These scans were segmented for cortical volume and medullary volume, reviewed for parenchymal cysts, and scored for kidney surface roughness. Nephrosclerosis (glomerulosclerosis, interstitial fibrosis/tubular atrophy, and arteriosclerosis) and nephron size (glomerular volume, mean profile tubular area, and cortical volume per glomerulus) determined from an implantation biopsy of the kidney cortex at donation. Among 1,520 living kidney donors, nephrosclerosis associated with increased kidney surface roughness, cysts, and smaller cortical to medullary volume ratio. Larger nephron size (nephron hypertrophy) associated with larger cortical volume. Nephron hypertrophy and larger cortical volume associated with higher systolic blood pressure, glomerular filtration rate, and urine albumin excretion; larger body mass index; higher serum uric acid level; and family history of end-stage renal disease. Both nephron hypertrophy and nephrosclerosis associated with older age and mild hypertension. The net effect of both nephron hypertrophy and nephrosclerosis associating with cortical volume was that nephron hypertrophy diminished volume loss with age-related nephrosclerosis and fully negated volume loss with mild hypertension-related nephrosclerosis. Kidney donors are selected on health, restricting the spectrum of pathologic findings. Kidney biopsies in living donors are a small tissue sample leading to imprecise estimates of structural findings. Among apparently healthy adults, the microstructural findings of nephron hypertrophy and nephrosclerosis differ in their associations with kidney function, macrostructure, and risk factors. Copyright © 2016 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

  9. Disseminated fungal infection in two species of captive sharks.

    PubMed

    Marancik, David P; Berliner, Aimee L; Cavin, Julie M; Clauss, Tonya M; Dove, Alistair D M; Sutton, Deanna A; Wickes, Brian L; Camus, Alvin C

    2011-12-01

    In this report, two cases of systemic mycosis in captive sharks are characterized. These cases were progressive and ultimately culminated in terminal disease. Paecilomyces lilacinus, an uncommon pathogen in human and veterinary medicine, was associated with areas of necrosis in the liver, heart, and gill in a great hammerhead shark (Sphyrna mokarran). Fungal growth was observed from samples of kidney, spleen, spinal fluid, and coelomic cavity swabs. Dual fungal infection by Exophiala pisciphila and Mucor circinelloides was diagnosed in a juvenile zebra shark (Stegostoma fasciatum). Both fungi were present in the liver, with more severe tissue destruction associated with E. pisciphila. E. pisciphila also produced significant necrosis in the spleen and gill, while M. circinelloides was associated with only minimal tissue changes in the heart. Fungal cultures from liver, kidney, and spleen were positive for both E. pisciphila and M. circinelloides. Identification of P. lilacinus and M. circinelloides was based on colonial and hyphal morphology. E. pisciphila was identified by sequence analysis of the 28S rRNA D1/D2 region and the internal transcribed spacer (ITS) region between the 18S and 28S rRNA subunit. These cases, and a lack of information in the literature, highlight the need for further research and diagnostic sampling to further characterize the host-pathogen interaction between elasmobranchs and fungi.

  10. Sunitinib-ibuprofen drug interaction affects the pharmacokinetics and tissue distribution of sunitinib to brain, liver, and kidney in male and female mice differently.

    PubMed

    Lau, Christine Li Ling; Chan, Sook Tyng; Selvaratanam, Manimegahlai; Khoo, Hui Wen; Lim, Adeline Yi Ling; Modamio, Pilar; Mariño, Eduardo L; Segarra, Ignacio

    2015-08-01

    Tyrosine kinase inhibitor sunitinib (used in GIST, advanced RCC, and pancreatic neuroendocrine tumors) undergoes CYP3A4 metabolism and is an ABCB1B and ABCG2 efflux transporters substrate. We assessed the pharmacokinetic interaction with ibuprofen (an NSAID used by patients with cancer) in Balb/c male and female mice. Mice (study group) were coadministered (30 min apart) 30 mg/kg of ibuprofen and 60 mg/kg of sunitinib PO and compared with the control groups, which received sunitinib alone (60 mg/kg, PO). Sunitinib concentration in plasma, brain, kidney, and liver was measured by HPLC as scheduled and noncompartmental pharmacokinetic parameters estimated. In female control mice, sunitinib AUC0→∞ decreased in plasma (P < 0.05), was higher in liver and brain (P < 0.001), and lower in kidney (P < 0.001) vs. male control mice. After ibuprofen coadministration, female mice showed lower AUC0→∞ in plasma (P < 0.01), brain, liver, and kidney (all P < 0.001). However, in male mice, AUC0→∞ remained unchanged in plasma, increased in liver and kidney, and decreased in brain (all P < 0.001). The tissue-to-plasma AUC0→∞ ratio was similar between male and female control mice, but changed after ibuprofen coadministration: Male mice showed 1.6-fold higher liver-to-plasma ratio (P < 0.001) while remained unchanged in female mice and in kidney (male and female mice) but decreased 55% in brain (P < 0.05). The tissue-to-plasma partial AUC ratio, the drug tissue targeting index, and the tissue-plasma hysteresis-like plots also showed sex-based ibuprofen-sunitinib drug interaction differences. The results illustrate the relevance of this DDI on sunitinib pharmacokinetics and tissue uptake. These may be due to gender-based P450 and efflux/transporters differences. © 2015 Société Française de Pharmacologie et de Thérapeutique.

  11. l-Methionine and silymarin: A comparison of prophylactic protective capabilities in acetaminophen-induced injuries of the liver, kidney and cerebral cortex.

    PubMed

    Onaolapo, Olakunle J; Adekola, Moses A; Azeez, Taiwo O; Salami, Karimat; Onaolapo, Adejoke Y

    2017-01-01

    We compared the relative protective abilities of silymarin and l-methionine pre-treatment in acetaminophen overdose injuries of the liver, kidney and cerebral cortex by assessing behaviours, antioxidant status, tissue histological changes and biochemical parameters of hepatic/renal function. Rats were divided into six groups of ten each; animals in five of these groups were pre-treated with oral distilled water, silymarin (25mg/kg) or l-methionine (2.5, 5 and 10mg/kg body weight) for 14days; and then administered intraperitoneal (i.p.) acetaminophen at 800mg/kg/day for 3days. Rats in the sixth group (normal control) received distilled water orally for 14days and then i.p. for 3days. Neurobehavioural tests were conducted 7days after last i.p treatment, and animals sacrificed on the 8th day. Plasma was assayed for biochemical markers of liver/kidney function; while sections of the liver, kidney and cerebral cortex were either homogenised for assay of antioxidant status or processed for histology. Acetaminophen overdose resulted in locomotor retardation, excessive self-grooming, working-memory impairment, anxiety, derangement of liver/kidney biochemistry, antioxidant imbalance, and histological changes in the liver, kidney and cerebral cortex. Administration of silymarin or increasing doses of l-methionine counteracted the behavioural changes, reversed biochemical indices of liver/kidney injury, and improved antioxidant activity. Silymarin and l-methionine also conferred variable degrees of tissue protection, on histology. Either silymarin or l-methionine can protect vulnerable tissues from acetaminophen overdose injury; however, each offers variable protection to different tissues. This study highlights an obstacle to seeking the 'ideal' protective agent against acetaminophen overdose. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  12. Albuminuria is associated with an increased prostasin in urine while aldosterone has no direct effect on urine and kidney tissue abundance of prostasin.

    PubMed

    Oxlund, Christina; Kurt, Birgül; Schwarzensteiner, Ilona; Hansen, Mie R; Stæhr, Mette; Svenningsen, Per; Jacobsen, Ib A; Hansen, Pernille B; Thuesen, Anne D; Toft, Anja; Hinrichs, Gitte R; Bistrup, Claus; Jensen, Boye L

    2017-06-01

    The proteinase prostasin is a candidate mediator for aldosterone-driven proteolytic activation of the epithelial sodium channel (ENaC). It was hypothesized that the aldosterone-mineralocorticoid receptor (MR) pathway stimulates prostasin abundance in kidney and urine. Prostasin was measured in plasma and urine from type 2 diabetic patients with resistant hypertension (n = 112) randomized to spironolactone/placebo in a clinical trial. Prostasin protein level was assessed by immunoblotting in (1) human and rat urines with/without nephrotic syndrome, (2) human nephrectomy tissue, (3) urine and kidney from aldosterone synthase-deficient (AS -/- ) mice and ANGII- and aldosterone-infused mice, and in (4) kidney from adrenalectomized rats. Serum aldosterone concentration related to prostasin concentration in urine but not in plasma. Plasma prostasin concentration increased significantly after spironolactone compared to control. Urinary prostasin and albumin related directly and were reduced by spironolactone. In patients with nephrotic syndrome, urinary prostasin protein was elevated compared to controls. In rat nephrosis, proteinuria coincided with increased urinary prostasin, unchanged kidney tissue prostasin, and decreased plasma prostasin while plasma aldosterone was suppressed. Prostasin protein abundance in human nephrectomy tissue was similar across gender and ANGII inhibition regimens. Prostasin urine abundance was not different in AS -/- and aldosterone-infused mice. Prostasin kidney level was not different from control in adrenalectomized rats and AS -/- mice. We found no evidence for a direct relationship between mineralocorticoid receptor signaling and kidney and urine prostasin abundance. The reduction of urinary prostasin in spironolactone-treated patients is most likely the result of an improved glomerular filtration barrier function and generally reduced proteinuria.

  13. Protective effects of piperine on lead acetate induced-nephrotoxicity in rats.

    PubMed

    Sudjarwo, Sri Agus; Eraiko, Koerniasari; Sudjarwo, Giftania Wardani; Koerniasari

    2017-11-01

    In this study, we investigated the protective effects of piperine on lead acetate-induced renal damage in rat kidney tissue. Forty male rats were divided into 5 groups: negative control (rats were given aquadest daily), positive control (rats were given lead acetate 30 mg/kg BW orally once a day for 60 days), and the treatment group (rats were given piperine 50 mg; 100 mg and 200 mg/kg BW orally once a day for 65 days, and on 5 th day, were given lead acetate 30 mg/kg BW one hr after piperine administration for 60 days). On day 65 levels of blood urea nitrogen (BUN), creatinine, malondialdehyde (MDA), Superoxide Dismutase (SOD), and Glutathione Peroxidase (GPx) were measured. Also, kidney samples were collected for histopathological studies. The results revealed that lead acetate toxicity induced a significant increase in the levels of BUN, creatinine, and MDA; moreover, a significant decrease in SOD and GPx. Lead acetate also altered kidney histopathology (kidney damage, necrosis of tubules) compared to the negative control. However, administration of piperine significantly improved the kidney histopathology, decreased the levels of BUN, creatinine, and MDA, and also significantly increased the SOD and GPx in the kidney of lead acetate-treated rats. From the results of this study it was concluded that piperine could be a potent natural herbal product exhibiting nephroprotective effect against lead acetate induced nephrotoxicity in rats.

  14. Influence of polychemotherapy on the morphology of metastases and kidney of resistant RLS-bearing mice.

    PubMed

    Zonov, E V; Voronina, E I; Zenkova, M A; Ageeva, T A; Ryabchikova, E I

    2013-03-01

    Polychemotherapy (PCT), widely used for the antitumor treatment has a pronounced toxic effect on the organism, and its cytostatic effect sometimes is canceled by multidrug resistance of a neoplasia. Comprehension of the nature and development of pathological changes caused by the PCT during the treatment of cancer is very important to improve the efficiency of the therapy and to clarify the mechanisms of tumor-host interactions. This study was aimed to examine PCT impact on kidney cells and tissues in mice with transplanted resistant lymphosacroma (RLS) and to analyze morphology of metastases of the tumor in kidney during PCT. Male mice CBA/LacSto (55 animals) were intramuscularly implanted in the right hind paw by 105 cells/ml of tumor RLS (a diffuse large B-cell lymphosarcoma) with multi-drug resistance (MDR) phenotype. Mice received combination of cyclophosphamide (50 mg/kg), oncovin (0.1 mg/kg), hydroxydaunorubicin (4 mg/kg), and prednisone (5 mg/kg) accordingly to CHOP scheme each 7 days after inoculation of the tumor. The kidneys were sampled on days 1, 3 and 7 after each series of injection of PCT preparations and processed for light and electron microscopy, immunohistochemical analysis of Ki-67 and Apaf-1 proteins also was performed. Tumor RLS produced metastases comprised of small cells in the kidneys of mice after 8 days post inoculation. Application of PCT resulted in destruction of small-cell metastases and development of many large-cell metastases in kidney. Application of PCT induced the development of prominent damage of nephron cells, primarily in S3 segments of proximal tubules. Even one series of PCT caused reduction of basal plasma folds in these cells and alteration of mitochondria. Damage of proximal tubules and involvement of distal tubules, renal bodies and interstitial tissue in the pathologic process, increased during the experiment. This work presents the description of morphological changes in kidney as well as of the tumor metastases under PCT influence. The obtained data should be considered while designing of remedies for recovery of internal organs functions after antitumor PCT.

  15. Renoprotective effects of combined endothelin-converting enzyme/neutral endopeptidase inhibitor SLV338 in acute and chronic experimental renal damage.

    PubMed

    Sharkovska, Yuliya; Kalk, Philipp; von Websky, Karoline; Relle, Katharina; Pfab, Thiemo; Alter, Markus; Fischer, Yvan; Hocher, Berthold

    2011-01-01

    Acute kidney injury (AKI) as well as chronic renal failure are associated with a huge mortality/morbidity. However, so far no drugs have been approved for the treatment of acute kidney failure and only a few for the treatment of chronic kidney disease (CKD). We analysed the effect of SLV338, a neutral endopeptidase (NEP)/endothelin converting enzyme (ECE)-inhibitor in animal models of acute kidney failure as well as chronic renal failure. Acute renal failure was induced in male Wistar rats by uninephrectomy and clamping of the remaining kidney for 55 minutes. SLV338 (total dose: 4.9 mg/kg) or vehicle was continuously infused for 2 hours (starting 20 minutes prior to clamping). Sham operated animals served as controls. Plasma creatinine was measured at baseline and day 2 and 8 after renal ischemia-reperfusion. Hypertensive renal damage was induced in male Sprague Dawley rats by nitric oxide deficiency using L-NAME (50 mg/kg per day, added to drinking water for 4 weeks). One group was treated over the same time period with SLV338 (30 mg/kg per day, mixed with food). Systolic blood pressure was monitored weekly. At study end, urine and blood samples were collected and kidneys were harvested. Acute renal ischemia-reperfusion caused a 5-fold plasma creatinine elevation (day 2), which was significantly attenuated by more than 50% in animals treated with SLV338 (p < 0.05). Renal failure was accompanied by a 67% mortality in vehicle-treated rats, but only 20% after SLV338 treatment (p = 0.03 compared to sham controls). Chronic L-NAME administration caused hypertension, urinary albumin excretion, glomerulosclerosis, renal arterial remodelling, and renal interstitial fibrosis. Treatment with SLV338 did not significantly affect blood pressure, but abolished renal tissue damage (interstitial fibrosis, glomerulosclerosis, renal arterial remodelling (p < 0.05 versus L-NAME group in each case). The dual ECE/NEP inhibitor SLV338 preserves kidney function and reduces mortality in severe acute ischemic renal failure. Moreover, combined ECE/NEP inhibition prevents hypertensive renal tissue damage in a blood pressure independent manner in L-NAME-treated rats.

  16. Apelin/APJ system: A novel potential therapy target for kidney disease.

    PubMed

    Huang, Zhen; Wu, Lele; Chen, Linxi

    2018-05-01

    Apelin is an endogenous ligand of seven-transmembrane G protein-coupled receptor APJ. Apelin and APJ are distributed in various tissues, including the heart, lung, kidney, and even in tumor tissues. Studies show that apelin mRNA is highly expressed in the inner stripe of kidney outer medulla, which plays an important role in process of water and sodium balance. Additionally, more studies also indicate that apelin/APJ system exerts a broad range of activities in kidney. Therefore, we review the role of apelin/APJ system in kidney diseases such as renal fibrosis, renal ischemia/reperfusion injury, diabetic nephropathy, polycystic kidney disease, and hemodialysis (HD). Apelin/APJ system can improve renal interstitial fibrosis by reducing the deposition of extracellular matrix. Apelin/APJ system significantly reduces renal ischemia/reperfusion injury by inhibiting renal cell death. Apelin/APJ system involves the progression of diabetic nephropathy (DN). Apelin/APJ system also predicts the process of polycystic kidney disease. Besides, apelin/APJ system prevents some dialysis complications in HD patients. And apelin/APJ system alleviates chronic kidney disease (CKD) by inhibiting vascular calcification (VC). Overall, apelin/APJ system plays diversified roles in kidney disease and may be a potential target for the treatment of kidney disease. © 2017 Wiley Periodicals, Inc.

  17. Application of Hanging Drop Technique for Kidney Tissue Culture.

    PubMed

    Wang, Shaohui; Wang, Ximing; Boone, Jasmine; Wie, Jin; Yip, Kay-Pong; Zhang, Jie; Wang, Lei; Liu, Ruisheng

    2017-01-01

    The hanging drop technique is a well-established method used in culture of animal tissues. However, this method has not been used in adult kidney tissue culture yet. This study was to explore the feasibility of using this technique for culturing adult kidney cortex to study the time course of RNA viability in the tubules and vasculature, as well as the tissue structural integrity. In each Petri dish with the plate covered with sterile buffer, a section of mouse renal cortex was cultured within a drop of DMEM culture medium on the inner surface of the lip facing downward. The tissue were then harvested at each specific time points for Real-time PCR analysis and histological studies. The results showed that the mRNA level of most Na+ related transporters and cotransporters were stably maintained within 6 hours in culture, and that the mRNA level of most receptors found in the vasculature and glomeruli were stably maintained for up to 9 days in culture. Paraffin sections of the cultured renal cortex indicated that the tubules began to lose tubular integrity after 6 hours, but the glomeruli and vasculatures were still recognizable up to 9 days in culture. We concluded that adult kidney tissue culture by hanging drop method can be used to study gene expressions in vasculature and glomeruli. © 2017 The Author(s). Published by S. Karger AG, Basel.

  18. Impact of industrial effluents on the biochemical composition of fresh water fish Labeo rohita.

    PubMed

    Muley, D V; Karanjkar, D M; Maske, S V

    2007-04-01

    In acute toxicity (96 hr) experiment the fingerlings of freshwater fish Labeo rohita was exposed to tannery, electroplating and textile mill effluents. The LC0 and LC50 concentrations were 15% and 20% for tannery effluents, 3% and 6% for electroplating effluents and 18% and 22% for textile mill effluents respectively. It was found that, electroplating effluent was more toxic than tannery and textile mill wastes. After acute toxicity experiments for different industrial effluents, various tissues viz. gill, liver, muscle and kidney were obtained separately from control, LC0 and LC50 groups. These tissues were used for biochemical estimations. The glycogen content in all the tissues decreased considerably upon acute toxicity of three industrial effluents except muscle in LC50 group of tannery effluent and kidney in LC50 group of textile mill effluent, when compared to control group. The total protein content decreased in all tissues in three effluents except gills in LC50 group of tannery effluent, kidney in LC50 group of electroplating effluent and kidney in LC0 group of textile mill effluent. In general total lipid content decreased in all tissues after acute exposure when compared to control group. The results obtained in the present study showed that, the industrial effluents from tannery, electroplating and textile mills caused marked depletion in biochemical composition in various tissues of the fish Labeo rohita after acute exposure.

  19. Influence of dietary magnesium on mineral, ascorbic acid and glutathione concentrations in tissues of a freshwater fish, the common carp.

    PubMed

    Dabrowska, H; Dabrowski, K

    1990-01-01

    Supplementation with dietary Mg at a minimum level of 0.06% seems to be essential to prevent the hypercalcinosis of the kidney and hepatopancreas in a fish, the common carp. Mg deficiency appears to have no effect on the Mg level in kidneys and hepatic tissue, whereas the Fe level in those tissues was significantly diminished by increasing dietary Mg supplementation up to 3.2 g.kg-1. Both hypercalcinosis and accumulation of Fe in soft tissues were more pronounced in fish offered diets high in protein (44%) compared to fish on low dietary protein (25%). The ascorbic acid in the hepatopancreas and kidney was greatly depleted in fish fed the high-protein diets, and this depletion did not correlate with the dietary Mg level nor with a high level of tissue Ca. However, the increased Ca concentration in the kidney coincided with the greatest depletion of ascorbate in fish fed a high-protein diet. The concentration of ascorbate in the brain was much less affected by a low level of vitamin C in the diets than in other tissues. Depletion of ascorbate in soft tissues did not correspond to fish growth but might be rather related to the metabolic rate imposed by the dietary nutrients. It is suggested that the Mg and ascorbic acid requirements in the carp are considerably elevated by the increased dietary protein level.

  20. Allometric scaling of fatty acyl chains in fowl liver, lung and kidney, but not in brain phospholipids.

    PubMed

    Szabó, András; Mézes, Miklós; Romvári, Róbert; Fébel, Hedvig

    2010-03-01

    The phospholipid (PL) fatty acyl chain (FA) composition (mol%) was determined in the kidney, liver, lung and brain of 8 avian species ranging in body mass from 150g (Japanese quail, Coturnix coturnix japonica) to 19kg (turkey, Meleagris gallopavo). In all organs except the brain, docosahexaenoic acid (C22:6 n3, DHA) was found to show a negative allometric scaling (allometric exponent: B=-0.18; -0.20 and -0.24, for kidney, liver and lung, respectively). With minor inter-organ differences, smaller birds had more n3 FAs and longer FA chains in the renal, hepatic and pulmonary PLs. Comparing our results with literature data on avian skeletal muscle, liver mitochondria and kidney microsomes and divergent mammalian tissues, the present findings in the kidney, liver and lung PLs seem to be a part of a general relationship termed "membranes as metabolic pacemakers". Marked negative allometric scaling was found furthermore for the tissue malondialdehyde concentrations in all organs except the brain (B=-0.17; -0.13 and -0.05, respectively). In the liver and kidney a strong correlation was found between the tissue MDA and DHA levels, expressing the role of DHA in shaping the allometric properties of membrane lipids. 2009 Elsevier Inc. All rights reserved.

  1. Protective effect of Urtica dioica L. on renal ischemia/reperfusion injury in rat.

    PubMed

    Sayhan, Mustafa Burak; Kanter, Mehmet; Oguz, Serhat; Erboga, Mustafa

    2012-12-01

    Renal ischemia-reperfusion (I/R) injury may occur after renal transplantation, thoracoabdominal aortic surgery, and renal artery interventions. This study was designed to investigate the effect of Urtica dioica L. (UD), in I/R induced renal injury. A total of 32 male Sprague-Dawley rats were divided into four groups: control, UD alone, I/R and I/R + UD; each group contain 8 animals. A rat model of renal I/R injury was induced by 45-min occlusion of the bilateral renal pedicles and 24-h reperfusion. In the UD group, 3 days before I/R, UD (2 ml/kg/day intraperitoneal) was administered by gastric gavage. All animals were sacrificed at the end of reperfusion and kidney tissues samples were obtained for histopathological investigation in all groups. To date, no more histopathological changes on intestinal I/R injury in rats by UD treatment have been reported. Renal I/R caused severe histopathological injury including tubular damage, atrophy dilatation, loss of brush border and hydropic epithelial cell degenerations, renal corpuscle atrophy, glomerular shrinkage, markedly focal mononuclear cell infiltrations in the kidney. UD treatment significantly attenuated the severity of intestinal I/R injury and significantly lowered tubulointerstitial damage score than the I/R group. The number of PCNA and TUNEL positive cells in the control and UD alone groups was negligible. When kidney sections were PCNA and TUNEL stained, there was a clear increase in the number of positive cells in the I/R group rats in the renal cortical tissues. However, there is a significant reduction in the activity of PCNA and TUNEL in kidney tissue of renal injury induced by renal I/R with UD therapy. Our results suggest that administration of UD attenuates renal I/R injury. These results suggest that UD treatment has a protective effect against renal damage induced by renal I/R. This protective effect is possibly due to its ability to inhibit I/R induced renal damage, apoptosis and cell proliferation.

  2. Effects of Carnosine (Beta-Alanyl-L-Histidine) in an Experimental Rat Model of Acute Kidney Injury Due to Septic Shock

    PubMed Central

    Sahin, Sabiha; Donmez, Dilek Burukoglu

    2018-01-01

    Background Acute kidney injury (AKI) secondary to sepsis is a major cause of morbidity and mortality in the human intensive care unit (ICU). Kidney function and the histological findings of AKI were investigated in an experimental rat model with sepsis induced by cecal ligation and puncture (CLP) and compared with and without treatment with carnosine (beta-alanyl-L-histidine). Material/Methods Twenty-four Sprague-Dawley rats were randomly divided into three groups consisting eight rats in each: Group 1 – control; Group 2 – septic shock; and Group 3 – septic shock treated with carnosine. Femoral vein and artery catheterization were applied in all rats. Rats in Group 1 underwent laparotomy and catheterization. The other two groups with septic shock underwent laparotomy, CLP, catheterization, and bladder cannulation. Rats in Group 3 received an intraperitoneal (IP) injection of 250 mg/kg carnosine, 60 min following CLP. Rats were monitored for blood pressure, pulse rate, and body temperature to assess responses to postoperative sepsis, and 10 mL/kg saline replacement was administered. Twenty-four hours following CLP, rats were sacrificed, and blood and renal tissue samples were collected. Results Statistically significant improvements were observed in kidney function, tissue and serum malondialdehyde levels, routine blood values, biochemical indices, and in histopathological findings in rats in Group 3 who were treated with carnosine, compared with Group 2 exposed to septic shock without carnosine treatment. Conclusions Carnosine (beta-alanyl-L-histidine) has been shown to have beneficial effects in reducing AKI due to septic shock in a rat model of septicemia. PMID:29334583

  3. Effects of Platelet-Rich Plasma (PRP) on a Model of Renal Ischemia-Reperfusion in Rats.

    PubMed

    Martín-Solé, Oriol; Rodó, Joan; García-Aparicio, Lluís; Blanch, Josep; Cusí, Victoria; Albert, Asteria

    2016-01-01

    Renal ischemia-reperfusion injury is a major cause of acute renal failure, causing renal cell death, a permanent decrease of renal blood flow, organ dysfunction and chronic kidney disease. Platelet-rich plasma (PRP) is an autologous product rich in growth factors, and therefore able to promote tissue regeneration and angiogenesis. This product has proven its efficacy in multiple studies, but has not yet been tested on kidney tissue. The aim of this work is to evaluate whether the application of PRP to rat kidneys undergoing ischemia-reperfusion reduces mid-term kidney damage. A total of 30 monorrenal Sprague-Dawley male rats underwent renal ischemia-reperfusion for 45 minutes. During ischemia, PRP (PRP Group, n = 15) or saline solution (SALINE Group, n = 15) was administered by subcapsular renal injection. Control kidneys were the contralateral organs removed immediately before the start of ischemia in the remaining kidneys. Survival, body weight, renal blood flow on Doppler ultrasound, kidney weight, kidney volume, blood biochemistry and histopathology were determined for all subjects and kidneys, as applicable. Correlations between these variables were searched for. The PRP Group showed significantly worse kidney blood flow (p = 0.045) and more histopathological damage (p<0.0001). Correlations were found between body weight, kidney volume, kidney weight, renal blood flow, histology, and serum levels of creatinine and urea. Our study provides the first evidence that treatment with PRP results in the deterioration of the kidney's response to ischemia-reperfusion injury.

  4. The AKT-mTOR signalling pathway in kidney cancer tissues

    NASA Astrophysics Data System (ADS)

    Spirina, L. V.; Usynin, Y. A.; Kondakova, I. V.; Yurmazov, Z. A.; Slonimskaya, E. M.; Kolegova, E. S.

    2015-11-01

    An increased expression of phospho-AKT, m-TOR, glycogen regulator GSK-3-beta and transcription inhibitor 4E-BP1 was observed in kidney cancer tissues. Tumor size growth was associated with a high level of c-Raf and low content of phospho-m-TOR. Cancer metastasis development led to a decreased PTEN and phospho-AKT expression.

  5. Assessment of heavy metals and metalloids in tissues of two frog species: Rana tigrina and Euphlyctis cyanophlyctis from industrial city Sialkot, Pakistan.

    PubMed

    Qureshi, Irfan Zia; Kashif, Zeshan; Hashmi, Muhammad Zaffar; Su, Xiaomei; Malik, Riffat Naseem; Ullah, Kalim; Hu, Jinxing; Dawood, Muhammad

    2015-09-01

    In the present study, we investigated the concentrations of Ni, Fe, Pb, Cu, Co, Zn, Cd, Mn, and Cr in selected body tissues (liver, stomach, kidney, heart, lungs, and skeletal muscles) of two frog species: Rana tigrina and Euphlyctis cyanophlyctis captured from industrial wastewater of Sialkot city known worldwide for its tanning industry. The both frog species had darker appearance, distinctively different wet body weight, and snout-vent length. The results revealed that the heavy metal concentrations were high in the samples collected from industrial sites as compared to non-industrial sites. The different tissues of R. tigrina and E. cyanophlyctis exhibited little significant differences from two sites. The concentrations of heavy metals were more in tissues of R. tigrina as compared to E. cyanophlyctis. Mean concentration of Cd, Fe, Ni, Mn, Cu, and Cr was comparatively greater in R. tigrina, whereas Pb and Co were higher in E. cyanophlyctis. The concentration of Cu and Cd in the liver and kidney were relatively more in both species as compared to other organs. Further, the results indicated that frogs collected from industrial sites showed decreased body length and weight, and greater metal accumulation. The results will help the authorities for the conservation of these frog species which are under the influence of heavy metal contamination.

  6. Nanoscale imaging of clinical specimens using pathology-optimized expansion microscopy

    PubMed Central

    Zhao, Yongxin; Bucur, Octavian; Irshad, Humayun; Chen, Fei; Weins, Astrid; Stancu, Andreea L.; Oh, Eun-Young; DiStasio, Marcello; Torous, Vanda; Glass, Benjamin; Stillman, Isaac E.; Schnitt, Stuart J.; Beck, Andrew H.; Boyden, Edward S.

    2017-01-01

    Expansion microscopy (ExM), a method for improving the resolution of light microscopy by physically expanding the specimen, has not been applied to clinical tissue samples. Here we report a clinically optimized form of ExM that supports nanoscale imaging of human tissue specimens that have been fixed with formalin, embedded in paraffin, stained with hematoxylin and eosin (H&E), and/or fresh frozen. The method, which we call expansion pathology (ExPath), converts clinical samples into an ExM-compatible state, then applies an ExM protocol with protein anchoring and mechanical homogenization steps optimized for clinical samples. ExPath enables ~70 nm resolution imaging of diverse biomolecules in intact tissues using conventional diffraction-limited microscopes, and standard antibody and fluorescent DNA in situ hybridization reagents. We use ExPath for optical diagnosis of kidney minimal-change disease, which previously required electron microscopy (EM), and demonstrate high-fidelity computational discrimination between early breast neoplastic lesions that to date have challenged human judgment. ExPath may enable the routine use of nanoscale imaging in pathology and clinical research. PMID:28714966

  7. Nanoscale imaging of clinical specimens using pathology-optimized expansion microscopy.

    PubMed

    Zhao, Yongxin; Bucur, Octavian; Irshad, Humayun; Chen, Fei; Weins, Astrid; Stancu, Andreea L; Oh, Eun-Young; DiStasio, Marcello; Torous, Vanda; Glass, Benjamin; Stillman, Isaac E; Schnitt, Stuart J; Beck, Andrew H; Boyden, Edward S

    2017-08-01

    Expansion microscopy (ExM), a method for improving the resolution of light microscopy by physically expanding a specimen, has not been applied to clinical tissue samples. Here we report a clinically optimized form of ExM that supports nanoscale imaging of human tissue specimens that have been fixed with formalin, embedded in paraffin, stained with hematoxylin and eosin, and/or fresh frozen. The method, which we call expansion pathology (ExPath), converts clinical samples into an ExM-compatible state, then applies an ExM protocol with protein anchoring and mechanical homogenization steps optimized for clinical samples. ExPath enables ∼70-nm-resolution imaging of diverse biomolecules in intact tissues using conventional diffraction-limited microscopes and standard antibody and fluorescent DNA in situ hybridization reagents. We use ExPath for optical diagnosis of kidney minimal-change disease, a process that previously required electron microscopy, and we demonstrate high-fidelity computational discrimination between early breast neoplastic lesions for which pathologists often disagree in classification. ExPath may enable the routine use of nanoscale imaging in pathology and clinical research.

