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Sample records for antagonist ameliorate renal

  1. Follistatin, an Activin Antagonist, Ameliorates Renal Interstitial Fibrosis in a Rat Model of Unilateral Ureteral Obstruction

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    Akito Maeshima

    2014-01-01

    Full Text Available Activin, a member of the TGF-β superfamily, regulates cell growth and differentiation in various cell types. Activin A acts as a negative regulator of renal development as well as tubular regeneration after renal injury. However, it remains unknown whether activin A is involved in renal fibrosis. To clarify this issue, we utilized a rat model of unilateral ureteral obstruction (UUO. The expression of activin A was significantly increased in the UUO kidneys compared to that in contralateral kidneys. Activin A was detected in glomerular mesangial cells and interstitial fibroblasts in normal kidneys. In UUO kidneys, activin A was abundantly expressed by interstitial α-SMA-positive myofibroblasts. Administration of recombinant follistatin, an activin antagonist, reduced the fibrotic area in the UUO kidneys. The number of proliferating cells in the interstitium, but not in the tubules, was significantly lower in the follistatin-treated kidneys. Expression of α-SMA, deposition of type I collagen and fibronectin, and CD68-positive macrophage infiltration were significantly suppressed in the follistatin-treated kidneys. These data suggest that activin A produced by interstitial fibroblasts acts as a potent profibrotic factor during renal fibrosis. Blockade of activin A action may be a novel approach for the prevention of renal fibrosis progression.

  2. Spironolactone ameliorates transplant vasculopathy in renal chronic transplant dysfunction in rats

    NARCIS (Netherlands)

    Waanders, Femke; Rienstra, Heleen; Boer, Mark Walther; Zandvoort, Andre; Rozing, Jan; Navis, Gerjan; van Goor, Harry; Hillebrands, Jan-Luuk

    Waanders F, Rienstra H, Walther Boer M, Zandvoort A, Rozing J, Navis G, van Goor H, Hillebrands JL. Spironolactone ameliorates transplant vasculopathy in renal chronic transplant dysfunction in rats. Am J Physiol Renal Physiol 296: F1072-F1079, 2009. First published February 25, 2009;

  3. The Histamine H3 Receptor Antagonist DL77 Ameliorates MK801-Induced Memory Deficits in Rats

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    Nermin Eissa

    2018-02-01

    Full Text Available The role of Histamine H3 receptors (H3Rs in memory, and the prospective of H3R antagonists in pharmacological control of neurodegenerative disorders, e.g., Alzheimer disease (AD is well-accepted. For that reason, the procognitive effects of the H3R antagonist DL77 on cognitive impairments induced with MK801 were tested in an inhibitory passive avoidance paradigm (PAP and novel object recognition (NOR task in adult male rats, using donepezil (DOZ as a standard drug. Acute systemic pretreatment with DL77 (2.5, 5, and 10 mg/kg, i.p. significantly ameliorated memory deficits induced with MK801 in PAP (all P < 0.05, n = 7. The ameliorative effect of most promising dose of DL77 (5 mg/kg, i.p. was reversed when rats were co-injected with the H3R agonist R-(α-methylhistamine (RAMH, 10 mg/kg, i.p. (p = 0.701 for MK801-amnesic group vs. MK801+DL77+RAMH group, n = 6. In the NOR paradigm, DL77 (5 mg/kg, i.p. counteracted long-term memory (LTM deficits induced with MK801 (P < 0.05, n = 6–8, and the DL77-provided effect was similar to that of DOZ (p = 0.788, n = 6–8, and was reversed when rats were co-injected with RAMH (10 mg/kg, i.p. (p = 0.877, n = 6, as compared to the (MK801-amnesic group. However, DL77 (5 mg/kg, i.p. did not alter short-term memory (STM impairment in NOR test (p = 0.772, n = 6–8, as compared to (MK801-amnesic group. Moreover, DL77 (5 mg/kg failed to modify anxiety and locomotor behaviors of animals innate to elevated-plus maze (EPM (p = 0.67 for percentage of time spent exploring the open arms, p = 0.52 for number of entries into the open arms, p = 0.76 for percentage of entries into the open arms, and p = 0.73 number of closed arm entries as compared to saline-treated groups, all n = 6, demonstrating that the procognitive effects observed in PAP or NOR tests were unconnected to alterations in emotions or in natural locomotion of tested animals. These results signify the potential involvement of H3Rs in modulating

  4. Amelioration of cold injury-induced cortical brain edema formation by selective endothelin ETB receptor antagonists in mice.

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    Michinaga, Shotaro; Nagase, Marina; Matsuyama, Emi; Yamanaka, Daisuke; Seno, Naoki; Fuka, Mayu; Yamamoto, Yui; Koyama, Yutaka

    2014-01-01

    Brain edema is a potentially fatal pathological condition that often occurs in stroke and head trauma. Following brain insults, endothelins (ETs) are increased and promote several pathophysiological responses. This study examined the effects of ETB antagonists on brain edema formation and disruption of the blood-brain barrier in a mouse cold injury model (Five- to six-week-old male ddY mice). Cold injury increased the water content of the injured cerebrum, and promoted extravasation of both Evans blue and endogenous albumin. In the injury area, expression of prepro-ET-1 mRNA and ET-1 peptide increased. Intracerebroventricular (ICV) administration of BQ788 (ETB antagonist), IRL-2500 (ETB antagonist), or FR139317 (ETA antagonist) prior to cold injury significantly attenuated the increase in brain water content. Bolus administration of BQ788, IRL-2500, or FR139317 also inhibited the cold injury-induced extravasation of Evans blue and albumin. Repeated administration of BQ788 and IRL-2500 beginning at 24 h after cold injury attenuated both the increase in brain water content and extravasation of markers. In contrast, FR139317 had no effect on edema formation when administrated after cold injury. Cold injury stimulated induction of glial fibrillary acidic protein-positive reactive astrocytes in the injured cerebrum. Induction of reactive astrocytes after cold injury was attenuated by ICV administration of BQ788 or IRL-2500. These results suggest that ETB receptor antagonists may be an effective approach to ameliorate brain edema formation following brain insults.

  5. Amelioration of cold injury-induced cortical brain edema formation by selective endothelin ETB receptor antagonists in mice.

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    Shotaro Michinaga

    Full Text Available Brain edema is a potentially fatal pathological condition that often occurs in stroke and head trauma. Following brain insults, endothelins (ETs are increased and promote several pathophysiological responses. This study examined the effects of ETB antagonists on brain edema formation and disruption of the blood-brain barrier in a mouse cold injury model (Five- to six-week-old male ddY mice. Cold injury increased the water content of the injured cerebrum, and promoted extravasation of both Evans blue and endogenous albumin. In the injury area, expression of prepro-ET-1 mRNA and ET-1 peptide increased. Intracerebroventricular (ICV administration of BQ788 (ETB antagonist, IRL-2500 (ETB antagonist, or FR139317 (ETA antagonist prior to cold injury significantly attenuated the increase in brain water content. Bolus administration of BQ788, IRL-2500, or FR139317 also inhibited the cold injury-induced extravasation of Evans blue and albumin. Repeated administration of BQ788 and IRL-2500 beginning at 24 h after cold injury attenuated both the increase in brain water content and extravasation of markers. In contrast, FR139317 had no effect on edema formation when administrated after cold injury. Cold injury stimulated induction of glial fibrillary acidic protein-positive reactive astrocytes in the injured cerebrum. Induction of reactive astrocytes after cold injury was attenuated by ICV administration of BQ788 or IRL-2500. These results suggest that ETB receptor antagonists may be an effective approach to ameliorate brain edema formation following brain insults.

  6. Sida rhomboidea.Roxb leaf extract ameliorates gentamicin induced nephrotoxicity and renal dysfunction in rats.

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    Thounaojam, Menaka C; Jadeja, Ravirajsinh N; Devkar, Ranjitsinh V; Ramachandran, A V

    2010-10-28

    Sida rhomboidea.Roxb (SR) known as "Mahabala" in Ayurveda and marketed as "Shahadeyi" is used in ethnomedicine to treat ailments such as dysuria and urinary disorders. To evaluate nephroprotective potential of SR against gentamicin (GM) induced nephrotoxicity and renal dysfunction. Nephrotoxicity was induced in rats with GM (100 mg/kg bodyweight (i.p.) for 8 days) and were treated with SR extract (200 and 400 mg/kg bodyweight (p.o.) for 8 days) or 0.5% carboxymethyl cellulose (vehicle). Plasma and urine urea and creatinine, renal enzymatic and non-enzymatic antioxidants along with lipid peroxidation were evaluated in various experimental groups. GM treatment induced significant elevation (p<0.05) in plasma and urine urea, creatinine, renal lipid peroxidation along with significant decrement (p<0.05) in renal enzymatic and non-enzymatic antioxidants. SR treatment to GM treated rats (GM+SR) recorded significant decrement (p<0.05) in plasma and urine urea and creatinine, renal lipid peroxidation along with significant increment (p<0.05) in renal enzymatic and non-enzymatic antioxidants. SR leaf extract ameliorates GM induced nephrotoxicity and renal dysfunction and thus validates its ethnomedicinal use. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

  7. Renal protection in diabetes--an emerging role for calcium antagonists

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    Parving, H H; Tarnow, L; Rossing, P

    1997-01-01

    The combination of diabetes and hypertension increases the changes of progressive renal disorder and ultimately renal failure. Roughly 40% of all diabetics, whether insulin dependent or not, develop diabetic nephropathy. Diabetic nephropathy is the single most important cause of end-stage renal...... disease in the western world and accounts for more than a quarter of all end-stage renal diseases. It is also a major cause of increased morbidity and mortality in diabetic patients. Increased arterial blood pressure is an early and common phenomenon in incipient and overt diabetic nephropathy...... the ability to retard renal growth and possibly to attenuate mesangial entrapment of macromolecules and to attenuate the mitogenic effects of diverse growth factors. Calcium antagonists (except the old short-acting dihydropyridine drugs) reduce microalbuminuria and preserve kidney function in diabetic...

  8. Inhibition of G0/G1 Switch 2 Ameliorates Renal Inflammation in Chronic Kidney Disease

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    Naoya Matsunaga

    2016-11-01

    Full Text Available Chronic kidney disease (CKD is a global health problem, and novel therapies to treat CKD are urgently needed. Here, we show that inhibition of G0/G1 switch 2 (G0s2 ameliorates renal inflammation in a mouse model of CKD. Renal expression of chemokine (C-C motif ligand 2 (Ccl2 was increased in response to p65 activation in the kidneys of wild-type 5/6 nephrectomy (5/6Nx mice. Moreover, 5/6Nx Clk/Clk mice, which carry homozygous mutations in the gene encoding circadian locomotor output cycles kaput (CLOCK, did not exhibit aggravation of apoptosis or induction of F4/80-positive cells. The renal expression of G0s2 in wild-type 5/6Nx mice was important for the transactivation of Ccl2 by p65. These pathologies were ameliorated by G0s2 knockdown. Furthermore, a novel small-molecule inhibitor of G0s2 expression was identified by high-throughput chemical screening, and the inhibitor suppressed renal inflammation in 5/6Nx mice. These findings indicated that G0s2 inhibitors may have applications in the treatment of CKD.

  9. Amelioration of Gamma-hexachlorocyclohexane (Lindane induced renal toxicity by Camellia sinensis in Wistar rats

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    W. L. N. V. Vara Prasad

    2016-11-01

    Full Text Available Aim: A study to assess the toxic effects of gamma-hexachlorocyclohexane (γ-HCH (lindane and ameliorative effects of Camellia sinensis on renal system has been carried out in male Wistar rats. Materials and Methods: Four groups of rats with 18 each were maintained under standard laboratory hygienic conditions and provided feed and water ad libitum. γ-HCH was gavaged at 20 mg/kg b.wt. using olive oil as vehicle to Groups II. C. sinensis at 100 mg/kg b.wt. was administered orally in distilled water to Group IV in addition to γ-HCH 20 mg/kg b.wt. up to 45 days to study ameliorative effects. Groups I and III were treated with distilled water and C. sinensis (100 mg/kg b.wt., respectively. Six rats from each group were sacrificed at fortnight intervals. Serum was collected for creatinine estimation. The kidney tissues were collected in chilled phosphate buffer saline for antioxidant profile and in also 10% buffered formalin for histopathological studies. Results: γ-HCH treatment significantly increased serum creatinine and significantly reduced the renal antioxidative enzymes catalase, superoxide dismutase, and glutathione peroxidase. Grossly, severe congestion was noticed in the kidneys. Microscopically, kidney revealed glomerular congestion, atrophy, intertubular hemorrhages, degenerative changes in tubular epithelium with vacuolated cytoplasm, desquamation of epithelium and urinary cast formation. A significant reduction in serum creatinine levels, significant improvement in renal antioxidant enzyme activities and near to normal histological appearance of kidneys in Group IV indicated that the green tea ameliorated the effects of γ-HCH, on renal toxicity. Conclusion: This study suggested that C. sinensis extract combined with γ-HCH could enhance antioxidant/detoxification system which consequently reduced the oxidative stress thus potentially reducing γ-HCH toxicity and tissue damage.

  10. Amelioration of renal lesions associated with diabetes by dietary curcumin in streptozotocin diabetic rats.

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    Suresh Babu, P; Srinivasan, K

    1998-04-01

    Curcumin, the coloring principle of the commonly used spice turmeric (Curcuma longa) was fed at 0.5% in the diet to streptozotocin-induced diabetic Wistar rats for 8 weeks. Renal damage was assessed by the amount of proteins excreted in the urine and the extent of leaching of renal tubular enzymes: NAG, LDH, AsAT, AlAT, alkaline and acid phosphatases. The integrity of kidney was assessed by measuring the activities of several key enzymes of the renal tissue: glucose-6-phosphate dehydrogenase, glucose-6-phosphatase, and LDH (Carbohydrate metabolism), aldose reductase and sorbitol dehydrogenase (polyol pathway), transaminases, ATPases and membrane PUFA/SFA ratio (membrane integrity). Data on enzymuria, albuminuria, activity of kidney ATPases and fatty acid composition of renal membranes in diabetic condition suggested that dietary curcumin brought about significant beneficial modulation of the progression of renal lesions in diabetes. These findings were also corroborated by histological examination of kidney sections. It is inferred that this beneficial ameliorating influence of dietary curcumin on diabetic nephropathy is possibly mediated through its ability to lower blood cholesterol levels.

  11. Erhuang Formula ameliorates renal damage in adenine-induced chronic renal failure rats via inhibiting inflammatory and fibrotic responses.

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    Zhang, Chun-Yan; Zhu, Jian-Yong; Ye, Ying; Zhang, Miao; Zhang, Li-Jun; Wang, Su-Juan; Song, Ya-Nan; Zhang, Hong

    2017-11-01

    The present study aimed to evaluate the protective effects of Erhuang Formula (EHF) and explore its pharmacological mechanisms on adenine-induced chronic renal failure (CRF). The compounds in EHF were analyzed by HPLC/MS. Adenine-induced CRF rats were administrated by EHF. The effects were evaluated by renal function examination and histology staining. Immunostaining of some proteins related cell adhesion was performedin renal tissues, including E-cadherin, β-catenin, fibronectin and laminin. The qRT-PCR was carried out determination of gene expression related inflammation and fibrosis including NF-κB, TNF-α, TGF-β1, α-SMA and osteopontin (OPN). Ten compounds in EHF were identified including liquiritigenin, farnesene, vaccarin, pachymic acid, cycloastragenol, astilbin, 3,5,6,7,8,3',4'-heptemthoxyflavone, physcion, emodin and curzerene. Abnormal renal function and histology had significant improvements by EHF treatment. The protein expression of β-catenin, fibronectin and laminin were significantly increased and the protein expression of E-cadherin significantly decreased in CRF groups. However, these protein expressions were restored to normal levels in EHF group. Furthermore, low expression of PPARγ and high expression of NF-κB, TNF-α, TGF-β1, α-SMA and OPN were substantially restored by EHF treatment in a dose-dependent manner. EHF ameliorated renal damage in adenine-induced CRF rats, and the mechanisms might involve in the inhibition of inflammatory and fibrotic responses and the regulation of PPARγ, NF-κB and TGF-β signaling pathways. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  12. The effects of angiotensin II receptor antagonist (candesartan on rat renal vascular resistance

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    Supatraviwat, J

    2004-05-01

    Full Text Available The present study aimed to investigate the action of angiotensin II (AII on renal perfusion pressure and renal vascular resistance using noncompetitive AT1-receptor antagonist (candesartan or CV 11974. Experiments were performed in isolated kidney of adult male Wistar rats. Kreb's Henseleit solution was perfused into the renal artery at the rate of 3.5 ml/min. This flow rate was designed in order to maintain renal perfusion pressure between 80-120 mm Hg. Dose-response relationship between perfusion flow rate and AII concentration were studied. Renal perfusion pressure in response to 1, 10 and 100 nM AII were increased from basal perfusion pressure of 94±8 mm Hg to 127±6, 157±12 and 190±16 mm Hg, respectively. Administration of perfusate containing 11.4 μM candesartan for 30 min had no effect on the basal perfusion pressure. However, this significantly reduced renal perfusion pressure in the presence of AII (1, 10 and 100 nM by 39%, 47% and 61%, (n=7, P<0.05 respectively. At the basal perfusion pressure, calculated renal vascular resistance was 27±2 mm Hg · min · ml-1. However, the vascular resistance were found to be 41±1, 45±2 and 47±2 mm Hg · min · ml-1 when 1, 10 and 100 nM AII were added. Moreover, this dose of candesartan also showed a significant decrease in renal vascular resistance at the corresponding doses of AII by 38%, 48% and 43%, (n=7, P<0.05 respectively. The higher dose of candesartan (22.7 μM completely inhibited the action of 1, 10 and 100 nM AII on renal vasoconstriction. These results may indicate that the action of AII on renal vascular resistance is via AT1-receptor, at least in rat isolated perfusion kidney.

  13. Lycium chinense leaves extract ameliorates diabetic nephropathy by suppressing hyperglycemia mediated renal oxidative stress and inflammation.

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    Olatunji, Opeyemi Joshua; Chen, Hongxia; Zhou, Yifeng

    2018-06-01

    Diabetic nephropathy is one of the most serious and most frequently encountered diabetic complication, accounting for the highest cause of end-stage renal disease. This present study was aimed at exploring the protective/attenuative effect of Lycium chinense leaf extract (MELC) on streptozotocin induced diabetic nephropathy in experimental Sprague Dawley rats. The oral administration of diabetic rats with MELC markedly ameliorated renal dysfunction as observed in the significant reduction in the serum levels of creatinine, blood urea nitrogen (BUN), albumin and TGF-β1 as compared to the untreated diabetic control rats. In addition, the elevated levels of renal oxidative stress markers and pro-inflammatory parameters (GSH, SOD, CAT, MDA, TNF-α, IL-6 and IL-1β) were significantly reduced in MELC treated diabetic rats. The results obtained in this study suggests that L. chinense leaf might have the potential as possible pharmacological agent against diabetic nephropathy by suppressing renal oxidative stress and inflammation. Copyright © 2018. Published by Elsevier Masson SAS.

  14. Deficiency of the Erc/mesothelin gene ameliorates renal carcinogenesis in Tsc2 knockout mice.

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    Zhang, Danqing; Kobayashi, Toshiyuki; Kojima, Tetsuo; Kanenishi, Kenji; Hagiwara, Yoshiaki; Abe, Masaaki; Okura, Hidehiro; Hamano, Yoshitomo; Sun, Guodong; Maeda, Masahiro; Jishage, Kou-ichi; Noda, Tetsuo; Hino, Okio

    2011-04-01

    Genetic crossing experiments were performed between tuberous sclerosis-2 (Tsc2) KO and expressed in renal carcinoma (Erc) KO mice to analyze the function of the Erc/mesothelin gene in renal carcinogenesis. We found the number and size of renal tumors were significantly less in Tsc2+/-;Erc-/- mice than in Tsc2+/-;Erc+/+ and Tsc2+/-;Erc+/- mice. Tumors from Tsc2+/-;Erc-/- mice exhibited reduced cell proliferation and increased apoptosis, as determined by proliferating cell nuclear antigen (Ki67) and TUNEL analysis, respectively. Adhesion to collagen-coated plates in vitro was enhanced in Erc-restored cells and decreased in Erc-suppressed cells with siRNA. Tumor formation by Tsc2-deficient cells in nude mice was remarkably suppressed by stable knockdown of Erc with shRNA. Western blot analysis showed that the phosphorylation of focal adhesion kinase, Akt and signal transducer and activator of transcription protein 3 were weaker in Erc-deficient/suppressed cells compared with Erc-expressed cells. These results indicate that deficiency of the Erc/mesothelin gene ameliorates renal carcinogenesis in Tsc2 KO mice and inhibits the phosphorylation of several kinases of cell adhesion mechanism. This suggests that Erc/mesothelin may have an important role in the promotion and/or maintenance of carcinogenesis by influencing cell-substrate adhesion via the integrin-related signal pathway. © 2011 Japanese Cancer Association.

  15. Dahuang Fuzi Decoction Attenuates Renal Fibrosis and Ameliorates Mitochondrial Dysfunction in Chronic Aristolochic Acid Nephropathy

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    Guang-xing Shui

    2017-01-01

    Full Text Available Objectives. The effects of the traditional formula Dahuang Fuzi Decoction (DFD on chronic aristolochic acid nephropathy (AAN in mice and its underlying mechanisms were studied. Methods. Mice were randomly divided into the following six groups: the control group, the model group (AAN, the saline-treated group (AAN + vehicle, the normal dose DFD-treated group (AAN + NDFD, the high dose DFD-treated group (AAN + HDFD, and the rosiglitazone treated group (AAN + Rosi. After treating for 8 weeks, 24 h urine and blood samples were collected and the mice sacrificed to study the biochemical parameters associated with renal function. The samples were analyzed for renal fibrosis and mitochondrial dysfunction (MtD markers. To achieve that, collagen III, collagen I, mitochondrial DNA copy numbers (mtDNA, mitochondrial membrane potential (MMP, ATP content, and ROS production were evaluated. Results. Our results showed that proteinuria, kidney function, and the renal pathological characteristics were improved by DFD and rosiglitazone. The expression of collagen III and collagen I decreased after treating with either DFD or rosiglitazone. Mitochondrial dysfunction based on the increase in ROS production, decrease in mitochondrial DNA copy numbers, and reduction of MMP and ATP content was improved by DFD and rosiglitazone. Conclusions. DFD could protect against renal impairments and ameliorate mitochondrial dysfunction in chronic AAN mice.

  16. Resveratrol, an Nrf2 activator, ameliorates aging-related progressive renal injury.

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    Kim, Eun Nim; Lim, Ji Hee; Kim, Min Young; Ban, Tae Hyun; Jang, In-Ae; Yoon, Hye Eun; Park, Cheol Whee; Chang, Yoon Sik; Choi, Bum Soon

    2018-01-11

    Two important issues in the aging kidney are mitochondrial dysfunction and oxidative stress. An Nrf2 activator, resveratrol, is known to have various effects. Resveratrol may prevent inflammation and oxidative stress by activating Nrf2 and SIRT1 signaling. We examined whether resveratrol could potentially ameliorate the cellular condition, such as renal injury due to cellular oxidative stress and mitochondrial dysfunction caused by aging. Male 18-month-old C57BL/6 mice were used. Resveratrol (40 mg/kg) was administered to aged mice for 6 months. We compared histological changes, oxidative stress, and aging-related protein expression in the kidney between the resveratrol-treated group (RSV) and the control group (cont). We performed experiments using small-interfering RNAs (siRNAs) for Nrf2 and SIRT1 in cultured HK2 cells. Resveratrol improved renal function, proteinuria, histological changes and inflammation in aging mice. Also, expression of Nrf2-HO-1-NOQ-1 signaling and SIRT1-AMPK-PGC-1α signaling was increased in the RSV group. Transfection with Nrf2 and SIRT1 siRNA prevented resveratrol-induced anti-oxidative effect in HK2 cells in media treated with H 2 O 2 . Activation of the Nrf2 and SIRT1 signaling pathways ameliorated oxidative stress and mitochondrial dysfunction. Pharmacological targeting of Nrf2 signaling molecules may reduce the pathologic changes of aging in the kidney.

  17. Influence of specific and non-specific endothelin receptor antagonists on renal morphology in rats with surgical renal ablation.

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    Nabokov, A; Amann, K; Wagner, J; Gehlen, F; Münter, K; Ritz, E

    1996-03-01

    Studies in experimental models of chronic renal failure suggest an important role for the endothelin system in the development of renal scarring. Endothelin receptor (ETR) anatagonists interfere with progression, but it has not been resolved (i) whether this is true for all models of renal damage, (ii) to what extent the effect is modulated by systemic blood pressure and (iii) whether the effect is similar for ETAR and ETA/ETBR antagonists. 5/6 subtotal nephrectomy (SNX) by surgical ablation in male Sprague-Dawley rats. Comparison of ACE inhibitor Trandolapril (0.1 mg/kg/day), ETAR antagonist BMS 182874 (30 mg/kg/day) and ETAR/ETBR antagonist Ro 46-2005 (30 mg/kg/day) by gavage. Duration of the experiment eight weeks. Systolic blood pressure by tail plethysmography. Perfusion fixation of kidneys and morphometric analysis ET-1 and ETA/ETBR by quantitative PCR. SNX caused a significant (P < 0.01) increase of systolic blood pressure (170 +/- 8.6 mmHg) compared to sham operated controls (131 +/- 5.3 mmHg). Blood pressure was significantly (P < 0.001) lower with Trandolapril (128 +/- 5.3 mmHg), but not with BMS 182874 (153 +/- 5.9 mmHg) or Ro 46-2005 (167 +/- 7.6 mmHg). Compared to sham operated rats (0.03 +/- 0.01) glomerulosclerosis index (GSI) was significantly (P < 0.01) higher in the untreated SNX group (0.9 +/- 0.15). Significantly lower GSI was found in Trandolapril treated (0.29 +/- 0.04), BMS 182874 treated (0.36 +/- 0.05), and Ro 46-2005 treated animals (0.45 +/- 0.11). The effect of BMS 182874 was accompanied by lower tubulointerstitial damage index. Mean glomerular volume was dramatically increased (P < 0.001) in SNX rats as compared to sham operated animals. This glomerular enlargement was partially prevented by Trandolapril (P < 0.05), but not by either ETR antagonist. ET-1 mRNA tended to be higher in SNX irrespective of treatment, while ETAR and ETBR mRNA were significantly lower. Both specific (ETAR) and non-specific (ETA/ETBR) endothelin antagonists

  18. Taurine Ameliorates Renal Oxidative Damage and Thyroid Dysfunction in Rats Chronically Exposed to Fluoride.

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    Adedara, Isaac A; Ojuade, Temini Jesu D; Olabiyi, Bolanle F; Idris, Umar F; Onibiyo, Esther M; Ajeigbe, Olufunke F; Farombi, Ebenezer O

    2017-02-01

    Excessive exposure to fluoride poses several detrimental effects to human health particularly the kidney which is a major organ involved in its elimination from the body. The influence of taurine on fluoride-induced renal toxicity was investigated in a co-exposure paradigm for 45 days using five groups of eight rats each. Group I rats received normal drinking water alone, group II rats were exposed to sodium fluoride (NaF) in drinking water at 15 mg/L alone, group III received taurine alone at a dose of 200 mg/kg group IV rats were co-administered with NaF and taurine (100 mg/kg), while group V rats were co-administered with NaF and taurine (200 mg/kg). Administration of taurine significantly reversed the fluoride-mediated decrease in absolute weight and organo-somatic index of the kidney in the exposed rats. Taurine significantly prevented fluoride-induced elevation in plasma urea and creatinine levels in the exposed rats. Moreover, taurine restored fluoride-mediated decrease in the circulatory concentrations of triiodothyronine, thyroxine, and the ratio of triiodothyronine to thyroxine. Taurine ameliorated fluoride-mediated decrease in renal antioxidant status by significantly enhancing the antioxidant enzyme activities as well as glutathione level in the exposed rats. Additionally, taurine inhibited fluoride-induced renal oxidative damage by markedly decreasing the hydrogen peroxide and malondialdehyde levels as well as improved the kidney architecture in the treated rats. Collectively, taurine protected against fluoride-induced renal toxicity via enhancement of thyroid gland function, renal antioxidant status, and histology in rats.

  19. Silymarin and Nigella sativa extract ameliorate paracetamol induced oxidative stress and renal dysfunction in male mice

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    Reham Zakaria Hamza

    2015-06-01

    Full Text Available Objective: To evaluate the ameliorative role of silymarin or/and Nigella sativa (N. sativa water extract against N-acetyl-p-aminophenol (APAP-induced renal function deterioration in male mice at the biochemical levels. Methods: The mice were divided into seven groups (10/group. The first group was served as control. The second group was treated with dose of APAP. The third and fourth groups were treated with silymarin alone and N. sativa water extract alone, respectively. The fifth and sixth groups were treated with combination of APAP with silymarin and APAP with N. sativa water extract, respectively. The seventh group was treated with a combination of both ameliorative compounds (silymarin and N. sativa water extract with APAP and all animals were treated for a period of 30 days. Results: Exposure to APAP at the treated dose for mice led to an alteration of kidney function parameters, increase in the level of serum urea and creatinine. Also, paracetamol administration induced oxidative stress in kidney homogenates by increasing malondialdhyde level and decreasing superoxide dismutase and catalase activities and this stress was ameliorated by administration of either silymarin or N. sativa water extract. Conclusions: Administration of silymarin or/and N. sativa water extract to APAP-treated mice alleviate the toxicity of APAP, and this appeared clearly by biochemical improvement of kidney function parameters and antioxidant parameters. But, the alleviation is more pronounced with the both antioxidants. Thus, the pronounce effect of silymarin and N. sativa water extract is most effective in reducing the toxicity induced by APAP and improving the kidney function parameters and antioxidant status of kidney of male mice.

  20. Honey Supplementation in Spontaneously Hypertensive Rats Elicits Antihypertensive Effect via Amelioration of Renal Oxidative Stress

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    Omotayo O. Erejuwa

    2012-01-01

    Full Text Available Oxidative stress is implicated in the pathogenesis and/or maintenance of elevated blood pressure in hypertension. This study investigated the effect of honey on elevated systolic blood pressure (SBP in spontaneously hypertensive rats (SHR. It also evaluated the effect of honey on the amelioration of oxidative stress in the kidney of SHR as a possible mechanism of its antihypertensive effect. SHR and Wistar Kyoto (WKY rats were randomly divided into 2 groups and administered distilled water or honey by oral gavage once daily for 12 weeks. The control SHR had significantly higher SBP and renal malondialdehyde (MDA levels than did control WKY. The mRNA expression levels of nuclear factor erythroid 2-related factor 2 (Nrf2 and glutathione S-transferase (GST were significantly downregulated while total antioxidant status (TAS and activities of GST and catalase (CAT were higher in the kidney of control SHR. Honey supplementation significantly reduced SBP and MDA levels in SHR. Honey significantly reduced the activities of GST and CAT while it moderately but insignificantly upregulated the Nrf2 mRNA expression level in the kidney of SHR. These results indicate that Nrf2 expression is impaired in the kidney of SHR. Honey supplementation considerably reduces elevated SBP via amelioration of oxidative stress in the kidney of SHR.

  1. The 6-hydroxychromanol derivative SUL-109 ameliorates renal injury after deep hypothermia and rewarming in rats.

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    Vogelaar, Pieter C; Roorda, Maurits; de Vrij, Edwin L; Houwertjes, Martin C; Goris, Maaike; Bouma, Hjalmar; van der Graaf, Adrianus C; Krenning, Guido; Henning, Robert H

    2018-04-11

    Mitochondrial dysfunction plays an important role in kidney damage in various pathologies, including acute and chronic kidney injury and diabetic nephropathy. In addition to the well-studied ischaemia/reperfusion (I/R) injury, hypothermia/rewarming (H/R) also inflicts acute kidney injury. Substituted 6-hydroxychromanols are a novel class of mitochondrial medicines that ameliorate mitochondrial oxidative stress and protect the mitochondrial network. To identify a novel 6-hydroxychromanol that protects mitochondrial structure and function in the kidney during H/R, we screened multiple compounds in vitro and subsequently assessed the efficacy of the 6-hydroxychromanol derivatives SUL-109 and SUL-121 in vivo to protect against kidney injury after H/R in rats. Human proximal tubule cell viability was assessed following exposure to H/R for 48/4 h in the presence of various 6-hydroxychromanols. Selected compounds (SUL-109, SUL-121) or vehicle were administered to ketamine-anaesthetized male Wistar rats (IV 135 µg/kg/h) undergoing H/R at 15°C for 3 h followed by rewarming and normothermia for 1 h. Metabolic parameters and body temperature were measured throughout. In addition, renal function, renal injury, histopathology and mitochondrial fitness were assessed. H/R injury in vitro lowered cell viability by 94 ± 1%, which was counteracted dose-dependently by multiple 6-hydroxychomanols derivatives. In vivo, H/R in rats showed kidney injury molecule 1 expression in the kidney and tubular dilation, accompanied by double-strand DNA breaks and protein nitrosylation. SUL-109 and SUL-121 ameliorated tubular kidney damage, preserved mitochondrial mass and maintained cortical adenosine 5'-triphosphate (ATP) levels, although SUL-121 did not reduce protein nitrosylation. The substituted 6-hydroxychromanols SUL-109 and SUL-121 ameliorate kidney injury during in vivo H/R by preserving mitochondrial mass, function and ATP levels. In addition, both 6-hydroxychromanols

  2. Emerging growth factor receptor antagonists for the treatment of renal cell carcinoma.

    Science.gov (United States)

    Zahoor, Haris; Rini, Brian I

    2016-12-01

    The landscape of systemic treatment for metastatic renal cell carcinoma (RCC) has dramatically changed with the introduction of targeted agents including vascular endothelial growth factor (VEGF) inhibitors. Recently, multiple new agents including growth factor receptor antagonists and a checkpoint inhibitor were approved for the treatment of refractory metastatic RCC based on encouraging benefit shown in clinical trials. Areas covered: The background and biological rationale of existing treatment options including a brief discussion of clinical trials which led to their approval, is presented. This is followed by reviewing the limitations of these therapeutic options, medical need to develop new treatments and major goals of ongoing research. We then discuss two recently approved growth factor receptor antagonists i.e. cabozantinib and lenvatinib, and a recently approved checkpoint inhibitor, nivolumab, and issues pertaining to drug development, and future directions in treatment of metastatic RCC. Expert opinion: Recently approved growth factor receptor antagonists have shown encouraging survival benefit but associated drug toxicity is a major issue. Nivolumab, a programmed death 1 (PD-1) checkpoint inhibitor, has similarly shown survival benefit and is well tolerated. With multiple options now available in this patient population, the right sequence of these agents remains to be determined.

  3. Inhibition of Extracellular Signal-Regulated Kinases Ameliorates Hypertension-Induced Renal Vascular Remodeling in Rat Models

    Directory of Open Access Journals (Sweden)

    Li Jing

    2011-11-01

    Full Text Available The aim of this study is to investigate the effect of the extracellular signal-regulated kinases 1/2 (ERK1/2 inhibitor, PD98059, on high blood pressure and related vascular changes. Blood pressure was recorded, thicknesses of renal small artery walls were measured and ERK1/2 immunoreactivity and erk2 mRNA in renal vascular smooth muscle cells (VSMCs and endothelial cells were detected by immunohistochemistry and in situ hybridization in normotensive wistar kyoto (WKY rats, spontaneously hypertensive rats (SHR and PD98059-treated SHR. Compared with normo-tensive WKY rats, SHR developed hypertension at 8 weeks of age, thickened renal small artery wall and asymmetric arrangement of VSMCs at 16 and 24 weeks of age. Phospho-ERK1/2 immunoreactivity and erk2 mRNA expression levels were increased in VSMCs and endothelial cells of the renal small arteries in the SHR. Treating SHR with PD98059 reduced the spontaneous hypertension-induced vascular wall thickening. This effect was associated with suppressions of erk2 mRNA expression and ERK1/2 phosphorylation in VSMCs and endothelial cells of the renal small arteries. It is concluded that inhibition of ERK1/2 ameliorates hypertension induced vascular remodeling in renal small arteries.

  4. Slit2 ameliorates renal inflammation and fibrosis after hypoxia-and lipopolysaccharide-induced epithelial cells injury in vitro

    Energy Technology Data Exchange (ETDEWEB)

    Zhou, Xiangjun [Department of Urology, Taihe Hospital, Hubei University of Medicine, Hubei (China); Yao, Qisheng, E-mail: yymcyqs@126.com [Department of Urology, Taihe Hospital, Hubei University of Medicine, Hubei (China); Sun, Xinbo; Gong, Xiaoxin; Yang, Yong; Chen, Congbo [Department of Urology, Taihe Hospital, Hubei University of Medicine, Hubei (China); Shan, Guang [Department of Urology, Renmin Hospital of Wuhan University, Hubei (China)

    2017-03-01

    Hypoxic acute kidney injury (AKI) is often incompletely repaired and leads to chronic kidney disease (CKD), which is characterized by tubulointerstitial inflammation and fibrosis. The Slit2 family of secreted glycoproteins is expressed in the kidney, it has been shown to exert an anti-inflammatory activity and prevent ischemic renal injury in vivo. However, whether Slit2 reduces renal fibrosis and inflammation after hypoxic and inflammatory epithelial cells injury in vitro remains unknown. In this study, we aimed to evaluate whether Slit2 ameliorated fibrosis and inflammation in two renal epithelial cells line challenged with hypoxia and lipopolysaccharide (LPS). Renal epithelial cells were treated with hypoxia and LPS to induce cell injury. Hoechst staining and Western blot analysis was conducted to examine epithelial cells injury. Immunofluorescence staining and Western blot analysis was performed to evaluate tubulointerstitial fibrosis. Real-time polymerase chain reaction (PCR) tested the inflammatory factor interleukin (IL)−1β and tumor necrosis factor (TNF)-α, and Western blot analysis determined the hypoxia-inducible factor (HIF)−1α, Toll-like receptor 4 (TLR4) and nuclear factor (NF)-κB. Results revealed that hypoxia induced epithelial cells apoptosis, inflammatory factor IL-1β and TNF-α release and tubulointerstitial fibrosis. LPS could exacerbate hypoxia -induced epithelial cells apoptosis, IL-1β and TNF-α release and fibrosis. Slit2 reduced the expression of fibronectin, the rate of epithelial cell apoptosis, and the expression of inflammatory factor. Slit2 could also inhibit the expression of TLR4 and NF-κB, but not the expression of HIF-1α. Therefore, Slit2 attenuated inflammation and fibrosis after LPS- and hypoxia-induced epithelial cells injury via the TLR4/NF-κB signaling pathway, but not depending on the HIF-1α signaling pathway. - Highlights: • Slit2 ameliorates inflammation after hypoxia-and LPS-induced epithelial cells injury

  5. The Soluble Epoxide Hydrolase Inhibitor AR9281 Decreases Blood Pressure, Ameliorates Renal Injury and Improves Vascular Function in Hypertension

    Directory of Open Access Journals (Sweden)

    Sean Shaw

    2009-12-01

    Full Text Available Soluble epoxide hydrolase inhibitors (sEHIs are demonstrating promise as potential pharmaceutical agents for the treatment of cardiovascular disease, diabetes, inflammation, and kidney disease. The present study determined the ability of a first-inclass sEHI, AR9281, to decrease blood pressure, improve vascular function, and decrease renal inflammation and injury in angiotensin hypertension. Rats were infused with angiotensin and AR9281 was given orally during the 14-day infusion period. Systolic blood pressure averaged 180 ± 5 mmHg in vehicle treated and AR9281 treatment significantly lowered blood pressure to 142 ± 7 mmHg in angiotensin hypertension. Histological analysis demonstrated decreased injury to the juxtamedullary glomeruli. Renal expression of inflammatory genes was increased in angiotensin hypertension and two weeks of AR9281 treatment decreased this index of renal inflammation. Vascular function in angiotensin hypertension was also improved by AR9281 treatment. Decreased afferent arteriolar and mesenteric resistance endothelial dependent dilator responses were ameliorated by AR9281 treatment of angiotensin hypertensive rats. These data demonstrate that the first-in-class sEHI, AR9281, lowers blood pressure, improves vascular function and reduces renal damage in angiotensin hypertension.

  6. Risk of renal failure with the non-vitamin K antagonist oral anticoagulants: systematic review and meta-analysis.

    Science.gov (United States)

    Caldeira, Daniel; Gonçalves, Nilza; Pinto, Fausto J; Costa, João; Ferreira, Joaquim J

    2015-07-01

    Vitamin K antagonists (VKA)-related nephropathy is a novel entity characterized by acute kidney injury related to International Normalized Ratio supratherapeutic levels. Non-vitamin K antagonists oral anticoagulants (NOACs) have a predictable dose-response relationship and an improved safety profile. We hypothesized that these drugs do not have an increased risk of incident renal failure, which may be detrimental for the use of NOACs. Systematic review and meta-analysis of phase III randomized controlled trials (RCTs). Trials were searched through Medline, Cochrane Library and public assessment reports in August 2014. Primary outcome was renal failure. NOACs were evaluated against any comparator. Random-effects meta-analysis was performed by default, and pooled estimates were expressed as Risk Ratio (RR) and 95%CI. Heterogeneity was evaluated with I(2) test. Ten RCTs fulfilled inclusion criteria (one apixaban RCT, three dabigatran RCTs, and six rivaroxaban RCTs), enrolling 75 100 patients. Overall NOACs did not increase the risk of renal failure with an RR 0.96, 95%CI 0.88-1.05 compared with VKA or Low-molecular weight heparin (LMWH), without significant statistical heterogeneity (I(2)  = 3.5%). Compared with VKA, NOACs did not increase the risk of renal failure (RR 0.96, 95%CI 0.87-1.07; I(2)  = 17.8%; six RCTs). Rivaroxaban did not show differences in the incidence of renal failure compared with LMWH (RR 1.20, 95%CI 0.37-3.94; four trials), but there was an increased risk of creatinine elevation RR 1.25, 95%CI 1.08-1.45; I(2)  = 0%. NOACs had a similar risk of renal failure compared with VKA/LMWH in phase III RCTs. Post-marketing surveillance should be warranted. Copyright © 2015 John Wiley & Sons, Ltd.

  7. Novel 5-HT5A receptor antagonists ameliorate scopolamine-induced working memory deficit in mice and reference memory impairment in aged rats.

    Science.gov (United States)

    Yamazaki, Mayako; Okabe, Mayuko; Yamamoto, Noriyuki; Yarimizu, Junko; Harada, Katsuya

    2015-03-01

    Despite the human 5-HT5A receptor being cloned in 1994, the biological function of this receptor has not been extensively characterized due to a lack of specific ligands. We recently reported that the selective 5-HT5A receptor antagonist ASP5736 ameliorated cognitive impairment in several animal models of schizophrenia. Given that areas of the brain with high levels of 5-HT5A receptor expression, such as the hippocampus and cerebral cortex, have important functions in cognition and memory, we evaluated the chemically diverse, potent and brain-penetrating 5-HT5A receptor antagonists ASP5736, AS2030680, and AS2674723 in rodent models of cognitive dysfunction associated with dementia. Each of these compounds exhibited a high affinity for recombinant 5-HT5A receptors that was comparable to that of the non-selective ligand of this receptor, lysergic acid diethylamide (LSD). Although each compound had a low affinity for other receptors, 5-HT5A was the only receptor for which all three compounds had a high affinity. Each of the three compounds ameliorated scopolamine-induced working memory deficit in mice and improved reference memory impairment in aged rats at similar doses. Further, ASP5736 decreased the binding of LSD to 5-HT5A receptors in the olfactory bulb of rats in a dose-dependent manner and occupied 15%-50% of brain 5-HT5A receptors at behaviorally effective doses. These results indicate that the 5-HT5A receptor is involved in learning and memory and that treatment with 5-HT5A receptor antagonists might be broadly effective for cognitive impairment associated with not only schizophrenia but also dementia. Copyright © 2015 The Authors. Production and hosting by Elsevier B.V. All rights reserved.

  8. The AT1 Receptor Antagonist, L-158,809, Prevents or Ameliorates Fractionated Whole-Brain Irradiation-Induced Cognitive Impairment

    International Nuclear Information System (INIS)

    Robbins, Mike E.; Payne, Valerie B.S.; Tommasi, Ellen B.S.; Diz, Debra I.; Hsu, Fang-Chi; Brown, William R.; Wheeler, Kenneth T.; Olson, John; Zhao Weiling

    2009-01-01

    Purpose: We hypothesized that administration of the angiotensin type 1 (AT1) receptor antagonist, L-158,809, to young adult male rats would prevent or ameliorate fractionated whole-brain irradiation (WBI)-induced cognitive impairment. Materials and Methods: Groups of 80 young adult male Fischer 344 x Brown Norway (F344xBN) rats, 12-14 weeks old, received either: (1) fractionated WBI; 40 Gy of γ rays in 4 weeks, 2 fractions/week, (2) sham-irradiation; (3) WBI plus L-158,809 (20 mg/L drinking water) starting 3 days prior, during, and for 14, 28, or 54 weeks postirradiation; and (4) sham-irradiation plus L-158,809 for 14, 28, or 54 weeks postirradiation. An additional group of rats (n = 20) received L-158,809 before, during, and for 5 weeks postirradiation, after which they received normal drinking water up to 28 weeks postirradiation. Results: Administration of L-158,809 before, during, and for 28 or 54 weeks after fractionated WBI prevented or ameliorated the radiation-induced cognitive impairment observed 26 and 52 weeks postirradiation. Moreover, giving L-158,809 before, during, and for only 5 weeks postirradiation ameliorated the significant cognitive impairment observed 26 weeks postirradiation. These radiation-induced cognitive impairments occurred without any changes in brain metabolites or gross histologic changes assessed at 28 and 54 weeks postirradiation, respectively. Conclusions: Administering L-158,809 before, during, and after fractionated WBI can prevent or ameliorate the chronic, progressive, cognitive impairment observed in rats at 26 and 52 weeks postirradiation. These findings offer the promise of improving the quality of life for brain tumor patients

  9. Lexipafant (BB-882), a platelet activating factor receptor antagonist, ameliorates mucosal inflammation in an animal model of colitis

    NARCIS (Netherlands)

    Meenan, J.; Grool, T. A.; Hommes, D. W.; Dijkhuizen, S.; ten Kate, F. J.; Wood, M.; Whittaker, M.; Tytgat, G. N.; van Deventer, S. J.

    1996-01-01

    To assess the anti-inflammatory action of lexipafant (BB-882), a platelet activating factor antagonist, in an animal model of acute colitis. An animal intervention study. Following the rectal instillation of formalin 0.75% into male New Zealand White (NZW) rabbits, 0.85 ml of aggregated

  10. Heat-processed ginseng saponin ameliorates the adenine-induced renal failure in rats

    OpenAIRE

    Kim, Eun Jin; Oh, Hyun-A; Choi, Hyuck Jai; Park, Jeong Hill; Kim, Dong-Hyun; Kim, Nam Jae

    2013-01-01

    To evaluate the effect of the saponin of heat-processed ginseng (Sun ginseng, SG), we investigated the protective effect of SG total saponin fraction against adenine-induced chronic renal failure in rats. SG saponin significantly decreased the levels of urea nitrogen and creatinine in the serum, but increased the urinary excretion of urea nitrogen and creatinine, indicating an improvement of renal function. SG saponin also inhibited adenine-induced kidney hypertrophy and edema. SG saponin red...

  11. Reducing VEGF-B Signaling Ameliorates Renal Lipotoxicity and Protects against Diabetic Kidney Disease.

    Science.gov (United States)

    Falkevall, Annelie; Mehlem, Annika; Palombo, Isolde; Heller Sahlgren, Benjamin; Ebarasi, Lwaki; He, Liqun; Ytterberg, A Jimmy; Olauson, Hannes; Axelsson, Jonas; Sundelin, Birgitta; Patrakka, Jaakko; Scotney, Pierre; Nash, Andrew; Eriksson, Ulf

    2017-03-07

    Diabetic kidney disease (DKD) is the most common cause of severe renal disease, and few treatment options are available today that prevent the progressive loss of renal function. DKD is characterized by altered glomerular filtration and proteinuria. A common observation in DKD is the presence of renal steatosis, but the mechanism(s) underlying this observation and to what extent they contribute to disease progression are unknown. Vascular endothelial growth factor B (VEGF-B) controls muscle lipid accumulation through regulation of endothelial fatty acid transport. Here, we demonstrate in experimental mouse models of DKD that renal VEGF-B expression correlates with the severity of disease. Inhibiting VEGF-B signaling in DKD mouse models reduces renal lipotoxicity, re-sensitizes podocytes to insulin signaling, inhibits the development of DKD-associated pathologies, and prevents renal dysfunction. Further, we show that elevated VEGF-B levels are found in patients with DKD, suggesting that VEGF-B antagonism represents a novel approach to treat DKD. Copyright © 2017 Elsevier Inc. All rights reserved.

  12. Amelioration of pancreatic and renal derangements in streptozotocin-induced diabetic rats by polyphenol extracts of Ginger (Zingiber officinale) rhizome.

    Science.gov (United States)

    Kazeem, Mutiu Idowu; Akanji, Musbau Adewunmi; Yakubu, Musa Toyin

    2015-12-01

    Free and bound polyphenol extracts of Zingiber officinale rhizome were investigated for their antidiabetic potential in the pancreatic and renal tissues of diabetic rats at a dose of 500mg/kg body weight. Forty Wistar rats were completely randomized into five groups: A-E consisting of eight animals each. Group A (control) comprises normal healthy animals and were orally administered 1.0mL distilled water on a daily basis for 42 days while group B-E were made up of 50mg/kg streptozotocin (STZ)-induced diabetic rats. Group C and D received 1.0mL 500mg/kg body weight free and bound polyphenol extracts respectively while group E received 1.0mL 0.6mg/kg of glibenclamide. Administration of the extracts to the diabetic rats significantly reduced (pZingiber officinale could ameliorate diabetes-induced pancreatic and renal derangements in rats. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  13. Loss of the BMP antagonist USAG-1 ameliorates disease in a mouse model of the progressive hereditary kidney disease Alport syndrome.

    Science.gov (United States)

    Tanaka, Mari; Asada, Misako; Higashi, Atsuko Y; Nakamura, Jin; Oguchi, Akiko; Tomita, Mayumi; Yamada, Sachiko; Asada, Nariaki; Takase, Masayuki; Okuda, Tomohiko; Kawachi, Hiroshi; Economides, Aris N; Robertson, Elizabeth; Takahashi, Satoru; Sakurai, Takeshi; Goldschmeding, Roel; Muso, Eri; Fukatsu, Atsushi; Kita, Toru; Yanagita, Motoko

    2010-03-01

    The glomerular basement membrane (GBM) is a key component of the filtering unit in the kidney. Mutations involving any of the collagen IV genes (COL4A3, COL4A4, and COL4A5) affect GBM assembly and cause Alport syndrome, a progressive hereditary kidney disease with no definitive therapy. Previously, we have demonstrated that the bone morphogenetic protein (BMP) antagonist uterine sensitization-associated gene-1 (USAG-1) negatively regulates the renoprotective action of BMP-7 in a mouse model of tubular injury during acute renal failure. Here, we investigated the role of USAG-1 in renal function in Col4a3-/- mice, which model Alport syndrome. Ablation of Usag1 in Col4a3-/- mice led to substantial attenuation of disease progression, normalization of GBM ultrastructure, preservation of renal function, and extension of life span. Immunohistochemical analysis revealed that USAG-1 and BMP-7 colocalized in the macula densa in the distal tubules, lying in direct contact with glomerular mesangial cells. Furthermore, in cultured mesangial cells, BMP-7 attenuated and USAG-1 enhanced the expression of MMP-12, a protease that may contribute to GBM degradation. These data suggest that the pathogenetic role of USAG-1 in Col4a3-/- mice might involve crosstalk between kidney tubules and the glomerulus and that inhibition of USAG-1 may be a promising therapeutic approach for the treatment of Alport syndrome.

  14. Elevated bilirubin levels are associated with a better renal prognosis and ameliorate kidney fibrosis.

    Science.gov (United States)

    Park, Sehoon; Kim, Do Hyoung; Hwang, Jin Ho; Kim, Yong-Chul; Kim, Jin Hyuk; Lim, Chun Soo; Kim, Yon Su; Yang, Seung Hee; Lee, Jung Pyo

    2017-01-01

    Bilirubin has been reported to protect against kidney injury. However, further studies highlighting the beneficial effects of bilirubin on renal fibrosis and chronic renal function decline are necessary. We assessed a prospective cohort with a reference range of total bilirubin levels. The primary outcome was a 30% reduction in the estimated glomerular filtration rate (eGFR) from baseline, and the secondary outcome was a doubling of the serum creatinine levels, halving of the eGFR and the initiation of dialysis. In addition, experiments with tubular epithelial cells and C57BL/6 mice were performed to investigate the protective effects of bilirubin on kidney fibrosis. As a result, 1,080 patients were included in the study cohort. The study group with relative hyperbilirubinemia (total bilirubin 0.8-1.2 mg/dL) showed a better prognosis in terms of the primary outcome (adjusted hazard ratio (HR) 0.33, 95% confidence interval (CI) 0.19-0.59, P bilirubin-treated mice showed less fibrosis in the unilateral ureteral obstruction (UUO) model (P bilirubin treatment decreased fibronectin expression in tubular epithelial cells in a dose-dependent manner (P bilirubin levels were associated with better renal prognosis, and bilirubin treatment induced a beneficial effect on renal fibrosis. Therefore, bilirubin could be a potential therapeutic target to delay fibrosis-related kidney disease progression.

  15. Shenqiwan Ameliorates Renal Fibrosis in Rats by Inhibiting TGF-β1/Smads Signaling Pathway

    Directory of Open Access Journals (Sweden)

    Hongshu Chen

    2017-01-01

    Full Text Available Epithelial-mesenchymal transition (EMT refers to the transition of epithelial cells into mesenchymal cells. Emerging evidence suggests that EMT is a key point in renal interstitial fibrosis (RIF. Traditional Chinese Medicine Shenqiwan (SQW is widely used in clinical treatment of chronic kidney disease, but the underlying mechanism remains unclear. The purpose of this study is to investigate the effect of SQW on renal fibrosis and its association with TGF-β1/Smads signaling pathway. A rat model of adenine (150 mg/kg was established and intragastrically treated with various concentrations of SQW at dose of 1.5 g/kg, 3 g/kg, and 6 g/kg. Control group and model group were given the same volume of saline. Meanwhile, the positive control group was treated with Enalapril (4 mg/kg. Animals were sacrificed on 21st day after administration. The results showed that SQW could significantly relieve renal pathological damage caused by adenine, increase gene and protein expression of E-cadherin, and decrease the expression of Vimentin in kidney samples. In addition, SQW efficiently inhibited the mRNA and protein expression of p-Smad2/3 by upregulating Smad7. These results suggest that SQW could slow down the progression of renal fibrosis, possibly by inhibiting TGF-β1/Smads signaling pathway.