  8. Sirolimus in kidney transplant donors and clinical and histologic improvement in recipients: rat model.

    PubMed

    Cicora, F; Lausada, N; Vasquez, D N; Cicora, P; Zalazar, G; Gonzalez, P; Palti, G; Raimondi, C

    2010-01-01

    Ischemia-reperfusion (I/R) injury is one of the risk factors for delayed graft function, acute rejection episodes, and impaired long-term allograft survival after kidney transplantation. This antigen-independent inflammatory process produces tissue damage. Isogeneic transplantation in a rat model is a useful method for study of nonimmunologic risk factors for kidney damage. To study the effect of sirolimus on I/R injury using only 1 dose of the drug in the donor. Eighteen rats were allocated to 3 groups of 6 rats each: sham group, control group, and rapamycin group. Improved renal function and systemic inflammatory response were observed in the rapamycin group compared with the control group (Deltaurea, Deltacreatinine, and DeltaC3, all P < .01). The number of apoptotic nuclei in the renal medulla in the control group was higher than in the rapamycin group (P < .01). Tubular damage was less severe in the rapamycin group compared with the control group (P < .01). Complement 3 and tumor necrosis factor-alpha expression in the kidney samples were significantly decreased when rapamycin was given to the donor rats (P > .01). Bcl-2 protein was upregulated in the rapamycin group compared with the control group (P < .01). Administration of rapamycin in donors attenuates the I/R injury process after kidney transplantation in a rat model.

  9. Transport of Gold Nanoparticles by Vascular Endothelium from Different Human Tissues

    PubMed Central

    Gromnicova, Radka; Kaya, Mehmet; Romero, Ignacio A.; Williams, Phil; Satchell, Simon; Sharrack, Basil; Male, David

    2016-01-01

    The selective entry of nanoparticles into target tissues is the key factor which determines their tissue distribution. Entry is primarily controlled by microvascular endothelial cells, which have tissue-specific properties. This study investigated the cellular properties involved in selective transport of gold nanoparticles (<5 nm) coated with PEG-amine/galactose in two different human vascular endothelia. Kidney endothelium (ciGENC) showed higher uptake of these nanoparticles than brain endothelium (hCMEC/D3), reflecting their biodistribution in vivo. Nanoparticle uptake and subcellular localisation was quantified by transmission electron microscopy. The rate of internalisation was approximately 4x higher in kidney endothelium than brain endothelium. Vesicular endocytosis was approximately 4x greater than cytosolic uptake in both cell types, and endocytosis was blocked by metabolic inhibition, whereas cytosolic uptake was energy-independent. The cellular basis for the different rates of internalisation was investigated. Morphologically, both endothelia had similar profiles of vesicles and cell volumes. However, the rate of endocytosis was higher in kidney endothelium. Moreover, the glycocalyces of the endothelia differed, as determined by lectin-binding, and partial removal of the glycocalyx reduced nanoparticle uptake by kidney endothelium, but not brain endothelium. This study identifies tissue-specific properties of vascular endothelium that affects their interaction with nanoparticles and rate of transport. PMID:27560685

  10. Effect of body condition on tissue distribution of perfluoroalkyl substances (PFASs) in Arctic fox (Vulpes lagopus).

    PubMed

    Aas, Camilla Bakken; Fuglei, Eva; Herzke, Dorte; Yoccoz, Nigel G; Routti, Heli

    2014-10-07

    Arctic animals undergo large seasonal fluctuations in body weight. The effect of body condition on the distribution and composition of 16 perfluoroalkyl substances (PFASs) was investigated in liver, blood, kidney, adipose tissue, and muscle of Arctic foxes (Vulpes lagopus) from Svalbard (n = 18, age 1-3 years). PFAS concentrations were generally highest in liver, followed by blood and kidney, while lowest concentrations were found in adipose tissue and muscle. Concentrations of summed perfluorocarboxylic acids and perfluoroalkyl sulfonates were five and seven times higher, respectively, in adipose tissue of lean compared to fat foxes. In addition, perfluorodecanoate (PFDA) and perfluoroheptanesulfonate (PFHpS) concentrations in liver, kidney, and blood, and, perfluorononanoate (PFNA) in liver and blood, were twice as high in the lean compared to the fat foxes. The ratio between perfluorooctane sulfonamide (FOSA) and its metabolite perfluorooctanesulfonate (PFOS) was lowest in liver, muscle, and kidney, while significantly higher proportions of FOSA were found in adipose tissue and blood. The results of the present study suggest that toxic potential of exposure to PFAS among other pollutants in Arctic mammals may increase during seasonal emaciation. The results also suggest that body condition should be taken into account when assessing temporal trends of PFASs.

  11. Uniform neural tissue models produced on synthetic hydrogels using standard culture techniques.

    PubMed

    Barry, Christopher; Schmitz, Matthew T; Propson, Nicholas E; Hou, Zhonggang; Zhang, Jue; Nguyen, Bao K; Bolin, Jennifer M; Jiang, Peng; McIntosh, Brian E; Probasco, Mitchell D; Swanson, Scott; Stewart, Ron; Thomson, James A; Schwartz, Michael P; Murphy, William L

    2017-11-01

    The aim of the present study was to test sample reproducibility for model neural tissues formed on synthetic hydrogels. Human embryonic stem (ES) cell-derived precursor cells were cultured on synthetic poly(ethylene glycol) (PEG) hydrogels to promote differentiation and self-organization into model neural tissue constructs. Neural progenitor, vascular, and microglial precursor cells were combined on PEG hydrogels to mimic developmental timing, which produced multicomponent neural constructs with 3D neuronal and glial organization, organized vascular networks, and microglia with ramified morphologies. Spearman's rank correlation analysis of global gene expression profiles and a comparison of coefficient of variation for expressed genes demonstrated that replicate neural constructs were highly uniform to at least day 21 for samples from independent experiments. We also demonstrate that model neural tissues formed on PEG hydrogels using a simplified neural differentiation protocol correlated more strongly to in vivo brain development than samples cultured on tissue culture polystyrene surfaces alone. These results provide a proof-of-concept demonstration that 3D cellular models that mimic aspects of human brain development can be produced from human pluripotent stem cells with high sample uniformity between experiments by using standard culture techniques, cryopreserved cell stocks, and a synthetic extracellular matrix. Impact statement Pluripotent stem (PS) cells have been characterized by an inherent ability to self-organize into 3D "organoids" resembling stomach, intestine, liver, kidney, and brain tissues, offering a potentially powerful tool for modeling human development and disease. However, organoid formation must be quantitatively reproducible for applications such as drug and toxicity screening. Here, we report a strategy to produce uniform neural tissue constructs with reproducible global gene expression profiles for replicate samples from multiple experiments.

  12. Safety evaluation of mercury based Ayurvedic formulation (Sidh Makardhwaj) on brain cerebrum, liver & kidney in rats

    PubMed Central

    Kumar, Gajendra; Srivastava, Amita; Sharma, Surinder Kumar; Gupta, Yogendra Kumar

    2014-01-01

    Background & objectives: Sidh Makardhwaj (SM) is a mercury based Ayurvedic formulation used in rheumatoid arthritis and neurological disorders. However, toxicity concerns due to mercury content are often raised. Therefore, the present study was carried out to evaluate the effect of SM on brain cerebrum, liver and kidney in rats. Methods: Graded doses of SM (10, 50, 100 mg/kg), mercuric chloride (1 mg/kg) and normal saline were administered orally to male Wistar rats for 28 days. Behavioural parameters were assessed on days 1, 7, 14 and 28 using Morris water maze, passive avoidance, elevated plus maze and rota rod. Liver and kidney function tests were done on day 28. Animals were sacrificed and brain cerebrum acetylcholinesterase activity, levels of malondialdehyde (MDA), reduced glutathione (GSH) in brain cerebrum, liver, kidney were estimated. The levels of mercury in brain cerebrum, liver and kidney were estimated and histopathology of these tissues was also performed. Results: SM in the doses used did not cause significant change in neurobehavioural parameters, brain cerebrum AChE activity, liver (ALT, AST, ALP bilirubin) and kidney (serum urea and creatinine) function tests as compared to control. The levels of mercury in brain cerebrum, liver, and kidney were found to be raised in dose dependent manner. However, the levels of MDA and GSH in these tissues did not show significant changes at doses of 10 and 50 mg/kg. Also, there was no histopathological change in cytoarchitecture of brain cerebrum, liver, and kidney tissues at doses of 10 and 50 mg/kg. Interpretation & conclusions: The findings of the present study suggest that Sidh Makardhwaj upto five times the equivalent human dose administered for 28 days did not show any toxicological effects on rat brain cerebrum, liver and kidney. PMID:24927349

  13. Safety evaluation of mercury based Ayurvedic formulation (Sidh Makardhwaj) on brain cerebrum, liver & kidney in rats.

    PubMed

    Kumar, Gajendra; Srivastava, Amita; Sharma, Surinder Kumar; Gupta, Yogendra Kumar

    2014-04-01

    Sidh Makardhwaj (SM) is a mercury based Ayurvedic formulation used in rheumatoid arthritis and neurological disorders. However, toxicity concerns due to mercury content are often raised. Therefore, the present study was carried out to evaluate the effect of SM on brain cerebrum, liver and kidney in rats. Graded doses of SM (10, 50, 100 mg/kg), mercuric chloride (1 mg/kg) and normal saline were administered orally to male Wistar rats for 28 days. Behavioural parameters were assessed on days 1, 7, 14 and 28 using Morris water maze, passive avoidance, elevated plus maze and rota rod. Liver and kidney function tests were done on day 28. Animals were sacrificed and brain cerebrum acetylcholinesterase activity, levels of malondialdehyde (MDA), reduced glutathione (GSH) in brain cerebrum, liver, kidney were estimated. The levels of mercury in brain cerebrum, liver and kidney were estimated and histopathology of these tissues was also performed. SM in the doses used did not cause significant change in neurobehavioural parameters, brain cerebrum AChE activity, liver (ALT, AST, ALP bilirubin) and kidney (serum urea and creatinine) function tests as compared to control. The levels of mercury in brain cerebrum, liver, and kidney were found to be raised in dose dependent manner. However, the levels of MDA and GSH in these tissues did not show significant changes at doses of 10 and 50 mg/kg. Also, there was no histopathological change in cytoarchitecture of brain cerebrum, liver, and kidney tissues at doses of 10 and 50 mg/kg. The findings of the present study suggest that Sidh Makardhwaj upto five times the equivalent human dose administered for 28 days did not show any toxicological effects on rat brain cerebrum, liver and kidney.

  14. Avian toxicologic diagnosis

    USGS Publications Warehouse

    Sigurdson, C.J.; Franson, J.C.; Fudge, A.M.

    2000-01-01

    This chapter describes the sources and pathophysiology of some potential poisons that affect birds and summarizes useful laboratory tests. The diagnosis of poisoning in birds, as in mammals, requires a complete and accurate history, careful observation of clinical signs, and a thorough necropsy evaluation. Appropriate sample handling and analysis, based on consultation with the diagnostic toxicologist, are critical (Table 19--1). Veterinary toxicology laboratories are becoming increasingly specialized, with only certain laboratories capable of analyzing for drug residues or anticoagulants, for example. Although a local laboratory may not be able to fulfill a specific test request, they may recommend an alternative laboratory or may be willing to forward the sample. As a general rule in suspect poisoning cases, large tissue samples of liver, kidney, brain, and subcutaneous fat and of crop, proventriculus, and ventriculus contents should be collected at necropsy and frozen. Appropriate samples should be submitted frozen, with the remainder held in the freezer for possible later testing. A second set of tissues should be placed in 10% formalin for histopathologic examination.

  15. Effects of chytridiomycosis on hematopoietic tissue in the spleen, kidney and bone marrow in three diverse amphibian species.

    PubMed

    Brannelly, Laura A; Webb, Rebecca J; Skerratt, Lee F; Berger, Lee

    2016-10-01

    One of the major causes of amphibian population decline is the deadly fungal pathogen Batrachochytrium dendrobatidis, Bd Research on pathogenesis and host immunity aims to inform development of targeted conservation interventions. Studies examining global host immune responses as well as effects on lymphocytes in vitro suggest that Bd infection causes immunosuppression. However, it is unknown which hematopoietic tissues are affected and if these effects differ among host species. We investigated the effect of experimental Bd infection on three diverse amphibian species by quantifying the amount of hematopoietic tissue in the spleen, bone marrow and kidney. Upon Bd infection, hematopoietic tissue in the kidney tended to be depleted, while the spleen appeared unaffected. The bone marrow in highly susceptible species was depleted, whereas an increase in hematopoietic tissue was observed in the more resistant species. Our study demonstrates that species and hematopoietic tissues behave differently in response to Bd infection, and may be related to the species' susceptibility to infection. © FEMS 2016. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  16. Pathogenesis of highly pathogenic avian influenza A virus (H7N1) infection in chickens inoculated with three different doses.

    PubMed

    Chaves, Aida J; Busquets, Nuria; Campos, Naiana; Ramis, Antonio; Dolz, Roser; Rivas, Raquel; Valle, Rosa; Abad, F Xavier; Darji, Ayub; Majo, Natalia

    2011-04-01

    To study the pathogenesis of a H7N1 highly pathogenic avian influenza virus strain, specific pathogen free chickens were inoculated with decreasing concentrations of virus: 10(5.5) median embryo lethal dose (ELD(50)) (G1), 10(3.5) ELD(50) (G2) and 10(1.5) ELD(50) (G3). Disease progression was monitored over a period of 16 days and sequential necropsies and tissue samples were collected for histological and immunohistochemical examination. Viral RNA loads were also quantified in different tissues, blood, oropharyngeal swabs, and cloacal swabs using quantitative real-time reverse transcriptase-polymerase chain reaction (RT-qPCR). Clinical signs of depression, apathy, listlessness, huddling and ruffled feathers were recorded in G1 and a few G2 birds, whilst neurological signs were only observed in chickens inoculated with the highest dose. Gross lesions of haemorrhages were observed in the unfeathered skin of the comb and legs, and skeletal muscle, lung, pancreas and kidneys of birds inoculated with 10(5.5) ELD(50) and 10(3.5) ELD(50) doses. Microscopic lesions and viral antigen were demonstrated in cells of the nasal cavity, lung, heart, skeletal muscle, brain, spinal cord, gastrointestinal tract, pancreas, liver, bone marrow, thymus, bursa of Fabricius, spleen, kidney, adrenal gland and skin. Viral RNA was detected by RT-qPCR in kidney, lung, intestine, and brain samples of G1 and G2 birds. However, in birds infected with the lowest dose, viral RNA was detected only in brain and lung samples in low amounts at 5 and 7 days post infection. Interestingly, viral shedding was observed in oropharyngeal and cloacal swabs with proportionate decrease with the inoculation dose. We conclude that although an adequate infectious dose is critical in reproducing the clinical infection, chickens exposed to lower doses can be infected and shed virus representing a risk for the dissemination of the viral agent.

  17. Quantitative Large-Scale Three-Dimensional Imaging of Human Kidney Biopsies: A Bridge to Precision Medicine in Kidney Disease.

    PubMed

    Winfree, Seth; Dagher, Pierre C; Dunn, Kenneth W; Eadon, Michael T; Ferkowicz, Michael; Barwinska, Daria; Kelly, Katherine J; Sutton, Timothy A; El-Achkar, Tarek M

    2018-06-05

    Kidney biopsy remains the gold standard for uncovering the pathogenesis of acute and chronic kidney diseases. However, the ability to perform high resolution, quantitative, molecular and cellular interrogation of this precious tissue is still at a developing stage compared to other fields such as oncology. Here, we discuss recent advances in performing large-scale, three-dimensional (3D), multi-fluorescence imaging of kidney biopsies and quantitative analysis referred to as 3D tissue cytometry. This approach allows the accurate measurement of specific cell types and their spatial distribution in a thick section spanning the entire length of the biopsy. By uncovering specific disease signatures, including rare occurrences, and linking them to the biology in situ, this approach will enhance our understanding of disease pathogenesis. Furthermore, by providing accurate quantitation of cellular events, 3D cytometry may improve the accuracy of prognosticating the clinical course and response to therapy. Therefore, large-scale 3D imaging and cytometry of kidney biopsy is poised to become a bridge towards personalized medicine for patients with kidney disease. © 2018 S. Karger AG, Basel.

  18. The effect of zinc on healing of renal damage in rats.

    PubMed

    Salehipour, Mehdi; Monabbati, Ahmad; Ensafdaran, Mohammad Reza; Adib, Ali; Babaei, Amir Hossein

    2017-07-01

    Several studies have previously been performed to promote kidney healing after injuries. Objectives: The aim of this study was to investigate the effect of zinc on renal healing after traumatic injury in rats. Forty healthy female rats were selected and one of their kidneys was incised. Half of the incisions were limited only to the cortex (renal injury type I) and the other ones reached the pelvocalyceal system of the kidney (renal injury type II). All the rats in the zinc treated group (case group) received 36.3 mg zinc sulfate (contained 8.25 mg zinc) orally. After 28 days, the damaged kidneys were removed for histopathological studies. In the rats with type I injury, kidney inflammation of the case group was significantly lower than that of the control group. However, the result was not significant in rats with type II injury. Tissue loss and granulation tissue formation were significantly lower in the case group than the control group in both type I and II kidney injuries. Overall, Zinc can contribute to better healing of the rat's kidneys after a traumatic injury.

  19. Micro and bulk analysis of prostate tissues classified as hyperplasia

    NASA Astrophysics Data System (ADS)

    Kwiatek, W. M.; Banaś, A.; Banaś, K.; Cinque, G.; Dyduch, G.; Falkenberg, G.; Kisiel, A.; Marcelli, A.; Podgórczyk, M.

    2007-07-01

    BPH (Benign Prostatic Hyperplasia) is the most common benign neoplasm (non cancerous enlargement of the prostate gland), whose prevalence increases with age. The gland, when increased in size, exerts pressure on the urethra, causing obstruction to urine flow. The latter may result in severe urinary tract and kidney conditions. In this work prostate samples from patients diagnosed with BPH were analyzed using synchrotron radiation. Micro-analysis of the hyperplastic samples was carried out on the L-beam line at HASYLAB, DESY (Germany), while bulk analysis on selected samples was performed at the DRX2 beamline at LNF, Frascati (Italy). Microanalysis with a mono-energetic beam 15 μm in diameter confirmed that concentrations of certain elements, such as S, Mn, Cu, Fe and Zn, are good indicators of pathological disorders in prostate tissue that may be considered effective tracers of developing compliant. The concentrations of Mn, Cu, Fe and Zn are higher in hyperplastic tissues, as compared to normal ones, while for sulphur the opposite is observed. Additionally, Fe and S K-edge XANES (X-ray Absorption Near Edge Structure) spectroscopy experiments were carried out in order to determine the chemical speciation of these elements in our samples.

  20. Determination of flunixin in edible bovine tissues using liquid chromatography coupled with tandem mass spectrometry.

    PubMed

    Boner, Pamela L; Liu, Dave D W; Feely, William F; Robinson, Robert A; Wu, Jinn

    2003-12-17

    An accurate, reliable, and reproducible assay was developed and validated to determine flunixin in bovine liver, kidney, muscle, and fat. The overall recovery and percent coefficient of variation (%CV) of twenty-eight determinations in each tissue for flunixin free acid were 85.9% (5.9% CV) for liver, 94.6% (9.9% CV) for kidney, 87.4% (4.7% CV) for muscle, and 87.6% (4.4% CV) for fat. The theoretical limit of detection was 0.1 microg/kg (ppb, ng/g) for liver and kidney, and 0.2 ppb for muscle and fat. The theoretical limit of quantitation was 0.3, 0.2, 0.6, and 0.4 ppb for liver, kidney, muscle, and fat, respectively. The validated lower limit of quantitation was 1 ppb for edible tissues with the upper limit of 400 ppb for liver and kidney, 100 ppb for fat, and 40 ppb for muscle. Accuracy, precision, linearity, specificity, ruggedness, and storage stability were demonstrated. Briefly, the method involves an initial acid hydrolysis, followed by pH adjustment ( approximately 9.5) and partitioning with ethyl acetate. A portion of the ethyl acetate extract was purified by solid-phase extraction using a strong cation exchange cartridge. The eluate was then evaporated to dryness, reconstituted, and analyzed using LC/MS/MS. The validated method is sensitive and specific for flunixin in edible bovine tissue.

  1. Black grape and garlic extracts protect against cyclosporine a nephrotoxicity.

    PubMed

    Durak, Ilker; Cetin, Recep; Candir, Ozden; Devrim, Erdinç; Kiliçoğlu, Bülent; Avci, Aslihan

    2007-01-01

    The aim of this study was to determine if the natural antioxidant foods, dried black grape and garlic, protect against cyclosporine nephrotoxicity. Forty-two Sprague-Dawley rats were given Cyclosporine A (CsA) orally for 10 days, with the antioxidant food supplementation begun 3 days before CsA treatment and continued during the study period (totaling 13 days). In each group (control, CsA alone, CsA plus black grape, CsA plus aqueous garlic extract, aqueous garlic extract alone and black grape alone), there were 7 animals. At the end of the study period, the animals were sacrificed; their kidneys were removed and prepared for biochemical and histopathological investigations. Oxidant (xanthine oxidase enzyme and malondialdehyde) and antioxidant (superoxide dismutase, glutathione peroxidase and catalase enzymes) parameters were measured in the kidney tissues of the groups. Histopathological examinations of the tissues were also performed. It has been found that CsA creates oxidant load to the kidneys through both xanthine oxidase activation and impaired antioxidant defense system, which accelerates oxidation reactions in the kidney tissue. Supplementation with either dried black grape or aqueous garlic extract led to reduced malondialdehyde level in the kidney tissue possibly, by preventing oxidant reactions. In conclusion, the results suggest that impaired oxidant/antioxidant balance may play part in the CsA-induced nephrotoxicity, and some foods with high antioxidant power may ameliorate this toxicity, in agreement with studies with antioxidant vitamins.

  2. [Distribution of aconitum alkaloids in the corpse died of acute aconite intoxication].

    PubMed

    Liu, Wei; Shen, Min; Qin, Zhi-Qiang

    2009-06-01

    To investigate the distribution of aconite alkaloids in biological fluids and tissues in the corpse died of acute aconite intoxication and to provide information for sample selection and result evaluation in forensic identification. The content of aconite alkaloids in biological fluids and tissues were determined by liquid chromatography-tandem mass spectrometry. The content of aconite displayed in decending order of urine, bile, gastric content, heart blood, pancreas, heart, intestine, liver, kidney, stomach, lung, gallbladder and spleen, with no aconite detected in the brain. It was indicated that urine, bile and blood are the best specimens for the determination of aconite in body of the acute aconite intoxication.

  3. Curcumin and dexmedetomidine prevents oxidative stress and renal injury in hind limb ischemia/reperfusion injury in a rat model.

    PubMed

    Karahan, M A; Yalcin, S; Aydogan, H; Büyükfirat, E; Kücük, A; Kocarslan, S; Yüce, H H; Taskın, A; Aksoy, N

    2016-06-01

    Curcumin and dexmedetomidine have been shown to have protective effects in ischemia-reperfusion injury on various organs. However, their protective effects on kidney tissue against ischemia-reperfusion injury remain unclear. We aimed to determine whether curcumin or dexmedetomidine prevents renal tissue from injury that was induced by hind limb ischemia-reperfusion in rats. Fifty rats were divided into five groups: sham, control, curcumin (CUR) group (200 mg/kg curcumin, n = 10), dexmedetomidine (DEX) group (25 μg/kg dexmedetomidine, n = 10), and curcumin-dexmedetomidine (CUR-DEX) group (200 mg/kg curcumin and 25 μg/kg dexmedetomidine). Curcumin and dexmedetomidine were administered intraperitoneally immediately after the end of 4 h ischemia, just 5 min before reperfusion. The extremity re-perfused for 2 h and then blood samples were taken and total antioxidant capacity (TAC), total oxidative status (TOS) levels, and oxidative stress index (OSI) were measured, and renal tissue samples were histopathologically examined. The TAC activity levels in blood samples were significantly lower in the control than the other groups (p < 0.01 for all comparisons). The TOS activity levels in blood samples were significantly higher in Control group and than the other groups (p <  0.01 for all comparison). The OSI were found to be significantly increased in the control group compared to others groups (p < 0.001 for all comparisons). Histopathological examination revealed less severe lesions in the sham, CUR, DEX, and CUR-DEX groups, compared with the control group (p < 0.01). Rat hind limb ischemia-reperfusion causes histopathological changes in the kidneys. Curcumin and dexmedetomidine administered intraperitoneally was effective in reducing oxidative stress and renal histopathologic injury in an acute hind limb I/R rat model.

  4. Microgravity

    NASA Image and Video Library

    1998-01-01

    Dr. Lisa E. Freed of the Massachusetts Institute of Technology and her colleagues have reported that initially disc-like specimens tend to become spherical in space, demonstrating that tissues can grow and differentiate into distinct structures in microgravity. The Mir Increment 3 (Sept. 16, 1996 - Jan. 22, 1997) samples were smaller, more spherical, and mechanically weaker than Earth-grown control samples. These results demonstrate the feasibility of microgravity tissue engineering and may have implications for long human space voyages and for treating musculoskeletal disorders on earth. The work is sponsored by NASA's Office of Biological and Physical Research. The bioreactor is managed by the Biotechnology Cell Science Program at NASA's Johnson Space Center (JSC). NASA-sponsored bioreactor research has been instrumental in helping scientists to better understand normal and cancerous tissue development. In cooperation with the medical community, the bioreactor design is being used to prepare better models of human colon, prostate, breast and ovarian tumors. Cartilage, bone marrow, heart muscle, skeletal muscle, pancreatic islet cells, liver and kidney are just a few of the normal tissues being cultured in rotating bioreactors by investigators.

  5. Tissue distribution of selenium and effect of season and age on selenium content in roe deer from northwestern Poland.

    PubMed

    Pilarczyk, Bogumiła; Tomza-Marciniak, Agnieszka; Pilarczyk, Renata; Hendzel, Diana; Błaszczyk, Barbara; Bąkowska, Małgorzata

    2011-06-01

    The aim of the study was to compare selenium concentrations in different organs of roe deer from northwestern Poland. Samples of liver, kidneys, heart and lungs, collected from 74 roe deer shot during the hunting seasons of 2008-2009 in northwestern Poland, were studied. Selenium concentration in the organs was determined spectrofluorimetrically. Mean selenium concentration was 0.06 µg/g w.w. in the liver, 0.41 µg/g w.w. in the kidneys and 0.05 µg/g w.w. in the heart and lungs. Season had a significant effect on selenium concentration in the liver, kidneys, lungs and heart. In all the organs, the highest selenium concentration was found in spring and the lowest in autumn and winter. All animals studied were deficient in selenium. The low selenium concentration in the liver or heart can disturb their function, and in the future, it may be a factor contributing to the population decline of roe deer in the northwestern part of Poland.

  6. Thyroid hormones and deiodinase activity in plasma and tissues in relation to high levels of organohalogen contaminants in East Greenland polar bears (Ursus maritimus).

    PubMed

    Gabrielsen, Kristin Møller; Krokstad, Julie Stene; Villanger, Gro Dehli; Blair, David A D; Obregon, Maria-Jesus; Sonne, Christian; Dietz, Rune; Letcher, Robert J; Jenssen, Bjørn Munro

    2015-01-01

    Previous studies have shown relationships between organohalogen contaminants (OHCs) and circulating levels of thyroid hormones (THs) in arctic wildlife. However, there is a lack of knowledge concerning the possible functional effects of OHCs on TH status in target tissues for TH-dependent activity. The relationships between circulating (plasma) levels of OHCs and various TH variables in plasma as well as in liver, muscle and kidney tissues from East Greenland sub-adult polar bears (Ursus maritimus) sampled in 2011 (n=7) were therefore investigated. The TH variables included 3.3',5.5'-tetraiodothyronine or thyroxine (T4), 3.3',5-triiodothyronine (T3) and type 1 (D1) and type 2 (D2) deiodinase activities. Principal component analysis (PCA) combined with correlation analyses demonstrated negative relationships between individual polychlorinated biphenyls (PCBs) and their hydroxylated (OH-) metabolites and T4 in both plasma and muscle. There were both positive and negative relationships between individual OHCs and D1 and D2 activities in muscle, liver and kidney tissues. In general, PCBs, OH-PCBs and polybrominated dipehenyl ethers (PBDEs) were positively correlated to D1 and D2 activities, whereas organochlorine pesticides and byproducts (OCPs) were negatively associated with D1 and D2 activities. These results support the hypothesis that OHCs can affect TH status and action in the target tissues of polar bears. TH levels and deiodinase activities in target tissues can be sensitive endpoints for exposure of TH-disrupting compounds in arctic wildlife, and thus, tissue-specific responses in target organs should be further considered when assessing TH disruption in wildlife studies. Copyright © 2014 Elsevier Inc. All rights reserved.

  7. Tissue residue depletion of moxidectin in lambs (Ovis aries) following subcutaneous administration.

    PubMed

    Cruz, Michelle Del Bianchi A; Fernandes, Maria Ângela M; Monteiro, Alda Lúcia G; Teles, Juliana A; Anadón, Arturo; Reyes, Felix G R

    2018-06-07

    To date, a tissue depletion study of moxidectin (MOX) in lambs is not available. Thus, considering that lamb meat is of great commercial interest in the world, the aim of the present study was to determine the residue levels of MOX in lamb target-tissues (muscle, liver, kidney and fat) and subsequently calculate the MOX withdrawal period. For this purpose, the target-tissues were analysed by ultra-high-performance liquid chromatography-tandem mass spectrometry. Method validation was performed based on Commission Decision 2002/657/EC and VICH GL49. To quantify the analyte, matrix-matched analytical curves were constructed with spiked blank tissues. The limits of detection and quantitation were 1.5 and 5 ng g -1 , respectively, for all matrices. The linearity, decision limit, detection capability accuracy and inter- and intra-day precision of the method are reported. The lambs were treated with a single subcutaneous dose of 0.2 mg MOX kg -1 body weight and were slaughtered in accordance with accepted animal care protocols. Samples of target-tissues were collected on 2, 4, 7, 14, 28 and 42 days after MOX administration. During the whole study, the highest drug residue level occurred in the fat. For the other target-tissues (muscle, liver and kidney), MOX concentrations were below the maximum residue limit (MRL). Considering the MRL value of 500 µg kg -1 for MOX residues in sheep fat, our results in lambs allowed the estimation of a MOX withdrawal period of 31 days. This indicates that the withdrawal period established for MOX in adult sheep (28 days) does not apply for lambs.

  8. Predictive assessment of kidney functional recovery following ischemic injury using optical spectroscopy

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

    Raman, Rajesh N.; Pivetti, Christopher D.; Ramsamooj, Rajendra

    Functional changes in rat kidneys during the induced ischemic injury and recovery phases were explored using multimodal autofluorescence and light scattering imaging. We aim to evaluate the use of noncontact optical signatures for rapid assessment of tissue function and viability. Specifically, autofluorescence images were acquired in vivo under 355, 325, and 266 nm illumination while light scattering images were collected at the excitation wavelengths as well as using relatively narrowband light centered at 500 nm. The images were simultaneously recorded using a multimodal optical imaging system. We also analyzed to obtain time constants, which were correlated to kidney dysfunction asmore » determined by a subsequent survival study and histopathological analysis. This analysis of both the light scattering and autofluorescence images suggests that changes in tissue microstructure, fluorophore emission, and blood absorption spectral characteristics, coupled with vascular response, contribute to the behavior of the observed signal, which may be used to obtain tissue functional information and offer the ability to predict posttransplant kidney function.« less

  9. Residue depletion of tilmicosin in chicken tissues.

    PubMed

    Zhang, Yue; Jiang, Haiyang; Jin, Xingjun; Shen, Zhangqi; Shen, Jianzhong; Fu, Caixia; Guo, Junlin

    2004-05-05

    A high-performance liquid chromatography (HPLC) method with detection at 290 nm was modified and validated for the determination of tilmicosin residues in broiler chicken tissues. The limits of detection (LOD) of the method were 0.01 microg/g for muscle and 0.025 microg/g for liver and kidney. Average recoveries ranged from 80.4 to 88.3%. Relative standard deviation values ranged from 5.2 to 12.1%. Residue depletion of tilmicosin in broiler chickens was examined after dosing over a 5-day period by incorporation of the drug into drinking water at 37.5 and 75.0 mg/L. Tilmicosin concentrations in liver and kidney were highest on day 3 of medication and on day 5 in muscle, in both low- and high-dose groups. The residue levels in both groups were significantly higher in liver than in kidney or muscle. A minimum withdrawal time of 9 days was indicated for residue levels in muscle, liver, and kidney tissues below the maximum residue level (MRL).

  10. Predictive assessment of kidney functional recovery following ischemic injury using optical spectroscopy

    DOE PAGES

    Raman, Rajesh N.; Pivetti, Christopher D.; Ramsamooj, Rajendra; ...

    2017-05-03

    Functional changes in rat kidneys during the induced ischemic injury and recovery phases were explored using multimodal autofluorescence and light scattering imaging. We aim to evaluate the use of noncontact optical signatures for rapid assessment of tissue function and viability. Specifically, autofluorescence images were acquired in vivo under 355, 325, and 266 nm illumination while light scattering images were collected at the excitation wavelengths as well as using relatively narrowband light centered at 500 nm. The images were simultaneously recorded using a multimodal optical imaging system. We also analyzed to obtain time constants, which were correlated to kidney dysfunction asmore » determined by a subsequent survival study and histopathological analysis. This analysis of both the light scattering and autofluorescence images suggests that changes in tissue microstructure, fluorophore emission, and blood absorption spectral characteristics, coupled with vascular response, contribute to the behavior of the observed signal, which may be used to obtain tissue functional information and offer the ability to predict posttransplant kidney function.« less

  11. Classification of kidney and liver tissue using ultrasound backscatter data

    NASA Astrophysics Data System (ADS)

    Aalamifar, Fereshteh; Rivaz, Hassan; Cerrolaza, Juan J.; Jago, James; Safdar, Nabile; Boctor, Emad M.; Linguraru, Marius G.

    2015-03-01

    Ultrasound (US) tissue characterization provides valuable information for the initialization of automatic segmentation algorithms, and can further provide complementary information for diagnosis of pathologies. US tissue characterization is challenging due to the presence of various types of image artifacts and dependence on the sonographer's skills. One way of overcoming this challenge is by characterizing images based on the distribution of the backscatter data derived from the interaction between US waves and tissue. The goal of this work is to classify liver versus kidney tissue in 3D volumetric US data using the distribution of backscatter US data recovered from end-user displayed Bmode image available in clinical systems. To this end, we first propose the computation of a large set of features based on the homodyned-K distribution of the speckle as well as the correlation coefficients between small patches in 3D images. We then utilize the random forests framework to select the most important features for classification. Experiments on in-vivo 3D US data from nine pediatric patients with hydronephrosis showed an average accuracy of 94% for the classification of liver and kidney tissues showing a good potential of this work to assist in the classification and segmentation of abdominal soft tissue.

  12. Effects of Platelet-Rich Plasma (PRP) on a Model of Renal Ischemia-Reperfusion in Rats

    PubMed Central

    Martín-Solé, Oriol; Rodó, Joan; García-Aparicio, Lluís; Blanch, Josep; Cusí, Victoria; Albert, Asteria

    2016-01-01

    Renal ischemia-reperfusion injury is a major cause of acute renal failure, causing renal cell death, a permanent decrease of renal blood flow, organ dysfunction and chronic kidney disease. Platelet-rich plasma (PRP) is an autologous product rich in growth factors, and therefore able to promote tissue regeneration and angiogenesis. This product has proven its efficacy in multiple studies, but has not yet been tested on kidney tissue. The aim of this work is to evaluate whether the application of PRP to rat kidneys undergoing ischemia-reperfusion reduces mid-term kidney damage. A total of 30 monorrenal Sprague-Dawley male rats underwent renal ischemia-reperfusion for 45 minutes. During ischemia, PRP (PRP Group, n = 15) or saline solution (SALINE Group, n = 15) was administered by subcapsular renal injection. Control kidneys were the contralateral organs removed immediately before the start of ischemia in the remaining kidneys. Survival, body weight, renal blood flow on Doppler ultrasound, kidney weight, kidney volume, blood biochemistry and histopathology were determined for all subjects and kidneys, as applicable. Correlations between these variables were searched for. The PRP Group showed significantly worse kidney blood flow (p = 0.045) and more histopathological damage (p<0.0001). Correlations were found between body weight, kidney volume, kidney weight, renal blood flow, histology, and serum levels of creatinine and urea. Our study provides the first evidence that treatment with PRP results in the deterioration of the kidney’s response to ischemia-reperfusion injury. PMID:27551718

  13. Murine lethal milk mutation causes maternal accumulation of zinc in intestine and kidney and reduced zinc transport to milk

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

    Dohyeel Lee; Cousins, R.J.

    1991-03-15

    The lethal milk (Lm) mutation is autosomal recessive in C57BL/6J mice and causes Zn deficiency in pups nursed by Lm dams. The genetic defect may cause a shift in the tissue Zn distribution in Lm dams since their milk has a 34-45% lower Zn concentration than milk of normal (N) dams. To examine tissue Zn distribution and Zn transport to milk and pups, 1 {mu}Ci of {sup 65}Zn was administered ip to lactating N and Lm dams. They also received 800 {mu}g Zn/ml in their drinking water to preclude short term, terminal zinc deficiency in the neonates nursed by Lmmore » dams. {sup 65}Zn content of milk and tissues of dams and tissues of pups was measured. Transport of {sup 65}Zn to milk of Lm dams was about 50% compared to milk of N dams. The percentage of the {sup 65}Zn dose recovered in the intestine, liver, and kidney of N pups nursed by LM dams was markedly lower than those of N pups nursed by N dams. In contrast, the percentage of {sup 65}Zn in the intestine and kidney of Lm dams was about twice that of N dams. The elevated intestinal {sup 65}Zn was paralleled by and elevated metallothionein concentration, but the increased {sup 65}Zn in the kidney was not. The Lm gene defect might limit Zn transport to milk by shifting the Zn distribution in lactating dams to the intestine, kidney, and perhaps other tissues.« less

  14. High-resolution imaging of selenium in kidneys: a localized selenium pool associated with glutathione peroxidase 3

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

    Malinouski, M.; Kehr, S.; Finney, L.

    2012-04-17

    Recent advances in quantitative methods and sensitive imaging techniques of trace elements provide opportunities to uncover and explain their biological roles. In particular, the distribution of selenium in tissues and cells under both physiological and pathological conditions remains unknown. In this work, we applied high-resolution synchrotron X-ray fluorescence microscopy (XFM) to map selenium distribution in mouse liver and kidney. Liver showed a uniform selenium distribution that was dependent on selenocysteine tRNA{sup [Ser]Sec} and dietary selenium. In contrast, kidney selenium had both uniformly distributed and highly localized components, the latter visualized as thin circular structures surrounding proximal tubules. Other parts ofmore » the kidney, such as glomeruli and distal tubules, only manifested the uniformly distributed selenium pattern that co-localized with sulfur. We found that proximal tubule selenium localized to the basement membrane. It was preserved in Selenoprotein P knockout mice, but was completely eliminated in glutathione peroxidase 3 (GPx3) knockout mice, indicating that this selenium represented GPx3. We further imaged kidneys of another model organism, the naked mole rat, which showed a diminished uniformly distributed selenium pool, but preserved the circular proximal tubule signal. We applied XFM to image selenium in mammalian tissues and identified a highly localized pool of this trace element at the basement membrane of kidneys that was associated with GPx3. XFM allowed us to define and explain the tissue topography of selenium in mammalian kidneys at submicron resolution.« less

  15. L-Arginine metabolism in cardiovascular and renal tissue from hyper- and hypothyroid rats.

    PubMed

    Rodríguez-Gómez, Isabel; Moliz, Juan N; Quesada, Andrés; Montoro-Molina, Sebastian; Vargas-Tendero, Pablo; Osuna, Antonio; Wangensteen, Rosemary; Vargas, Félix

    2016-03-01

    This study assessed the effects of thyroid hormones on the enzymes involved in l-arginine metabolism and the metabolites generated by the different metabolic pathways. Compounds of l-arginine metabolism were measured in the kidney, heart, aorta, and liver of euthyroid, hyperthyroid, and hypothyroid rats after 6 weeks of treatment. Enzymes studied were NOS isoforms (neuronal [nNOS], inducible [iNOS], and endothelial [eNOS]), arginases I and II, ornithine decarboxylase (ODC), ornithine aminotransferase (OAT), and l-arginine decarboxylase (ADC). Metabolites studied were l-arginine, l-citrulline, spermidine, spermine, and l-proline. Kidney heart and aorta levels of eNOS and iNOS were augmented and reduced (P < 0.05, for each tissue and enzyme) in hyper- and hypothyroid rats, respectively. Arginase I abundance in aorta, heart, and kidney was increased (P < 0.05, for each tissue) in hyperthyroid rats and was decreased in kidney and aorta of hypothyroid rats (P < 0.05, for each tissue). Arginase II was augmented in aorta and kidney (P < 0.05, for each tissue) of hyperthyroid rats and remained unchanged in all organs of hypothyroid rats. The substrate for these enzymes, l-arginine, was reduced (P < 0.05, for all tissues) in hyperthyroid rats. Levels of ODC and spermidine, its product, were increased and decreased (P < 0.05) in hyper- and hypothyroid rats, respectively, in all organs studied. OAT and proline levels were positively modulated by thyroid hormones in liver but not in the other tissues. ADC protein levels were positively modulated by thyroid hormones in all tissues. According to these findings, thyroid hormone treatment positively modulates different l-arginine metabolic pathways. The changes recorded in the abundance of eNOS, arginases I and II, and ADC protein in renal and cardiovascular tissues may play a role in the hemodynamic and renal manifestations observed in thyroid disorders. Furthermore, the changes in ODC and spermidine might contribute to the changes in cardiac and renal mass observed in thyroid disorders. © 2015 by the Society for Experimental Biology and Medicine.

  16. l-Arginine metabolism in cardiovascular and renal tissue from hyper- and hypothyroid rats

    PubMed Central

    Moliz, Juan N; Quesada, Andrés; Montoro-Molina, Sebastian; Vargas-Tendero, Pablo; Osuna, Antonio; Wangensteen, Rosemary; Vargas, Félix

    2015-01-01

    This study assessed the effects of thyroid hormones on the enzymes involved in l-arginine metabolism and the metabolites generated by the different metabolic pathways. Compounds of l-arginine metabolism were measured in the kidney, heart, aorta, and liver of euthyroid, hyperthyroid, and hypothyroid rats after 6 weeks of treatment. Enzymes studied were NOS isoforms (neuronal [nNOS], inducible [iNOS], and endothelial [eNOS]), arginases I and II, ornithine decarboxylase (ODC), ornithine aminotransferase (OAT), and l-arginine decarboxylase (ADC). Metabolites studied were l-arginine, l-citrulline, spermidine, spermine, and l-proline. Kidney heart and aorta levels of eNOS and iNOS were augmented and reduced (P < 0.05, for each tissue and enzyme) in hyper- and hypothyroid rats, respectively. Arginase I abundance in aorta, heart, and kidney was increased (P < 0.05, for each tissue) in hyperthyroid rats and was decreased in kidney and aorta of hypothyroid rats (P < 0.05, for each tissue). Arginase II was augmented in aorta and kidney (P < 0.05, for each tissue) of hyperthyroid rats and remained unchanged in all organs of hypothyroid rats. The substrate for these enzymes, l-arginine, was reduced (P < 0.05, for all tissues) in hyperthyroid rats. Levels of ODC and spermidine, its product, were increased and decreased (P < 0.05) in hyper- and hypothyroid rats, respectively, in all organs studied. OAT and proline levels were positively modulated by thyroid hormones in liver but not in the other tissues. ADC protein levels were positively modulated by thyroid hormones in all tissues. According to these findings, thyroid hormone treatment positively modulates different l-arginine metabolic pathways. The changes recorded in the abundance of eNOS, arginases I and II, and ADC protein in renal and cardiovascular tissues may play a role in the hemodynamic and renal manifestations observed in thyroid disorders. Furthermore, the changes in ODC and spermidine might contribute to the changes in cardiac and renal mass observed in thyroid disorders. PMID:26674221

  17. Automated quantification of renal interstitial fibrosis for computer-aided diagnosis: A comprehensive tissue structure segmentation method.

    PubMed

    Tey, Wei Keat; Kuang, Ye Chow; Ooi, Melanie Po-Leen; Khoo, Joon Joon

    2018-03-01

    Interstitial fibrosis in renal biopsy samples is a scarring tissue structure that may be visually quantified by pathologists as an indicator to the presence and extent of chronic kidney disease. The standard method of quantification by visual evaluation presents reproducibility issues in the diagnoses. This study proposes an automated quantification system for measuring the amount of interstitial fibrosis in renal biopsy images as a consistent basis of comparison among pathologists. The system extracts and segments the renal tissue structures based on colour information and structural assumptions of the tissue structures. The regions in the biopsy representing the interstitial fibrosis are deduced through the elimination of non-interstitial fibrosis structures from the biopsy area and quantified as a percentage of the total area of the biopsy sample. A ground truth image dataset has been manually prepared by consulting an experienced pathologist for the validation of the segmentation algorithms. The results from experiments involving experienced pathologists have demonstrated a good correlation in quantification result between the automated system and the pathologists' visual evaluation. Experiments investigating the variability in pathologists also proved the automated quantification error rate to be on par with the average intra-observer variability in pathologists' quantification. Interstitial fibrosis in renal biopsy samples is a scarring tissue structure that may be visually quantified by pathologists as an indicator to the presence and extent of chronic kidney disease. The standard method of quantification by visual evaluation presents reproducibility issues in the diagnoses due to the uncertainties in human judgement. An automated quantification system for accurately measuring the amount of interstitial fibrosis in renal biopsy images is presented as a consistent basis of comparison among pathologists. The system identifies the renal tissue structures through knowledge-based rules employing colour space transformations and structural features extraction from the images. In particular, the renal glomerulus identification is based on a multiscale textural feature analysis and a support vector machine. The regions in the biopsy representing interstitial fibrosis are deduced through the elimination of non-interstitial fibrosis structures from the biopsy area. The experiments conducted evaluate the system in terms of quantification accuracy, intra- and inter-observer variability in visual quantification by pathologists, and the effect introduced by the automated quantification system on the pathologists' diagnosis. A 40-image ground truth dataset has been manually prepared by consulting an experienced pathologist for the validation of the segmentation algorithms. The results from experiments involving experienced pathologists have demonstrated an average error of 9 percentage points in quantification result between the automated system and the pathologists' visual evaluation. Experiments investigating the variability in pathologists involving samples from 70 kidney patients also proved the automated quantification error rate to be on par with the average intra-observer variability in pathologists' quantification. The accuracy of the proposed quantification system has been validated with the ground truth dataset and compared against the pathologists' quantification results. It has been shown that the correlation between different pathologists' estimation of interstitial fibrosis area has significantly improved, demonstrating the effectiveness of the quantification system as a diagnostic aide. Copyright © 2017 Elsevier B.V. All rights reserved.

  18. Direct fluorescent antibody technique for the detection of bacterial kidney disease in paraffin-embedded tissues

    USGS Publications Warehouse

    Ochiai, T.; Yasutake, W.T.; Gould, R.W.

    1985-01-01

    The direct fluorescent antibody technique (FAT) was successfully used to detect the causative agent of bacterial kidney disease (BKD), Renibacterium salmoninarum, in Bouin's solution flexed and paraffinembedded egg and tissue sections. This method is superior to gram stain and may be particularly useful in detecting the BKD organism in fish with low-grade infection.

  19. Evaluation of penicillin G residues by kidney inhibition swab tests in sow body fluids and tissues following intramuscular injection

    USDA-ARS?s Scientific Manuscript database

    In 2011, the USDA-Food Safety and Inspection Service (FSIS) changed the method used for screening swine tissues for antimicrobial residues from the Fast Antimicrobial Screen Test to the Kidney Inhibition Swab (KIS(TM)). Here, we describe the use of KIS(TM) test for the detection of penicillin G res...

  20. Evaluation of penicillin G residues by kidney inhibition swab tests in sow body fluids and tissues following intramuscular injection

    USDA-ARS?s Scientific Manuscript database

    In 2011, the USDA-Food Safety and Inspection Service (FSIS) changed the method used for screening swine tissues for antimicrobial residues to the Kidney Inhibition Swab (KIS(TM)) from the Fast Antimicrobial Screen Test. A high dose of penicillin G procaine relative to a label dose is commonly used ...

  1. Detection of cytomegalovirus (CMV) antigens in kidney biopsies and transplant nephrectomies as a marker for renal graft dysfunction.

    PubMed

    Gerstenkorn, C; Robertson, H; Mohamed, M A; O'Donnell, M; Ali, S; Talbot, D

    2000-11-01

    Chronic rejection accounts for the greatest loss of renal allografts. HLA mismatching has been minimised by organ allocation and new immunosuppressive drugs have been employed, but the average cadaveric graft survival still does not exceed 12 years. Though the aetiology is multifactorial, one contributory factor for this condition is cytomegalovirus (CMV). Detection of CMV in kidney biopsies and sera can diagnose and monitor this inflammatory event and define its role in chronic nephropathy. Twenty five biopsies taken at the time of transplantation, 10 biopsies for graft dysfunction and tissue blocks from 20 explanted kidney grafts were collected and investigated for CMV antigens by immunohistochemistry. Tissue samples were snap frozen and cryostat sections were incubated with monoclonal antibodies for CMV antigens followed by immunoperoxidase staining. In 12 out of 20 transplant nephrectomies CMV antigens were found. Only two of these patients had clinical CMV disease. Time 0 biopsies from CMV seronegative donors (n = 11) and CMV seropositive donors (n = 14) were negative for CMV antigens. The prevalence of CMV antigens in grafts lost due to chronic rejection was 60%. These antigens were not found within the time 0 biopsies, but were detected in 30% of biopsies taken at the time of clinical graft dysfunction. CMV appears to contribute to chronic rejection even without clinical disease.

  2. Lung Matrix Metalloproteinase Activation following Partial Hepatic Ischemia/Reperfusion Injury in Rats

    PubMed Central

    Ferrigno, Andrea; Rizzo, Vittoria; Tarantola, Eleonora

    2014-01-01

    Purpose. Warm hepatic ischemia-reperfusion (I/R) injury can lead to multiorgan dysfunction. The aim of the present study was to investigate whether acute liver I/R does affect the function and/or structure of remote organs such as lung, kidney, and heart via modulation of extracellular matrix remodelling. Methods. Male Sprague-Dawley rats were subjected to 30 min partial hepatic ischemia by clamping the hepatic artery and the portal vein. After a 60 min reperfusion, liver, lung, kidney, and heart biopsies and blood samples were collected. Serum hepatic enzymes, creatinine, urea, Troponin I and TNF-alpha, and tissue matrix metalloproteinases (MMP-2, MMP-9), myeloperoxidase (MPO), malondialdehyde (MDA), and morphology were monitored. Results. Serum levels of hepatic enzymes and TNF-alpha were concomitantly increased during hepatic I/R. An increase in hepatic MMP-2 and MMP-9 activities was substantiated by tissue morphology alterations. Notably, acute hepatic I/R affect the lung inasmuch as MMP-9 activity and MPO levels were increased. No difference in MMPs and MPO was observed in kidney and heart. Conclusions. Although the underlying mechanism needs further investigation, this is the first study in which the MMP activation in a distant organ is reported; this event is probably TNF-alpha-mediated and the lung appears as the first remote organ to be involved in hepatic I/R injury. PMID:24592193

  3. Bioaccumulation of Cd, Pb and Zn in the edible and inedible tissues of three sturgeon species in the Iranian coastline of the Caspian Sea.

    PubMed

    Mashroofeh, Abdulreza; Bakhtiari, Alireza Riyahi; Pourkazemi, Mohammad; Rasouli, Sana

    2013-01-01

    The accumulations of Cd, Pb and Zn were determined in edible and inedible tissues of Persian sturgeon (Acipenser persicus; n=27), stellate sturgeon (Acipenser stellatus; n=5) and beluga (Huso huso; n=4) collected from coastal waters of the South Caspian Sea from March to April 2011. Concentrations of metals evaluated in the caviar, muscle, liver, kidney, gills, ovary and heart of the three species of sturgeons have been assessed using the flame and graphite furnace atomic absorption spectrophotometer. Concentrations of Zn, Pb and Cd in the edible and inedible tissues were apparently different among the three species of sturgeons. Especially, beluga heart showed the highest concentrations of Zn and Pb and Cd in Persian sturgeon liver. The analyzed metals were found in the caviar and muscle samples of Persian sturgeon and likewise muscle samples two other sturgeon species at mean concentrations under the permissible limits proposed by MAFF (2000). Copyright © 2012 Elsevier Ltd. All rights reserved.

  4. Validation of endogenous internal real-time PCR controls in renal tissues.

    PubMed

    Cui, Xiangqin; Zhou, Juling; Qiu, Jing; Johnson, Martin R; Mrug, Michal

    2009-01-01

    Endogenous internal controls ('reference' or 'housekeeping' genes) are widely used in real-time PCR (RT-PCR) analyses. Their use relies on the premise of consistently stable expression across studied experimental conditions. Unfortunately, none of these controls fulfills this premise across a wide range of experimental conditions; consequently, none of them can be recommended for universal use. To determine which endogenous RT-PCR controls are suitable for analyses of renal tissues altered by kidney disease, we studied the expression of 16 commonly used 'reference genes' in 7 mildly and 7 severely affected whole kidney tissues from a well-characterized cystic kidney disease model. Expression levels of these 16 genes, determined by TaqMan RT-PCR analyses and Affymetrix GeneChip arrays, were normalized and tested for overall variance and equivalence of the means. Both statistical approaches and both TaqMan- and GeneChip-based methods converged on 3 out of the 4 top-ranked genes (Ppia, Gapdh and Pgk1) that had the most constant expression levels across the studied phenotypes. A combination of the top-ranked genes will provide a suitable endogenous internal control for similar studies of kidney tissues across a wide range of disease severity. Copyright 2009 S. Karger AG, Basel.

  5. Protective effects of Tribulus terrestris L extract against acute kidney injury induced by reperfusion injury in rats.

    PubMed

    Najafi, Houshang; Firouzifar, Mohammad Reza; Shafaat, Omid; Changizi Ashtiyani, Saeed; Hosseini, Nasser

    2014-07-01

    This study aimed to investigate the protective effect of aerial parts of the Tribulus terrestris L extract on acute kidney injury (AKI) induced by ischemia for 30 minutes and reperfusion for 24 hours in rats. Ten male Sprague-Dawley rats in the AKI and 10 in the Tribulus terrestris groups received the extract solvent and extract of the plant (11 mg/kg), respectively, for 13 days (oral administration). On day 14, ischemia for 30 minutes and reperfusion for 24 hours were induced on the rats. In the last 6 hours of the reperfusion period (24 hours), urine samples were collected in metabolic cages. At the end of this period, blood samples were also taken to determine plasma urea nitrogen, creatinine, and electrolyte concentrations. The kidney tissues were collected for measuring the level of oxidative stress and histological studies. They were compared with the sham operation group and a control group with normal diet and no operation. In the Tribulus terrestris group, the increase in plasma creatinine and urea nitrogen concentrations was significantly less following reperfusion, and their values reached the same level as that in the sham group. Creatinine clearance and urine osmolarity in the Tribulus terrestris group was higher in comparison with the AKI group, whereas sodium absolute excretion, fractional excretion of potassium, oxidative stress, and cellular damages were less. Oral administration of Tribulus terrestris extract for 2 weeks can decrease kidney functional disturbance, oxidative stress, and cellular damages following reperfusion injury in rats.

  6. Logic programming to infer complex RNA expression patterns from RNA-seq data.

    PubMed

    Weirick, Tyler; Militello, Giuseppe; Ponomareva, Yuliya; John, David; Döring, Claudia; Dimmeler, Stefanie; Uchida, Shizuka

    2018-03-01

    To meet the increasing demand in the field, numerous long noncoding RNA (lncRNA) databases are available. Given many lncRNAs are specifically expressed in certain cell types and/or time-dependent manners, most lncRNA databases fall short of providing such profiles. We developed a strategy using logic programming to handle the complex organization of organs, their tissues and cell types as well as gender and developmental time points. To showcase this strategy, we introduce 'RenalDB' (http://renaldb.uni-frankfurt.de), a database providing expression profiles of RNAs in major organs focusing on kidney tissues and cells. RenalDB uses logic programming to describe complex anatomy, sample metadata and logical relationships defining expression, enrichment or specificity. We validated the content of RenalDB with biological experiments and functionally characterized two long intergenic noncoding RNAs: LOC440173 is important for cell growth or cell survival, whereas PAXIP1-AS1 is a regulator of cell death. We anticipate RenalDB will be used as a first step toward functional studies of lncRNAs in the kidney.

  7. Fish consumption and risk of contamination by mercury---considerations on the definition of edible parts based on the case study of European sea bass.

    PubMed

    Mieiro, C L; Pacheco, M; Duarte, A C; Pereira, M E

    2011-12-01

    In the present study, the risk to humans by consuming European sea bass (Dicentrarchus labrax), captured at three sites along a Hg contamination gradient, was evaluated by comparing muscle and kidney total Hg (T-Hg) levels with the European regulations for marketed fish. Moreover, T-Hg and organic Hg (O-Hg) levels in muscle were compared with the Provisional Tolerable Weekly Intake (PTWI) and the Reference Dose (RfD). Although T-Hg levels in muscle were below the European value allowable for marketed fish, kidney's levels were higher than the set value, stressing the importance of redefining the concept of edible tissue and which tissues should be considered. Mercury weekly ingestion in the contaminated areas was higher than the PTWI, and O-Hg daily ingestion rates were higher than the RfD in all sampling sites. Thus, populations consuming sea bass from the contaminated sites may be at risk, with particular relevance for children and pregnant women. Copyright © 2011 Elsevier Ltd. All rights reserved.

  8. Detection and quantification of Renibacterium salmoninarum DNA in salmonid tissues by real-time quantitative polymerase chain reaction analysis

    USGS Publications Warehouse

    Chase, D.M.; Elliott, D.G.; Pascho, R.J.

    2006-01-01

    Renibacterium salmoninarum is an important salmonid pathogen that is difficult to culture. We developed and assessed a real-time, quantitative, polymerase chain reaction (qPCR) assay for the detection and enumeration of R. salmoninarum. The qPCR is based on TaqMan technology and amplifies a 69-base pair (bp) region of the gene encoding the major soluble antigen (MSA) of R. salmoninarum. The qPCR assay consistently detected as few as 5 R. salmoninarum cells per reaction in kidney tissue. The specificity of the qPCR was confirmed by testing the DNA extracts from a panel of microorganisms that were either common fish pathogens or reported to cause false-positive reactions in the enzyme-linked immunosorbent assay (ELISA). Kidney samples from 38 juvenile Chinook salmon (Oncorhynchus tshawytscha) in a naturally infected population were examined by real-time qPCR, a nested PCR, and ELISA, and prevalences of R. salmoninarum detected were 71, 66, and 71%, respectively. The qPCR should be a valuable tool for evaluating the R. salmoninarum infection status of salmonids.

  9. Residue depletion of tilmicosin in cattle after subcutaneous administration.

    PubMed

    Jiang, Haiyang; Ding, Shuangyang; Li, Jiancheng; An, Dianjin; Li, Cun; Shen, Jianzhong

    2006-07-12

    A study of tissue residue depletion of tilmicosin in cattle was conducted after a single subcutaneous injection at the therapeutic level of 10 mg per kg body weight. Eighteen cross cattle were treated with the tilmicosin oil formulation (30%). Three treated animals (two males and one female) were selected randomly to be scarified at 1, 7, 14, 28, and 35 days withdrawal after injection. Samples of the injection site and of muscle, liver, kidney, and fat were collected. Tilmicosin residue concentrations were determined using a high-performance liquid chromatography (HPLC) method with a UV detector at 290 nm. Using a statistical method recommended by the Committee for Veterinary Medical Products of European Medical Evaluation Agency, the withdrawal time of 34 days was established when all tissue residues except samples in the injection site were below the accepted maximum residue limits.

  10. Association between Randall's Plaque and Calcifying Nanoparticles

    NASA Technical Reports Server (NTRS)

    Ciftcioglu, Neva; Vejdani, Kaveh; Lee, Olivia; Mathew, Grace; Aho, Katja M.; Kajander, Olavi; McKay, David S.; Jones, Jeff A.; Hayat, Matthew; Stoller, Marshall L.

    2007-01-01

    Randall's plaques, first described by Alexander Randall in the 1930s, are small subepithelial calcifications in the renal papillae (RP) that also extend deeply into the renal medulla. Despite the strong correlation between the presence of these plaques and the formation of renal stones, the precise origin and pathogenesis of Randall s plaque formation remain elusive. The discovery of calcifying nanoparticles (CNP) and their detection in many calcifying processes of human tissues has raised hypotheses about their possible involvement in renal stone formation. We collected RP and blood samples from 17 human patients who had undergone laparoscopic nephrectomy due to neoplasia. Homogenized RP tissues and serum samples were cultured for CNP. Scanning electron microscopy (SEM) and energy dispersive X-ray spectroscopy (EDS) analysis were performed on fixed RP samples. Immunohistochemical staining (IHS) was applied on the tissue samples using CNP-specific monoclonal antibody (mAb). Randall s plaques were visible on gross inspection in 11 out of 17 collected samples. Cultures of all serum samples and 13 tissue homogenates had CNP growth within 4 weeks. SEM revealed spherical apatite formations in 14 samples, with calcium and phosphate peaks detected by EDS analysis. IHS was positive in 9 out of 17 samples. A strong link was found between the presence of Randall s plaques and the detection of CNP, also referred to as nanobacteria. These results suggest new insights into the etiology of Randall's plaque formation, and will help us understand the pathogenesis of stone formation. Further studies on this topic may lead us to new approaches on early diagnosis and novel medical therapies of kidney stone formation.

  11. Relationship of antioxidant and oxidative stress markers in different organs following copper toxicity in a rat model

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

    Kumar, Vijay; Kalita, Jayantee, E-mail: jayanteek@yahoo.com; Bora, Himangsu K.

    Copper (Cu) at a higher level becomes toxic and it can catalyze the formation of highly reactive hydroxyl radical. We report the vulnerability of liver, kidney and brain to different dose of copper sulfate (CuSO{sub 4}) induced oxidative stress at different time duration. Fifty-four male Wistar rats (weight range = 205 ± 10 g) were equally divided into three groups. CuSO{sub 4} was administered orally to the experimental groups (Group-II and III) up to 90 days in a dose of 100 and 200 mg/Kg body weight per day. Saline water was given to the control group (Group-I). At the endmore » of 30, 60 and 90 days of administration, neurobehavioral studies were done and six rats from each group were sacrificed. Their liver, kidney and brain tissues were subjected for Cu, glutathione (GSH), malondialdehyde (MDA) and total antioxidant capacity (TAC) assay. Blood urea nitrogen (BUN), serum creatinine, bilirubin and transaminases were measured. GSH, TAC and MDA levels were correlated with the markers of respective organ dysfunction. Administration of CuSO{sub 4} resulted in increased free Cu and MDA level, and decrease GSH and TAC levels in group-II and III compared with group-I. In experimental groups, the reduction in TAC and GSH levels was maximum in liver tissue followed by brain and kidney; whereas increase in MDA level was highest in liver followed by brain and kidney at 30, 60 and 90 days. TAC and GSH levels in the liver inversely correlated with serum transaminases and bilirubin, and tissue free Cu, and positively correlated with MDA levels. Free Cu level in kidney tissue and BUN inversely correlated with TAC and GSH, and positively with MDA level. Grip-strength, rotarod and Y-maze findings were inversely correlated with brain free Cu and MDA levels and positively with GSH and TAC levels. The oxidative stress was highest in liver followed by brain and kidney after oral CuSO{sub 4} exposure in a rat model. These levels correlated with the respective organ dysfunction and tissue free Cu concentration. - Highlights: • Oral dosing of CuSO{sub 4} leads to oxidative stress in liver, brain and kidney. • Liver has maximum oxidative stress followed by brain and kidney. • Oxidative stress correlated with the respective organ dysfunction and tissue Cu concentration.« less

  12. Differences in GFR and Tissue Oxygenation, and Interactions between Stenotic and Contralateral Kidneys in Unilateral Atherosclerotic Renovascular Disease.