  16. 14S,21R-dihydroxy-docosahexaenoic acid treatment enhances mesenchymal stem cell amelioration of renal ischemia/reperfusion injury.

    Science.gov (United States)

    Tian, Haibin; Lu, Yan; Shah, Shraddha P; Wang, Quansheng; Hong, Song

    2012-05-01

    Bone marrow mesenchymal stem cells (MSCs) have shown potential to improve treatment of renal failure. The prohealing functions of MSCs have been found to be enhanced by treatment with the lipid mediator, 14S,21R-dihydroxy-docosa4Z,7Z,10Z,12E,16Z,19Z-hexaenoic acid (14S,21R-diHDHA). In this article, using a murine model of renal ischemia/reperfusion (I/R) injury, we found that treatment with 14S,21R-diHDHA enhanced MSC amelioration of renal I/R injury. Treated MSCs more efficiently inhibited I/R-induced elevation of serum creatinine levels, reduced renal tubular cell death, and inhibited infiltration of neutrophils, macrophages, and dendritic cells in kidneys. Conditioned medium from treated MSCs reduced the generation of tumor necrosis factor-α and reactive oxygen species by macrophages under I/R conditions. Infusion of treated MSCs more efficiently reduced I/R-damage to renal histological structures compared with untreated MSCs (injury score: 7.9±0.4 vs. 10.5±0.5). Treated MSCs were resistant to apoptosis in vivo when transplanted under capsules of I/R-injured kidneys (active caspase-3+ MSCs: 4.2%±2.8% vs. 11.7%±2.4% of control) and in vitro when cultured under I/R conditions. Treatment with 14S,21R-diHDHA promoted viability of MSCs through a mechanism involving activation of the phosphoinositide 3-kinase -Akt signaling pathway. Additionally, treatment of MSCs with 14S,21R-diHDHA promoted secretion of renotrophic hepatocyte growth factor and insulin growth factor-1. Similar results were obtained when 14S,21RdiHDHA was used to inhibit apoptosis of human MSCs (hMSCs) and to increase the generation of renotrophic cytokines from hMSCs. These findings provide a lead for new strategies in the treatment of acute kidney injury with MSCs.

  17. Perivascular radiofrequency renal denervation lowers blood pressure and ameliorates cardiorenal fibrosis in spontaneously hypertensive rats

    Science.gov (United States)

    Zhang, Yan; Su, Linan; Zhang, Yunrong; Wang, Qiang; Yang, Dachun; Li, De; Yang, Yongjian; Ma, Shuangtao

    2017-01-01

    Background Catheter-based renal denervation (RDN) is a promising approach to treat hypertension, but innervation patterns limit the response to endovascular RDN and the post-procedural renal artery narrowing or stenosis questions the endovascular ablation strategy. This study was performed to investigate the anti-hypertensive and target organ protective effects of perivascular RDN in spontaneously hypertensive rats (SHR). Methods SHR and normotensive Wistar-Kyoto (WKY) rats were divided into sham group (n = 10), radiofrequency ablation group (n = 20) in which rats received bilateral perivascular ablation with radiofrequency energy (2 watts), and chemical (10% phenol in 95% ethanol) ablation group (n = 12). The tail-cuff blood pressure was measured before the ablation and on day 14 and day 28 after the procedure. The plasma levels of creatinine, urea nitrogen, and catecholamines, urinary excretion of electrolytes and protein, and myocardial and glomerular fibrosis were analyzed and compared among the groups on day 28 after the procedure. Results We identified that 2-watt is the optimal radiofrequency power for perivascular RDN in rats. Perivascular radiofrequency and chemical ablation achieved roughly comparable blood pressure reduction in SHR but not in WKY on day 14 and day 28 following the procedure. Radiofrequency-mediated ablation substantially destroyed the renal nerves surrounding the renal arteries of both SHR and WKY without damaging the renal arteries and diminished the expression of tyrosine hydroxylase, the enzyme marker for postganglionic sympathetic nerves. Additionally, perivascular radiofrequency ablation also decreased the plasma catecholamines of SHR. Interestingly, both radiofrequency and chemical ablation decreased the myocardial and glomerular fibrosis of SHR, while neither increased the plasma creatinine and blood urea nitrogen nor affected the urinary excretion of electrolytes and protein when compared to sham group. Conclusions Radiofrequency

  18. Cordyceps cicadae extracts ameliorate renal malfunction in a remnant kidney model*

    Science.gov (United States)

    Zhu, Rong; Chen, Yi-ping; Deng, Yue-yi; Zheng, Rong; Zhong, Yi-fei; Wang, Lin; Du, Lan-ping

    2011-01-01

    Background and Objectives: Chronic kidney disease (CKD) is a growing public health problem with an urgent need for new pharmacological agents. Cordyceps cicadae is widely used in traditional Chinese medicine (TCM) and has potential renoprotective benefits. The current study aimed to determine any scientific evidence to support its clinical use. Methods: We analyzed the potential of two kinds of C. cicadae extract, total extract (TE) and acetic ether extract (AE), in treating kidney disease simulated by a subtotal nephrectomy (SNx) model. Sprague-Dawley rats were divided randomly into seven groups: sham-operated group, vehicle-treated SNx, Cozaar, 2 g/(kg∙d) TE SNx, 1 g/(kg∙d) TE SNx, 92 mg/(kg∙d) AE SNx, and 46 mg/(kg∙d) AE SNx. Renal injury was monitored using urine and serum analyses, and hematoxylin and eosin (HE) and periodic acid-Schiff (PAS) stainings were used to analyze the level of fibrosis. The expression of type IV collagen (Col IV), fibronectin (FN), transforming growth factor-β1 (TGF-β1), and connective tissue growth factor (CTGF) was detected by immunohistochemistry. Results: Renal injury, reflected in urine and serum analyses, and pathological changes induced by SNx were attenuated by TE and AE intervention. The depositions of Col IV and FN were also decreased by the treatments and were accompanied by reduced expression of TGF-β1 and CTGF. In some respects, 2 g/(kg∙d) of TE produced better effects than Cozaar. Conclusions: For the first time, we have shown that C. cicadae may inhibit renal fibrosis in vivo through the TGF-β1/CTGF pathway. Therefore, we conclude that the use of C. cicadae could provide a rational strategy for combating renal fibrosis. PMID:22135152

  19. Cordyceps cicadae extracts ameliorate renal malfunction in a remnant kidney model.

    Science.gov (United States)

    Zhu, Rong; Chen, Yi-ping; Deng, Yue-yi; Zheng, Rong; Zhong, Yi-fei; Wang, Lin; Du, Lan-ping

    2011-12-01

    Chronic kidney disease (CKD) is a growing public health problem with an urgent need for new pharmacological agents. Cordyceps cicadae is widely used in traditional Chinese medicine (TCM) and has potential renoprotective benefits. The current study aimed to determine any scientific evidence to support its clinical use. We analyzed the potential of two kinds of C. cicadae extract, total extract (TE) and acetic ether extract (AE), in treating kidney disease simulated by a subtotal nephrectomy (SNx) model. Sprague-Dawley rats were divided randomly into seven groups: sham-operated group, vehicle-treated SNx, Cozaar, 2 g/(kg∙d) TE SNx, 1 g/(kg∙d) TE SNx, 92 mg/(kg∙d) AE SNx, and 46 mg/(kg∙d) AE SNx. Renal injury was monitored using urine and serum analyses, and hematoxylin and eosin (HE) and periodic acid-Schiff (PAS) stainings were used to analyze the level of fibrosis. The expression of type IV collagen (Col IV), fibronectin (FN), transforming growth factor-β1 (TGF-β1), and connective tissue growth factor (CTGF) was detected by immunohistochemistry. Renal injury, reflected in urine and serum analyses, and pathological changes induced by SNx were attenuated by TE and AE intervention. The depositions of Col IV and FN were also decreased by the treatments and were accompanied by reduced expression of TGF-β1 and CTGF. In some respects, 2 g/(kg∙d) of TE produced better effects than Cozaar. For the first time, we have shown that C. cicadae may inhibit renal fibrosis in vivo through the TGF-β1/CTGF pathway. Therefore, we conclude that the use of C. cicadae could provide a rational strategy for combating renal fibrosis.

  20. Ameliorating activity of ginger (Zingiber officinale) extract against lead induced renal toxicity in male rats.

    Science.gov (United States)

    Reddy, Y Amarnath; Chalamaiah, M; Ramesh, B; Balaji, G; Indira, P

    2014-05-01

    Lead poisoning has been known to be associated with structural and functional abnormalities of multiple organ systems of human body. The aim of this investigation was to study the renal protective effects of ginger (Zingiber officinale) extract in lead induced toxicity rats. In this study renal glutathione (GSH) level, glutathione peroxidase (GPX), glutathione-s-transferase (GST), and catalase enzymes were measured in lead nitrate (300 mg/kg BW), and lead nitrate plus ginger extract (150 mg/kg BW) treated rat groups for 1 week and 3 weeks respectively. The glutathione level and GSH dependent antioxidant enzymes such as glutathione peroxidase, glutathione-s-transferase, and catalase significantly (P < 0.05) increased in ginger extract treated rat groups. In addition, histological studies showed lesser renal changes in lead plus ginger extract treated rat groups than that of lead alone treated rat groups. These results indicate that ginger extract alleviated lead toxic effects by enhancing the levels of glutathione, glutathione peroxidase, glutathione-s-transferase and catalase.

  1. Human pluripotent stem cell-derived erythropoietin-producing cells ameliorate renal anemia in mice.

    Science.gov (United States)

    Hitomi, Hirofumi; Kasahara, Tomoko; Katagiri, Naoko; Hoshina, Azusa; Mae, Shin-Ichi; Kotaka, Maki; Toyohara, Takafumi; Rahman, Asadur; Nakano, Daisuke; Niwa, Akira; Saito, Megumu K; Nakahata, Tatsutoshi; Nishiyama, Akira; Osafune, Kenji

    2017-09-27

    The production of erythropoietin (EPO) by the kidneys, a principal hormone for the hematopoietic system, is reduced in patients with chronic kidney disease (CKD), eventually resulting in severe anemia. Although recombinant human EPO treatment improves anemia in patients with CKD, returning to full red blood cell production without fluctuations does not always occur. We established a method to generate EPO-producing cells from human induced pluripotent stem cells (hiPSCs) by modifying previously reported hepatic differentiation protocols. These cells showed increased EPO expression and secretion in response to low oxygen conditions, prolyl hydroxylase domain-containing enzyme inhibitors, and insulin-like growth factor 1. The EPO protein secreted from hiPSC-derived EPO-producing (hiPSC-EPO) cells induced the erythropoietic differentiation of human umbilical cord blood progenitor cells in vitro. Furthermore, transplantation of hiPSC-EPO cells into mice with CKD induced by adenine treatment improved renal anemia. Thus, hiPSC-EPO cells may be a useful tool for clarifying the mechanisms of EPO production and may be useful as a therapeutic strategy for treating renal anemia. Copyright © 2017 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

  2. Gold nanoparticles ameliorate acetaminophen induced hepato-renal injury in rats.

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    Reshi, Mohd Salim; Shrivastava, Sadhana; Jaswal, Amita; Sinha, Neelu; Uthra, Chhavi; Shukla, Sangeeta

    2017-04-04

    Valuable effects of gold particles have been reported and used in complementary medicine for decades. The aim of this study was to evaluate the therapeutic efficacy of gold nanoparticles (AuNPs) against acetaminophen (APAP) induced toxicity. Albino rats were administered APAP at a dose of 2g/kg p.o. once only. After 24h of APAP intoxication, animals were treated with three different doses of AuNPs (50μg/kg, 100μg/kg, 150μg/kg) orally or silymarin at a dose of 50mg/kg p.o., once only. Animals of all the groups were sacrificed after 24h of last treatment. APAP administered group showed a significant rise in the AST, ALT, SALP, LDH, cholesterol, bilirubin, albumin, urea and creatinine in serum which indicated the hepato-renal damage. A significantly enhanced LPO and a depleted level of GSH were observed in APAP intoxicated rats. Declined activities of SOD and Catalase, after acetaminophen exposure indicated oxidative stress in liver and kidney. The activities of ATPase and glucose-6-Phosphatase were significantly inhibited after APAP administration. AuNPs treatment reversed all variables significantly towards normal level and was found nontoxic. Thus it is concluded that gold nanoparticles played a beneficial role in reducing acetaminophen induced toxicity and can be used in the development of drug against hepatic as well as renal diseases, after further preclinical and clinical studies. Copyright © 2017 Elsevier GmbH. All rights reserved.

  3. Sorafenib ameliorates renal fibrosis through inhibition of TGF-β-induced epithelial-mesenchymal transition.

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    Lining Jia

    Full Text Available This study was to investigate whether sorafenib can inhibit the progression of renal fibrosis and to study the possible mechanisms of this effect.Eight-week-old rats were subjected to unilateral ureteral obstruction (UUO and were intragastrically administered sorafenib, while control and sham groups were administered vehicle for 14 or 21 days. NRK-52E cells were treated with TGF-β1 and sorafenib for 24 or 48 hours. HE and Masson staining were used to visualize fibrosis of the renal tissue in each group. The expression of α-SMA and E-cadherin in kidney tissue and NRK-52E cells were performed using immunohistochemistry and immunofluorescence. The apoptosis rate of NRK-52E cells was determined by flow cytometry analysis. The protein levels of Smad3 and p-Smad3 in kidney tissue and NRK-52E cells were detected by western blot analysis.HE staining demonstrated that kidney interstitial fibrosis, tubular atrophy, and inflammatory cell infiltration in the sorafenib-treated-UUO groups were significantly decreased compared with the vehicle-treated-UUO group (p<0.05. Masson staining showed that the area of fibrosis was significantly decreased in the sorafenib-treated-UUO groups compared with vehicle-treated-UUO group (p<0.01. The size of the kidney did not significantly increase; the cortex of the kidney was thicker and had a richer blood supply in the middle-dose sorafenib group compared with the vehicle-treated-UUO group (p<0.05. Compared with the vehicle-treated-UUO and TGF-β-stimulated NRK-52E groups, the expression of a-SMA and E-cadherin decreased and increased, respectively, in the UUO kidneys and NRK-52E cells of the sorafenib-treated groups (p<0.05. The apoptotic rate of NRK-52E cells treated with sorafenib decreased for 24 hours in a dose-dependent manner (p<0.05. Compared with the vehicle-treated UUO and TGF-β-stimulated NRK-52E groups, the ratio of p-Smad3 to Smad3 decreased in the sorafenib-treated groups (p<0.05.Our results suggest that

  4. An Aqueous-Ethanol Extract of Liriope spicata var. prolifera Ameliorates Diabetic Nephropathy through Suppression of Renal Inflammation

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    Hung-Jen Lu

    2013-01-01

    Full Text Available The tuberous root of Liriope spicata var. prolifera (TRLS; Liliaceae family is valued for the ability to promote glucose homeostasis, and it may therefore be utilized as an adjuvant therapy in the control of diabetic complications. The aim of the present study was to examine the effects of an aqueous ethanol extract from TRLS (TRLS-ext (100 or 200 mg kg−1 per day for eight weeks on rats with streptozotocin-induced diabetic nephropathy (DN. Renal dysfunction in diabetic rats was ameliorated by TRLS-ext as evidenced by reduced creatinine clearance, as well as increased blood urea nitrogen and proteinuria. Treatment with TRLS-ext was found to markedly improve histological architecture in the diabetic kidney. Hyperglycemia induced degradation of inhibitory kappa B and reduced nuclear factor kappa B activation, leading to increased infiltration of macrophages and increased levels of proinflammatory cytokines, including interleukin-1 and tumor necrosis factor-α. All of the above abnormalities were reversed by TRLS-ext treatment, which also decreased the expression of intercellular adhesion molecule-1, monocyte chemoattractant protein-1, and fibronectin in the diabetic kidneys. These findings provide a perspective on the renoprotective effects of TRLS-ext in DN.

  5. Calcium, zinc and vitamin E ameliorate cadmium-induced renal oxidative damage in albino Wistar rats

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    Pradeepkiran Jangampalli Adi

    Full Text Available This study was aimed to examine the protective effects of supplementation with calcium + zinc (Ca + Zn or vitamin E (Vit-E on Cd-induced renal oxidative damage. Young albino Wistar rats (180 ± 10 g (n = 6 control rats, Cd, Cd + Ca + Zn, and Cd + Vit-E experimental groups and the experimental period was 30 days. Rats were exposed to Cd (20 mg/kg body weight alone treated as Cd treated group and the absence or presence of Ca + Zn (2 mg/kg each or Vit-E (20 mg/kg body weight supplementation treated as two separate groups. The activities of the stress marker enzymes superoxide dismutase (SOD, catalase (CAT, glutathione reductase (GR, glutathione peroxidase (GPx, glutathione-S-transferase (GST and lipid peroxidase (LPx were determined in renal mitochondrial fractions of experimental rats. We observed quantitative changes in SOD isoenzymatic patterns by non-denaturing PAGE analysis, and quantified band densities. These results showed that Cd exposure leads to decreases in SOD, CAT, GR, and GPx activities and a concomitant increase in LPx and GST activities. Ca + Zn and Vit-E administration with Cd significantly reversed Cd-induced perturbations in oxidative stress marker enzymes. However, Vit-E showed more inhibitory activity against Cd than did Ca + Zn, and it protected against Cd-induced nephrotoxicity. Keywords: Cadmium (Cd, Oxidative stress, Lipid peroxidation, Nephrotoxicity, PAGE analysis

  6. Renal-protective and ameliorating impacts of omega-3 fatty acids against aspartame damaged MDCK cells.

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    Pandurangan, Muthuraman; Enkhtaivan, Gansukh; Veerappan, Muthuviveganandavel; Mistry, Bhupendra; Patel, Rahul; Moon, So Hyun; Nagajyothi, Patnamsetty Chidanandha; Kim, Doo Hwan

    2017-11-01

    Aspartame is widely used artificial sweeteners as food additives. Several researchers have pointed that the controversial report on the use of aspartame over more than decades. Omega-3 fatty acids are essential and unsaturated fatty acids, and it plays a remarkable role in vision, intelligence, neural development, and metabolism of neurotransmitters. Therefore, the present study was aimed to investigate the effect of omega-3 fatty acids on aspartame treated renal cells. Experimental groups were divided into three such as sham control, aspartame treated, and aspartame with omega-3 fatty acids. Cell viability was determined by sulforhodamine-b assay and flow cytometric analysis. The experimental results showed that the aspartame induced altered cell viability were reduced following treatment of aspartame with omega-3 fatty acids. Altered cell morphology was recovered by omega-3 fatty acids. DNA damage appeared in the highest concentration of aspartame used in this study. DNA damage characteristics such as comet tail and tiny head sections did not appear in the omega-3 fatty acids treated cells. Several microvilli and vesicular structures were found in aspartame treated cells. Altered morphology such as rounding, microvilli, and formation of dome-like structures did not appear in the omega-3 fatty acids with aspartame treated cells. Caspase-3 mRNA and protein expression were increased in aspartame treated cells, and these levels were reduced following omega-3 fatty acids treatment. Taking all these data together, it is suggested that the omega-3 fatty acids may be a therapeutic agent to reduce the aspartame induced biochemical and morphological alterations in normal renal cells. © 2017 BioFactors, 43(6):847-857, 2017. © 2017 International Union of Biochemistry and Molecular Biology.

  7. Association between renin-angiotensin system antagonist use and mortality in heart failure with severe renal insufficiency: a prospective propensity score-matched cohort study.

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    Edner, Magnus; Benson, Lina; Dahlström, Ulf; Lund, Lars H

    2015-09-07

    In heart failure (HF) with reduced ejection fraction (EF), renin-angiotensin receptor (RAS) antagonists reduce mortality. However, severe renal insufficiency was an exclusion criterion in trials. We tested the hypothesis that RAS antagonists are associated with reduced mortality also in HF with severe renal insufficiency. We studied patients with EF ≤39% registered in the prospective Swedish Heart Failure Registry. In patients with creatinine >221 µmol/L or creatinine clearance renal insufficiency. Between 2000 and 2013, there were 24 283 patients of which 2410 [age, mean (SD), 82 (9), 45% women] had creatinine >221 µmol/L or creatinine clearance renal insufficiency [n = 21 873; age 71 (12), 27% women], the matched HR was 0.79 (95% CI 0.72-0.86, P renal insufficiency, the use of RAS antagonists was associated with lower all-cause mortality. Prospective randomized trials are needed before these findings can be applied to clinical practice. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2015. For permissions please email: journals.permissions@oup.com.

  8. Kidney stone matrix proteins ameliorate calcium oxalate monohydrate induced apoptotic injury to renal epithelial cells.

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    Narula, Shifa; Tandon, Simran; Singh, Shrawan Kumar; Tandon, Chanderdeep

    2016-11-01

    Kidney stone formation is a highly prevalent disease, affecting 8-10% of the human population worldwide. Proteins are the major constituents of human kidney stone's organic matrix and considered to play critical role in the pathogenesis of disease but their mechanism of modulation still needs to be explicated. Therefore, in this study we investigated the effect of human kidney stone matrix proteins on the calcium oxalate monohydrate (COM) mediated cellular injury. The renal epithelial cells (MDCK) were exposed to 200μg/ml COM crystals to induce injury. The effect of proteins isolated from human kidney stone was studied on COM injured cells. The alterations in cell-crystal interactions were examined by phase contrast, polarizing, fluorescence and scanning electron microscopy. Moreover, its effect on the extent of COM induced cell injury, was quantified by flow cytometric analysis. Our study indicated the antilithiatic potential of human kidney stone proteins on COM injured MDCK cells. Flow cytometric analysis and fluorescence imaging ascertained that matrix proteins decreased the extent of apoptotic injury caused by COM crystals on MDCK cells. Moreover, the electron microscopic studies of MDCK cells revealed that matrix proteins caused significant dissolution of COM crystals, indicating cytoprotection against the impact of calcium oxalate injury. The present study gives insights into the mechanism implied by urinary proteins to restrain the pathogenesis of kidney stone disease. This will provide a better understanding of the formation of kidney stones which can be useful for the proper management of the disease. Copyright © 2016 Elsevier Inc. All rights reserved.

  9. Soluble Receptor for Advanced Glycation End Product Ameliorates Chronic Intermittent Hypoxia Induced Renal Injury, Inflammation, and Apoptosis via P38/JNK Signaling Pathways

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    Xu Wu

    2016-01-01

    Full Text Available Obstructive sleep apnea (OSA associated chronic kidney disease is mainly caused by chronic intermittent hypoxia (CIH triggered tissue damage. Receptor for advanced glycation end product (RAGE and its ligand high mobility group box 1 (HMGB1 are expressed on renal cells and mediate inflammatory responses in OSA-related diseases. To determine their roles in CIH-induced renal injury, soluble RAGE (sRAGE, the RAGE neutralizing antibody, was intravenously administered in a CIH model. We also evaluated the effect of sRAGE on inflammation and apoptosis. Rats were divided into four groups: (1 normal air (NA, (2 CIH, (3 CIH+sRAGE, and (4 NA+sRAGE. Our results showed that CIH accelerated renal histological injury and upregulated RAGE-HMGB1 levels involving inflammatory (NF-κB, TNF-α, and IL-6, apoptotic (Bcl-2/Bax, and mitogen-activated protein kinases (phosphorylation of P38, ERK, and JNK signal transduction pathways, which were abolished by sRAGE but p-ERK. Furthermore, sRAGE ameliorated renal dysfunction by attenuating tubular endothelial apoptosis determined by immunofluorescence staining of CD31 and TUNEL. These findings suggested that RAGE-HMGB1 activated chronic inflammatory transduction cascades that contributed to the pathogenesis of the CIH-induced renal injury. Inhibition of RAGE ligand interaction by sRAGE provided a therapeutic potential for CIH-induced renal injury, inflammation, and apoptosis through P38 and JNK pathways.

  10. Green Tea Polyphenols Ameliorate the Early Renal Damage Induced by a High-Fat Diet via Ketogenesis/SIRT3 Pathway

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    Weijie Yi

    2017-01-01

    Full Text Available Scope. Several reports in the literature have suggested the renoprotective effects of ketone bodies and green tea polyphenols (GTPs. Our previous study found that GTP consumption could elevate the renal expression of the ketogenic rate-limiting enzyme, which was decreased by a high-fat diet (HFD in rats. Here, we investigated whether ketogenesis can mediate renoprotection by GTPs against an HFD. Methods and Results. Wistar rats were fed a standard or HFD with or without GTPs for 18 weeks. The renal oxidative stress level, kidney function, renal expression, and activity levels of mitochondrial 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA synthase 2 (HMGCS2 and sirtuin 3(SIRT3 were detected. The increased renal oxidative stress and the loss of renal function induced by the HFD were ameliorated by GTPs. Renal ketogenesis and SIRT3 expression and activity levels, which were reduced by the HFD, were restored by GTPs. In vitro, HEK293 cells were transfected with the eukaryotic expression plasmid pcDNA HMGCS2. GTP treatment could upregulate HMGCS2 and SIRT3 expression. Although SIRT3 expression was not affected by HMGCS2 transfection, the 4-hydroxy-2-nonenal (4-HNE level and the acetyl-MnSOD (K122/MnSOD ratio were reduced in HMGCS2-transfected cells in the context of H2O2. Conclusion. The ketogenesis/SIRT3 pathway mediates the renoprotection of GTPs against the oxidative stress induced by an HFD.

  11. Phosphodiesterase 2A Inhibitor TAK-915 Ameliorates Cognitive Impairments and Social Withdrawal in N-Methyl-d-Aspartate Receptor Antagonist-Induced Rat Models of Schizophrenia.

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    Nakashima, Masato; Imada, Haruka; Shiraishi, Eri; Ito, Yuki; Suzuki, Noriko; Miyamoto, Maki; Taniguchi, Takahiko; Iwashita, Hiroki

    2018-04-01

    The pathophysiology of schizophrenia has been associated with glutamatergic dysfunction. Modulation of the glutamatergic signaling pathway, including N -methyl-d-aspartate (NMDA) receptors, can provide a new therapeutic target for schizophrenia. Phosphodiesterase 2A (PDE2A) is highly expressed in the forebrain, and is a dual substrate enzyme that hydrolyzes both cAMP and cGMP, which play pivotal roles as intracellular second messengers downstream of NMDA receptors. Here we characterize the in vivo pharmacological profile of a selective and brain-penetrant PDE2A inhibitor, ( N -{(1 S )-1-[3-fluoro-4-(trifluoromethoxy)phenyl]-2-methoxyethyl}-7-methoxy-2-oxo-2,3-dihydropyrido[2,3- b ]pyrazine-4(1 H )-carboxamide) (TAK-915) as a novel treatment of schizophrenia. Oral administration of TAK-915 at 3 and 10 mg/kg significantly increased cGMP levels in the frontal cortex, hippocampus, and striatum of rats. TAK-915 at 10 mg/kg significantly upregulated the phosphorylation of α -amino-3-hydroxy-5-methylisoxazole-4-proprionic acid receptor subunit GluR1 in the rat hippocampus. TAK-915 at 3 and 10 mg/kg significantly attenuated episodic memory deficits induced by the NMDA receptor antagonist (+)-MK-801 hydrogen maleate (MK-801) in the rat passive avoidance test. TAK-915 at 10 mg/kg significantly attenuated working memory deficits induced by MK-801 in the rat radial arm maze test. Additionally, TAK-915 at 10 mg/kg prevented subchronic phencyclidine-induced social withdrawal in social interaction in rats. In contrast, TAK-915 did not produce antipsychotic-like activity; TAK-915 had little effect on MK-801- or methamphetamine-induced hyperlocomotion in rats. These results suggest that TAK-915 has a potential to ameliorate cognitive impairments and social withdrawal in schizophrenia. Copyright © 2018 by The American Society for Pharmacology and Experimental Therapeutics.

  12. Maraviroc, a CCR5 antagonist, ameliorates the development of hepatic steatosis in a mouse model of non-alcoholic fatty liver disease (NAFLD).

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    Pérez-Martínez, Laura; Pérez-Matute, Patricia; Aguilera-Lizarraga, Javier; Rubio-Mediavilla, Susana; Narro, Judit; Recio, Emma; Ochoa-Callejero, Laura; Oteo, José-Antonio; Blanco, José-Ramón

    2014-07-01

    Non-alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease in the general population. The NAFLD spectrum ranges from simple steatosis to cirrhosis. The chemokine CCL5/RANTES plays an important role in the progression of hepatic inflammation and fibrosis. The objective of this study was to examine the effects of maraviroc, a CCR5 antagonist, on liver pathology in a NAFLD mouse model. A total of 32 male C57BL/6 mice were randomly assigned to one of four groups: (i) control group (chow diet plus tap water); (ii) maraviroc group (chow diet plus maraviroc in drinking water); (iii) high-fat diet (HFD) group (HFD plus tap water); and (iv) maraviroc/HFD group (HFD plus maraviroc). All mice were sacrificed 16 weeks after the beginning of the experiment. Biochemical analyses and liver examinations were performed. Mice in the HFD group showed a tendency towards increased body mass gain and liver damage compared with the maraviroc/HFD group. Moreover, liver weight in the HFD group was significantly higher than in the maraviroc/HFD group. Hepatic triglyceride concentration in the maraviroc/HFD group was significantly lower than in the HFD group. Interestingly, the maraviroc/HFD group exhibited a lower degree of steatosis. Furthermore, hepatic CCL5/RANTES expression was significantly lower in the maraviroc/HFD group than in the HFD group. Overall, no differences were observed between the control group and the maraviroc group. Maraviroc ameliorates hepatic steatosis in an experimental model of NAFLD. © The Author 2014. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  13. Microvesicles derived from human Wharton's Jelly mesenchymal stem cells ameliorate ischemia-reperfusion-induced renal fibrosis by releasing from G2/M cell cycle arrest.

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    Chen, Wenxia; Yan, Yongbin; Song, Chundong; Ding, Ying; Du, Tao

    2017-12-14

    Studies have demonstrated that microvesicles (MVs) derived from human Wharton's Jelly mesenchymal stromal cells (hWJMSCs) could ameliorate renal ischemia/reperfusion injury (IRI); however, the underlying mechanisms were not clear yet. Here, MVs were isolated and injected intravenously into rats immediately after ischemia of the left kidney, and Erk1/2 activator hepatocyte growth factor (HGF) or inhibitor U0126 was administrated. Tubular cell proliferation and apoptosis were identified by Ki67 or terminal-deoxynucleotidyl transferase-mediated nick end labeling immunostaining. Masson's tri-chrome straining and alpha-smooth muscle actin staining were used for assessing renal fibrosis. The mRNA or protein expression in the kidney was measured by quantitative reverse transcription-PCR or Western blot, respectively. The total collagen concentration was also determined. In vitro , NRK-52E cells that treated with MVs under hypoxia injury and with HGF or U0126 administration were used, and cell cycle analysis was performed. The effects of hWJMSC-MVs on enhancing the proliferation and mitigating the apoptosis of renal cells, abrogating IRI-induced fibrosis, improving renal function, decreasing collagen deposition, and altering the expression levels of epithelial-mesenchymal transition and cell cycle-related proteins in IRI rats were found. In vitro experiment showed that hWJMSC-MVs could induce G2/M cell cycle arrest and decrease the expression of collagen deposition-related proteins in NRK-52E cells after 24 or 48 h. However, U0126 treatment reversed these effects. In conclusion, MVs derived from hWJMSCs ameliorate IR-induced renal fibrosis by inducing G2/M cell cycle arrest via Erk1/2 signaling. © 2017 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.

  14. Peri- and Postoperative Treatment with the Interleukin-1 Receptor Antagonist Anakinra Is Safe in Patients Undergoing Renal Transplantation: Case Series and Review of the Literature

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    Catharina M. Mulders-Manders

    2017-05-01

    Full Text Available In patients undergoing solid organ transplantation, the presence of an interleukin-1 (IL-1 driven disease may require the addition of IL-1 inhibiting drugs to the standard immunosuppressive regimen to protect against inflammation and negative graft outcome. Three patients undergoing renal transplantation were treated perioperatively with the interleukin-1 receptor antagonist anakinra. Kidney function increased rapidly in all three and the only complications seen were minor infections. In vitro studies report associations between serum and urinary levels of IL-1β and IL-1 receptor antagonist and negative graft outcome, and studies in animals and two small human trials illustrate a possible protective effect of anti-IL-1 therapy after solid organ transplantation. Peri- and postoperative use of anakinra is safe and effective in patients undergoing renal transplantation.

  15. Magnesium Lithospermate B from Salvia miltiorrhiza Bunge Ameliorates Aging-Induced Renal Inflammation and Senescence via NADPH Oxidase-Mediated Reactive Oxygen Generation.

    Science.gov (United States)

    Park, Chan Hum; Shin, Sung Ho; Lee, Eun Kyeong; Kim, Dae Hyun; Kim, Min-Jo; Roh, Seong-Soo; Yokozawa, Takako; Chung, Hae Young

    2017-05-01

    The present study was conducted to examine whether magnesium lithospermate B (MLB) extracted from Salviae miltiorrhizae radix was renoprotective in pathways related to age-related oxidative stress in aged rats. Magnesium lithospermate B was orally administered at a dose of 2- or 8-mg/kg body weight for 16 consecutive days, and the effects were compared with those of vehicle in old and young rats. Magnesium lithospermate B administration to old rats ameliorated renal oxidative stress through reduction of reactive oxygen species. The old rats exhibited a dysregulation of the expression of proteins related to oxidative stress and inflammation in the kidneys, and MLB administration significantly reduced the protein expression of major subunits of nicotinamide adenine dinucleotide phosphate oxidase (Nox4 and p22 phox ), phospho-p38, nuclear factor-kappa B p65, cyclooxygenase-2, and inducible nitric oxide synthase. In addition, MLB-treated old rats showed lower levels of senescence-related proteins such as p16, ADP-ribosylation factor 6, p53, and p21 through effects on the mitogen-activated protein kinase pathway. Magnesium lithospermate B administration also significantly attenuated the age-related increase in serum urea nitrogen, reflecting renal dysfunction, up-regulated podocyte structural proteins, and reduced renal structural injury. Our results provide important evidence that MLB reduces the renal damage of oxidative stress in old rats. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

  16. Amelioration of renal ischaemia-reperfusion injury by liposomal delivery of curcumin to renal tubular epithelial and antigen-presenting cells.

    Science.gov (United States)

    Rogers, N M; Stephenson, M D; Kitching, A R; Horowitz, J D; Coates, P T H

    2012-05-01

    Renal ischaemia-reperfusion (IR) injury is an inevitable consequence of renal transplantation, causing significant graft injury, increasing the risk of rejection and contributing to poor long-term graft outcome. Renal injury is mediated by cytokine and chemokine synthesis, inflammation and oxidative stress resulting from activation of the NF-κB pathway. We utilized liposomal incorporation of a potent inhibitor of the NF-κB pathway, curcumin, to target delivery to renal tubular epithelial and antigen-presenting cells. Liposomes containing curcumin were administered before bilateral renal ischaemia in C57/B6 mice, with subsequent reperfusion. Renal function was assessed from plasma levels of urea and creatinine, 4 and 24 h after reperfusion. Renal tissue was examined for NF-κB activity and oxidative stress (histology, immunostaining) and for apoptosis (TUNEL). Cytokines and chemokines were measured by RT-PCR and Western blotting. Liposomal curcumin significantly improved serum creatinine, reduced histological injury and cellular apoptosis and lowered Toll-like receptor-4, heat shock protein-70 and TNF-α mRNA expression. Liposomal curcumin also reduced neutrophil infiltration and diminished inflammatory chemokine expression. Curcumin liposomes reduced intracellular superoxide generation and increased superoxide dismutase levels, decreased inducible NOS mRNA expression and 3-nitrotyrosine staining consistent with limitations in nitrosative stress and inhibited renal tubular mRNA and protein expression of thioredoxin-interacting protein. These actions of curcumin were mediated by inhibition of NF-κB, MAPK and phospho-S6 ribosomal protein. Liposomal delivery of curcumin promoted effective, targeted delivery of this non-toxic compound that provided cytoprotection via anti-inflammatory and multiple antioxidant mechanisms following renal IR injury. © 2011 The Authors. British Journal of Pharmacology © 2011 The British Pharmacological Society.

  17. Effects of felodipine, a newly developed calcium antagonist, on blood pressure, and cerebral and renal blood flow in patients with essential hypertension

    International Nuclear Information System (INIS)

    Ono, Yoshiaki; Konno, Yoshio; Shibuya, Hiroshi; Watanabe, Tsuyoshi; Mizuno, Kenji.

    1997-01-01

    Felodipine, a recently developed calcium channel antagonist, was administered twice daily (10 mg/day) for 1 month to 5 patients with mild to moderate essential hypertension. Its antihypertensive effect, as well as its effect on cerebral and renal blood flow, was investigated. After 1 month of therapy, sitting systolic and diastolic blood pressure were significantly decreased. The antihypertensive effect was well tolerated and sustained during the administration period. Total cerebral blood flow, as assessed by 99m Tc-hexamethyl-propyleneamine oxime, increased to 46.8±6.4 ml/100 g/min from a pretreatment level of 43.6±6.4 ml/100 g/min (P 99m Tc-diethylenetriamine pentaacetic acid, unchanged: 70.2±19.9 ml/ min before and 71.8±13.6 ml/min after. Blood viscosity and the number of blood platelet tended to decrease during treatment. There were essentially no significant changes in biochemical parameters, and no severe side effects were encountered during the administration. These results not only confirmed the safety and usefulness of felodipine as an antihypertensive agent for the treatment of essential hypertension, but also suggested that this new calcium channel antagonist may exert beneficial effects on central as well as renal hemodynamics in essential hypertensives. (author)

  18. [3H]AVP binding to rat renal tubular receptors during long-term treatment with an antagonist of arginine vasopressin

    International Nuclear Information System (INIS)

    Mah, S.C.; Whitebread, S.E.; De Gasparo, M.; Hofbauer, K.G.

    1988-01-01

    The interaction of an antagonist of arginine vasopressin (AVP), d(CH2)5-D-Tyr(Et)VAVP, with renal tubular V2 receptors were studied in medullary membrane preparations from kidneys of Sprague-Dawley and Brattleboro rats. In both rat strains, V2 receptors had comparable KD and Bmax values for binding of [3H]AVP. In vitro studies revealed that the V2-antagonist was more potent than cold AVP in displacing [3H]AVP. In vivo treatment of Sprague-Dawley rats with the antagonist over one week resulted only in a transient state of diabetes insipidus (DI). No specific [3H]AVP binding was detectable throughout the period of administration. Chronic treatment of Brattleboro rats resulted in a complete normalization of water intake. This agonistic effect was also associated with undetectable [3H]AVP binding. After stopping the infusion of d(CH2)5-D-Tyr(Et)VAVP, Bmax values tended to rise but had still not reached base line values after 6 days. In contrast, the chronic infusion of AVP in Brattleboro rats resulted in a reduction in water intake which was accompanied by a decreased Bmax. [3H]AVP binding remained detectable during the entire treatment period. Thereafter Bmax was restored to base line values within 2 days of stopping the infusion. These results suggest that d(CH2)5-D-Tyr(Et)VAVP has a high affinity for V2 receptors in both Sprague-Dawley and Brattleboro rats. Its rate of dissociation from the receptor appears to be much slower than that of AVP. In Brattleboro rats, the binding of d(CH2)5-D-Tyr(Et)VAVP leads to an antidiuretic response. In Sprague-Dawley rats, a transient diuretic response is followed by a progressive normalization in water intake. This occurs despite persistent and complete blockade of renal medullary V2 receptors

  19. Small Molecule Inhibiting Nuclear Factor-kB Ameliorates Oxidative Stress and Suppresses Renal Inflammation in Early Stage of Alloxan-Induced Diabetic Nephropathy in Rat.

    Science.gov (United States)

    Borgohain, Manash P; Lahkar, Mangala; Ahmed, Sahabuddin; Chowdhury, Liakat; Kumar, Saurabh; Pant, Rajat; Choubey, Abhinav

    2017-05-01

    Diabetic nephropathy is one of the major microvascular complications of diabetes mellitus which ultimately gives rise to cardiovascular diseases. Prolonged hyperglycaemia and chronic renal inflammation are the two key players in the development and progression of diabetic nephropathy. Nuclear factor kB (NF-kB)-mediated inflammatory cascade is a strong contributor to the renovascular inflammation in diabetic nephropathy. Here, we studied the effects of piceatannol, a potent NF-kB inhibitor, on various oxidative stress markers and NF-kB dependent diabetic renoinflammatory cascades in rat induced by alloxan (ALX). Experimental diabetes was induced in male Wistar rats by a single intraperitoneal dose, 150 mg/kg body-weight (b.w.) of ALX. Diabetic rats were treated with Piceatannol (PCTNL) at a dose of 30 and 50 mg/kg b.w. After 14 days of oral treatment, PCTNL significantly restored blood sugar level, glomerular filtration rate, serum markers and plasma lipids. PCTNL administration also reversed the declined activity of cellular antioxidant machineries namely superoxide dismutase and glutathione and the elevated levels of malondialdehyde and nitric oxide. Moreover, piceatannol-treated groups showed marked inhibition of renal pro-inflammatory cytokines and NF-kB p65/p50 binding to DNA. Renal histopathological investigations also supported its ameliorative effects against diabetic kidney damage. Importantly, effects were more prominent at a dose of 50 mg/kg, and in terms of body-weight gain, PCTNL failed to effect significantly. However, overall findings clearly demonstrated that PCTNL provides remarkable renoprotection in diabetes by abrogating oxidative stress and NF-kB activation - and might be helpful in early stage of diabetic nephropathy. © 2016 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).

  20. Phytochemical screening, and assessment of ameliorating effect of aqueous and ethanolic extracts of Gmelina arborea on drug induced hepatic and renal insufficiency in rats.

    Science.gov (United States)

    Anthony, Ogbonnaya Enyinnaya; Mbuh, Awah Francis; Emmanuel, Mounmbegna Philippe

    2012-04-01

    Phytochemical screening of stem bark and leaves of Gmelina arborea; and effect of aqueous and ethanolic extracts of Gmelina arborea stembark on hepatic and renal insufficiency in rats was assessed in this study. Phytochemical screening was carried out on the air-dried leaf, oven-dried leaf, air-dried stembark and oven-dried stembark samples. Sixty five (65) wister albino rats, (50.7-117.5 g) were divided into thirteen groups of five animals each. Three groups serve as Controls and were administered Cisplatin (5mg/kg b.w; i.p), Paracetamol (200mg/kg b.w; i.p) and Normal saline (0.002 ml/kg b.w; oral). Other groups were administered, either, cisplatin and extracts (1g/kg b.w; oral); Paracetamol and extracts (1g/kg b.w; oral); extracts alone; or drugs and combination of extracts. Animals were starved, 24 hours prior to sacrifice and sacrificed on the 9th day after commencement of treatment. Phytochemical screening results show the presence of alkaloid, flavonoid, tannin, saponin, cyanogenic glycoside, phytate, and carbohydrate. Saponin and carbohydrate were shown to be much higher in concentration than other phytochemicals. The percentage composition of cyanogenic glycoside and phytate were highest in air-dried stembark and oven-dried leaf samples, respectively. All the Gmelina arborea extracts and extract mixture administered to both paracetamol and cisplatin treated animals, significantly, lowers both the activities of the SGOT and SGPT, and the levels of serum creatinine and urea. When administered alone, the aqueous and ethanolic extracts show little or no sign of toxicity. Thus Gmelina arborea extracts may have ameliorating effect on hepatic and renal insufficiency caused by paracetamol and cisplatin respectively, and any inherent toxicity may be reduced or eliminated through adequate heat treatment.

  1. Electroacupuncture Ameliorates Acute Renal Injury in Lipopolysaccharide-Stimulated Rabbits via Induction of HO-1 through the PI3K/Akt/Nrf2 Pathways.

    Science.gov (United States)

    Yu, Jian-Bo; Shi, Jia; Zhang, Yuan; Gong, Li-Rong; Dong, Shu-An; Cao, Xin-Shun; Wu, Li-Li; Wu, Li-Na

    2015-01-01

    Electroacupuncture at select acupoints have been verified to protect against organ dysfunctions during endotoxic shock. And, heme oxygenase (HO)-1 as a phase II enzyme and antioxidant contributed to the protection of kidney in septic shock rats. The phosphatidylinositol 3-kinase (PI3K)-Akt pathway mediated the activation of NF-E2 related factor-2 (Nrf2), which was involved in HO-1 induction. To understand the efficacy of electroacupuncture stimulation in ameliorating acute kidney injury (AKI) through the PI3K/Akt/Nrf2 pathway and subsequent HO-1 upregulation, a dose of LPS 5mg/kg was administered intravenously to replicate the rabbit model of AKI induced by endotoxic shock. Electroacupuncture pretreatment was handled bilaterally at Zusanli and Neiguan acupoints for five consecutive days while sham electroacupuncture at non-acupoints as control. Results displayed that electroacupuncture stimulation significantly alleviated the morphologic renal damage, attenuated renal tubular apoptosis, suppressed the elevated biochemical indicators of AKI caused by LPS, enhanced the expressions of phospho-Akt, HO-1protein, Nrf2 total and nucleoprotein, and highlighted the proportions of Nrf2 nucleoprotein as a parallel. Furthermore, partial protective effects of elecroacupuncture were counteracted by preconditioning with wortmannin (the selective PI3K inhibitor), indicating a direct involvement of PI3K/Akt pathway. Inconsistently, wortmannin pretreatment made little difference to the expressions of HO-1, Nrf2 nucleoprotein and total protein, which indicated that PI3K/Akt may be not the only pathway responsible for electroacupuncture-afforded protection against LPS-induced AKI. These findings provide new insights into the potential future clinical applications of electroacupuncture for AKI induced by endotoxic shock instead of traditional remedies.

  2. Renal graft failure after addition of an angiotensin II receptor antagonist to an angiotensin-converting enzyme inhibitor

    DEFF Research Database (Denmark)

    Kamper, Anne-Lise; Nielsen, Arne Høj; Baekgaard, Niels

    2002-01-01

    Combined treatment with an angiotensin-converting enzyme (ACE) inhibitor and an angiotensin II (Ang II) receptor blocker (ARB) has been suggested in order to achieve a more complete blockade of the renin-angiotensin-aldosterone system in cardiovascular and renal disease. The present report descri...

  3. PF-03882845, a non-steroidal mineralocorticoid receptor antagonist, prevents renal injury with reduced risk of hyperkalemia in an animal model of nephropathy

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    Stephen eOrena

    2013-10-01

    Full Text Available The mineralocorticoid receptor (MR antagonists PF 03882845 and eplerenone were evaluated for renal protection against aldosterone mediated renal disease in uninephrectomized Sprague Dawley (SD rats maintained on a high salt diet and receiving aldosterone by osmotic mini pump for 27 days. Serum K+ and the urinary albumin to creatinine ratio (UACR were assessed following 14 and 27 days of treatment. Aldosterone induced renal fibrosis as evidenced by increases in UACR, collagen IV staining in kidney cortex, and expression of pro fibrotic genes relative to sham operated controls not receiving aldosterone. While both PF 03882845 and eplerenone elevated serum K+ levels with similar potencies, PF 03882845 was more potent than eplerenone in suppressing the rise in UACR. PF 03882845 prevented the increase in collagen IV staining at 5, 15 and 50 mg/kg BID while eplerenone was effective only at the highest dose tested (450 mg/kg BID. All doses of PF 03882845 suppressed aldosterone induced increases in collagen IV, transforming growth factor 1 (Tgf 1, interleukin 6 (Il-6, intermolecular adhesion molecule 1 (Icam-1 and osteopontin gene expression in kidney while eplerenone was only effective at the highest dose. The therapeutic index (TI, calculated as the ratio of the EC50 for increasing serum K+ to the EC50 for UACR lowering, was 83.8 for PF 03882845 and 1.47 for eplerenone. Thus the TI of PF 03882845 against hyperkalemia was 57 fold superior to that of eplerenone indicating that PF 03882845 may present significantly less risk for hyperkalemia compared to eplerenone.

  4. Dalteparin versus vitamin K antagonists for the prevention of recurrent venous thromboembolism in patients with cancer and renal impairment: a Canadian pharmacoeconomic analysis

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    Dranitsaris G

    2017-01-01

    Full Text Available George Dranitsaris,1 Lesley G Shane,2 Mark Crowther,3 Guillaume Feugere,4 Seth Woodruff2 1Health Economic and Outcomes Research, Augmentium Pharma Consulting Inc, Toronto, ON, Canada; 2Pfizer Inc, New York, NY, USA; 3McMaster University, Hamilton, ON, 4Pfizer Canada, Montreal, QC, Canada Background: Patients with cancer are at increased risk of venous thromboembolism (VTE and the risk is further elevated after a primary VTE. To reduce the risk of recurrent events, extended prophylaxis with vitamin K antagonists (VKA is available for use. However, in a large randomized trial (Comparison of Low-Molecular-Weight Heparin versus Oral Anticoagulant Therapy for the Prevention of Recurrent Venous Thromboembolism in Patients with Cancer [CLOT]; Lee et al, extended duration dalteparin reduced the relative risk of recurrent VTE by 52% compared to VKA (p=0.002. A recent subgroup analysis of patients with moderate-to-severe renal impairment also revealed lower absolute VTE rates with dalteparin (3% vs. 17%; p=0.011. To measure the economic value of dalteparin as an alternative to VKA, a patient-level cost utility analysis was conducted from a Canadian perspective. Methods: Resource use data captured during the CLOT trial were extracted and linked to 2015 Canadian unit cost estimates. Health state utilities were then measured using the Time-Trade-Off technique in 24 randomly selected members of the general Canadian public to estimate the gains in quality-adjusted life years (QALYs. Results: For the entire CLOT trial population (n=676, the dalteparin group had significantly higher mean costs compared to the VKA group ($Can5,771 vs. $Can2,569; p<0.001. However, the utility assessment revealed that 21 of 24 respondents (88% selected dalteparin over VKA, with an associated gain of 0.14 (95% confidence interval [CI]: 0.10–0.18 QALYs. When the incremental cost of dalteparin was combined with the QALY gain, dalteparin had a cost of $Can23,100 (95% CI: $Can19,200

  5. A CD1d-dependent lipid antagonist to NKT cells ameliorates atherosclerosis in ApoE-/- mice by reducing lesion necrosis and inflammation.

    Science.gov (United States)

    Li, Yi; Kanellakis, Peter; Hosseini, Hamid; Cao, Anh; Deswaerte, Virginie; Tipping, Peter; Toh, Ban-Hock; Bobik, Alex; Kyaw, Tin

    2016-02-01

    Atherosclerosis-related deaths from heart attacks and strokes remain leading causes of global mortality, despite the use of lipid-lowering statins. Thus, there is an urgent need to develop additional therapies. Reports that NKT cells promote atherosclerosis and an NKT cell CD1d-dependent lipid antagonist (DPPE-PEG350, 1,2-dipalmitoyl-sn-glycero-3-phosphoethanolamine-N[methoxy(polyethyleneglycol)-350]) reduces allergen-induced inflammation led us to investigate its therapeutic potential in preventing the development and progression of experimental atherosclerosis. DPPE-PEG350 was administered to hyperlipidaemic ApoE(-/-) mice with/without established atherosclerosis. Atherosclerosis and immune cells were assessed in the aortic sinus lesions. Lesion expression of monocyte chemoattractant protein-1 (MCP-1) and vascular cell adhesion protein-1 (VCAM-1) responsible for inflammatory immune cell recruitment as well as mRNA expression of IFNγ and its plasma levels were investigated. Necrotic cores and lesion smooth muscle and collagen contents important in plaque stability were determined as were plasma lipid levels. DPPE-PEG350 reduced atherosclerosis development and delayed progression of established atherosclerosis without affecting plasma lipids. CD4 and CD8 T cells and B cells in atherosclerotic lesions were decreased in DPPE-PEG350-treated mice. Lesion MCP-1 and VCAM-1 protein expression and necrotic core size were reduced without affecting lesion smooth muscle and collagen content. IFNγ and lymphocytes were unaffected by the treatment. The attenuation of progression of established atherosclerosis together with reduced development of atherosclerosis in hyperlipidaemic mice by the NKT antagonist, without affecting NKT cell or other lymphocyte numbers, suggests that targeting lesion inflammation via CD1d-dependent activation of NKT cells using DPPE-PEG350 has a therapeutic potential in treating atherosclerosis. Published on behalf of the European Society of

  6. The Non-Peptide Vasopressin V1b Receptor Antagonist, SSR149415, Ameliorates Spermatogenesis Function in a Mouse Model of Chronic Social Defeat Stress.