    PubMed

    Herrmann, Sandra M S; Saad, Ahmed; Eirin, Alfonso; Woollard, John; Tang, Hui; McKusick, Michael A; Misra, Sanjay; Glockner, James F; Lerman, Lilach O; Textor, Stephen C

    2016-03-07

    Atherosclerotic renal artery stenosis (ARAS) can reduce renal blood flow, tissue oxygenation, and GFR. In this study, we sought to examine associations between renal hemodynamics and tissue oxygenation with single-kidney function, pressor hormones, and inflammatory biomarkers in patients with unilateral ARAS undergoing medical therapy alone or stent revascularization. Nonrandomized inpatient studies were performed in patients with unilateral ARAS (>60% occlusion) before and 3 months after revascularization (n=10) or medical therapy (n=20) or patients with essential hypertension (n=32) under identical conditions. The primary study outcome was change in single-kidney GFR. Individual kidney hemodynamics and volume were measured using multidetector computed tomography. Tissue oxygenation (using R(2)* as a measure of deoxyhemoglobin) was determined by blood oxygen level-dependent magnetic resonance imaging at 3 T. Renal vein neutrophil gelatinase-associated lipocalin (NGAL), monocyte chemoattractant protein-1 (MCP-1), and plasma renin activity were measured. Total GFR did not change over 3 months in either group, but the stenotic kidney (STK) GFR rose over time in the stent compared with the medical group (+2.2[-1.8 to 10.5] versus -5.3[-7.3 to -0.3] ml/min; P=0.03). Contralateral kidney (CLK) GFR declined in the stent group (43.6±19.7 to 36.6±19.5 ml/min; P=0.03). Fractional tissue hypoxia fell in the STK (fraction R(2)* >30/s: 22.1%±20% versus 14.9%±18.3%; P<0.01) after stenting. Renal vein biomarkers correlated with the degree of hypoxia in the STK: NGAL(r=0.3; P=0.01) and MCP-1(r=0.3; P=0.02; more so after stenting). Renal vein NGAL was inversely related to renal blood flow in the STK (r=-0.65; P<0.001). Biomarkers were highly correlated between STK and CLK, NGAL (r=0.94; P<0.001), and MCP-1 (r=0.96; P<0.001). These results showed changes over time in single-kidney GFR that were not evident in parameters of total GFR. Furthermore, they delineate the relationship of measurable tissue hypoxia within the STK and markers of inflammation in human ARAS. Renal vein NGAL and MCP-1 indicated persistent interactions between the ischemic kidney and both CLK and systemic levels of inflammatory cytokines. Copyright © 2016 by the American Society of Nephrology.

  13. Mass Spectrometry Imaging of Drug Related Crystal-Like Structures in Formalin-Fixed Frozen and Paraffin-Embedded Rabbit Kidney Tissue Sections

    NASA Astrophysics Data System (ADS)

    Bruinen, Anne L.; van Oevelen, Cateau; Eijkel, Gert B.; Van Heerden, Marjolein; Cuyckens, Filip; Heeren, Ron M. A.

    2016-01-01

    A multimodal mass spectrometry imaging (MSI) based approach was used to characterize the molecular content of crystal-like structures in a frozen and paraffin embedded piece of a formalin-fixed rabbit kidney. Matrix assisted laser desorption/ionization time-of-flight (MALDI-TOF) imaging and desorption electrospray ionization (DESI) mass spectrometry imaging were combined to analyze the frozen and paraffin embedded sample without further preparation steps to remove the paraffin. The investigated rabbit kidney was part of a study on a drug compound in development, in which severe renal toxicity was observed in dosed rabbits. Histological examination of the kidney showed tubular degeneration with precipitation of crystal-like structures in the cortex, which were assumed to cause the renal toxicity. The MS imaging approach was used to find out whether the crystal-like structures were composed of the drug compound, metabolites, or an endogenous compound as a reaction to the drug administration. The generated MALDI-MSI data were analyzed using principal component analysis. In combination with the MS/MS results, this way of data processing demonstrates that the crystal structures were mainly composed of metabolites and relatively little parent drug.

  14. Ablation of clinically relevant kidney tissue volumes by high-intensity focused ultrasound: Preliminary results of standardized ex-vivo investigations.

    PubMed

    Häcker, Axel; Peters, Kristina; Knoll, Thomas; Marlinghaus, Ernst; Alken, Peter; Jenne, Jürgen W; Michel, Maurice Stephan

    2006-11-01

    To investigate strategies to achieve confluent kidney-tissue ablation by high-intensity focused ultrasound (HIFU). Our model of the perfused ex-vivo porcine kidney was used. Tissue ablation was performed with an experimental HIFU device (Storz Medical, Kreuzlingen, Switzerland). Lesion-to-lesion interaction was investigated by varying the lesion distance (5 to 2.5 mm), generator power (300, 280, and 260 W), cooling time (10, 20, and 30 seconds), and exposure time (4, 3, and 2 seconds). The lesion rows were analyzed grossly and by histologic examination (hematoxylin-eosin and nicotinamide adenine dinucleotide staining). It was possible to achieve complete homogeneous ablation of a clinically relevant tissue volume but only by meticulous adjustment of the exposure parameters. Minimal changes in these parameters caused changes in lesion formation with holes within the lesions and lesion-to-lesion interaction. Our preliminary results show that when using this new device, HIFU can ablate a large tissue volume homogeneously in perfused ex-vivo porcine tissue under standardized conditions with meticulous adjustment of exposure parameters. Further investigations in vivo are necessary to test whether large tissue volumes can be ablated completely and reliably despite the influence of physiologic tissue and organ movement.

  15. Enhanced hepatic and kidney cytochrome p-450 activities in nandrolone decanoate treated albino mice.

    PubMed

    Acharjee, B K; Mahanta, R

    2009-04-01

    Anabolic androgenic steroids are the xenobiotic substrates that are metabolized in the body by the protective enzyme systems. Mixed function oxygenase enzymes include a group of enzymes which play an essential role in the metabolism of a broad range of xenobiotics including endogenous and exogenous substrates. Cytochrome P-450, a member of mixed function oxygenase enzymes, plays an important role in oxidative metabolism of drugs and xenobiotics entering human body. Various anabolic steroids are found either to increase or decrease the activity of cytochrome P-450. However, effect of nandrolone decanoate, most commonly abused anabolic steroid, on cytochrome P-450 activity is still fragmentary. In the present study, albino mice were administered intramuscular 2.5 mg of nandrolone decanoate injection at 15 days interval. Cytochrome P-450 activity is determined by following the method of Omura and Sato (1964) in liver and kidney tissues of both normal and experimental groups upto 90 days. Investigation shows a significant (p <0.01) increase of cytochrome P-450 (nmol/mg) activity in liver tissue as compared to that of kidney tissues. A tissue specific and dose specific increase of cytochrome P-450 activity is observed. Mean cytochrome P-450 is found highest in liver tissue on 45(th) day whereas the activity in kidney tissue is noticed on 90(th) day of treatment. From the above observation, nandrolone decanoate can be suggested as a potent inducer of cytochrome P-450 activity like other anabolic steroids.

  16. Characterization of inter-tissue and inter-strain variability of TCE glutathione conjugation metabolites DCVG, DCVC, and NAcDCVC in the mouse.

    PubMed

    Luo, Yu-Syuan; Furuya, Shinji; Chiu, Weihsueh; Rusyn, Ivan

    2018-01-01

    Trichloroethylene (TCE) is a ubiquitous environmental toxicant that is a liver and kidney carcinogen. Conjugation of TCE with glutathione (GSH) leads to formation of nepthrotoxic and mutagenic metabolites postulated to be critical for kidney cancerdevelopment; however, relatively little is known regarding their tissue levels as previous analytical methods for their detection lacked sensitivity. Here, an LC-MS/MS-based method for simultaneous detection of S-(1,2-dichlorovinyl)-glutathione (DCVG), S-(1,2-dichlorovinyl)-L-cysteine (DCVC), and N-acetyl-S-(1,2-dichlorovinyl)-L-cysteine (NAcDCVC) in multiple mouse tissues was developed. This analytical method is rapid, sensitive (limits of detection (LOD) 3-30 fmol across metabolites and tissues), and robust to quantify all three metabolites in liver, kidneys, and serum. The method was used to characterize inter-tissue and inter-strain variability in formation of conjugative metabolites of TCE. Single oral dose of TCE (24, 240 or 800 mg/kg) was administered to male mice from 20 inbred strains of Collaborative Cross. Inter-strain variability in the levels of DCVG, DCVC, and NAcDCVC (GSD = 1.6-2.9) was observed. Whereas NAcDCVC was distributed equally among analyzed tissues, highest levels of DCVG were detected in liver and DCVC in kidneys. Evidence indicated that inter-strain variability in conjugative metabolite formation of TCE might affect susceptibility to adverse health effects and that this method might aid in filling data gaps in human health assessment of TCE.

  17. Effect of 3-methylcholanthrene-induced increases in ascorbic acid levels on tissue. beta. -glucuronidase activity in rats

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

    Calabrese, E.J.; Barrett, T.J.; Leonard, D.A.

    1988-01-01

    The interrelationship between tissue ascorbic acid levels and tissue ..beta..-glucuronidase activity was examined in rats injected with 3-methylcholanthrene, an agent which induces ascorbic acid synthesis in rats. Six Fisher 344 rats were dosed intraperitoneally (IP) with 30 mg/kg of 3-methylcholanthrene. Ascorbic acid levels and ..beta..-glucuronidase (..beta..-G) activity were determined for lung, liver and kidney tissues. In a follow-up study, rats were dosed for three consecutive days with 3-methylcholanthrene. Controls in both groups were dosed IP with Emulphor (EL-620). Animals were sacrificed one week after the final dosage and lung, liver and kidney tissues were examined.

  18. Characterization of renal biomarkers for use in clinical trials: effect of preanalytical processing and qualification using samples from subjects with diabetes.

    PubMed

    Brott, David A; Furlong, Stephen T; Adler, Scott H; Hainer, James W; Arani, Ramin B; Pinches, Mark; Rossing, Peter; Chaturvedi, Nish

    2015-01-01

    Identifying the potential for drug-induced kidney injury is essential for the successful research and development of new drugs. Newer and more sensitive preclinical drug-induced kidney injury biomarkers are now qualified for use in rat toxicology studies, but biomarkers for clinical studies are still undergoing qualification. The current studies investigated biomarkers in healthy volunteer (HV) urine samples with and without the addition of stabilizer as well as in urine from patients with normoalbuminuric diabetes mellitus (P-DM). Urine samples from 20 male HV with stabilizer, 69 male HV without stabilizer, and 95 male DM without stabilizer (39 type 1 and 56 type 2) were analyzed for the following bio-markers using multiplex assays: α-1-microglobulin (A1M), β-2-microglobulin, calbindin, clusterin, connective tissue growth factor (CTGF), creatinine, cystatin-C, glutathione S-transferase α (GSTα), kidney injury marker-1 (KIM-1), microalbumin, neutrophil gelatinase-associated lipocalin, osteopontin, Tamm-Horsfall urinary glycoprotein (THP), tissue inhibitor of metalloproteinase 1, trefoil factor 3 (TFF3), and vascular endothelial growth factor. CTGF and GSTα assays on nonstabilized urine were deemed nonoptimal (>50% of values below assay lower limits of quantification). "Expected values" were determined for HV with stabilizer, HV without stabilizer, and P-DM without stabilizer. There was a statistically significant difference between HV with stabilizer compared to HV without stabilizer for A1M, CTGF, GSTα, and THP. DM urine samples differed from HV (without stabilizer) for A1M CTGF, GSTα, KIM-1, microalbumin, osteopontin, and TFF3. A1M also correctly identified HV and DM with an accuracy of 89.0%. These studies: 1) determined that nonstabilized urine can be used for assays under qualification; and 2) documented that A1M, CTGF, GSTα, KIM-1, microalbumin, osteopontin, and TFF3 were significantly increased in urine from P-DM. In addition, the 89.0% accuracy of A1M in distinguishing P-DM from HV may allow this biomarker to be used to monitor efficacy of potential renal protective agents.

  19. Fetal Tissues Tested for Microbial Sterility by Culture- and PCR-Based Methods Can be Safely Used in Clinics.

    PubMed

    Vitrenko, Yakov; Kostenko, Iryna; Kulebyakina, Kateryna; Duda, Alla; Klunnyk, Mariya; Sorochynska, Khrystyna

    2017-02-16

    Cell preparations to be used in clinical practice must be free of infectious agents. Safety concerns are especially elevated upon the use of human fetal tissues, which are otherwise highly advantageous in cell therapy. We demonstrate that treating fetal samples with antibiotic, extensive washing, and homogenization prior to cryoconservation efficiently removes microbes in general. Screening a large collection by an automatic culture system showed that 89.2% fetal tissue samples were sterile, while contamination was detected in 10.8% samples. Liver and chorion were contaminated more than the brain, kidney, lung, and soft tissues. Broad-range PCR from the bacterial 16s rRNA gene was adopted as a confirmatory assay; however, the concordance between the culture-based and PCR assays was weak. Taxonomic identification was done for contaminated samples by bacteriological methods and sequencing 16s rRNA PCR products. The two approaches revealed different spectra of taxonomic groups sharing only Lactobacillus, the most frequently found genus. In addition, other representatives of vaginal microbiota were detected by culture-based identification, while PCR product sequencing has also revealed a subset of nosocomial microorganisms. Importantly, species known to cause sepsis were identified by both techniques, arguing for their indispensability and mutual complementarity. We suggest that most contaminations are taken up during collection of fetal material rather than originating from an in utero infection. In conclusion, a rigorous microbiological control by culture and PCR is a prerequisite for safe clinical use of fetal tissue suspensions.

  20. How to grow a kidney: patient-specific kidney organoids come of age.

    PubMed

    Schmidt-Ott, Kai M

    2017-01-01

    The notion of regrowing a patient's kidney in a dish has fascinated researchers for decades and has spurred visions of revolutionary clinical applications. Recently, this option has come closer to reality. Key technologies have been developed to generate patient-specific pluripotent stem cells and to edit their genome. Several laboratories have devised protocols to differentiate patient-specific pluripotent stem cells into kidney cells or into in vitro organoids that resemble the kidney with respect to cell types, tissue architecture and disease pathology. This was possible because of rapidly expanding knowledge regarding the cellular and molecular basis of embryonic kidney development. Generating kidney cells or organoids from patient-specific stem cells may prove to be clinically useful in several ways. First, patient-specific kidney cells or organoids could be used to predict an individual's response to stressors, toxins or medications and thereby develop personalized treatment decisions. Second, patient-specific stem cells harbour the individual's genetic defects. This may potentially enable genetic rescue attempts to establish the significance of a genetic defect in a stem cell-derived organoid or it may allow testing of patient-specific targeted therapies for kidney disease in vitro. From a tissue engineering perspective, patient-specific kidney organoids might provide a key advance towards engineering immunocompatible transplantable kidneys. This review article summarizes recent developments in the field and discusses its current limitations and future perspectives. © The Author 2016. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.

  1. HMGB1 redox during sepsis.

    PubMed

    Abdulmahdi, Wasan; Patel, Devika; Rabadi, May M; Azar, Tala; Jules, Edson; Lipphardt, Mark; Hashemiyoon, Rameen; Ratliff, Brian B

    2017-10-01

    During sepsis, the alarmin HMGB1 is released from tissues and promotes systemic inflammation that results in multi-organ damage, with the kidney particularly susceptible to injury. The severity of inflammation and pro-damage signaling mediated by HMGB1 appears to be dependent on the alarmin's redox state. Therefore, we examined HMGB1 redox in kidney cells during sepsis. Using intravital microscopy, CellROX labeling of kidneys in live mice indicated increased ROS generation in the kidney perivascular endothelium and tubules during lipopolysaccharide (LPS)-induced sepsis. Subsequent CellROX and MitoSOX labeling of LPS-stressed endothelial and kidney proximal tubule cells demonstrated increased ROS generation in these cells as sepsis worsens. Consequently, HMGB1 oxidation increased in the cytoplasm of kidney cells during its translocation from the nucleus to the circulation, with the degree of oxidation dependent on the severity of sepsis, as measured in in vivo mouse samples using a thiol assay and mass spectrometry (LC-MS/MS). The greater the oxidation of HMGB1, the greater the ability of the alarmin to stimulate pro-inflammatory cyto-/chemokine release (measured by Luminex Multiplex) and alter mitochondrial ATP generation (Luminescent ATP Detection Assay). Administration of glutathione and thioredoxin inhibitors to cell cultures enhanced HMGB1 oxidation during sepsis in endothelial and proximal tubule cells, respectively. In conclusion, as sepsis worsens, ROS generation and HMGB1 oxidation increases in kidney cells, which enhances HMGB1's pro-inflammatory signaling. Conversely, the glutathione and thioredoxin systems work to maintain the protein in its reduced state. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

  2. High-resolution, 2- and 3-dimensional imaging of uncut, unembedded tissue biopsy samples.

    PubMed

    Torres, Richard; Vesuna, Sam; Levene, Michael J

    2014-03-01

    Despite continuing advances in tissue processing automation, traditional embedding, cutting, and staining methods limit our ability for rapid, comprehensive visual examination. These limitations are particularly relevant to biopsies for which immediate therapeutic decisions are most necessary, faster feedback to the patient is desired, and preservation of tissue for ancillary studies is most important. The recent development of improved tissue clearing techniques has made it possible to consider use of multiphoton microscopy (MPM) tools in clinical settings, which could address difficulties of established methods. To demonstrate the potential of MPM of cleared tissue for the evaluation of unembedded and uncut pathology samples. Human prostate, liver, breast, and kidney specimens were fixed and dehydrated by using traditional histologic techniques, with or without incorporation of nucleic acid fluorescent stains into dehydration steps. A benzyl alcohol/benzyl benzoate clearing protocol was substituted for xylene. Multiphoton microscopy was performed on a home-built system. Excellent morphologic detail was achievable with MPM at depths greater than 500 μm. Pseudocoloring produced images analogous to hematoxylin-eosin-stained images. Concurrent second-harmonic generation detection allowed mapping of collagen. Subsequent traditional section staining with hematoxylin-eosin did not reveal any detrimental morphologic effects. Sample immunostains on renal tissue showed preservation of normal reactivity. Complete reconstructions of 1-mm cubic samples elucidated 3-dimensional architectural organization. Multiphoton microscopy on cleared, unembedded, uncut biopsy specimens shows potential as a practical clinical tool with significant advantages over traditional histology while maintaining compatibility with gold standard techniques. Further investigation to address remaining implementation barriers is warranted.

  3. Continuous monitoring of kidney transplant perfusion with near-infrared spectroscopy.

    PubMed

    Malakasioti, Georgia; Marks, Stephen D; Watson, Tom; Williams, Fariba; Taylor-Allkins, Mariesa; Mamode, Nizam; Morgan, Justin; Hayes, Wesley N

    2018-05-11

    Current reliance on clinical, laboratory and Doppler ultrasound (DUS) parameters for monitoring kidney transplant perfusion in the immediate post-operative period in children risks late recognition of allograft hypoperfusion and vascular complications. Near-infrared spectroscopy (NIRS) is a real-time, non-invasive technique for monitoring tissue oxygenation percutaneously. NIRS monitoring of kidney transplant perfusion has not previously been validated to the gold standard of DUS. We examined whether NIRS tissue oxygenation indices can reliably assess blood flow in established paediatric kidney transplants. Paediatric kidney transplant recipients ages 1-18 years with stable allograft function were eligible. Participants underwent routine DUS assessment of kidney transplant perfusion, including resistive index (RI) and peak systolic velocity at the upper and lower poles. NIRS data [tissue oxygenation index (TOI%)] were recorded for a minimum of 2 min with NIRS sensors placed on the skin over upper and lower allograft poles. Twenty-nine subjects with a median age of 13.3 (range 4.8-17.8) years and a median transplant vintage of 26.5 months participated. Thirteen (45%) were female and 20 (69%) were living donor kidney recipients. NIRS monitoring was well tolerated by all, with 96-100% valid measurements. Significant negative correlations were observed between NIRS TOI% and DUS RI at both the upper and lower poles (r = -0.4 and -0.6, P = 0.04 and 0.001, respectively). Systolic blood pressure but not estimated glomerular filtration rate also correlated with NIRS TOI% (P = 0.01). NIRS indices correlate well with DUS perfusion and haemodynamic parameters in established paediatric kidney transplant recipients. Further studies are warranted to extend NIRS use for continuous real-time monitoring of early post-transplant perfusion status.

  4. Diuretic renography in hydronephrosis: delayed tissue tracer transit accompanies both functional decline and tissue reorganization.

    PubMed

    Schlotmann, Andreas; Clorius, John H; Rohrschneider, Wiltrud K; Clorius, Sandra N; Amelung, Folker; Becker, Kristianna

    2008-07-01

    The significance of delayed tissue tracer transit (TTT) of (99m)Tc-mercaptoacetyltriglycine ((99m)Tc-MAG3) has not been systematically evaluated in hydronephrosis. We sought to demonstrate that delayed TTT accompanies both functional decline and histomorphologic restructuring. Twenty 2- to 3-mo-old piglets with surgically induced partial unilateral ureteral stenosis were examined with magnetic resonance urography (MRU) to evaluate morphology and with (99m)Tc-MAG3 diuretic renography (DR) to determine single-kidney function (SKF), evaluate the response to furosemide stimulation (RFS), and assess TTT. All animals had DR and MRU before and after surgery and a third DR after surgery. Piglets were sacrificed after the final DR for renal histology. A total histologic score (THS) was generated. Preoperative DR demonstrated nonobstructive RFS, timely TTT, and balanced SKF in all 20 kidneys. After ureteral ligature, MRU demonstrated pelvic dilatation in all piglets. The postoperative DRs revealed 12 kidneys with delayed TTT in one or both follow-ups. In these 12 kidneys, the SKF declined from 51% +/- 4% to 18% +/- 14%, and the THS was 9.0 +/- 4.0. Three kidneys always had timely TTT, balanced SKF, and a THS of 1.8 +/- 0.3. The contralateral, nonoperated kidneys had timely TTT and a THS of 1.2 +/- 0.9. Postoperative scintigrams showed that 3 of 8 kidneys (38%) with an obstructive RFS had timely TTT, which demonstrates that TTT and RFS are not equivalent. In hydronephrosis, a delayed TTT of (99m)Tc-MAG3 accompanies both functional decline and histomorphologic restructuring in obstruction. According to the literature, a delayed TTT is determined by the filtration fraction of the kidneys and appears to identify an obstruction-mediated upregulated renin-angiotensin system.

  5. Identification of organ tissue types and skin from forensic samples by microRNA expression analysis.

    PubMed

    Sauer, Eva; Extra, Antje; Cachée, Philipp; Courts, Cornelius

    2017-05-01

    The identification of organ tissues in traces recovered from scenes and objects with regard to violent crimes involving serious injuries can be of considerable relevance in forensic investigations. Molecular genetic approaches are provably superior to histological and immunological assays in characterizing organ tissues, and micro-RNAs (miRNAs), due to their cell type specific expression patterns and stability against degradation, emerged as a promising molecular species for forensic analyses, with a range of tried and tested indicative markers. Thus, herein we present the first miRNA based approach for the forensic identification of organ tissues. Using quantitative PCR employing an empirically derived strategy for data normalization and unbiased statistical decision making, we assessed the differential expression of 15 preselected miRNAs in tissues of brain, kidney, lung, liver, heart muscle, skeletal muscle and skin. We show that not only can miRNA expression profiling be used to reliably differentiate between organ tissues but also that this method, which is compatible with and complementary to forensic DNA analysis, is applicable to realistic forensic samples e.g. mixtures, aged and degraded material as well as traces generated by mock stabbings and experimental shootings at ballistic models. Copyright © 2017 Elsevier B.V. All rights reserved.

  6. Glomerular Diseases

    MedlinePlus

    ... dialysis or transplantation to replace renal function. Bacterial endocarditis, infection of the tissues inside the heart, is ... the most effective way of minimizing kidney damage. Endocarditis sometimes produces chronic kidney disease (CKD) . HIV, the ...

  7. [Determination of Trace Elements in Marine Cetaceans by ICP-MS and Health Risk Assessment].

    PubMed

    Ding, Yu-long; Ning, Xi; Gui, Duan; Mo, Hui; Li, Yu-sen; Wu, Yu-ping

    2015-09-01

    The liver, kidney and muscle samples from seven cetaceans were digested by microwave digestion, and trace elements amounts of V, Cd, Cu, Zn, As, Cr, Ni, Mn, Se, Hg and Pb were determined by inductively coupled plasma mass spectrometry (ICP-MS), and the health risk assessment for Zn, Cu, Cd, Hg, Se in the liver was conducted. The results of international lobster hepatopancreas standard (TORT-2) showed acceptable agreement with the certified values, and the relative standard deviation (RSD) of eleven kinds of trace elements were less than 3.54%, showing that the method is suitable for the determination of trace elements in cetaceans. The experimental results indicated that different tissues and organs of the dolphins had different trace elements, presenting the tissue specificity. There is a certain inter-species difference among different dolphins about the bioaccumulation ability of the trace elements. The distribution of trace elements in whales presented a certain regularity: the contents of most elements in liver, kidney were much higher than the contents of muscle tissues, Cu, Mn, Hg, Se, and Zn exhibit the higher concentrations in liver, while Cd was mainly accumulated in kidney. And according to the health risk assessment in liver, the exceeding standardrate of selenium and copper in seven kinds of whales was 100%, suggesting that these whales were suffering the contamination of trace elements. The experimental results is instructive to the study of trace elements in cetaceans, while this is the first report for the concentrations in organs of Striped dolphin, Bottlenose dolphin, Fraser's Dolphin and Risso's dolphin in China, it may provide us valuable data for the conservation of cetaceans.

  8. Protective effects of piperine on lead acetate induced-nephrotoxicity in rats

    PubMed Central

    Sudjarwo, Sri Agus; Eraiko, Koerniasari; Sudjarwo, Giftania Wardani; Koerniasari

    2017-01-01

    Objective(s): In this study, we investigated the protective effects of piperine on lead acetate-induced renal damage in rat kidney tissue. Materials and Methods: Forty male rats were divided into 5 groups: negative control (rats were given aquadest daily), positive control (rats were given lead acetate 30 mg/kg BW orally once a day for 60 days), and the treatment group (rats were given piperine 50 mg; 100 mg and 200 mg/kg BW orally once a day for 65 days, and on 5th day, were given lead acetate 30 mg/kg BW one hr after piperine administration for 60 days). On day 65 levels of blood urea nitrogen (BUN), creatinine, malondialdehyde (MDA), Superoxide Dismutase (SOD), and Glutathione Peroxidase (GPx) were measured. Also, kidney samples were collected for histopathological studies. Results: The results revealed that lead acetate toxicity induced a significant increase in the levels of BUN, creatinine, and MDA; moreover, a significant decrease in SOD and GPx. Lead acetate also altered kidney histopathology (kidney damage, necrosis of tubules) compared to the negative control. However, administration of piperine significantly improved the kidney histopathology, decreased the levels of BUN, creatinine, and MDA, and also significantly increased the SOD and GPx in the kidney of lead acetate-treated rats. Conclusion: From the results of this study it was concluded that piperine could be a potent natural herbal product exhibiting nephroprotective effect against lead acetate induced nephrotoxicity in rats. PMID:29299200

  9. Fell-Muir lecture: connective tissue growth factor (CCN2) – a pernicious and pleiotropic player in the development of kidney fibrosis

    PubMed Central

    Mason, Roger M

    2013-01-01

    Connective tissue growth factor (CTGF, CCN2) is a member of the CCN family of matricellular proteins. It interacts with many other proteins, including plasma membrane proteins, modulating cell function. It is expressed at low levels in normal adult kidney cells but is increased in kidney diseases, playing important roles in inflammation and in the development of glomerular and interstitial fibrosis in chronic disease. This review reports the evidence for its expression in human and animal models of chronic kidney disease and summarizes data showing that anti-CTGF therapy can successfully attenuate fibrotic changes in several such models, suggesting that therapies targeting CTGF and events downstream of it in renal cells may be useful for the treatment of human kidney fibrosis. Connective tissue growth factor stimulates the development of fibrosis in the kidney in many ways including activating cells to increase extracellular matrix synthesis, inducing cell cycle arrest and hypertrophy, and prolonging survival of activated cells. The relationship between CTGF and the pro-fibrotic factor TGFβ is examined and mechanisms by which CTGF promotes signalling by the latter are discussed. No specific cellular receptors for CTGF have been discovered but it interacts with and activates several plasma membrane proteins including low-density lipoprotein receptor-related protein (LRP)-1, LRP-6, tropomyosin-related kinase A, integrins and heparan sulphate proteoglycans. Intracellular signalling and downstream events triggered by such interactions are reviewed. Finally, the relationships between CTGF and several anti-fibrotic factors, such as bone morphogenetic factor-4 (BMP4), BMP7, hepatocyte growth factor, CCN3 and Oncostatin M, are discussed. These may determine whether injured tissue heals or progresses to fibrosis. PMID:23110747

  10. Oxytetracycline and penicillin-G residues in cattle slaughtered in south-western Nigeria: implications for livestock disease management and public health.

    PubMed

    Adesokan, Hezekiah K; Agada, Charity A; Adetunji, Victoria O; Akanbi, Ibikunle M

    2013-01-01

    After the discovery of indiscriminate antibiotic use in ready-for-slaughter cattle in south-western Nigeria, 90 tissue samples from randomly selected slaughtered cattle were evaluated for oxytetracycline and penicillin-G residues using high performance liquid chromatography and the data analysed by one-way Analysis of variance (ANOVA). The findings revealed residues of oxytetracycline (kidney: 9.47 µ/kg ± 3.24 µ/kg; liver: 12.73 µ/kg ± 4.39 µ/kg; muscle: 16.17 µ/kg ± 5.52 µ/kg) and penicillin-G (kidney: 6.27 µ/kg ± 2.46 µ/kg; liver: 8.5 µ/kg ± 2.80 µ/kg; muscle: 11.67 µ/kg ± 2.94 µ/kg) in all tissues screened. Significantly high levels (oxytetracycline: F = 16.77; penicillin-G: F = 29.38) were, however, found in muscles, followed by liver and then kidney – findings confirming recent antibiotic administration to the animals before slaughter. The dietary intakes through the tissues screened were 0.024% (oxytetracycline) and 0.017% (penicillin-G) of the acceptable daily intake (ADI). Although the concentrations in the tissues screened were below the maximum residue limits despite recent administration of these antibiotics before slaughter, the lower concentrations are suggestive of the probable low dosages often administered by those involved in indiscriminate use of antibiotics. This therefore raises serious concerns for the livestock industry as well as human health, given the resultant emergence and spread of resistant strains of bacterial pathogens that could ensue from prolonged use of low dosages of antibiotics. Additionally, the lower concentrations of the daily intakes notwithstanding, the plausible exposure to these antibiotics from other food sources is a cause for concern. Since antimicrobial misuse and its consequent effects are not just a problem limited to Nigeria but also a concern in sub-Saharan Africa, the need for national and international stakeholder intervention is emphasised.

  11. Beneficial effects of Aesculus hippocastanum L. seed extract on the body's own antioxidant defense system on subacute administration.

    PubMed

    Küçükkurt, Ismail; Ince, Sinan; Keleş, Hikmet; Akkol, Esra Küpeli; Avci, Gülcan; Yeşilada, Erdem; Bacak, Elif

    2010-05-04

    Seeds of Aesculus hippocastanum L. have long been used in European phytotherapy to treat inflammatory and vascular problems. In Turkish folk medicine, tea prepared from the crushed seeds was used to pass kidney stone and against stomach ache, while a fraction of seed was swallowed to alleviate hemorrhoids symptoms. In order to evaluate the in vivo effects of escin mixture from Aesculus hippocastanum seed on the blood and tissue antioxidant defense systems in standard pellet diet (SPD) and in high-fat diet (HFD) consumed male mice. Escin mixture was obtained from the ethanol extract of seeds. Escin mixture was administered orally to male mice fed either standard pellet diet (SPD) or high-fat diet (HFD) at 100mg/kg doses daily for 5 weeks and the tissue (liver, kidney and heart) and blood samples were collected at the end of experimental period. The effect of escin mixture on the plasma antioxidant activity; blood and tissue malondialdehyde (MDA) and reduced glutathione (GSH) levels; erythrocyte and tissue superoxide dismutase (SOD) and catalase activity (CAT) in SPD and HFD consumed animals were experimentally studied. Escin mixture prohibited the adverse effects of oxidative stress and showed a protective effect on the liver architecture both in SPD and HFD consumed male mice. Escin mixture prohibited the adverse effects of oxidative stress and showed a protective effect on the liver architecture both in SPD and HFD consumed male mice. Combined administration of high-fat diet with escin mixture decreased blood (p<0.01), liver (p<0.01), kidney (p<0.05), and heart (p<0.05) of MDA, liver SOD (p<0.01) and CAT (p<0.05) levels and increased blood (p<0.01) and liver GSH (p<0.001) levels in mice. The present results indicate that Aesculus hippocastanum increase the antioxidative defense system of the body and prevent HFD-induced lipid peroxidation in male mice. (c) 2010 Elsevier Ireland Ltd. All rights reserved.

  12. A national level assessment of metal contamination in bats.

    PubMed

    Hernout, Béatrice V; Arnold, Kathryn E; McClean, Colin J; Walls, Michael; Baxter, Malcolm; Boxall, Alistair B A

    2016-07-01

    Many populations of bat species across the globe are declining, with chemical contamination one of many potential stressors implicated in these demographic changes. Metals still contaminate a wide range of habitats, but the risks to bats remain poorly understood. This study is the first to present a national scale assessment of toxic metal (Cd, Pb) and essential trace metal (Cu, Zn) concentrations in bats. Metal concentrations in tissues (kidneys, liver, stomach -stomach content, bones and fur) were measured in 193 Pipistrellus sp. in England and Wales using ICP-MS, and compared to critical toxic concentrations for small mammals. The concentrations of metals determined in bat tissues were generally lower than those reported elsewhere. Strong positive associations were found between concentrations in tissues for a given metal (liver and kidneys for Cd, Cu and Pb; stomach and fur and fur and bones for Pb), suggesting recent as well as long term exposure to these contaminants. In addition, positive correlations between concentrations of different metals in the same tissues (Cd and Zn, Cu and Zn, Cd and Pb, Pb and Zn) suggest a co-exposure of metals to bats. Approximately 21% of the bats sampled contained residues of at least one metal at concentrations high enough to elicit toxic effects (associated with kidney damage), or to be above the upper level measured in other mammal species. Pb was found to pose the greatest risk (with 7-11% of the bats containing concentrations of toxicological concern), followed by Cu (4-9%), Zn (0.5-5.2%) and Cd (0%). Our data suggest that leaching of metals into our storage matrix, formaldehyde, may have occurred, especially for Cu. The overall findings suggest that metal contamination is an environmental stressor affecting bat populations, and that further research is needed into the direct links between metal contamination and bat population declines worldwide. Copyright © 2016 Elsevier Ltd. All rights reserved.

  13. Mercury and Selenium in Stranded Indo-Pacific Humpback Dolphins and Implications for Their Trophic Transfer in Food Chains

    PubMed Central

    Gui, Duan; Yu, Ri-Qing; Sun, Yong; Chen, Laiguo; Tu, Qin; Mo, Hui; Wu, Yuping

    2014-01-01

    As top predators in the Pearl River Estuary (PRE) of China, Indo-Pacific humpback dolphins (Sousa chinensis) are bioindicators for examining regional trends of environmental contaminants in the PRE. We examined samples from stranded S. chinensis in the PRE, collected since 2004, to study the distribution and fate of total mercury (THg), methylmercury (MeHg) and selenium (Se) in the major tissues, in individuals at different ages and their prey fishes from the PRE. This study also investigated the potential protective effects of Se against the toxicities of accumulated THg. Dolphin livers contained the highest concentrations of THg (32.34±58.98 µg g−1 dw) and Se (15.16±3.66 µg g−1 dw), which were significantly different from those found in kidneys and muscles, whereas the highest residue of MeHg (1.02±1.11 µg g−1 dw) was found in dolphin muscles. Concentrations of both THg and MeHg in the liver, kidney and muscle of dolphins showed a significantly positive correlation with age. The biomagnification factors (BMFs) of inorganic mercury (Hginorg) in dolphin livers (350×) and MeHg in muscles (18.7×) through the prey fishes were the highest among all three dolphin tissues, whereas the BMFs of Se were much lower in all dolphin tissues. The lower proportion of MeHg in THg and higher Se/THg ratios in tissues were demonstrated. Our studies suggested that S. chinensis might have the potential to detoxify Hg via the demethylation of MeHg and the formation of tiemannite (HgSe) in the liver and kidney. The lower threshold of hepatic THg concentrations for the equimolar accumulation of Se and Hg in S. chinensis suggests that this species has a greater sensitivity to THg concentrations than is found in striped dolphins and Dall’s porpoises. PMID:25310100

  14. Mercury and selenium in stranded Indo-Pacific humpback dolphins and implications for their trophic transfer in food chains.

    PubMed

    Gui, Duan; Yu, Ri-Qing; Sun, Yong; Chen, Laiguo; Tu, Qin; Mo, Hui; Wu, Yuping

    2014-01-01

    As top predators in the Pearl River Estuary (PRE) of China, Indo-Pacific humpback dolphins (Sousa chinensis) are bioindicators for examining regional trends of environmental contaminants in the PRE. We examined samples from stranded S. chinensis in the PRE, collected since 2004, to study the distribution and fate of total mercury (THg), methylmercury (MeHg) and selenium (Se) in the major tissues, in individuals at different ages and their prey fishes from the PRE. This study also investigated the potential protective effects of Se against the toxicities of accumulated THg. Dolphin livers contained the highest concentrations of THg (32.34±58.98 µg g(-1) dw) and Se (15.16±3.66 µg g(-1) dw), which were significantly different from those found in kidneys and muscles, whereas the highest residue of MeHg (1.02±1.11 µg g(-1) dw) was found in dolphin muscles. Concentrations of both THg and MeHg in the liver, kidney and muscle of dolphins showed a significantly positive correlation with age. The biomagnification factors (BMFs) of inorganic mercury (Hginorg) in dolphin livers (350×) and MeHg in muscles (18.7×) through the prey fishes were the highest among all three dolphin tissues, whereas the BMFs of Se were much lower in all dolphin tissues. The lower proportion of MeHg in THg and higher Se/THg ratios in tissues were demonstrated. Our studies suggested that S. chinensis might have the potential to detoxify Hg via the demethylation of MeHg and the formation of tiemannite (HgSe) in the liver and kidney. The lower threshold of hepatic THg concentrations for the equimolar accumulation of Se and Hg in S. chinensis suggests that this species has a greater sensitivity to THg concentrations than is found in striped dolphins and Dall's porpoises.

  15. The role of renal proximal tubule P450 enzymes in chloroform-induced nephrotoxicity: Utility of renal specific P450 reductase knockout mouse models

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

    Liu, Senyan; Wadsworth Center, New York State Department of Health, and School of Public Health, State University of New York, Albany, NY 12201; Yao, Yunyi

    The kidney is a primary target for numerous toxic compounds. Cytochrome P450 enzymes (P450) are responsible for the metabolic activation of various chemical compounds, and in the kidney are predominantly expressed in proximal tubules. The aim of this study was to test the hypothesis that renal proximal tubular P450s are critical for nephrotoxicity caused by chemicals such as chloroform. We developed two new mouse models, one having proximal tubule-specific deletion of the cytochrome P450 reductase (Cpr) gene (the enzyme required for all microsomal P450 activities), designated proximal tubule-Cpr-null (PTCN), and the other having proximal tubule-specific rescue of CPR activity withmore » the global suppression of CPR activity in all extra-proximal tubular tissues, designated extra-proximal tubule-Cpr-low (XPT-CL). The PTCN, XPT-CL, Cpr-low (CL), and wild-type (WT) mice were treated with a single oral dose of chloroform at 200 mg/kg. Blood, liver and kidney samples were obtained at 24 h after the treatment. Renal toxicity was assessed by measuring BUN and creatinine levels, and by pathological examination. The blood and tissue levels of chloroform were determined. The severity of toxicity was less in PTCN and CL mice, compared with that of WT and XPT-CL mice. There were no significant differences in chloroform levels in the blood, liver, or kidney, between PTCN and WT mice, or between XPT-CL and CL mice. These findings indicate that local P450-dependent activities play an important role in the nephrotoxicity induced by chloroform. Our results also demonstrate the usefulness of these novel mouse models for studies of chemical-induced kidney toxicity. - Highlights: • New mouse models were developed with varying P450 activities in the proximal tubule. • These mouse models were treated with chloroform, a nephrotoxicant. • Studies showed the importance of local P450s in chloroform-induced nephrotoxicity.« less

  16. Lead, cadmium and organochlorine pesticide residues in hunted red deer and wild boar from northern Italy.

    PubMed

    Chiari, Mario; Cortinovis, Cristina; Bertoletti, Marco; Alborali, Loris; Zanoni, Mariagrazia; Ferretti, Enrica; Caloni, Francesca

    2015-01-01

    The objectives of the present study were to assess heavy metal cadmium (Cd), lead (Pb) and organochlorine pesticide concentrations in tissues of red deer (Cervus elaphus) and wild boar (Sus scrofa) from nine hunting areas and to evaluate related risk factors for the host animal. Over a period of 2 years, a total of 1055 and 210 masseters, 424 and 201 livers, 642 and 152 kidneys were collected from wild boar and red deer, respectively, and concentrations of Cd, Pb and organochlorine pesticides were determined. Comparing the two species, Cd concentration in the kidney (3.72 mg/kg), liver (0.67 mg/kg) and muscle (0.02 mg/kg) of wild boar was found to be significantly higher than in the organs of red deer (1.02 mg/kg in the kidneys, 0.07 mg/kg in the liver and 0.006 mg/kg in muscle). Mean Pb concentrations were found to be similar in both animals, with 0.39, 0.52 and 2.60 mg/kg detected in the wild boar kidney, liver and muscle, respectively, and 0.24, 0.21 and 2.04 mg/kg in the respective organs of the red deer. No difference in concentrations were found based on age class, location of tissue sample or contaminant in the case of wild boar. By contrast, a significantly lower Cd concentration was found in the kidney of the young red deer. The search for organochlorine pesticides in both red deer and wild boar produced negative results with values below the limits of detection. Due to the high levels of renal Cd and muscle Pb detected in wild boar and red deer, further research needs to be carried out in an effort to identify the source of contamination and preserve the health of animals and humans.

  17. Heat shock protein 60 expression in heart, liver and kidney of broilers exposed to high temperature.

    PubMed

    Yan, Jianyan; Bao, Endong; Yu, Jimian

    2009-06-01

    The objective of this study was to investigate the expression and localization of HSP60 in the heart, liver, and kidney of acutely heat-stressed broilers at various stressing times. The plasma creatine kinase (CK) and glutamic pyruvic transaminase (GPT) concentrations statistic increased following heat stress. After 2h of heat stress, the tissues showed histopathological changes. Hsp60 expressed mainly in the cytoplasm of parenchyma cells heat stress. The intensity of the cytoplasmic staining varied and exhibited an organ-specific distribution pattern. Hsp60 levels in the hearts of heat-stressed chickens gradually increased at 1h (p<0.05) and peaked (p<0.05) at 5h; Hsp60 levels in the liver gradually decreased at 3h (p<0.05); Hsp60 levels in the kidney had no fluctuation. It is suggested that Hsp60 expression is tissue-specific and this may be linked to tissue damage in response to heat stress. The Hsp60 level is distinct in diverse tissues, indicating that Hsp60 may exert its protective effect by a tissue- and time-specific mechanism.

  18. Comparison of 1.5 and 3 T BOLD MR to study oxygenation of kidney cortex and medulla in human renovascular disease.

    PubMed

    Gloviczki, Monika L; Glockner, James; Gomez, Sabas I; Romero, Juan C; Lerman, Lilach O; McKusick, Michael; Textor, Stephen C

    2009-09-01

    Imaging of the kidney using blood oxygen level dependent MR presents a major opportunity to examine differences in tissue oxygenation within the cortex and medulla applicable to human disease. We sought to define the differences between regions within kidneys and to optimize selection of regions of interest for study with 1.5 and 3 Tesla systems. Studies in 38 subjects were performed under baseline conditions and after administration of furosemide intravenously to examine changes in R2* as a result of suppressing oxygen consumption related to medullary tubular solute transport. These studies were carried out in patients with atherosclerotic renal artery stenosis (n = 24 kidneys) or essential hypertension or nonstenotic kidneys (n = 39). All patients but one were treated with agents to block the renin angiotensin system (ACE inhibitors or angiotensin receptor blockers). For each kidney, 3 levels (upper pole, hilum, and lower pole) were examined, including 3 individual segments (anterior, lateral, and posterior). Low basal R2* levels in kidney cortex (12.06 +/- 0.84 s(-1)) at 1.5 Tesla reflected robust blood flow and oxygenation and agreed closely with values obtained at 3.0 Tesla (13.62 +/- 0.56 s(-1), NS). Coefficients of variation ranged between 15% and 20% between segments and levels at both field strengths. By contrast, inner medullary R2* levels were higher at 3 T (31.66 +/- 0.74 s(-1)) as compared with 1.5 T (22.19 +/- 1.52 s(-1), P < 0.01). Medullary R2* values fell after furosemide administration reflecting reduced deoxyhemoglobin levels associated with blocked energy-dependent transport. The fall in medullary R2* at 3.0 Tesla (-12.61 +/- 0.97 s(-1)) was greater than observed at 1.5 T (-6.07 +/- 1.38 s(-1), P < 0.05). Cortical R2* levels remained low after furosemide and did not vary with field strength. Correlations between measurements of defined cortical and medullary regions of interest within kidneys were greater at each sampling level and segment at 3.0 T as compared to 1.5 T. For patients studied with 3.0 T, furosemide administration induced a lesser fall in R2* in poststenotic kidneys at 3.0 T (-10.61 +/- 1.61 s(-1)) versus nonstenotic kidneys (-13.21 +/- 0.72 s(-1), P < 0.05). This difference was not evident in comparisons made at 1.5 T. The magnitude of furosemide-suppressible oxygen consumption at 3.0 T (-43%) corresponded more closely with reported experimental differences observed during direct measurement with tissue electrodes (45%-50%) than changes measured at 1.5 T. These results indicate that blood oxygen level dependent MR measurements at high field strength can better distinguish discrete cortical and inner medullary regions of the kidney and approximate measured differences in oxygen tension. Maneuvers that reduce oxygen consumption related to tubular solute transport allow functional evaluation of the interstitial compartment as a function of tissue oxygenation. Impaired response to alterations in oxygen consumption can be detected at 3 T more effectively than at 1.5 T and may provide real-time tools to examine developing parenchymal injury associated with impaired oxygenation.

  19. Role of mesenchymal stem cells versus angiotensin converting enzyme inhibitor in kidney repair.

    PubMed

    Ahmed, Hanaa H; Toson, Elshahat A; El-Mezayen, Hatem A; Rashed, Laila A; Elsherbiny, Eslam S

    2017-07-01

    The current study sought to clarify the role of bone marrow derived mesenchymal stem cells (BM-MSCs) and adipose tissue derived mesenchymal stem cells (AD-MSCs) in repressing nephropathy in the experimental model. Moreover, the aim of this work was extended to compare between stem cells role and angiotensin converting enzyme inhibitor in kidney repair. Isolation and preparation of MSCs culture, flow cytometry using CD34, CD44 and CD105 cell surface markers, biochemical analyses for determination of serum creatinine, urea, transforming growth factor β (TGF-β), cystatin C (CYS-C) and urinary N-Acetyl-ß-D-Glucosaminidase (UNAG), and histopathological investigation of kidney tissue sections were performed. The results of the present study revealed that single intravenous infusion of MSCs either derived from bone marrow or adipose tissue was able to enhance renal reparative processes through significantly decreased serum creatinine, urea, TGF-β and CYS-C levels as well as UNAG level and significantly increase glomerular filtration rate. Additionally, the histopathological investigations of kidney tissues showed that MSCs have significant regenerative effects as evidenced by the decrease in focal inflammatory cells infiltration, focal interstitial nephritis and congested glomeruli as well as degenerated tubules. The current data provided distinct evidence about the favourable impact of AD-MSCs and BM-MSCs in attenuation of cyclosporine-induced nephropathy in rats through their ability to promote functional and structural kidney repair via transdifferentiation. © 2016 Asian Pacific Society of Nephrology.

  20. Mercury and selenium levels, and selenium:mercury molar ratios of brain, muscle and other tissues in bluefish (Pomatomus saltatrix) from New Jersey, USA

    PubMed Central

    Burger, Joanna; Jeitner, Christian; Donio, Mark; Pittfield, Taryn; Gochfeld, Michael

    2015-01-01

    A number of contaminants affect fish health, including mercury and selenium, and the selenium: mercury molar ratio. Recently the protective effects of selenium on methylmercury toxicity have been publicized, particularly for consumption of saltwater fish. Yet the relative ameliorating effects of selenium on toxicity within fish have not been examined, nor has the molar ratio in different tissues, (i.e. brain). We examined mercury and selenium levels in brain, kidney, liver, red and white muscle, and skin and scales in bluefish (Pomatomus saltatrix) from New Jersey to determine whether there were toxic levels of either metal, and we computed the selenium: mercury molar ratios by tissues. Total mercury averaged 0.32 ± 0.02 ppm wet weight in edible muscle and 0.09 ± 0.01 ppm in brain. Selenium concentration averaged 0.37 ± 0.03 in muscle and 0.36 ± 0.03 ppm in brain. There were significant differences in levels of mercury, selenium, and selenium: mercury molar ratios, among tissues. Mercury and selenium levels were correlated in kidney and skin/scales. Mercury levels were highest in kidney, intermediate in muscle and liver, and lowest in brain and skin/scales; selenium levels were also highest in kidney, intermediate in liver, and were an order of magnitude lower in the white muscle and brain. Mercury levels in muscle, kidney and skin/scales were positively correlated with fish size (length). Selenium levels in muscle, kidney and liver were positively correlated with fish length, but in brain; selenium levels were negatively correlated with fish length. The selenium: mercury molar ratio was negatively correlated with fish length for white muscle, liver, kidney, and brain, particularly for fish over 50 cm in length, suggesting that older fish experience less protective advantages of selenium against mercury toxicity than smaller fish, and that consumers of bluefish similarly receive less advantage from eating larger fish. PMID:23202378

  1. Comparison of tissue injury from focused ultrasonic propulsion of kidney stones versus extracorporeal shock wave lithotripsy.

    PubMed

    Connors, Bret A; Evan, Andrew P; Blomgren, Philip M; Hsi, Ryan S; Harper, Jonathan D; Sorensen, Mathew D; Wang, Yak-Nam; Simon, Julianna C; Paun, Marla; Starr, Frank; Cunitz, Bryan W; Bailey, Michael R; Lingeman, James E

    2014-01-01

    Focused ultrasonic propulsion is a new noninvasive technique designed to move kidney stones and stone fragments out of the urinary collecting system. However, to our knowledge the extent of tissue injury associated with this technique is not known. We quantitated the amount of tissue injury produced by focused ultrasonic propulsion under simulated clinical treatment conditions and under conditions of higher power or continuous duty cycles. We compared those results to extracorporeal shock wave lithotripsy injury. A human calcium oxalate monohydrate stone and/or nickel beads were implanted by ureteroscopy in 3 kidneys of live pigs weighing 45 to 55 kg and repositioned using focused ultrasonic propulsion. Additional pig kidneys were exposed to extracorporeal shock wave lithotripsy level pulse intensity or continuous ultrasound exposure 10 minutes in duration using an ultrasound probe transcutaneously or on the kidney. These kidneys were compared to 6 treated with an unmodified Dornier HM3 lithotripter (Dornier Medical Systems, Kennesaw, Georgia) using 2,400 shocks at 120 shock waves per minute and 24 kV. Histological analysis was performed to assess the volume of hemorrhagic tissue injury created by each technique according to the percent of functional renal volume. Extracorporeal shock wave lithotripsy produced a mean ± SEM lesion of 1.56% ± 0.45% of functional renal volume. Ultrasonic propulsion produced no detectable lesion with simulated clinical treatment. A lesion of 0.46% ± 0.37% or 1.15% ± 0.49% of functional renal volume was produced when excessive treatment parameters were used with the ultrasound probe placed on the kidney. Focused ultrasonic propulsion produced no detectable morphological injury to the renal parenchyma when using clinical treatment parameters but produced injury comparable in size to that of extracorporeal shock wave lithotripsy when using excessive treatment parameters. Copyright © 2014 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

  2. 3D element imaging using NSECT for the detection of renal cancer: a simulation study in MCNP.

    PubMed

    Viana, R S; Agasthya, G A; Yoriyaz, H; Kapadia, A J

    2013-09-07

    This work describes a simulation study investigating the application of neutron stimulated emission computed tomography (NSECT) for noninvasive 3D imaging of renal cancer in vivo. Using MCNP5 simulations, we describe a method of diagnosing renal cancer in the body by mapping the 3D distribution of elements present in tumors using the NSECT technique. A human phantom containing the kidneys and other major organs was modeled in MCNP5. The element composition of each organ was based on values reported in literature. The two kidneys were modeled to contain elements reported in renal cell carcinoma (RCC) and healthy kidney tissue. Simulated NSECT scans were executed to determine the 3D element distribution of the phantom body. Elements specific to RCC and healthy kidney tissue were then analyzed to identify the locations of the diseased and healthy kidneys and generate tomographic images of the tumor. The extent of the RCC lesion inside the kidney was determined using 3D volume rendering. A similar procedure was used to generate images of each individual organ in the body. Six isotopes were studied in this work - (32)S, (12)C, (23)Na, (14)N, (31)P and (39)K. The results demonstrated that through a single NSECT scan performed in vivo, it is possible to identify the location of the kidneys and other organs within the body, determine the extent of the tumor within the organ, and to quantify the differences between cancer and healthy tissue-related isotopes with p ≤ 0.05. All of the images demonstrated appropriate concentration changes between the organs, with some discrepancy observed in (31)P, (39)K and (23)Na. The discrepancies were likely due to the low concentration of the elements in the tissue that were below the current detection sensitivity of the NSECT technique.

  3. Separate physiological roles for two isozymes of pyridine nucleotide-linked glycerol-3-phosphate dehydrogenase in chicken.

    NASA Technical Reports Server (NTRS)

    White, H. B., III; Kaplan, N. O.

    1972-01-01

    The isozymes considered are designated 'liver type' and 'muscle type' based on the tissue of highest concentration. Electrophoretic analysis shows that the liver type is found in small amounts or is undetectable in all tissues studied except liver. The muscle type is found in skeletal muscles and kidney. Presumptive hybrid enzymes occur at low levels in chicken liver and kidney. The tissue distribution of glyceron-3-P dehydrogenase in several birds capable of sustained flight is different than in chicken.

  4. Tissue metabolic changes for effects of pirfenidone in rats of acute paraquat poisoning by GC-MS.

    PubMed

    Ma, Jianshe; Sun, Fa; Chen, Bingbao; Tu, Xiaoting; Peng, Xiufa; Wen, Congcong; Hu, Lufeng; Wang, Xianqin

    2017-12-01

    We developed a metabolomic method to evaluate the effect of pirfenidone on rats with acute paraquat (PQ) poisoning, through the analysis of various tissues (lung, liver, kidney, and heart), by gas chromatography-mass spectrometry (GC-MS). Thirty-eight rats were randomly divided into a control group, an acute PQ (20 mg kg -1 ) poisoning group, a pirfenidone (20 mg kg -1 ) treatment group, and a pirfenidone (40 mg kg -1 ) treatment group. Partial least squares-discriminate analysis (PLS-DA) revealed metabolic alterations in rat tissue samples from the two pirfenidone treatment groups after acute PQ poisoning. The PLS-DA 3D score chart showed that the rats in the acute PQ poisoning group were clearly distinguished from the rats in the control group. Also, the two pirfenidone treatment groups were distinguished from the acute PQ poisoning group and control group. Additionally, the pirfenidone (40 mg kg -1 ) treatment group was separated farther than the pirfenidone (20 mg kg -1 ) treatment group from the acute PQ poisoning group. Evaluation of the pathological changes in the rat tissues revealed that treatment with pirfenidone appeared to decrease pulmonary fibrosis in the acute PQ poisoning rats. The results indicate that pirfenidone induced beneficial metabolic alterations in the tissues of rats with acute PQ poisoning. Rats with acute PQ poisoning exhibited a certain reduction in biochemical indicators after treatment with pirfenidone, indicating that pirfenidone could protect liver and kidney function. Accordingly, the developed metabolomic approach proved to be useful to elucidate the effect of pirfenidone in rats of acute PQ poisoning.

  5. The effect of zinc on healing of renal damage in rats

    PubMed Central

    Salehipour, Mehdi; Monabbati, Ahmad; Ensafdaran, Mohammad Reza; Adib, Ali; Babaei, Amir Hossein

    2017-01-01

    Background: Several studies have previously been performed to promote kidney healing after injuries. Objectives: The aim of this study was to investigate the effect of zinc on renal healing after traumatic injury in rats. Materials and Methods: Forty healthy female rats were selected and one of their kidneys was incised. Half of the incisions were limited only to the cortex (renal injury type I) and the other ones reached the pelvocalyceal system of the kidney (renal injury type II). All the rats in the zinc treated group (case group) received 36.3 mg zinc sulfate (contained 8.25 mg zinc) orally. After 28 days, the damaged kidneys were removed for histopathological studies. Results: In the rats with type I injury, kidney inflammation of the case group was significantly lower than that of the control group. However, the result was not significant in rats with type II injury. Tissue loss and granulation tissue formation were significantly lower in the case group than the control group in both type I and II kidney injuries. Conclusions: Overall, Zinc can contribute to better healing of the rat’s kidneys after a traumatic injury. PMID:28975095

  6. Establishment of donor Chimerism Using Allogeneic Bone Marrow with AMP Cell Co-infusion

    DTIC Science & Technology

    2017-09-01

    the ideal solution. Combined mixed allogeneic chimerism induction and kidney transplantation has been shown to induce robust tolerance to the kidney ...induction to kidney allografts in non-human primates and humans despite the transience of donor chimerism. However, evidence indicates that durable mixed...chimerism may be required for tolerance induction to tissues or organs other than kidney . Amnion-derived multipotent progenitor (AMP) cells possess

  7. Formation of phosphatidylethanol from endogenous phosphatidylcholines in animal tissues from pig, calf, and goat.

    PubMed

    Luginbühl, Marc; Willem, Sytske; Schürch, Stefan; Weinmann, Wolfgang

    2018-02-01

    In the presence of alcohol, phosphatidylcholine (PC) is transformed to the direct alcohol biomarker phosphatidylethanol (PEth). This reaction is catalyzed by the enzyme phospholipase D (PLD) and dependent on substrate availability. As recent methods have solely focused on the determination of PEth, information about the PC composition was generally missing. To address this issue and monitor PC (16:0/18:1 and 16:0/18:2) and PEth (16:0/18:1 and 16:0/18:2) simultaneously, a reversed phase LC-MS/MS method based on a C8 core-shell column, coupled to a Sciex 5500 QTrap instrument was developed. By application of polarity switching, at first, PC was measured in ESI positive SRM mode, while PEth was determined at a later stage in ESI negative SRM mode. The PEth method was validated for human blood samples to show its robustness and subsequently applied for the investigation of systematic in vitro PEth formation in animal tissue samples (brain, kidney, liver, and blood) from a pig, a calf, and a goat. Homogenized tissue was incubated at 37°C with varying ethanol concentrations from 1 to 7g/kg (determined by HS-GC-FID) for 5h, whereby a sample was taken every 30min. For all tissue samples, an increase in PEth was measurable. PEth concentrations formed in blood remained below the LLOQ, in agreement with literature. Data analysis of Michaelis-Menten kinetics and PC within the tissue provided a detailed insight about PEth formation, as the occurrence of PEth species can be linked to the observed PC composition. The results of this study show that PEth formation rates vary from tissue to tissue and among different species. Furthermore, new recommendations for PEth analysis are presented. Copyright © 2018 Elsevier B.V. All rights reserved.

  8. Multiple immunofluorescence labelling of formalin-fixed paraffin-embedded (FFPE) tissue

    PubMed Central

    Robertson, David; Savage, Kay; Reis-Filho, Jorge S; Isacke, Clare M

    2008-01-01

    Background Investigating the expression of candidate genes in tissue samples usually involves either immunohistochemical labelling of formalin-fixed paraffin-embedded (FFPE) sections or immunofluorescence labelling of cryosections. Although both of these methods provide essential data, both have important limitations as research tools. Consequently, there is a demand in the research community to be able to perform routine, high quality immunofluorescence labelling of FFPE tissues. Results We present here a robust optimised method for high resolution immunofluorescence labelling of FFPE tissues, which involves the combination of antigen retrieval, indirect immunofluorescence and confocal laser scanning microscopy. We demonstrate the utility of this method with examples of immunofluorescence labelling of human kidney, human breast and a tissue microarray of invasive human breast cancers. Finally, we demonstrate that stained slides can be stored in the short term at 4°C or in the longer term at -20°C prior to images being collected. This approach has the potential to unlock a large in vivo database for immunofluorescence investigations and has the major advantages over immunohistochemistry in that it provides higher resolution imaging of antigen localization and the ability to label multiple antigens simultaneously. Conclusion This method provides a link between the cell biology and pathology communities. For the cell biologist, it will enable them to utilise the vast archive of pathology specimens to advance their in vitro data into in vivo samples, in particular archival material and tissue microarrays. For the pathologist, it will enable them to utilise multiple antibodies on a single section to characterise particular cell populations or to test multiple biomarkers in limited samples and define with greater accuracy cellular heterogeneity in tissue samples. PMID:18366689

  9. Patulin in apple juice and its risk assessments on albino mice.

    PubMed

    Al-Hazmi, Mansour A

    2014-07-01

    The contamination of apple juice with patulin mycotoxin is a major risk factor in food safety. This study focuses to assess the biochemical and histopathological effects of patulin in apple juice samples collected from different outlets retailing in Jeddah, Kingdom of Saudi Arabia. On the basis of the selected dose level, 152.5 ppb patulin/ml was administered daily orally for up to 6 weeks to male albino mice. The exposure to contaminated samples revealed significant elevation of all the studied blood parameters (alanine aminotransferase, aspartate aminotransferase and alkaline phosphatase activities as well as creatinine, urea and uric acid contents). On the other hand, and with regard to the accumulated neuronal toxicity of the tested dose level, the toxic signs were recorded as significant increase in the aggressive and locomotor behavioral changes. In addition, the brain areas monoamines concentration revealed variable increased changes. The potential maximal changes in norepinephrine, dopamine and serotonin5-hydroxytryptamine levels attained in cortex, hypothalamus, striatum, hippocampus, midbrain and pons and medulla were assessed. Moreover, the histological examination revealed degeneration and necrosis in liver tissues and degenerated glomeruli and hemorrhage between the tubules of the cortical region in kidney tissues. The study declared that patulin-contaminated (152.5 ppb) apple juice exhibited liver, kidney and neurotoxicological effects in 6 weeks orally administered mice. © The Author(s) 2012.

  10. Polyhalogenated compounds (PCBs, chlordanes, HCB and BFRs) in four polar bears (Ursus maritimus) that swam malnourished from East Greenland to Iceland.

    PubMed

    Vetter, Walter; Gall, Vanessa; Skírnisson, Karl

    2015-11-15

    Levels of organohalogen compounds (PCBs, chlordane, PBB 153, PBDEs, HCB) were determined in adipose tissue, liver, kidney and muscle of four polar bears which swam and/or drifted to Iceland in extremely malnourished condition. Since the colonization in the 9th century polar bears have been repeatedly observed in Iceland. However, in recent years three of the animals have clearly left their natural habitat in poor condition in May or June, i.e. at the end of the major feeding season. The fourth bear is believed to have drifted with melting ice to North-Eastern Iceland in mid-winter. The concentrations of the POPs were within the range or higher than the typical concentrations measured in polar bears from the East Greenland population. In addition to the targeted compounds, we tentatively detected Dechlorane 602 and its potential hydrodechlorinated Cl11-metabolite in all samples. Moreover, a polychlorinated compound which partly co-eluted with PCB 209 was detected in all liver samples but not in adipose tissue, kidney or muscle. The mass spectrum of the potential metabolite did not allow determining its structure. Polar bears are good swimmers and can reach Iceland from the ice edge of East Greenland within a few days. Potential reasons for the swims are briefly discussed. Copyright © 2015 Elsevier B.V. All rights reserved.

  11. Kidney Biopsy Adequacy: A Metric-based Study.

    PubMed

    Ferrer, German; Andeen, Nicole K; Lockridge, Joseph; Norman, Douglas; Foster, Bryan R; Houghton, Donald C; Troxell, Megan L

    2018-06-05

    There are differences in renal biopsy yield related to on-site evaluation, tissue division, and operator, among others. To understand these variations, we collected adequacy-associated data (%cortex, glomeruli, arteries, length) from consecutive native and allograft kidney biopsies over a 22-month period. In total, 1332 biopsies (native: 873, allograft: 459) were included, 617 obtained by nephrologists, 663 by radiologists, and 559 with access to on-site division. Proceduralists with access to on-site evaluation had significantly lower inadequacy rates and better division of tissue for light microscopy (LM), immunofluorescence, and electron microscopy than those without access to on-site evaluation. Radiologists in our region were significantly less likely to have access to on-site evaluation than nephrologists. On multivariate analysis for native kidney biopsies, the effect of having a radiologist perform the biopsy and having access to on-site division were both significant predictors of obtaining greater calculated amount of cortex for LM. Despite the trend for radiologists to obtain more tissue in general, biopsies from nephrologists contained a greater percentage of cortex and were more likely to be considered adequate for LM (native kidney inadequacy rate for LM: 1.11% vs. 5.41%, P=0.0086). Biopsies in which inadequate or marginal cortical tissue was submitted for LM had only minor decreases in the amount of cortex submitted for immunofluorescence and electron microscopy, revealing an opportunity for improved specimen triaging when limited tissue is obtained. In conclusion, both on-site evaluation/division and proceduralist significantly affect quantitative kidney biopsy metrics, which in turn affects the pathologist's ability to render an accurate diagnosis with appropriate prognostic information for the patient and treating nephrologist.