    Science.gov (United States)

    Wang, Bin; Zhou, Jian; Zhuang, Yan-Yan; Wang, Liang-Liang; Pu, Jin-Xian; Huang, Yu-Hua; Xia, Fei; Lv, Jin-Xing

    2017-11-01

    To determine the effects of SSR149415 on testis and spermatogenesis in male mice subjected to chronic social defeat stress, C57BL/6 male mice were divided into two groups: Control and Stress. Then Stress group was subdivided into four subgroups administered water, SSR149415 (1 mg/kg/day), SSR149415 (10 mg/kg/day), SSR149415 (30 mg/kg/day), respectively. The behavioral alterations revealed by social interaction test and open field test were measured. The physical indices, including body weight and gonad weight (testis and epididymis) as well as testis/body weight and cauda epididymis/body weight were detected. Serum hormones, including testosterone, luteinizing hormone (LH), and follicle-stimulating hormone (FSH) were determined. Sperm count and abnormality as well as testicular histology structure were assessed. The germ cells apoptosis were also evaluated. Chronic social defeat stress-induced behavioral abnormality, as well as gonad atrophy (testis and epididymis) was significantly alleviated in stressed male mice exposed to SSR149415. Regressed serum testosterone levels and elevated serum FSH and LH levels exhibited by stressed male mice were observably reversed following SSR149415 administration. Chronic social defeat stress-induced damage in testicular histology structure and semen quality were also improved after SSR149415 administration. In addition, SSR149415 significantly reversed chronic social defeat stress-induced germ cells apoptosis. Overall, we provide clear evidence indicating the amelioration of chronic social defeat stress-induced behavioral abnormality and testicular dysfunction via SSR149415, promoting the development of drug-directed therapy against this disease. J. Cell. Biochem. 118: 3891-3898, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  7. Exercise Ameliorates Renal Cell Apoptosis in Chronic Kidney Disease by Intervening in the Intrinsic and the Extrinsic Apoptotic Pathways in a Rat Model

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    Kuan-Chou Chen

    2013-01-01

    Full Text Available We hypothesized that doxorubicin (DR induced chronic kidney disease (CKD could trigger the intrinsic and the extrinsic renal cell apoptotic pathways, while treadmill exercise could help prevent adverse effects. Male Sprague-Dawley rats were subjected to treadmill running exercise at a speed of 30 m/min, 30 or 60 min/day, 3 times per week, for a total period of 11 weeks. The physiological and biochemical parameters were seen substantially improved (DR-CKD control, 30 min, 60 min exercise: the ratio of kidney weight/body weight (0.89, 0.74, and 0.72; the WBC (1.35, 1.08, and 1.42 × 104 cells/μL; RBC (5.30, 6.38, and 6.26 × 106 cells/μL; the platelet count (15.1, 12.8, and 11.3 × 105/μL; serum cholesterol (659, 360, and 75 mg/dL; serum triglyceride (542, 263, and 211 mg/dL; BUN (37, 25, and 22 mg/dL. Bcl-2 and intramitochondrial cytochrome c were upregulated, while the levels of Bax, SOD, MDA, cleaved caspases 9, 3, 8, 12, and calpain were all downregulated in DRCKD groups with exercise. CHOP (GADD153 and GRP78 were totally unaffected. FAS (CD95 was only slightly suppressed in the 60 min exercise DRCKD group. Conclusively, exercise can ameliorate CKD through the regulation of the intrinsic and extrinsic apoptosis pathways. The 60 min exercise yields more beneficial effect than the 30 min counterpart.

  8. Sjögren's syndrome associated dry eye in a mouse model is ameliorated by topical application of integrin α4 antagonist GW559090.

    Science.gov (United States)

    Contreras-Ruiz, Laura; Mir, Fayaz A; Turpie, Bruce; Krauss, Achim H; Masli, Sharmila

    2016-02-01

    Sjögren's syndrome is an autoimmune disease associated with inflammation of exocrine glands with clinical manifestations of dry eye and dry mouth. Dry eye in this disease involves inflammation of the ocular surface tissues - cornea and conjunctiva. While systemic blockade of adhesion molecules has been used to treat autoimmune diseases, the purpose of this study was to determine the therapeutic efficacy of topical application of an integrin α4 adhesion molecule antagonist in a mouse model of dry eye associated with Sjögren's syndrome. To assess this spontaneously developed ocular surface inflammation related to Sjögren's syndrome in TSP-1null mice (12 wks) was evaluated. Mice were treated with topical formulations containing 0.1% dexamethasone or 30 mg/ml GW559090 or vehicle control. Corneal fluorescein staining and conjunctival goblet cell density were assessed. Real-time PCR analysis was performed to assess expression of the inflammatory marker IL-1β in the cornea and Tbet and RORγt in the draining lymph nodes. Ocular surface inflammation was detectable in TSP-1null mice (≥12 wk old), which resulted in increased corneal fluorescein staining indicative of corneal barrier disruption and reduced conjunctival goblet cell density. These changes were accompanied by increased corneal expression of IL-1β as compared to WT controls and an altered balance of Th1 (Tbet) and Th17 (RORγt) markers in the draining lymph nodes. Topically applied dexamethasone and GW559090 significantly reduced corneal fluorescein staining compared to vehicle treatment (p = 0.023 and p syndrome. Copyright © 2015 Elsevier Ltd. All rights reserved.

  9. Role of Mas Receptor Antagonist A799 in Renal Blood Flow Response to Ang 1-7 after Bradykinin Administration in Ovariectomized Estradiol-Treated Rats

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    Aghdas Dehghani

    2015-01-01

    Full Text Available Background. The accompanied role of Mas receptor (MasR, bradykinin (BK, and female sex hormone on renal blood flow (RBF response to angiotensin 1-7 is not well defined. We investigated the role of MasR antagonist (A779 and BK on RBF response to Ang 1-7 infusion in ovariectomized estradiol-treated rats. Methods. Ovariectomized Wistar rats received estradiol (OVE or vehicle (OV for two weeks. Catheterized animals were subjected to BK and A799 infusion and mean arterial pressure (MAP, RBF, and renal vascular resistance (RVR responses to Ang 1-7 (0, 100, and 300 ng kg−1 min−1 were determined. Results. Percentage change of RBF (%RBF in response to Ang1-7 infusion increased in a dose-dependent manner. In the presence of BK, when MasR was not blocked, %RBF response to Ang 1-7 in OVE group was greater than OV group significantly (P<0.05. Infusion of 300 ng kg−1 min−1 Ang 1-7 increased RBF by 6.9±1.9% in OVE group versus 0.9±1.8% in OV group. However when MasR was blocked, %RBF response to Ang 1-7 in OV group was greater than OVE group insignificantly. Conclusion. Coadministration of BK and A779 compared to BK alone increased RBF response to Ang 1-7 in vehicle treated rats. Such observation was not seen in estradiol treated rats.

  10. Late acute humoral rejection in low-risk renal transplant recipients induced with an interleukin-2 receptor antagonist and maintained with standard therapy: preliminary communication.

    Science.gov (United States)

    Morales, J; Contreras, L; Zehnder, C; Pinto, V; Elberg, M; Araneda, S; Herzog, C; Calabran, L; Aguiló, J; Ferrario, M; Buckel, E; Fierro, J A

    2011-01-01

    Low-risk renal transplant recipients treated with standard immunosuppressive therapy including interleukin-2 receptor (IL-2R) antagonist show a low incidence of early rejection episodes but few reports have examined the incidence and severity of late rejection processes. This study evaluated retrospectively cellular and antibody-mediated rejection (AMR) among 42 recipients selected because they showed low panel-reactive-antibodies, short cold ischemia time, no delayed graft function, and therapy including basiliximab (Simulect) induction. The mean observation time was 6.6 years. Sixty-seven percent of donors were deceased. Ten-year patient and death-censored graft survivals were 81% and 78%, respectively. Seven patients lost their kidneys due to nonimmunologic events. The seven recipients who experienced cellular rejection episodes during the first posttransplant year had them reversed with steroids. Five patients displayed late acute AMR causing functional deterioration in four cases including 1 graft loss. De novo sensitization occurred in 48% of recipients including patients without clinical rejection. In conclusion, long-term follow-up of kidney transplant recipients selected by a low immunologic risk showed a persistent risk of de novo sensitization evolving to acute AMR in 11% of cases. Although immunologic events were related to late immunosuppressive reduction, most graft losses were due to nonimmunologic factors. Copyright © 2011 Elsevier Inc. All rights reserved.

  11. Effect of Angiotensin-Converting Enzyme Inhibitor/Calcium Antagonist Combination Therapy on Renal Function in Hypertensive Patients With Chronic Kidney Disease: Chikushi Anti-Hypertension Trial - Benidipine and Perindopril.

    Science.gov (United States)

    Okuda, Tetsu; Okamura, Keisuke; Shirai, Kazuyuki; Urata, Hidenori

    2018-02-01

    Appropriate blood pressure control suppresses progression of chronic kidney disease (CKD). If an angiotensin-converting enzyme (ACE) inhibitor is ineffective, adding a calcium antagonist is recommended. We compared the long-term effect of two ACE inhibitor/calcium antagonist combinations on renal function in hypertensive patients with CKD. Patients who failed to achieve the target blood pressure (systolic/diastolic: < 130/80 mm Hg) with perindopril monotherapy were randomized to either combined therapy with perindopril and the L-type calcium antagonist amlodipine (group A) or perindopril and the T/L type calcium antagonist benidipine (group B). The primary endpoint was the change of the estimated glomerular filtration rate (eGFR) after 2 years. Eligible patients had a systolic pressure ≥ 130 mm Hg and/or diastolic pressure ≥ 80 mm Hg and CKD (urine protein (+) or higher, eGFR < 60 min/mL/1.73 m 2 ). After excluding 38 patients achieving the target blood pressure with perindopril monotherapy, 121 patients were analyzed (62 in group A and 59 in group B). Blood pressure decreased significantly in both groups, but there was no significant change of the eGFR. However, among patients with diabetes, eGFR unchanged in group B (n = 37, 59.1 ± 15.1 vs. 61.2 ± 27.9, P = 0.273), whereas decreased significantly in group A (n = 31, 57.3 ± 16.0 vs. 53.7 ± 16.7, P = 0.005). In hypertensive patients with diabetic nephropathy, combined therapy with an ACE inhibitor and T/L type calcium antagonist may prevent deterioration of renal function more effectively than an ACE inhibitor/L type calcium antagonist combination.

  12. D-Saccharic acid 1,4-lactone protects diabetic rat kidney by ameliorating hyperglycemia-mediated oxidative stress and renal inflammatory cytokines via NF-κB and PKC signaling

    Energy Technology Data Exchange (ETDEWEB)

    Bhattacharya, Semantee [Department of Life Sciences and Biotechnology, Jadavpur University, 188, Raja S C Mullick Road, Kolkata 700 032 (India); Manna, Prasenjit [Division of Molecular Medicine, Bose Institute, P-1/12, CIT Scheme VII M, Kolkata-700054 (India); Gachhui, Ratan [Department of Life Sciences and Biotechnology, Jadavpur University, 188, Raja S C Mullick Road, Kolkata 700 032 (India); Sil, Parames C., E-mail: parames@bosemain.boseinst.ac.in [Division of Molecular Medicine, Bose Institute, P-1/12, CIT Scheme VII M, Kolkata-700054 (India)

    2013-02-15

    Increasing evidence suggests that oxidative stress is involved in the pathogenesis of diabetic nephropathy (DN) and this can be attenuated by antioxidants. D-Saccharic acid 1,4-lactone (DSL) is known for its detoxifying and antioxidant properties. Our early investigation showed that DSL can ameliorate alloxan (ALX) induced diabetes mellitus and oxidative stress in rats by inhibiting pancreatic β-cell apoptosis. In the present study we, therefore, investigated the protective role of DSL against renal injury in ALX induced diabetic rats. ALX exposure (at a dose of 120 mg/kg body weight, i. p., once) elevated the blood glucose level, serum markers related to renal injury, the production of reactive oxygen species (ROS), and disturbed the intra-cellular antioxidant machineries. Oral administration of DSL (80 mg/kg body weight) restored all these alterations close to normal. In addition, DSL could also normalize the aldose reductase activity which was found to increase in the diabetic rats. Investigating the mechanism of its protective activity, we observed the activation of different isoforms of PKC along with the accumulation of matrix proteins like collagen and fibronectin. The diabetic rats also showed nuclear translocation of NF-κB and increase in the concentration of inflammatory cytokines in the renal tissue. The activation of mitochondria dependent apoptotic pathway was observed in the diabetic rat kidneys. However, treatment of diabetic rats with DSL counteracted all these changes. These findings, for the first time, demonstrated that DSL could ameliorate renal dysfunction in diabetic rats by suppressing the oxidative stress related signalling pathways. - Highlights: ► Sustained hyperglycemia and oxidative stress lead to diabetic renal injury. ► D-saccharic acid 1,4-lactone prevents renal damage in alloxan-induced diabetes. ► It restores intra-cellular antioxidant machineries and kidney apoptosis. ► DSL reduces hyperglycemia-mediated oxidative stress

  13. Combination of active components of Xiexin decoction ameliorates renal fibrosis through the inhibition of NF-κB and TGF-β1/Smad pathways in db/db diabetic mice.

    Directory of Open Access Journals (Sweden)

    Jia-Sheng Wu

    Full Text Available Xiexin decoction, a herbal therapeutic agent commonly used in traditional Chinese medicine, is recognized for its beneficial effects on diabetic nephropathy exerted through the combined action of multiple components, including Rhizoma Coptidis alkaloids (A, Radix et Rhizoma Rhei polysaccharides (P, and Radix Scutellaria flavones (F. Our previous studies have shown that a combination of A, P, and F (APF exhibits renoprotective effects against diabetic nephropathy. This study was aimed at determining the effects of APF on renal fibrosis in diabetic nephropathy and elucidating the underlying molecular mechanisms. To evaluate the effects of APF, in vivo, db/db diabetic mice were orally administered a low or high dose of APF (300 or 600 mg/kg, respectively once a day for 8 weeks. We evaluated the blood and urine indices of metabolic and renal function, renal tissue histopathology, renal inflammation, and fibrosis. APF treatment significantly ameliorated glucose and lipid metabolism dysfunction, decreased urinary albumin excretion, normalized creatinine clearance, and reduced the morphological changes in renal tissue. Additionally, APF administration in db/db diabetic mice reduced the elevated levels of renal inflammation mediators such as intercellular adhesion molecule-1, monocyte chemotactic protein-1, tumor necrosis factor-α, interleukin-1β, and active nuclear factor κB (NF-κB. APF treatment also reduced type I and IV collagen, transforming growth factor-β1 (TGF-β1, and TGF-β1 type II receptor expression levels, and decreased the phosphorylation of Smad2/3 in the kidneys of db/db diabetic mice. These results suggest that APF reduces renal fibrosis in diabetic nephropathy through the NF-κB and TGF-β1/Smad signaling pathways. In vitro, APF treatment reduced cell proliferation and protein expression of α-smooth muscle actin, collagen I, TGF-β1 and NF-κB in mesangial cells cultured with high glucose concentrations. Our findings indicate

  14. Acute Kidney Injury in Heart Failure Revisited-The Ameliorating Impact of "Decongestive Diuresis" on Renal Dysfunction in Type 1 Acute Cardiorenal Syndrome: Accelerated Rising Pro B Naturetic Peptide Is a Predictor of Good Renal Prognosis.

    Science.gov (United States)

    Onuigbo, Macaulay Amechi Chukwukadibia; Agbasi, Nneoma; Sengodan, Mohan; Rosario, Karen Flores

    2017-08-29

    There is mounting evidence that forward heart failure as manifested by low cardiac output alone does not define the degree of renal dysfunction in cardiorenal syndrome. As a result, the term "congestive renal failure" was coined in 2012 by Ross to depict the role of renal venous hypertension in type 1 acute cardiorenal syndrome. If so, aggressive decongestive therapies, either through mechanical ultrafiltration with dialysis machines or pharmacologic ultrafiltration with potent diuretics, would lead to improved cardio and renal outcomes. Nevertheless, as recently as 2012, a review of this literature had concluded that a renal venous hypertension-directed approach using diuretics to manage cardio-renal syndrome was yet to be fully investigated. We, in this review, with three consecutive case series, describe our experience with pharmacologic decongestive diuresis in this paradigm of care and argue for studies of such therapeutic interventions in the management of cardiorenal syndrome. Finally, based on our observations in the Renal Unit, Mayo Clinic Health System, in Northwestern Wisconsin, we have hypothesized that patients with cardiorenal syndrome presenting with accelerated rising Pro B Naturetic Peptide levels appear to represent a group that would have good cardio- and renal-outcomes with such decongestive pharmacologic therapies.

  15. An aqueous extract of Portulaca oleracea ameliorates diabetic nephropathy through suppression of renal fibrosis and inflammation in diabetic db/db mice.

    Science.gov (United States)

    Lee, An Sook; Lee, Yun Jung; Lee, So Min; Yoon, Jung Joo; Kim, Jin Sook; Kang, Dae Gill; Lee, Ho Sub

    2012-01-01

    Diabetic nephropathy is one of the most common microvascular complications of diabetes and the leading cause of end-stage renal disease. In the present study, we investigated the renoprotective effect of the aqueous extract of Portulaca oleracea (AP) on diabetic nephropathy accelerated by renal fibrosis and inflammation in type 2 diabetic db/db mice. The mice were treated with AP (300 mg/kg/day, p.o.) for ten weeks to examine the long-term effects on diabetic nephropathy and renal dysfunction. We found that AP treatment markedly lowered blood glucose to 412 ± 11.4 mg/dl and plasma creatinine level to 2.3 ± 0.8 mg/dl compared to db/db mice (p < 0.05, p < 0.01, respectively). This study also showed that treatment with AP significantly decreased water intake and urine volume in diabetic db/db mice (p < 0.05). In immunohistological study, the renal expression of transforming growth factor-β1 (TGF-β1), advanced glycation end products (AGE), and intercellular adhesion molecule (ICAM)-1 markedly increased in the renal cortex of untreated db/db mice (p < 0.01). In contrast, AP treatment significantly reduced these expressions to 50 ± 2.1%, 48 ± 2.8%, 61 ± 1.1%, respectively (p < 0.01). Furthermore, NF-κB p65 activation in renal tissues markedly increased in untreated db/db mice, which was significantly suppressed by AP treatment. Taken together, these findings suggest that AP attenuates diabetic nephropathy through inhibition of renal fibrosis and inflammation in db/db mice.

  16. The Flavonoid Apigenin Ameliorates Cisplatin-Induced Nephrotoxicity through Reduction of p53 Activation and Promotion of PI3K/Akt Pathway in Human Renal Proximal Tubular Epithelial Cells

    Directory of Open Access Journals (Sweden)

    Sung Min Ju

    2015-01-01

    Full Text Available Apigenin is a member of the flavone subclass of flavonoids present in fruits and vegetables. Apigenin has long been considered to have various biological activities, such as antioxidant, anti-inflammatory, and antitumorigenic properties, in various cell types. Cisplatin was known to exhibit cytotoxic effect to renal cells by inducing apoptosis through activation of p53. The present study investigated the antiapoptotic effects of apigenin on the cisplatin-treated human renal proximal tubular epithelial (HK-2 cells. HK-2 cells were pretreated with apigenin (5, 10, 20 μM for 1 h and then treated with 40 μM cisplatin for various times. Apigenin inhibited the cisplatin-induced apoptosis of HK-2 cells. Interestingly, apigenin itself exerted cytostatic activity because of its ability to induce cell cycle arrest. Apigenin inhibited caspase-3 activity and PARP cleavage in cisplatin-treated cells. Apigenin reduced cisplatin-induced phosphorylation and expression of p53, with no significant influence on production of ROS that is known to induce p53 activation. Furthermore, apigenin promoted cisplatin-induced Akt phosphorylation, suggesting that enhanced Akt activation may be involved in cytoprotection. Taken together, these results suggest that apigenin ameliorates cisplatin-induced apoptosis through reduction of p53 activation and promotion of PI3K/Akt pathway in HK-2 cells.

  17. Conversion to Sirolimus Ameliorates Cyclosporine-Induced Nephropathy in the Rat: Focus on Serum, Urine, Gene, and Protein Renal Expression Biomarkers

    Directory of Open Access Journals (Sweden)

    José Sereno

    2014-01-01

    Full Text Available Protocols of conversion from cyclosporin A (CsA to sirolimus (SRL have been widely used in immunotherapy after transplantation to prevent CsA-induced nephropathy, but the molecular mechanisms underlying these protocols remain nuclear. This study aimed to identify the molecular pathways and putative biomarkers of CsA-to-SRL conversion in a rat model. Four animal groups (n=6 were tested during 9 weeks: control, CsA, SRL, and conversion (CsA for 3 weeks followed by SRL for 6 weeks. Classical and emergent serum, urinary, and kidney tissue (gene and protein expression markers were assessed. Renal lesions were analyzed in hematoxylin and eosin, periodic acid-Schiff, and Masson’s trichrome stains. SRL-treated rats presented proteinuria and NGAL (serum and urinary as the best markers of renal impairment. Short CsA treatment presented slight or even absent kidney lesions and TGF-β, NF-κβ, mTOR, PCNA, TP53, KIM-1, and CTGF as relevant gene and protein changes. Prolonged CsA exposure aggravated renal damage, without clear changes on the traditional markers, but with changes in serums TGF-β and IL-7, TBARs clearance, and kidney TGF-β and mTOR. Conversion to SRL prevented CsA-induced renal damage evolution (absent/mild grade lesions, while NGAL (serum versus urine seems to be a feasible biomarker of CsA replacement to SRL.

  18. Camel Milk Ameliorates 5-Fluorouracil-Induced Renal Injury in Rats: Targeting MAPKs, NF-κB and PI3K/Akt/eNOS Pathways

    Directory of Open Access Journals (Sweden)

    Hany H. Arab

    2018-04-01

    Full Text Available Background/Aims: The clinical utility of 5-fluorouracil (5-FU is limited by its nephrotoxicity. Camel milk (CM has previously displayed beneficial effects in toxicant-induced nephropathies. The current study aimed to investigate the potential of CM to attenuate 5-FU-induced nephrotoxicity in rats. Methods: Renal tissues were studied in terms of oxidative stress, inflammation and apoptosis. The levels of renal injury markers, inflammatory cytokines along with NOX-1, Nrf-2 and HO-1 were assessed by ELISA. The expression of MMP-2, MMP-9, NF-κBp65, p53, Bax and PCNA were detected by Immunohistochemistry. To gain an insight into the molecular signaling mechanisms, we determined the effect of CM on MAPKs, NF-κB and PI3K/Akt/eNOS pathways by Western blotting. Results: CM lowered 5-FU-triggered increase of creatinine, BUN, Kim-1 and NGAL renal injury biomarkers and attenuated the histopathological aberrations. It suppressed oxidative stress and augmented renal antioxidant armory (GSH, SOD, GPx, TAC with restoration of NOX-1, Nrf-2 and HO-1 levels. CM also suppressed renal inflammation as indicated by inhibition of MPO, TNF-α, IL-1β, IL-18 and MCP-1 proinflammatory mediators and downregulation of MMP-2 and MMP-9 expression with boosting of IL-10. Regarding MAPKs signaling, CM suppressed the phosphorylation of p38 MAPK, JNK1/2 and ERK1/2 and inhibited NF-κB activation. For apoptosis, CM downregulated p53, Bax, CytC and caspase-3 proapoptotic signals with enhancement of Bcl-2 and PCNA. It also enhanced PI3K p110α, phospho-Akt and phospho-eNOS levels with augmentation of renal NO, favoring cell survival. Equally important, CM preconditioning enhanced 5-FU cytotoxicity in MCF-7, HepG-2, HCT-116 and PC-3 cells, thus, justifying their concomitant use. Conclusion: The current findings pinpoint, for the first time, the marked renoprotective effects of CM that were mediated via ROS scavenging, suppression of MAPKs and NF-κB along with activation of PI3K

  19. Antigen-specific immature dendritic cell vaccine ameliorates anti-dsDNA antibody-induced renal damage in a mouse model.

    Science.gov (United States)

    Xia, Yumin; Jiang, Shan; Weng, Shenhong; Lv, Xiaochun; Cheng, Hong; Fang, Chunhong

    2011-12-01

    Dendritic cells (DCs) can inhibit immune response by clonal anergy when immature. Recent studies have shown that immature DCs (iDCs) may serve as a live cell vaccine after specific antigen pulse based on its potential of blocking antibody production. In this study, we aimed to investigate the effects of nuclear antigen-pulsed iDCs in the treatment of lupus-like renal damages induced by anti-dsDNA antibodies. iDCs were generated from haemopoietic stem cells in bone marrow and then pulsed in vitro with nuclear antigen. The iDC vaccine and corresponding controls were injected into mice with lupus-like renal damages. The evaluation of disease was monitored by biochemical parameters and histological scores. Anti-dsDNA antibody isotypes and T-lymphocyte-produced cytokines were analysed for elucidating therapeutic mechanisms. RESULTS; The mice treated with antigen-pulsed iDCs had a sustained remission of renal damage compared with those injected with non-pulsed iDCs or other controls, including decreased anti-dsDNA antibody level, less proteinuria, lower blood urea nitrogen and serum creatinine values, and improved histological evaluation. Analysis on isotypes of anti-dsDNA antibody showed that iDC vaccine preferentially inhibited the production of IgG3, IgG2b and IgG2a. Furthermore, administration of antigen-treated iDCs to mice resulted in significantly reduced IL-2, IL-4 and IL-12 and IFN-γ produced by T-memory cells. Conversely, the vaccination of antigen-pulsed mature DCs led to increased anti-dsDNA antibody production and an aggravation of lupus-like disease in the model. CONCLUSIONS; These results suggested the high potency of iDC vaccine in preventing lupus-like renal injuries induced by pathogenic autoantibodies.

  20. Dipeptidyl peptidase-4 inhibitor ameliorates early renal injury through its anti-inflammatory action in a rat model of type 1 diabetes

    Energy Technology Data Exchange (ETDEWEB)

    Kodera, Ryo, E-mail: kodera@cc.okayama-u.ac.jp [Center for Innovative Clinical Medicine, Okayama University Hospital, 2-5-1 Shikata-cho, Kita-ku, Okayama 700-8558 (Japan); Shikata, Kenichi [Center for Innovative Clinical Medicine, Okayama University Hospital, 2-5-1 Shikata-cho, Kita-ku, Okayama 700-8558 (Japan); Department of Medicine and Clinical Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama 700-8558 (Japan); Takatsuka, Tetsuharu; Oda, Kaori; Miyamoto, Satoshi; Kajitani, Nobuo; Hirota, Daisho; Ono, Tetsuichiro [Department of Medicine and Clinical Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama 700-8558 (Japan); Usui, Hitomi Kataoka [Department of Primary Care and Medical Education, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama 700-8558 (Japan); Makino, Hirofumi [Department of Medicine and Clinical Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama 700-8558 (Japan)

    2014-01-17

    Highlights: •DPP-4 inhibitor decreased urinary albumin excretion in a rat of type 1 diabetes. •DPP-4 inhibitor ameliorated histlogical changes of diabetic nephropathy. •DPP-4 inhibitor has reno-protective effects through anti-inflammatory action. •DPP-4 inhibitor is beneficial on diabetic nephropathy besides lowering blood glucose. -- Abstract: Introduction: Dipeptidyl peptidase-4 (DPP-4) inhibitors are incretin-based drugs in patients with type 2 diabetes. In our previous study, we showed that glucagon-like peptide-1 (GLP-1) receptor agonist has reno-protective effects through anti-inflammatory action. The mechanism of action of DPP-4 inhibitor is different from that of GLP-1 receptor agonists. It is not obvious whether DPP-4 inhibitor prevents the exacerbation of diabetic nephropathy through anti-inflammatory effects besides lowering blood glucose or not. The purpose of this study is to clarify the reno-protective effects of DPP-4 inhibitor through anti-inflammatory actions in the early diabetic nephropathy. Materials and methods: Five-week-old male Sprague–Dawley (SD) rats were divided into three groups; non-diabetes, diabetes and diabetes treated with DPP-4 inhibitor (PKF275-055; 3 mg/kg/day). PKF275-055 was administered orally for 8 weeks. Results: PKF275-055 increased the serum active GLP-1 concentration and the production of urinary cyclic AMP. PKF275-055 decreased urinary albumin excretion and ameliorated histological change of diabetic nephropathy. Macrophage infiltration was inhibited, and inflammatory molecules were down-regulated by PKF275-055 in the glomeruli. In addition, nuclear factor-κB (NF-κB) activity was suppressed in the kidney. Conclusions: These results indicate that DPP-4 inhibitor, PKF275-055, have reno-protective effects through anti-inflammatory action in the early stage of diabetic nephropathy. The endogenous biological active GLP-1 might be beneficial on diabetic nephropathy besides lowering blood glucose.

  1. Dipeptidyl peptidase-4 inhibitor ameliorates early renal injury through its anti-inflammatory action in a rat model of type 1 diabetes

    International Nuclear Information System (INIS)

    Kodera, Ryo; Shikata, Kenichi; Takatsuka, Tetsuharu; Oda, Kaori; Miyamoto, Satoshi; Kajitani, Nobuo; Hirota, Daisho; Ono, Tetsuichiro; Usui, Hitomi Kataoka; Makino, Hirofumi

    2014-01-01

    Highlights: •DPP-4 inhibitor decreased urinary albumin excretion in a rat of type 1 diabetes. •DPP-4 inhibitor ameliorated histlogical changes of diabetic nephropathy. •DPP-4 inhibitor has reno-protective effects through anti-inflammatory action. •DPP-4 inhibitor is beneficial on diabetic nephropathy besides lowering blood glucose. -- Abstract: Introduction: Dipeptidyl peptidase-4 (DPP-4) inhibitors are incretin-based drugs in patients with type 2 diabetes. In our previous study, we showed that glucagon-like peptide-1 (GLP-1) receptor agonist has reno-protective effects through anti-inflammatory action. The mechanism of action of DPP-4 inhibitor is different from that of GLP-1 receptor agonists. It is not obvious whether DPP-4 inhibitor prevents the exacerbation of diabetic nephropathy through anti-inflammatory effects besides lowering blood glucose or not. The purpose of this study is to clarify the reno-protective effects of DPP-4 inhibitor through anti-inflammatory actions in the early diabetic nephropathy. Materials and methods: Five-week-old male Sprague–Dawley (SD) rats were divided into three groups; non-diabetes, diabetes and diabetes treated with DPP-4 inhibitor (PKF275-055; 3 mg/kg/day). PKF275-055 was administered orally for 8 weeks. Results: PKF275-055 increased the serum active GLP-1 concentration and the production of urinary cyclic AMP. PKF275-055 decreased urinary albumin excretion and ameliorated histological change of diabetic nephropathy. Macrophage infiltration was inhibited, and inflammatory molecules were down-regulated by PKF275-055 in the glomeruli. In addition, nuclear factor-κB (NF-κB) activity was suppressed in the kidney. Conclusions: These results indicate that DPP-4 inhibitor, PKF275-055, have reno-protective effects through anti-inflammatory action in the early stage of diabetic nephropathy. The endogenous biological active GLP-1 might be beneficial on diabetic nephropathy besides lowering blood glucose

  2. Dietary docosahexaenoic acid ameliorates, but rapeseed oil and safflower oil accelerate renal injury in stroke-prone spontaneously hypertensive rats as compared with soybean oil, which is associated with expression for renal transforming growth factor-beta, fibronectin and renin.

    Science.gov (United States)

    Miyazaki, M; Takemura, N; Watanabe, S; Hata, N; Misawa, Y; Okuyama, H

    2000-01-03

    We have noted that n-3 fatty acid-rich oils, such as fish oil, perilla oil and flaxseed oil as well as ethyl docosahexaenoate (DHA) prolonged the survival time of stroke-prone spontaneously hypertensive rats (SHRSP) rats by approximately 10% as compared with linoleate (n-6)-rich safflower oil. Rapeseed oil with a relatively low n-6/n-3 ratio unusually shortened the survival time by approximately 40%, suggesting the presence of minor components unfavorable to SHRSP rats. This study examined the effects of dietary oils and DHA on renal injury and gene expression related to renal injury in SHRSP rats. Rats fed rapeseed oil- and safflower oil-supplemented diets developed more severe proteinuria than those fed soybean oil-supplemented diet used as a control, but there were no significant differences in blood pressure. In contrast, the DHA-supplemented diet inhibited the development of proteinuria and suppressed hypertension. The mRNA levels for renal TGF-beta, fibronectin and renin were higher in the rapeseed oil and safflower oil groups after 9 weeks of feeding of the experimental diet than in the soybean oil and DHA groups. The fatty acid composition of kidney phospholipids was markedly affected by these diets. These results indicate that the renal injury observed in the groups fed safflower oil with a high n-6/n-3 ratio and rapeseed oil with presumed minor components is accompanied by increased expression of the TGF-beta, renin and fibronectin genes, and that dietary DHA suppresses renal injury and gene expression as compared with soybean oil.

  3. Effects of single and repeated doses of the calcium antagonist felodipine on blood pressure, renal function, electrolytes and water balance, and renin-angiotensin-aldosterone system in hypertensive patients.

    Science.gov (United States)

    Leonetti, G; Gradnik, R; Terzoli, L; Fruscio, M; Rupoli, L; Cuspidi, C; Sampieri, L; Zanchetti, A

    1986-01-01

    Doses of 10 mg b.i.d. of the new dihydropyridine calcium antagonist, felodipine, were tested for seven consecutive days in 11 hospitalized hypertensive patients. A significant reduction of both systolic and diastolic blood pressures, with patients in both the supine and upright positions, occurred immediately after the first dose and was maintained (daily average 15%) throughout the following days. An increase in heart rate was observed after the first dose (15 and 23 beats/min, in supine and upright postures), and subsequently declined to average values of 8 and 14 beats/min on the seventh day. There was a marked natriuretic response during the first and second day, during which an average negative sodium balance of 95 mmol developed; on the following days sodium output was not significantly different from control, but a negative balance averaging 135 mmol was still present on the seventh day of felodipine administration. A moderate negative potassium balance also progressively developed and reached -48 mmol on the seventh day. Glomerular filtration rate was unchanged, but renal plasma flow increased significantly during administration of felodipine. Plasma renin activity and plasma aldosterone were also increased very moderately by felodipine. Compared with previous observations by our group with higher doses of felodipine (12.5, 25, and 50 mg t.i.d.), 10 mg b.i.d. of this new calcium antagonist appear to exert a marked and prolonged blood pressure reduction, accompanied by a definite natriuretic instead of an antinatriuretic effect.

  4. Andrographolide ameliorates diabetic nephropathy by attenuating hyperglycemia-mediated renal oxidative stress and inflammation via Akt/NF-κB pathway.

    Science.gov (United States)

    Ji, Xiaoqian; Li, Changzheng; Ou, Yitao; Li, Ning; Yuan, Kai; Yang, Guizhi; Chen, Xiaoyan; Yang, Zhicheng; Liu, Bing; Cheung, Wai W; Wang, Lijing; Huang, Ren; Lan, Tian

    2016-12-05

    Diabetic nephropathy (DN) is characterized by proliferation of mesangial cells, mesangial hypertrophy and extracellular matrix (ECM) accumulation. Our recent study found that andrographolide inhibited high glucose-induced mesangial cell proliferation and fibronectin expression through inhibition of AP-1 pathway. However, whether andrographolide has reno-protective roles in DN has not been fully elucidated. Here, we studied the pharmacological effects of andrographolide against the progression of DN and high glucose-induced mesangial dysfunction. Diabetes was induced in C57BL/6 mice by intraperitoneal injection of streptozotocin (STZ). After 1 weeks after STZ injection, normal diet was substituted with a high-fat diet (HFD). Diabetic mice were intraperitoneal injected with andrographolide (2 mg/kg, twice a week). After 8 weeks, functional and histological analyses were carried out. Parallel experiments uncovering the molecular mechanism by which andrographolide prevents from DN was performed in mesangial cells. Andrographolide inhibited the increases in fasting blood glucose, triglyceride, kidney/body weight ratio, blood urea nitrogen, serum creatinine and 24-h albuminuria in diabetic mice. Andrographolide also prevented renal hypertrophy and ECM accumulation. Furthermore, andrographolide markedly attenuated NOX1 expression, ROS production and pro-inflammatory cytokines as well. Additionally, andrographolide inhibited Akt/NF-κB signaling pathway. These results demonstrate that andrographolide is protective against the progression of experimental DN by inhibiting renal oxidative stress, inflammation and fibrosis. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  5. Mitochondrial Modulation by Epigallocatechin 3-Gallate Ameliorates Cisplatin Induced Renal Injury through Decreasing Oxidative/Nitrative Stress, Inflammation and NF-kB in Mice

    Science.gov (United States)

    Wang, Xueping; Wang, Ping; Fu, Guanghou; Meng, Hongzhou; Wang, Yimin; Jin, Baiye

    2015-01-01

    Cancer chemotherapy drug cisplatin is known for its nephrotoxicity. The aim of this study is to investigate whether Epigallocatechin 3-Gallate (EGCG) can reduce cisplatin mediated side effect in kidney and to understand its mechanism of protection against tissue injury. We used a well-established 3-day cisplatin induced nephrotoxicity mice model where EGCG were administered. EGCG is a major active compound in Green Tea and have strong anti-oxidant and anti-inflammatory properties. EGCG protected against cisplatin induced renal dysfunction as measured by serum creatinine and blood urea nitrogen (BUN). EGCG improved cisplatin induced kidney structural damages such as tubular dilatation, cast formation, granulovaculoar degeneration and tubular cell necrosis as evident by PAS staining. Cisplatin induced kidney specific mitochondrial oxidative stress, impaired activities of mitochondrial electron transport chain enzyme complexes, impaired anti-oxidant defense enzyme activities such as glutathione peroxidase (GPX) and manganese superoxide dismutase (MnSOD) in mitochondria, inflammation (tumor necrosis factor α and interleukin 1β), increased accumulation of NF-κB in nuclear fraction, p53 induction, and apoptotic cell death (caspase 3 activity and DNA fragmentation). Treatment of mice with EGCG markedly attenuated cisplatin induced mitochondrial oxidative/nitrative stress, mitochondrial damages to electron transport chain activities and antioxidant defense enzyme activities in mitochondria. These mitochondrial modulations by EGCG led to protection mechanism against cisplatin induced inflammation and apoptotic cell death in mice kidney. As a result, EGCG improved renal function in cisplatin mediated kidney damage. In addition to that, EGCG attenuated cisplatin induced apoptotic cell death and mitochondrial reactive oxygen species (ROS) generation in human kidney tubular cell line HK-2. Thus, our data suggest that EGCG may represent new promising adjunct candidate for

  6. Pharmacological investigations of Punica granatum in glycerol-induced acute renal failure in rats.

    Science.gov (United States)

    Singh, Amrit Pal; Singh, Amteshwar Jaggi; Singh, Nirmal

    2011-09-01

    The present study was designed to investigate the ameliorative potential and possible mechanism of hydroalcoholic extract of flowers of P. granatum in glycerol-induced acute renal failure (ARF) in rats. The rats were subjected to rhabdomyolytic ARF by single intramuscular injection of hypertonic glycerol (50% v/v; 8 ml/kg) and the animals were sacrificed after 24 hours of glycerol injection. The plasma creatinine, blood urea nitrogen, creatinine clearance, and histopathological studies were performed to assess the degree of renal injury. Pretreatment with hydroalcoholic extract of flowers of P. granatum (125 and 250 mg/kg p.o. twice daily for 3 days) significantly attenuated hypertonic glycerol-induced renal dysfunction in a dose-dependent manner. BADGE (Bisphenol-A-diglycidyl ether) (30 mg/kg), a peroxisome proliferator-activated receptor (PPAR)-γ antagonist, and N(omega)-nitro-l-arginine-methyl ester (L-NAME) (10, 20, and 40 mg/kg), nitric oxide synthase inhibitor, were employed to explore the mechanism of renoprotective effects of Punica granatum. Administration of BADGE (30 mg/kg) and L-NAME (40 mg/kg) abolished the beneficial effects of P. granatum in glycerol-induced renal dysfunction. Hydroalcoholic extract of flowers of P. granatum has ameliorative potential in attenuating myoglobinuric renal failure and its renoprotective effects involve activation of PPAR-γ and nitric oxide-dependent signaling pathway.

  7. ACTH antagonists

    Directory of Open Access Journals (Sweden)

    Adrian John Clark

    2016-08-01

    Full Text Available ACTH acts via a highly selective receptor that is a member of the melanocortin receptor subfamily of type 1 G protein-coupled receptors. The ACTH receptor, also known as the melanocortin 2 receptor (MC2R is unusual in that it is absolutely dependent on a small accessory protein, melanocortin receptor accessory protein (MRAP for cell surface expression and function. ACTH is the only known naturally occurring agonist for this receptor. This lack of redundancy and high degree of ligand specificity suggests that antagonism of this receptor could provide a useful therapeutic aid and a potential investigational tool. Clinical situations in which this could be useful include (1 Cushing’s disease and ectopic ACTH syndrome – especially whilst preparing for definitive treatment of a causative tumour, or in refractory cases, or (2 congenital adrenal hyperplasia – as an adjunct to glucocorticoid replacement. A case for antagonism in other clinical situations in which there is ACTH excess can also be made. In this article we will explore the scientific and clinical case for an ACTH antagonist, and will review the evidence for existing and recently described peptides and modified peptides in this role.

  8. Vitamin K antagonist use and mortality in dialysis patients

    NARCIS (Netherlands)

    Voskamp, Pauline W.M.; Rookmaaker, Maarten B.; Verhaar, Marianne C.; Dekker, Friedo W.; Ocak, Gurbey

    2018-01-01

    Background. The risk-benefit ratio of vitamin K antagonists for different CHA2DS2-VASc scores in patients with end-stage renal disease treated with dialysis is unknown. The aim of this study was to investigate the association between vitamin K antagonist use and mortality for different CHA2DS2-VASc

  9. Renal artery stenosis.

    Science.gov (United States)

    Tafur-Soto, Jose David; White, Christopher J

    2015-02-01

    Atherosclerotic renal artery stenosis (RAS) is the single largest cause of secondary hypertension; it is associated with progressive renal insufficiency and causes cardiovascular complications such as refractory heart failure and flash pulmonary edema. Medical therapy, including risk factor modification, renin-angiotensin-aldosterone system antagonists, lipid-lowering agents, and antiplatelet therapy, is advised in all patients. Patients with uncontrolled renovascular hypertension despite optimal medical therapy, ischemic nephropathy, and cardiac destabilization syndromes who have severe RAS are likely to benefit from renal artery revascularization. Screening for RAS can be done with Doppler ultrasonography, CT angiography, and magnetic resonance angiography. Copyright © 2015 Elsevier Inc. All rights reserved.

  10. Renal protection in diabetes

    DEFF Research Database (Denmark)

    Parving, H H; Tarnow, L; Rossing, P

    1996-01-01

    BACKGROUND: The combination of diabetes and hypertension increases the chances of progressive renal disorder and, ultimately, renal failure. Roughly 40% of all diabetics, whether insulin-dependent or not, develop diabetic nephropathy. Diabetic nephropathy is the single most important cause of end...... function in diabetic patients with incipient diabetic nephropathy. There are still no long-term trials using the new long-acting dihydropyridine calcium antagonists to treat patients with incipient nephropathy. A recent, 1-year, randomized, double-blind study in hypertensive insulin-dependent diabetic...... identical in both treatment groups, at 103 (SD 9) and 101 (SD 11) mmHg, respectively. Furthermore, a recent 5-year randomized open study in hypertensive non-insulin-dependent patients with diabetic nephropathy has revealed the same beneficial effect of a calcium antagonist and of ACE inhibition...

  11. Combination decongestion therapy in hospitalized heart failure: loop diuretics, mineralocorticoid receptor antagonists and vasopressin antagonists.

    Science.gov (United States)

    Vaduganathan, Muthiah; Mentz, Robert J; Greene, Stephen J; Senni, Michele; Sato, Naoki; Nodari, Savina; Butler, Javed; Gheorghiade, Mihai

    2015-01-01

    Congestion is the most common reason for admissions and readmissions for heart failure (HF). The vast majority of hospitalized HF patients appear to respond readily to loop diuretics, but available data suggest that a significant proportion are being discharged with persistent evidence of congestion. Although novel therapies targeting congestion should continue to be developed, currently available agents may be utilized more optimally to facilitate complete decongestion. The combination of loop diuretics, natriuretic doses of mineralocorticoid receptor antagonists and vasopressin antagonists represents a regimen of currently available therapies that affects early and persistent decongestion, while limiting the associated risks of electrolyte disturbances, hemodynamic fluctuations, renal dysfunction and mortality.

  12. Ameliorative effect of antioxidants (vitamins C and E against abamectin toxicity in liver, kidney and testis of male albino rats

    Directory of Open Access Journals (Sweden)

    B. Wilson Magdy

    2016-10-01

    In conclusion, it appears that vitamins C and E, or in combination (as antioxidants ameliorate the hepato-renal and testicular toxicity of abamectin, but are not completely protective, especially in liver tissue.

  13. Ameliorative percutaneous lumbar discectomy

    International Nuclear Information System (INIS)

    Xiao Chengjiang; Su Huanbin; He Xiaofeng; Li Yanhao

    2005-01-01

    Objective: To ameliorate the percutaneous lumbar discectomy (APLD) for improving the effectiveness and amplifying the indicative range of PLD. Methods: To ameliorate percutaneous punctured route based on classic PLD and discectomy of extracting pulp out of the herniated disc with special pulpforceps. The statistical analysis of the therapeutic results on 750 disc protrusions of 655 cases undergone APLD following up from 6 to 54 months retrospectively. Results: The effective ratios were excellent in 40.2%, good for 46.6% and bad of 13.3%. No occurrance of intervertebral inflammation and paradiscal hematoma, there were only 1 case complicated with injuried cauda equina, and 4 cases with broken appliance within disc. Conclusions: APLD is effective and safe, not only indicative for inclusion disc herniation, but also for noninclusion herniation. (authors)

  14. Renal rescue of dopamine D2 receptor function reverses renal injury and high blood pressure

    Science.gov (United States)

    Konkalmatt, Prasad R.; Asico, Laureano D.; Zhang, Yanrong; Yang, Yu; Drachenberg, Cinthia; Zheng, Xiaoxu; Han, Fei; Jose, Pedro A.; Armando, Ines

    2016-01-01

    Dopamine D2 receptor (DRD2) deficiency increases renal inflammation and blood pressure in mice. We show here that long-term renal-selective silencing of Drd2 using siRNA increases renal expression of proinflammatory and profibrotic factors and blood pressure in mice. To determine the effects of renal-selective rescue of Drd2 expression in mice, the renal expression of DRD2 was first silenced using siRNA and 14 days later rescued by retrograde renal infusion of adeno-associated virus (AAV) vector with DRD2. Renal Drd2 siRNA treatment decreased the renal expression of DRD2 protein by 55%, and DRD2 AAV treatment increased the renal expression of DRD2 protein by 7.5- to 10-fold. Renal-selective DRD2 rescue reduced the expression of proinflammatory factors and kidney injury, preserved renal function, and normalized systolic and diastolic blood pressure. These results demonstrate that the deleterious effects of renal-selective Drd2 silencing on renal function and blood pressure were rescued by renal-selective overexpression of DRD2. Moreover, the deleterious effects of 45-minute bilateral ischemia/reperfusion on renal function and blood pressure in mice were ameliorated by a renal-selective increase in DRD2 expression by the retrograde ureteral infusion of DRD2 AAV immediately after the induction of ischemia/reperfusion injury. Thus, 14 days after ischemia/reperfusion injury, the renal expression of profibrotic factors, serum creatinine, and blood pressure were lower in mice infused with DRD2 AAV than in those infused with control AAV. These results indicate an important role of renal DRD2 in limiting renal injury and preserving normal renal function and blood pressure. PMID:27358912

  15. Dopamine antagonists and brief vision distinguish lens-induced- and form-deprivation-induced myopia

    OpenAIRE

    Nickla, Debora L.; Totonelly, Kristen

    2011-01-01

    In eyes wearing negative lenses, the D2 dopamine antagonist spiperone was only partly effective in preventing the ameliorative effects of brief periods of vision (Nickla et al., 2010), in contrast to reports from studies using form deprivation. The present study was done to directly compare the effects of spiperone, and the D1 antagonist SCH-23390, on the two different myopiagenic paradigms. 12-day old chickens wore monocular diffusers (form deprivation) or − 10 D lenses attached to the feath...

  16. Hypogonadism and renal failure: An update.

    Science.gov (United States)

    Thirumavalavan, Nannan; Wilken, Nathan A; Ramasamy, Ranjith

    2015-01-01

    The prevalence of both hypogonadism and renal failure is increasing. Hypogonadism in men with renal failure carries with it significant morbidity, including anemia and premature cardiovascular disease. It remains unclear whether testosterone therapy can affect the morbidity and mortality associated with renal failure. As such, in this review, we sought to evaluate the current literature addressing hypogonadism and testosterone replacement, specifically in men with renal failure. The articles chosen for this review were selected by performing a broad search using Pubmed, Embase and Scopus including the terms hypogonadism and renal failure from 1990 to the present. This review is based on both primary sources as well as review articles. Hypogonadism in renal failure has a multifactorial etiology, including co-morbid conditions such as diabetes, hypertension, old age and obesity. Renal failure can lead to decreased luteinizing hormone production and decreased prolactin clearance that could impair testosterone production. Given the increasing prevalence of hypogonadism and the potential morbidity associated with hypogonadism in men with renal failure, careful evaluation of serum testosterone would be valuable. Testosterone replacement therapy should be considered in men with symptomatic hypogonadism and renal failure, and may ameliorate some of the morbidity associated with renal failure. Patients with all stages of renal disease are at an increased risk of hypogonadism that could be associated with significant morbidity. Testosterone replacement therapy may reduce some of the morbidity of renal failure, although it carries risk.

  17. Nitro-oleic acid ameliorates oxygen and glucose deprivation/re-oxygenation triggered oxidative stress in renal tubular cells via activation of Nrf2 and suppression of NADPH oxidase.

    Science.gov (United States)

    Nie, Huibin; Xue, Xia; Liu, Gang; Guan, Guangju; Liu, Haiying; Sun, Lina; Zhao, Long; Wang, Xueling; Chen, Zhixin

    2016-01-01

    Nitroalkene derivative of oleic acid (OA-NO 2 ), due to its ability to mediate revisable Michael addition, has been demonstrated to have various biological properties and become a therapeutic agent in various diseases. Though its antioxidant properties have been reported in different models of acute kidney injury (AKI), the mechanism by which OA-NO 2 attenuates intracellular oxidative stress is not well investigated. Here, we elucidated the anti-oxidative mechanism of OA-NO 2 in an in vitro model of renal ischemia/reperfusion (I/R) injury. Human tubular epithelial cells were subjected to oxygen and glucose deprivation/re-oxygenation (OGD/R) injury. Pretreatment with OA-NO 2 (1.25 μM, 45 min) attenuated OGD/R triggered reactive oxygen species (ROS) generation and subsequent mitochondrial membrane potential disruption. This action was mediated via up-regulating endogenous antioxidant defense components including superoxide dismutase (SOD1), heme oxygenase 1 (HO-1), and γ-glutamyl cysteine ligase modulatory subunits (GCLM). Moreover, subcellular fractionation analyses demonstrated that OA-NO 2 promoted nuclear translocation of nuclear factor-E2- related factor-2 (Nrf2) and Nrf2 siRNA partially abrogated these protective effects. In addition, OA-NO 2 inhibited NADPH oxidase activation and NADPH oxidase 4 (NOX4), NADPH oxidase 2 (NOX2) and p22 phox up-regulation after OGD/R injury, which was not relevant to Nrf2. These results contribute to clarify that the mechanism of OA-NO 2 reno-protection involves both inhibition of NADPH oxidase activity and induction of SOD1, Nrf2-dependent HO-1, and GCLM.

  18. Renal Osteodystrophy

    Directory of Open Access Journals (Sweden)

    Aynur Metin Terzibaşoğlu

    2004-12-01

    Full Text Available Chronic renal insufficiency is a functional definition which is characterized by irreversible and progressive decreasing in renal functions. This impairment is in collaboration with glomeruler filtration rate and serum creatinine levels. Besides this, different grades of bone metabolism disorders develop in chronic renal insufficiency. Pathologic changes in bone tissue due to loss of renal paranchyme is interrelated with calcium, phosphorus vitamine-D and parathyroid hormone. Clinically we can see high turnover bone disease, low turnover bone disease, osteomalacia, osteosclerosis and osteoporosis in renal osteodystropy. In this article we aimed to review pathology of bone metabolism disorders due to chronic renal insufficiency, clinic aspects and treatment approaches briefly.

  19. Mesenchymal Stem Cells May Ameliorate Nephrotic Syndrome Post-Allogeneic Hematopoietic Stem Cell Transplantation-Case Report

    Directory of Open Access Journals (Sweden)

    Xin Zhang

    2017-08-01

    Full Text Available IntroductionBecause of their immunomodulatory and anti-inflammatory effects, mesenchymal stem cells (MSCs have been considered as potential therapeutic agents for treating immune-related or autoimmune diseases, such as graft-versus-host disease (GVHD. Nephrotic syndrome (NS after allogeneic hematopoietic stem cell transplantation (allo-HSCT is an uncommon complication with unclear etiology and pathogenesis. It may be an immune disorder involving immune complex deposition, B cells, regulatory T cells (Tregs, and Th1 cytokines and be a manifestation of chronic GVHD. Corticosteroids and calcium antagonists, alone or in combination, are the most common therapeutic agents in this setting. Rituximab is commonly administered as salvage treatment. However, treatment failure and progressive renal function deterioration has been reported to occur in approximately 20% of patients in a particular cohort.Case presentationWe present a patient who developed NS 10 months after allo-HSCT. After treatment failure with cyclosporine A, prednisone, and rituximab, she achieved a complete response with MSC treatment. The clinical improvement of this patient was accompanied by a decreased B cell population together with an increased frequency of regulatory B cells (Bregs and Tregs after MSC treatment.ConclusionMSCs could modulate NS after allo-HSCT by suppressing B cell proliferation, inducing Tregs and Bregs, and inhibiting inflammatory cytokine production by monocytes and NK cells. Among all these, Bregs might play an important role in ameliorating the NS of this patient.

  20. Renal venogram

    Science.gov (United States)

    ... be black. Other structures will be shades of gray. Veins are not normally seen in an x- ... Venogram - kidney; Renal vein thrombosis - venogram Images Kidney anatomy Kidney - blood and urine flow Renal veins References ...

  1. Dual antagonists of integrins.

    Science.gov (United States)

    Nadrah, K; Dolenc, M Sollner

    2005-01-01

    The roles of integrins in pathologies have been studied intensively and only partially explained. This has resulted in the development of several nanomolar antagonists to certain integrins. In most cases, the aim was to produce compounds which are highly selective towards specific integrins. This paradigm has recently shifted a little. Targeting two or more integrins with one compound has become a very attractive concept, especially since it has become clear that several severe disorders, such as pathological angiogenesis, cannot be treated just with highly specific integrin antagonists. This review is aimed to elucidate some aspects regarding the design of drugs with dual activity towards integrins. Integrin structure and tissue distribution will first be described, in order to provide the basis for their functions in various pathologies which will follow. Inhibitors of several pairs of integrins will be described.

  2. Renal perfusion scintiscan

    Science.gov (United States)

    ... Radionuclide renal perfusion scan; Perfusion scintiscan - renal; Scintiscan - renal perfusion Images Kidney anatomy Kidney - blood and urine flow Intravenous pyelogram References Rottenberg G, Andi AC. Renal ...

  3. Uricosuric effect of losartan in patients with renal transplants

    DEFF Research Database (Denmark)

    Kamper, A L; Nielsen, A H

    2001-01-01

    BACKGROUND: The aim of the study was to evaluate the uricosuric effect of the angiotensin II receptor antagonist, losartan, in hypertensive patients with renal transplants who are treated with cyclosporin A (CsA). METHODS: Twenty-six patients with stable renal function and hypertension, 16 men......-daily administration of 50 mg of losartan in hypertensive CsA-treated patients with renal transplants caused a 17% increase in FE(uric acid) and an 8% fall in plasma uric acid....

  4. Purinergic Signalling in Inflammatory Renal Disease

    Directory of Open Access Journals (Sweden)

    Nishkantha eArulkumaran

    2013-07-01

    Full Text Available Extracellular purines have a role in renal physiology and adaption to inflammation. However, inflammatory renal disease may be mediated by extracellular purines, resulting in renal injury. The role of purinergic signalling is dependent on the concentrations of extracellular purines. Low basal levels of purines are important in normal homeostasis and growth. Concentrations of extracellular purines are significantly elevated during inflammation and mediate either an adaptive role or propagate local inflammation. Adenosine signalling mediates alterations in regional renal blood flow by regulation of the renal microcirculation, tubulo-glomerular feedback, and tubular transport of sodium and water. Increased extracellular ATP and renal P2 receptor-mediated inflammation are associated with various renal diseases, including hypertension, diabetic nephropathy, and glomerulonephritis. Experimental data suggests P2 receptor deficiency or receptor antagonism is associated with amelioration of antibody-mediated nephritis, suggesting a pathogenic (rather than adaptive role of purinergic signalling. We discuss the role of extracellular nucleotides in adaptation to ischaemic renal injury and in the pathogenesis of inflammatory renal disease.

  5. Endothelin receptor antagonists influence cardiovascular morphology in uremic rats.

    Science.gov (United States)

    Nabokov, A V; Amann, K; Wessels, S; Münter, K; Wagner, J; Ritz, E

    1999-02-01

    In is generally held that renal failure results in blood pressure (BP)-independent structural changes of the myocardium and the vasculature. The contribution, if any, of endothelin (ET) to these changes has been unknown. We morphometrically studied random samples of the left ventricle myocardium and small intramyocardial arteries in subtotally (5/6) nephrectomized (SNx) male Sprague-Dawley rats treated with either the selective ETA receptor antagonist BMS182874 (30 mg/kg/day) or the nonselective ETA/ETB receptor antagonist Ro46-2005 (30 mg/kg/day) in comparison with either sham-operated rats, untreated SNx, or SNx rats treated with the angiotensin-converting enzyme inhibitor trandolapril (0.1 mg/kg/day). Eight weeks later, systolic BP was lower in trandolapril-treated SNx compared with untreated SNx animals. No decrease in BP was seen following either ET receptor antagonist at the dose used. A significantly increased volume density of the myocardial interstitium was found in untreated SNx rats as compared with sham-operated controls. Such interstitial expansion was prevented by trandolapril and either ET receptor antagonist. SNx caused a substantial increase in the wall thickness of small intramyocardial arteries. The increase was prevented by trandolapril or BMS182874 treatment. The arteriolar wall:lumen ratio was significantly lower in all treated groups when compared with untreated SNx. In contrast, only trandolapril, but not the ET receptor antagonists, attenuated thickening of the aortic media in SNx animals. The ETA-selective and ETA/ETB-nonselective receptor antagonists appear to prevent development of myocardial fibrosis and structural changes of small intramyocardial arteries in experimental chronic renal failure. This effect is independent of systemic BP.

  6. Serotonin 2A receptor antagonists for treatment of schizophrenia

    DEFF Research Database (Denmark)

    Ebdrup, Bjørn Hylsebeck; Rasmussen, Hans; Arnt, Jørn

    2011-01-01

    Introduction: All approved antipsychotic drugs share an affinity for the dopamine 2 (D2) receptor; however, these drugs only partially ameliorate the symptoms of schizophrenia. It is, therefore, of paramount importance to identify new treatment strategies for schizophrenia. Areas covered......: Preclinical, clinical and post-mortem studies of the serotonin 5-HT2A system in schizophrenia are reviewed. The implications of a combined D2 and 5-HT2A receptor blockade, which is obtained by several current antipsychotic drugs, are discussed, and the rationale for the development of more selective 5-HT2A...... receptor antagonists is evaluated. Moreover, the investigational pipeline of major pharmaceutical companies is examined and an Internet search conducted to identify other pharmaceutical companies investigating 5-HT2A receptor antagonists for the treatment of schizophrenia. Expert opinion: 5-HT2A receptor...

  7. Are peripheral opioid antagonists the solution to opioid side effects?

    LENUS (Irish Health Repository)

    Bates, John J

    2012-02-03

    Opioid medication is the mainstay of therapy for severe acute and chronic pain. Unfortunately, the side effects of these medications can affect patient comfort and safety, thus limiting their proven therapeutic potential. Whereas the main analgesic effects of opioids are centrally mediated, many of the common side effects are mediated via peripheral receptors. Novel peripheral opioid antagonists have been recently introduced that can block the peripheral actions of opioids without affecting centrally mediated analgesia. We review the clinical and experimental evidence of their efficacy in ameliorating opioid side effects and consider what further information might be useful in defining their role. IMPLICATIONS: The major analgesic effects of opioid medication are mediated within the brain and spinal cord. Many of the side effects of opioids are caused by activation of receptors outside these areas. Recently developed peripherally restricted opioid antagonists have the ability to block many opioid side effects without affecting analgesia.

  8. RENAL CRYOABLATION

    Directory of Open Access Journals (Sweden)

    A. V. Govorov

    2012-01-01

    Full Text Available Renal cryoablation is an alternative minimally-invasive method of treatment for localized renal cell carcinoma. The main advantages of this methodology include visualization of the tumor and the forming of "ice ball" in real time, fewer complications compared with other methods of treatment of renal cell carcinoma, as well as the possibility of conducting cryotherapy in patients with concomitant pathology. Compared with other ablative technologies cryoablation has a low rate of repeat sessions and good intermediate oncological results. The studies of long-term oncological and functional results of renal cryoablation are presently under way.

  9. P2Y12 Receptor Localizes in the Renal Collecting Duct and Its Blockade Augments Arginine Vasopressin Action and Alleviates Nephrogenic Diabetes Insipidus.

    Science.gov (United States)

    Zhang, Yue; Peti-Peterdi, Janos; Müller, Christa E; Carlson, Noel G; Baqi, Younis; Strasburg, David L; Heiney, Kristina M; Villanueva, Karie; Kohan, Donald E; Kishore, Bellamkonda K

    2015-12-01

    P2Y12 receptor (P2Y12-R) signaling is mediated through Gi, ultimately reducing cellular cAMP levels. Because cAMP is a central modulator of arginine vasopressin (AVP)-induced water transport in the renal collecting duct (CD), we hypothesized that if expressed in the CD, P2Y12-R may play a role in renal handling of water in health and in nephrogenic diabetes insipidus. We found P2Y12-R mRNA expression in rat kidney, and immunolocalized its protein and aquaporin-2 (AQP2) in CD principal cells. Administration of clopidogrel bisulfate, an irreversible inhibitor of P2Y12-R, significantly increased urine concentration and AQP2 protein in the kidneys of Sprague-Dawley rats. Notably, clopidogrel did not alter urine concentration in Brattleboro rats that lack AVP. Clopidogrel administration also significantly ameliorated lithium-induced polyuria, improved urine concentrating ability and AQP2 protein abundance, and reversed the lithium-induced increase in free-water excretion, without decreasing blood or kidney tissue lithium levels. Clopidogrel administration also augmented the lithium-induced increase in urinary AVP excretion and suppressed the lithium-induced increase in urinary nitrates/nitrites (nitric oxide production) and 8-isoprostane (oxidative stress). Furthermore, selective blockade of P2Y12-R by the reversible antagonist PSB-0739 in primary cultures of rat inner medullary CD cells potentiated the expression of AQP2 and AQP3 mRNA, and cAMP production induced by dDAVP (desmopressin). In conclusion, pharmacologic blockade of renal P2Y12-R increases urinary concentrating ability by augmenting the effect of AVP on the kidney and ameliorates lithium-induced NDI by potentiating the action of AVP on the CD. This strategy may offer a novel and effective therapy for lithium-induced NDI. Copyright © 2015 by the American Society of Nephrology.

  10. Renal cancer.

    NARCIS (Netherlands)

    Corgna, E.; Betti, M.; Gatta, G.; Roila, F.; Mulder, P.H.M. de

    2007-01-01

    In Europe, renal cancer (that is neoplasia of the kidney, renal pelvis or ureter (ICD-9 189 and ICD-10 C64-C66)) ranks as the seventh most common malignancy in men amongst whom there are 29,600 new cases each year (3.5% of all cancers). Tobacco, obesity and a diet poor in vegetables are all

  11. Renal cancer

    NARCIS (Netherlands)

    Corgna, Enrichetta; Betti, Maura; Gatta, Gemma; Roila, Fausto; De Mulder, Pieter H. M.

    2007-01-01

    In Europe, renal cancer (that is neoplasia of the kidney, renal pelvis or ureter (ICD-9 189 and ICD-10 C64-C66)) ranks as the seventh most common malignancy in men amongst whom there are 29,600 new cases each year (3.5% of all cancers). Tobacco, obesity and a diet poor in vegetables are all

  12. Ameliorating effect of hawthorn ( Crataegus oxyacantha ) and ...

    African Journals Online (AJOL)

    Ameliorating effect of hawthorn ( Crataegus oxyacantha ) and physical exercise on ... Conclusion: Crataegus oxyacantha extract has shown positive affect to ameliorate on ... Key words: Crataegus oxyacantha, physical activity, epilepsy, gerbil, ...

  13. Coenzyme Q10 treatment ameliorates acute cisplatin nephrotoxicity in mice

    International Nuclear Information System (INIS)

    Fouad, Amr A.; Al-Sultan, Ali Ibrahim; Refaie, Shereen M.; Yacoubi, Mohamed T.

    2010-01-01

    The nephroprotective effect of coenzyme Q10 was investigated in mice with acute renal injury induced by a single i.p. injection of cisplatin (5 mg/kg). Coenzyme Q10 treatment (10 mg/kg/day, i.p.) was applied for 6 consecutive days, starting 1 day before cisplatin administration. Coenzyme Q10 significantly reduced blood urea nitrogen and serum creatinine levels which were increased by cisplatin. Coenzyme Q10 significantly compensated deficits in the antioxidant defense mechanisms (reduced glutathione level and superoxide dismutase activity), suppressed lipid peroxidation, decreased the elevations of tumor necrosis factor-α, nitric oxide and platinum ion concentration, and attenuated the reductions of selenium and zinc ions in renal tissue resulted from cisplatin administration. Also, histopathological renal tissue damage mediated by cisplatin was ameliorated by coenzyme Q10 treatment. Immunohistochemical analysis revealed that coenzyme Q10 significantly decreased the cisplatin-induced overexpression of inducible nitric oxide synthase, nuclear factor-κB, caspase-3 and p53 in renal tissue. It was concluded that coenzyme Q10 represents a potential therapeutic option to protect against acute cisplatin nephrotoxicity commonly encountered in clinical practice.

  14. Effects of adenosine infusion into renal interstitium on renal hemodynamics

    International Nuclear Information System (INIS)

    Pawlowska, D.; Granger, J.P.; Knox, F.G.

    1987-01-01

    This study was designed to investigate the hemodynamic effects of exogenous adenosine in the interstitium of the rat kidney. Adenosine or its analogues were infused into the renal interstitium by means of chronically implanted capsules. In fusion of adenosine decreased glomerular filtration rate (GFR) from 0.81 +/- 0.06 to 0.37 +/- 0.06 ml/min while having no effect on renal blood flow (RBF). The metabolically stable analogue, 2-chloradenosine (2-ClAdo), decreased GFR from 0.73 +/- 0.07 to 021 +/- 0.06 ml/min. Interstitial infusion of theophylline, an adenosine receptor antagonist, completely abolished the effects of adenosine and 2-ClAdo on GFR. The distribution of adenosine, when infused into the renal interstitium, was determined using radiolabeled 5'-(N-ethyl)-carboxamidoadenosine (NECA), a metabolically stable adenosine agonist. After continuous infusion, [ 3 H]NECA was distributed throughout the kidney. The effects of NECA to reduce GFR were similar to those of adenosine and 2-ClAdo. They conclude that increased levels of adenosine in the renal interstitium markedly decrease GFR without affecting RBF in steady-state conditions. The marked effects of adenosine agonists during their infusion into the renal interstitium and the complete blockade of these effects by theophylline suggest an extracellular action of adenosine

  15. Celecoxib offsets the negative renal influences of cyclosporine via modulation of the TGF-β1/IL-2/COX-2/endothelin ET(B) receptor cascade.

    Science.gov (United States)

    El-Gowelli, Hanan M; Helmy, Maged W; Ali, Rabab M; El-Mas, Mahmoud M

    2014-03-01

    Endothelin (ET) signaling provokes nephrotoxicity induced by the immunosuppressant drug cyclosporine A (CSA). We tested the hypotheses that (i): celecoxib, a selective cyclooxygenase-2 (COX-2) inhibitor, counterbalances renal derangements caused by CSA in rats and (ii) the COX-2/endothelin ET(B) receptor signaling mediates the CSA-celecoxib interaction. Ten-day treatment with CSA (20 mg/kg/day) significantly increased biochemical indices of renal function (serum urea, creatinine), inflammation (interleukin-2, IL-2) and fibrosis (transforming growth factor-β₁, TGF-β₁). Histologically, CSA caused renal tubular atrophy along with interstitial fibrosis. These detrimental renal effects of CSA were largely reduced in rats treated concurrently with celecoxib (10 mg/kg/day). We also report that cortical glomerular and medullary tubular protein expressions of COX-2 and ET(B) receptors were reduced by CSA and restored to near-control values in rats treated simultaneously with celecoxib. The importance of ET(B) receptors in renal control and in the CSA-celecoxib interaction was further verified by the findings (i) most of the adverse biochemical, inflammatory, and histopathological profiles of CSA were replicated in rats treated with the endothelin ETB receptor antagonist BQ788 (0.1 mg/kg/day, 10 days), and (ii) the BQ788 effects, like those of CSA, were alleviated in rats treated concurrently with celecoxib. Together, the data suggest that the facilitation of the interplay between the TGF-β1/IL-2/COX-2 pathway and the endothelin ET(B) receptors constitutes the cellular mechanism by which celecoxib ameliorates the nephrotoxic manifestations of CSA in rats. Copyright © 2014 Elsevier Inc. All rights reserved.

  16. Renal complications of anaesthesia.

    Science.gov (United States)

    McKinlay, J; Tyson, E; Forni, L G

    2018-01-01

    Peri-operative acute kidney injury is common, accounting for 30-40% of all in-hospital cases of acute kidney injury. It is associated with clinically significant morbidity and mortality even with what was hitherto regarded as relatively trivial increases in serum creatinine, and carries over a 12-fold relative risk of death following major abdominal surgery. Comorbid conditions such as diabetes, hypertension, liver disease and particularly pre-existing chronic kidney disease, as well as the type and urgency of surgery, are major risk factors for the development of postoperative acute kidney injury. As yet, there are no specific treatment options for the injured kidney, although there are several modifiable risk factors of which the anaesthetist should be aware. As well as the avoidance of potential nephrotoxins and appropriate volume balance, optimal anaesthetic management should aim to reduce the risk of postoperative renal complications. This may include careful ventilatory management and blood pressure control, as well as appropriate analgesic strategies. The choice of anaesthetic agent may also influence renal outcomes. Rather than concentrate on the classical management of acute kidney injury, this review focuses on the potential development of acute kidney injury peri-operatively, and the means by which this may be ameliorated. © 2018 The Association of Anaesthetists of Great Britain and Ireland.

  17. Mechanisms by which heme oxygenase rescue renal dysfunction in obesity

    Directory of Open Access Journals (Sweden)

    Joseph Fomusi Ndisang

    2014-01-01

    Collectively, these data suggest that hemin ameliorates nephropathy by potentiating the expression of proteins of repair/regeneration, abating oxidative/inflammatory mediators, reducing renal histo-pathological lesions, while enhancing nephrin, podocin, podocalyxin, CD2AP and creatinine clearance, with corresponding reduction of albuminuria/proteinuria suggesting improved renal function in hemin-treated ZFs. Importantly, the concomitant potentiation regeneration proteins and podocyte cytoskeletal proteins are novel mechanisms by which hemin rescue nephropathy in obesity.

  18. Naloxone : actions of an antagonist

    NARCIS (Netherlands)

    Dorp, Eveline Louise Arianna van

    2009-01-01

    The opioid antagonist naloxone has a special place in pharmacology – it has no intrinsic action of its own, but it is able to save lives in the case of life threatening side-effects caused by other drugs. Naloxone is an antagonist for all opioid receptors, but most specifically for the μ-opioid

  19. Carbon adaptation influence the antagonistic ability of ...

    African Journals Online (AJOL)

    Jane

    2011-10-24

    Oct 24, 2011 ... INTRODUCTION. The use of antagonistic bacteria to control soil-borne ... plant was used to evaluate the antifungal activities of antagonistic bacteria. ..... antagonistic bacteria and cloning of its phenazine carboxylic acid genes.

  20. Renal scan

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/article/003790.htm Renal scan To use the sharing features on this ... anaphylaxis . Alternative Names Renogram; Kidney scan Images Kidney anatomy Kidney - blood and urine flow References Chernecky CC, ...

  1. Renal Hemangiopericytoma

    Directory of Open Access Journals (Sweden)

    İbrahim Halil Bozkurt

    2015-03-01

    Full Text Available Hemangiopericytoma is an uncommon perivascular tumor originating from pericytes in the pelvis, head and tneck, and the meninges; extremely rarely in the urinary system. We report a case of incidentally detected renal mass in which radiologic evaluation was suggestive of renal cell carcinoma. First, we performed partial nephrectomy, and then, radical nephrectomy because of positive surgical margins and the pathological examination of the surgical specimen that revealed a hemangiopericytoma. No additional treatment was administered.

  2. ANTAGONISTIC POTENTIAL OF FLUORESCENT Pseudomonas ...

    African Journals Online (AJOL)

    Prof. Adipala Ekwamu

    GROWTH OF TOMATO CHALLENGED WITH PHTOPATHOGENS ... This study focused on the antagonistic potential of fluorescent Pseudomonas in vitro, and its inoculation effect on growth .... the 5 days old culture in starch agar with Lugol's.

  3. Naltrexone ameliorates functional network abnormalities in alcohol‐dependent individuals

    Science.gov (United States)

    Baek, Kwangyeol; Tait, Roger; Elliott, Rebecca; Ersche, Karen D.; Flechais, Remy; McGonigle, John; Murphy, Anna; Nestor, Liam J.; Orban, Csaba; Passetti, Filippo; Paterson, Louise M.; Rabiner, Ilan; Reed, Laurence; Smith, Dana; Suckling, John; Taylor, Eleanor M.; Bullmore, Edward T.; Lingford‐Hughes, Anne R.; Deakin, Bill; Nutt, David J.; Sahakian, Barbara J.; Robbins, Trevor W.; Voon, Valerie

    2017-01-01

    Abstract Naltrexone, an opioid receptor antagonist, is commonly used as a relapse prevention medication in alcohol and opiate addiction, but its efficacy and the mechanisms underpinning its clinical usefulness are not well characterized. In the current study, we examined the effects of 50‐mg naltrexone compared with placebo on neural network changes associated with substance dependence in 21 alcohol and 36 poly‐drug‐dependent individuals compared with 36 healthy volunteers. Graph theoretic and network‐based statistical analysis of resting‐state functional magnetic resonance imaging (MRI) data revealed that alcohol‐dependent subjects had reduced functional connectivity of a dispersed network compared with both poly‐drug‐dependent and healthy subjects. Higher local efficiency was observed in both patient groups, indicating clustered and segregated network topology and information processing. Naltrexone normalized heightened local efficiency of the neural network in alcohol‐dependent individuals, to the same levels as healthy volunteers. Naltrexone failed to have an effect on the local efficiency in abstinent poly‐substance‐dependent individuals. Across groups, local efficiency was associated with substance, but no alcohol exposure implicating local efficiency as a potential premorbid risk factor in alcohol use disorders that can be ameliorated by naltrexone. These findings suggest one possible mechanism for the clinical effects of naltrexone, namely, the amelioration of disrupted network topology. PMID:28247526

  4. Acute Radiation Sickness Amelioration Analysis

    Science.gov (United States)

    1994-05-01

    Emetic Drugs 16. PRICE CODE Antagonists 17. SECURITY CLASSIFICATION 18. SECURITY CLASSIFICATION 19, SECURITY CLASSIFICATION 20. LIMITATION OF ABSTRACT OF...102 UNCLASSIFIED mcuIw IA IIIcaIIin or Isis PAW CLASSFIED BY: N/A since Unclassified. DECLASSIFY ON: N/A since Unclassified. SECURITY CLASSIFICATION OF...Approximately 2000 documents relevant to the development of the candidate anti-emetic drugs ondansetron (Zofran, Glaxo Pharmaceuticals) and granisetron

  5. 75 FR 70933 - Cardiovascular and Renal Drugs Advisory Committee; Notice of Meeting

    Science.gov (United States)

    2010-11-19

    ...] Cardiovascular and Renal Drugs Advisory Committee; Notice of Meeting AGENCY: Food and Drug Administration, HHS... of Committee: Cardiovascular and Renal Drugs Advisory Committee. General Function of the Committees... appropriate clinical study design for thromboxane receptor antagonists for prevention of cardiovascular events...

  6. Renal candidiasis

    International Nuclear Information System (INIS)

    Khanna, S.; Malik, N.; Khandelwal, N.

    1990-01-01

    Most fungal infections of the urinary tract are caused by Candida albicans, a yeast-like saprophytic fungus which may become apathogen under various conditions which lower the host resistance. The use of computed tomography in the diagnosis of renal fungus balls is the subject of this communication with emphasis on the radiologists role in the recognition of this entity. (H.W.). 6 refs.; 2 figs

  7. Renal hemangioma

    Directory of Open Access Journals (Sweden)

    Theodorico F. da Costa Neto

    2004-06-01

    Full Text Available INTRODUCTION: Renal hemangioma is a relatively rare benign tumor, seldom diagnosed as a cause of hematuria. CASE REPORT: A female 40-year old patient presented with continuous gross hematuria, anemia and episodic right lumbar pain, with onset about 3 months previously. The patient underwent multiple blood transfusions during her hospital stay and extensive imaging propedeutics was performed. Semi-rigid ureterorenoscopy evidenced a bleeding focus in the upper calix of the right kidney, with endoscopic treatment being unfeasible. The patient underwent right upper pole nephrectomy and presented a favorable outcome. Histopathological analysis of the surgical specimen showed that it was a renal hemangioma. COMMENTS: Imaging methods usually employed for diagnostic investigation of hematuria do not have good sensitivity for renal hemangioma. However, they are important to exclude the most frequent differential diagnoses. The ureterorenoscopy is the diagnostic method of choice and endoscopic treatment can be feasible when the lesion is accessible and electrocautery or laser are available. We emphasize the open surgical treatment as a therapeutic option upon failure of less invasive methods.

  8. Excitatory amino acid receptor antagonists

    DEFF Research Database (Denmark)

    Johansen, T N; Frydenvang, Karla Andrea; Ebert, B

    1997-01-01

    We have previously shown that (RS)-2-amino-2-(5-tert-butyl-3-hydroxyisoxazol-4-yl)acetic acid (ATAA) is an antagonist at N-methyl-D-aspartic acid (NMDA) and (RS)-2-amino-3-(3-hydroxy-5-methylisoxazol-4-yl)propionic acid (AMPA) receptors. We have now resolved ATAA via diastereomeric salt formation......)-phenylethylamine salt of N-BOC-(R)-ATAA. Like ATAA, neither (R)- nor (S)-ATAA significantly affected (IC50 > 100 microM) the receptor binding of tritiated AMPA, kainic acid, or (RS)-3-(2-carboxypiperazin-4-yl)propyl-1-phosphonic acid, the latter being a competitive NMDA antagonist. Electrophysiological experiments......, using the rat cortical wedge preparation, showed the NMDA antagonist effect as well as the AMPA antagonist effect of ATAA to reside exclusively in the (R)-enantiomer (Ki = 75 +/- 5 microM and 57 +/- 1 microM, respectively). Neither (R)- nor (S)-ATAA significantly reduced kainic acid-induced excitation...

  9. Obesity and renal hemodynamics

    NARCIS (Netherlands)

    Bosma, R. J.; Krikken, J. A.; van der Heide, J. J. Homan; de Jong, P. E.; Navis, G. J.

    2006-01-01

    Obesity is a risk factor for renal damage in native kidney disease and in renal transplant recipients. Obesity is associated with several renal risk factors such as hypertension and diabetes that may convey renal risk, but obesity is also associated with an unfavorable renal hemodynamic profile

  10. Radiopharmaceuticals for renal studies

    International Nuclear Information System (INIS)

    Verdera, Silvia

    1994-01-01

    Between the diagnostic techniques using radiopharmaceuticals in nuclear medicine it find renal studies.A brief description about renal glomerular filtration(GFR) and reliability renal plasma flux (ERPF),renal blood flux measurement agents (RBF),renal scintillation agents and radiation dose estimates by organ physiology was given in this study.tabs

  11. Specific immunotherapy ameliorates ulcerative colitis.

    Science.gov (United States)

    Cai, Min; Zeng, Lu; Li, Lin-Jing; Mo, Li-Hua; Xie, Rui-Di; Feng, Bai-Sui; Zheng, Peng-Yuan; Liu, Zhi-Gang; Liu, Zhan-Ju; Yang, Ping-Chang

    2016-01-01

    Hypersensitivity reaction to certain allergens plays a role in the pathogenesis of inflammatory bowel disease (IBD). This study aims to observe the effect of specific immunotherapy in a group of IBD patients. Patients with both ulcerative colitis (UC) and food allergy were recruited into this study. Food allergy was diagnosed by skin prick test and serum specific IgE. The patients were treated with specific immunotherapy (SIT) and Clostridium butyricum (CB) capsules. After treating with SIT and CB, the clinical symptoms of UC were markedly suppressed as shown by reduced truncated Mayo scores and medication scores. The serum levels of specific IgE, interleukin (IL)-4 and tumor necrosis factor (TNF)-α were also suppressed. Treating with SIT alone or CB alone did not show appreciable improvement of the clinical symptoms of UC. UC with food allergy can be ameliorated by administration with SIT and butyrate-production probiotics.

  12. Minocycline exacerbates apoptotic neurodegeneration induced by the NMDA receptor antagonist MK-801 in the early postnatal mouse brain.

    Science.gov (United States)

    Inta, Ioana; Vogt, Miriam A; Vogel, Anne S; Bettendorf, Markus; Gass, Peter; Inta, Dragos

    2016-10-01

    NMDA receptor (NMDAR) antagonists induce in perinatal rodent cortical apoptosis and protracted schizophrenia-like alterations ameliorated by antipsychotic treatment. The broad-spectrum antibiotic minocycline elicits antipsychotic and neuroprotective effects. Here we tested, if minocycline protects also against apoptosis triggered by the NMDAR antagonist MK-801 at postnatal day 7. Surprisingly, minocycline induced widespread cortical apoptosis and exacerbated MK-801-triggered cell death. In some areas such as the subiculum, the pro-apoptotic effect of minocycline was even more pronounced than that elicited by MK-801. These data reveal among antipsychotics unique pro-apoptotic properties of minocycline, raising concerns regarding consequences for brain development and the use in children.

  13. Bilateral renal artery variation

    OpenAIRE

    Üçerler, Hülya; Üzüm, Yusuf; İkiz, Z. Aslı Aktan

    2014-01-01

    Each kidney is supplied by a single renal artery, although renal artery variations are common. Variations of the renal arteryhave become important with the increasing number of renal transplantations. Numerous studies describe variations in renalartery anatomy. Especially the left renal artery is among the most critical arterial variations, because it is the referred side forresecting the donor kidney. During routine dissection in a formalin fixed male cadaver, we have found a bilateral renal...

  14. The effects of heart failure on renal function.

    Science.gov (United States)

    Udani, Suneel M; Koyner, Jay L

    2010-08-01

    Heart-kidney interactions have been increasingly recognized by clinicians and researchers who study and treat heart failure and kidney disease. A classification system has been developed to categorize the different manifestations of cardiac and renal dysfunction. Work has highlighted the significant negative prognostic effect of worsening renal function on outcomes for individuals with heart failure. The etiology of concomitant cardiac and renal dysfunction remains unclear; however, evidence supports alternatives to the established theory of underfilling, including effects of venous congestion and changes in intra-abdominal pressure. Conventional therapy focuses on blockade of the renin-angiotensin-aldosterone system with expanding use of direct renin and aldosterone antagonists. Novel therapeutic interventions using extracorporeal therapy and antagonists of the adenosine pathway show promise and require further investigation. 2010 Elsevier Inc. All rights reserved.

  15. Renal tuberculosis

    Directory of Open Access Journals (Sweden)

    Džamić Zoran

    2016-01-01

    Full Text Available Tuberculosis is still a significant health problem in the world, mostly in developing countries. The special significance lies in immunocompromised patients, particularly those suffering from the HIV. Urogenital tuberculosis is one of the most common forms of extrapulmonary tuberculosis, while the most commonly involved organ is the kidney. Renal tuberculosis occurs by hematogenous dissemination of mycobacterium tuberculosis from a primary tuberculosis foci in the body. Tuberculosis is characterized by the formation of pathognomonic lesions in the tissues - granulomata. These granulomata may heal spontaneously or remain stable for years. In certain circumstances in the body associated with immunosuppression, the disease may be activated. Central caseous necrosis occurs within tuberculoma, leading to formation of cavities that destroy renal parenchyma. The process may gain access to the collecting system, forming the caverns. In this way, infection can be spread distally to renal pelvis, ureter and bladder. Scaring of tissue by tuberculosis process may lead to development of strictures of the urinary tract. The clinical manifestations are presented by nonspecific symptoms and signs, so tuberculosis can often be overlooked. Sterile pyuria is characteristic for urinary tuberculosis. Dysuric complaints, flank pain or hematuria may be presented in patients. Constitutional symptoms of fever, weight loss and night sweats are presented in some severe cases. Diagnosis is made by isolation of mycobacterium tuberculosis in urine samples, by cultures carried out on standard solid media optimized for mycobacterial growth. Different imaging studies are used in diagnostics - IVU, CT and NMR are the most important. Medical therapy is the main modality of tuberculosis treatment. The first line anti-tuberculosis drugs include isoniazid, rifampicin, pyrazinamide and ethambutol. Surgical treatment is required in some cases, to remove severely damaged kidney, if

  16. Renal denervation

    DEFF Research Database (Denmark)

    Olsen, Lene Kjær; Kamper, Anne-Lise; Svendsen, Jesper Hastrup

    2015-01-01

    PURPOSE OF REVIEW: Renal denervation (RDN) has, within recent years, been suggested as a novel treatment option for patients with resistant hypertension. This review summarizes the current knowledge on this procedure as well as limitations and questions that remain to be answered. RECENT FINDINGS...... selection, anatomical and physiological effects of RDN as well as possible beneficial effects on other diseases with increased sympathetic activity. The long awaited Symplicity HTN-3 (2014) results illustrated that the RDN group and the sham-group had similar reductions in BP. SUMMARY: Initial studies...

  17. Renal papillary necrosis

    Science.gov (United States)

    ... asking your provider. Alternative Names Necrosis - renal papillae; Renal medullary necrosis Images Kidney anatomy Kidney - blood and urine flow References Bushinsky DA, Monk RD. Nephrolithiasis and nephrocalcinosis. ...

  18. Histologic and inflammatory lamellar changes in horses with oligofructose-induced laminitis treated with a CXCR1/2 antagonist

    OpenAIRE

    Lima, Leonardo R. de; Mendes, Heloisa M.F.; Soriani, Frederico M.; Souza, Danielle G. de; Alves, Geraldo Eleno S.; Teixeira, Mauro M.; Faleiros, Rafael R.

    2016-01-01

    Abstract: With the hypothesis that blocking chemokine signaling can ameliorate acute laminitis, the aim was to evaluate the therapeutic effect of intravenous DF1681B, a selective antagonist for CXCR1 and CXCR2 (chemokine receptors), in an oligofructose equine laminitis model. To twelve mixed breed clinically healthy hoses with no previous history of hoof-related lameness was administered oligofructose (10g/kg given by nasogastric tube) and divided into two groups: treated (intravenous DF1681B...

  19. Green Tea Polyphenols, Mimicking the Effects of Dietary Restriction, Ameliorate High-Fat Diet-Induced Kidney Injury via Regulating Autophagy Flux

    Directory of Open Access Journals (Sweden)

    Xiao Xie

    2017-05-01

    Full Text Available Epidemiological and experimental studies reveal that Western dietary patterns contribute to chronic kidney disease, whereas dietary restriction (DR or dietary polyphenols such as green tea polyphenols (GTPs can ameliorate the progression of kidney injury. This study aimed to investigate the renal protective effects of GTPs and explore the underlying mechanisms. Sixty Wistar rats were randomly divided into 6 groups: standard diet (STD, DR, high-fat diet (HFD, and three diets plus 200 mg/kg(bw/day GTPs, respectively. After 18 weeks, HFD group exhibited renal injuries by increased serum cystatin C levels and urinary N-acetyl-β-d-glucosaminidase activity, which can be ameliorated by GTPs. Meanwhile, autophagy impairment as denoted by autophagy-lysosome related proteins, including LC3-II, Beclin-1, p62, cathepsin B, cathepsin D and LAMP-1, was observed in HFD group, whereas DR or GTPs promoted renal autophagy activities and GTPs ameliorated HFD-induced autophagy impairment. In vitro, autophagy flux suppression was detected in palmitic acid (PA-treated human proximal tubular epithelial cells (HK-2, which was ameliorated by epigallocatechin-3-gallate (EGCG. Furthermore, GTPs (or EGCG elevated phosphorylation of AMP-activated protein kinase in the kidneys of HFD-treated rats and in PA-treated HK-2 cells. These findings revealed that GTPs mimic the effects of DR to induce autophagy and exert a renal protective effect by alleviating HFD-induced autophagy suppression.

  20. Angiotensin antagonists in the dog with chronic pericardial tamponade

    International Nuclear Information System (INIS)

    Moore, G.J.; Taub, K.J.

    1980-01-01

    Assessing the role played by angiotensin in the pathogenesis and maintenance of the renal function and perfusion abnormalities dogs with chronic pericardial tamponade were used in the experiment as a stable model of chronic low output heart failure. The heptapeptide and octapeptide antagonist were used. The results of the experiments suggest that there is a role for angiotensin in the pathologenesis of congestive heart failure. The renin-angiotensin system was activated in the model. Plasma renin activity was elevated and increased further in response to angiotensin blockade. Under the experiment condition there was no evidence for a role for angiotensin in the maintenance of arterial blood pressure. But there was angiotensin-mediated renal vasoconstriction and a reduction in renal blood flow. Both analogues of angiotensin were able to antagonize this effect in similar fashion. Failure to achieve a natriuresis in response to angiotensin blockade may reflect the redistribution of blood flow that occured and suggests that additional factors are operative in this model. (APR)

  1. Palliation of bone cancer pain by antagonists of platelet-activating factor receptors.

    Directory of Open Access Journals (Sweden)

    Katsuya Morita

    Full Text Available Bone cancer pain is the most severe among cancer pain and is often resistant to current analgesics. Thus, the development of novel analgesics effective at treating bone cancer pain are desired. Platelet-activating factor (PAF receptor antagonists were recently demonstrated to have effective pain relieving effects on neuropathic pain in several animal models. The present study examined the pain relieving effect of PAF receptor antagonists on bone cancer pain using the femur bone cancer (FBC model in mice. Animals were injected with osteolytic NCTC2472 cells into the tibia, and subsequently the effects of PAF receptor antagonists on pain behaviors were evaluated. Chemical structurally different type of antagonists, TCV-309, BN 50739 and WEB 2086 ameliorated the allodynia and improved pain behaviors such as guarding behavior and limb-use abnormalities in FBC model mice. The pain relieving effects of these antagonists were achieved with low doses and were long lasting. Blockade of spinal PAF receptors by intrathecal injection of TCV-309 and WEB 2086 or knockdown of the expression of spinal PAF receptor protein by intrathecal transfer of PAF receptor siRNA also produced a pain relieving effect. The amount of an inducible PAF synthesis enzyme, lysophosphatidylcholine acyltransferase 2 (LPCAT2 protein significantly increased in the spinal cord after transplantation of NCTC 2472 tumor cells into mouse tibia. The combination of morphine with PAF receptor antagonists develops marked enhancement of the analgesic effect against bone cancer pain without affecting morphine-induced constipation. Repeated administration of TCV-309 suppressed the appearance of pain behaviors and prolonged survival of FBC mice. The present results suggest that PAF receptor antagonists in combination with, or without, opioids may represent a new strategy for the treatment of persistent bone cancer pain and improve the quality of life of patients.

  2. From Chemotherapy-Induced Emesis to Neuroprotection: Therapeutic Opportunities for 5-HT3 Receptor Antagonists.

    Science.gov (United States)

    Fakhfouri, Gohar; Mousavizadeh, Kazem; Mehr, Sharam Ejtemaei; Dehpour, Ahmad Reza; Zirak, Mohammad Reza; Ghia, Jean-Eric; Rahimian, Reza

    2015-12-01

    5-HT3 receptor antagonists are extensively used as efficacious agents in counteracting chemotherapy-induced emesis. Recent investigations have shed light on other potential effects (analgesic, anxiolytic, and anti-psychotic). Some studies have reported neuroprotective properties for the 5-HT3 receptor antagonists in vitro and in vivo. When administered to Aβ-challenged rat cortical neurons, 5-HT3 receptor antagonists substantially abated apoptosis, elevation of cytosolic Ca(2), glutamate release, reactive oxygen species (ROS) generation, and caspase-3 activity. In addition, in vivo studies show that 5-HT3 receptor antagonists possess, alongside their anti-emetic effects, notable immunomodulatory properties in CNS. We found that pretreatment with tropisetron significantly improved neurological deficits and diminished leukocyte transmigration into the brain, TNF-α level, and brain infarction in a murine model of embolic stroke. Our recent investigation revealed that tropisetron protects against Aβ-induced neurotoxicity in vivo through both 5-HT3 receptor-dependent and -independent pathways. Tropisetron, in vitro, was found to be an efficacious inhibitor of the signaling pathway leading to the activation of pro-inflammatory NF-κB, a transcription factor pivotal to the upregulation of several neuroinflammatory mediators in brain. This mini review summarizes novel evidence concerning effects of 5-HT3 antagonists and their possible mechanisms of action in ameliorating neurodegenerative diseases including Alzheimer, multiple sclerosis, and stroke. Further, we discuss some newly synthesized 5-HT3 receptor antagonists with dual properties of 5-HT3 receptor blockade/alpha-7 nicotinic receptor activator and their potential in management of memory impairment. Since 5-HT3 receptor antagonists possess a large therapeutic window, they can constitute a scaffold for design and synthesis of new neuroprotective medications.

  3. Renal calculus

    CERN Document Server

    Pyrah, Leslie N

    1979-01-01

    Stone in the urinary tract has fascinated the medical profession from the earliest times and has played an important part in the development of surgery. The earliest major planned operations were for the removal of vesical calculus; renal and ureteric calculi provided the first stimulus for the radiological investigation of the viscera, and the biochemical investigation of the causes of calculus formation has been the training ground for surgeons interested in metabolic disorders. It is therefore no surprise that stone has been the subject of a number of monographs by eminent urologists, but the rapid development of knowledge has made it possible for each one of these authors to produce something new. There is still a technical challenge to the surgeon in the removal of renal calculi, and on this topic we are always glad to have the advice of a master craftsman; but inevitably much of the interest centres on the elucidation of the causes of stone formation and its prevention. Professor Pyrah has had a long an...

  4. Ameliorative Effect of Different Concentration of Mushroom ...

    African Journals Online (AJOL)

    Prof. Ogunji

    ameliorative effect of mushroom in the post-experimental stage. Samples of liver and ... except in the liver which showed mild periportal chronic inflammatory cell. However, the .... alcohol for 12 hours and through absolute alcohol to remove ...

  5. Portulaca oleracea Linn seed extract ameliorates hydrogen ...

    African Journals Online (AJOL)

    Portulaca oleracea Linn seed extract ameliorates hydrogen ... induced cell death by inhibiting oxidative stress and ROS generation. Keywords: ... culture medium; therefore the stock solutions of ... acetic acid (1 %) and ethanol (50 %) to extract.

  6. Ameliorative effects of selenium and zinc

    African Journals Online (AJOL)

    Methidathion-induced hematological, biochemical and hepatohistological alterations in rat: Ameliorative effects of selenium and zinc. L Barkat, A Boumendjel, C Abdennour, MS Boulakoud, A El Feki, M Messarah ...

  7. Black ginseng extract ameliorates hypercholesterolemia in rats

    Directory of Open Access Journals (Sweden)

    Evelyn Saba

    2016-04-01

    Conclusion: Administration of BG extracts to Sprague Dawley rats fed with high-cholesterol diet ameliorated hypercholesterolemia, which was mediated via modulation of cholesterol-metabolizing marker genes. This data throw a light on BG's cardioprotective effects.

  8. Dietary Amelioration of Helicobacter Infection

    Science.gov (United States)

    Fahey, Jed W.; Stephenson, Katherine K.; Wallace, Alison J.

    2015-01-01

    We review herein the basis for using dietary components to treat and/or prevent Helicobacter pylori infection, with emphasis on: (a) work reported in the last decade, (b) dietary components for which there is mechanism-based plausibility, and (c) components for which clinical results on H. pylori amelioration are available. There is evidence that a diet-based treatment may reduce the levels and/or the virulence of H. pylori colonization without completely eradicating the organism in treated individuals. This concept was endorsed a decade ago by the participants in a small international consensus conference held in Honolulu, Hawaii, USA, and interest in such a diet-based approach has increased dramatically since then. This approach is attractive in terms of cost, treatment, tolerability and cultural acceptability. This review therefore highlights specific foods, food components, and food products, grouped as follows: bee products (e.g. honey and propolis), probiotics, dairy products, vegetables, fruits, oils, essential oils, and herbs, spices and other plants. A discussion of the small number of clinical studies that are available is supplemented by supportive in vitro and animal studies. This very large body of in vitro and pre-clinical evidence must now be followed up with rationally designed, unambiguous human trials. PMID:25799054

  9. Naringin ameliorates gentamicin-induced nephrotoxicity and associated mitochondrial dysfunction, apoptosis and inflammation in rats: Possible mechanism of nephroprotection

    Energy Technology Data Exchange (ETDEWEB)

    Sahu, Bidya Dhar [Medicinal Chemistry and Pharmacology Division, Indian Institute of Chemical Technology (IICT), Hyderabad 500 007 (India); Tatireddy, Srujana [National Institute of Pharmaceutical Education and Research (NIPER), Hyderabad 500 037 (India); Koneru, Meghana [Medicinal Chemistry and Pharmacology Division, Indian Institute of Chemical Technology (IICT), Hyderabad 500 007 (India); Borkar, Roshan M. [National Centre for Mass Spectrometry, Indian Institute of Chemical Technology (IICT), Hyderabad 500 007 (India); Kumar, Jerald Mahesh [CSIR-Centre for Cellular and Molecular Biology (CCMB), Hyderabad 500 007 (India); Kuncha, Madhusudana [Medicinal Chemistry and Pharmacology Division, Indian Institute of Chemical Technology (IICT), Hyderabad 500 007 (India); Srinivas, R. [National Centre for Mass Spectrometry, Indian Institute of Chemical Technology (IICT), Hyderabad 500 007 (India); Shyam Sunder, R. [Faculty of Pharmacy, Osmania University, Hyderabad 500 007 (India); Sistla, Ramakrishna, E-mail: sistla@iict.res.in [Medicinal Chemistry and Pharmacology Division, Indian Institute of Chemical Technology (IICT), Hyderabad 500 007 (India)

    2014-05-15

    Gentamicin-induced nephrotoxicity has been well documented, although its underlying mechanisms and preventive strategies remain to be investigated. The present study was designed to investigate the protective effect of naringin, a bioflavonoid, on gentamicin-induced nephrotoxicity and to elucidate the potential mechanism. Serum specific renal function parameters (blood urea nitrogen and creatinine) and histopathology of kidney tissues were evaluated to assess the gentamicin-induced nephrotoxicity. Renal oxidative stress (lipid peroxidation, protein carbonylation, enzymatic and non-enzymatic antioxidants), inflammatory (NF-kB [p65], TNF-α, IL-6 and MPO) and apoptotic (caspase 3, caspase 9, Bax, Bcl-2, p53 and DNA fragmentation) markers were also evaluated. Significant decrease in mitochondrial NADH dehydrogenase, succinate dehydrogenase, cytochrome c oxidase and mitochondrial redox activity indicated the gentamicin-induced mitochondrial dysfunction. Naringin (100 mg/kg) treatment along with gentamicin restored the mitochondrial function and increased the renal endogenous antioxidant status. Gentamicin induced increased renal inflammatory cytokines (TNF-α and IL-6), nuclear protein expression of NF-κB (p65) and NF-κB-DNA binding activity and myeloperoxidase (MPO) activity were significantly decreased upon naringin treatment. In addition, naringin treatment significantly decreased the amount of cleaved caspase 3, Bax, and p53 protein expression and increased the Bcl-2 protein expression. Naringin treatment also ameliorated the extent of histologic injury and reduced inflammatory infiltration in renal tubules. U-HPLS-MS data revealed that naringin co-administration along with gentamicin did not alter the renal uptake and/or accumulation of gentamicin in kidney tissues. These findings suggest that naringin treatment attenuates renal dysfunction and structural damage through the reduction of oxidative stress, mitochondrial dysfunction, inflammation and apoptosis in

  10. TRANSPLANTE RENAL

    Directory of Open Access Journals (Sweden)

    Soraia Geraldo Rozza Lopes

    2014-01-01

    Full Text Available El objetivo del estudio fue comprender el significado de espera del trasplante renal para las mujeres en hemodiálisis. Se trata de un estudio cualitativo-interpretativo, realizado con 12 mujeres en hemodiálisis en Florianópolis. Los datos fueron recolectados a través de entrevistas en profundidad en el domicilio. Fue utilizado el software Etnografh 6.0 para la pre-codificación y posterior al análisis interpretativo emergieron dos categorías: “las sombras del momento actual”, que mostró que las dificultades iniciales de la enfermedad están presentes, pero las mujeres pueden hacer frente mejor a la enfermedad y el tratamiento. La segunda categoría, “la luz del trasplante renal”, muestra la esperanza impulsada por la entrada en la lista de espera para un trasplante.

  11. Muscarinic Receptor Agonists and Antagonists

    Directory of Open Access Journals (Sweden)

    David R. Kelly

    2001-02-01

    Full Text Available A comprehensive review of pharmacological and medical aspects of the muscarinic class of acetylcholine agonists and antagonists is presented. The therapeutic benefits of achieving receptor subtype selectivity are outlined and applications in the treatment of Alzheimer’s disease are discussed. A selection of chemical routes are described, which illustrate contemporary methodology for the synthesis of chiral medicinal compounds (asymmetric synthesis, chiral pool, enzymes. Routes to bicyclic intrannular amines and intramolecular Diels-Alder reactions are highlighted.

  12. Effect of Cuscuta chinensis on renal function in ischemia/reperfusion-induced acute renal failure rats.

    Science.gov (United States)

    Shin, Sun; Lee, Yun Jung; Kim, Eun Ju; Lee, An Sook; Kang, Dae Gill; Lee, Ho Sub

    2011-01-01

    The kidneys play a central role in regulating water, ion composition and excretion of metabolic waste products in the urine. Cuscuta chinensis has been known as an important traditional Oriental medicine for the treatment of liver and kidney disorders. Thus, we studied whether an aqueous extract of Cuscuta chinensis (ACC) seeds has an effect on renal function parameters in ischemia/reperfusion-induced acute renal failure (ARF) rats. Administration of 250 mg/kg/day ACC showed that renal functional parameters including urinary excretion rate, osmolality, Na(+), K(+), Cl(-), creatinine clearance, solute-free water reabsorption were significantly recovered in ischemia/reperfusion-induced ARF. Periodic acid Schiff staining showed that administration of ACC improved tubular damage in ischemia/reperfusion-induced ARF. In immunoblot and immunohistological examinations, ischemia/reperfusion-induced ARF decreased the expressions of water channel AQP 2, 3 and sodium potassium pump Na,K-ATPase in the renal medulla. However, administration of ACC markedly incremented AQP 2, 3 and Na,K-ATPase expressions. Therefore, these data indicate that administration of ACC ameliorates regulation of the urine concentration and renal functions in rats with ischemia/reperfusion-induced ARF.

  13. BILATERAL DUPLICATION OF RENAL ARTERIES

    OpenAIRE

    Prajkta A Thete; Mehera Bhoir; M.V.Ambiye

    2014-01-01

    Routine dissection of a male cadaver revealed the presence of bilateral double renal arteries. On the right side the accessory renal artery originated from the abdominal aorta just above the main renal artery. On the left side the accessory renal artery originated from the abdominal aorta about 1 cm above the main renal artery. Knowledge of the variations of renal vascular anatomy has importance in exploration and treatment of renal trauma, renal transplantation, renal artery embolization, su...

  14. 5-HT2A receptor antagonists improve motor impairments in the MPTP mouse model of Parkinson's disease.

    Science.gov (United States)

    Ferguson, Marcus C; Nayyar, Tultul; Deutch, Ariel Y; Ansah, Twum A

    2010-01-01

    Clinical observations have suggested that ritanserin, a 5-HT(2A/C) receptor antagonist may reduce motor deficits in persons with Parkinson's Disease (PD). To better understand the potential antiparkinsonian actions of ritanserin, we compared the effects of ritanserin with the selective 5-HT(2A) receptor antagonist M100907 and the selective 5-HT(2C) receptor antagonist SB 206553 on motor impairments in mice treated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). MPTP-treated mice exhibited decreased performance on the beam-walking apparatus. These motor deficits were reversed by acute treatment with L-3,4-dihydroxyphenylalanine (levodopa). Both the mixed 5-HT(2A/C) antagonist ritanserin and the selective 5-HT(2A) antagonist M100907 improved motor performance on the beam-walking apparatus. In contrast, SB 206553 was ineffective in improving the motor deficits in MPTP-treated mice. These data suggest that 5-HT(2A) receptor antagonists may represent a novel approach to ameliorate motor symptoms of Parkinson's disease. Published by Elsevier Ltd.

  15. Hypothyroidism presenting as reversible renal impairment: an interesting case report.

    Science.gov (United States)

    Vikrant, Sanjay; Chander, Subhash; Kumar, Satish; Gupta, Dalip

    2013-10-01

    We describe an interesting case of reversible renal impairment secondary to hypothyroidism. A 57-years-old man was referred from peripheral institution for evaluation of elevated serum creatinine. He had vague complaints of weakness, lethargy and muscle ache but no urinary symptoms. He was found to have hypothyroidism, and thyroid hormone replacement therapy (THRT) was started which resulted in reversal of the renal dysfunction. There was marked improvement in estimated glomerular filtration rate. 99mTc DTPA renal scans done before and after THRT suggested hypothyroidism responsible for this reversible renal impairment. Several studies have described the pathophysiology of diminished renal function in hypothyroidism. Few studies or case reports have shown total amelioration of renal impairment as seen in our patient. The etiology is presumed to be multifactorial, in which hemodynamic effects and a direct effect of thyroid hormone on the kidney play an important role. We suggest that patients with renal impairment of unknown cause have thyroid function tests undertaken as part of routine investigation.

  16. Acitretin treatment in (pre)malignant skin disorders of renal transplant recipients: Histologic and immunohistochemical effects.

    NARCIS (Netherlands)

    Smit, J.V.; Sevaux, R.G.L. de; Blokx, W.A.M.; Kerkhof, P.C.M. van de; Hoitsma, A.J.; Jong, E.M.G.J. de

    2004-01-01

    BACKGROUND: The incidence of (pre)malignant skin lesions after renal transplantation is high. Acitretin treatment appears to decrease the number of new squamous cell carcinomas and ameliorates the aspect and reduces the number of actinic keratoses. However, no histologic and immunohistochemical

  17. GABAA receptor partial agonists and antagonists

    DEFF Research Database (Denmark)

    Krall, Jacob; Balle, Thomas; Krogsgaard-Larsen, Niels

    2015-01-01

    to the local temporal pattern of GABA impact, enabling phasic or tonic inhibition. Specific GABAAR antagonists are essential tools for physiological and pharmacological elucidation of the different type of GABAAR inhibition. However, distinct selectivity among the receptor subtypes (populations) has been shown...... antagonists have been essential in defining the tonic current but both remaining issues concerning the GABAARs involved and the therapeutic possibilities of modulating tonic inhibition underline the need for GABAAR antagonists with improved selectivity....

  18. Ghrelin ameliorates acute lung injury induced by oleic acid via inhibition of endoplasmic reticulum stress.

    Science.gov (United States)

    Tian, Xiuli; Liu, Zhijun; Yu, Ting; Yang, Haitao; Feng, Linlin

    2018-03-01

    Acute lung injury (ALI) is associated with excessive mortality and lacks appropriate therapy. Ghrelin is a novel peptide that protects the lung against ALI. This study aimed to investigate whether endoplasmic reticulum stress (ERS) mediates the protective effect of ghrelin on ALI. We used a rat oleic acid (OA)-induced ALI model. Pulmonary impairment was detected by hematoxylin and eosin (HE) staining, lung mechanics, wet/dry weight ratio, and arterial blood gas analysis. Plasma and lung content of ghrelin was examined by ELISA, and mRNA expression was measured by quantitative real-time PCR. Protein levels were detected by western blot. Rats with OA treatment showed significant pulmonary injury, edema, inflammatory cellular infiltration, cytokine release, hypoxia and CO 2 retention as compared with controls. Plasma and pulmonary content of ghrelin was reduced in rats with ALI, and mRNA expression was downregulated. Ghrelin (10nmol/kg) treatment ameliorated the above symptoms, but treatment with the ghrelin antagonists D-Lys 3 GHRP-6 (1μmol/kg) and JMV 2959 (6mg/kg) exacerbated the symptoms. ERS induced by OA was prevented by ghrelin and augmented by ghrelin antagonist treatment. The ERS inducer, tunicamycin (Tm) prevented the ameliorative effect of ghrelin on ALI. The decreased ratio of p-Akt and Akt induced by OA was improved by ghrelin treatment, and was further exacerbated by ghrelin antagonists. Ghrelin protects against ALI by inhibiting ERS. These results provide a new target for prevention and therapy of ALI. Copyright © 2017 Elsevier Inc. All rights reserved.