  12. Involvement of S100A8/A9-TLR4-NLRP3 Inflammasome Pathway in Contrast-Induced Acute Kidney Injury.

    PubMed

    Tan, Xuexian; Zheng, Xiaohe; Huang, Zena; Lin, Jiaqiong; Xie, Chuli; Lin, Yan

    2017-01-01

    Contrast-induced acute kidney injury (CIAKI) is a common cause of hospital-acquired acute kidney injury (AKI). S100A8/A9-TLR4-NLRP3 inflammasome pathway triggers inflammation, apoptosis and tissue injury in several AKI models. Nevertheless, the underlying mechanism of S100A8/A9-TLR4-NLRP3 inflammasome pathway in CIKAI is not clear. We aimed to investigate the possible role of S100A8/A9-TLR4-NLRP3 inflammasome in the pathophysiology of CIAKI. We treated male rats and NRK-52E cells by iopromide to establish in vivo and in vitro models of CIAKI. We collected serum and urine samples to detect renal function. We obtained kidney tissue for histological analysis and detection of protein concentration. We used inhibitor of TLR4 and NLRP3-siRNA to further testify their role in CIAKI in NRK-52E cells. Iopromide caused elevation of SCr, BUN and NGAL level, decrease of endogenous creatinine clearance, morphological injury and tubular apoptosis, enhanced IL-1β and IL-18 expression, and increased expression of S100A8/A9, TLR4 and NLRP3 inflammsome. In NRK-52E cells, iopromide caused enhanced apoptotic rates and ROS generation, which could be ameliorated by inhibitor of TLR4 and NLRP3-siRNA. Moreover, inhibition of TLR4 dampened NLRP3 expression. S100A8/A9-TLR4-NLRP3 inflammasome pathway represented a key mechanism of CI-AKI, which provided a potential therapeutic target. © 2017 The Author(s). Published by S. Karger AG, Basel.

  13. Trace elements in loggerhead turtles (Caretta caretta) stranded in mainland Portugal: Bioaccumulation and tissue distribution.

    PubMed

    Nicolau, Lídia; Monteiro, Sílvia S; Pereira, Andreia T; Marçalo, Ana; Ferreira, Marisa; Torres, Jordi; Vingada, José; Eira, Catarina

    2017-07-01

    Pollution is among the most significant threats that endanger sea turtles worldwide. Waters off the Portuguese mainland are acknowledged as important feeding grounds for juvenile loggerheads. However, there is no data on trace element concentrations in marine turtles occurring in these waters. We present the first assessment of trace element concentrations in loggerhead turtles (Caretta caretta) occurring off the coast of mainland Portugal. Also, we compare our results with those from other areas and discuss parameters that may affect element concentrations. Trace element concentrations (As, Cd, Cu, Pb, Mn, Hg, Ni, Se, Zn) were determined in kidney, liver and muscle samples from 38 loggerheads stranded between 2011 and 2013. As was the only element with higher concentrations in muscle (14.78 μg g -1 ww) than in liver or kidney. Considering non-essential elements, Cd presented the highest concentrations in kidney (34.67 μg g -1 ) and liver (5.03 μg g -1 ). Only a weak positive link was found between renal Cd and turtle size. Inter-elemental correlations were observed in both liver and kidney tissues. Hepatic Hg values (0.30 ± 0.03 μg g -1 ) were higher than values reported in loggerheads in the Canary Islands but lower than in Mediterranean loggerheads. Cd concentrations in the present study were only exceeded by values found in turtles from the Pacific. Although many endogenous and exogenous parameters related with complex life cycle changes and wide geographic range may influence trace element accumulation, the concentrations of Cd are probably related to the importance of crustaceans in loggerhead diet in the Portuguese coast. Copyright © 2017 Elsevier Ltd. All rights reserved.

  14. Effects of Orthosiphon grandiflorus, Hibiscus sabdariffa and Phyllanthus amarus extracts on risk factors for urinary calcium oxalate stones in rats.

    PubMed

    Woottisin, Surachet; Hossain, Rayhan Zubair; Yachantha, Chatchai; Sriboonlue, Pote; Ogawa, Yoshihide; Saito, Seiichi

    2011-01-01

    We evaluated the antilithic effect of Orthosiphon grandiflorus, Hibiscus sabdariffa and Phyllanthus amarus extracts on known risk factors for calcium oxalate stones in rats. We divided 30 male Wistar rats into 5 equal groups. Controls were fed a standard diet and the remaining groups received a 3% glycolate diet for 4 weeks to induce hyperoxaluria. One glycolate fed group served as the untreated group and the others were given oral extracts of Orthosiphon grandiflorus, Hibiscus sabdariffa or Phyllanthus amarus at a dose of 3.5 mg daily. We collected 24-hour urine and blood samples. Kidneys were harvested for histological examination. We measured the renal tissue content of calcium and oxalate. The Hibiscus sabdariffa group showed significantly decreased serum oxalate and glycolate, and higher oxalate urinary excretion. The Phyllanthus amarus group showed significantly increased urinary citrate vs the untreated group. Histological examination revealed less CaOx crystal deposition in the kidneys of Hibiscus sabdariffa and Phyllanthus amarus treated rats than in untreated rats. Those rats also had significantly lower renal tissue calcium content than untreated rats. All parameters in the Orthosiphon grandiflorus treated group were comparable to those in the untreated group. Hibiscus sabdariffa and Phyllanthus amarus decreased calcium crystal deposition in the kidneys. The antilithic effect of Hibiscus sabdariffa may be related to decreased oxalate retention in the kidney and more excretion into urine while that of Phyllanthus amarus may depend on increased urinary citrate. In contrast, administering Orthosiphon grandiflorus had no antilithic effect. Copyright © 2011 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

  15. High-Resolution Imaging of Selenium in Kidneys: A Localized Selenium Pool Associated with Glutathione Peroxidase 3

    PubMed Central

    Malinouski, Mikalai; Kehr, Sebastian; Finney, Lydia; Vogt, Stefan; Carlson, Bradley A.; Seravalli, Javier; Jin, Richard; Handy, Diane E.; Park, Thomas J.; Loscalzo, Joseph; Hatfield, Dolph L.

    2012-01-01

    Abstract Aim: Recent advances in quantitative methods and sensitive imaging techniques of trace elements provide opportunities to uncover and explain their biological roles. In particular, the distribution of selenium in tissues and cells under both physiological and pathological conditions remains unknown. In this work, we applied high-resolution synchrotron X-ray fluorescence microscopy (XFM) to map selenium distribution in mouse liver and kidney. Results: Liver showed a uniform selenium distribution that was dependent on selenocysteine tRNA[Ser]Sec and dietary selenium. In contrast, kidney selenium had both uniformly distributed and highly localized components, the latter visualized as thin circular structures surrounding proximal tubules. Other parts of the kidney, such as glomeruli and distal tubules, only manifested the uniformly distributed selenium pattern that co-localized with sulfur. We found that proximal tubule selenium localized to the basement membrane. It was preserved in Selenoprotein P knockout mice, but was completely eliminated in glutathione peroxidase 3 (GPx3) knockout mice, indicating that this selenium represented GPx3. We further imaged kidneys of another model organism, the naked mole rat, which showed a diminished uniformly distributed selenium pool, but preserved the circular proximal tubule signal. Innovation: We applied XFM to image selenium in mammalian tissues and identified a highly localized pool of this trace element at the basement membrane of kidneys that was associated with GPx3. Conclusion: XFM allowed us to define and explain the tissue topography of selenium in mammalian kidneys at submicron resolution. Antioxid. Redox Signal. 16, 185–192. PMID:21854231

  16. Association between Randall's Plaque and Calcifying Nanoparticles

    NASA Technical Reports Server (NTRS)

    Citfcioglu, Neva; Vejdani, Kaveh; Lee, Olivia; Mathew, Grace; Aho, Katja M.; Kajander, Olavi; McKay, David S.; Jones, Jeffrey A.; Feiveson, Alan H.; Stoller, Marshall L.

    2007-01-01

    Randall initially described calcified subepithelial papillary plaques, which he hypothesized as nidi for kidney stone formation. The discovery of calcifying nanoparticles (CNP) in many calcifying processes of human tissues has raised another hypothesis about their possible involvement in urinary stone formation. This research is the first attempt to investigate the potential association of these two hypotheses. We collected renal papilla and blood samples from 17 human patients who had undergone laparoscopic nephrectomy due to neoplasia. Immunohistochemical staining (IHS) was applied on the tissue samples using monoclonal antibody 8D10 (mAb) against CNP. Homogenized papillary tissues and serum samples were cultured for CNP. Scanning electron microscopy (SEM) and energy dispersive X-ray spectroscopy (EDS) analysis were performed on fixed papillary samples. Randall's plaques were visible on gross inspection in 11 out of 17 collected samples. IHS was positive for CNP antigen in 8 of these 11 visually positive samples, but in only 1 of the remaining 6 samples. SEM revealed spherical apatite formations in 14 samples, all of which had calcium and phosphate peaks detected by EDS analysis. From this study, there was some evidence of a link between the presence of Randall's plaques and the detection of CNP, also referred to as nanobacteria. Although causality was not demonstrated, these results suggest that further studies with negative control samples should be made to explore the etiology of Randall's plaque formation, thus leading to a better understanding of the pathogenesis of stone formation.

  17. 9 CFR 311.3 - Hog cholera.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... kidneys and the lymph nodes which resemble lesions of hog cholera, they shall be regarded as those of hog... kidneys and lymph nodes of carcasses of hogs which appeared normal on ante-mortem inspection, further..., characteristic lesions of hog cholera are found in some organ or tissue in addition to those in the kidneys or in...

  18. 9 CFR 311.3 - Hog cholera.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... kidneys and the lymph nodes which resemble lesions of hog cholera, they shall be regarded as those of hog... kidneys and lymph nodes of carcasses of hogs which appeared normal on ante-mortem inspection, further..., characteristic lesions of hog cholera are found in some organ or tissue in addition to those in the kidneys or in...

  19. Tissue content of mercury in rats given methylmercuric chloride orally: influence of intestinal flora

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

    Rowland, I.R.; Davies, M.J.; Evans, J.G.

    1980-05-01

    The effect of intestinal flora on the absorption and disposition of mercury in tissues was investigated using conventional rats, and rats treated with antibiotics to eliminate their gut flora. Antibiotic-treated rats given (/sup 203/Hg) -labeled methylmercuric chloride orally had significantly more mercury in their tissues, especially in kidney, brain, lung, blood, and skeletal muscle, and also excreted less mercury in the feces than conventional rats. Furthermore, in the kidneys of the antibiotic-treated rats, the proportion of mercury present as organic mercury was greater than in the kidneys of the conventional rats. The results support the hypothesis that the metabolism ofmore » methylmercuric chloride by the gut flora reduces the tissue content of mercury. When rats were administered 10 mg methylmercuric chloride/Kg.day for 6 days, four or five of those given antibiotics developed neurological symptoms of toxicity, whereas only one of five conventional rats given methylmercuric chloride was affected.« less

  20. Quantitation of two endogenous lactose-inhibitable lectins in embryonic and adult chicken tissues

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

    Beyer, E.C.; Barondes, S.H.

    Two lactose-binding lectins from chicken tissues, chicken-lactose-lectin-I (CLL-I) and chicken-lactose-lectin-II (CLL-II) were quantified with a radioimmunoassay in extracts of a number of developing and adult chicken tissues. Both lectins could be measured in the same extract without separation, because they showed no significant immunological cross- reactivity. Many embryonic and adult tissues, including brain, heart, intestine, kidney, liver, lung, muscle, pancreas, and spleen, contained one or both lectins, although their concentrations differed markedly. For example, embryonic muscle, the richest source of CLL-I contained only traces of CLL-II whereas embryonic kidney, a very rich source of CLL-II contained substantial CLL-I. In bothmore » muscle and kidney, lectin levels in adulthood were much lower than in the embryonic state. In contrast, CLL-I in liver and CLL-II in intestine were 10-fold to 30-fold more concentrated in the adult than in the 15-d embryo. CLL-I and CLL-II from several tissues were purified by affinity chromatography and their identity in the various tissues was confirmed by polyacrylamide gel electrophoresis, isoelectric focusing, and peptide mapping. The results suggest that these lectins might have different functions in the many developing and adult tissues in which they are found.« less

  1. Angiogenic effects of borate glass microfibers in a rodent model.

    PubMed

    Lin, Yinan; Brown, Roger F; Jung, Steven B; Day, Delbert E

    2014-12-01

    The primary objective of this research was to evaluate the use of bioactive borate-based glass microfibers for angiogenesis in soft tissue repair applications. The effect of these fibers on growth of capillaries and small blood vessels was compared to that of 45S5 silica glass microfibers and sham implant controls. Compressed mats of three types of glass microfibers were implanted subcutaneously in rats and tissues surrounding the implant sites histologically evaluated 2-4 weeks post surgery. Bioactive borate glass 13-93B3 supplemented with 0.4 wt % copper promoted extensive angiogenesis as compared to silica glass microfibers and sham control tissues. The angiogenic responses suggest the copper-containing 13-93B3 microfibers may be effective for treating chronic soft tissue wounds. A second objective was to assess the possible systemic cytotoxicity of dissolved borate ions and other materials released from implanted borate glass microfibers. Cytotoxicity was assessed via histological evaluation of kidney tissue collected from animals 4 weeks after subcutaneously implanting high amounts of the borate glass microfibers. The evaluation of the kidney tissue from these animals showed no evidence of chronic histopathological changes in the kidney. The overall results indicate the borate glass microfibers are safe and effective for soft tissue applications. © 2014 Wiley Periodicals, Inc.

  2. 21 CFR 556.113 - Ceftiofur.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... desfuroylceftiofur (marker residue) are: (i) Kidney (target tissue). 0.25 parts per million (ppm). (ii)Liver. 3 ppm. (iii) Muscle. 2 ppm. (3) Cattle. The tolerances for desfuroylceftiofur (marker residue) are: (i) Kidney...

  3. 21 CFR 556.113 - Ceftiofur.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... desfuroylceftiofur (marker residue) are: (i) Kidney (target tissue). 0.25 parts per million (ppm). (ii)Liver. 3 ppm. (iii) Muscle. 2 ppm. (3) Cattle. The tolerances for desfuroylceftiofur (marker residue) are: (i) Kidney...

  4. Diuretic renography in hydronephrosis: renal tissue tracer transit predicts functional course and thereby need for surgery.

    PubMed

    Schlotmann, Andreas; Clorius, John H; Clorius, Sandra N

    2009-10-01

    The recognition of those hydronephrotic kidneys which require therapy to preserve renal function remains difficult. We retrospectively compared the 'tissue tracer transit' (TTT) of (99m)Tc-mercaptoacetyltriglycine ((99m)Tc-MAG(3)) with 'response to furosemide stimulation' (RFS) and with 'single kidney function < 40%' (SKF < 40%) to predict functional course and thereby need for surgery. Fifty patients with suspected unilateral obstruction and normal contralateral kidney had 115 paired (baseline/follow-up) (99m)Tc-MAG(3) scintirenographies. Three predictions of the functional development were derived from each baseline examination: the first based on TTT (visually assessed), the second on RFS and the third on SKF < 40%. Each prediction also considered whether the patient had surgery. Possible predictions were 'better', 'worse' or 'stable' function. A comparison of SKF at baseline and follow-up verified the predictions. The frequency of correct predictions for functional improvement following surgery was 8 of 10 kidneys with delayed TTT, 9 of 22 kidneys with obstructive RFS and 9 of 21 kidneys with SKF < 40%; for functional deterioration without surgery it was 2 of 3 kidneys with delayed TTT, 3 of 20 kidneys with obstructive RFS and 3 of 23 kidneys with SKF < 40%. Without surgery 67 of 70 kidneys with timely TTT maintained function. Without surgery 0 of 9 kidneys with timely TTT but obstructive RFS and only 1 of 16 kidneys with timely TTT but SKF < 40% lost function. Delayed TTT appears to identify the need for therapy to preserve function of hydronephrotic kidneys, while timely TTT may exclude risk even in the presence of an obstructive RFS or SKF < 40%.

  5. Evaluation of bovine abortion cases and tissue suitability for identification of infectious agents in California diagnostic laboratory cases from 2007 to 2012.

    PubMed

    Clothier, K; Anderson, M

    2016-03-15

    Establishing a definitive cause of bovine abortion is a challenging problem faced by veterinary practitioners and diagnosticians. Detection of an infectious or noninfectious source for abortion may facilitate interventions that mitigate future fetal loss in the herd. The purposes of this study were to identify the most common causes of bovine abortion in cases submitted to the California Animal Health and Food Safety Laboratory System, Davis (CAHFS) from 2007 to 2013 and to determine if detection of infectious pathogens differed with the fetal tissue evaluated. Records of 665 bovine abortion cases of 709 animals were reviewed for pathologic diagnoses, test methods used to identify causative conditions, and which tissues yielded successful identification of infectious agents associated with abortion. Over 58% of abortions were attributed to an infectious cause and 46.9% had an infectious agent identified. The most common infectious conditions were Epizootic Bovine Abortion (EBA) (16.2% of all fetuses), other fetal bacterial infections (14.7% of all fetuses), and Neospora caninum (9.3% of all fetuses.) The bacterium associated with EBA (currently named Pajaroellobacter abortibovis) was most commonly identified by immunohistochemistry (IHC) in lymphoid organs (thymus and spleen); N. caninum IHC was most frequently positive in brain, kidney, and placenta. In cases of pathogenic and opportunistic bacterial infections, abomasal samples yielded a significantly greater proportion of definitive aerobic culture results than lung or liver tissues. Direct fluorescent antibody test results for Bovine Viral Diarrhea Virus testing were identical between lung and kidney tissues and nearly identical (96.0%) for Bovine Herpesvirus I. Noninfectious abortive conditions included fetal stress (10.5%), dystocia (3.9%), congenital defects (3.3%), toxicological or mineral problems (1.8%), and death of the cow (1.1%). Just over 20% of the aborted fetuses had no gross or histopathological lesions to explain the abortion. This review highlights the need for submission of critical samples including abomasal contents, lymphoid tissues (thymus, spleen, and lymph nodes), and brain to maximize the diagnosticians' ability to identify causes of abortion. Copyright © 2016 Elsevier Inc. All rights reserved.

  6. The use of histology in 638 coronial post-mortem examinations of adults: an audit.

    PubMed

    Langlois, Neil E I

    2006-10-01

    An audit was performed to determine the effectiveness of histological sampling of forensic post-mortem cases based on a review of three years' data, which comprised 638 adult autopsy cases. During the study period organs and tissues that appeared macroscopically normal and abnormal were extensively sampled. Histology was regarded as in some way contributory (providing, altering or confirming a cause of death) 53% of the time. The use of histology provided the cause of death in 49 (24%) of the 203 cases not given a cause of death after the completion of the macroscopic examination. When an interim cause of death had been supplied following the completion of the gross examination it was changed in 4.8% of cases, but there were no changes of the manner of death. The majority of the histological diagnoses or discrepancies involved the lungs and the heart. All diagnoses relevant to determining the cause of death would have been made if samples had been taken only from the left ventricle, right ventricle, coronary arteries, lungs, kidneys and brain with any tissue or organ that appeared abnormal macroscopically. A macroscopically identified abnormality that appeared to have been responsible for death was not sampled in 20 cases; consequently, more attention will be paid to sampling macroscopically abnormal tissues. As a result of this audit histology sampling practice has been revised and will be re-audited in the future.

  7. Mesenchymal stem cells correct haemodynamic dysfunction associated with liver injury after extended resection in a pig model.

    PubMed

    Tautenhahn, Hans-Michael; Brückner, Sandra; Uder, Christiane; Erler, Silvio; Hempel, Madlen; von Bergen, Martin; Brach, Janine; Winkler, Sandra; Pankow, Franziska; Gittel, Claudia; Baunack, Manja; Lange, Undine; Broschewitz, Johannes; Dollinger, Matthias; Bartels, Michael; Pietsch, Uta; Amann, Kerstin; Christ, Bruno

    2017-06-01

    In patients, acute kidney injury (AKI) is often due to haemodynamic impairment associated with hepatic decompensation following extended liver surgery. Mesenchymal stem cells (MSCs) supported tissue protection in a variety of acute and chronic diseases, and might hence ameliorate AKI induced by extended liver resection. Here, 70% liver resection was performed in male pigs. MSCs were infused through a central venous catheter and haemodynamic parameters as well as markers of acute kidney damage were monitored under intensive care conditions for 24 h post-surgery. Cytokine profiles were established to anticipate the MSCs' potential mode of action. After extended liver resection, hyperdynamic circulation, associated with hyponatraemia, hyperkalaemia, an increase in serum aldosterone and low urine production developed. These signs of hepatorenal dysfunction and haemodynamic impairment were corrected by MSC treatment. MSCs elevated PDGF levels in the serum, possibly contributing to circulatory homeostasis. Another 14 cytokines were increased in the kidney, most of which are known to support tissue regeneration. In conclusion, MSCs supported kidney and liver function after extended liver resection. They probably acted through paracrine mechanisms improving haemodynamics and tissue homeostasis. They might thus provide a promising strategy to prevent acute kidney injury in the context of post-surgery acute liver failure.

  8. Malignant lymphoma in a West Indian manatee (Trichechus manatus).

    PubMed

    Hammer, Anne S; Klausen, Bjarne; Knold, Steffen; Dietz, Hans H; Dutoit, Stephen J Hamilton

    2005-10-01

    We identified a malignant lymphoma infiltrating the lung, liver, kidney, mesenteric lymph nodes, and eye as the cause of death in a male West Indian manatee (Trichechus manatus). Diagnosis was based on gross, histopathologic, and immunohistochemical studies. Tissue samples from ten organs were included in a tissue microarray and sections from this array were subjected to immunohistochemical staining. The cytoplasm of the neoplastic lymphocytes identified in six organs was positive for CD3, a marker for T-cell differentiation. The neoplastic cells were negative for CD79alpha, a marker for B-cell differentiation. The cause of this neoplasm was not determined. This is the first report of malignant lymphoma in the mammal order Sirenia.

  9. Decreased Nephrin and GLEPP-1, But Increased VEGF, Flt-1, and Nitrotyrosine, Expressions in Kidney Tissue Sections From Women With Preeclampsia

    PubMed Central

    Zhao, Shuang; Gu, Xin; Groome, Lynn J.; Wang, Yuping

    2011-01-01

    Renal injury is a common pathophysiological feature in women with preeclampsia as evidenced by increased protein leakage (proteinuria) and glomerular injury (glomerular endotheliosis). Recently, podocyturia was found in preeclampsia, suggesting podocyte shedding occurs in this pregnancy disorder. However, podocyte function in preeclampsia is poorly understood. In this study, the authors have examined podocyte-specific protein expressions for nephrin, glomerular epithelial protein 1 (GLEPP-1), and ezrin in kidney biopsy tissue sections from women with preeclampsia. Expressions for vascular endothelial growth factor (VEGF) and its receptor Flt-1 and oxidative stress marker nitrotyrosine and antioxidant CuZn-superoxide dismutase (CuZn-SOD) were also examined. Kidney tissue sections from nonhypertensive and chronic hypertensive participants were stained as controls. The findings were (1) nephrin and GLEPP-1 were mainly expressed in glomerular podocytes; (2) ezrin was expressed in both glomerular podocytes and tubular epithelial cells; (3) compared to tissue sections from nonhypertensive and chronic hypertensive participants, nephrin and GLEPP-1 expressions were much reduced in tissue sections from preeclampsia and ezrin expression was reduced in podocytes; (4) enhanced VEGF, Flt-1, and nitrotyrosine, but reduced CuZn-SOD, expressions were observed in both glomerular podocytes and endothelial cells in tissue sections from preeclampsia; and (5) the expression pattern for nephrin, GLEPP-1, ezrin, VEGF, Flt-1, and CuZn-SOD were similar between tissue sections from nonhypertensive and chronic hypertensive participants. Although the authors could not conclude from this biopsy study whether the podocyte injury is the cause or effect of the preeclampsia phenotype, the data provide compelling evidence that podocyte injury accompanied by altered angiogenesis process and increased oxidative stress occurs in kidney of patients with preeclampsia. PMID:19528353

  10. Pharmacokinetic evaluation of tissue distribution of pirfenidone and its metabolites for idiopathic pulmonary fibrosis therapy.

    PubMed

    Togami, Kohei; Kanehira, Yukimune; Tada, Hitoshi

    2015-05-01

    Pirfenidone is the first and only clinically used anti-fibrotic drug for the treatment of idiopathic pulmonary fibrosis (IPF). It was reported previously that pirfenidone metabolites (5-hydroxypirfenidone and 5-carboxypirfenidone) also have anti-fibrotic effects. The present study evaluated the distribution of pirfenidone and its metabolites in the lung, liver and kidney tissues in rats. The time course for the different concentrations of pirfenidone, 5-hydroxypirfenidone and 5-carboxypirfenidone in the lung tissue following oral administration (30 mg/kg) to rats was lower than that in plasma, and the area under the drug concentration-time curve (AUC) ratios of lung/plasma for pirfenidone, 5-hydroxypirfenidone and 5-carboxypirfenidone were 0.52, 0.40 and 0.61, respectively. In in vitro transport experiments, the basolateral-to-apical transport of pirfenidone and its metabolites through the model of lung epithelial cell (Calu-3) monolayers was not significantly different from their apical-to-basolateral transport. In binding experiments, the binding rate of these drugs to the lung tissue was lower than that to the plasma protein. These findings suggest that the low distribution of pirfenidone and its metabolites in the lungs was based on their low affinities with lung tissue and not the transport characteristics of lung epithelial cells. On the other hand, the AUC ratios of liver/plasma for pirfenidone and 5-carboxypirfenidone were 2.3 and 6.5 and the AUC ratios of kidney/plasma were 1.5 and 20, respectively. The binding rates to the liver and kidney tissues were higher than those to the plasma protein. These results suggest that high concentrations of these drugs were found in the liver and kidney tissues. Copyright © 2014 John Wiley & Sons, Ltd.

  11. Validation of Endogenous Internal Real-Time PCR Controls in Renal Tissues

    PubMed Central

    Cui, Xiangqin; Zhou, Juling; Qiu, Jing; Johnson, Martin R.; Mrug, Michal

    2009-01-01

    Background Endogenous internal controls (‘reference’ or ‘housekeeping’ genes) are widely used in real-time PCR (RT-PCR) analyses. Their use relies on the premise of consistently stable expression across studied experimental conditions. Unfortunately, none of these controls fulfills this premise across a wide range of experimental conditions; consequently, none of them can be recommended for universal use. Methods To determine which endogenous RT-PCR controls are suitable for analyses of renal tissues altered by kidney disease, we studied the expression of 16 commonly used ‘reference genes’ in 7 mildly and 7 severely affected whole kidney tissues from a well-characterized cystic kidney disease model. Expression levels of these 16 genes, determined by TaqMan® RT-PCR analyses and Affymetrix GeneChip® arrays, were normalized and tested for overall variance and equivalence of the means. Results Both statistical approaches and both TaqMan- and GeneChip-based methods converged on 3 out of the 4 top-ranked genes (Ppia, Gapdh and Pgk1) that had the most constant expression levels across the studied phenotypes. Conclusion A combination of the top-ranked genes will provide a suitable endogenous internal control for similar studies of kidney tissues across a wide range of disease severity. PMID:19729889

  12. Crataegus songarica methanolic extract accelerates enzymatic status in kidney and heart tissue damage in albino rats and its in vitro cytotoxic activity.

    PubMed

    Ganie, Showkat Ahmad; Ali Dar, Tanveer; Zargar, Sabuhi; Bhat, Aashiq Hussain; Dar, Khalid Bashir; Masood, Akbar; Zargar, Mohammad Afzal

    2016-07-01

    Crataegus songarica K. Koch (Rosaceae) has been used in folk medicine to treat various diseases. This study evaluates the effect of C. songarica methanol extract on the kidney and heart tissue damage of albino rats, and to determine cytotoxic activity of various extracts of songarica on various human cancer cell lines. Rats were divided into six groups, Group I received water only; Group II received CCl4 (1 mL/kg b wt) intraperitoneal; C. songarica extract (at doses of 100, 200 and 300 mg/kg b wt) orally for 15 days. Cytotoxic activity was determined by SRB method using MCF-7, HeLa, HepG2, SF-295, SW480 and IMR-32 cell lines. Compared with CCl4 group, administration of C. songarica extract at the dose of 300 mg/kg b wt, significantly decreases serum creatinine (59.74%), urea (40.23%) and cholesterol (54 mg/dL), MDA (0.007 nmol/mg protein) in kidney and (0.025 nmol/mg protein) in heart tissue, along with evaluation of GSH (209.79 ± 54.6), GR (111.45 ± 2.84), GPx (94.01 ± 14.80), GST (201.71) in kidney tissue and GSH (51.47 ± 1.47), GR (45.42 ± 6.69), GPx (77.19 ± 10.94), GST (49.89) in heart tissue. In addition, methanol, ethanol and ethyl acetate extracts exhibited potent anticancer activity on six cancer cell lines with IC50 values ranging from 28.57 to 85.106 µg/mL. Crataegus songarica methanol extract has a potential antioxidant effect as it protects the kidney and heart tissue against CCl4-induced toxicity, prevents DNA damage and showed strong anticancer activity.

  13. The evaluation of renal ischaemic damage: the value of CD10 monoclonal antibody staining and of biochemical assessments of tissue viability

    PubMed Central

    Tagboto, S; Griffiths, A Paul

    2007-01-01

    Background It is well recognised that there is often a disparity between the structural changes observed in the kidney following renal injury and the function of the organ. For this reason, we carried out studies to explore possible means of studying and quantifying the severity of renal ischaemic damage using a laboratory model. Methods To do this, freshly isolated rabbit kidney tissue was subjected to warm (37°C) or cold (1°C) ischaemia for 20 hours. Following this, the tissue was stained using Haematoxylin and Eosin (H+E), Periodic Schiff reagent (PAS) and the novel monoclonal antibody CD10 stain. Additionally, ischaemic damage to the kidneys was assessed by biochemical tests of tissue viability using formazan-based colorimetry. Results CD 10 antibody intensely stained the brush border of control kidney tissue with mild or no cytoplasmic staining. Cell injury was accompanied by a redistribution of CD10 into the lumen and cell cytoplasm. There was good correlation between a score of histological damage using the CD 10 monoclonal antibody stain and the biochemical assessment of viability. Similarly, a score of histological damage using traditional PAS staining correlated well with that using the CD10 antibody stain. In particular, the biochemical assay and the monoclonal antibody staining techniques were able to demonstrate the efficacy of Soltran (this solution is used cold to preserve freshly isolated human kidneys prior to transplantation) in preserving renal tissue at cold temperatures compared to other randomly selected solutions. Conclusion We conclude that the techniques described using the CD10 monoclonal antibody stain may be helpful in the diagnosis and assessment of ischaemic renal damage. In addition, biochemical tests of viability may have an important role in routine histopathological work by giving additional information about cellular viability which may have implications on the function of the organ. PMID:17531101

  14. Immunosuppressants

    MedlinePlus

    ... Menu Menu Search Home Prevention Kidney Disease Patients Organ Donation & Transplantation Professionals Events Advocacy Donate A to Z ... Exchange Programs Knowing Your Immunosuppressive (anti-rejection) Medications Organ and Tissue Donation The National Kidney Foundation (NKF) is the largest, ...

  15. Pharmacokinetics and tissue distribution of furanodiene W/O/W multiple emulsions in rats by a fast and sensitive HPLC-APCI-MS/MS method.

    PubMed

    Zhang, Li-Feng; Lu, Tao-Tao; Zhang, Shu-Qiu; Lin, Wen-Han; Li, Qing-Shan

    2013-12-01

    A sensitive and specific HPLC-APCI-MS/MS method was developed and validated for the quantification of furanodiene, a natural antitumor compound in rat plasma and tissues. W/O/W multiple emulsions of furanodiene, identified through microscope-observation and eosin staining method, were prepared with a two-step-procedure. Pharmacokinetics and tissue distribution were studied in rats after oral, intraperitoneal and intravenous injection with the dose of 5, 10 and 50 mg/kg, respectively. The assay achieved a good sensitivity and specificity for the determination of furanodiene in biological samples. The results showed that the concentration-time curves of furanodiene in rats after intravenous injection were fitted to a two-compartment model and the linear pharmacokinetic characteristic. The highest concentration in rat tissue was observed in the spleen, followed by heart, liver, lung, kidney, small intestine and brain. Comparing with the low concentration in plasma, furanodiene could be detected in various tissue samples after oral or intraperitoneal injection which indicated furanodiene had good and rapid tissue uptake. The results suggested that the wide tissue distribution of furanodiene could conduce to the therapeutic effects, but the short biological half-life limited its further application as an antitumor agent. The results are helpful for the structure modification of furanodiene as an antitumor candidate.