  19. Interleukin-1 antagonists for diabetes

    DEFF Research Database (Denmark)

    Mandrup-Poulsen, Thomas

    2013-01-01

    pathways. The testing of specific anti-inflammatory biologics targeting single pro-inflammatory cytokines has provided clinical proof-of-concept. EXPERT OPINION: IL-1 antagonists have so far failed to meet primary end points in recent-onset type 1 diabetes in Phase IIa, and promising Phase I and IIa trials......INTRODUCTION: Diabetes is a currently incurable, epidemically growing global health concern. Contemporary symptomatic treatment targets acute and chronic metabolic consequences of relative or absolute insulin deficiency. Intensive multifactorial therapy is required to attenuate morbidity...... and mortality from late micro- and macrovascular complications, and despite current best clinical practice diabetes is still associated with shortened lifespan. There is an unmet need for interventions targeting pathogenetic mechanisms in diabetes, and the market for such therapies is huge. AREAS COVERED...

  20. Antidepressant activity of the adenosine A2A receptor antagonist, istradefylline (KW-6002) on learned helplessness in rats.

    Science.gov (United States)

    Yamada, Koji; Kobayashi, Minoru; Shiozaki, Shizuo; Ohta, Teruko; Mori, Akihisa; Jenner, Peter; Kanda, Tomoyuki

    2014-07-01

    Istradefylline, an adenosine A2A receptor antagonist, improves motor function in animal models of Parkinson's disease (PD) and in patients with PD. In addition, some A2A antagonists exert antidepressant-like activity in rodent models of depression, such as the forced swim and the tail suspension tests. We have investigated the effect of istradefylline on depression-like behaviors using the rat learned helplessness (LH) model. Acute, as well as chronic, oral administration of istradefylline significantly improved the inescapable shock (IES)-induced escape deficit with a degree of efficacy comparable to chronic treatment with the tricyclic antidepressant desipramine and the selective serotonin (5-HT) reuptake inhibitor, fluoxetine. Both the A1/A2A receptor nonspecific antagonist theophylline and the moderately selective antagonist CGS15943, but not the A1 selective antagonist DPCPX, ameliorated the IES-induced escape deficit. The enhancement of escape response by istradefylline was reversed by a local injection of the A2A specific agonist CGS21680 either into the nucleus accumbens, the caudate-putamen, or the paraventricular nucleus of the hypothalamus, but not by the A1 specific agonist R-PIA into the nucleus accumbens. Moreover, neither the 5-HT2A/2C receptor antagonist methysergide or the adrenergic α 2 antagonist yohimbine, nor the β-adrenergic antagonist propranolol, affected the improvement of escape response induced by istradefylline. Istradefylline exerts antidepressant-like effects via modulation of A2A receptor activity which is independent of monoaminergic transmission in the brain. Istradefylline may represent a novel treatment option for depression in PD as well as for the motor symptoms.

  1. Radionuclide evaluation of renal transplants

    International Nuclear Information System (INIS)

    Yang Hong; Zhao Deshan

    2000-01-01

    Radionuclide renal imaging and plasma clearance methods can quickly quantitate renal blood flow and function in renal transplants. They can diagnose acute tubular necrosis and rejection, renal scar, surgical complications such as urine leaks, obstruction and renal artery stenosis after renal transplants. At the same time they can assess the therapy effect of renal transplant complications and can also predict renal transplant survival from early post-operative function studies

  2. Myeloid-Derived Suppressor Cells Ameliorate Cyclosporine A-Induced Hypertension in Mice.

    Science.gov (United States)

    Chiasson, Valorie L; Bounds, Kelsey R; Chatterjee, Piyali; Manandhar, Lochana; Pakanati, Abhinandan R; Hernandez, Marcos; Aziz, Bilal; Mitchell, Brett M

    2018-01-01

    The calcineurin inhibitor cyclosporine A (CsA) suppresses the immune system but promotes hypertension, vascular dysfunction, and renal damage. CsA decreases regulatory T cells and this contributes to the development of hypertension. However, CsA's effects on another important regulatory immune cell subset, myeloid-derived suppressor cells (MDSCs), is unknown. We hypothesized that augmenting MDSCs would ameliorate the CsA-induced hypertension and vascular and renal injury and dysfunction and that CsA reduces MDSCs in mice. Daily interleukin-33 treatment, which increased MDSC levels, completely prevented CsA-induced hypertension and vascular and renal toxicity. Adoptive transfer of MDSCs from control mice into CsA-treated mice after hypertension was established dose-dependently reduced blood pressure and vascular and glomerular injury. CsA treatment of aortas and kidneys isolated from control mice for 24 hours decreased relaxation responses and increased inflammation, respectively, and these effects were prevented by the presence of MDSCs. MDSCs also prevented the CsA-induced increase in fibronectin in microvascular and glomerular endothelial cells. Last, CsA dose-dependently reduced the number of MDSCs by inhibiting calcineurin and preventing cell proliferation, as other direct calcineurin signaling pathway inhibitors had the same dose-dependent effect. These data suggest that augmenting MDSCs can reduce the cardiovascular and renal toxicity and hypertension caused by CsA. © 2017 American Heart Association, Inc.

  3. Distal renal tubular acidosis

    Science.gov (United States)

    ... this disorder. Alternative Names Renal tubular acidosis - distal; Renal tubular acidosis type I; Type I RTA; RTA - distal; Classical RTA Images Kidney anatomy Kidney - blood and urine flow References Bose A, Monk RD, Bushinsky DA. Kidney ...

  4. Activation of GLP-1 receptors on vascular smooth muscle cells reduces the autoregulatory response in afferent arterioles and increases renal blood flow

    DEFF Research Database (Denmark)

    Jensen, Elisa Pouline; Poulsen, Steen Seier; Kissow, Hannelouise

    2015-01-01

    was to localize renal GLP-1 receptors and describe GLP-1 mediated effects on the renal vasculature. We hypothesized that renal GLP-1 receptors are located in the renal microcirculation and activation of these affects renal autoregulation and increases renal blood flow. In vivo autoradiography using 125I-GLP-1......, 125I-exendin-4 (GLP-1 analog) and 125I-exendin 9-39 (GLP-1 receptor antagonist) was performed in rodents to localize specific GLP-1 receptor binding. GLP-1 mediated effects on blood pressure (BP), renal blood flow (RBF), heart rate (HR), renin secretion, urinary flow rate and Na+ and K+ excretion were...... conclude that GLP-1 receptors are located in the renal vasculature including afferent arterioles. Activation of these receptors reduces the autoregulatory response of afferent arterioles to acute pressure increases and increases renal blood flow in normotensive rats....

  5. Ameliorative effect of Lentinus squarrosulus mycomeat against ...

    African Journals Online (AJOL)

    Ameliorative effect of Lentinus squarrosulus mycomeat against Pseudomonas aeruginosa infection using albino rat as animal model. ... Morphological appearance and behavior of the rats were used as the assessment method for adverse reactions. After a period of 26 days, the rats were sacrificed with the liver, spleen and ...

  6. Histamine ameliorates spatial memory deficits induced by MK-801 infusion into ventral hippocampus as evaluated by radial maze task in rats

    Institute of Scientific and Technical Information of China (English)

    Li-sha XU; Li-xia YANG; Wei-wei HU; Xiao YU; Li MA; Lu-ying LIU; Er-qing WEI; Zhong CHEN

    2005-01-01

    Aim: To investigate the role of histamine in memory deficits induced by MK-801 infusion into the ventral hippocampus in rats. Methods: An 8-arm radial maze (4arms baited) was used to assess spatial memory. Results: Bilateral ventral intrahippocampal (ih) infusion of MK-801 (0.3 μg/site), an N-methyl-D-aspartate (NMDA) antagonist, impaired the retrieval process in both working memory and reference memory. Intrahippocampal injection of histamine (25 or 50 ng/site) or intraperitoneal (ip) injection of histidine (25, 50 or 100 mg/kg) markedly ameliorated the spatial memory deficits induced by MK-801. Both the histamine H1 antagonist pyrilamine (0.5 or 1.0 μg/site, ih) and the H2 antagonist cimetidine (2.5 μg/site,ih) abolished the ameliorating effect of histidine (100 mg/kg, ip) on reference memory deficits, but not that on working memory deficits induced by MK-801. Conclusion:The results indicate that histamine in the ventral hippocampus can ameliorate MK-801-induced spatial memory deficits, and that histamine's effect on reference memory is mediated by postsynaptic histamine H1 and H2 receptors.

  7. Cardio-renal syndrome

    OpenAIRE

    Gnanaraj, Joseph; Radhakrishnan, Jai

    2016-01-01

    Cardio-renal syndrome is a commonly encountered problem in clinical practice. Its pathogenesis is not fully understood. The purpose of this article is to highlight the interaction between the cardiovascular system and the renal system and how their interaction results in the complex syndrome of cardio-renal dysfunction. Additionally, we outline the available therapeutic strategies to manage this complex syndrome.

  8. Renal inflammatory myofibroblastic tumor

    DEFF Research Database (Denmark)

    Heerwagen, S T; Jensen, C; Bagi, P

    2007-01-01

    Renal inflammatory myofibroblastic tumor (IMT) is a rare soft-tissue tumor of controversial etiology with a potential for local recurrence after incomplete surgical resection. The radiological findings in renal IMT are not well described. We report two cases in adults with a renal mass treated...

  9. Less contribution of mast cells to the progression of renal fibrosis in Rat kidneys with chronic renal failure.

    Science.gov (United States)

    Baba, Asuka; Tachi, Masahiro; Ejima, Yutaka; Endo, Yasuhiro; Toyama, Hiroaki; Saito, Kazutomo; Abe, Nozomu; Yamauchi, Masanori; Miura, Chieko; Kazama, Itsuro

    2017-02-01

    Chronic renal failure (CRF) is histopathologically characterized by tubulointerstitial fibrosis in addition to glomerulosclerosis. Although mast cells are known to infiltrate into the kidneys with chronic inflammation, we know little about their contribution to the pathogenesis of renal fibrosis associated with CRF. The aim of this study was to reveal the involvement of mast cells in the progression of renal fibrosis in CRF. Using a rat model with CRF resulting from 5/6 nephrectomy, we examined the histopathological features of the kidneys and the infiltration of mast cells into the renal interstitium. By treating the rats with a potent mast cell stabilizer, tranilast, we also examined the involvement of mast cells in the progression of renal fibrosis associated with CRF. The CRF rat kidneys were characterized by the wide staining of collagen III and increased number of myofibroblasts, indicating the progression of renal fibrosis. Compared to T-lymphocytes or macrophages, the number of tryptase-positive mast cells was much smaller within the fibrotic kidneys and they did not proliferate in situ. The mRNA expression of mast cell-derived fibroblast-activating factors was not increased in the renal cortex isolated from CRF rat kidneys. Treatment with tranilast did not suppress the progression of renal fibrosis, nor did it ameliorate the progression of glomerulosclerosis and the interstitial proliferation of inflammatory leukocytes. This study demonstrated for the first time that mast cells are neither increased nor activated in the fibrotic kidneys of CRF rats. Compared to T-lymphocytes or macrophages that proliferate in situ within the fibrotic kidneys, mast cells were less likely to contribute to the progression of renal fibrosis associated with CRF. © 2016 Asian Pacific Society of Nephrology.

  10. Endothelin-1 receptor antagonists protect the kidney against the nephrotoxicity induced by cyclosporine-A in normotensive and hypertensive rats.

    Science.gov (United States)

    Caires, A; Fernandes, G S; Leme, A M; Castino, B; Pessoa, E A; Fernandes, S M; Fonseca, C D; Vattimo, M F; Schor, N; Borges, F T

    2017-12-11

    Cyclosporin-A (CsA) is an immunosuppressant associated with acute kidney injury and chronic kidney disease. Nephrotoxicity associated with CsA involves the increase in afferent and efferent arteriole resistance, decreased renal blood flow (RBF) and glomerular filtration. The aim of this study was to evaluate the effect of Endothelin-1 (ET-1) receptor blockade with bosentan (BOS) and macitentan (MAC) antagonists on altered renal function induced by CsA in normotensive and hypertensive animals. Wistar and genetically hypertensive rats (SHR) were separated into control group, CsA group that received intraperitoneal injections of CsA (40 mg/kg) for 15 days, CsA+BOS and CsA+MAC that received CsA and BOS (5 mg/kg) or MAC (25 mg/kg) by gavage for 15 days. Plasma creatinine and urea, mean arterial pressure (MAP), RBF and renal vascular resistance (RVR), and immunohistochemistry for ET-1 in the kidney cortex were measured. CsA decreased renal function, as shown by increased creatinine and urea. There was a decrease in RBF and an increase in MAP and RVR in normotensive and hypertensive animals. These effects were partially reversed by ET-1 antagonists, especially in SHR where increased ET-1 production was observed in the kidney. Most MAC effects were similar to BOS, but BOS seemed to be better at reversing cyclosporine-induced changes in renal function in hypertensive animals. The results of this work suggested the direct participation of ET-1 in renal hemodynamics changes induced by cyclosporin in normotensive and hypertensive rats. The antagonists of ET-1 MAC and BOS reversed part of these effects.

  11. Endothelin-1 receptor antagonists protect the kidney against the nephrotoxicity induced by cyclosporine-A in normotensive and hypertensive rats

    Directory of Open Access Journals (Sweden)

    A. Caires

    2017-12-01

    Full Text Available Cyclosporin-A (CsA is an immunosuppressant associated with acute kidney injury and chronic kidney disease. Nephrotoxicity associated with CsA involves the increase in afferent and efferent arteriole resistance, decreased renal blood flow (RBF and glomerular filtration. The aim of this study was to evaluate the effect of Endothelin-1 (ET-1 receptor blockade with bosentan (BOS and macitentan (MAC antagonists on altered renal function induced by CsA in normotensive and hypertensive animals. Wistar and genetically hypertensive rats (SHR were separated into control group, CsA group that received intraperitoneal injections of CsA (40 mg/kg for 15 days, CsA+BOS and CsA+MAC that received CsA and BOS (5 mg/kg or MAC (25 mg/kg by gavage for 15 days. Plasma creatinine and urea, mean arterial pressure (MAP, RBF and renal vascular resistance (RVR, and immunohistochemistry for ET-1 in the kidney cortex were measured. CsA decreased renal function, as shown by increased creatinine and urea. There was a decrease in RBF and an increase in MAP and RVR in normotensive and hypertensive animals. These effects were partially reversed by ET-1 antagonists, especially in SHR where increased ET-1 production was observed in the kidney. Most MAC effects were similar to BOS, but BOS seemed to be better at reversing cyclosporine-induced changes in renal function in hypertensive animals. The results of this work suggested the direct participation of ET-1 in renal hemodynamics changes induced by cyclosporin in normotensive and hypertensive rats. The antagonists of ET-1 MAC and BOS reversed part of these effects.

  12. Traumatic renal infarction

    International Nuclear Information System (INIS)

    Yashiro, Naobumi; Ohtomo, Kuni; Kokubo, Takashi; Itai, Yuji; Iio, Masahiro

    1986-01-01

    Four cases of traumatic renal artery occlusion were described and illustrated. In two cases, direct blows to the abdomen compressed the renal artery against the vertebral column. Clinically, they were severely injured with macroscopic hematuria. Aortograms showed abrupt truncation of renal arteries. In the other two, rapid deceleration caused sudden displacement of the kidney producing an intimal tear with resultant thrombosis. Although they showed little injury without macrohematuria, aortograms revealed tapered occlusion of renal arteries. One of them developed hypertension. ''Rim sign'' of post-contrast CT and hypertension resulted from traumatic renal artery occlusion were reviewed. (author)

  13. Antagonistic Phenomena in Network Dynamics

    Science.gov (United States)

    Motter, Adilson E.; Timme, Marc

    2018-03-01

    Recent research on the network modeling of complex systems has led to a convenient representation of numerous natural, social, and engineered systems that are now recognized as networks of interacting parts. Such systems can exhibit a wealth of phenomena that not only cannot be anticipated from merely examining their parts, as per the textbook definition of complexity, but also challenge intuition even when considered in the context of what is now known in network science. Here, we review the recent literature on two major classes of such phenomena that have far-reaching implications: (a) antagonistic responses to changes of states or parameters and (b) coexistence of seemingly incongruous behaviors or properties - both deriving from the collective and inherently decentralized nature of the dynamics. They include effects as diverse as negative compressibility in engineered materials, rescue interactions in biological networks, negative resistance in fluid networks, and the Braess paradox occurring across transport and supply networks. They also include remote synchronization, chimera states, and the converse of symmetry breaking in brain, power-grid, and oscillator networks as well as remote control in biological and bioinspired systems. By offering a unified view of these various scenarios, we suggest that they are representative of a yet broader class of unprecedented network phenomena that ought to be revealed and explained by future research.

  14. The renoprotective effect of angiotensin-converting enzyme inhibitors in experimental chronic renal failure is not dependent on enhanced kinin activity.

    Science.gov (United States)

    Nabokov, A; Amann, K; Gassmann, P; Schwarz, U; Orth, S R; Ritz, E

    1998-01-01

    Angiotensin-converting enzyme (ACE) inhibitors have been shown to ameliorate the progression of glomerulosclerosis both in experimental models of uraemia and in patients with renal failure. It has not been documented, however, whether this is due to a decrease in angiotensin II generation or is a consequence of elevated local level of bradykinin. Morphometric investigation of renal tissue was performed in 5/6 nephrectomized (SNx) rats, i.e. untreated or treated with the ACE inhibitor ramipril (SNx-RAM), the B2 kinin receptor antagonist HOE 140 (SNx-HOE), or a combination of both (SNx-RAM + HOE) over 8 weeks. A further group of SNx received delayed treatment with ramipril from week 5 onward (SNx-RAMD). In addition, a sham-operated (SHAM) control group was studied. Systolic blood pressure was significantly lower in both SNx-RAM and SNx-RAM + HOE groups compared to (untreated) SNx. The glomerulosclerosis index (GSI) was substantially higher in the (untreated) SNx group (0.24 +/- 0.04) vs SHAM (0.02 +/- 0.01). A significantly higher GSI was found in the SNx-HOE group (0.45 +/- 0.08) as compared to (untreated) SNx. However, in the SNx-RAM, SNx-RAM + HOE, and SNx-RAMD groups, the GSI was lowered to a similar extent (0.1 +/- 0.02, 0.09 +/- 0.02, and 0.07 +/- 0.01 respectively). In addition, a concomitant attenuation of tubulointerstitial damage was noted in all the above groups. Increased kinin activity does not appear to play a major role in the renoprotective effect of ACE inhibitors in the remnant kidney model.

  15. Proinflammatory genotype of interleukin-1 and interleukin-1 receptor antagonist is associated with ESRD in proteinase 3-ANCA vasculitis patients.

    Science.gov (United States)

    Borgmann, Stefan; Endisch, Georg; Hacker, Ulrich T; Song, Bong-Seok; Fricke, Harald

    2003-05-01

    Small-vessel vasculitides are associated with antineutrophil cytoplasmic antibodies (ANCAs). Cytoplasmic ANCAs are targeted mainly against proteinase 3 (PR3), whereas myeloperoxidase (MPO) is the major antigen of perinuclear ANCAs. These relapsing vasculitides show heterogeneous clinical pictures, and disease severity may vary broadly from mild local organ manifestation to acute organ failure (eg, renal failure). We tested whether two cytokine polymorphisms in the interleukin-1beta (IL-1beta) and IL-1 receptor antagonist (IL-1ra) genes, known to determine cytokine secretion, are associated with clinical manifestations and outcome of ANCA-associated vasculitides. Polymerase chain reaction and restriction fragment length polymorphism analyses were performed to determine polymorphisms in the IL-1beta and IL-1ra genes in 79 patients with PR3-ANCA, 30 patients with MPO-ANCA vasculitis, and 196 healthy controls. The frequency of the so-called proinflammatory genotype, characterized by high secretion of IL-1beta and low secretion of its antagonist IL-1ra, was increased significantly in patients with PR3-ANCA with end-stage renal disease. Patients with a renal manifestation of PR3-ANCA vasculitis have an increased risk for developing end-stage renal disease when carrying the proinflammatory IL-1beta/IL-1ra genotype. Anti-inflammatory therapy specifically antagonizing the proinflammatory effect of IL-1beta may be a promising treatment for patients with Wegener's granulomatosis with renal manifestations.

  16. Efferent pathways in sodium overload-induced renal vasodilation in rats.

    Directory of Open Access Journals (Sweden)

    Nathalia O Amaral

    Full Text Available Hypernatremia stimulates the secretion of oxytocin (OT, but the physiological role of OT remains unclear. The present study sought to determine the involvement of OT and renal nerves in the renal responses to an intravenous infusion of hypertonic saline. Male Wistar rats (280-350 g were anesthetized with sodium thiopental (40 mg. kg(-1, i.v.. A bladder cannula was implanted for collection of urine. Animals were also instrumented for measurement of mean arterial pressure (MAP and renal blood flow (RBF. Renal vascular conductance (RVC was calculated as the ratio of RBF by MAP. In anesthetized rats (n = 6, OT infusion (0.03 µg • kg(-1, i.v. induced renal vasodilation. Consistent with this result, ex vivo experiments demonstrated that OT caused renal artery relaxation. Blockade of OT receptors (OXTR reduced these responses to OT, indicating a direct effect of this peptide on OXTR on this artery. Hypertonic saline (3 M NaCl, 1.8 ml • kg(-1 b.wt., i.v. was infused over 60 s. In sham rats (n = 6, hypertonic saline induced renal vasodilation. The OXTR antagonist (AT; atosiban, 40 µg • kg(-1 • h(-1, i.v.; n = 7 and renal denervation (RX reduced the renal vasodilation induced by hypernatremia. The combination of atosiban and renal denervation (RX+AT; n = 7 completely abolished the renal vasodilation induced by sodium overload. Intact rats excreted 51% of the injected sodium within 90 min. Natriuresis was slightly blunted by atosiban and renal denervation (42% and 39% of load, respectively, whereas atosiban with renal denervation reduced sodium excretion to 16% of the load. These results suggest that OT and renal nerves are involved in renal vasodilation and natriuresis induced by acute plasma hypernatremia.

  17. Intraperitoneal administration of the globular adiponectin gene ameliorates diabetic nephropathy in Wistar rats.

    Science.gov (United States)

    Yuan, Fang; Liu, Ying-Hong; Liu, Fu-You; Peng, You-Ming; Tian, Jun-Wei

    2014-06-01

    The present study investigated the potential effects of the long-term expression of exogenous adiponectin (ADPN) on normal and diabetic kidneys. Type 2 diabetes mellitus models were induced by high-lipid and high-sucrose feeding plus intraperitoneal injection of streptozotocin. The recombinant plasmid pIRES2-EGFP-gAd, which is able to co-express globular ADPN (gAd) and enhanced green fluorescent protein (EGFP), was intraperitoneally injected into rat models mediated by Lipofectamine. In total, 32 Wistar rats were randomly assigned into four groups: the normal control group, the diabetes group, the diabetes group treated with pIRES2-EGFP-gAd and the diabetes group treated with pIRES2-EGFP. After 12 weeks, serum biochemistry and urine albumin levels were measured. The kidneys were collected to assess the generation of reactive oxygen species (ROS) and the renal pathological changes were observed by light microcopy. The protein expression of endothelial nitric oxide synthase (eNOS), transforming growth factor-β1 (TGF-β1) and phosphorylated adenosine monophosphate-activated protein kinase (p-AMPK) were determined by an immunohistochemical staining method and western blot analysis. Intraperitoneal injection of the human gAd gene via Lipofectamine resulted in abundant ADPN protein in the kidney. In the diabetic rats, the delivery of the exogenous gAd gene ameliorated the progression of diabetic nephropathy (DN). ADPN attenuated urine albumin excretion in the diabetic rats. ADPN also mitigated glomerular mesangial expansion, reduced the generation of ROS and prevented interstitial fibrosis. In addition, the expression of gAd inhibited the renal expression of TGF-β1, promoted the protein expression of eNOS and activated the opening of the AMPK signaling pathway in the renal tissues of the diabetic rats. Despite the effects of ADPN on DN being controversial, these observations indicate that the supplementation of ADPN is beneficial in ameliorating DN in rats.

  18. Ameliorative effects of arctiin from Arctium lappa on experimental glomerulonephritis in rats.

    Science.gov (United States)

    Wu, Jian-Guo; Wu, Jin-Zhong; Sun, Lian-Na; Han, Ting; Du, Jian; Ye, Qi; Zhang, Hong; Zhang, Yu-Guang

    2009-11-01

    Membranous glomerulonephritis (MGN) remains the most common cause of adult-onset nephrotic syndrome in the world and up to 40% of untreated patients will progress to end-stage renal disease. Although the treatment of MGN with immunosuppressants or steroid hormones can attenuate the deterioration of renal function, numerous treatment-related complications have also been established. In this study, the ameliorative effects of arctiin, a natural compound isolated from the fruits of Arctium lappa, on rat glomerulonephritis induced by cationic bovine serum albumin (cBSA) were determined. After oral administration of arctiin (30, 60, 120 mg/kgd) for three weeks, the levels of serum creatinine (Scr) and blood urea nitrogen (BUN) and 24-h urine protein content markedly decreased, while endogenous creatinine clearance rate (ECcr) significantly increased. The parameters of renal lesion, hypercellularity, infiltration of polymorphonuclear leukocyte (PMN), fibrinoid necrosis, focal and segmental proliferation and interstitial infiltration, were reversed. In addition, we observed that arctiin evidently reduced the levels of malondialdehyde (MDA) and pro-inflammatory cytokines including interleukin-6 (IL-6) and tumor necrosis factor (TNF-alpha), suppressed nuclear factor-kappaB p65 (NF-kappaB) DNA binding activity, and enhanced superoxide dismutase (SOD) activity. These findings suggest that the ameliorative effects of arctiin on glomerulonephritis is carried out mainly by suppression of NF-kappaB activation and nuclear translocation and the decreases in the levels of these pro-inflammatory cytokines, while SOD is involved in the inhibitory pathway of NF-kappaB activation. Arctiin has favorable potency for the development of an inhibitory agent of NF-kappaB and further application to clinical treatment of glomerulonephritis, though clinical studies are required.

  19. Calcium antagonists for aneurysmal subarachnoid haemorrhage

    NARCIS (Netherlands)

    Dorhout Mees, S. M.; Rinkel, G. J. E.; Feigin, V. L.; Algra, A.; van den Bergh, W. M.; Vermeulen, M.; van Gijn, J.

    2007-01-01

    BACKGROUND: Secondary ischaemia is a frequent cause of poor outcome in patients with subarachnoid haemorrhage (SAH). Its pathogenesis has been incompletely elucidated, but vasospasm probably is a contributing factor. Experimental studies have suggested that calcium antagonists can prevent or reverse

  20. sup(99m)Tc-DMSA renal scintigraphy in renal failure due to various renal diseases

    Energy Technology Data Exchange (ETDEWEB)

    Hosokawa, S; Daijo, K; Okabe, T; Kawamura, J; Hara, A [Kyoto Univ. (Japan). Hospital

    1979-08-01

    Renal contours in renal failure were studied by means of sup(99m)Tc-dimercaptosuccinic acid (DMSA) renoscintigraphy. Renal cortical images were obtained even in renal failure cases. Causes of renal failure were chronic glomerulonephritis in 7, bilateral renal tuberculosis in 2, chronic pyelonephritis in 3, bilateral renal calculi in 3, diabetic nephropathy in 2, polycystic kidney disease in 2 and stomach cancer in 1.

  1. sup(99m)Tc-DMSA renal scintigraphy in renal failure due to various renal diseases

    International Nuclear Information System (INIS)

    Hosokawa, Shin-ichi; Daijo, Kazuyuki; Okabe, Tatsushiro; Kawamura, Juichi; Hara, Akira

    1979-01-01

    Renal contours in renal failure were studied by means of sup(99m)Tc-dimercaptosuccinic acid (DMSA) renoscintigraphy. Renal cortical images were obtained even in renal failure cases. Causes of renal failure were chronic glomerulonephritis in 7, bilateral renal tuberculosis in 2, chronic pyelonephritis in 3, bilateral renal calculi in 3, diabetic nephropathy in 2, polycystic kidney disease in 2 and stomach cancer in 1. (author)

  2. An α4β1 integrin antagonist decreases airway inflammation in ovalbumin-exposed mice

    Science.gov (United States)

    Kenyon, Nicholas J.; Liu, Ruiwu; O’Roark, Erin M.; Huang, Wenzhe; Peng, Li; Lam, Kit S.

    2008-01-01

    Inhibition of the α4 subunit of both the α4β1 and α4β7 integrins has shown promise in decreasing airway inflammation and airway hyperresponsiveness in various animal models. We hypothesized that a novel, high-affinity α4β1 antagonist (LLP2A) would decrease the migration of eosinophils to the lung and ameliorate the airway hyperresponsiveness in a mouse model of ovalbumin-induced airway inflammation. To test this hypothesis, we administered LLP2A, or scrambled LLP2A (a negative control), prior to exposure of sensitized BALB/c mice to ovalbumin aerosol. We can partially prevent, or reverse, the airway inflammatory response, but not airways hyperresponsiveness, by treatment of mice with LLP2A, a synthetic peptidomimetic α4β1 antagonist LLP2A. Specifically engineered, PEGylated (PEG) formulations of this antagonist further reduce the airway inflammatory response to ovalbumin lbumin, presumably by improving the circulating half-life of the drug. PMID:19103195

  3. Benzodiazepine receptor antagonists for hepatic encephalopathy

    DEFF Research Database (Denmark)

    Als-Nielsen, B; Gluud, L L; Gluud, C

    2004-01-01

    Hepatic encephalopathy may be associated with accumulation of substances that bind to a receptor-complex in the brain resulting in neural inhibition. Benzodiazepine receptor antagonists may have a beneficial effect on patients with hepatic encephalopathy.......Hepatic encephalopathy may be associated with accumulation of substances that bind to a receptor-complex in the brain resulting in neural inhibition. Benzodiazepine receptor antagonists may have a beneficial effect on patients with hepatic encephalopathy....

  4. Pharmacokinetics and pharmacodynamics of candesartan cilexetil in patients with normal to severely impaired renal function

    NARCIS (Netherlands)

    Buter, H; Navis, GY; Woittiez, AJJ; de Zeeuw, D; de Jong, PE

    Objective: We studied the pharmacokinetics and pharmacodynamics of single and multiple doses of candesartan cilexetil 8 mg per day in hypertensive patients with different degrees of renal function impairment. Candesartan is an angiotensin II subtype I (AT1) receptor antagonist that is administered

  5. Renal denervation prevents long-term sequelae of ischemic renal injury

    Science.gov (United States)

    Kim, Jinu; Padanilam, Babu J.

    2014-01-01

    Signals that drive interstitial fibrogenesis after renal ischemia reperfusion injury remain undefined. Sympathetic activation is manifest even in the early clinical stages of chronic kidney disease and is directly related to disease severity. A role for renal nerves in renal interstitial fibrogenesis in the setting of ischemia reperfusion injury has not been studied. In male 129S1/SvImJ mice, ischemia reperfusion injury induced tubulointerstitial fibrosis as indicated by collagen deposition and profibrotic protein expression 4 to 16 days after the injury.. Leukocyte influx, proinflammatory protein expression, oxidative stress, apoptosis, and cell cycle arrest at G2/M phase were enhanced after ischemia reperfusion injury. Renal denervation at the time of injury or up to 1 day post-injury improved histology, decreased proinflammatory/profibrotic responses and apoptosis, and prevented G2/M cell cycle arrest in the kidney. Treatment with afferent nerve-derived calcitonin gene-related peptide (CGRP) or efferent nerve-derived norepinephrine in denervated and ischemia reperfusion injury-induced kidneys mimicked innervation, restored inflammation and fibrosis, induced G2/M arrest, and enhanced TGF-β1 activation. Blocking norepinephrine or CGRP function using respective receptor blockers prevented these effects. Consistent with the in vivo study, treatment with either norepinephrine or CGRP induced G2/M cell cycle arrest in HK-2 proximal tubule cells, whereas antagonists against their respective receptors prevented G2/M arrest. Thus, renal nerve stimulation is a primary mechanism and renal nerve-derived factors drive epithelial cell cycle arrest and the inflammatory cascade causing interstitial fibrogenesis after ischemia reperfusion injury. PMID:25207878

  6. Inhibition of p38 MAPK attenuates renal atrophy and fibrosis in a murine renal artery stenosis model.

    Science.gov (United States)

    Wang, Diping; Warner, Gina M; Yin, Ping; Knudsen, Bruce E; Cheng, Jingfei; Butters, Kim A; Lien, Karen R; Gray, Catherine E; Garovic, Vesna D; Lerman, Lilach O; Textor, Stephen C; Nath, Karl A; Simari, Robert D; Grande, Joseph P

    2013-04-01

    Renal artery stenosis (RAS) is an important cause of chronic renal dysfunction. Recent studies have underscored a critical role for CCL2 (MCP-1)-mediated inflammation in the progression of chronic renal damage in RAS and other chronic renal diseases. In vitro studies have implicated p38 MAPK as a critical intermediate for the production of CCL2. However, a potential role of p38 signaling in the development and progression of chronic renal disease in RAS has not been previously defined. We sought to test the hypothesis that inhibition of p38 MAPK ameliorates chronic renal injury in mice with RAS. We established a murine RAS model by placing a cuff on the right renal artery and treated mice with the p38 inhibitor SB203580 or vehicle for 2 wk. In mice treated with vehicle, the cuffed kidney developed interstitial fibrosis, tubular atrophy, and interstitial inflammation. In mice treated with SB203580, the RAS-induced renal atrophy was reduced (70% vs. 39%, P < 0.05). SB203580 also reduced interstitial inflammation and extracellular matrix deposition but had no effect on the development of hypertension. SB203580 partially blocked the induction of CCL2, CCL7 (MCP-3), CC chemokine receptor 2 (CCR2), and collagen 4 mRNA expression in the cuffed kidneys. In vitro, blockade of p38 hindered both TNF-α and TGF-β-induced CCL2 upregulation. Based on these observations, we conclude that p38 MAPK plays a critical role in the induction of CCL2/CCL7/CCR2 system and the development of interstitial inflammation in RAS.

  7. Imaging of renal osteodystrophy

    Energy Technology Data Exchange (ETDEWEB)

    Jevtic, V. E-mail: vladimir.jevtic@mf.uni-lj.si

    2003-05-01

    Chronic renal insufficiency, hemodialysis, peritoneal dialysis, renal transplantation and administration of different medications provoke complex biochemical disturbances of the calcium-phosphate metabolism with wide spectrum of bone and soft tissue abnormalities termed renal osteodystrophy. Clinically most important manifestation of renal bone disease includes secondary hyperparathyroidism, osteomalacia/rickets, osteoporosis, adynamic bone disease and soft tissue calcification. As a complication of long-term hemodialysis and renal transplantation amyloid deposition, destructive spondyloarthropathy, osteonecrosis, and musculoskeletal infections may occur. Due to more sophisticated diagnostic methods and more efficient treatment classical radiographic features of secondary hyperparathyroidism and osteomalacia/rickets are now less frequently seen. Radiological investigations play an important role in early diagnosis and follow-up of the renal bone disease. Although numerous new imaging modalities have been introduced in clinical practice (scintigraphy, CT, MRI, quantitative imaging), plain film radiography, especially fine quality hand radiograph, still represents most widely used examination.

  8. Imaging of renal osteodystrophy

    International Nuclear Information System (INIS)

    Jevtic, V.

    2003-01-01

    Chronic renal insufficiency, hemodialysis, peritoneal dialysis, renal transplantation and administration of different medications provoke complex biochemical disturbances of the calcium-phosphate metabolism with wide spectrum of bone and soft tissue abnormalities termed renal osteodystrophy. Clinically most important manifestation of renal bone disease includes secondary hyperparathyroidism, osteomalacia/rickets, osteoporosis, adynamic bone disease and soft tissue calcification. As a complication of long-term hemodialysis and renal transplantation amyloid deposition, destructive spondyloarthropathy, osteonecrosis, and musculoskeletal infections may occur. Due to more sophisticated diagnostic methods and more efficient treatment classical radiographic features of secondary hyperparathyroidism and osteomalacia/rickets are now less frequently seen. Radiological investigations play an important role in early diagnosis and follow-up of the renal bone disease. Although numerous new imaging modalities have been introduced in clinical practice (scintigraphy, CT, MRI, quantitative imaging), plain film radiography, especially fine quality hand radiograph, still represents most widely used examination

  9. Clinical observation of calcium dobesilate in the treatment of chronic renal allograft dysfunction

    Institute of Scientific and Technical Information of China (English)

    Zheng Xue-yang; Han Shu; Zhou Mei-sheng; Fu Shang-xi; Wang Li-ming

    2014-01-01

    Abstract BACKGROUND: Calcium dobesilate (calcium dihydroxy-2, 5-benzenesulfonate) has been widely used to treat chronic venous insufficiency and diabetic retinopathy, especialy many clinical studies showed that calcium dobesilate as vasoprotective compound ameliorates renal lesions in diabetic nephropathy. However, there are few literatures reported calcium dobesilate in the treatment of chronic renal alograft dysfunction after renal transplantation. OBJECTIVE:To observe the efficacy and safety of calcium dobesilate on chronic renal dysfunction after renal transplantation. METHODS:A total of 152 patients with chronic renal alograft dysfunction after renal transplantation were enroled from the Military Institute of Organ Transplantation, Changzheng Hospital, Second Military Medical University of Chinese PLA. They were randomly divided into the treatment group (n=78) and the control group (n=74). Patients in the treatment group received 500 mg of calcium dobesilate three times daily for eight weeks. Al patients were treated with calcineurin inhibitor-based triple immunosuppressive protocols and comprehensive therapies. RESULTS AND CONCLUSION: For patients receiving calcium dobesilate, serum creatinine, blood urea nitrogen and uric acid decreased significantly at two weeks after treatment and maintained a stable level (P 0.05). Administration of calcium dobesilate did not change the general condition of patients with renal insufficiency, nor did it affect blood concentrations of the immunosuppressive agents. Calcium dobesilate may help to delay the progress of graft injury in patients with chronic renal graft dysfunction by conjugating with creatinine, ameliorating the impaired microcirculation and its antioxidant property. The decline in serum creatinine aleviates patients’ anxiety and concern arising from the elevation of creatinine. However, the negative interference with serum creatinine caused by calcium dobesilate should be cautious in order to avoid

  10. Renal artery stenosis

    International Nuclear Information System (INIS)

    Desberg, A.; Paushter, D.M.; Lammert, G.K.; Hale, J.; Troy, R.; Novic, A.; Nally, J. Jr.

    1989-01-01

    Renal artery disease is a potentially correctable cause of hypertension. Previous studies have suggested the utility of duplex sonography in accurately detecting and grading the severity of renal artery stenosis. The purpose of this paper is to evaluate color flow Doppler for this use. Forty-three kidneys were examined by color-flow Doppler and conventional duplex sampling in patients with suspected renovascular hypertension or those undergoing aortography for unrelated reasons. Doppler tracings were obtained from the renal arteries and aorta with calculation of the renal aortic ratio (RAR) and resistive index (RI). Results of Doppler sampling with color flow guidance were compared with aortograms in a blinded fashion

  11. Incidental renal neoplasms

    DEFF Research Database (Denmark)

    Rabjerg, Maj; Mikkelsen, Minne Nedergaard; Walter, Steen

    2014-01-01

    On the basis of associations between tumor size, pathological stage, histological subtype and tumor grade in incidentally detected renal cell carcinoma vs symptomatic renal cell carcinoma, we discussed the need for a screening program of renal cell carcinoma in Denmark. We analyzed a consecutive...... series of 204 patients with renal tumors in 2011 and 2012. The tumors were classified according to detection mode: symptomatic and incidental and compared to pathological parameters. Eighty-nine patients (44%) were symptomatic, 113 (55%) were incidental. Information was not available in two patients...

  12. Close to Transplant Renal Artery Stenosis and Percutaneous Transluminal Treatment

    Directory of Open Access Journals (Sweden)

    Leonardou Polytimi

    2011-01-01

    Full Text Available Purpose. To evaluate the efficacy of percutaneous transluminal angioplasty (PTA in the management of arterial stenosis located close to the allograft anastomosis (close-TRAS. Materials and Methods. 31 patients with renal transplants were admitted to our institution because of persistent hypertension and impairment of transplant renal function and underwent angiography for vascular investigation. 27 were diagnosed suffering from transplant renal artery stenosis (TRAS, whereas 4 had severe iliac artery stenosis proximal to the transplant anastomosis (Prox-TRAS. 3 cases of TRAS coexisted with segmental renal arterial stenosis, whereas 3 other cases of TRAS were caused by kinking and focal stenosis in the middle of the transplanted renal artery. Results. Angioplasty and stenting were successfully applied to all patients with iliac artery stenosis as well as to those with TRAS and segmental artery stenosis. Two of three patients with kinking were well treated with angioplasty and stenting, whereas one treated only with angioplasty necessitated surgery. No major procedure-related complications appeared, and the result was decrease of the serum creatinine level and of the blood pressure. Conclusions. PTA is the appropriate initial treatment of TRAS and close-TRAS, with low morbidity and mortality rates, achieving improvement of graft function and amelioration of hypertension.

  13. Renal cell carcinoma in patient with crossed fused renal ectopia

    Directory of Open Access Journals (Sweden)

    Ozgur Cakmak

    2016-01-01

    Full Text Available Primary renal cell carcinomas have rarely been reported in patients with crossed fused renal ectopia. We presented a patient with right to left crossed fused kidney harbouring renal tumor. The most frequent tumor encountered in crossed fused renal ectopia is renal cell carcinoma. In this case, partial nephrectomy was performed which pave way to preservation of the uninvolved both renal units. Due to unpredictable anatomy, careful preoperative planning and meticulous delineation of renal vasculature is essential for preservation of the uninvolved renal units.

  14. Effect of tolvaptan on renal water and sodium excretion and blood pressure during nitric oxide inhibition

    DEFF Research Database (Denmark)

    Therwani, Safa Al; Rosenbæk, Jeppe Bakkestrøm; Mose, Frank Holden

    2017-01-01

    BACKGROUND: Tolvaptan is a selective vasopressin receptor antagonist. Nitric Oxide (NO) promotes renal water and sodium excretion, but the effect is unknown in the nephron's principal cells. In a dose-response study, we measured the effect of tolvaptan on renal handling of water and sodium....... CONCLUSIONS: During baseline, fractional excretion of sodium was unchanged. During tolvaptan with NO-inhibition, renal water excretion was reduced dose dependently, and renal sodium excretion was reduced unrelated to the dose, partly via an AVP dependent mechanism. Thus, tolvaptan antagonized the reduction...... in renal water and sodium excretion during NO-inhibition. Most likely, the lack of decrease in AQP2 excretion by tolvaptan could be attributed to a counteracting effect of the high level of p-AVP....

  15. Tolvaptan alleviates excessive fluid retention of nephrotic diabetic renal failure unresponsive to furosemide.

    Science.gov (United States)

    Takada, Tesshu; Masaki, Tsuguto; Hoshiyama, Ayako; Toki, Takuya; Kamata, Yuji; Shichiri, Masayoshi

    2018-04-17

    Patients with diabetic nephropathy develop nephrotic syndrome, and may show limited response to conventional therapy. They often require earlier initiation of renal replacement therapy because they become refractory to diuretics, and experience excessive fluid retention. We aimed to investigate the efficacy of tolvaptan, an oral arginine vasopressin type 2 receptor antagonist, in a case series of 14 severe diabetic renal failure patients who were severely refractory to maximal doses of furosemide and had excessive fluid retention despite preserved cardiac function and residual renal function. All 14 patients experienced immediate and sustained water diuretic effects, resulting in alleviation of congestive heart failure. None required initiation of renal replacement therapy. Tolvaptan promptly increased urine volume and free water clearance, reversed progressive fluid retention, and alleviated congestive heart failure. Thus, tolvaptan could serve as a potential adjunct therapy for severe diabetic renal failure patients with excessive fluid retention and congestive heart failure. This article is protected by copyright. All rights reserved.

  16. Stages of Renal Cell Cancer

    Science.gov (United States)

    ... Tumors Treatment Genetics of Kidney Cancer Research Renal Cell Cancer Treatment (PDQ®)–Patient Version General Information About Renal Cell Cancer Go to Health Professional Version Key Points Renal ...

  17. Bilateral papillary renal cell carcinoma

    International Nuclear Information System (INIS)

    Gossios, K.; Vazakas, P.; Argyropoulou, M.; Stefanaki, S.; Stavropoulos, N.E.

    2001-01-01

    Papillary renal cell carcinoma is a subgroup of malignant renal epithelial neoplasms. We report the clinical and imaging findings of a case with multifocal and bilateral renal cell carcinoma which are nonspecific. (orig.)

  18. Iohexol clearance is superior to creatinine-based renal function estimating equations in detecting short-term renal function decline in chronic heart failure.

    Science.gov (United States)

    Cvan Trobec, Katja; Kerec Kos, Mojca; von Haehling, Stephan; Anker, Stefan D; Macdougall, Iain C; Ponikowski, Piotr; Lainscak, Mitja

    2015-12-01

    To compare the performance of iohexol plasma clearance and creatinine-based renal function estimating equations in monitoring longitudinal renal function changes in chronic heart failure (CHF) patients, and to assess the effects of body composition on the equation performance. Iohexol plasma clearance was measured in 43 CHF patients at baseline and after at least 6 months. Simultaneously, renal function was estimated with five creatinine-based equations (four- and six-variable Modification of Diet in Renal Disease, Cockcroft-Gault, Cockcroft-Gault adjusted for lean body mass, Chronic Kidney Disease Epidemiology Collaboration equation) and body composition was assessed using bioimpedance and dual-energy x-ray absorptiometry. Over a median follow-up of 7.5 months (range 6-17 months), iohexol clearance significantly declined (52.8 vs 44.4 mL/[min ×1.73 m2], P=0.001). This decline was significantly higher in patients receiving mineralocorticoid receptor antagonists at baseline (mean decline -22% of baseline value vs -3%, P=0.037). Mean serum creatinine concentration did not change significantly during follow-up and no creatinine-based renal function estimating equation was able to detect the significant longitudinal decline of renal function determined by iohexol clearance. After accounting for body composition, the accuracy of the equations improved, but not their ability to detect renal function decline. Renal function measured with iohexol plasma clearance showed relevant decline in CHF patients, particularly in those treated with mineralocorticoid receptor antagonists. None of the equations for renal function estimation was able to detect these changes. ClinicalTrials.gov registration number: NCT01829880.

  19. Iohexol clearance is superior to creatinine-based renal function estimating equations in detecting short-term renal function decline in chronic heart failure

    Science.gov (United States)

    Cvan Trobec, Katja; Kerec Kos, Mojca; von Haehling, Stephan; Anker, Stefan D.; Macdougall, Iain C.; Ponikowski, Piotr; Lainscak, Mitja

    2015-01-01

    Aim To compare the performance of iohexol plasma clearance and creatinine-based renal function estimating equations in monitoring longitudinal renal function changes in chronic heart failure (CHF) patients, and to assess the effects of body composition on the equation performance. Methods Iohexol plasma clearance was measured in 43 CHF patients at baseline and after at least 6 months. Simultaneously, renal function was estimated with five creatinine-based equations (four- and six-variable Modification of Diet in Renal Disease, Cockcroft-Gault, Cockcroft-Gault adjusted for lean body mass, Chronic Kidney Disease Epidemiology Collaboration equation) and body composition was assessed using bioimpedance and dual-energy x-ray absorptiometry. Results Over a median follow-up of 7.5 months (range 6-17 months), iohexol clearance significantly declined (52.8 vs 44.4 mL/[min ×1.73 m2], P = 0.001). This decline was significantly higher in patients receiving mineralocorticoid receptor antagonists at baseline (mean decline -22% of baseline value vs -3%, P = 0.037). Mean serum creatinine concentration did not change significantly during follow-up and no creatinine-based renal function estimating equation was able to detect the significant longitudinal decline of renal function determined by iohexol clearance. After accounting for body composition, the accuracy of the equations improved, but not their ability to detect renal function decline. Conclusions Renal function measured with iohexol plasma clearance showed relevant decline in CHF patients, particularly in those treated with mineralocorticoid receptor antagonists. None of the equations for renal function estimation was able to detect these changes. ClinicalTrials.gov registration number NCT01829880 PMID:26718759

  20. Maslinic acid ameliorates NMDA receptor blockade-induced schizophrenia-like behaviors in mice.

    Science.gov (United States)

    Jeon, Se Jin; Kim, Eunji; Lee, Jin Su; Oh, Hee Kyong; Zhang, Jiabao; Kwon, Yubeen; Jang, Dae Sik; Ryu, Jong Hoon

    2017-11-01

    Schizophrenia is a chronic psychotic disorder characterized by positive, negative, and cognitive symptoms. Primary treatments for schizophrenia relieve the positive symptoms but are less effective against the negative and cognitive symptoms. In the present study, we investigated whether maslinic acid, isolated from Syzygium aromaticum (clove), can ameliorate schizophrenia-like behaviors in mice induced by MK-801, an N-methyl-d-aspartate (NMDA) receptor antagonist. After maslinic acid treatment in the MK-801 model, we examined the behavioral alteration and signaling pathways in the prefrontal cortex. Mice were treated with maslinic acid (30 mg/kg), and their behaviors were evaluated through an array of behavioral tests. The effects of maslinic acid were also examined in the signaling pathways in the prefrontal cortex. A single administration of maslinic acid blocked the MK-801-induced hyperlocomotion and reversed the MK-801-induced sensorimotor gating deficit in the acoustic startle response test. In the social novelty preference test, maslinic acid ameliorated the social behavior deficits induced by MK-801. The MK-801-induced attention and recognition memory impairments were also alleviated by a single administration of maslinic acid. Furthermore, maslinic acid normalized the phosphorylation levels of Akt-GSK-3β and ERK-CREB in the prefrontal cortex. Overall, maslinic acid ameliorated the schizophrenia-like symptoms induced by MK-801, and these effects may be partly mediated through Akt-GSK-3β and ERK-CREB activation. These findings suggest that maslinic acid could be a candidate for the treatment of several symptoms of schizophrenia, including positive symptoms, sensorimotor gating disruption, social interaction deficits, and cognitive impairments. Copyright © 2017 Elsevier Ltd. All rights reserved.

  1. NMDA receptor antagonists inhibit catalepsy induced by either dopamine D1 or D2 receptor antagonists.

    Science.gov (United States)

    Moore, N A; Blackman, A; Awere, S; Leander, J D

    1993-06-11

    In the present study, we investigated the ability of NMDA receptor antagonists to inhibit catalepsy induced by haloperidol, or SCH23390 and clebopride, selective dopamine D1 and D2 receptor antagonists respectively. Catalepsy was measured by recording the time the animal remained with its forepaws placed over a rod 6 cm above the bench. Pretreatment with either the non-competitive NMDA receptor antagonist, MK-801 (0.25-0.5 mg/kg i.p.) or the competitive antagonist, LY274614 (10-20 mg/kg i.p.) reduced the cataleptic response produced by haloperidol (10 mg/kg), SCH23390 (2.5-10 mg/kp i.p.) or clebopride (5-20 mg/kg i.p.). This demonstrates that NMDA receptor antagonists will reduce both dopamine D1 and D2 receptor antagonist-induced catalepsy. Muscle relaxant doses of chlordiazepoxide (10 mg/kg i.p.) failed to reduce the catalepsy induced by haloperidol, suggesting that the anticataleptic effect of the NMDA receptor antagonists was not due to a non-specific action. These results support the hypothesis that NMDA receptor antagonists may have beneficial effects in disorders involving reduced dopaminergic function, such as Parkinson's disease.

  2. A toll-like receptor 9 antagonist improves bladder function and white matter sparing in spinal cord injury.

    Science.gov (United States)

    David, Brian T; Sampath, Sujitha; Dong, Wei; Heiman, Adee; Rella, Courtney E; Elkabes, Stella; Heary, Robert F

    2014-11-01

    Spinal cord injury (SCI) affects motor, sensory, and autonomic functions. As current therapies do not adequately alleviate functional deficits, the development of new and more effective approaches is of critical importance. Our earlier investigations indicated that intrathecal administration of a toll-like receptor 9 (TLR9) antagonist, cytidine-phosphate-guanosine oligodeoxynucleotide 2088 (CpG ODN 2088), to mice sustaining a severe, mid-thoracic contusion injury diminished neuropathic pain but did not alter locomotor deficits. These changes were paralleled by a decrease in the pro-inflammatory response at the injury epicenter. Using the same SCI paradigm and treatment regimen, the current studies investigated the effects of the TLR9 antagonist on bladder function. We report that the TLR9 antagonist decreases SCI-elicited urinary retention and ameliorates bladder morphopathology without affecting kidney function. A significant improvement in white matter sparing was also observed, most likely due to alterations in the inflammatory milieu. These findings indicate that the TLR9 antagonist has beneficial effects not only in reducing sensory deficits, but also on bladder dysfunction and tissue preservation. Thus, modulation of innate immune receptor signaling in the spinal cord can impact the effects of SCI.

  3. Renal Function in Hypothyroidism

    International Nuclear Information System (INIS)

    Khalid, S.; Khalid, M; Elfaki, M.; Hassan, N.; Suliman, S.M.

    2007-01-01

    Background Hypothyroidism induces significant changes in the function of organ systems such as the heart, muscles and brain. Renal function is also influenced by thyroid status. Physiological effects include changes in water and electrolyte metabolism, notably hyponatremia, and reliable alterations of renal hemodynamics, including decrements in renal blood flow, renal plasma flow, glomerular filtration rate (GFR). Objective Renal function is profoundly influenced by thyroid status; the purpose of the present study was to determine the relationship between renal function and thyroid status of patients with hypothyroidism. Design and Patients In 5 patients with primary hypothyroidism and control group renal functions are measured by serum creatinine and glomerular filtration rate (GFR) using modified in diet renal disease (MDRD) formula. Result In hypothyroidism, mean serum creatinine increased and mean estimated GFR decreased, compared to the control group mean serum creatinine decreased and mean estimated GFR Increased. The hypothyroid patients showed elevated serum creatinine levels (> 1.1mg/dl) compared to control group (p value .000). In patients mean estimated GFR decreased, compared to mean estimated GFR increased in the control group (p value= .002).

  4. Renal Function in Hypothyroidism

    International Nuclear Information System (INIS)

    Khalid, A. S; Ahmed, M.I; Elfaki, H.M; Hassan, N.; Suliman, S. M.

    2006-12-01

    Background hypothyroidism induces significant changes in the function of organ systems such as the heart, muscles and brain. Renal function is also influenced by thyroid status. Physiological effects include changes in water and electrolyte metabolism, notably hyponatraemia, and reliable alterations of renal hemodynamics, including decrements in renal blood flow, renal plasma flow, glomerular filtration rate (GFR). Objective renal function is profoundly influenced by thyroid status, the purpose of the present study was to determine the relationship between renal function and thyroid status of patients with hypothyroidism. Design and patients in 5 patients with primary hypothyroidism and control group renal functions are measured by serum creatinine and glomerular filtration rate(GFR) using modified in diet renal disease (MDRD) formula. Result in hypothyroidism, mean serum creatinine increased and mean estimated GFR decreased, compared to the control group mean serum creatinine decreased and mean estimated GFR increased. The hypothyroid patients showed elevated serum creatinine levels(>1.1 mg/d1) compared to control group (p value= 000). In patients mean estimated GFR increased in the control group (p value=.002).Conclusion thus the kidney, in addition to the brain, heart and muscle, is an important target of the action of thyroid hormones.(Author)

  5. Disappearing renal calculus.

    Science.gov (United States)

    Cui, Helen; Thomas, Johanna; Kumar, Sunil

    2013-04-10

    We present a case of a renal calculus treated solely with antibiotics which has not been previously reported in the literature. A man with a 17 mm lower pole renal calculus and concurrent Escherichia coli urine infection was being worked up to undergo percutaneous nephrolithotomy. However, after a course of preoperative antibiotics the stone was no longer seen on retrograde pyelography or CT imaging.

  6. Resveratrol plays important role in protective mechanisms in renal disease - mini-review

    Directory of Open Access Journals (Sweden)

    Guilherme Albertoni

    2015-03-01

    Full Text Available Resveratrol (RESV is a polyphenolic compound found in various plants, including grapes, berries and peanuts, and its processed foods as red wine. RESV possesses a variety of bioactivities, including antioxidant, anti-inflammatory, cardioprotective, antidiabetic, anticancer, chemopreventive, neuroprotective, renal lipotoxicity preventative, and renal protective effects. Numerous studies have demonstrated that polyphenols promote cardiovascular health. Furthermore, RESV can ameliorate several types of renal injury in animal models, including diabetic nephropathy, hyperuricemic, drug-induced injury, aldosterone-induced injury, ischemia-reperfusion injury, sepsis-related injury, and endothelial dysfunction. In addition, RESV can prevent the increase in vasoconstrictors, such as angiotensin II (AII and endothelin-1 (ET-1, as well as intracellular calcium, in mesangial cells. Together, these findings suggest a potential role for RESV as a supplemental therapy for the prevention of renal injury.

  7. Calcium antagonists and the diabetic hypertensive patient

    DEFF Research Database (Denmark)

    Parving, H H; Rossing, P

    1993-01-01

    Roughly 40% of all diabetic patients, whether insulin dependent or not, develop persistent albuminuria (over 300 mg/24 hr), a decrease in the glomerular filtration rate, and elevated blood pressure, ie, diabetic nephropathy. Diabetic nephropathy is the single most important cause of end stage renal...... disease in the Western world, and accounts for over a quarter of all end stage renal disease. It also is a major cause of the increased morbidity and mortality seen in diabetic patients; for example, the cost of end stage renal care in the United States currently exceeds +1.8 billion per year for diabetic...... nephropathy alone and is rapidly rising. Increased arterial blood pressure is an early and common finding in incipient and overt diabetic nephropathy. Fluid and sodium retention with normal concentrations of active renin, angiotensin I and II, and aldosterone has been demonstrated in diabetic renal disease...

  8. Bilateral triple renal arteries

    International Nuclear Information System (INIS)

    Pestemalci, Turan; Yildiz, Yusuf Zeki; Yildirim, Mehmet; Mavi, Ayfer; Gumusburun, Erdem

    2009-01-01

    Knowledge of the variations of the renal artery has grown in importance with increasing numbers of renal transplants, vascular reconstructions and various surgical and radio logic techniques being performed in recent years. We report the presence of bilateral triple renal arteries, discovered on routine dissection of a male cadaver. On the right side, one additional renal artery originated from the abdominal aorta (distributed to superior pole of the kidney) and one other originated from the right common iliac artery (distributed to lower pole of the kidney). On the left side, both additional renal arteries originated from the abdominal aorta. Our observation has been compared with variations described in the literature and their clinical importance has been emphasized. (author)

  9. Radiology of renal failure

    International Nuclear Information System (INIS)

    Griffiths, H.J.

    1990-01-01

    This book covers most aspects of imaging studies in patients with renal failure. The initial chapter provides basic information on contrast agents, intravenous urography, and imaging findings in the urinary tract disorders responsible for renal failure and in patients who have undergone transplantation. It illustrates common gastro-intestinal abnormalities seen on barium studies in patients with renal failure. It illustrates the cardiopulmonary complications of renal failure and offers advice for radiologic differentiation. It details different aspects of skeletal changes in renal failure, including a basic description of the pathophysiology of the changes; many excellent illustrations of classic bone changes, arthritis, avascular necrosis, and soft-tissue calcifications; and details of bone mineral analysis

  10. [Hypertension and renal disease

    DEFF Research Database (Denmark)

    Kamper, A.L.; Pedersen, E.B.; Strandgaard, S.

    2009-01-01

    Renal mechanisms, in particular the renin-angiotensin system and renal salt handling, are of major importance in blood pressure regulation. Co-existence of hypertension and decreased renal function may be due to nephrosclerosis secondary to hypertension, or primary renal disease with secondary...... hypertension. Mild degrees of chronic kidney disease (CKD) can be detected in around 10% of the population, and detection is important as CKD is an important risk factor for atherosclerotic cardiovascular disease. Conversely, heart failure may cause an impairment of renal function. In chronic progressive...... nephropathy, effective blood pressure lowering is of paramount importance, and angiotensin converting enzyme inhibitors and angiotensin receptor blockers are agents of choice Udgivelsesdato: 2009/6/15...

  11. Renal expression of FGF23 in progressive renal disease of diabetes and the effect of ACE inhibitor.

    Directory of Open Access Journals (Sweden)

    Cristina Zanchi

    Full Text Available Fibroblast growth factor 23 (FGF23 is a phosphaturic hormone mainly produced by bone that acts in the kidney through FGF receptors and Klotho. Here we investigated whether the kidney was an additional source of FGF23 during renal disease using a model of type 2 diabetic nephropathy. Renal expression of FGF23 and Klotho was assessed in Zucker diabetic fatty (ZDF and control lean rats at 2, 4, 6, 8 months of age. To evaluate whether the renoprotective effect of angiotensin converting enzyme (ACE inhibitor in this model was associated with changes in FGF23 and Klotho, ZDF rats received ramipril from 4, when proteinuric, to 8 months of age. FGF23 mRNA was not detectable in the kidney of lean rats, nor of ZDF rats at 2 months of age. FGF23 became measurable in the kidney of diabetic rats at 4 months and significantly increased thereafter. FGF23 protein localized in proximal and distal tubules. Renal Klotho mRNA and protein decreased during time in ZDF rats. As renal disease progressed, serum phosphate levels increased in parallel with decline of fractional phosphorus excretion. Ramipril limited proteinuria and renal injury, attenuated renal FGF23 upregulation and ameliorated Klotho expression. Ramipril normalized serum phosphate levels and tended to increase fractional phosphorus excretion. These data indicate that during progressive renal disease the kidney is a site of FGF23 production which is limited by ACE inhibition. Interfering pharmacologically with the delicate balance of FGF23 and phosphorus in diabetes may have implications in clinics.

  12. Patients with a failed renal transplant.

    Science.gov (United States)

    Marcén, R; Teruel Briones, J L

    2011-03-01

    Despite the advances in the care of recipients and in immunosuppression, long-term graft survival has experienced little improvement in the last 10 years. An important number of recipients present progressive loss of graft function and have to be readmitted on dialysis therapy. Before starting dialysis, these patients are re-exposed to the complications of chronic renal failure but there are no specific guidelines for their treatment. The Kidney Disease Quality Initiative Advisory Board clinical practice guidelines given for the non-transplant chronic kidney disease patients have been recommended for ameliorating their clinical situation and the rate of progression of graft failure. The time when dialysis has to be restarted and the type of dialysis procedure, hemodialysis or peritoneal dialysis, are under discusion. But there is no evidence about the superiority of either type of dialysis procedure. Systematic graft nephrectomy has been considered to improve the inflammatory status of the patients with a failed graft which could contribute to a worse control of some complications such as anemia and to the increased rates of cardiovascular mortality. As in the patients with primary end-stage renal disease, retransplantation is the best treatment for a patient with a failed graft. Due to the shortage of organs for transplantation the number of patients who are retransplanted has remained stable. Recurrent diseases such as glomerulonephritis, lyphoproliferative diseases, BK virus nephopathy and previous non-adherence to the treatment do not necessarily preclude retransplantation.

  13. Kidney transplantation in the context of renal replacement therapy.

    Science.gov (United States)

    Pesavento, Todd E

    2009-12-01

    Kidney transplantation has dramatically evolved from a life-saving yet unproven therapy for patients with renal failure to a mature field that is the preferred treatment for those suffering from ESRD. Patients who receive a transplant experience a 68% lower risk of death compared with those waiting on dialysis for a transplant. This benefit is afforded to all patient subgroups including the elderly (> or =70 yr), and diabetics, who can gain 11 yr of extra life with transplantation. Prolonged transplant wait times result in a higher risk of death but this can be ameliorated with preemptive transplantation. Future challenges will focus on appropriate organ allocation and addressing long-term renal function and comorbid conditions so patients can enjoy the full benefits of transplantation.

  14. Acetylcholinesterase inhibition ameliorates deficits in motivational drive

    Directory of Open Access Journals (Sweden)

    Martinowich Keri

    2012-03-01

    Full Text Available Abstract Background Apathy is frequently observed in numerous neurological disorders, including Alzheimer's and Parkinson's, as well as neuropsychiatric disorders including schizophrenia. Apathy is defined as a lack of motivation characterized by diminished goal-oriented behavior and self-initiated activity. This study evaluated a chronic restraint stress (CRS protocol in modeling apathetic behavior, and determined whether administration of an anticholinesterase had utility in attenuating CRS-induced phenotypes. Methods We assessed behavior as well as regional neuronal activity patterns using FosB immunohistochemistry after exposure to CRS for 6 h/d for a minimum of 21 d. Based on our FosB findings and recent clinical trials, we administered an anticholinesterase to evaluate attenuation of CRS-induced phenotypes. Results CRS resulted in behaviors that reflect motivational loss and diminished emotional responsiveness. CRS-exposed mice showed differences in FosB accumulation, including changes in the cholinergic basal forebrain system. Facilitating cholinergic signaling ameliorated CRS-induced deficits in initiation and motivational drive and rescued immediate early gene activation in the medial septum and nucleus accumbens. Conclusions Some CRS protocols may be useful for studying deficits in motivation and apathetic behavior. Amelioration of CRS-induced behaviors with an anticholinesterase supports a role for the cholinergic system in remediation of deficits in motivational drive.

  15. Probiotic Amelioration of Azotemia in 5/6th Nephrectomized Sprague-Dawley Rats

    Directory of Open Access Journals (Sweden)

    Natarajan Ranganathan

    2005-01-01

    Full Text Available The present study was to test the hypothesis that selected bacteria instilled into the gastrointestinal tract could help in converting nitrogenous wastes accumulated due to renal insufficiency into nontoxic compounds; thereby, ameliorating the biochemical imbalance. Herein we describe a prospective, blinded, placebo-controlled pilot study, using 5/6th nephrectomized Sprague Dawley rat as a chronic renal failure model. The study group consisted of 36 nephrectomized and 7 non-nephrectomized (control rats. After two-week nephrectomy stabilization, cohorts of six nephrectomized rats were fed casein-based diet plus one of the following regimens: (A Control, (B Placebo (casein-based diet without probiotics, (C Bacillus pasteurii, (D Sporolac®, (E Kibow cocktail, (F CHR Hansen Cocktail, and (G ECONORMTM. Subsequently, blood (retro-orbital and urine (collected for measurements of blood urea-nitrogen and creatinine respectively, body weight and bacterial counts (feces were obtained at regular intervals. The study end-points were to determine if any of the probiotic dietary supplements facilitated, (1 decreased blood concentrations of uremic toxins, (2 altered renal function, and (3 prolonged survival. After 16 weeks of treatment, regimens C and D significantly prolonged the life span of uremic rats, in addition to showing a reduction in blood urea-nitrogen levels, concluding that supplementation of probiotic formulation to uremic rats slows the progression of azotemia, which may correlate with prolonged life span of uremic rats. Derivative trials of probiotic treatment of larger animals and humans will further assess the potential role of probiotic formulations in delaying the onset and clinical severity of clinical illness at different stages of renal failure.

  16. Using megestrol acetate to ameliorate protein-energy wasting in chronic kidney disease.

    Science.gov (United States)

    Smith, Christine Skouberdis; Logomarsino, John V

    2016-03-01

    Various populations are affected by chronic kidney disease (CKD), and a low dose appetite stimulant megestrol acetate (MA) is sometimes recommended in patients with CKD to ameliorate protein-energy wasting (PEW). Patients with CKD are at greater risk of developing PEW since the progression of their disease can cause decreased nutrient intake, catabolic effects, systemic inflammation and metabolic changes. Providers can detect PEW in CKD by identifying low serum levels ≤3.8 g/dl of albumin, protein and energy intake increases from 27% to 42%. There are potential adverse effects of using MA in CKD. After reviewing the available literature, the benefits of using MA should be evaluated against the potential side effects. For further examination of MA's potential benefits, long-term, prospective, large clinical trials should be carried out. © 2015 European Dialysis and Transplant Nurses Association/European Renal Care Association.

  17. The clinical application of 99Tcm-DMSA renal cortical scintigraphy in children with urinary tract infection

    International Nuclear Information System (INIS)

    Zhao Ruifang; Zeng Jihua; Xu Hong; Ji Zhiying; Yuan Hong

    2002-01-01

    Objective: To study the value of 99 Tc m -dimercaptosuccinic acid (DMSA) renal cortical scintigraphy in distinguishing between upper urinary tract infection (UUTI) and lower UTI (LUTI), determining renal scarring, and following-up curative effect for UTI in children. Methods: The authors reviewed 252 results of 99 Tc m -DMSA renal cortical scintigraphy in children with UTIs during a period of the past five years. The age of the patients was from 1 month to 14 years. The ratio of males: females was 94:158. A standard 99 Tc m -DMSA renal cortical scintigraphic protocol was used. The studies were scored as normal (indicating LUTI) and abnormal (indicating acute pyelonephritis or renal scarring). And differential function of renal was calculated. Results: Of 252 children with UTI, 110 cases had normal images diagnosed as with LUTI. 142 cases had abnormal images, 116 cases were diagnosed as with acute pyelonephritis, 26 cases were diagnosed as with renal cortical scars. The differential function range of LUTI was 46%-54%. Of UUTIs, the differential function of single renal involved was less than 45%. Of 142 UUTIs, 17 cases repeatedly underwent renal cortical scan after therapy. 12 of 13 cases with acute pyelonephritis completely recovered normal or obviously ameliorated after 6 months, 1 cases did not show any change after 4 months. Four cases were found with renal scarring, and showed little change on repeated images for the following 6 months. conclusions: 99 Tc m -DMSA renal cortical scintigraphy is of valuable significance in distinguishing between upper and lower UTI, and in estimating renal scarring. The sequelae of renal infection can be monitored by renal cortical scan. A follow-up of 6 months may be recommended after therapy

  18. Renal imaging in paediatrics

    International Nuclear Information System (INIS)

    Porn, U.; Hahn, K.; Fischer, S.

    2003-01-01

    The most frequent renal diseases in paediatrics include urinary tract infections, hydronephrosis, kidney anomalies and reflux. The main reason for performing DMSA scintigraphy in paediatrics is the detection of cortical abnormalities related to urinary tract infection. Because the amount of tracer retained in the tubular cells is associated with the distribution of functioning renal parenchyma in the kidney, it is possible, to evaluate the split renal function. In comparison to ultrasound and intravenous urography the sensitivity in the detection of acute as well as chronic inflammatory changes is very high, however less specific. An indication for a renography in neonates and children is beside an estimation of the total renal function and the calculation of the split renal function, the assessment of renal drainage in patients with unclear dilatation of the collecting system in ultrasound. The analysis of the time activity curve provides, especially for follow-up studies, a reproducible method to assess the urinary outflow. The diuretic scintigraphy allows the detection of urinary obstruction. Subsequently it is possible to image the micturition phase to detect vesico-ureteric reflux (indirect MCU) after drainage of tracer from the renal pelvis. An reflux in the ureters or the pelvicalyceal system is visible on the scintigraphic images and can be confirmed by time activity curves. A more invasive technique is the direct isotope cystography with bladder catheterization. The present paper should give an overview about the role of nuclear medicine in paediatric urology. (orig.) [de

  19. Perioperative acute renal failure.

    LENUS (Irish Health Repository)

    Mahon, Padraig

    2012-02-03

    PURPOSE OF REVIEW: Recent biochemical evidence increasingly implicates inflammatory mechanisms as precipitants of acute renal failure. In this review, we detail some of these pathways together with potential new therapeutic targets. RECENT FINDINGS: Neutrophil gelatinase-associated lipocalin appears to be a sensitive, specific and reliable biomarker of renal injury, which may be predictive of renal outcome in the perioperative setting. For estimation of glomerular filtration rate, cystatin C is superior to creatinine. No drug is definitively effective at preventing postoperative renal failure. Clinical trials of fenoldopam and atrial natriuretic peptide are, at best, equivocal. As with pharmacological preconditioning of the heart, volatile anaesthetic agents appear to offer a protective effect to the subsequently ischaemic kidney. SUMMARY: Although a greatly improved understanding of the pathophysiology of acute renal failure has offered even more therapeutic targets, the maintenance of intravascular euvolaemia and perfusion pressure is most effective at preventing new postoperative acute renal failure. In the future, strategies targeting renal regeneration after injury will use bone marrow-derived stem cells and growth factors such as insulin-like growth factor-1.

  20. Nigella sativa oil Ameliorates ionizing Radiation induced cellular injury in Male Albino Rats

    International Nuclear Information System (INIS)

    Mohamed, E.T.; El-Kady, A.A.

    2013-01-01

    Nigella sativa (NS), commonly known as black seed, is a plant spices in which thymoquinone is the main active ingredient isolated from the black seeds. The seeds of Nigella sativa are used in herbal medicine all over the world for the treatment and prevention of a number of diseases. The aim of this study was focused on investigating the possible protective effect of NS against gamma radiation induced nephrotoxicity and inflammatory changes in male albino rats. Twenty four albino rats were divided into four equal groups as follows: control group, irradiated group (animals subjected to whole body gamma irradiation at a dose of 6 Gy), treated group (rats treated with 0.2 ml/kg, i.p., NS oil for 4 weeks), and treated irradiated group (animals treated with 0.2 mL/kg, i.p., NS oil for 4 weeks then exposed to whole body gamma irradiation at a dose of 6 Gy). The obtained results revealed that the administration of Nigella sativa oil to irradiated rats significantly ameliorated the changes induced in kidney antioxidant system; catalase and glutathione peroxidase activities as well as reduced glutathione concentration. Also, NS oil restored the kidney function indices (urea and creatinine) near normal level when compared with their equivalent values in irradiated rats. In addition, the changes in serum tumor necrosis factor alpha (TNF-α), Interleukin-1β (IL-1β) and Interleukin-6 (IL-6) activities were markedly improved compared to the corresponding values of irradiated group. The histopathological results showed distinctive pattern of ischemic renal injury in irradiated group, while in treated- irradiated group the renal tissues showed relatively well-preserved architecture with or without focal degeneration. In conclusion, NS acts in the kidney as a potent scavenger of free radicals to prevent or ameliorates the toxic effects of gamma irradiation as shown in the biochemical and histopathological study and also NS oil might provide substantial protection against

  1. Cadmium and renal cancer

    International Nuclear Information System (INIS)

    Il'yasova, Dora; Schwartz, Gary G.

    2005-01-01

    Background: Rates of renal cancer have increased steadily during the past two decades, and these increases are not explicable solely by advances in imaging modalities. Cadmium, a widespread environmental pollutant, is a carcinogen that accumulates in the kidney cortex and is a cause of end-stage renal disease. Several observations suggest that cadmium may be a cause of renal cancer. Methods: We performed a systematic review of the literature on cadmium and renal cancer using MEDLINE for the years 1966-2003. We reviewed seven epidemiological and eleven clinical studies. Results: Despite different methodologies, three large epidemiologic studies indicate that occupational exposure to cadmium is associated with increased risk renal cancer, with odds ratios varying from 1.2 to 5.0. Six of seven studies that compared the cadmium content of kidneys from patients with kidney cancer to that of patients without kidney cancer found lower concentrations of cadmium in renal cancer tissues. Conclusions: Exposure to cadmium appears to be associated with renal cancer, although this conclusion is tempered by the inability of studies to assess cumulative cadmium exposure from all sources including smoking and diet. The paradoxical findings of lower cadmium content in kidney tissues from patients with renal cancer may be caused by dilution of cadmium in rapidly dividing cells. This and other methodological problems limit the interpretation of studies of cadmium in clinical samples. Whether cadmium is a cause of renal cancer may be answered more definitively by future studies that employ biomarkers of cadmium exposure, such as cadmium levels in blood and urine

  2. The performance of maize crop during acid amelioration with ...

    African Journals Online (AJOL)

    Tanzania Journal of Science ... This study evaluated acid ameliorative potential and their effects on maize growth of four organic residues namely wild spikenard, cordia, cowpea and pigeon peas ... The finding suggests different acid ameliorating potential of residues, pigeon peas and cordia being the most effective.

  3. Renal Branch Artery Stenosis

    DEFF Research Database (Denmark)

    Andersson, Zarah; Thisted, Ebbe; Andersen, Ulrik Bjørn

    2017-01-01

    Renovascular hypertension is a common cause of pediatric hypertension. In the fraction of cases that are unrelated to syndromes such as neurofibromatosis, patients with a solitary stenosis on a branch of the renal artery are common and can be diagnostically challenging. Imaging techniques...... that perform well in the diagnosis of main renal artery stenosis may fall short when it comes to branch artery stenosis. We report 2 cases that illustrate these difficulties and show that a branch artery stenosis may be overlooked even by the gold standard method, renal angiography....

  4. Cryoablation of Renal Angiomyolipoma

    DEFF Research Database (Denmark)

    Makki, Ahmad; Graumann, Ole; Hoyer, Soren

    2017-01-01

    BACKGROUND: Small series have reported that cryoablation (CA) is a safe and feasible minimally invasive nephron-sparing alternative for the treatment of renal angiomyolipomas (renal AMLs). The aim of the present study was to investigate the safety and efficacy of CA in patients with renal AML......-guided CA. The mean patient age was 46 years [interquartile range (IQR) 30] and the mean tumor volume was 50.1 cm(3) (IQR 53.3). In all cases, the procedure was effectively conducted with no conversion to open surgery, and no major complications were experienced. The mean follow-up time was 25 months (IQR...

  5. Endothelin-like action of Pausinystalia yohimbe aqueous extract on vascular and renal regional hemodynamics in Sprague Dawley rats.

    Science.gov (United States)

    Ajayi, A A; Newaz, M; Hercule, H; Saleh, M; Bode, C O; Oyekan, A O

    2003-12-01

    The bark of the African tree Pausinystalia yohimbe has been used as a food additive with aphrodisiac and penile erection enhancing properties. The effect of an aqueous extract of P. yohimbe (CCD-X) on renal circulation was assessed in order to test the hypothesis that it possesses additional effects on nitric oxide production and/or endothelin-1 (ET-1)-like actions. In vivo studies with CCD-X in Sprague Dawley rats demonstrated a dose-dependent (1-1000 ng/kg) increase in mean blood pressure (p < 0.001) and an increase in medullary blood flow (MBF) (p < 0.001). Both the pressor action and renal medullary vasodilation were blocked by endothelinA (ETA) receptor antagonist BMS182874 and endothelinB (ETB) receptor antagonist BQ788 in combination. L-Nomega-nitro-l-arginine methyl ester (L-NAME; 10 mg/kg) also inhibited the increase in MBF induced by CCD-X. In vitro studies in isolated perfused kidney and in pressurized renal microvessels confirmed the dose-dependent vasoconstrictor action of this extract. ETA receptor antagonist BQ610 and ETB receptor antagonist BQ788 separately and significantly attenuated the renal vasoconstrictor actions of the extract (p < 0.001 ANOVA). These preliminary observations indicate that, in addition to the alpha-adrenergic antagonist actions that characterize yohimbine, CCD-X possesses endothelin-like actions and affects nitric oxide (NO) production in renal circulation. These findings suggest a strong possibility of post-receptor cross-talk between alpha2-adrenoceptors and endothelin, as well as a direct effect of alpha2-adrenoceptors on renal NO production. (c) 2003 Prous Science

  6. Antagonistic properties of microogranisms associated with cassava ...

    African Journals Online (AJOL)

    The antagonistic properties of indigenous microflora from cassava starch, flour and grated cassava were investigated using the conventional streak, novel ring and well diffusion methods. Antagonism was measured by zone of inhibition between the fungal plug and bacterial streak/ring. Bacillus species were more effective ...

  7. Carbon adaptation influence the antagonistic ability of ...

    African Journals Online (AJOL)

    Influences of carbon adaptation on antagonistic activities of three Pseudomonas aeruginosa strains V4, V7 and V10 against Fusarium oxysporum f. sp. melonis were determined in this study. Results from this study showed that the P. aeruginosa strains and their adapted strains significantly inhibited the growth of mycelium ...

  8. Small molecule antagonists of integrin receptors.

    Science.gov (United States)

    Perdih, A; Dolenc, M Sollner

    2010-01-01

    The complex and widespread family of integrin receptors is involved in numerous physiological processes, such as tissue remodeling, angiogenesis, development of the immune response and homeostasis. In addition, their key role has been elucidated in important pathological disorders such as cancer, cardiovascular diseases, osteoporosis, autoimmune and inflammatory diseases and in the pathogenesis of infectious diseases, making them highly important targets for modern drug design campaigns. In this review we seek to present a concise overview of the small molecule antagonists of this diverse and highly complex receptor family. Integrin antagonists are classified according to the targeted integrin receptor and are discussed in four sections. First we present the fibrinogen alpha(IIb)beta3 and the vitronectin alpha (V)beta(3) receptor antagonists. The remaining selective integrin antagonists are examined in the third section. The final section is dedicated to molecules with dual or multiple integrin activity. In addition, the use of antibodies and peptidomimetic approaches to modulate the integrin receptors are discussed, as well providing the reader with an overall appreciation of the field.

  9. Acute renal failure in children

    International Nuclear Information System (INIS)

    Vergesslich, K.A.; Balzar, E.; Weninger, M.; Ponhold, W.; Sommer, G.; Wittich, G.R.; Vienna Univ.

    1987-01-01

    Acute renal failure (ARF) may be due to obstructive uropathy or renal parenchymal disease. Twenty-five children with acute renal failure secondary to renal parenchymal disease underwent ultrasonographic examination of the kidneys. Changes of renal size and cortical echogenicity were correlated with renal function. All patients presented with bilaterally enlarged kidneys with the exception in renal function resulted in normalization of renal size. With regard to cortical echogenicity two groups were formed. Group A comprised 11 patients whose kidneys had the same echogenicity as the liver, while in group B the kidneys were more echogenic (14 patients). Cortical echogenicity was always increased. Determination of creatinine levels showed a statistically significant difference between group A (3.32 mg% ± 1.40 S.D.) and group B (5.95 mg% ± 1.96 S.D.), p < 0.001. Changes in renal function were paralleled by rapid changes in renal size and cortical echogenicity. (orig.)

  10. Use of Coffee Pulp and Minerals for Natural Soil Ameliorant

    Directory of Open Access Journals (Sweden)

    Pujiyanto Pujiyanto

    2007-05-01

    Full Text Available In coffee plantation, solid waste of coffee pulp is usually collected as heap nearby processing facilities for several months prior being used as compost. The practice is leading to the formation of odor and liquid which contaminate the environment. Experiments to evaluate the effect of natural soil ameliorant derived from coffee pulp and minerals were conducted at The Indonesian Coffee and Cocoa Research Institute in Jember, East Java. The experiments were intended to optimize the use of coffee pulp to support farming sustainability and minimize negative impacts of solid waste disposal originated from coffee cherry processing. Prior to applications, coffee pulp was hulled to organic paste. The paste was then mixed with 10% minerals (b/b. Composition of the minerals was 50% zeolite and 50% rock phosphate powder. The ameliorant was characterized for their physical and chemical properties. Agronomic tests were conducted on coffee and cocoa seedling. The experiments were arranged according to Randomized Completely Design with 2 factors, consisted of natural ameliorant and inorganic fertilizer respectively. Natural ameliorant derived from coffee pulp was applied at 6 levels: 0, 30, 60, 90, 120 and 150 g dry ameliorant/seedling of 3 kg soil, equivalent to 0, 1, 2, 3, 4 and 5% (b/b of ameliorant respectively. Inorganic fertilizer was applied at 2 levels: 0 and 2 g fertilizer/application of N-P-K compound fertilizer of 15-15-15 respectively. The inorganic fertilizer was applied 4 times during nursery of coffee and cocoa. The result of the experiment indicated that coffee pulp may be used as natural soil ameliorant. Composition of ameliorant of 90% coffee pulp and 10% of minerals has good physical and chemical characteristics for soil amelioration. The composition has high water holding capacity; cations exchange capacity, organic carbon and phosphorus contents which are favorable to increase soil capacity to support plant growth. Application of

  11. 2-Methoxyestradiol Reduces Angiotensin II-Induced Hypertension and Renal Dysfunction in Ovariectomized Female and Intact Male Mice.

    Science.gov (United States)

    Pingili, Ajeeth K; Davidge, Karen N; Thirunavukkarasu, Shyamala; Khan, Nayaab S; Katsurada, Akemi; Majid, Dewan S A; Gonzalez, Frank J; Navar, L Gabriel; Malik, Kafait U

    2017-06-01

    Cytochrome P450 1B1 protects against angiotensin II (Ang II)-induced hypertension and associated cardiovascular changes in female mice, most likely via production of 2-methoxyestradiol. This study was conducted to determine whether 2-methoxyestradiol ameliorates Ang II-induced hypertension, renal dysfunction, and end-organ damage in intact Cyp1b1 -/- , ovariectomized female, and Cyp1b1 +/+ male mice. Ang II or vehicle was infused for 2 weeks and administered concurrently with 2-methoxyestradiol. Mice were placed in metabolic cages on day 12 of Ang II infusion for urine collection for 24 hours. 2-Methoxyestradiol reduced Ang II-induced increases in systolic blood pressure, water consumption, urine output, and proteinuria in intact female Cyp1b1 -/- and ovariectomized mice. 2-Methoxyestradiol also reduced Ang II-induced increase in blood pressure, water intake, urine output, and proteinuria in Cyp1b1 +/+ male mice. Treatment with 2-methoxyestradiol attenuated Ang II-induced end-organ damage in intact Cyp1b1 -/- and ovariectomized Cyp1b1 +/+ and Cyp1b1 -/- female mice and Cyp1b1 +/+ male mice. 2-Methoxyestradiol mitigated Ang II-induced increase in urinary excretion of angiotensinogen in intact Cyp1b1 -/- and ovariectomized Cyp1b1 +/+ and Cyp1b1 -/- female mice but not in Cyp1b1 +/+ male mice. The G protein-coupled estrogen receptor 1 antagonist G-15 failed to alter Ang II-induced increases in blood pressure and renal function in Cyp1b1 +/+ female mice. These data suggest that 2-methoxyestradiol reduces Ang II-induced hypertension and associated end-organ damage in intact Cyp1b1 -/- , ovariectomized Cyp1b1 +/+ and Cyp1b1 -/- female mice, and Cyp1b1 +/+ male mice independent of G protein-coupled estrogen receptor 1. Therefore, 2-methoxyestradiol could serve as a therapeutic agent for treating hypertension and associated pathogenesis in postmenopausal females, and in males. © 2017 American Heart Association, Inc.

  12. Renal tumors in infancy

    International Nuclear Information System (INIS)

    Lucaya, J.; Garcia, P.

    1997-01-01

    The classification of childhood renal masses in updated, including the clinical signs and imaging techniques currently employed to confirm their presence and type them. Several bening and malignant childhood tumors are described in substantial detail. (Author) 24 refs

  13. Renal cell carcinoma

    Science.gov (United States)

    ... kidney Patient Instructions Kidney removal - discharge Images Kidney anatomy Kidney tumor - CT scan Kidney metastases, CT scan Kidney - blood and urine flow References Campbell SC, Lane BR. Malignant renal tumors. In: Wein AJ, Kavoussi LR, Partin AW, ...

  14. Primary renal synovial sarcoma

    Directory of Open Access Journals (Sweden)

    Girish D. Bakhshi

    2012-03-01

    Full Text Available Primary Renal Sarcoma is rare tumor comprising only 1% of all renal tumours. Synovial sarcomas are generally deep-seated tumors arising in the proximity of large joints of adolescents and young adults and account for 5-10% of all soft tissue tumours. Primary synovial sarcoma of kidney is rare and has poor prognosis. It can only be diagnosed by immunohistochemistry. It should be considered as a differential in sarcomatoid and spindle cell tumours. We present a case of 33-year-old female, who underwent left sided radical nephrectomy for renal tumour. Histopathology and genetic analysis diagnosed it to be primary renal synovial sarcoma. Patient underwent radiation therapy and 2 years follow up is uneventful. A brief case report with review of literature is presented.

  15. [Small renal mass].

    Science.gov (United States)

    Prokofiev, D; Kreutzer, N; Kress, A; Wissing, F; Pfeifer, H; Stolzenburg, J-U; Dietel, A; Schwalenberg, T; Do, M; Truß, M C

    2012-10-01

    The frequent application of ultrasound and radiological imaging for non-urological indications in recent years has resulted in an increase in the diagnosis of small renal masses. The treatment options for patients with a small renal mass include active surveillance, surgery (both open and minimally invasive) as well as ablative techniques. As there is a risk for metastatic spread even in small renal masses surgical extirpation remains the treatment of choice in most patients. Ablative procedures, such as cryoablation and radiofrequency ablation are appropriate for old and multi-morbid patients who require active treatment of a small renal mass. Active surveillance is an alternative for high-risk patients. Meticulous patient selection by the urologist and patient preference will determine the choice of treatment option in the future.

  16. Common paediatric renal conditions

    African Journals Online (AJOL)

    Few children in South Africa have access to dialysis or renal transplantation, so it is important to .... the chronic administration of antibiotics increases the risk of a UTI with a resistant .... factors for recurrent urinary tract infection in young women.

  17. Renal and perirenal abscesses

    International Nuclear Information System (INIS)

    Patterson, J.E.; Andriole, V.T.

    1987-01-01

    Our knowledge of the spectrum of renal abscesses has increased as a result of more sensitive radiologic techniques. The classification of intrarenal abscess now includes acute focal bacterial nephritis and acute multifocal bacterial nephritis, as well as the previously recognized renal cortical abscess, renal corticomedullary abscess, and xanthogranulomatous pyelonephritis. In general, the clinical presentation of these entities does not differentiate them; various radiographic studies can distinguish them, however. The intrarenal abscess is usually treated successfully with antibiotic therapy alone. Antistaphylococcal therapy is indicated for the renal cortical abscess, whereas therapy directed against the common gram-negative uropathogens is indicated for most of the other entities. The perinephric abscess is often an elusive diagnosis, has a more serious prognosis, and is more difficult to treat. Drainage of the abscess and sometimes partial or complete nephrectomy are required for resolution. 73 references

  18. Lithium and Renal Impairment

    DEFF Research Database (Denmark)

    Nielsen, René Ernst; Kessing, Lars Vedel; Nolen, Willem A

    2018-01-01

    INTRODUCTION: Lithium is established as an effective treatment of mania, of depression in bipolar and unipolar disorder, and in maintenance treatment of these disorders. However, due to the necessity of monitoring and concerns about irreversible adverse effects, in particular renal impairment......, after long-term use, lithium might be underutilized. METHODS: This study reviewed 6 large observational studies addressing the risk of impaired renal function associated with lithium treatment and methodological issues impacting interpretation of results. RESULTS: An increased risk of renal impairment...... associated with lithium treatment is suggested. This increased risk may, at least partly, be a result of surveillance bias. Additionally, the earliest studies pointed toward an increased risk of end-stage renal disease associated with lithium treatment, whereas the later and methodologically most sound...

  19. Renal dynamic scintigraphy in renal graft evaluation; Cintilografia renal dinamica na avaliacao do transplante renal

    Energy Technology Data Exchange (ETDEWEB)

    Cervo, Marco Antonio Cadorna; Amarante Junior, Jose Luiz de Medeiros; Souza, Ricardo Alberto Manhaes de; Evangelista, Maria Gardenia; Cavalcante, Carlos Alberto Provasi; Neder, Jacqueline de Roure e; Espinola, Ircania Jorge [Hospital Naval Marcilio Dias, Rio de Janeiro, RJ (Brazil). Servico de Medicina Nuclear

    1996-12-31

    The goal of this was to describe the use of the dynamic renal scintigraphy in patients grafted. The authors described the scintigraphy method utilised and results were discussed 8 refs., 9 figs., 1 tab.

  20. OBSTETRIC RENAL FAILURE

    Directory of Open Access Journals (Sweden)

    Rajeshwari

    2015-11-01

    Full Text Available Renal failure in obstetrics is rare but important complication, associated with significant mortality and long term morbidity.1,2 It includes acute renal failure due to obstetrical complications or due to deterioration of existing renal disease. AIMS AND OBJECTIVES: To evaluate the etiology and outcome of renal failure in obstetric patients. METHODS: We prospectively analyzed 30 pregnant and puerperal women with acute renal failure or pre-existing renal disease developing renal failure during pregnancy between November 2007 to sep-2009. Patients who presented/developed ARF during the hospital stay were included in this study. RESULTS: Among 30 patients, mean age was 23 years and 33 years age group. 12 cases (40% patients were primigravidae and 9(30% patients were multigravidae and 9 cases (30% presented in post-partum period. Eighteen cases (60% with ARF were seen in third trimester, followed by in postpartum period 9 cases (30%. Most common contributing factors to ARF were Pre-eclampsia, eclampsia and HELLP syndrome 60%, sepsis 56.6%, post abortal ARF 10%. DIC 40%. Haemorrhage as the aetiology for ARF was present 46%, APH in 20% and PPH in 26.6%. The type of ARF was renal in (63% and prerenal (36%; Oliguric seen in 10 patients (33% and high mortality (30%. Among the 20 pregnant patients with ARF, The average period of gestation was 33±2 weeks (30 -36 weeks, 5 cases (25% presented with intrauterine fetal demise and 18 cases (66% had preterm vaginal delivery and 2 cases (10% had induced abortion. And the average birth weight was 2±0.5 kg (1.5 kg. Eight cases (26% required dialysis. 80% of patients recovered completely of renal functions. 63% patients recovered without renal replacement therapy whereas 17% required dialysis. the maternal mortality was 20%, the main reason for mortality was septic shock and multi organ dysfunction (66%. CONCLUSION: ARF related pregnancy was seen commonly in the primigravidae and in the third trimester, the most

  1. Berberine ameliorates chronic kidney injury caused by atherosclerotic renovascular disease through the suppression of NFκB signaling pathway in rats.

    Directory of Open Access Journals (Sweden)

    Xin Wan

    Full Text Available BACKGROUND AND OBJECTIVES: Impaired renal function in atherosclerotic renovascular disease (ARD may be the result of crosstalk between atherosclerotic renovascular stenosis and amplified oxidative stress, inflammation and fibrosis. Berberine (BBR regulates cholesterol metabolism and exerts antioxidant effects. Accordingly, we hypothesized that BBR treatment may ameliorate ARD-induced kidney injury through its cholesterol-lowering effect and also suppression of the pathways involved in oxidative stress, inflammation and NFκB activation. METHODS: Male rats were subjected to unilateral renal artery stenosis with silver-irritant coil, and then fed with 12-week hypercholesterolemic diet. Rats with renal artery stenosis were randomly assigned to two groups (n = 6 each - ARD, or ARD+BBR - according to diet alone or in combination with BBR. Similarly, age-matched rats underwent sham operation and were also fed with hypercholesterolemic diet alone or in combination with BBR as two corresponding controls. Single-kidney hemodynamic metrics were measured in vivo with Doppler ultrasound to determine renal artery flow. The metrics reflecting hyperlipidemia, oxidative stress, renal structure and function, inflammation and NFκB activation were measured, respectively. RESULTS: Compared with control rats, ARD rats had a significant increase in urinary albumin, plasma cholesterol, LDL and thiobarbituric acid reactive substances (TBARS and a significant decrease in SOD activity. When exposed to 12-week BBR, ARD rats had significantly lower levels in blood pressure, LDL, urinary albumin, and TBARS. In addition, there were significantly lower expression levels of iNOS and TGF-β in the ARD+BBR group than in the ARD group, with attenuated NFκB-DNA binding activity and down-regulated protein levels of subunits p65 and p50 as well as IKKβ. CONCLUSIONS: We conclude that BBR can improve hypercholesterolemia and redox status in the kidney, eventually ameliorating

  2. antagonistic effect of native bacillus isolates against black root rot

    African Journals Online (AJOL)

    ACSS

    A number of fungi and bacteria are known to be very effective .... Round. Convex. Smooth. Wrinkled. Slow. BS024. Irregular and spreading. Flat. Wavy .... Antibiotic effect of bacterial antagonist ..... antagonistic Bacillus and Trichoderma isolates ...

  3. Renal artery pseudoaneurysm

    Directory of Open Access Journals (Sweden)

    Luiz Inácio Roman

    Full Text Available Abstract The renal artery pseudoaneurysm embody a rare vascular complication coming of percutaneous procedures, renal biopsy, nephrectomy, penetrating traumas and more rarely blunt traumas. The clinical can be vary according the patient, the haematuria is the symptom more commom. Is necessary a high level of clinical suspicion for your diagnosis, this can be elucidated by through complementary exams as the eco-color Doppler and the computed tomography scan (CT. This report is a case of a patient submitted a right percutaneous renal biopsy and that, after the procedure started with macroscopic haematuria, urinary tenesmus and hypogastric pain. The diagnosis of pseudoaneurysm was given after one week of evolution when the patient was hospitalized because gross haematuria, tachycardia, hypotension and hypochondrium pain. In the angiotomography revealed a focal dilation of the accessory right renal inferior polar artery, dilation of renal pelvis and all the ureteral course with presence hyperdenso material (clots inside the middle third of the ureter. The treatment for the majority of this cases are conservative, through arterial embolization, indicated for thouse of smaller dimensions in patients who are hemodynamically stable. However, it was decided by clinical treatment with aminocaproic acid 1 g, according to previous studies for therapy of haematuria. The patient received discharge without evidence of macroscopic haematuria and with normal renal ultrasound, following ambulatory care.

  4. Tangshen Formula Attenuates Diabetic Nephropathy by Promoting ABCA1-Mediated Renal Cholesterol Efflux in db/db Mice.

    Science.gov (United States)

    Liu, Peng; Peng, Liang; Zhang, Haojun; Tang, Patrick Ming-Kuen; Zhao, Tingting; Yan, Meihua; Zhao, Hailing; Huang, Xiaoru; Lan, Huiyao; Li, Ping

    2018-01-01

    The commonly prescribed Tangshen Formula (TSF) is a traditional Chinese formulation that has been shown to reduce plasma lipid metabolism and proteinuria and improve the estimated glomerular filtration rate (eGFR) in patients with diabetic kidney disease. This study investigated the underlying mechanism whereby TSF regulates renal lipid accumulation and ameliorates diabetic renal injuries in spontaneous diabetic db/db mice and in vitro in sodium palmitate (PA)-stimulated and Abca1-SiRNA-transfected mouse tubular epithelial cells (mTECs). The results revealed that TSF treatment significantly ameliorated the renal injuries by lowering urinary albumin excretion and improving renal tissue injuries in diabetic (db/db) mice. Interestingly, the treatment with TSF also resulted in decreased cholesterol levels in the renal tissues of db/db mice, which was associated with increased expression of the peroxisome proliferator-activated receptor γ coactivator 1-α (PGC-1α), the Liver X receptors (LXR), and ATP-binding cassette subfamily A member 1 (ABCA1), suggesting that TSF might attenuate diabetic kidney injury via a mechanism associated with improving cholesterol efflux in the diabetic kidney. This was investigated in vitro in mTECs, and the results showed that TSF reduced the PA-stimulated cholesterol accumulation in mTECs. Mechanistically, the addition of TSF was capable of reversing PA-induced downregulation of PGC-1α, LXR, and ABCA1 expression and cholesterol accumulation in mTECs, suggesting that TSF might act the protection via the PGC-1α-LXR-ABCA1 pathway to improve the cholesterol efflux in the renal tissues of db/db mice. This was further confirmed by silencing ABCA1 to block the promotive effect of TSF on cholesterol efflux in vitro . In conclusion, TSF might ameliorate diabetic kidney injuries by promoting ABCA1-mediated renal cholesterol efflux.

  5. RENAL MALIGNANT NEOPLASMS: RENAL CELL CARCINOMA

    Directory of Open Access Journals (Sweden)

    Elisangela Giachini

    2017-06-01

    Full Text Available The aim of this study is to evaluate the incidence and prevalence of malignant kidney tumors, to contribute to identifying factors which the diagnosis of renal cell carcinomas. Through this study, we understand that kidney disease over the years had higher incidence rates, especially in adults in the sixth decade of life. The renal cell carcinoma (RCC is the third most common malignancy of the genitourinary tract, affecting 2% to 3% of the population. There are numerous ways of diagnosis; however, the most important are ultrasonography, magnetic resonance imaging and computed tomography. In general most of the patients affected by the CCR, have a good prognosis when diagnosed early and subjected to an effective treatment. This study conducted a literature review about the CCR, through this it was possible to understand the development needs of the imaging methods used for precise diagnosis and classification of RCC through the TNM system.

  6. The lymphotoxin β receptor is a potential therapeutic target in renal inflammation.

    Science.gov (United States)

    Seleznik, Gitta; Seeger, Harald; Bauer, Judith; Fu, Kai; Czerkowicz, Julie; Papandile, Adrian; Poreci, Uriana; Rabah, Dania; Ranger, Ann; Cohen, Clemens D; Lindenmeyer, Maja; Chen, Jin; Edenhofer, Ilka; Anders, Hans J; Lech, Maciej; Wüthrich, Rudolf P; Ruddle, Nancy H; Moeller, Marcus J; Kozakowski, Nicolas; Regele, Heinz; Browning, Jeffrey L; Heikenwalder, Mathias; Segerer, Stephan

    2016-01-01

    Accumulation of inflammatory cells in different renal compartments is a hallmark of progressive kidney diseases including glomerulonephritis (GN). Lymphotoxin β receptor (LTβR) signaling is crucial for the formation of lymphoid tissue, and inhibition of LTβR signaling has ameliorated several non-renal inflammatory models. Therefore, we tested whether LTβR signaling could also have a role in renal injury. Renal biopsies from patients with GN were found to express both LTα and LTβ ligands, as well as LTβR. The LTβR protein and mRNA were localized to tubular epithelial cells, parietal epithelial cells, crescents, and cells of the glomerular tuft, whereas LTβ was found on lymphocytes and tubular epithelial cells. Human tubular epithelial cells, mesangial cells, and mouse parietal epithelial cells expressed both LTα and LTβ mRNA upon stimulation with TNF in vitro. Several chemokine mRNAs and proteins were expressed in response to LTβR signaling. Importantly, in a murine lupus model, LTβR blockade improved renal function without the reduction of serum autoantibody titers or glomerular immune complex deposition. Thus, a preclinical mouse model and human studies strongly suggest that LTβR signaling is involved in renal injury and may be a suitable therapeutic target in renal diseases. Copyright © 2015 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

  7. Pegvisomant: a growth hormone receptor antagonist used in the treatment of acromegaly.

    Science.gov (United States)

    Tritos, Nicholas A; Biller, Beverly M K

    2017-02-01

    To review published data on pegvisomant and its therapeutic role in acromegaly. Electronic searches of the published literature were conducted using the keywords: acromegaly, growth hormone (GH) receptor (antagonist), pegvisomant, therapy. Relevant articles (n = 141) were retrieved and considered for inclusion in this manuscript. Pegvisomant is a genetically engineered, recombinant growth hormone receptor antagonist, which is effective in normalizing serum insulin-like growth factor 1 (IGF-1) levels in the majority of patients with acromegaly and ameliorating symptoms and signs associated with GH excess. Pegvisomant does not have direct antiproliferative effects on the underlying somatotroph pituitary adenoma, which is the etiology of GH excess in the vast majority of patients with acromegaly. Therefore, patients receiving pegvisomant monotherapy require regular pituitary imaging in order to monitor for possible increase in tumor size. Adverse events in patients on pegvisomant therapy include skin rashes, lipohypertrophy at injection sites, and idiosyncratic liver toxicity (generally asymptomatic transaminitis that is reversible upon drug discontinuation), thus necessitating regular patient monitoring. Pegvisomant is an effective therapeutic agent in patients with acromegaly who are not in remission after undergoing pituitary surgery. It mitigates excess GH action, as demonstrated by IGF-1 normalization, but has no direct effects on pituitary tumors causing acromegaly. Regular surveillance for possible tumor growth and adverse effects (hepatotoxicity, skin manifestations) is warranted.

  8. Cordyceps cicadae extracts ameliorate renal malfunction in a remnant kidney model*

    OpenAIRE

    Zhu, Rong; Chen, Yi-ping; Deng, Yue-yi; Zheng, Rong; Zhong, Yi-fei; Wang, Lin; Du, Lan-ping

    2011-01-01

    Background and Objectives: Chronic kidney disease (CKD) is a growing public health problem with an urgent need for new pharmacological agents. Cordyceps cicadae is widely used in traditional Chinese medicine (TCM) and has potential renoprotective benefits. The current study aimed to determine any scientific evidence to support its clinical use. Methods: We analyzed the potential of two kinds of C. cicadae extract, total extract (TE) and acetic ether extract (AE), in treating kidney disease si...

  9. Bmi-1 plays a critical role in protection from renal tubulointerstitial injury by maintaining redox balance

    Science.gov (United States)

    Jin, Jianliang; Lv, Xianhui; Chen, Lulu; Zhang, Wei; Li, Jinbo; Wang, Qian; Wang, Rong; Lu, Xiang; Miao, Dengshun

    2014-01-01

    To determine whether Bmi-1 deficiency could lead to renal tubulointerstitial injury by mitochondrial dysfunction and increased oxidative stress in the kidney, 3-week-old Bmi-1-/- mice were treated with the antioxidant N-acetylcysteine (NAC, 1 mg mL−1) in their drinking water, or pyrro-quinoline quinone (PQQ, 4 mg kg−1 diet) in their diet for 2 weeks, and their renal phenotypes were compared with vehicle-treated Bmi1-/- and wild-type mice. Bmi-1 was knocked down in human renal proximal tubular epithelial (HK2) cells which were treated with 1 mm NAC for 72 or 96 h, and their phenotypes were compared with control cells. Five-week-old vehicle-treated Bmi-1-/- mice displayed renal interstitial fibrosis, tubular atrophy, and severe renal function impairment with decreased renal cell proliferation, increased renal cell apoptosis and senescence, and inflammatory cell infiltration. Impaired mitochondrial structure, decreased mitochondrial numbers, and increased oxidative stress occurred in Bmi-1-/- mice; subsequently, this caused DNA damage, the activation of TGF-β1/Smad signaling, and the imbalance between extracellular matrix synthesis and degradation. Oxidative stress-induced epithelial-to-mesenchymal transition of renal tubular epithelial cells was enhanced in Bmi-1 knocked down HK2 cells. All phenotypic alterations caused by Bmi-1 deficiency were ameliorated by antioxidant treatment. These findings indicate that Bmi-1 plays a critical role in protection from renal tubulointerstitial injury by maintaining redox balance and will be a novel therapeutic target for preventing renal tubulointerstitial injury. PMID:24915841

  10. Interactions of CB1 and mGlu5 receptor antagonists in food intake, anxiety and memory models in rats.

    Science.gov (United States)

    Varga, Balázs; Kassai, Ferenc; Gyertyán, István

    2012-12-01

    CB(1) receptor antagonists proved to be effective anti-obesity drugs, however, their depressive and anxiogenic effects became also evident. Finding solution to overcome these psychiatric side effects is still in focus of research. Based on the available clinical and preclinical results we hypothesized that the combination of CB(1) and mGlu(5) receptor antagonisms may result in a pharmacological intervention, where the anxiolytic mGlu(5) receptor inhibition may counteract the anxiogenic psychiatric side effects of CB(1) antagonism, while CB(1) antagonism may ameliorate the memory impairing effect of mGlu(5) receptor antagonism. Further, the two components will synergistically interact in blocking food-intake and reducing obesity. For testing the interaction of mGlu(5) and CB(1) receptor antagonism MTEP [3-[(2-methyl-1,3-thiazol-4-yl)ethynyl]pridine; SIB-1757, 6-methyl-2-(phenylazo)-3-pyridinol)] (mGlu(5) antagonist) and rimonabant [(5-(4-Chlorophenyl)-1-(2,4-dichloro-phenyl)-4-methyl-N-(piperidin-1-yl)-1H-pyrazole-3-carboxamide)hydrochloride] (CB(1) antagonist) were used. All experiments were carried out in rats. Effects of the compounds on anxiety were tested in two foot shock induced ultrasonic vocalization paradigms, appetite suppression was assessed in the food intake test, while memory effects were tested in a context conditioned ultrasonic vocalization setup. MTEP abolished the anxiogenic effect of rimonabant, while there was an additive cooperation in suppressing appetite. However, rimonabant did not ameliorate the memory impairing effect of MTEP. By combination of CB(1) and mGluR5 antagonism, anxiety related side effects might be attenuated, appetite suppression maintained, nevertheless, the possible emergence of unwanted memory impairments can overshadow its therapeutic success. Copyright © 2012 Elsevier Inc. All rights reserved.