  16. Lipidomic Perturbations in Lung, Kidney, and Liver Tissues of p53 Knockout Mice Analyzed by Nanoflow UPLC-ESI-MS/MS.

    PubMed

    Park, Se Mi; Byeon, Seul Kee; Sung, Hyerim; Cho, Soo Young; Seong, Je Kyung; Moon, Myeong Hee

    2016-10-07

    Lipids are important signaling molecules regulating biological processes under normal and diseased conditions. Although p53 mutation is well-known for causing cancer, the relationship between p53-related tumorigenesis and altered lipid profile is unclear. We profiled differences in lipid expressions in liver, lung, and kidney in p53 knockout (KO) mice by high-speed quantitative analysis of 320 lipids (399 species identified) using nanoflow ultrahigh performance liquid chromatography-tandem mass spectrometry (nUPLC-MS/MS). Lung tissues were most severely affected by the lack of p53 gene, as shown by significant reduction (24-44%, P < 0.05) in total phosphatidylcholine (PC), phosphatidylethanolamine (PE), sphingomyelin (SM), diacylglycerol (DG), and triacylglycerol (TG), and significant increases (30-50%) in phosphatidylserine (PS), phosphatidylinositol (PI), and monohexosylceramide (MHC). MHC levels increased in all tissues. Dihexosylceramide (DHC) level decreased only in kidney tissue. Most PI, PS, and phosphatidic acid (PA) species showing significant increases contained a saturated acyl chain (18:0) in lung and liver tissues. Neutral glycerolipids (16:0/22:0-DG and most TGs with saturated and monounsaturated acyl chains) decreased 2-4-fold in the liver tissue. Our results suggest that the lack of p53 and altered lipid profiles are closely related, but as their changes vary from one tissue to another, the lipid alterations are tissue-specific.

  17. Detection of cocaine and benzoylecgonine in formalin fixed rat tissues.

    PubMed

    Hilal, Ahmet; Dağlioğlu, Nebīle; Battal, Dīlek; Yener, Fadīle; Dağlioğlu, Kenan

    2009-09-01

    The stability of drugs in formalin solution is an important factor in forensic investigation. Tissues (liver, lung, kidney, brain) taken from rats, which have been poisoned acutely with cocaine, were preserved in two different conditions, analyzed by GC-MS, and then compared. Organs of the first group were preserved and stored at -20 degrees C without adding formalin, whereas the organs of the second group were preserved and stored in formalin solution at room temperature (25 degrees C). Serum samples were taken immediately after poisoning and studied as well. In specimens stored at -20 degrees C, cocaine and its metabolite benzoylecgonine were detected in the tissues. Only benzoylecgonine was detected both in tissues and their formalin solution. It was observed that the distribution of cocaine in tissues had differed depending on the preservation conditions. The formalin solution in which benzoylecgonine was mostly detected was from liver. As a result, cocaine was detected in tissues stored at -20 degrees C. It is recommended that both the formalin-fixed tissues and formalin solution should be analyzed concurrently to assure the accurate results (LOD = 3 ng/ml).

  18. Systems Toxicology of Chemically Induced Liver and Kidney Injuries: Histopathology-Associated Gene Co-Expression Modules

    DTIC Science & Technology

    2016-01-04

    2016 (wileyonlinelibrary.com) DOI 10.1002/jat.3278Systems toxicology of chemically induced liver and kidney injuries: histopathology-associated gene...injuries that classify 11 liver and eight kidney histopathology endpoints based on dose-dependent activation of the identified modules. We showed that...well as determine whether the injury module activation was specific to the tissue of origin (liver and kidney ). The generated modules provide a link

  19. Depletion of penicillin G residues in heavy sows after intramuscular injection. Part II: application of kidney inhibition swab tests.

    PubMed

    Shelver, Weilin L; Lupton, Sara J; Newman, David J; Larsen, Steven; Smith, David J

    2014-07-30

    Sows (n = 126; 228 ± 30.1 kg) were administered daily IM doses of penicillin G procaine (33 000 IU/kg bw; 5× the label dose) for 3 consecutive days using three different administration patterns. Within treatment, six sows each were slaughtered on withdrawal day 5, 10, 15, 20, 25, 32, and 39. Tissues (injection site, kidney, liver, skeletal muscle) or body fluids (serum and urine) were screened for penicillin G using the KIS test, recently adopted by the USDA Food Safety and Inspection Service. The IM administration patterns had no discernible effect on penicillin G depletion. Residues were depleted more rapidly from liver and skeletal muscle and more slowly from kidney and urine. Kidney was the most sensitive and suitable tissue for detecting penicillin G residues on-site, with two positive results after a 39-day withdrawal period. Urine was the most suitable ante-mortem surrogate to predict the results of kidney tests.

  20. [Antioxidant properties of cluster rhenium compounds and their effect on erythropoiesis of rats with guerin carcinoma].

    PubMed

    Voronkova, Y S; Babiy, S O; Ivans'kar, L V; Shtemenko, O V; Shtemenko, N I

    2015-01-01

    Biochemical characteristics of kidneys, pe- ripheral blood and bone marrow of rats in model of tumor growth under introduction of cisplatin and cis-tetrachlorodi-μ-isobutyratodirhenium(III), cis-Re2(i-C3H7COO)2Cl4 (I) have been investigated. It was shown that introduction of I alone and together with cisplatin led to decrease of biochemical markers of oxidation of lipids and proteins in tissue homogenates of the kidneys, change of enzyme activity in the urea and tissue homogenates of the kidneys, by a decrease of filtration function of kidneys. Introduction of nanoliposomal forms of the rhenium cluster compound led to a practically normal morphological picture of bone marrow and increase of the RBC (by 60%) with normalization of hematocrit counts, and decrease of quantities of destructed RBC (3.2 times) in comparison with the tumor-bearing animals. A tentative scheme of influence of cluster rhenium compound on erythropoiesis through regulation of synthesis of erythropoietin in kidneys has been proposed.

  1. Comparative absorption, distribution, and excretion of titanium dioxide and zinc oxide nanoparticles after repeated oral administration.

    PubMed

    Cho, Wan-Seob; Kang, Byeong-Cheol; Lee, Jong Kwon; Jeong, Jayoung; Che, Jeong-Hwan; Seok, Seung Hyeok

    2013-03-26

    The in vivo kinetics of nanoparticles is an essential to understand the hazard of nanoparticles. Here, the absorption, distribution, and excretion patterns of titanium dioxide (TiO2) and zinc oxide (ZnO) nanoparticles following oral administration were evaluated. Nanoparticles were orally administered to rats for 13 weeks (7 days/week). Samples of blood, tissues (liver, kidneys, spleen, and brain), urine, and feces were obtained at necropsy. The level of Ti or Zn in each sample was measured using inductively coupled plasma-mass spectrometry. TiO₂ nanoparticles had extremely low absorption, while ZnO nanoparticles had higher absorption and a clear dose-response curve. Tissue distribution data showed that TiO₂ nanoparticles were not significantly increased in sampled organs, even in the group receiving the highest dose (1041.5 mg/kg body weight). In contrast, Zn concentrations in the liver and kidney were significantly increased compared with the vehicle control. ZnO nanoparticles in the spleen and brain were minimally increased. Ti concentrations were not significantly increased in the urine, while Zn levels were significantly increased in the urine, again with a clear dose-response curve. Very high concentrations of Ti were detected in the feces, while much less Zn was detected in the feces. Compared with TiO₂ nanoparticles, ZnO nanoparticles demonstrated higher absorption and more extensive organ distribution when administered orally. The higher absorption of ZnO than TiO₂ nanoparticles might be due to the higher dissolution rate in acidic gastric fluid, although more thorough studies are needed.

  2. Validation of a Real Time PCR for Classical Swine Fever Diagnosis

    PubMed Central

    Dias, Natanael Lamas; Fonseca Júnior, Antônio Augusto; Oliveira, Anapolino Macedo; Sales, Érica Bravo; Alves, Bruna Rios Coelho; Dorella, Fernanda Alves

    2014-01-01

    The viral disease classical swine fever (CSF), caused by a Pestivirus, is one of the major causes of economic losses for pig farming. The aim of this work was to validate a RT-qPCR using Taqman for detection of CSF in swine tissues. The parameters for the validation followed the specifications of the Manual of Diagnostic Tests and Vaccines for Terrestrial Animals of the World Organization for Animal Health (OIE) and the guide ABNT NBR ISO/IEC 17025:2005. The analysis of the 5′NTR region of CSF virus was performed in 145 samples from 29 infected pigs and in 240 samples from 80 pigs originated in the Brazilian CSF-free zone. The tissues tested were spleen, kidney, blood, tonsils, and lymph nodes. Sequencing of the positive samples for 5′NTR region was performed to evaluate the specificity of the RT-qPCR. Tests performed for the RT-qPCR validation demonstrated that the PCR assay was efficient in detecting RNA from CSF virus in all materials from different tissues of infected animals. Furthermore, RNA from CSF virus was not detected in samples of swine originated from the Brazilian CSF-free zone. Hence, it is concluded that RT-qPCR can be used as a complementary diagnostic for CSF. PMID:24818039

  3. Validation of a real time PCR for classical Swine Fever diagnosis.

    PubMed

    Dias, Natanael Lamas; Fonseca Júnior, Antônio Augusto; Oliveira, Anapolino Macedo; Sales, Erica Bravo; Alves, Bruna Rios Coelho; Dorella, Fernanda Alves; Camargos, Marcelo Fernandes

    2014-01-01

    The viral disease classical swine fever (CSF), caused by a Pestivirus, is one of the major causes of economic losses for pig farming. The aim of this work was to validate a RT-qPCR using Taqman for detection of CSF in swine tissues. The parameters for the validation followed the specifications of the Manual of Diagnostic Tests and Vaccines for Terrestrial Animals of the World Organization for Animal Health (OIE) and the guide ABNT NBR ISO/IEC 17025:2005. The analysis of the 5'NTR region of CSF virus was performed in 145 samples from 29 infected pigs and in 240 samples from 80 pigs originated in the Brazilian CSF-free zone. The tissues tested were spleen, kidney, blood, tonsils, and lymph nodes. Sequencing of the positive samples for 5'NTR region was performed to evaluate the specificity of the RT-qPCR. Tests performed for the RT-qPCR validation demonstrated that the PCR assay was efficient in detecting RNA from CSF virus in all materials from different tissues of infected animals. Furthermore, RNA from CSF virus was not detected in samples of swine originated from the Brazilian CSF-free zone. Hence, it is concluded that RT-qPCR can be used as a complementary diagnostic for CSF.

  4. Simultaneous determination of bioactive components of Radix Angelicae Sinensis-Radix Paeoniae Alba herb couple in rat plasma and tissues by UPLC-MS/MS and its application to pharmacokinetics and tissue distribution.

    PubMed

    Luo, Niancui; Li, Zhenhao; Qian, Dawei; Qian, Yefei; Guo, Jianming; Duan, Jin-Ao; Zhu, Min

    2014-07-15

    A highly sensitive and rapid ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) has been developed and validated for simultaneous quantification of seven components in rat plasma and five components in rat tissues after oral administration of the extracts of different combination Radix Angelicae Sinensis-Radix Paeoniae Alba herb couple and has been applied to compare the different pharmacokinetics and tissue distribution properties of these bioactive components. The extracts of Radix Angelicae Sinensis (RAS), Radix Paeoniae Alba (RPA) and Radix Angelicae Sinensis-Radix Paeoniae Alba herb couple (RRHC) were orally administrated to rats, respectively. The concentrations of ferulic acid, caffeic acid, vanillic acid, ligustilide, paeoniflorin, albiflorin and oxypaeoniflorin in rat plasma and the concentrations of ferulic acid, vanillic acid, paeoniflorin, albiflorin and oxypaeoniflorin in tissues were determined by UPLC-MS/MS. The plasma samples were pretreated by protein precipitation with methanol and the tissue samples were homogenated with water and pretreated by protein precipitation with methanol. Chromatographic separation was performed on a C18 column using 0.1% formic acid-acetonitrile as mobile phase for gradient elution. A triple quadrupole (TQ) tandem mass spectrometry equipped with an electrospray ionization source was used as detector operating both in positive and negative ionization mode and operated by multiple-reaction monitoring (MRM) scanning. Noncompartmental pharmacokinetic parameters were calculated by DAS 2.0 program. The differences between each group were compared by SPSS 16.0 with Independent-Samples T-test. The pharmacokinetic parameters (such as Cmax, Tmax, T1/2, AUC0-T, MRT0-T, Vz/F or CLz/F) of all the detected components between the single herb (RAS or RPA) and herb pair (RRHP) showed significant differences (P<0.05). It indicated that the compatibility of RAS and RPA could alter the pharmacokinetics features of each component. Tissue distribution results showed that ferulic acid, vanillic acid, paeoniflorin, albiflorin and oxypaeoniflorin mostly distributed in liver and kidney both in herb couple and single herb distributed most in liver and kidney. Compared with single herb, RRHC could increase or decrease the concentrations of five components at different time points compared with the sing herb. The results indicated the method was successfully applied to the comparative study on pharmacokinetics and tissue distribution of different combination of RRHC in rats. The compatibility of two Chinese herbs could alter the pharmacokinetics and tissue distribution properties of major bio-active components in the single herb. The results might be helpful for further investigation of compatibility mechanism of RRHC. Copyright © 2014 Elsevier B.V. All rights reserved.

  5. Application of kidney inhibition swab tests to evaluate penicillin-G residues in sow tissues and body fluids following intramuscular injection

    USDA-ARS?s Scientific Manuscript database

    Kidney inhibition swab (KIS) tests, recently adapted by the US FSIS for antibiotics on-site screening, were employed to evaluate the depletion of penicillin-G residues from kidney, liver, muscle, serum, and urine of sows after intramuscular (IM) penicillin-G procaine administration. Sows (n=130; 22...

  6. Endothelial sirtuin 1 inactivation enhances capillary rarefaction and fibrosis following kidney injury through Notch activation

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

    Kida, Yujiro; Zullo, Joseph A.; Renal Research Institute, Department of Physiology, New York Medical College, Valhalla, NY

    Peritubular capillary (PTC) rarefaction along with tissue fibrosis is a hallmark of chronic kidney disease (CKD). However, molecular mechanisms of PTC loss have been poorly understood. Previous studies have demonstrated that functional loss of endothelial sirtuin 1 (SIRT1) impairs angiogenesis during development and tissue damage. Here, we found that endothelial SIRT1 dysfunction causes activation of endothelial Notch1 signaling, which leads to PTC rarefaction and fibrosis following kidney injury. In mice lacking functional SIRT1 in the endothelium (Sirt1 mutant), kidney injury enhanced apoptosis and senescence of PTC endothelial cells with impaired endothelial proliferation and expanded myofibroblast population and collagen deposition. Comparedmore » to wild-type kidneys, Sirt1 mutant kidneys up-regulated expression of Delta-like 4 (DLL4, a potent Notch1 ligand), Hey1 and Hes1 (Notch target genes), and Notch intracellular domain-1 (NICD1, active form of Notch1) in microvascular endothelial cells (MVECs) post-injury. Sirt1 mutant primary kidney MVECs reduced motility and vascular assembly and enhanced senescence compared to wild-type kidney MVECs. This difference in the phenotype was negated with Notch inhibition. Concurrent stimulation of DLL4 and transforming growth factor (TGF)-β1 increased trans-differentiation of primary kidney pericytes into myofibroblast more than TGF-β1 treatment alone. Collectively, these results indicate that endothelial SIRT1 counteracts PTC rarefaction by repression of Notch1 signaling and antagonizes fibrosis via suppression of endothelial DLL4 expression. - Highlights: • SIRT1 represses Notch1 signaling in capillary endothelial cells in the kidney. • Endothelial SIRT1 is depleted in the kidney following injury. • Activation of endothelial Notch impairs angiogenesis in the kidney. • Increased expression of endothelial DLL4 enhances renal fibrosis.« less

  7. Substantial Differences between Organ and Muscle Specific Tracer Incorporation Rates in a Lactating Dairy Cow

    PubMed Central

    Burd, Nicholas A.; Hamer, Henrike M.; Pennings, Bart; Pellikaan, Wilbert F.; Senden, Joan M. G.; Gijsen, Annemie P.; van Loon, Luc J. C.

    2013-01-01

    We aimed to produce intrinsically L-[1-13C]phenylalanine labeled milk and beef for subsequent use in human nutrition research. The collection of the various organ tissues after slaughter allowed for us to gain insight into the dynamics of tissue protein turnover in vivo in a lactating dairy cow. One lactating dairy cow received a constant infusion of L-[1-13C]phenylalanine (450 µmol/min) for 96 h. Plasma and milk were collected prior to, during, and after the stable isotope infusion. Twenty-four hours after cessation of the infusion the cow was slaughtered. The meat and samples of the various organ tissues (liver, heart, lung, udder, kidney, rumen, small intestine, and colon) were collected and stored. Approximately 210 kg of intrinsically labeled beef (bone and fat free) with an average L-[1-13C]phenylalanine enrichment of 1.8±0.1 mole percent excess (MPE) was obtained. The various organ tissues differed substantially in L-[1-13C]phenylalanine enrichments in the tissue protein bound pool, the highest enrichment levels were achieved in the kidney (11.7 MPE) and the lowest enrichment levels in the skeletal muscle tissue protein of the cow (between 1.5–2.4 MPE). The estimated protein synthesis rates of the various organ tissues should be regarded as underestimates, particularly for the organs with the higher turnover rates and high secretory activity, due to the lengthened (96 h) measurement period necessary for the production of the intrinsically labeled beef. Our data demonstrates that there are relatively small differences in L-[1-13C]phenylalanine enrichments between the various meat cuts, but substantial higher enrichment values are observed in the various organ tissues. We conclude that protein turnover rates of various organs are much higher when compared to skeletal muscle protein turnover rates in large lactating ruminants. PMID:23826365

  8. Comparison of immunohistochemistry and polymerase chain reaction for detection of West Nile virus in naturally infected dead birds.

    PubMed

    Sandhu, Tejbir; Sidhu, Dalbinder; Dhillon, Major; Fang, Ying

    2010-10-04

    Credible vector-borne disease surveillance programs, especially in developing countries with limited resources, must include diagnostic tests that are efficient, inexpensive and simple and safe to administer while maintaining high levels of sensitivity and specificity. Since immunohistochemistry (IHC) includes most of these features, its sensitivity, specificity, predictive positive value (PPV) and predictive negative value (PNV) for West Nile virus (WNv) screening were compared to those of the gold standard, RT-PCR testing of kidney tissue in dead birds. IHC and RT-PCR were performed for WNv antigen on 41 dead birds (belonging to five orders) collected from the northwest region of the Riverside County of California. Fixed tissue sections were screened by IHC using polyclonal antibodies, and frozen kidney tissues were tested with RT-PCR. Kidney screening with IHC showed sensitivity, specificity, PPV and NPV of 95.45%, 73.68%, 80.77% and 93.33%, respectively. Based on WNv screening of kidney tissue, IHC and RT-PCR were in agreement with 95.45% (21/22) for positive dead birds and were in 100% (22/22) agreement when multi-organ screening by IHC was performed. The present study showed that IHC is as equally effective as RT-PCR in screening for WNv in dead birds. Therefore, IHC can effectively serve as a competent screening technique for those disease surveillance agencies that lack expensive RT-PCR technology while promoting safer biohazardous conditions, except at the initial stage of tissue collection.

  9. MRI-compatible pipeline for three-dimensional MALDI imaging mass spectrometry using PAXgene fixation.

    PubMed

    Oetjen, Janina; Aichler, Michaela; Trede, Dennis; Strehlow, Jan; Berger, Judith; Heldmann, Stefan; Becker, Michael; Gottschalk, Michael; Kobarg, Jan Hendrik; Wirtz, Stefan; Schiffler, Stefan; Thiele, Herbert; Walch, Axel; Maass, Peter; Alexandrov, Theodore

    2013-09-02

    MALDI imaging mass spectrometry (MALDI-imaging) has emerged as a spatially-resolved label-free bioanalytical technique for direct analysis of biological samples and was recently introduced for analysis of 3D tissue specimens. We present a new experimental and computational pipeline for molecular analysis of tissue specimens which integrates 3D MALDI-imaging, magnetic resonance imaging (MRI), and histological staining and microscopy, and evaluate the pipeline by applying it to analysis of a mouse kidney. To ensure sample integrity and reproducible sectioning, we utilized the PAXgene fixation and paraffin embedding and proved its compatibility with MRI. Altogether, 122 serial sections of the kidney were analyzed using MALDI-imaging, resulting in a 3D dataset of 200GB comprised of 2million spectra. We show that elastic image registration better compensates for local distortions of tissue sections. The computational analysis of 3D MALDI-imaging data was performed using our spatial segmentation pipeline which determines regions of distinct molecular composition and finds m/z-values co-localized with these regions. For facilitated interpretation of 3D distribution of ions, we evaluated isosurfaces providing simplified visualization. We present the data in a multimodal fashion combining 3D MALDI-imaging with the MRI volume rendering and with light microscopic images of histologically stained sections. Our novel experimental and computational pipeline for 3D MALDI-imaging can be applied to address clinical questions such as proteomic analysis of the tumor morphologic heterogeneity. Examining the protein distribution as well as the drug distribution throughout an entire tumor using our pipeline will facilitate understanding of the molecular mechanisms of carcinogenesis. Copyright © 2013 Elsevier B.V. All rights reserved.

  10. Production of monoclonal antibodies specific for antigens derived from tissue of chinook salmon (Oncorhynchus tshawytscha) affected with plasmacytoid leukemia.

    PubMed

    Newbound, G C; Markham, R J; Speare, D J; Saksida, S M; Després, B M; Horney, B S; Kibenge, F S; Sheppard, J A; Wright, G M; Kent, M L

    1993-09-01

    Two distinct monoclonal antibodies (MAB) were prepared for testing with kidney, spleen, and retrobulbar tissue imprints made from chinook salmon (Oncorhynchus tshawytscha) affected with plasmacytoid leukemia. (PL). Hybridomas were prepared from mice immunized with whole and lysed cells purified from renal or retrobulbar PL-positive tissues, which had been obtained from naturally and experimentally infected fish from British Columbia, Canada. The MAB reacted with at least 4 morphologically different cell types; fluorescence was associated with the plasma membrane and cytoplasm. The MAB also reacted with kidney imprints made from chinook salmon affected with a PL-like lymphoproliferative disease in California, indicating that these 2 diseases might be caused by a similar agent. The MAB did not react with any of the kidney or spleen imprints made from wild chinook salmon collected from a river in Ontario, Canada.

  11. Bioprinting of 3D Convoluted Renal Proximal Tubules on Perfusable Chips

    NASA Astrophysics Data System (ADS)

    Homan, Kimberly A.; Kolesky, David B.; Skylar-Scott, Mark A.; Herrmann, Jessica; Obuobi, Humphrey; Moisan, Annie; Lewis, Jennifer A.

    2016-10-01

    Three-dimensional models of kidney tissue that recapitulate human responses are needed for drug screening, disease modeling, and, ultimately, kidney organ engineering. Here, we report a bioprinting method for creating 3D human renal proximal tubules in vitro that are fully embedded within an extracellular matrix and housed in perfusable tissue chips, allowing them to be maintained for greater than two months. Their convoluted tubular architecture is circumscribed by proximal tubule epithelial cells and actively perfused through the open lumen. These engineered 3D proximal tubules on chip exhibit significantly enhanced epithelial morphology and functional properties relative to the same cells grown on 2D controls with or without perfusion. Upon introducing the nephrotoxin, Cyclosporine A, the epithelial barrier is disrupted in a dose-dependent manner. Our bioprinting method provides a new route for programmably fabricating advanced human kidney tissue models on demand.

  12. Bioprinting of 3D Convoluted Renal Proximal Tubules on Perfusable Chips

    PubMed Central

    Homan, Kimberly A.; Kolesky, David B.; Skylar-Scott, Mark A.; Herrmann, Jessica; Obuobi, Humphrey; Moisan, Annie; Lewis, Jennifer A.

    2016-01-01

    Three-dimensional models of kidney tissue that recapitulate human responses are needed for drug screening, disease modeling, and, ultimately, kidney organ engineering. Here, we report a bioprinting method for creating 3D human renal proximal tubules in vitro that are fully embedded within an extracellular matrix and housed in perfusable tissue chips, allowing them to be maintained for greater than two months. Their convoluted tubular architecture is circumscribed by proximal tubule epithelial cells and actively perfused through the open lumen. These engineered 3D proximal tubules on chip exhibit significantly enhanced epithelial morphology and functional properties relative to the same cells grown on 2D controls with or without perfusion. Upon introducing the nephrotoxin, Cyclosporine A, the epithelial barrier is disrupted in a dose-dependent manner. Our bioprinting method provides a new route for programmably fabricating advanced human kidney tissue models on demand. PMID:27725720

  13. Adaptation of plastic surfaces for tissue culture by glow discharge.

    PubMed Central

    Amstein, C F; Hartman, P A

    1975-01-01

    Plastic petri dishes and microtitration plates were electrically charged by a glow discharge unit installed in a vacuum evaporator. Charged and uncharged plates, as well as plates commercially treated for tissue culture, were inoculated with Vero and BHK-21 cell lines; secondary cultures of monkey kidney, chicken lung, canine kidney, and embryonic bovine kidney; and primary chicken embryo fibroblasts and chicken lung cells. All cell cultures grew normally on petri plates charged with the covers open. Growth rate and cell density compared favorably with growth on the commercial tissue culture plates; cell growth was somewhat less dense, however, on plates charged with the covers closed. Charged plates could be sterilized by ultraviolet light and ethylene oxide with no adverse effects on cell growth. Cells inoculated onto plates charged up to 7 months before inoculation grew as well as on freshly charged plates. Images PMID:818106

  14. Salix alba attenuated oxidative stress in the heart and kidney of hypercholesterolemic rabbits.

    PubMed

    Amel Zabihi, Narges; Mahmoudabady, Maryam; Soukhtanloo, Mohammad; Hayatdavoudi, Parichehr; Beheshti, Farimah; Niazmand, Saeed

    2018-01-01

    Oxidative stress plays a critical role in the development of hypercholesterolemia-induced complications. This study evaluated the effects of aspirin and Salix alba hydroethanolic extract on oxidative stress in the heart and kidney of hypercholesterolemic rabbits. The antioxidant activity, as well as total phenolic and salicin content of S. alba (Sa) extract were assessed by DPPH radical scavenging activity, Folin-Ciocalteu and HPLC methods, respectively. Animals were divided into two groups of control (fed with normal chow), and HD (fed with high cholesterol diet for 6 weeks). Then, hypercholesterolemic animals allocated to the following treatment groups: CHO (received HD), Sa extract (HD plus extract 60 and 120 mg/kg), and aspirin (HD plus aspirin 120 mg/kg) and received the treatments on a daily basis for 6 weeks. MDA, GSH, and nitrite concentrations as well as the activities of SOD and CAT were evaluated in cardiac and kidney tissues. The scavenging activity, total phenolic content and salicin were 19.1 µg/ml (IC50), 153.75 ± 3.6 mg of gallic acid/g, and 18.03 µg/mg, respectively. In comparison to CHO group, MDA levels were diminished in Sa and ASA groups but GSH levels were improved. NO metabolites increased in the heart of Sa 120 mg/kg group and in the kidney of all Sa and ASA treated groups. SOD activity increased only in the heart of Sa groups and in the kidney of Sa and ASA groups. CAT activity increased in the heart and kidney tissues of all Sa and ASA treated groups. The results showed S. alba extract improved redox homeostasis in heart and kidney tissues of hypercholesterolemic rabbits. The extract antioxidant property may be related to its phenolic content.

  15. Salix alba attenuated oxidative stress in the heart and kidney of hypercholesterolemic rabbits

    PubMed Central

    Amel Zabihi, Narges; Mahmoudabady, Maryam; Soukhtanloo, Mohammad; Hayatdavoudi, Parichehr; Beheshti, Farimah; Niazmand, Saeed

    2018-01-01

    Objective: Oxidative stress plays a critical role in the development of hypercholesterolemia-induced complications. This study evaluated the effects of aspirin and Salix alba hydroethanolic extract on oxidative stress in the heart and kidney of hypercholesterolemic rabbits. Materials and Methods: The antioxidant activity, as well as total phenolic and salicin content of S. alba (Sa) extract were assessed by DPPH radical scavenging activity, Folin-Ciocalteu and HPLC methods, respectively. Animals were divided into two groups of control (fed with normal chow), and HD (fed with high cholesterol diet for 6 weeks). Then, hypercholesterolemic animals allocated to the following treatment groups: CHO (received HD), Sa extract (HD plus extract 60 and 120 mg/kg), and aspirin (HD plus aspirin 120 mg/kg) and received the treatments on a daily basis for 6 weeks. MDA, GSH, and nitrite concentrations as well as the activities of SOD and CAT were evaluated in cardiac and kidney tissues. Results: The scavenging activity, total phenolic content and salicin were 19.1 µg/ml (IC50), 153.75 ± 3.6 mg of gallic acid/g, and 18.03 µg/mg, respectively. In comparison to CHO group, MDA levels were diminished in Sa and ASA groups but GSH levels were improved. NO metabolites increased in the heart of Sa 120 mg/kg group and in the kidney of all Sa and ASA treated groups. SOD activity increased only in the heart of Sa groups and in the kidney of Sa and ASA groups. CAT activity increased in the heart and kidney tissues of all Sa and ASA treated groups. Conclusion: The results showed S. alba extract improved redox homeostasis in heart and kidney tissues of hypercholesterolemic rabbits. The extract antioxidant property may be related to its phenolic content. PMID:29379769

  16. Understanding Thiel Embalming in Pig Kidneys to Develop a New Circulation Model

    PubMed Central

    Willaert, Wouter; De Vos, Marie; Van Hoof, Tom; Delrue, Louke; Pattyn, Piet; D’Herde, Katharina

    2015-01-01

    The quality of tissue preservation in Thiel embalmed bodies varies. Research on the administered embalming volume and its vascular distribution may elucidate one of the mechanisms of tissue preservation and allow for new applications of Thiel embalming. Vascular embalming with (group 1, n = 15) or without (group 2, n = 20) contrast agent was initiated in pig kidneys. The distribution of Thiel embalming solution in group 1 was visualized using computed tomography. The kidneys in both groups were then immersed in concentrated salt solutions to reduce their weight and volume. Afterwards, to mimic a lifelike circulation in the vessels, group 2 underwent pump-driven reperfusion for 120 minutes with either paraffinum perliquidum or diluted polyethylene glycol. The circulation was imaged with computed tomography. All of the kidneys were adequately preserved. The embalming solution spread diffusely in the kidney, but fluid accumulation was present. Subsequent immersion in concentrated salt solutions reduced weight (P < 0.01) and volume (P < 0.01). Reperfusion for 120 minutes was established in group 2. Paraffinum perliquidum filled both major vessels and renal tissue, whereas diluted polyethylene glycol spread widely in the kidney. There were no increases in weight (P = 0.26) and volume (P = 0.79); and pressure further decreased (P = 0.032) after more than 60 minutes of reperfusion with paraffinum perliquidum, whereas there were increases in weight (P = 0.005), volume (P = 0.032) and pressure (P < 0.0001) after reperfusion with diluted polyethylene glycol. Arterial embalming of kidneys results in successful preservation due to complete parenchymatous spreading. More research is needed to determine whether other factors affect embalming quality. Dehydration is an effective method to regain the organs’ initial status. Prolonged vascular reperfusion with paraffinum perliquidum can be established in this model without increases in weight, volume and pressure. PMID:25806527

  17. Stem cells for kidney repair: useful tool for acute renal failure?

    PubMed

    Yokoo, Takashi; Kawamura, Tetsuya; Kobayashi, Eiji

    2008-10-01

    Several cell types isolated from adult tissues have been reported to differentiate into mature kidney cells that may participate in renal repair after systemic administration. Chen et al. report that local mesenchymal stem cells derived from adult mouse kidneys are another source of cells with similar properties. Although these cells have the potential to differentiate into endothelial-lineage cell types, their therapeutic benefit to the ischemic kidney is mainly via the production of renoprotective factors.