  11. Nicotinic cholinergic antagonists: a novel approach for the treatment of autism.

    Science.gov (United States)

    Lippiello, P M

    2006-01-01

    Evidence supports the hypothesis that normalization of cholinergic tone by selective antagonism of neuronal nicotinic acetylcholine receptors (NNRs) may ameliorate the core symptoms of autism. As often is the case, epidemiology has provided the first important clues. It is well recognized that psychiatric patients are significantly more often smokers than the general population. The only known exceptions are obsessive-compulsive disorder (OCD), catatonic schizophrenia and interestingly, autism. In this regard, clinical studies with nicotine have demonstrated amelioration of symptoms of a number of diseases and disorders, including Alzheimer's disease, Parkinson's disease, ADHD and Tourette's syndrome. Nicotine's agonist properties at CNS NNRs have been implicated in these effects and support the concept of self-medication as a strong motivation for smoking in cognitively compromised individuals. On the other hand, the inverse correlation between autism and smoking suggests that smoking does not provide symptomatic relief and may actually be indicative of an active avoidance of nicotine's agonist effects in this disorder. Neuroanatomical evidence is consistent with this idea based on the presence of hypercholinergic architecture in the autistic brain, particularly during the first few years of development, making the avoidance of further stimulation of an already hyperactive cholinergic system plausible. This may also explain why stimulants (known to increase dopamine levels as do NNR agonists) appear to aggravate autistic symptoms and why studies with cholinesterase inhibitors that increase acetylcholine levels in the brain have yielded variable effects in autism. Taken together, the evidence suggests the possibility that nicotinic cholinergic antagonism may in fact be palliative. Pharmacological evidence supports this hypothesis. For example, antidepressants, many of which are now known to be non-competitive NNR antagonists, have been used successfully to treat a

  12. Renal PTA stenting

    International Nuclear Information System (INIS)

    Tsetis, D.

    2012-01-01

    Full text: Renal artery stenosis (RAS) is a common condition that may lead to hypertension, progressive renal dysfunction and cardiovascular morbidity. Catheter-based therapy for symptomatic, haemodynamically significant, RAS has become the preferred method of revascularization. Balloon angioplasty has been the traditional treatment of choice for fibromuscular dysplasia, however stents are increasingly used for the treatment of atheromatous lesions; in many cases-such as in ostial lesions-, direct stenting is strongly indicated. Despite the increased use of endovascular therapy for renal artery stenosis, there is still controversy regarding the optimal management and the net benefit of this treatment. Several randomized trials of balloon angioplasty or stenting for renal artery stenosis compared with medical therapy alone have been conducted, however these could not show definite advantage of endovascular therapy. Problems encountered with those trials include enrollment of small number of patients, frequent crossover from medical to interventional therapy compromising the intention-to-treat results, or selection of patients that are not expected to show clear benefit. The Angioplasty and Stenting for Renal Artery Lesions (ASTRAL) is the most important of these trials; however, it,s study design was faulty and therefore did not provide conclusive evidence to answer the question of whether angioplasty and stenting or medical therapy is the best treatment for haemodynamically significant RAS. All expectations are now focused on the Cardiovascular Outcomes in Renal Atherosclerotic Lesions (CORAL) trial which was designed to answer the same question, and its methodologies took into consideration the weaknesses of the ASTRAL trial. Regarding stent device itself, it seems that the optimal design is probably a stainless steel, laser cut, open-cells stent mounted on a rapid exchange delivery balloon catheter compatible with 0.014-in and 0.018-in guidewire. As a future

  13. Antagonistic parent-offspring co-adaptation.

    Directory of Open Access Journals (Sweden)

    Mathias Kölliker

    2010-01-01

    Full Text Available In species across taxa, offspring have means to influence parental investment (PI. PI thus evolves as an interacting phenotype and indirect genetic effects may strongly affect the co-evolutionary dynamics of offspring and parental behaviors. Evolutionary theory focused on explaining how exaggerated offspring solicitation can be understood as resolution of parent-offspring conflict, but the evolutionary origin and diversification of different forms of family interactions remains unclear.In contrast to previous theory that largely uses a static approach to predict how "offspring individuals" and "parental individuals" should interact given conflict over PI, we present a dynamic theoretical framework of antagonistic selection on the PI individuals obtain/take as offspring and the PI they provide as parents to maximize individual lifetime reproductive success; we analyze a deterministic and a stochastic version of this dynamic framework. We show that a zone for equivalent co-adaptation outcomes exists in which stable levels of PI can evolve and be maintained despite fast strategy transitions and ongoing co-evolutionary dynamics. Under antagonistic co-adaptation, cost-free solicitation can evolve as an adaptation to emerging preferences in parents.We show that antagonistic selection across the offspring and parental life-stage of individuals favors co-adapted offspring and parental behavior within a zone of equivalent outcomes. This antagonistic parent-offspring co-adaptation does not require solicitation to be costly, allows for rapid divergence and evolutionary novelty and potentially explains the origin and diversification of the observed provisioning forms in family life.

  14. Enhancement of Cisplatin Nephrotoxicity by Morphine and Its Attenuation by the Opioid Antagonist Naltrexone

    Directory of Open Access Journals (Sweden)

    Atefeh Aminian

    2016-07-01

    Full Text Available Nephrotoxicity is a major side effect of cisplatin, a widely used chemotherapy agent. Morphine and other opioids are also used extensively in different types of cancer for the clinical management of pain associated with local or metastatic neoplastic lesions. In addition to its analgesic effects, morphine has also been reported to possess potential immunomodulatory and antioxidant properties. Herein, we investigated the effects of morphine in a rat model of cisplatin-induced nephrotoxicity. Following administration of a single dose of cisplatin (5 mg/kg, animals received intraperitoneal injections of morphine (5 mg/kg/day and/or naltrexone (20 mg/kg/day, an opioid antagonist, for 5 days. Cisplatin-induced nephrotoxicity was detected by a significant increase in plasma urea and creatinine levels in addition to alterations in kidney tissue morphology. Levels of TNF-α and IL-1β were significantly increased in the renal tissue in cisplatin group. Moreover, glutathione (GSH concentration and superoxide dismutase activity were significantly reduced in renal tissue in cisplatin group compared with control animals. Treatment with morphine aggravated the deleterious effects of cisplatin at clinical, biochemical and histopathological levels; whereas naltrexone diminished the detrimental effects of morphine in animals receiving morphine and cisplatin. Morphine or naltrexone alone had no effect on the mentioned parameters. Our findings indicate that concomitant treatment with morphine might intensify cisplatin-induced renal damage in rats. These findings suggest that morphine and other opioids should be administered cautiously in patients receiving cisplatin chemotherapy.

  15. Medicinal Chemistry of Competitive Kainate Receptor Antagonists

    Science.gov (United States)

    2010-01-01

    Kainic acid (KA) receptors belong to the group of ionotropic glutamate receptors and are expressed throughout in the central nervous system (CNS). The KA receptors have been shown to be involved in neurophysiological functions such as mossy fiber long-term potentiation (LTP) and synaptic plasticity and are thus potential therapeutic targets in CNS diseases such as schizophrenia, major depression, neuropathic pain and epilepsy. Extensive effort has been made to develop subtype-selective KA receptor antagonists in order to elucidate the physiological function of each of the five subunits known (GluK1−5). However, to date only selective antagonists for the GluK1 subunit have been discovered, which underlines the strong need for continued research in this area. The present review describes the structure−activity relationship and pharmacological profile for 10 chemically distinct classes of KA receptor antagonists comprising, in all, 45 compounds. To the medicinal chemist this information will serve as reference guidance as well as an inspiration for future effort in this field. PMID:22778857

  16. Pharmacological analysis of calcium antagonist receptors

    International Nuclear Information System (INIS)

    Reynolds, I.J.

    1987-01-01

    This work focuses on two aspects of the action of calcium antagonist drugs, namely, the interaction of drugs with receptors for verapamil-like calcium antagonists, and the interactions of drugs with voltage-sensitive calcium fluxes in rat brain synaptosomes. From binding studies I have found that the ligand of choice for labeling the verapamil receptor is (-)[ 3 H]desmethoxy-verapamil. This drug labels potently, reversibly and stereoselectively two receptors in membranes prepared from rat brain and rabbit skeletal muscle tissues. In equilibrium studies dihydropyridine calcium antagonists interact in a non-competitive fashion, while many non-DHPs are apparently competitive. In-depth kinetic studies in skeletal muscle membranes indicate that the two receptors are linked in a negative heterotropic fashion, and that low-affinity binding of (-) [ 3 H]desmethoxy-verapamil may be to the diltiazem receptor. However, these studies were not able to distinguish between the hypothesis that diltiazem binds to spatially separate, allosterically coupled receptors, and the hypothesis that diltiazem binds to a subsite of the verapamil receptor

  17. Bardoxolone methyl (BARD) ameliorates aristolochic acid (AA)-induced acute kidney injury through Nrf2 pathway.

    Science.gov (United States)

    Wu, Juan; Liu, Xinhui; Fan, Jinjin; Chen, Wenfang; Wang, Juan; Zeng, Youjia; Feng, Xiaorang; Yu, Xueqing; Yang, Xiao

    2014-04-06

    Bardoxolone methyl (BARD) is an antioxidant modulator that acts through induction of the nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway. This study aimed to investigate the role of BARD in protecting kidneys from aristolochic acid (AA)-induced acute kidney injury (AKI). Male C57BL/6 mice received intraperitoneal (i.p.) injections of aristolochic acid I (AAI) (5mg/kg/day) for 5 days to produce acute AA nephropathy (AAN) model. BARD (10mg/kg/day, i.p.) was applied for 7 consecutive days, starting 2 days prior to AAI administration. The mice in the AA group showed AKI as evidenced by worsening kidney function evaluated by blood urea nitrogen (BUN) and serum creatinine (SCr) levels, and severe tubulointerstitial injury marked by massive tubule necrosis in kidney tissues. BARD significantly reduced BUN and SCr levels which were elevated by AAI. Additionally, AAI-induced histopathological renal damage was ameliorated by BARD. Furthermore, the expression of Nrf2 was reduced, and its repressor Kelch-like ECH-associated protein 1 (Keap1) was increased significantly, whereas heme oxygenase-1 (HO-1) was upregulated and NAD(P)H quinone oxidoreductase-1 (NQO1) was barely increased in the cytoplasm of tubules in kidneys after treatment with AAI. BARD significantly upregulated renal Nrf2, NQO1 and HO-1 expression and downregulated Keap1 expression compared with those in the AA group. Moreover, it was found that Nrf2 was expressed both in the cytoplasm and nuclear of glomeruli and tubules, whereas NQO1 and HO-1 were localized in the cytoplasm of tubules only. In conclusion, AA-induced acute renal injury was associated with impaired Nrf2 activation and expression of its downstream target genes in renal tissues. BARD prevented renal damage induced by AAI, and this renoprotective effect may be exerted by activating the Nrf2 signaling pathway and increasing expression of the downstream target genes. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  18. Distal renal tubular acidosis in recurrent renal stone formers

    DEFF Research Database (Denmark)

    Osther, P J; Hansen, A B; Røhl, H F

    1989-01-01

    Renal acidification ability was examined in 90 recurrent renal stone formers, using fasting morning urinary pH levels followed by a short ammonium chloride loading test in subjects with pH levels above 6.0. Fifteen patients (16.6%) revealed a distal renal tubular acidification defect: one patient......, this has important therapeutic implications. The pathological sequence in renal stone formers with dRTA is discussed....

  19. Renal sympathetic denervation: MDCT evaluation of the renal arteries.

    LENUS (Irish Health Repository)

    Hutchinson, Barry D

    2013-08-01

    Percutaneous transluminal renal sympathetic denervation is a new treatment of refractory systemic hypertension. The purpose of this study was to assess the clinical utility of MDCT to evaluate the anatomic configuration of the renal arteries in the context of renal sympathetic denervation.

  20. Imaging chronic renal disease and renal transplant in children

    International Nuclear Information System (INIS)

    Carmichael, Jim; Easty, Marina

    2010-01-01

    At Great Ormond Street Hospital we have the highest number of paediatric renal transplant patients in Europe, taking cases from across the United Kingdom and abroad. Our caseload includes many children with rare complicating medical problems and chronic renal failure related morbidity. This review aims to provide an overview of our experience of imaging children with chronic renal failure and transplants. (orig.)

  1. Triiodothyronine regulates cell growth and survival in renal cell cancer.

    Science.gov (United States)

    Czarnecka, Anna M; Matak, Damian; Szymanski, Lukasz; Czarnecka, Karolina H; Lewicki, Slawomir; Zdanowski, Robert; Brzezianska-Lasota, Ewa; Szczylik, Cezary

    2016-10-01

    Triiodothyronine plays an important role in the regulation of kidney cell growth, differentiation and metabolism. Patients with renal cell cancer who develop hypothyreosis during tyrosine kinase inhibitor (TKI) treatment have statistically longer survival. In this study, we developed cell based model of triiodothyronine (T3) analysis in RCC and we show the different effects of T3 on renal cell cancer (RCC) cell growth response and expression of the thyroid hormone receptor in human renal cell cancer cell lines from primary and metastatic tumors along with human kidney cancer stem cells. Wild-type thyroid hormone receptor is ubiquitously expressed in human renal cancer cell lines, but normalized against healthy renal proximal tube cell expression its level is upregulated in Caki-2, RCC6, SKRC-42, SKRC-45 cell lines. On the contrary the mRNA level in the 769-P, ACHN, HKCSC, and HEK293 cells is significantly decreased. The TRβ protein was abundant in the cytoplasm of the 786-O, Caki-2, RCC6, and SKRC-45 cells and in the nucleus of SKRC-42, ACHN, 769-P and cancer stem cells. T3 has promoting effect on the cell proliferation of HKCSC, Caki-2, ASE, ACHN, SK-RC-42, SMKT-R2, Caki-1, 786-0, and SK-RC-45 cells. Tyrosine kinase inhibitor, sunitinib, directly inhibits proliferation of RCC cells, while thyroid hormone receptor antagonist 1-850 (CAS 251310‑57-3) has less significant inhibitory impact. T3 stimulation does not abrogate inhibitory effect of sunitinib. Renal cancer tumor cells hypostimulated with T3 may be more responsive to tyrosine kinase inhibition. Moreover, some tumors may be considered as T3-independent and present aggressive phenotype with thyroid hormone receptor activated independently from the ligand. On the contrary proliferation induced by deregulated VHL and or c-Met pathways may transgress normal T3 mediated regulation of the cell cycle.

  2. Bacterial mediated amelioration of drought stress in drought tolerant ...

    African Journals Online (AJOL)

    Bacterial mediated amelioration of drought stress in drought tolerant and susceptible cultivars of rice ( Oryza sativa L.) ... and IR-64 (drought sensitive) cultivars of rice (Oryza sativa L.) under different level of drought stress. ... from 32 Countries:.

  3. Improvement for Amelioration Inventory Model with Weibull Distribution

    Directory of Open Access Journals (Sweden)

    Han-Wen Tuan

    2017-01-01

    Full Text Available Most inventory models dealt with deteriorated items. On the contrary, just a few papers considered inventory systems under amelioration environment. We study an amelioration inventory model with Weibull distribution. However, there are some questionable results in the amelioration paper. We will first point out those questionable results in the previous paper that did not derive the optimal solution and then provide some improvements. We will provide a rigorous analytical work for different cases dependent on the size of the shape parameter. We present a detailed numerical example for different ranges of the sharp parameter to illustrate that our solution method attains the optimal solution. We developed a new amelioration model and then provided a detailed analyzed procedure to find the optimal solution. Our findings will help researchers develop their new inventory models.

  4. Eligibility for renal denervation

    DEFF Research Database (Denmark)

    Persu, Alexandre; Jin, Yu; Baelen, Marie

    2014-01-01

    -resistant hypertension (ENCOReD). The analysis included 731 patients. Age averaged 61.6 years, office blood pressure at screening was 177/96 mm Hg, and the number of blood pressure-lowering drugs taken was 4.1. Specialists referred 75.6% of patients. The proportion of patients eligible for renal denervation according...... undetected secondary causes of hypertension (11.1%). In conclusion, after careful screening and treatment adjustment at hypertension expert centers, only ≈40% of patients referred for renal denervation, mostly by specialists, were eligible for the procedure. The most frequent cause of ineligibility...... (approximately half of cases) was blood pressure normalization after treatment adjustment by a hypertension specialist. Our findings highlight that hypertension centers with a record in clinical experience and research should remain the gatekeepers before renal denervation is considered....

  5. [Renal colic in pregnancy].

    Science.gov (United States)

    Negru, Irina; Pricop, C; Costăchescu, Gh

    2010-01-01

    Renal colic in pregnant women is a serious condition, mainly when is associated with fever. Our retro-prospective study analyzes 111 cases managed conservatively or with endourological procedures for renal colic--insertion of JJ stents and percutaneous nephrostomy. Clinical evolution determined the insertion of JJ stents in 60 cases and the failure of this procedure imposed percutaneous nephrostomy in 5 cases. In 56 cases urinary tract infection was associated and in 2 cases, despite all efforts, the patients deceased due to sever sepsis. The immediate drainage of the upper urinary tract for renal colic in pregnancy is the recommended treatment, especially when the pain is associated with fever. JJ stens were well tolerated, even when they were replaced after 3 months. Pregnant women with a history of UTI or stone disease should be carefully followed-up.

  6. Renal cell karcinoma trial

    International Nuclear Information System (INIS)

    Werf-Messing, B. van der; Heul, R.O. van der; Ledeboer, R.C.

    1981-01-01

    A total of 174 patients underwent simple nephrectomy in case of clinically operable kidney cancer without demonstrable metastases. Of these 85 received preoperative irradiation to the kidney and the regional lymph nodes (3000-4000 rad in 3-4 weeks). Prognosis was not influenced by preoperative irradiation. The preoperatively assessable prognostic criteria were sex and sedimentation rate: ESR >= 30 and being male worsened prognosis. The clinical T-categories of the UICC were not related to prognosis. Of the microscopic examination of the nephrectomy specimen, renal vein invasion and to a lesser extent a low degree of differentiation appeared to worsen prognosis. The prognostic influence of the P-categories was caused by a higher incidence of renal vein involvement in case of higher P-category. The most important prognostic factors - ESR, renal vein involvement, and sex - were not interrelated. Elective chemotherapy, radiation therapy, and hormone therapy could be considered in certain high-risk groups. (orig.)

  7. Scintigraphy of renal transplant

    International Nuclear Information System (INIS)

    Ramackers, J.M.; Marrast, A.C.; Touraine, J.L.; Peyrin, J.O.

    1995-01-01

    Scintigraphy is useful for monitoring perfusion and function of renal transplant, as well as for diagnosing miscellaneous surgical. This non-invasive imaging technique, which uses no deleterious products, is an attractive alternative for patients. This is especially true for those patients in early post-transplant course, with immunity depression and often impairment of renal function. Otherwise, multiple indices with a large range of inter-patient values has not favoured a methodological and interpretative consensus. Furthermore, the poor specificity of renogram patterns does not allow for discrimination of all etiologies with only one scintigraphy. Nevertheless, follow-up with iterative scintigraphy may be helpful due to the high intra-patient reproducibility and to the early appreciate change of parameters, according to clinical and histological renal post-transplant outcome. (authors). 43 refs., 8 figs

  8. Drug-induced renal injury

    African Journals Online (AJOL)

    The kidney receives a rich blood flow of 25% of resting cardiac output ... Drugs can cause acute renal failure by causing pre-renal, intrinsic or .... tubular epithelial cells causing cell swelling ... the dose as required or prescribe alternative drugs.

  9. Leiomyosarcoma of the renal pelvis

    Directory of Open Access Journals (Sweden)

    Dhamne Sagar

    2009-10-01

    Full Text Available Leiomyosarcomas are rare malignant tumors of the kidney. They may arise from the renal capsule, renal vein, renal pelvic musculature or renal parenchyma. Renal pelvis is an uncommon site of occurrence, with around 10 cases reported in the literature so far. Here we present a 60-year-old male who presented with increased urinary frequency, lower limb weakness, anorexia and weight loss. Imaging showed a right renal mass. A renal cell carcinoma was suspected clinically. A right nephrectomy was performed, which showed a large circumscribed mass in the hilar region. Histology revealed a tumor mass arising from the renal pelvis. The tumor was composed of spindle cells arranged in fascicles. Immunohistochemistry showed tumor cells to be positive for smooth muscle actin (SMA and desmin (Des and negative for cytokeratin (CK, HMB 45, CD117 (C-kit, and CD34. That confirmed the diagnosis of leiomyosarcoma.

  10. Riboflavin ameliorates cisplatin induced toxicities under photoillumination.

    Directory of Open Access Journals (Sweden)

    Iftekhar Hassan

    Full Text Available BACKGROUND: Cisplatin is an effective anticancer drug that elicits many side effects mainly due to induction of oxidative and nitrosative stresses during prolonged chemotherapy. The severity of these side effects consequently restricts its clinical use under long term treatment. Riboflavin is an essential vitamin used in various metabolic redox reactions in the form of flavin adenine dinucleotide and flavin mononucleotide. Besides, it has excellent photosensitizing property that can be used to ameliorate these toxicities in mice under photodynamic therapy. METHODS AND FINDINGS: Riboflavin, cisplatin and their combinations were given to the separate groups of mice under photoilluminated condition under specific treatment regime. Their kidney and liver were excised for comet assay and histopathological studies. Furthermore, Fourier Transform Infrared Spectroscopy of riboflavin-cisplatin combination in vitro was also conducted to investigate any possible interaction between the two compounds. Their comet assay and histopathological examination revealed that riboflavin in combination with cisplatin was able to protect the tissues from cisplatin induced toxicities and damages. Moreover, Fourier Transform Infrared Spectroscopy analysis of the combination indicated a strong molecular interaction among their constituent groups that may be assigned for the protective effect of the combination in the treated animals. CONCLUSION: Inclusion of riboflavin diminishes cisplatin induced toxicities which may possibly make the cisplatin-riboflavin combination, an effective treatment strategy under chemoradiotherapy in pronouncing its antineoplastic activity and sensitivity towards the cancer cells as compared to cisplatin alone.

  11. Renal denervation and hypertension.

    Science.gov (United States)

    Schlaich, Markus P; Krum, Henry; Sobotka, Paul A; Esler, Murray D

    2011-06-01

    Essential hypertension remains one of the biggest challenges in medicine with an enormous impact on both individual and society levels. With the exception of relatively rare monogenetic forms of hypertension, there is now general agreement that the condition is multifactorial in nature and hence requires therapeutic approaches targeting several aspects of the underlying pathophysiology. Accordingly, all major guidelines promote a combination of lifestyle interventions and combination pharmacotherapy to reach target blood pressure (BP) levels in order to reduce overall cardiovascular risk in affected patients. Although this approach works for many, it fails in a considerable number of patients for various reasons including drug-intolerance, noncompliance, physician inertia, and others, leaving them at unacceptably high cardiovascular risk. The quest for additional therapeutic approaches to safely and effectively manage hypertension continues and expands to the reappraisal of older concepts such as renal denervation. Based on the robust preclinical and clinical data surrounding the role of renal sympathetic nerves in various aspects of BP control very recent efforts have led to the development of a novel catheter-based approach using radiofrequency (RF) energy to selectively target and disrupt the renal nerves. The available evidence from the limited number of uncontrolled hypertensive patients in whom renal denervation has been performed are auspicious and indicate that the procedure has a favorable safety profile and is associated with a substantial and presumably sustained BP reduction. Although promising, a myriad of questions are far from being conclusively answered and require our concerted research efforts to explore the full potential and possible risks of this approach. Here we briefly review the science surrounding renal denervation, summarize the current data on safety and efficacy of renal nerve ablation, and discuss some of the open questions that need

  12. Brain-derived neurotrophic factor ameliorates brain stem cardiovascular dysregulation during experimental temporal lobe status epilepticus.

    Directory of Open Access Journals (Sweden)

    Ching-Yi Tsai

    Full Text Available BACKGROUND: Status epilepticus (SE is an acute, prolonged epileptic crisis with a mortality rate of 20-30%; the underlying mechanism is not completely understood. We assessed the hypothesis that brain stem cardiovascular dysregulation occurs during SE because of oxidative stress in rostral ventrolateral medulla (RVLM, a key nucleus of the baroreflex loop; to be ameliorated by brain-derived neurotrophic factor (BDNF via an antioxidant action. METHODOLOGY/PRINCIPAL FINDINGS: In a clinically relevant experimental model of temporal lobe SE (TLSE using Sprague-Dawley rats, sustained hippocampal seizure activity was accompanied by progressive hypotension that was preceded by a reduction in baroreflex-mediated sympathetic vasomotor tone; heart rate and baroreflex-mediated cardiac responses remained unaltered. Biochemical experiments further showed concurrent augmentation of superoxide anion, phosphorylated p47(phox subunit of NADPH oxidase and mRNA or protein levels of BDNF, tropomyosin receptor kinase B (TrkB, angiotensin AT1 receptor subtype (AT1R, nitric oxide synthase II (NOS II or peroxynitrite in RVLM. Whereas pretreatment by microinjection bilaterally into RVLM of a superoxide dismutase mimetic (tempol, a specific antagonist of NADPH oxidase (apocynin or an AT1R antagonist (losartan blunted significantly the augmented superoxide anion or phosphorylated p47(phox subunit in RVLM, hypotension and the reduced baroreflex-mediated sympathetic vasomotor tone during experimental TLSE, pretreatment with a recombinant human TrkB-Fc fusion protein or an antisense bdnf oligonucleotide significantly potentiated all those events, alongside peroxynitrite. However, none of the pretreatments affected the insignificant changes in heart rate and baroreflex-mediated cardiac responses. CONCLUSIONS/SIGNIFICANCE: We conclude that formation of peroxynitrite by a reaction between superoxide anion generated by NADPH oxidase in RVLM on activation by AT1R and NOS II

  13. Effects of taurine and housing density on renal function in laying hens.

    Science.gov (United States)

    Ma, Zi-Li; Gao, Yang; Ma, Hai-Tian; Zheng, Liu-Hai; Dai, Bin; Miao, Jin-Feng; Zhang, Yuan-Shu

    This study investigated the putative protective effects of supplemental 2-aminoethane sulfonic acid (taurine) and reduced housing density on renal function in laying hens. We randomly assigned fifteen thousand green-shell laying hens into three groups: a free range group, a low-density caged group, and a high-density caged group. Each group was further divided equally into a control group (C) and a taurine treatment group (T). After 15 d, we analyzed histological changes in kidney cells, inflammatory mediator levels, oxidation and anti-oxidation levels. Experimental data revealed taurine supplementation, and rearing free range or in low-density housing can lessen morphological renal damage, inflammatory mediator levels, and oxidation levels and increase anti-oxidation levels. Our data demonstrate that taurine supplementation and a reduction in housing density can ameliorate renal impairment, increase productivity, enhance health, and promote welfare in laying hens.

  14. A Role for Cytosolic Fumarate Hydratase in Urea Cycle Metabolism and Renal Neoplasia

    Directory of Open Access Journals (Sweden)

    Julie Adam

    2013-05-01

    Full Text Available The identification of mutated metabolic enzymes in hereditary cancer syndromes has established a direct link between metabolic dysregulation and cancer. Mutations in the Krebs cycle enzyme, fumarate hydratase (FH, predispose affected individuals to leiomyomas, renal cysts, and cancers, though the respective pathogenic roles of mitochondrial and cytosolic FH isoforms remain undefined. On the basis of comprehensive metabolomic analyses, we demonstrate that FH1-deficient cells and tissues exhibit defects in the urea cycle/arginine metabolism. Remarkably, transgenic re-expression of cytosolic FH ameliorated both renal cyst development and urea cycle defects associated with renal-specific FH1 deletion in mice. Furthermore, acute arginine depletion significantly reduced the viability of FH1-deficient cells in comparison to controls. Our findings highlight the importance of extramitochondrial metabolic pathways in FH-associated oncogenesis and the urea cycle/arginine metabolism as a potential therapeutic target.

  15. Imaging of Renal Leiomyomas

    Energy Technology Data Exchange (ETDEWEB)

    Derchi, L. E.; Grenier, N.; Heinz-Peer, G.; Dogra, V.; Franco, F.; Rollandi, G. A.; Deminiere, C. (Radiologia - DICMI, Univ. di Genova, Genova (Italy))

    2008-09-15

    Background: Renal leiomyomas are rare benign tumors of the kidney which can be found at autopsy as small capsular nodules in about 5% of cases. The clinical incidence of such lesions is much smaller, and only case reports or small series have been reported in the imaging literature. Purpose: To describe the imaging characteristics observed in a series of eight patients with pathology-proven asymptomatic leiomyomas of the kidney. Material and Methods: We reviewed the imaging findings observed in eight patients with pathologically proven asymptomatic renal leiomyomas discovered during studies performed for reasons unrelated to the kidney. All patients had undergone computed tomography (CT), two ultrasonography, and one magnetic resonance imaging (MRI). Results: Lesions ranged in size from 1.2 to 13 cm. Six were at the periphery of the kidney, compressed its outer surface, but did not cause disruption of the cortex; two involved the renal cortex. All had regular outer margins. A cleavage plane between the tumor and the kidney was revealed at CT and/or ultrasonography in three of the cases located at the periphery. At ultrasonography, leiomyomas appeared hypoechogenic. At CT, they were slightly hyperdense before contrast medium injection; all were hypodense to the renal cortex after contrast medium. Four were homogeneous, two were slightly heterogeneous, and the remaining two were frankly heterogeneous. The lesion studied by MRI, which was homogeneous at the postcontrast CT study, had a heterogeneous structure on both T1- and T2-weighted images, with internal areas of hypointensity on T1. Conclusion: There are some imaging findings that can help to suggest the diagnosis of renal leiomyomas. First, their density: all tumors examined before contrast were hyperdense to the kidney, with density similar to that of muscles, and all had lower enhancement than the adjacent renal parenchyma. Second, the location and margins of the tumors: most were peripheral, without

  16. Renal lithiasis and nutrition

    Directory of Open Access Journals (Sweden)

    Prieto Rafel M

    2006-09-01

    Full Text Available Abstract Renal lithiasis is a multifactorial disease. An important number of etiologic factors can be adequately modified trough diet, since it must be considered that the urine composition is directly related to diet. In fact, the change of inappropriate habitual diet patterns should be the main measure to prevent kidney stones. In this paper, the relation between different dietary factors (liquid intake, pH, calcium, phosphate, oxalate, citrate, phytate, urate and vitamins and each type of renal stone (calcium oxalate monohydrate papillary, calcium oxalate monohydrate unattached, calcium oxalate dihydrate, calcium oxalate dihydrate/hydroxyapatite, hydroxyapatite, struvite infectious, brushite, uric acid, calcium oxalate/uric acid and cystine is discussed.

  17. Erythropoietin-enhanced endothelial progenitor cell recruitment in peripheral blood and renal vessels during experimental acute kidney injury in rats.

    Science.gov (United States)

    Cakiroglu, Figen; Enders-Comberg, Sora Maria; Pagel, Horst; Rohwedel, Jürgen; Lehnert, Hendrik; Kramer, Jan

    2016-03-01

    Beneficial effects of erythropoietin (EPO) have been reported in acute kidney injury (AKI) when administered prior to induction of AKI. We studied the effects of EPO administration on renal function shortly after ischemic AKI. For this purpose, rats were subjected to renal ischemia for 30 min and EPO was administered at a concentration of 500 U/kg either i.v. as a single shot directly after ischemia or with an additional i.p. dose until 3 days after surgery. The results were compared with AKI rats without EPO application and a sham-operated group. Renal function was assessed by measurement of serum biochemical markers, histological grading, and using an isolated perfused kidney (IPK) model. Furthermore, we performed flow cytometry to analyze the concentration of endothelial progenitor cells (EPCs) in the peripheral blood and renal vessels. Following EPO application, there was only a statistically non-significant tendency of serum creatinine and urea to improve, particularly after daily EPO application. Renal vascular resistance and the renal perfusion rate were not significantly altered. In the histological analysis, acute tubular necrosis was only marginally ameliorated following EPO administration. In summary, we could not demonstrate a significant improvement in renal function when EPO was applied after AKI. Interestingly, however, EPO treatment resulted in a highly significant increase in CD133- and CD34-positive EPC both in the peripheral blood and renal vessels. © 2015 International Federation for Cell Biology.

  18. Management of chronic renal failure.

    NARCIS (Netherlands)

    de Zeeuw, D.; Apperloo, AJ; de Jong, P.

    1992-01-01

    There is growing evidence that treatment of patients with renal function impairment will undergo a major shift within the next few years. Along with more or less successful attempts to alleviate the signs and symptoms of reduced renal function, new insights into renal pathophysiology as well as new

  19. Exogenous and endogenous angiotensin-II decrease renal cortical oxygen tension in conscious rats by limiting renal blood flow.

    Science.gov (United States)

    Emans, Tonja W; Janssen, Ben J; Pinkham, Maximilian I; Ow, Connie P C; Evans, Roger G; Joles, Jaap A; Malpas, Simon C; Krediet, C T Paul; Koeners, Maarten P

    2016-11-01

    Our understanding of the mechanisms underlying the role of hypoxia in the initiation and progression of renal disease remains rudimentary. We have developed a method that allows wireless measurement of renal tissue oxygen tension in unrestrained rats. This method provides stable and continuous measurements of cortical tissue oxygen tension (PO2) for more than 2 weeks and can reproducibly detect acute changes in cortical oxygenation. Exogenous angiotensin-II reduced renal cortical tissue PO2 more than equi-pressor doses of phenylephrine, probably because it reduced renal oxygen delivery more than did phenylephrine. Activation of the endogenous renin-angiotensin system in transgenic Cyp1a1Ren2 rats reduced cortical tissue PO2; in this model renal hypoxia precedes the development of structural pathology and can be reversed acutely by an angiotensin-II receptor type 1 antagonist. Angiotensin-II promotes renal hypoxia, which may in turn contribute to its pathological effects during development of chronic kidney disease. We hypothesised that both exogenous and endogenous angiotensin-II (AngII) can decrease the partial pressure of oxygen (PO2) in the renal cortex of unrestrained rats, which might in turn contribute to the progression of chronic kidney disease. Rats were instrumented with telemeters equipped with a carbon paste electrode for continuous measurement of renal cortical tissue PO2. The method reproducibly detected acute changes in cortical oxygenation induced by systemic hyperoxia and hypoxia. In conscious rats, renal cortical PO2 was dose-dependently reduced by intravenous AngII. Reductions in PO2 were significantly greater than those induced by equi-pressor doses of phenylephrine. In anaesthetised rats, renal oxygen consumption was not affected, and filtration fraction was increased only in the AngII infused animals. Oxygen delivery decreased by 50% after infusion of AngII and renal blood flow (RBF) fell by 3.3 ml min -1 . Equi-pressor infusion of

  20. Exogenous and endogenous angiotensin‐II decrease renal cortical oxygen tension in conscious rats by limiting renal blood flow

    Science.gov (United States)

    Emans, Tonja W.; Janssen, Ben J.; Pinkham, Maximilian I.; Ow, Connie P. C.; Evans, Roger G.; Joles, Jaap A.; Malpas, Simon C.; Krediet, C. T. Paul

    2016-01-01

    Key points Our understanding of the mechanisms underlying the role of hypoxia in the initiation and progression of renal disease remains rudimentary.We have developed a method that allows wireless measurement of renal tissue oxygen tension in unrestrained rats.This method provides stable and continuous measurements of cortical tissue oxygen tension (PO2) for more than 2 weeks and can reproducibly detect acute changes in cortical oxygenation.Exogenous angiotensin‐II reduced renal cortical tissue PO2 more than equi‐pressor doses of phenylephrine, probably because it reduced renal oxygen delivery more than did phenylephrine.Activation of the endogenous renin–angiotensin system in transgenic Cyp1a1Ren2 rats reduced cortical tissue PO2; in this model renal hypoxia precedes the development of structural pathology and can be reversed acutely by an angiotensin‐II receptor type 1 antagonist.Angiotensin‐II promotes renal hypoxia, which may in turn contribute to its pathological effects during development of chronic kidney disease. Abstract We hypothesised that both exogenous and endogenous angiotensin‐II (AngII) can decrease the partial pressure of oxygen (PO2) in the renal cortex of unrestrained rats, which might in turn contribute to the progression of chronic kidney disease. Rats were instrumented with telemeters equipped with a carbon paste electrode for continuous measurement of renal cortical tissue PO2. The method reproducibly detected acute changes in cortical oxygenation induced by systemic hyperoxia and hypoxia. In conscious rats, renal cortical PO2 was dose‐dependently reduced by intravenous AngII. Reductions in PO2 were significantly greater than those induced by equi‐pressor doses of phenylephrine. In anaesthetised rats, renal oxygen consumption was not affected, and filtration fraction was increased only in the AngII infused animals. Oxygen delivery decreased by 50% after infusion of AngII and renal blood flow (RBF) fell by 3.3 ml min−1

  1. Screening renal stone formers for distal renal tubular acidosis

    DEFF Research Database (Denmark)

    Osther, P J; Hansen, A B; Røhl, H F

    1989-01-01

    A group of 110 consecutive renal stone formers were screened for distal renal tubular acidosis (RTA) using morning fasting urinary pH (mfUpH) levels followed by a short ammonium chloride loading test in patients with levels above 6.0. In 14 patients (12.7%) a renal acidification defect was noted...... RTA in renal stone formers. Regardless of whether the acidification defect is primary or secondary to stone formation, however, all renal stone formers with distal RTA can expect to benefit from prophylactic alkaline therapy and it is recommended that the screening procedure, which is easy to use...

  2. Allopurinol attenuates rhabdomyolysis-associated acute kidney injury: Renal and muscular protection.

    Science.gov (United States)

    Gois, Pedro H F; Canale, Daniele; Volpini, Rildo A; Ferreira, Daniela; Veras, Mariana M; Andrade-Oliveira, Vinicius; Câmara, Niels O S; Shimizu, Maria H M; Seguro, Antonio C

    2016-12-01

    Acute kidney injury (AKI) is the most severe complication of rhabdomyolysis. Allopurinol (Allo), a xanthine oxidase inhibitor, has been in the spotlight in the last decade due to new therapeutic applications related to its potent antioxidant effect. The aim of this study was to evaluate the efficacy of Allo in the prevention and treatment of rhabdomyolysis-associated AKI. Male Wistar rats were divided into five groups: saline control group; prophylactic Allo (300mg/L of drinking water, 7 days); glycerol (50%, 5ml/kg, IM); prophylactic Allo + glycerol; and therapeutic Allo (50mg/Kg, IV, 30min after glycerol injection) + glycerol. Glycerol-injected rats showed markedly reduced glomerular filtration rate associated with renal vasoconstriction, renal tubular damage, increased oxidative stress, apoptosis and inflammation. Allo ameliorated all these alterations. We found 8-isoprostane-PGF 2a (F2-IsoP) as a main factor involved in the oxidative stress-mediated renal vasoconstriction following rhabdomyolysis. Allo reduced F2-IsoP renal expression and restored renal blood flow. Allo also reduced oxidative stress in the damaged muscle, attenuated muscle lesion/inflammation and accelerated muscular recovery. Moreover, we showed new insights into the pathogenesis of rhabdomyolysis-associated AKI, whereas Allo treatment reduced renal inflammation by decreasing renal tissue uric acid levels and consequently inhibiting the inflammasome cascade. Allo treatment attenuates renal dysfunction in a model of rhabdomyolysis-associated AKI by reducing oxidative stress (systemic, renal and muscular), apoptosis and inflammation. This may represent a new therapeutic approach for rhabdomyolysis-associated AKI - a new use for an old and widely available medication. Copyright © 2016 Elsevier Inc. All rights reserved.

  3. Mitochondrial autophagy involving renal injury and aging is modulated by caloric intake in aged rat kidneys.

    Science.gov (United States)

    Cui, Jing; Shi, Suozhu; Sun, Xuefeng; Cai, Guangyan; Cui, Shaoyuan; Hong, Quan; Chen, Xiangmei; Bai, Xue-Yuan

    2013-01-01

    A high-calorie (HC) diet induces renal injury and promotes aging, and calorie restriction (CR) may ameliorate these responses. However, the effects of long-term HC and CR on renal damage and aging have been not fully determined. Autophagy plays a crucial role in removing protein aggregates and damaged organelles to maintain intracellular homeostasis and function. The role of autophagy in HC-induced renal damage is unknown. We evaluated the expression of LC3/Atg8 as a marker of the autophagosome; p62/SQSTM1; polyubiquitin aggregates as markers of autophagy flux; Ambra1, PINK1, Parkin and Bnip3 as markers of mitophagy; 8-hydroxydeoxyguanosine (8-OHdG) as a marker of DNA oxidative damage; and p16 as a marker of organ aging by western blot and immunohistochemical staining in the kidneys of 24-month-old Fischer 344 rats. We also observed mitochondrial structure and autolysosomes by transmission electron microscopy. Expression of the autophagosome formation marker LC3/Atg8 and markers of mitochondrial autophagy (mitophagy) were markedly decreased in the kidneys of the HC group, and markedly increased in CR kidneys. p62/SQSTM1 and polyubiquitin aggregates increased in HC kidneys, and decreased in CR kidneys. Transmission electron microscopy demonstrated that HC kidneys showed severe abnormal mitochondrial morphology with fewer autolysosomes, while CR kidneys exhibited normal mitochondrial morphology with numerous autolysosomes. The level of 8-hydroxydeoxyguanosine was increased in HC kidneys and decreased in CR kidneys. Markers of aging, such as p16 and senescence-associated-galactosidase, were increased significantly in the HC group and decreased significantly in the CR group. The study firstly suggests that HC diet inhibits renal autophagy and aggravates renal oxidative damage and aging, while CR enhances renal autophagy and ameliorates oxidative damage and aging in the kidneys.

  4. Ischemic preconditioning provides both acute and delayed protection against renal ischemia and reperfusion injury in mice.

    Science.gov (United States)

    Joo, Jin Deok; Kim, Mihwa; D'Agati, Vivette D; Lee, H Thomas

    2006-11-01

    Acute as well as delayed ischemic preconditioning (IPC) provides protection against cardiac and neuronal ischemia reperfusion (IR) injury. This study determined whether delayed preconditioning occurs in the kidney and further elucidated the mechanisms of renal IPC in mice. Mice were subjected to IPC (four cycles of 5 min of ischemia and reperfusion) and then to 30 min of renal ischemia either 15 min (acute IPC) or 24 h (delayed IPC) later. Both acute and delayed renal IPC provided powerful protection against renal IR injury. Inhibition of Akt but not extracellular signal-regulated kinase phosphorylation prevented the protection that was afforded by acute IPC. Neither extracellular signal-regulated kinase nor Akt inhibition prevented protection that was afforded by delayed renal IPC. Pretreatment with an antioxidant, N-(2-mercaptopropionyl)-glycine, to scavenge free radicals prevented the protection that was provided by acute but not delayed renal IPC. Inhibition of protein kinase C or pertussis toxin-sensitive G-proteins attenuated protection from both acute and delayed renal IPC. Delayed renal IPC increased inducible nitric oxide synthase (iNOS) as well as heat-shock protein 27 synthesis, and the renal protective effects of delayed preconditioning were attenuated by a selective inhibitor of iNOS (l-N(6)[1-iminoethyl]lysine). Moreover, delayed IPC was not observed in iNOS knockout mice. Both acute and delayed IPC were independent of A(1) adenosine receptors (AR) as a selective A(1)AR antagonist failed to block preconditioning and acute and delayed preconditioning occurred in mice that lacked A(1)AR. Therefore, this study demonstrated that acute or delayed IPC provides renal protection against IR injury in mice but involves distinct signaling pathways.

  5. Suppression of Rapidly Progressive Mouse Glomerulonephritis with the Non-Steroidal Mineralocorticoid Receptor Antagonist BR-4628.

    Science.gov (United States)

    Ma, Frank Y; Han, Yingjie; Nikolic-Paterson, David J; Kolkhof, Peter; Tesch, Greg H

    2015-01-01

    Steroidal mineralocorticoid receptor antagonists (MRAs) are effective in the treatment of kidney disease; however, the side effect of hyperkalaemia, particularly in the context of renal impairment, is a major limitation to their clinical use. Recently developed non-steroidal MRAs have distinct characteristics suggesting that they may be superior to steroidal MRAs. Therefore, we explored the benefits of a non-steroidal MRA in a model of rapidly progressive glomerulonephritis. Accelerated anti-glomerular basement membrane (GBM) glomerulonephritis was induced in groups of C57BL/6J mice which received no treatment, vehicle or a non-steroidal MRA (BR-4628, 5mg/kg/bid) from day 0 until being killed on day 15 of disease. Mice were examined for renal injury. Mice with anti-GBM glomerulonephritis which received no treatment or vehicle developed similar disease with severe albuminuria, impaired renal function, glomerular tuft damage and crescents in 40% of glomeruli. In comparison, mice which received BR-4628 displayed similar albuminuria, but had improved renal function, reduced severity of glomerular tuft lesions and a 50% reduction in crescents. The protection seen in BR-4628 treated mice was associated with a marked reduction in glomerular macrophages and T-cells and reduced kidney gene expression of proinflammatory (CCL2, TNF-α, IFN-γ) and profibrotic molecules (collagen I, fibronectin). In addition, treatment with BR-4626 did not cause hyperkalaemia or increase urine Na+/K+ excretion (a marker of tubular dysfunction). The non-steroidal MRA (BR-4628) provided substantial suppression of mouse crescentic glomerulonephritis without causing tubular dysfunction. This finding warrants further investigation of non-steroidal MRAs as a therapy for inflammatory kidney diseases.

  6. Suppression of Rapidly Progressive Mouse Glomerulonephritis with the Non-Steroidal Mineralocorticoid Receptor Antagonist BR-4628.

    Directory of Open Access Journals (Sweden)

    Frank Y Ma

    Full Text Available Steroidal mineralocorticoid receptor antagonists (MRAs are effective in the treatment of kidney disease; however, the side effect of hyperkalaemia, particularly in the context of renal impairment, is a major limitation to their clinical use. Recently developed non-steroidal MRAs have distinct characteristics suggesting that they may be superior to steroidal MRAs. Therefore, we explored the benefits of a non-steroidal MRA in a model of rapidly progressive glomerulonephritis.Accelerated anti-glomerular basement membrane (GBM glomerulonephritis was induced in groups of C57BL/6J mice which received no treatment, vehicle or a non-steroidal MRA (BR-4628, 5mg/kg/bid from day 0 until being killed on day 15 of disease. Mice were examined for renal injury.Mice with anti-GBM glomerulonephritis which received no treatment or vehicle developed similar disease with severe albuminuria, impaired renal function, glomerular tuft damage and crescents in 40% of glomeruli. In comparison, mice which received BR-4628 displayed similar albuminuria, but had improved renal function, reduced severity of glomerular tuft lesions and a 50% reduction in crescents. The protection seen in BR-4628 treated mice was associated with a marked reduction in glomerular macrophages and T-cells and reduced kidney gene expression of proinflammatory (CCL2, TNF-α, IFN-γ and profibrotic molecules (collagen I, fibronectin. In addition, treatment with BR-4626 did not cause hyperkalaemia or increase urine Na+/K+ excretion (a marker of tubular dysfunction.The non-steroidal MRA (BR-4628 provided substantial suppression of mouse crescentic glomerulonephritis without causing tubular dysfunction. This finding warrants further investigation of non-steroidal MRAs as a therapy for inflammatory kidney diseases.

  7. Physical Exercise and Patients with Chronic Renal Failure: A Meta-Analysis.

    Science.gov (United States)

    Qiu, Zhenzhen; Zheng, Kai; Zhang, Haoxiang; Feng, Ji; Wang, Lizhi; Zhou, Hao

    2017-01-01

    Chronic renal failure is a severe clinical problem which has some significant socioeconomic impact worldwide and hemodialysis is an important way to maintain patients' health state, but it seems difficult to get better in short time. Considering these, the aim in our research is to update and evaluate the effects of exercise on the health of patients with chronic renal failure. The databases were used to search for the relevant studies in English or Chinese. And the association between physical exercise and health state of patients with chronic renal failure has been investigated. Random-effect model was used to compare the physical function and capacity in exercise and control groups. Exercise is helpful in ameliorating the situation of blood pressure in patients with renal failure and significantly reduces VO 2 in patients with renal failure. The results of subgroup analyses show that, in the age >50, physical activity can significantly reduce blood pressure in patients with renal failure. The activity program containing warm-up, strength, and aerobic exercises has benefits in blood pressure among sick people and improves their maximal oxygen consumption level. These can help patients in physical function and aerobic capacity and may give them further benefits.

  8. Physical Exercise and Patients with Chronic Renal Failure: A Meta-Analysis

    Science.gov (United States)

    Qiu, Zhenzhen; Zheng, Kai; Zhang, Haoxiang; Feng, Ji; Wang, Lizhi

    2017-01-01

    Chronic renal failure is a severe clinical problem which has some significant socioeconomic impact worldwide and hemodialysis is an important way to maintain patients' health state, but it seems difficult to get better in short time. Considering these, the aim in our research is to update and evaluate the effects of exercise on the health of patients with chronic renal failure. The databases were used to search for the relevant studies in English or Chinese. And the association between physical exercise and health state of patients with chronic renal failure has been investigated. Random-effect model was used to compare the physical function and capacity in exercise and control groups. Exercise is helpful in ameliorating the situation of blood pressure in patients with renal failure and significantly reduces VO2 in patients with renal failure. The results of subgroup analyses show that, in the age >50, physical activity can significantly reduce blood pressure in patients with renal failure. The activity program containing warm-up, strength, and aerobic exercises has benefits in blood pressure among sick people and improves their maximal oxygen consumption level. These can help patients in physical function and aerobic capacity and may give them further benefits. PMID:28316986

  9. Mesenchymal stem cell-derived microparticles ameliorate peritubular capillary rarefaction via inhibition of endothelial-mesenchymal transition and decrease tubulointerstitial fibrosis in unilateral ureteral obstruction.

    Science.gov (United States)

    Choi, Hoon Young; Lee, Hyun Gyu; Kim, Beom Seok; Ahn, Sun Hee; Jung, Ara; Lee, Mirae; Lee, Jung Eun; Kim, Hyung Jong; Ha, Sung Kyu; Park, Hyeong Cheon

    2015-03-11

    Microparticles (MPs) derived from kidney-derived mesenchymal stem cells (KMSCs) have recently been reported to ameliorate rarefaction of peritubular capillaries (PTC) in ischemic kidneys via delivery of proangiogenic effectors. This study aimed to investigate whether KMSC-derived MPs show anti-fibrotic effects by ameliorating endothelial-to-mesenchymal transition (EndoMT) in human umbilical vein endothelial cells (HUVEC) in vitro and by preserving PTC in kidneys with unilateral ureteral obstruction (UUO) in vivo. MPs isolated from the supernatants of KMSC were co-cultured with HUVEC to assess their in vitro biologic effects on endothelial cells. Mice were treated with MPs via the tail vein after UUO injury to assess their anti-fibrotic and PTC sparing effects. Renal tubulointerstitial damage and inflammatory cell infiltration were examined with Masson's trichrome, F4/80 and α-smooth muscle actin (α-SMA) staining and PTC rarefaction index was determined by CD31 staining. KMSC-derived MPs significantly ameliorated EndoMT and improved in vitro proliferation of TGF-β1 treated HUVEC. In vivo administration of KMSC-derived MPs significantly inhibited EndoMT of PTC endothelial cells and improved PTC rarefaction in UUO kidneys. Furthermore, administration of KMSC-derived MPs inhibited inflammatory cell infiltration as well as tubulointerstitial fibrosis in UUO mice as demonstrated by decreased F4/80 and α-SMA-positive cells and Masson's trichrome staining, respectively. Our results suggest that KMSC-derived MPs ameliorate PTC rarefaction via inhibition of EndoMT and protect against progression of renal damage by inhibiting tubulointerstitial fibrosis.

  10. Angiography for renal hypertension

    International Nuclear Information System (INIS)

    Chuang, V.P.; Ernst, C.B.

    1985-01-01

    As angioplasty and operative techniques have become more precise and successful, so have evaluation techniques. Preoperative arteriography is indispensible for deciding on the appropriate treatment modality and the specifics of the procedure. Arteriography, therefore, remains the cornerstone in managing renovascular hypertension and renal arterial disease

  11. Dopamins renale virkninger

    DEFF Research Database (Denmark)

    Olsen, Niels Vidiendal

    1990-01-01

    is frequently employed in cases of acute oliguric renal failure but the results available concerning the therapeutic effect are frequently retrospective and uncontrolled. The results suggest that early treatment with 1-3 micrograms/kg/min dopamine combined with furosemide can postpone or possibly render...