  18. Hyperactivation of Akt/mTOR and deficiency in tuberin increased the oxidative DNA damage in kidney cancer patients with diabetes

    PubMed Central

    Habib, Samy L.; Liang, Sitai

    2014-01-01

    Recent study from our laboratory showed that patients with diabetes are at a higher risk of developing kidney cancer. In the current study, we have explored one of the mechanisms by which diabetes accelerates tumorigenesis in the kidney. Kidney cancer tissue from patients with diabetes showed a higher activity of Akt and decreased in total protein of tuberin compared to kidney cancer patient without diabetes or diabetes alone. In addition, a significant increase in phospho-Akt/tuberin expression was associated with an increase in Ki67 expression and activation of mTOR in kidney tumor with or without diabetes compared to diabetes alone. In addition, decrease in tuberin expression resulted in a significant decrease in protein expression of OGG1 and increased in oxidative DNA damage, 8-oxodG in kidney tissues from patients with cancer or cancer+diabetes. Importantly, these data showed that the majority of the staining of Akt/tuberin/p70S6K phosphorylation was more prominently in the tubular cells. In addition, accumulation of oxidative DNA damage is localized only in the nucleus of tubular cells within the cortex region. These data suggest that Akt/tuberin/mTOR pathway plays an important role in the regulation DNA damage and repair pathways that may predispose diabetic kidneys to pathogenesis of renal cell carcinoma. PMID:24797175

  19. Heavy metal contamination status of Japanese cranes (Grus japonensis) in east Hokkaido, Japan--extensive mercury pollution.

    PubMed

    Teraoka, Hiroki; Kumagai, Yoshihiro; Iwai, Hisae; Haraguchi, Kensaku; Ohba, Takashi; Nakai, Kunihiko; Satoh, Hiroshi; Sakamoto, Mineshi; Momose, Kunikazu; Masatomi, Hiroyuki; Hiraga, Takeo

    2007-02-01

    Japanese cranes (Grus japonensis) of eastern Hokkaido, Japan, and migrants between the Amur River basin and the eastern China-Korea Peninsula, live around fresh and brackish wetlands. Only a few thousand cranes are confirmed to exist in the world, so they are under threat of extinction. To understand the adverse effects of metal accumulation, we measured concentrations of three heavy metals in the liver, kidney, and muscle of 93 Japanese cranes from Hokkaido. The cranes were classified into six categories according to their sex and three life stages. Cadmium and mercury (Hg: total mercury) showed age-dependent but not sex-dependent accumulation in the liver and kidney. Twenty cranes showed 30 microg/g or higher levels of Hg in dry tissue and five adult cranes had more than 100 microg/g in their livers or kidneys. Cadmium concentrations were generally lower in all samples. Two adult cranes showed extremely high lead levels of more than 30 microg/g in their livers, suggesting lead poisoning. These results have highlighted the widespread and high levels of Hg pollution in Japanese cranes in Hokkaido, Japan.

  20. Metabolomics Reveals Signature of Mitochondrial Dysfunction in Diabetic Kidney Disease

    PubMed Central

    Karl, Bethany; Mathew, Anna V.; Gangoiti, Jon A.; Wassel, Christina L.; Saito, Rintaro; Pu, Minya; Sharma, Shoba; You, Young-Hyun; Wang, Lin; Diamond-Stanic, Maggie; Lindenmeyer, Maja T.; Forsblom, Carol; Wu, Wei; Ix, Joachim H.; Ideker, Trey; Kopp, Jeffrey B.; Nigam, Sanjay K.; Cohen, Clemens D.; Groop, Per-Henrik; Barshop, Bruce A.; Natarajan, Loki; Nyhan, William L.; Naviaux, Robert K.

    2013-01-01

    Diabetic kidney disease is the leading cause of ESRD, but few biomarkers of diabetic kidney disease are available. This study used gas chromatography-mass spectrometry to quantify 94 urine metabolites in screening and validation cohorts of patients with diabetes mellitus (DM) and CKD(DM+CKD), in patients with DM without CKD (DM–CKD), and in healthy controls. Compared with levels in healthy controls, 13 metabolites were significantly reduced in the DM+CKD cohorts (P≤0.001), and 12 of the 13 remained significant when compared with the DM–CKD cohort. Many of the differentially expressed metabolites were water-soluble organic anions. Notably, organic anion transporter-1 (OAT1) knockout mice expressed a similar pattern of reduced levels of urinary organic acids, and human kidney tissue from patients with diabetic nephropathy demonstrated lower gene expression of OAT1 and OAT3. Analysis of bioinformatics data indicated that 12 of the 13 differentially expressed metabolites are linked to mitochondrial metabolism and suggested global suppression of mitochondrial activity in diabetic kidney disease. Supporting this analysis, human diabetic kidney sections expressed less mitochondrial protein, urine exosomes from patients with diabetes and CKD had less mitochondrial DNA, and kidney tissues from patients with diabetic kidney disease had lower gene expression of PGC1α (a master regulator of mitochondrial biogenesis). We conclude that urine metabolomics is a reliable source for biomarkers of diabetic complications, and our data suggest that renal organic ion transport and mitochondrial function are dysregulated in diabetic kidney disease. PMID:23949796

  1. Temporal monitoring of liver and kidney lesions in contaminated East Greenland polar bears (Ursus maritimus) during 1999-2010.

    PubMed

    Sonne, Christian; Letcher, Robert J; Leifsson, Pall S; Rigét, Frank F; Bechshøft, Thea Ø; Bossi, Rossana; Asmund, Gert; Dietz, Rune

    2012-11-01

    Organohalogen contaminants bioaccumulate to high concentrations in tissues of polar bears (Ursus maritimus). The exposure levels are in the order to be toxic to inner organs like liver and kidney. We therefore investigated the temporal development of lesions in liver (n=115) and kidney (n=122) samples from East Greenland polar bears taken over the 12 year period from 1999 to 2010. Seven liver and seven kidney lesions were observed of which six were age-related. Controlling for this, the analyses showed that hepatic steatosis and renal cell infiltrations, glomerular sclerosis and tubular hyperplasia decreased over the investigated time period (all p<0.05). Similarly, hypertrophy of hepatic Ito cells, renal glomerular capillary wall thickening and interstitial fibrosis increased over the study period (all p<0.05). Regarding contaminant, concentrations of polybrominated diphenyl ethers in adipose tissue were negatively associated with hepatic mononuclear cell infiltrations (p=0.05) and a similar trend was found for Hg (p=0.09). Hexachlorobenzene was positively associated with portal cell infiltrations and hepatic lipid granulomas, while polychlorinated biphenyls were negatively associated with the prevalence of steatosis (both p<0.05) and a similar trend was found for hexachlorocyclohexanes (p=0.08). Mercury was positively correlated with the frequencies of hypertrophic Ito cells (p=0.002) and a similar trend was found for perfluorooctanesulfonic acid (p=0.07). In renal tissue, hexachlorocyclohexanes were positively associated with medullar hyaline casts (p=0.03) and a similar trend was found for cell infiltrations (p=0.08). There was a trend of trans-nonachlor being positively associated with glomerular sclerosis (p=0.06) while dichlorodiphenyltrichloroethanes were negatively associated with tubular hyperplasia (p=0.02). These results suggest that specific liver and renal lesions have decreased or increased over time and that long-range transported organohalogen contaminants and mercury may be among the co-factors responsible for these observations. These relationships are important to take into account when biomonitoring health and pollution in wildlife species such as polar bears. Copyright © 2012 Elsevier Ltd. All rights reserved.

  2. Protective effects of zingerone on oxidative stress and inflammation in cisplatin-induced rat nephrotoxicity.

    PubMed

    Alibakhshi, Tuba; Khodayar, Mohammad Javad; Khorsandi, Layasadat; Rashno, Mohammad; Zeidooni, Leila

    2018-05-29

    Cisplatin is one of the most commonly used and highly effective cancer chemotherapeutic agents. Use of cisplatin is limited due to persistence of severe side effects such as nephrotoxicity, neurotoxicity, and hearing loss. Nephrotoxicity is the most common limiting side effect of cisplatin use. Zingerone is one of the active ingredients present in ginger plant that has anti-inflammatory and antioxidant effects. In this study, Wistar rats were assigned randomly to 6 groups with 5 animals in each group. The control group; cisplatin group which received 7.5 mg/kg of cisplatin intraperitoneally (i.p.) at the 4th day; zingerone group received 50 mg/kg of zingerone orally for 7 days. Three other groups were pretreated with 10, 20, and 50 mg/kg of zingerone orally for 7 days and cisplatin administered 7.5 mg/kg i.p. at the 4th day, respectively. The animals were sacrificed 72 h after cisplatin injection and blood samples were taken to evaluate the serum factors. Right kidneys were collected for histopathological studies and left kidneys were considered to measure the oxidative stress parameters and TNF-α cytokine. Co-administration of zingerone along with cisplatin resulted a statistically significant reduction in lactate dehydrogenase (LDH) activity, creatinine and BUN levels of serum in comparison with cisplatin alone group (P < 0.01). Zingerone significantly decreased the tissue levels of malondialdehyde (MDA) (P < 0.05) and significantly retained the enzyme activity of catalase (CAT) (P < 0.05) and glutathione peroxidase (GPX) (P < 0.05) in kidney tissue compared to cisplatin. Zingerone did not permit the reduction of glutathione (GSH) levels (P < 0.001) in kidney tissue and by reducing the level of tumor necrosis factor (TNF)-α (P < 0.05) suppressed the inflammation produced by cisplatin. Furthermore, zingerone improved histopathological changes such as vacuolation (fat deposit), brush border loss, infiltration of leukocytes, glomerular diameters and congestion of RBCs. However, our findings suggest that zingerone has nephroprotective effects in cisplatin rat model of nephrotoxicity mostly through suppression of oxidative stress and inflammation. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

  3. COMPLEMENT FIXATION IN DISEASED TISSUES

    PubMed Central

    Burkholder, Peter M.

    1961-01-01

    An immunohistologic complement fixation test has been used in an effort to detect immune complexes in sections of kidney from rats injected with rabbit anti-rat kidney serum and in sections of biopsied kidneys from four humans with membranous glomerulonephritis. Sections of the rat and human kidneys were treated with fluorescein-conjugated anti-rabbit globulin or antihuman globulin respectively. Adjacent sections in each case were incubated first with fresh guinea pig serum and then in a second step were treated with fluorescein-conjugated antibodies against fixed guinea pig complement to detect sites of fixation of the complement. It was demonstrated that the sites of rabbit globulin in glomerular capillary walls of the rat kidneys and the sites of localized human globulin in thickened glomerular capillary walls and swollen glomerular endothelial cells of the human kidneys were the same sites in which guinea pig complement was fixed in vitro. It was concluded from these studies that rabbit nephrotoxic antibodies localize in rat glomeruli in complement-fixing antigen-antibody complexes. Furthermore, it was concluded that the deposits of human globulin in the glomeruli of the human kidneys behaved like antibody globulin in complement-fixing antigen-antibody complexes. The significance of demonstrating complement-fixing immune complexes in certain diseased tissues is discussed in regard to determination of the causative role of allergic reactions in disease. PMID:19867205

  4. Expression Analysis of Interferon-Stimulated Gene 15 in the Rock Bream Oplegnathus fasciatus against Rock Bream Iridovirus (RSIV) Challenge.

    PubMed

    Kim, Kyung-Hee; Yang, In Jung; Kim, Woo-Jin; Park, Choul-Ji; Park, Jong-Won; Noh, Gyeong Eon; Lee, Seunghyung; Lee, Young Mee; Hwang, Hyung Kyu; Kim, Hyun Chul

    2017-12-01

    Interferon-stimulated gene 15 (ISG15) is known to interfere with viral replication and infection by limiting the viral infection of cells. Interferon-stimulated gene 15 (ISG15) interferes with viral replication and infectivity by limiting viral infection in cells. It also plays an important role in the immune response. In this study, tissue-specific expression of ISG15 in healthy rock bream samples and spatial and temporal expression analysis of rock bream ISG15 (RbISG15) were performed following rock bream iridovirus (RSIV) infection. RbISG15 expression was significantly higher in the eye, gill, intestine, kidney, liver, muscle, spleen, and stomach, but low in the brain. There were particularly high levels of expression in the liver and muscle. RbISG15 expression was also examined in several tissues and at various times following RSIV infection. ISG15 expression increased within 3 h in the whole body and decreased at 24 h after infection. In addition, temporal expression of several tissues following RSIV infection showed a similar pattern in the muscle, kidney, and spleen, increasing at 3 h and decreasing at 72 h. These results suggest that ISG15 plays an important role in the immune response of rock bream. Overall, this study characterizes the response of RbISG15 following RSIV infection.

  5. Municipal sewage sludge application on Ohio farms: tissue metal residues and infections

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

    Reddy, C.S.; Dorn, C.R.; Lamphere, D.N.

    1985-12-01

    Transmission of infectious agents and translocation of Cd, Cu, Pb, and Zn from anaerobically digested sludge to the tissues of farm animals grazing on pastures to which sludge was applied (2-10 metric tons per hectare) were studied on eight farms. No significant health risk associated with the possible presence in sludge of Salmonella spp., or of common animal parasites including Nematodirus spp., Strongylus spp., Strongyloides spp., Trichuris spp., Eimeria spp., Ascaris spp., and Ancylostomum spp. was noted. Caudal fold as well as cervical tuberculin testing indicated no conversions from negative to positive following exposure of cattle to sludge. Significantly highermore » fecal Cd concentrations were detected in samples collected from cattle soon after being placed on sludge-treated pastures compared to preexposure values in the same animals. Significant Cd and Pb accumulations were found in the kidneys of calves grazing sludge-treated pastures compared to control calves. Although older cows grazing sludge-treated pastures had significantly higher blood Pb levels, no metal accumulation was observed in other tissues. Statistically significant accumulations of Cd and Pb in the kidney of calves grazing these pastures for a relatively short period suggest that caution should be exercised to avoid prolonged grazing of cattle on pastures receiving heavy sludge applications, especially with sludges containing high concentrations of heavy metals.« less

  6. Intraperitoneal Administration of Silymarin Protects End Organs from Multivisceral Ischemia/Reperfusion Injury in a Rat Model.

    PubMed

    Koçarslan, Aydemir; Koçarslan, Sezen; Aydin, Mehmet Salih; Gunay, Şamil; Karahan, Mahmut Alp; Taşkın, Abdullah; Üstunel, Murat; Aksoy, Nurten

    2016-01-01

    To determine whether intraperitoneal silymarin administration has favorable effects on the heart, lungs, kidney, and liver and on oxidative stress in a rat model of supraceliac aorta ischemia/reperfusion injury. Thirty male Wistar albino rats were divided equally into three groups: sham, control, and silymarin. The control and silymarin groups underwent supraceliac aortic occlusion for 45 min, followed by a 60 min period of reperfusion under terminal anesthesia. In the silymarin group, silymarin was administered intraperitoneally during ischemia at a dose of 200 mg/kg. Rats were euthanized using terminal anesthesia, and blood was collected from the inferior vena cava for total antioxidant capacity, total oxidative status, and oxidative stress index measurement. Lungs, heart, liver and kidney tissues were histologically examined. Ischemia/reperfusion injury significantly increased histopathological damage as well as the total oxidative status and oxidative stress index levels in the blood samples. The silymarin group incurred significantly lesser damage to the lungs, liver and kidneys than the control group, while no differences were observed in the myocardium. Furthermore, the silymarin group had significantly lower total oxidative status and oxidative stress index levels than the control group. Intraperitoneal administration of silymarin reduces oxidative stress and protects the liver, kidney, and lungs from acute supraceliac abdominal aorta ischemia/reperfusion injury in the rat model.

  7. Giant kidney worms in a patient with renal cell carcinoma

    PubMed Central

    Kuehn, Jemima; Lombardo, Lindsay; Janda, William M; Hollowell, Courtney M P

    2016-01-01

    Dioctophyma renale (D. renale), or giant kidney worms, are the largest nematodes that infect mammals. Approximately 20 cases of human infection have been reported. We present a case of a 71-year-old man with a recent history of unintentional weight loss and painless haematuria, passing elongated erythematous tissue via his urethra. CT revealed a left renal mass with pulmonary nodules and hepatic lesions. On microscopy, the erythematous tissue passed was identified as D. renale. On subsequent renal biopsy, pathology was consistent with renal cell carcinoma. This is the first reported case of concomitant D. renale infection and renal cell carcinoma, and the second reported case of D. renale infection of the left kidney alone. PMID:26952087

  8. Effects of pre-transplant azithromycin administration on kidney graft function: study protocol for a double-blind randomized clinical trial.

    PubMed

    Mokhtari, Gholamreza; Teimoori, Mojtaba

    2018-06-28

    Kidney transplantation is the best strategy for the management of end-stage renal disease; however, the outcomes need to improve further. Macrolides show antimicrobial and anti-inflammatory properties in chronic diseases and intraoperatively, and can accumulate in tissues for extended periods. Therefore, theoretically, when administered to a donor and because of accumulation in the donor kidney, macrolides can cause graft immunomodulation and improve kidney transplantation outcomes. This study is a single-center, randomized clinical trial. A total of 60 kidney donors will be randomly allocated to the azithromycin or placebo group and treated with a single dose (1 g) of azithromycin or placebo, respectively, 1 day before surgery. Recruitment commenced in September 2016 and is expected to be completed by March 2018. The primary outcome is kidney graft function. The secondary outcomes include rejection rate, urinary tract infections in graft recipients, pain and systemic inflammatory response syndrome in live donors, and complications in both donors and recipients. Outcomes will be evaluated at baseline and every day in the first week after transplantation, as well as at 1 and 3 months post transplantation. Adverse reactions will be documented. If the efficacy of azithromycin in reducing adverse outcomes is confirmed, it would serve as an easy to use, economic intervention able to lower post-transplantation risks. Short and mid-term analyses of blood and urine samples as well as immunological assays will facilitate a more in-depth analysis of the effects of azithromycin on transplantation outcomes. Iranian Clinical Trial Registry, IRCT201606141853N11 , registered on September 5, 2016.

  9. Tetracapsuloides bryosalmonae infection affects the expression of genes involved in cellular signal transduction and iron metabolism in the kidney of the brown trout Salmo trutta.

    PubMed

    Kumar, Gokhlesh; Sarker, Subhodeep; Menanteau-Ledouble, Simon; El-Matbouli, Mansour

    2015-06-01

    Tetracapsuloides bryosalmonae is an enigmatic endoparasite which causes proliferative kidney disease in various species of salmonids in Europe and North America. The life cycle of the European strain of T. bryosalmonae generally completes in an invertebrate host freshwater bryozoan and vertebrate host brown trout (Salmo trutta) Linnaeus, 1758. Little is known about the gene expression in the kidney of brown trout during the developmental stages of T. bryosalmonae. In the present study, quantitative real-time PCR was applied to quantify the target genes of interest in the kidney of brown trout at different time points of T. bryosalmonae development. PCR primers specific for target genes were designed and optimized, and their gene expression levels were quantified in the cDNA kidney samples using SYBR Green Supermix. Expression of Rab GDP dissociation inhibitor beta, integral membrane protein 2B, NADH dehydrogenase 1 beta subcomplex subunit 6, and 26S protease regulatory subunit S10B were upregulated significantly in infected brown trout, while the expression of the ferritin M middle subunit was downregulated significantly. These results suggest that host genes involved in cellular signal transduction, proteasomal activities, including membrane transporters and cellular iron storage, are differentially upregulated or downregulated in the kidney of brown trout during parasite development. The gene expression pattern of infected renal tissue may support the development of intraluminal sporogonic stages of T. bryosalmonae in the renal tubular lumen of brown trout which may facilitate the release of viable parasite spores to transmit to the invertebrate host bryozoan.

  10. Azilsartan improves glycemic status and reduces kidney damage in zucker diabetic fatty rats.

    PubMed

    Hye Khan, Md Abdul; Neckář, Jan; Haines, Jasmine; Imig, John D

    2014-08-01

    Azilsartan medoxomil (AZL-M), an angiotensin II receptor blocker, demonstrates antihypertensive and organ protective effects in hypertension. We investigated the efficacy of AZL-M to ameliorate metabolic syndrome and kidney damage associated with type 2 diabetes using Zucker diabetic fatty (ZDF) rats. ZDF rats were treated with vehicle or AZL-M for 8 weeks. Zucker diabetic lean (ZDL) rats were used as controls. Urine and plasma samples were collected for biochemical analysis, and kidney tissues were used for histopathological and immunohistopathological examination at the end of the 8-week protocol. ZDF rats were diabetic with hyperglycemia and impaired glucose tolerance, and AZL-M ameliorated the diabetic phenotype. ZDF rats were hypertensive compared with ZDL rats (181±6 vs. 129±7mm Hg), and AZL-M decreased blood pressure in ZDF rats (116±7mm Hg). In ZDF rats, there was marked renal damage with elevated proteinuria, albuminuria, nephrinuria, 2-4-fold higher tubular cast formation, and glomerular injury compared with ZDL rats. AZL-M treatment reduced renal damage in ZDF rats. ZDF rats demonstrated renal inflammation and oxidative stress with elevated urinary monocyte chemoattractant protein 1 excretion, renal infiltration of macrophages, and elevated kidney malondialdehyde levels. AZL-M reduced oxidative stress and inflammation in ZDF rats. Overall, we demonstrate that AZL-M attenuates kidney damage in type 2 diabetes. We further demonstrate that anti-inflammatory and antioxidative activities of AZL-M contribute to its kidney protective action. © American Journal of Hypertension, Ltd 2014. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  11. Microgravity

    NASA Image and Video Library

    1996-01-01

    Interior of a Biotechnology Refrigerator that preserves samples for use in (or after culturing in) the NASA Bioreactor. The unit is shown extracted from a middeck locker shell. The NASA Bioreactor provides a low turbulence culture environment which promotes the formation of large, three-dimensional cell clusters. The Bioreactor is rotated to provide gentle mixing of fresh and spent nutrient without inducing shear forces that would damage the cells. Due to their high level of cellular organization and specialization, samples constructed in the bioreactor more closely resemble the original tumor or tissue found in the body. The work is sponsored by NASA's Office of Biological and Physical Research. The bioreactor is managed by the Biotechnology Cell Science Program at NASA's Johnson Space Center (JSC). NASA-sponsored bioreactor research has been instrumental in helping scientists to better understand normal and cancerous tissue development. In cooperation with the medical community, the bioreactor design is being used to prepare better models of human colon, prostate, breast and ovarian tumors. Cartilage, bone marrow, heart muscle, skeletal muscle, pancreatic islet cells, liver and kidney are just a few of the normal tissues being cultured in rotating bioreactors by investigators.

  12. Microgravity

    NASA Image and Video Library

    1996-01-01

    Biotechnology Refrigerator that preserves samples for use in (or after culturing in) the NASA Bioreactor. The unit is shown extracted from a middeck locker shell and with thermal blankets partially removed. The NASA Bioreactor provides a low turbulence culture environment which promotes the formation of large, three-dimensional cell clusters. The Bioreactor is rotated to provide gentle mixing of fresh and spent nutrient without inducing shear forces that would damage the cells. Due to their high level of cellular organization and specialization, samples constructed in the bioreactor more closely resemble the original tumor or tissue found in the body. The work is sponsored by NASA's Office of Biological and Physical Research. The bioreactor is managed by the Biotechnology Cell Science Program at NASA's Johnson Space Center (JSC). NASA-sponsored bioreactor research has been instrumental in helping scientists to better understand normal and cancerous tissue development. In cooperation with the medical community, the bioreactor design is being used to prepare better models of human colon, prostate, breast and ovarian tumors. Cartilage, bone marrow, heart muscle, skeletal muscle, pancreatic islet cells, liver and kidney are just a few of the normal tissues being cultured in rotating bioreactors by investigators.

  13. Microgravity

    NASA Image and Video Library

    1996-01-01

    Biotechnology Refrigerator that preserves samples for use in (or after culturing in) the NASA Bioreactor. The unit is shown extracted from a middeck locker shell. The NASA Bioreactor provides a low turbulence culture environment which promotes the formation of large, three-dimensional cell clusters. The Bioreactor is rotated to provide gentle mixing of fresh and spent nutrient without inducing shear forces that would damage the cells. Due to their high level of cellular organization and specialization, samples constructed in the bioreactor more closely resemble the original tumor or tissue found in the body. The work is sponsored by NASA's Office of Biological and Physical Research. The bioreactor is managed by the Biotechnology Cell Science Program at NASA's Johnson Space Center (JSC). NASA-sponsored bioreactor research has been instrumental in helping scientists to better understand normal and cancerous tissue development. In cooperation with the medical community, the bioreactor design is being used to prepare better models of human colon, prostate, breast and ovarian tumors. Cartilage, bone marrow, heart muscle, skeletal muscle, pancreatic islet cells, liver and kidney are just a few of the normal tissues being cultured in rotating bioreactors by investigators.

  14. Laser-induced Breakdown Spectroscopy: A New Approach for Nanoparticle's Mapping and Quantification in Organ Tissue

    PubMed Central

    Sancey, Lucie; Motto-Ros, Vincent; Kotb, Shady; Wang, Xiaochun; Lux, François; Panczer, Gérard; Yu, Jin; Tillement, Olivier

    2014-01-01

    Emission spectroscopy of laser-induced plasma was applied to elemental analysis of biological samples. Laser-induced breakdown spectroscopy (LIBS) performed on thin sections of rodent tissues: kidneys and tumor, allows the detection of inorganic elements such as (i) Na, Ca, Cu, Mg, P, and Fe, naturally present in the body and (ii) Si and Gd, detected after the injection of gadolinium-based nanoparticles. The animals were euthanized 1 to 24 hr after intravenous injection of particles. A two-dimensional scan of the sample, performed using a motorized micrometric 3D-stage, allowed the infrared laser beam exploring the surface with a lateral resolution less than 100 μm. Quantitative chemical images of Gd element inside the organ were obtained with sub-mM sensitivity. LIBS offers a simple and robust method to study the distribution of inorganic materials without any specific labeling. Moreover, the compatibility of the setup with standard optical microscopy emphasizes its potential to provide multiple images of the same biological tissue with different types of response: elemental, molecular, or cellular. PMID:24962015

  15. NASA Bioreactor

    NASA Technical Reports Server (NTRS)

    1996-01-01

    Interior of a Biotechnology Refrigerator that preserves samples for use in (or after culturing in) the NASA Bioreactor. The unit is shown extracted from a middeck locker shell. The NASA Bioreactor provides a low turbulence culture environment which promotes the formation of large, three-dimensional cell clusters. The Bioreactor is rotated to provide gentle mixing of fresh and spent nutrient without inducing shear forces that would damage the cells. Due to their high level of cellular organization and specialization, samples constructed in the bioreactor more closely resemble the original tumor or tissue found in the body. The work is sponsored by NASA's Office of Biological and Physical Research. The bioreactor is managed by the Biotechnology Cell Science Program at NASA's Johnson Space Center (JSC). NASA-sponsored bioreactor research has been instrumental in helping scientists to better understand normal and cancerous tissue development. In cooperation with the medical community, the bioreactor design is being used to prepare better models of human colon, prostate, breast and ovarian tumors. Cartilage, bone marrow, heart muscle, skeletal muscle, pancreatic islet cells, liver and kidney are just a few of the normal tissues being cultured in rotating bioreactors by investigators.

  16. NASA Bioreactor

    NASA Technical Reports Server (NTRS)

    1996-01-01

    Biotechnology Refrigerator that preserves samples for use in (or after culturing in) the NASA Bioreactor. The unit is shown extracted from a middeck locker shell. The NASA Bioreactor provides a low turbulence culture environment which promotes the formation of large, three-dimensional cell clusters. The Bioreactor is rotated to provide gentle mixing of fresh and spent nutrient without inducing shear forces that would damage the cells. Due to their high level of cellular organization and specialization, samples constructed in the bioreactor more closely resemble the original tumor or tissue found in the body. The work is sponsored by NASA's Office of Biological and Physical Research. The bioreactor is managed by the Biotechnology Cell Science Program at NASA's Johnson Space Center (JSC). NASA-sponsored bioreactor research has been instrumental in helping scientists to better understand normal and cancerous tissue development. In cooperation with the medical community, the bioreactor design is being used to prepare better models of human colon, prostate, breast and ovarian tumors. Cartilage, bone marrow, heart muscle, skeletal muscle, pancreatic islet cells, liver and kidney are just a few of the normal tissues being cultured in rotating bioreactors by investigators.

  17. NASA Bioreactor

    NASA Technical Reports Server (NTRS)

    1996-01-01

    Biotechnology Refrigerator that preserves samples for use in (or after culturing in) the NASA Bioreactor. The unit is shown extracted from a middeck locker shell and with thermal blankets partially removed. The NASA Bioreactor provides a low turbulence culture environment which promotes the formation of large, three-dimensional cell clusters. The Bioreactor is rotated to provide gentle mixing of fresh and spent nutrient without inducing shear forces that would damage the cells. Due to their high level of cellular organization and specialization, samples constructed in the bioreactor more closely resemble the original tumor or tissue found in the body. The work is sponsored by NASA's Office of Biological and Physical Research. The bioreactor is managed by the Biotechnology Cell Science Program at NASA's Johnson Space Center (JSC). NASA-sponsored bioreactor research has been instrumental in helping scientists to better understand normal and cancerous tissue development. In cooperation with the medical community, the bioreactor design is being used to prepare better models of human colon, prostate, breast and ovarian tumors. Cartilage, bone marrow, heart muscle, skeletal muscle, pancreatic islet cells, liver and kidney are just a few of the normal tissues being cultured in rotating bioreactors by investigators.

  18. [Rhein promotes the expression of SIRT1 in kidney tissues of type 2 diabetic rat].

    PubMed

    Chen, Weidong; Chang, Baochao; Zhang, Yan; Yang, Ping; Liu, Lei

    2015-05-01

    To observe the effect of rhein on the expression of SIRT1(Sirtuin 1) in kidney of diabetic rats, and to explore the role of rhein in protecting rat kidney against diabetic nephropathy and possible mechanism. The type 2 diabetic rats were induced by high-glucose and high-fat diet combined with streptozotocin (35 mg/kg body mass). Seventy-five eight-week-old male SD rats were randomly divided into 6 groups: normal group, diabetic group, low-, medium- and high-dose (50, 100, 150 mg/kg) rhein treatment groups and 10 mg/kg pioglitazone treatment group. The rats were given corresponding substances intragastrically once a day. At the end of the 16th week, the fasting plasma glucose (FPG), fasting insulin (FINS), triglycerides (TG), total cholesterol (TC), serum creatinine (Scr) and 24 hours urine protein (24 h U-PRO) were determined. The renal hypertrophy index (KM/BM), insulin resistance index (HOMA-IR) were calculated. The pathological changes in renal tissues were examined by PAS staining under a light microscopy. The mean glomerular area (MGA) and mean glomerular volume (MGV) were measured by pathological image analysis system. Western blotting and real-time quantitative PCR were used to determine the expression of SIRT1 in renal tissues at protein and mRNA levels, respectively. The expression of SIRT1 was down-regulated in the kidney of diabetic rats. The levels of FPG, FINS, HOMA-IR, TG, TC, Scr, 24 h U-PRO, KM/BM, MGA and MGV significantly decreased and the histopathology of renal tissues were significantly improved in all treatment groups compared with diabetic group. The expression of SIRT1 mRNA and protein markedly increased in rhein treatment groups and pioglitazone treatment group compared with diabetic group. The indicators in high-dose rhein treatment group were improved more significantly than those in the other groups. Correlation analysis showed that the expression of SIRT1 was negatively correlated with 24 h U-PRO and MGV. The expression of SIRT1 was reduced in kidney tissues of diabetic rats. Rhein could attenuate kidney damage in diabetic rats by improving the insulin resistance and dyslipidemia, and increasing the SIRT1 expression.

  19. Organoids: Modelling polycystic kidney disease

    NASA Astrophysics Data System (ADS)

    Romagnani, Paola

    2017-11-01

    Cysts were generated from organoids in vitro and the removal of adherent cues was shown to play a key role in polycystic kidney disease progression. These cysts resembled those of diseased tissue phenotypically and were capable of remodelling their microenvironment.

  20. Shock waves: a new physical principle in medicine.

    PubMed

    Brendel, W

    1986-01-01

    Shock wave therapy of kidney- and gallstones, i.e. extracorporeal shock wave lithotripsy (ESWL), is a new, noninvasive technique to destroy concrements in the kidney, the gallbladder and in the ductus choledochus. This method was developed by the Dornier Company, Friedrichshafen, FRG, and tested in animal experiments at the Institute for Surgical Research of the University of Munich. In the meantime, kidney lithotripsy has gained world-wide acceptance. More than 60,000 patients suffering from urolithiasis have been treated successfully, what made surgical removal of their kidney stones obsolete. Gallstone lithotripsy is, however, still at the very beginning of clinical trial. Lithotripsy of gallbladder stones will have to be applied in combination with urso- or chenodesoxycholic acid in order to obtain complete dissolution of the fragments. Potential hazards to living tissues are briefly mentioned. Since the lung is particularly susceptible, shock waves must enter the body at an angle which ensures that lung tissue is not affected.

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