  12. Primary renal graft thrombosis

    NARCIS (Netherlands)

    Bakir, N; Sluiter, WJ; Ploeg, RJ; van Son, WJ; Tegzess, Adam

    Background. Renal allograft thrombosis is a serious complication of kidney transplantation that ultimately leads to graft loss. Its association with acute and hyperacute rejection is well documented; however, in a large proportion of patients the precise cause remains obscure. The exact incidence

  13. Black ginseng extract ameliorates hypercholesterolemia in rats.

    Science.gov (United States)

    Saba, Evelyn; Jeon, Bo Ra; Jeong, Da-Hye; Lee, Kija; Goo, Youn-Kyoung; Kim, Seung-Hyung; Sung, Chang-Keun; Roh, Seong-Soo; Kim, Sung Dae; Kim, Hyun-Kyoung; Rhee, Man-Hee

    2016-04-01

    Ginseng (Panax ginseng Meyer) is a well-characterized medicinal herb listed in the classic oriental herbal dictionary as "Shin-nong-bon-cho-kyung." Ginseng has diverse pharmacologic and therapeutic properties. Black ginseng (BG, Ginseng Radix nigra) is produced by repeatedly steaming fresh ginseng nine times. Studies of BG have shown that prolonged heat treatment enhances the antioxidant activity with increased radical scavenging activity. Several recent studies have showed the effects of BG on increased lipid profiles in mice. In this study report the effects of water and ethanol extracts of BG on hypercholesterolemia in rats. To our knowledge, this is the first time such an effect has been reported. Experiments were conducted on male Sprague Dawley rats fed with a high-cholesterol diet supplemented with the water and ethanol extracts of BG (200 mg/kg). Their blood cholesterol levels, serum white blood cell levels, and cholesterol-metabolizing marker genes messenger RNA (mRNA) expression were determined. Liver and adipose tissues were histologically analyzed. We found that BG extracts efficiently reduced the total serum cholesterol levels, low-density lipoprotein (LDL) levels with increased food efficiency ratio and increased number of neutrophil cells. It also attenuated the key genes responsible for lipogenesis, that is, acetyl-coenzyme A (CoA) acetyltransferase 2, 3-hydroxy-3-methyl-glutaryl-CoA reductase, and sterol regulatory element-binding protein 2, at the mRNA level inside liver cells. Furthermore, the BG extract also reduced the accumulation of fat in adipose tissues, and inhibited the neutral fat content in liver cells stained with hematoxylin and eosin and oil red O. Administration of BG extracts to Sprague Dawley rats fed with high-cholesterol diet ameliorated hypercholesterolemia, which was mediated via modulation of cholesterol-metabolizing marker genes. This data throw a light on BG's cardioprotective effects.

  14. Stem cells and their role in renal ischaemia reperfusion injury.

    Science.gov (United States)

    Bagul, Atul; Frost, Jodie H; Drage, Martin

    2013-01-01

    Ischaemia-reperfusion injury (IRI) remains one of the leading causes of acute kidney injury (AKI). IRI is an underlying multifactorial pathophysiological process which affects the outcome in both native and transplanted patients. The high morbidity and mortality associated with IRI/AKI and disappointing results from current available clinical therapeutic approaches prompt further research. Stem cells (SC) are undifferentiated cells that can undergo both renewal and differentiation into one or more cell types which can possibly ameliorate IRI. To carry out a detailed literature analysis and construct a comprehensive literature review addressing the role of SC in AKI secondary to IRI. Evidence favouring the role of SC in renal IRI and evidence showing no benefits of SC in renal IRI are the two main aspects to be studied. The search strategy was based on an extensive search addressing MESH terms and free text terms. The majority of studies in the field of renal IRI and stem cell therapy show substantial benefits. Studies were mostly conducted in small animal models, thus underscoring the need for further pre-clinical studies in larger animal models, and results should be taken with caution. SC therapy may be promising though controversy exists in the exact mechanism. Thorough scientific exploration is required to assess mechanism, safety profile, reproducibility and methods to monitor administered SC. Copyright © 2012 S. Karger AG, Basel.

  15. Dopamine antagonists and brief vision distinguish lens-induced- and form-deprivation-induced myopia.

    Science.gov (United States)

    Nickla, Debora L; Totonelly, Kristen

    2011-11-01

    In eyes wearing negative lenses, the D2 dopamine antagonist spiperone was only partly effective in preventing the ameliorative effects of brief periods of vision (Nickla et al., 2010), in contrast to reports from studies using form-deprivation. The present study was done to directly compare the effects of spiperone, and the D1 antagonist SCH-23390, on the two different myopiagenic paradigms. 12-day old chickens wore monocular diffusers (form-deprivation) or -10 D lenses attached to the feathers with matching rings of Velcro. Each day for 4 days, 10 μl intravitreal injections of the dopamine D2/D4 antagonist spiperone (5 nmoles) or the D1 antagonist SCH-23390, were given under isoflurane anesthesia, and the diffusers (n = 16; n = 5, respectively) or lenses (n = 20; n = 6) were removed for 2 h immediately after. Saline injections prior to vision were done as controls (form-deprivation: n = 11; lenses: n = 10). Two other saline-injected groups wore the lenses (n = 12) or diffusers (n = 4) continuously. Axial dimensions were measured by high frequency A-scan ultrasonography at the start, and on the last day immediately prior to, and 3 h after the injection. Refractive errors were measured at the end of the experiment using a Hartinger's refractometer. In form-deprived eyes, spiperone, but not SCH-23390, prevented the ocular growth inhibition normally effected by the brief periods of vision (change in vitreous chamber depth, spiperone vs saline: 322 vs 211 μm; p = 0.01). By contrast, neither had any effect on negative lens-wearing eyes given similar unrestricted vision (210 and 234 μm respectively, vs 264 μm). The increased elongation in the spiperone-injected form-deprived eyes did not, however, result in a myopic shift, probably due to the inhibitory effect of the drug on anterior chamber growth (drug vs saline: 96 vs 160 μm; p effects of brief periods of unrestricted vision differ for form-deprivation versus negative lens-wear, which may imply different growth

  16. Zinc Ameliorate Oxidative Stress and Hormonal Disturbance Induced by Methomyl, Abamectin, and Their Mixture in Male Rats

    Directory of Open Access Journals (Sweden)

    Sameeh A. Mansour

    2017-12-01

    Full Text Available Exposure to mixtures of toxicants (e.g., pesticides is common in real life and a subject of current concern. The present investigation was undertaken to assess some toxicological effects in male rats following exposure to methomyl (MET, abamectin (ABM, and their combination (MET+ABM, and to evaluate the ameliorative effect of zinc co-administration. Three groups of rats were designated for MET, ABM, and the mixture treatments. Three other groups were designated for zinc in conjunction with the pesticides. Additionally, one group received water only (control, and the other represented a positive zinc treatment. The obtained results revealed that MET was acutely more toxic than ABM. The tested pesticides induced significant elevation in lipid peroxidation and catalase levels, while declined the levels of the other tested parameters e.g., Superoxide dismutase (SOD, Glutathione-S-transferase (GST, Glutathione peroxidase (GPx, Glutathione reductase (GR, Cytochrome P450 (CYP450, testosterone, and thyroxine. Biochemical alterations induced by the mixture were greater than those recorded for each of the individual insecticides. The joint action analysis, based on the obtained biochemical data, revealed the dominance of antagonistic action among MET and ABM. Zinc supplementation achieved noticeable ameliorative effects. It was concluded that zinc may act as a powerful antioxidant, especially in individuals who are occupationally exposed daily to low doses of such pesticides.

  17. Daikenchuto, a traditional Japanese herbal medicine, ameliorates postoperative ileus by anti-inflammatory action through nicotinic acetylcholine receptors.

    Science.gov (United States)

    Endo, Mari; Hori, Masatoshi; Ozaki, Hiroshi; Oikawa, Tetsuro; Hanawa, Toshihiko

    2014-06-01

    Daikenchuto (DKT), a gastrointestinal prokinetic Japanese herbal medicine, is prescribed for patients with postoperative ileus (POI) and adhesive bowel obstruction following abdominal surgery. Several mechanisms for the amelioration of POI by DKT have been suggested; however, it has remained unclear whether DKT shows anti-inflammatory effects in POI. In the present study, we investigated the effects of DKT in a mouse POI model and attempted to clarify the detailed mechanisms of action. Intestinal manipulation (IM) was applied to the distal ileum of mice. DKT was administered orally to the animals 4 times before and after IM. Gastrointestinal transit in vivo, leukocyte infiltration, cytokine mRNA expression and gastrointestinal motility were analyzed. We also investigated the effects of the α7nAChR antagonist methyllycaconitine citrate (MLA) on the DKT-mediated ameliorative action against POI, and we studied the effects of DKT on inflammatory activity in α7nAChR knockout mice. DKT treatment led to recovery of the delayed intestinal transit induced by IM. DKT significantly inhibited the infiltration of neutrophils and CD68-positive macrophages, and inhibited mRNA expressions of TNF-α and MCP-1. MLA significantly reduced the anti-inflammatory action of DKT, and the amelioration of macrophage infiltration by DKT was partially suppressed in α7nAChR knockout mice. In conclusion, in addition to the gastrointestinal prokinetic action, DKT serves as a novel therapeutic agent for POI characterized by its anti-inflammatory potency. The DKT-induced anti-inflammatory activity may be partly mediated by activation of α7nAChR.

  18. Berberine ameliorates collagen-induced arthritis in rats by suppressing Th17 cell responses via inducing cortistatin in the gut.

    Science.gov (United States)

    Yue, Mengfan; Xia, Yufeng; Shi, Can; Guan, Chunge; Li, Yunfan; Liu, Rui; Wei, Zhifeng; Dai, Yue

    2017-09-01

    Berberine, an isoquinoline alkaloid, has been reported to ameliorate various autoimmune diseases including rheumatoid arthritis by oral administration. However, its mechanism remains mysterious due to an extremely low bioavailability. The fact that berberine readily accumulates in the gut, the largest endocrine organ in the body, attracted us to explore its anti-arthritic mechanism in view of the induction of intestinal immunosuppressive neuropeptides. In this study, berberine (200 mg·kg -1 , i.g.) was shown to ameliorate collagen-induced arthritis in rats, which was manifested by the reduction of clinical signs and joint destruction, as well as marked down-regulation of Th17 cell frequency and interleukin-17 level in blood. In contrast, an intravenous injection of berberine failed to affect arthritis in rats, implying that its anti-arthritic effect was gut-dependent. Further studies revealed that oral berberine selectively elevated the levels of cortistatin, of five gut-derived neuropeptides tested, in the intestines and sera of arthrititic rats. Antagonists of ghrelin/growth hormone secretagogue receptor 1 (a subtype of cortistatin receptor) almost completely abolished the ameliorative effect of berberine on arthritis and Th17 cell responses in rats. In vitro, berberine showed a moderate ability to promote the expression of cortistatin in nerve cells, which was strengthened when the nerve cells were cocultured with enteroendocrine cells to induce an autocrine/paracrine environment. In summary, oral berberine exerted anti-arthritic effect through inhibiting the Th17 cell response, which was closely associated with the induction of cortistatin generation from gut through augmenting autocrine/paracrine action between enteric nerve cells and endocrine cells. © 2017 Federation of European Biochemical Societies.

  19. Sexually antagonistic selection in human male homosexuality.

    Directory of Open Access Journals (Sweden)

    Andrea Camperio Ciani

    Full Text Available Several lines of evidence indicate the existence of genetic factors influencing male homosexuality and bisexuality. In spite of its relatively low frequency, the stable permanence in all human populations of this apparently detrimental trait constitutes a puzzling 'Darwinian paradox'. Furthermore, several studies have pointed out relevant asymmetries in the distribution of both male homosexuality and of female fecundity in the parental lines of homosexual vs. heterosexual males. A number of hypotheses have attempted to give an evolutionary explanation for the long-standing persistence of this trait, and for its asymmetric distribution in family lines; however a satisfactory understanding of the population genetics of male homosexuality is lacking at present. We perform a systematic mathematical analysis of the propagation and equilibrium of the putative genetic factors for male homosexuality in the population, based on the selection equation for one or two diallelic loci and Bayesian statistics for pedigree investigation. We show that only the two-locus genetic model with at least one locus on the X chromosome, and in which gene expression is sexually antagonistic (increasing female fitness but decreasing male fitness, accounts for all known empirical data. Our results help clarify the basic evolutionary dynamics of male homosexuality, establishing this as a clearly ascertained sexually antagonistic human trait.

  20. Hypocretin antagonists in insomnia treatment and beyond.

    Science.gov (United States)

    Ruoff, Chad; Cao, Michelle; Guilleminault, Christian

    2011-01-01

    Hypocretin neuropeptides have been shown to regulate transitions between wakefulness and sleep through stabilization of sleep promoting GABAergic and wake promoting cholinergic/monoaminergic neural pathways. Hypocretin also influences other physiologic processes such as metabolism, appetite, learning and memory, reward and addiction, and ventilatory drive. The discovery of hypocretin and its effect upon the sleep-wake cycle has led to the development of a new class of pharmacologic agents that antagonize the physiologic effects of hypocretin (i.e. hypocretin antagonists). Further investigation of these agents may lead to novel therapies for insomnia without the side-effect profile of currently available hypnotics (e.g. impaired cognition, confusional arousals, and motor balance difficulties). However, antagonizing a system that regulates the sleep-wake cycle while also influencing non-sleep physiologic processes may create an entirely different but equally concerning side-effect profile such as transient loss of muscle tone (i.e. cataplexy) and a dampened respiratory drive. In this review, we will discuss the discovery of hypocretin and its receptors, hypocretin and the sleep-wake cycle, hypocretin antagonists in the treatment of insomnia, and other implicated functions of the hypocretin system.

  1. Ameliorative Effect of Honey and Propolis Mixture on Rats Exposed to Gamma Irradiation

    International Nuclear Information System (INIS)

    Hemieda, S.F.; Abd-El Nour, K.N.; Hassan, A.I.; Abdou, M.I.; Khalil, W.A.

    2016-01-01

    This study aims to evaluate the ameliorative effect of honey and propolis mixture treatment on some biochemical and biophysical parameters in rats exposed to oxidative stress of gamma irradiation. Male rats were exposed to a fractionated dose gamma irradiation of total 5 Gy in five successive days. A mixture of dose 250 mg/kg/day honey and 90 mg/kg/day propolis was administrated to rats, ten days before irradiation, five days during irradiation and 14 days post irradiation. Blood samples were collected at 1 st , 7 th and 14 th day post the 5 th day of irradiation. Biochemical parameters such as serum liver enzymes (ALT and AST), serum renal function as (BUN and Creatinine) and serum total antioxidants were estimated. Also biophysical studies including hemoglobin investigations (Hb absorption spectra and dielectric measurements) were investigated.The results demonstrated that the levels of AST, ALT, BUN and creatinine were significantly elevated, while levels of total antioxidants were significantly reduced post irradiation. Moreover the absolute values of permittivity ε', dielectric loss ε'' and ac - conductivity σ ac increased in addition to a pronounced decrease in the absorbance at Sort band after irradiation compared to control group.Treatment of the irradiated group with honey and propolis mixture showed significant amelioration in the levels of the biochemical parameters. Also, the values of ε', ε'' and σ ac were nearly close to those of control group. Finally, the average value of peak height of Sort band was significantly increased compared to irradiated rat.

  2. Total saponin of Dioscoreae hypoglaucae rhizoma ameliorates streptozotocin-induced diabetic nephropathy

    Directory of Open Access Journals (Sweden)

    Guo C

    2016-02-01

    Full Text Available Changrun Guo,1 Gang Ding,2 Wenzhe Huang,2 Zhenzhong Wang,2 Zhaoqing Meng,1,2 Wei Xiao2 1State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, People’s Republic of China; 2Jiangsu Kanion Pharmaceutical Co. Ltd, Lianyungang City, People’s Republic of China Background: Diabetic nephropathy has become the most common cause of morbidity and mortality in diabetic patients. Therefore, there is an urgent need for more effective and safer drugs for use in this condition.Purpose: The aims of this study were to investigate the ameliorative effects of total saponin of Dioscoreae hypoglaucae rhizoma (TSD on diabetic nephropathy and to explore the potential underlying mechanism(s.Methods: Rats with streptozotocin-induced diabetes were orally treated with TSD at 40, 80, and 160 mg/kg/d for 12 weeks. At the end of the treatment, blood, urine, and kidneys were collected for biochemical and histological examination.Results: The results demonstrated that TSD significantly decreased the fasting blood glucose, glycosylated hemoglobin, urinary protein, serum creatinine, and blood urea nitrogen levels in diabetic rats. The results of histological examinations showed that TSD ameliorated glomerular and tubular pathological changes in diabetic rats. Furthermore, TSD significantly prevented oxidative stress and reduced the renal levels of advanced glycation end products, transforming growth factor-β1, connective tissue growth factor, and tumor necrosis factor-α.Conclusion: This study demonstrated the renoprotective effects of TSD in experimental diabetic nephropathy via a number of different mechanisms. Keywords: total saponin of Dioscoreae hypoglaucae rhizoma, diabetic nephropathy, oxidative stress, AGEs, TGF-β1

  3. Distinct action of aranidipine and its active metabolite on renal arterioles, with special reference to renal protection.

    Science.gov (United States)

    Nakamura, A; Hayashi, K; Fujiwara, K; Ozawa, Y; Honda, M; Saruta, T

    2000-06-01

    Aranidipine, a newly developed calcium antagonist, possesses unique pharmacologic characteristics in that its metabolite (M-1) still has antihypertensive action. We examined the effects of both agents on renal microcirculation using the isolated perfused hydronephrotic rat kidney. During norepinephrine-induced constriction, the addition of aranidipine dilated both afferent and efferent arterioles in a dose-dependent manner; at 10(-6) M, 83 +/- 6% and 90 +/- 6% reversal, respectively. In contrast, its active metabolite exerted dilator action predominantly on the afferent arteriole (79 +/- 4% vs. 44 +/- 17% at 10(-6) M for afferent and efferent arterioles, respectively). We further examined the long-term (8 weeks) effect of these agents on the development of renal injury in salt-loaded subtotally nephrectomized spontaneously hypertensive rats. Both aranidipine and M-1 reduced blood pressure by a similar magnitude. The decreases in proteinuria were observed in the aranidipine-treated group at weeks 6, 8, and 10, whereas in the M-1 group, significant reduction was attained only at week 6. Histopathologic examination revealed that both treatments improved glomerular and arteriolar sclerosis. Glomerular sclerosis, however, was less pronounced in the aranidipine-treated group than in the M-1 group. In conclusion, aranidipine has dilator action on both arterioles, whereas M-1 caused predominant dilation of afferent arterioles. Such metabolic changes may constitute a determinant of efferent arteriolar action of the calcium antagonist.

  4. Acute renal dysfunction in liver diseases

    OpenAIRE

    Betrosian, Alex P; Agarwal, Banwari; Douzinas, Emmanuel E

    2007-01-01

    Renal dysfunction is common in liver diseases, either as part of multiorgan involvement in acute illness or secondary to advanced liver disease. The presence of renal impairment in both groups is a poor prognostic indicator. Renal failure is often multifactorial and can present as pre-renal or intrinsic renal dysfunction. Obstructive or post renal dysfunction only rarely complicates liver disease. Hepatorenal syndrome (HRS) is a unique form of renal failure associated with advanced liver dise...

  5. Chronic renal failure due to unilateral renal agenesis and total renal dysplasia (=aplasia)

    International Nuclear Information System (INIS)

    Kroepelin, T.; Ziupa, J.; Wimmer, B.

    1983-01-01

    Three adult patients with unilateral renal agenesis/total dysplasia (= aplasia) and with an early chronic renal failure are presented. One patient had renal agenesis without ureter bud and ureteric ostium on one side, and reflux pyelonephritis on the other; one had small compact total renal dysplasia (= aplasia) on one side, while chronic uric acid nephropathy (chronic renal disease as a cause of gout) was diagnosed on the other; the third patient had a total large multicystic dysplasia on one side, and on the other a segmental large multicystic dysplasia. Radiological steps and radiodiagnostic criteria are discussed and the combination of urogenital and extraurogenital anomalies is referred to. (orig.)

  6. History of the 'geste antagoniste' sign in cervical dystonia.

    Science.gov (United States)

    Poisson, A; Krack, P; Thobois, S; Loiraud, C; Serra, G; Vial, C; Broussolle, E

    2012-08-01

    The geste antagoniste is a voluntary maneuver that temporarily reduces the severity of dystonic posture or movements. It is a classical feature of focal and particularly cervical dystonia. However, the precise historical aspects of geste antagoniste still remain obscure. The goals of this review were (1) to clarify the origin of the geste antagoniste sign; (2) to identify the factors that led to its diffusion in the international literature; (3) to follow the evolution of that term across the twentieth century. We used medical and neurological French, German and English literature of the late nineteenth and early twentieth centuries, and the PubMed database by entering the terms geste antagoniste, antagonistic gesture and sensory trick. The geste antagoniste sign is a legacy of the Paris Neurological School of the end of the nineteenth century. The term was introduced by Meige and Feindel in their 1902 book on tics, written in the vein of their master, Brissaud, who first described this sign in 1893. The almost immediate translations of this book by Giese into German and Kinnier Wilson into English contributed to the rapid spreading of the term geste antagoniste, which is still in use worldwide today. The term antagonistic gesture is the translation proposed by Kinnier Wilson, which also led to the use of the term geste antagonistique. The geste antagoniste sign has long been considered a solid argument for the psychogenic origins of dystonia until the 1980s when Marsden made strong arguments for its organic nature.

  7. Pharmacological characterization of BR-A-657, a highly potent nonpeptide angiotensin II receptor antagonist.

    Science.gov (United States)

    Chi, Yong Ha; Lee, Joo Han; Kim, Je Hak; Tan, Hyun Kwang; Kim, Sang Lin; Lee, Jae Yeol; Rim, Hong-Kun; Paik, Soo Heui; Lee, Kyung-Tae

    2013-01-01

    The pharmacological profile of BR-A-657, 2-n-butyl-5-dimethylamino-thiocarbonyl-methyl-6-methyl-3-{[2-(1H-tetrazole-5-yl)biphenyl-4-yl]methyl}-pyrimidin-4(3H)-one, a new nonpeptide AT1-selective angiotensin receptor antagonist, has been investigated in a variety of in vitro and in vivo experimental models. In the present study, BR-A-657 displaced [(125)I][Sar(1)-Ile(8)]angiotensin II (Ang II) from its specific binding sites to AT1 subtype receptors in membrane fractions of HEK-293 cells with an IC50 of 0.16 nM. In a functional assay using isolated rabbit thoracic aorta, BR-A-657 inhibited the contractile response to Ang II (pD'2: 9.15) with a significant reduction in the maximum. In conscious rats, BR-A-657 (0.01, 0.1, 1 mg/kg; intravenously (i.v.)) dose-dependently antagonized Ang II-induced pressor responses. In addition, BR-A-657 dose-dependently decreased mean arterial pressure in furosemide-treated rats and renal hypertensive rats. Moreover, BR-A-657 given orally at 1 and 3 mg/kg reduced blood pressure in conscious renal hypertensive rats. Taken together, these findings indicate that BR-A-657 is a potent and specific antagonist of Ang II at the AT1 receptor subtype, and reveal the molecular basis responsible for the marked lowering of blood pressure in conscious rats.

  8. Neural correlates underlying naloxone-induced amelioration of sexual behavior deterioration due to an alarm pheromone

    Directory of Open Access Journals (Sweden)

    Tatsuya eKobayashi

    2015-02-01

    Full Text Available Sexual behavior is suppressed by various types of stressors. We previously demonstrated that an alarm pheromone released by stressed male Wistar rats is a stressor to other rats, increases the number of mounts needed for ejaculation, and decreases the hit rate (described as the number of intromissions/sum of the mounts and intromissions. This deterioration in sexual behavior was ameliorated by pretreatment with the opioid receptor antagonist naloxone. However, the neural mechanism underlying this remains to be elucidated. Here, we examined Fos expression in 31 brain regions of pheromone-exposed rats and naloxone-pretreated pheromone-exposed rats 60 min after 10 intromissions. As previously reported, the alarm pheromone increased the number of mounts and decreased the hit rate. In addition, Fos expression was increases in the anterior medial division, anterior lateral division and posterior division of the bed nucleus of the stria terminalis, parvocellular part of the paraventricular nucleus of the hypothalamus, arcuate nucleus, dorsolateral and ventrolateral periaqueductal gray, and nucleus paragigantocellularis. Fos expression decreased in the magnocellular part of the paraventricular nucleus of the hypothalamus. Pretreatment with naloxone blocked the pheromone-induced changes in Fos expression in the magnocellular part of the paraventricular nucleus of the hypothalamus, ventrolateral periaqueductal gray, and nucleus paragigantocellularis. Based on these results, we hypothesize that the alarm pheromone deteriorated sexual behavior by activating the ventrolateral periaqueductal gray-nucleus paragigantocellularis cluster and suppressing the magnocellular part of the paraventricular nucleus of the hypothalamus via the opioidergic pathway.

  9. Fimasartan Ameliorates Nonalcoholic Fatty Liver Disease through PPARδ Regulation in Hyperlipidemic and Hypertensive Conditions

    Directory of Open Access Journals (Sweden)

    Yong-Jik Lee

    2017-01-01

    Full Text Available To investigate the effects of fimasartan on nonalcoholic fatty liver disease in hyperlipidemic and hypertensive conditions, the levels of biomarkers related to fatty acid metabolism were determined in HepG2 and differentiated 3T3-L1 cells treated by high fatty acid and liver and visceral fat tissue samples of spontaneously hypertensive rats (SHRs given high-fat diet. In HepG2 cells and liver tissues, fimasartan was shown to increase the protein levels of peroxisome proliferator-activated receptor delta (PPARδ, phosphorylated 5′ adenosine monophosphate-activated protein kinase (p-AMPK, phosphorylated acetyl-CoA carboxylase (p-ACC, malonyl-CoA decarboxylase (MCD, medium chain acyl-CoA dehydrogenase (MCAD, and peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α, and it led to a decrease in the protein levels of 11 beta-hydroxysteroid dehydrogenase 1 (11β-HSDH1, fatty acid synthase (FAS, and tumor necrosis factor-alpha (TNF-α. Fimasartan decreased lipid contents in HepG2 and differentiated 3T3-L1 cells and liver tissues. In addition, fimasartan increased the adiponectin level in visceral fat tissues. The antiadipogenic effects of fimasartan were offset by PPARδ antagonist (GSK0660. Consequently, fimasartan ameliorates nonalcoholic fatty liver disease mainly through the activation of oxidative metabolism represented by PPARδ-AMPK-PGC-1α pathway.

  10. Zinc Deficiency in Humans and its Amelioration

    Directory of Open Access Journals (Sweden)

    Yashbir Singh Shivay

    2015-01-01

    Full Text Available Zinc (Zn deficiency in humans has recently received considerable attention. Global mortality in children under 5 years of age in 2004 due to Zn deficiency was estimated at 4,53,207 as against 6,66,771 for vitamin A deficiency; 20,854 for iron deficiency and 3,619 for iodine deficiency. In humans 2800-3000 proteins contain Zn prosthetic group and Zn is an integral component of zinc finger prints that regulate DNA transcription. Zinc is a Type-2 nutrient, which means that its concentration in blood does not decrease in proportion of the Zn deficiency. Adverse effects of Zn deficiency vary with age: low weight gain, diarrhoea, aneroxia and neurobehavioral disturbances are observed in infants, while skin changes and dwarfism are frequent in toddlers and adolescents. Common manifestations of Zn deficiency among elderly include hypogeusia, chronic non-healing ulcers and recurrent infections.Ameliorative measures of Zn deficiency in humans can be classified in two groups, namely, nutraceutical and biofortification of food grains. Nutraceutical interventions include pharmaceutical supplements, dietary supplements and dietary diversification, while biofortification of food grains can be achieved by genetic modification (GM of crops or by agronomic techniques that include soil or/and foliar fertilization of crops.The major disadvantage of nutraceutical approaches is that the major beneficiaries are urban people and the poor rural masses that need adequate Zn nutrition most are left out. Genetic biofortification of food grains requires large amounts of funds and a fairly long-period of time. Further, a large number of countries have not yet accepted genetically modified (GM foods. On the other hand agronomic biofortification of food grains yields immediate effects and rural and urban people are equally benefitted. Our studies have shown that Zn concentration in cereals (rice, wheat etc and pulses can be considerably increased by soil or/and foliar

  11. Zinc Deficiency in Humans and its Amelioration

    Directory of Open Access Journals (Sweden)

    Yashbir Singh Shivay

    2015-12-01

    Full Text Available Zinc (Zn deficiency in humans has recently received considerable attention. Global mortality in children under 5 years of age in 2004 due to Zn deficiency was estimated at 4,53,207 as against 6,66,771 for vitamin A deficiency; 20,854 for iron deficiency and 3,619 for iodine deficiency. In humans 2800-3000 proteins contain Zn prosthetic group and Zn is an integral component of zinc finger prints that regulate DNA transcription. Zinc is a Type-2 nutrient, which means that its concentration in blood does not decrease in proportion of the Zn deficiency. Adverse effects of Zn deficiency vary with age: low weight gain, diarrhoea, aneroxia and neurobehavioral disturbances are observed in infants, while skin changes and dwarfism are frequent in toddlers and adolescents. Common manifestations of Zn deficiency among elderly include hypogeusia, chronic non-healing ulcers and recurrent infections. Ameliorative measures of Zn deficiency in humans can be classified in two groups, namely, nutraceutical and biofortification of food grains. Nutraceutical interventions include pharmaceutical supplements, dietary supplements and dietary diversification, while biofortification of food grains can be achieved by genetic modification (GM of crops or by agronomic techniques that include soil or/and foliar fertilization of crops. The major disadvantage of nutraceutical approaches is that the major beneficiaries are urban people and the poor rural masses that need adequate Zn nutrition most are left out. Genetic biofortification of food grains requires large amounts of funds and a fairly long-period of time. Further, a large number of countries have not yet accepted genetically modified (GM foods. On the other hand agronomic biofortification of food grains yields immediate effects and rural and urban people are equally benefitted. Our studies have shown that Zn concentration in cereals (rice, wheat etc and pulses can be considerably increased by soil or/and foliar

  12. Vasopressin and Vasopressin Antagonists in Heart Failure

    DEFF Research Database (Denmark)

    Vishram-Nielsen, Julie K; Gustafsson, Finn

    2017-01-01

    Despite the introduction of multiple new pharmacological agents over the past three decades in the field of heart failure (HF), overall prognosis remains poor. Hyponatremia is prevalent in HF patients and has been suggested as a contributor to poor response to standard therapy. Elevated levels...... by the V2 receptors in the renal collecting tubules. The optimal use of VRAs is yet to be determined, especially in patients with congestive HF. Although long-term effects on improvement in mortality have not been shown in the Efficacy of Vasopressin Antagonism in Heart Failure Outcome Study with Tolvaptan...

  13. Carbachol ameliorates lipopolysaccharide-induced intestinal epithelial tight junction damage by down-regulating NF-{kappa}{beta} and myosin light-chain kinase pathways

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Ying [Department of Anesthesia, Critical Care Medicine and Emergency Medicine Center, Zhongnan Hospital, Wuhan University, Wuhan 430071, Hubei Province, People' s Republic of China (China); Li, Jianguo, E-mail: 2010lijianguo@sina.cn [Department of Anesthesia, Critical Care Medicine and Emergency Medicine Center, Zhongnan Hospital, Wuhan University, Wuhan 430071, Hubei Province, People' s Republic of China (China)

    2012-11-16

    Highlights: Black-Right-Pointing-Pointer Carbachol reduced the lipopolysaccharide-induced intestinal barrier breakdown. Black-Right-Pointing-Pointer Carbachol ameliorated the lipopolysaccharide-induced ileal tight junction damage. Black-Right-Pointing-Pointer Carbachol prevented the LPS-induced NF-{kappa}{beta} and myosin light-chain kinase activation. Black-Right-Pointing-Pointer Carbachol exerted its beneficial effects in an {alpha}7 nicotinic receptor-dependent manner. -- Abstract: Carbachol is a cholinergic agonist that protects the intestines after trauma or burn injury. The present study determines the beneficial effects of carbachol and the mechanisms by which it ameliorates the lipopolysaccharide (LPS)-induced intestinal barrier breakdown. Rats were injected intraperitoneally with 10 mg/kg LPS. Results showed that the gut barrier permeability was reduced, the ultrastructural disruption of tight junctions (TJs) was prevented, the redistribution of zonula occludens-1 and claudin-2 proteins was partially reversed, and the nuclear factor-kappa beta (NF-{kappa}{beta}) and myosin light-chain kinase (MLCK) activation in the intestinal epithelium were suppressed after carbachol administration in LPS-exposed rats. Pretreatment with the {alpha}7 nicotinic acetylcholine receptor ({alpha}7nAchR) antagonist {alpha}-bungarotoxin blocked the protective action of carbachol. These results suggested that carbachol treatment can protect LPS-induced intestinal barrier dysfunction. Carbachol exerts its beneficial effect on the amelioration of the TJ damage by inhibiting the NF-{kappa}{beta} and MLCK pathways in an {alpha}7nAchR-dependent manner.

  14. CT findings of renal abscess

    International Nuclear Information System (INIS)

    Lee, Myung Jun; Kim, Mi Young; Woo, Jung Ju; Kim, Ho Kyun; Kim, Won Hong; Jeon, Jeong Dong; Jeon, Woo Ki; Han, Chang Yul

    1996-01-01

    The purpose of this study is to determine characteristic CT findings in renal abscess. Twenty cases of renal abscess were retrospectively analyzed for CT findings relating to the shape and extent of the abscess, change of nephrogram, peripheral rim enhancement, wedge-shaped enhancement on delayed scans, enlargement of the kidney involved and associated findings. Seven patients had a renal abscess at the right kidney, nine at the lift kidney and two bilaterally. The abscesses were round in 18 cases and finger-like in two. Rim enhancement around renal abscess was seen in four cases (20%). Changes in the nephrogram around the abscess were seen in 12 cases (60%). In all six patients who had undergone delayed postcontrast scans, wedge-shaped enhancement was shown around the abscess (100%). In the observation of the extent of renal abscesses, 14 cases were within the kidney, six cases extended the beyond renal capsule, and two were loculated in the renal fascia itself. Renal enlargement was seen in nine cases (45%). These results suggest that CT findings such as delayed wedge-shaped enhancement, change of nephrogram, peripheral rim enhancement, renal enlargement, and associated findings are valuable for diagnosis, and that CT also gives information concerning the extent, evolution and complication of a renal abscess

  15. The Role of Endothelin System in Renal Structure and Function during the Postnatal Development of the Rat Kidney.

    Science.gov (United States)

    Albertoni Borghese, María F; Ortiz, María C; Balonga, Sabrina; Moreira Szokalo, Rocío; Majowicz, Mónica P

    2016-01-01

    Renal development in rodents, unlike in humans, continues during early postnatal period. We aimed to evaluate whether the pharmacological inhibition of Endothelin system during this period affects renal development, both at structural and functional level in male and female rats. Newborn rats were treated orally from postnatal day 1 to 20 with vehicle or bosentan (Actelion, 20 mg/kg/day), a dual endothelin receptor antagonist (ERA). The animals were divided in 4 groups: control males, control females, ERA males and ERA females. At day 21, we evaluated renal function, determined the glomerular number by a maceration method and by morphometric analysis and evaluated possible structural renal alterations by three methods: 〈alpha〉-Smooth muscle actin (α-SMA) immunohistochemistry, Masson's trichrome and Sirius red staining. The pharmacological inhibition of Endothelin system with a dual ERA during the early postnatal period of the rat did not leads to renal damage in the kidneys of male and female rats. However, ERA administration decreased the number of glomeruli, the juxtamedullary filtration surface area and the glomerular filtration rate and increased the proteinuria. These effects could predispose to hypertension or renal diseases in the adulthood. On the other hand, these effects were more pronounced in male rats, suggesting that there are sex differences that could be greater later in life. These results provide evidence that Endothelin has an important role in rat renal postnatal development. However these results do not imply that the same could happen in humans, since human renal development is complete at birth.

  16. Bilateral renal calculi

    Science.gov (United States)

    Sreenevasan, G

    1974-01-01

    Bilateral renal calculi were present in 114 (10.7%) of 1,070 cases of proved urinary calculus admitted to the Urological Department of the General Hospital, Kuala Lumpur, during the period November 1968—May 1973. The management of bilateral renal calculi is discussed with reference to the first 100 cases in this series. The introduction of renography has greatly facilitated the decision as to which kidney should be operated on first. The management of patients with and without uraemia is discussed and the use of the modified V and V—Y incisions for the removal of staghorn calculi is described. Complications and results are briefly reviewed. ImagesFig. 1Fig. 4Fig. 6Fig. 7 PMID:4845653

  17. Effects of mineralocorticoid receptor antagonists in patients with hypertension and diabetes mellitus: a systematic review and meta-analysis.

    Science.gov (United States)

    Takahashi, S; Katada, J; Daida, H; Kitamura, F; Yokoyama, K

    2016-09-01

    Blood pressure (BP) control is important to ameliorate cardiovascular events in patients with diabetes mellitus (DM). However, achieving the target BP with a single drug is often difficult. The objective of this study was to evaluate the antihypertensive effects of mineralocorticoid receptor antagonists (MRAs) as add-on therapy to renin-angiotensin system (RAS) inhibitor(s) in patients with hypertension and DM. Studies were searched through October 2014 in MEDLINE, Embase and the Cochrane Central Register of Controlled Trials. Randomized, controlled trials or prospective, observational studies regarding concomitant administration of MRA and RAS inhibitor(s) in patients with DM were included. Articles were excluded if the mean systolic BP (SBP) was hypertension and DM already taking RAS inhibitors. Serum potassium levels should be monitored to prevent hyperkalemia.

  18. Apixaban: Effective and Safe in Preventing Thromboembolic Events in Patients with Atrial Fibrillation and Renal Failure.

    Science.gov (United States)

    Cortese, Francesca; Scicchitano, Pietro; Gesualdo, Michele; Ricci, Gabriella; Carbonara, Santa; Franchini, Carlo; Pia Schiavone, Brigida Immacolata; Corbo, Filomena; Ciccone, Marco Matteo

    2017-11-17

    Thromboembolic events, principally stroke, represent one of the leading causes of morbidity and mortality among subjects with atrial fibrillation. Chronic kidney disease determines a further increase of thromboembolic events, bleeding and mortality and complicates the pharmacological management of patients with atrial fibrillation, mainly due to the side effects of antiarrhythmic and anticoagulant drugs with renal excretion. Apixaban is a new oral anticoagulant characterized by good bioavailability and renal elimination accounting for only 25%, showing a safety profile and effectiveness in patients with renal impairment. In this manuscript, we reviewed literature data on the use of apixaban in the management of non-valvular atrial fibrillation in patients with renal failure, in order to clarify an often-debated topic in clinical practice. A PubMed search was performed on the terms atrial fibrillation, apixaban and renal failure with the aim of identifying relevant manuscripts, large randomized clinical trials, meta-analyses, and current guidelines. Literature data show that apixaban could represent an interesting alternative to warfarin and other selective antagonists of coagulation factors in patients with impaired renal function. About the risk of major bleeding, apixaban appears to be safer than warfarin in the presence of any degree of renal failure. Apixaban show to be an effective anticoagulant in patients with atrial fibrillation, even superior to warfarin in reducing the risk of stroke and systemic embolism regardless of the presence of renal insufficiency. Moreover, Food and Drug Administration allows the use of apixaban in patients with end stage renal disease on hemodialysis. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  19. Renal computed angiography. Part I: Renal CT arteriography in hypertension

    International Nuclear Information System (INIS)

    Al-Amin, M.; Hadjidekov, V.

    2012-01-01

    Visualization of renal vasculature is needed in several clinical condition among which hypertension is dominant. CT angiography now day replaces catheter angiography as non-invasive method. The goal of this study is to present initial authors experience in visualization of renal arteries using 64 MDCT and to evaluated the utility in hypertensive patients. MDCT assures excellent assessment of renal arteries conditions. Multiplanar reconstruction and allow better delineation in tortuous vessels course and anatomic variants. (authors)

  20. Renal phosphate handling: Physiology

    Directory of Open Access Journals (Sweden)

    Narayan Prasad

    2013-01-01

    Full Text Available Phosphorus is a common anion. It plays an important role in energy generation. Renal phosphate handling is regulated by three organs parathyroid, kidney and bone through feedback loops. These counter regulatory loops also regulate intestinal absorption and thus maintain serum phosphorus concentration in physiologic range. The parathyroid hormone, vitamin D, Fibrogenic growth factor 23 (FGF23 and klotho coreceptor are the key regulators of phosphorus balance in body.

  1. Chemical chaperon 4-phenylbutyrate protects against the endoplasmic reticulum stress-mediated renal fibrosis in vivo and in vitro.

    Science.gov (United States)

    Liu, Shing-Hwa; Yang, Ching-Chin; Chan, Ding-Cheng; Wu, Cheng-Tien; Chen, Li-Ping; Huang, Jenq-Wen; Hung, Kuan-Yu; Chiang, Chih-Kang

    2016-04-19

    Renal tubulointerstitial fibrosis is the common and final pathologic change of kidney in end-stage renal disease. Interesting, endoplasmic reticulum (ER) stress is known to contribute to the pathophysiological mechanisms during the development of renal fibrosis. Here, we investigated the effects of chemical chaperon sodium 4-phenylbutyrate (4-PBA) on renal fibrosis in vivo and in vitro. In a rat unilateral ureteral obstruction (UUO) model, 4-PBA mimicked endogenous ER chaperon in the kidneys and significantly reduced glucose regulated protein 78 (GRP78), CCAAT/enhancer binding protein (C/EBP) homologous protein (CHOP), activating transcription factor 4 (ATF4), and phosphorylated JNK protein expressions as well as restored spliced X-box-binding protein 1 (XBP1) expressions in the kidneys of UUO rats. 4-PBA also attenuated the increases of α-smooth muscle actin (α-SMA), connective tissue growth factor (CTGF) protein expressions, tubulointerstitial fibrosis, and apoptosis in the kidneys of UUO rats. Moreover, transforming growth factor (TGF)-β markedly increased ER stress-associated molecules, profibrotic factors, and apoptotic markers in the renal tubular cells (NRK-52E), all of which could be significantly counteracted by 4-PBA treatment. 4-PBA also diminished TGF-β-increased CTGF promoter activity and CTGF mRNA expression in NRK-52E cells. Taken together, our results indicated that 4-PBA acts as an ER chaperone to ameliorate ER stress-induced renal tubular cell apoptosis and renal fibrosis.

  2. The Attractiveness of Opposites: Agonists and Antagonists.

    LENUS (Irish Health Repository)

    O'Brien, Tony

    2015-02-02

    ABSTRACT Opioid-induced bowel dysfunction, of which constipation is the most common aspect, is a major limiting factor in the use of opioids for pain management. The availability of an oral, long-acting formulation of oxycodone and naloxone represents a highly significant development in pain management. The combination of an opioid analgesic with an opioid antagonist offers reliable pain control with a significant reduction in the burden of opioid-induced constipation. This report is adapted from paineurope 2014; Issue 3, ©Haymarket Medical Publications Ltd, and is presented with permission. paineurope is provided as a service to pain management by Mundipharma International, LTD and is distributed free of charge to healthcare professionals in Europe. Archival issues can be accessed via the website: http:\\/\\/www.paineurope.com at which European health professionals can register online to receive copies of the quarterly publication.

  3. Antiallergic effects of H1-receptor antagonists.

    Science.gov (United States)

    Baroody, F M; Naclerio, R M

    2000-01-01

    The primary mechanism of antihistamine action in the treatment of allergic diseases is believed to be competitive antagonism of histamine binding to cellular receptors (specifically, the H1-receptors), which are present on nerve endings, smooth muscles, and glandular cells. This notion is supported by the fact that structurally unrelated drugs antagonize the H1-receptor and provide clinical benefit. However, H1-receptor antagonism may not be their sole mechanism of action in treating allergic rhinitis. On the basis of in vitro and animal experiments, drugs classified as H1-receptor antagonists have long been recognized to have additional pharmacological properties. Most first-generation H1-antihistamines have anticholinergic, sedative, local anaesthetic, and anti-5-HT effects, which might favourably affect the symptoms of the allergic response but also contribute to side-effects. These additional properties are not uniformly distributed among drugs classified as H1-receptor antagonists. Azatadine, for example, inhibits in vitro IgE-mediated histamine and leukotriene (LT) release from mast cells and basophils. In human challenge models, terfenadine, azatadine, and loratadine reduce IgE-mediated histamine release. Cetirizine reduces eosinophilic infiltration at the site of antigen challenge in the skin, but not the nose. In a nasal antigen challenge model, cetirizine pretreatment did not affect the levels of histamine and prostaglandin D2 recovered in postchallenge lavages, whereas the levels of albumin, N-tosyl-L-arginine methyl ester (TAME) esterase activity, and LTs were reduced. Terfenadine, cetirizine, and loratadine blocked allergen-induced hyperresponsiveness to methacholine. In view of the complexity of the pathophysiology of allergy, a number of H1 antagonists with additional properties are currently under development for allergic diseases. Mizolastine, a new H1-receptor antagonist, has been shown to have additional actions that should help reduce the

  4. Antagonistic activity of marine sponges associated Actinobacteria

    Directory of Open Access Journals (Sweden)

    Selvakumar Dharmaraj

    2016-06-01

    Full Text Available Objective: To focus on the isolation and preliminary characterization of marine sponges associated Actinobacteria particularly Streptomyces species and also their antagonistic activities against bacterial and fungal pathogens. Methods: The sponges were collected from Kovalam and Vizhinjam port of south-west coast of Kerala, India. Isolation of strains was carried out from sponge extracts using international Streptomyces project media. For preliminary identification of the strains, morphological (mycelial colouration, soluble pigments, melanoid pigmentation, spore morphology, nutritional uptake (carbon utilisation, amonoacids influence, sodium chloride tolerance, physiological (pH, temperature and chemotaxonomical characterization were done. Antimicrobial studies were also carried out for the selected strains. Results: With the help of the spicule structures, the collected marine sponges were identified as Callyspongia diffusa, Mycale mytilorum, Tedania anhelans and Dysidea fragilis. Nearly 94 strains were primarily isolated from these sponges and further they were sub-cultured using international Streptomyces project media. The strains exhibited different mycelial colouration (aerial and substrate, soluble and melanoid pigmentations. The strains possessed three types of sporophore morphology namely rectus flexibilis, spiral and retinaculiaperti. Among the 94 isolates, seven exhibited antibacterial and antifungal activities with maximal zone of inhibition of 30 mm. The nutritional, physiological and chemotaxonomical characteristic study helped in the conventional identification of the seven strains and they all suggest that the strains to be grouped under the genus Streptomyces. Conclusions: The present study clearly helps in the preliminary identification of the isolates associated with marine sponges. Antagonistic activities prove the production of antimicrobial metabolites against the pathogens. Marine sponges associated Streptomyces are

  5. Assay method for organic calcium antagonist drugs and a kit for such an assay

    International Nuclear Information System (INIS)

    Snyder, S. H.; Gould, R. J.

    1985-01-01

    A method for measuring the level of organic calcium antagonist drug in a body fluid comprises preparing a mixture of a radioactive calcium antagonist drug, a body fluid containing a calcium antagonist drug and a calcium antagonist receptor material, measuring the radioactivity of the radioactive calcium antagonist drug bound to said calcium antagonist receptor material and deriving the concentration of the calcium antagonist drug in the body fluid from a standard curve indicating the concentration of calcium antagonist drug versus inhibition of binding of said radioactive calcium antagonist drug to said receptor sites caused by the calcium antagonist drug in said body fluid. A kit for measuring the level of an organic calcium drug comprises a receptacle containing a radioactive calcium antagonist drug, a calcium antagonist receptor material and a standard amount of a nonradioactive calcium antagonist drug

  6. Efficacy of ultrasonography-guided renal biopsy for the evaluation of renal dysfunction following renal transplantation

    International Nuclear Information System (INIS)

    Kim, Young Jae; Choi, Chul Soon; Min, Seon Jeong; Lee, Gyung Kyu; Lee, Eil Seong; Kang, Ik Won; Bae, Sang Hoon

    2003-01-01

    To evaluate the usefulness and complications of renal biopsy under ultrasonography-guidance in renal dysfunction after renal transplantation. Ultrasonography-guided renal biopsy was done in 47 patients with the transplanted kidney. The subjects consisted of 30 males and 17 females, age ranged from 16 to 66 years (average age=38 years). Biopsies were done once in 27 patients, twice in 17 patients, three times in 3 patients, a total of 70 biopsies. The success rate of renal biopsy for the accurate pathologic diagnosis and the incidence and types of complications following biopsy were evaluated. The success rate of renal biopsy for the accurate pathologic diagnosis was 96%(67/70). Pathologic diagnosis included 27 cases of acute rejection (39%), 8 cases of acute tubular necrosis (11%), 4 cases of acute rejection and acute tubular necrosis (6%), 4 cases of cyclosporin toxicity (6%), 4 cases of primary disease recurrence (6%), 4 cases of infection (6%) and others. Complications after renal biopsy included 15 cases of microscopic hematuria (21%), 1 case of gross hematuria with spontaneous cessation and 1 case of life threatening hemorrhage. Ultrasonography-guided renal biopsy is a safe and effective diagnostic method for the evaluation of renal dysfunction following renal transplantation.

  7. Cardiac and renal antioxidant enzymes and effects of tempol in hyperthyroid rats.

    Science.gov (United States)

    Moreno, Juan Manuel; Rodríguez Gómez, Isabel; Wangensteen, Rosemary; Osuna, Antonio; Bueno, Pablo; Vargas, Félix

    2005-11-01

    This study evaluated the activity of cardiac and renal antioxidant enzymes [superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPX), and glutathione reductase (GR)] and whether chronic treatment with tempol, a cell membrane-permeable SOD mimetic, ameliorates the hypertension of hyperthyroidism. Two experiments were performed. In experiment I, the following four groups of male Wistar rats were used: control group and three groups that received thyroxine (T4) at 10, 50, or 75 microg x rat(-1) x day(-1). In experiment II, tempol was orally administered (18 mg x kg(-1) x day(-1)) to control and T4-treated (75 microg x rat(-1) x day(-1)) rats. All treatments were maintained for 6 wk. Body weight, tail systolic blood pressure (BP), and heart rate were measured one time a week, and direct BP and morphological, metabolic, plasma, and renal variables were measured at the end of the experiment. Enzymatic activities were measured in renal cortex and medulla and right and left ventricles. In renal cortex, SOD activity was decreased in the T4-75 group, and there was a dose-related increase in CAT activity and decrease in GPX and GR activities in T4-treated groups. Activity of all antioxidant enzymes was reduced in left ventricle in T4-50 and T4-75 groups and in right ventricle in the T4-75 group. Tempol reduced BP, plasma malondialdehyde, and total urinary excretion of F2 isoprostanes in hypertensive hyperthyroid rats but not in controls. Tempol did not improve cardiac hypertrophy, proteinuria, or creatinine clearance in hyperthyroid rats. In conclusion, the results obtained indicate that the activity of SOD, GPX, and GR in renal and cardiac tissues is decreased in hyperthyroidism and that antioxidant treatment with tempol ameliorates T4-induced hypertension.

  8. Thrombin-receptor antagonist vorapaxar in acute coronary syndromes

    DEFF Research Database (Denmark)

    Tricoci, Pierluigi; Huang, Zhen; Held, Claes

    2012-01-01

    Vorapaxar is a new oral protease-activated-receptor 1 (PAR-1) antagonist that inhibits thrombin-induced platelet activation.......Vorapaxar is a new oral protease-activated-receptor 1 (PAR-1) antagonist that inhibits thrombin-induced platelet activation....

  9. Adverse cutaneous reactions induced by TNF-alpha antagonist therapy.

    Science.gov (United States)

    Borrás-Blasco, Joaquín; Navarro-Ruiz, Andrés; Borrás, Consuelo; Casterá, Elvira

    2009-11-01

    To review adverse cutaneous drug reactions induced by tumor necrosis factor alpha (TNF-alpha) antagonist therapy. A literature search was performed using PubMed (1996-March 2009), EMBASE, and selected MEDLINE Ovid bibliography searches. All language clinical trial data, case reports, letters, and review articles identified from the data sources were used. Since the introduction of TNF-alpha antagonist, the incidence of adverse cutaneous drug reactions has increased significantly. A wide range of different skin lesions might occur during TNF-alpha antagonist treatment. New onset or exacerbation of psoriasis has been reported in patients treated with TNF-alpha antagonists for a variety of rheumatologic conditions. TNF-alpha antagonist therapy has been associated with a lupus-like syndrome; most of these case reports occurred in patients receiving either etanercept or infliximab. Serious skin reactions such as erythema multiforme, Stevens-Johnson syndrome, and toxic epidermal necrolysis have been reported rarely with the use of TNF-alpha antagonists. As the use of TNF-alpha antagonists continues to increase, the diagnosis and management of cutaneous side effects will become an increasingly important challenge. In patients receiving TNF-alpha antagonist treatment, skin disease should be considered, and clinicians need to be aware of the adverse reactions of these drugs.

  10. Antagonistic and Bargaining Games in Optimal Marketing Decisions

    Science.gov (United States)

    Lipovetsky, S.

    2007-01-01

    Game theory approaches to find optimal marketing decisions are considered. Antagonistic games with and without complete information, and non-antagonistic games techniques are applied to paired comparison, ranking, or rating data for a firm and its competitors in the market. Mix strategy, equilibrium in bi-matrix games, bargaining models with…

  11. Evaluation of antagonistic fungi against charcoal rot of sunflower ...

    African Journals Online (AJOL)

    In vitro, sensitivity of Macrophomina phaseolina (Tassi) Goid determined through inhibition zone technique to various antagonistic fungi viz., Aspergillus niger, Aspergillus flavus, Trichoderma viride, Trichoderma harzianum and Penicillium capsulatum amended into PDA medium. All the antagonists reduced the colony ...

  12. Interaction between Antagonist of Cannabinoid Receptor and Antagonist of Adrenergic Receptor on Anxiety in Male Rat

    Directory of Open Access Journals (Sweden)

    Alireza Komaki

    2014-07-01

    Full Text Available Introduction: Anxiety is among the most common and treatable mental disorders. Adrenergic and cannabinoid systems have an important role in the neurobiology of anxiety. The elevated plus-maze (EPM has broadly been used to investigate anxiolytic and anxiogenic compounds. The present study investigated the effects of intraperitoneal (IP injection of cannabinoid CB1 receptor antagonist (AM251 in the presence of alpha-1 adrenergic antagonist (Prazosin on rat behavior in the EPM. Methods: In this study, the data were obtained from male Wistar rat, which weighing 200- 250 g. Animal behavior in EPM were videotaped and saved in computer for 10 min after IP injection of saline, AM251 (0.3 mg/kg, Prazosin (0.3 mg/kg and AM251 + Prazosin, subsequently scored for conventional indices of anxiety. During the test period, the number of open and closed arms entries, the percentage of entries into the open arms of the EPM, and the spent time in open and closed arms were recorded. Diazepam was considered as a positive control drug with anxiolytic effect (0.3, 0.6, 1.2 mg/kg. Results: Diazepam increased the number of open arm entries and the percentage of spent time on the open arms. IP injection of AM251 before EPM trial decreased open arms exploration and open arm entry. Whereas, Prazosin increased open arms exploration and open arm entry. This study showed that both substances in simultaneous injection have conflicting effects on the responses of each of these two compounds in a single injection. Discussion: Injection of CB1 receptor antagonist may have an anxiogenic profile in rat, whereas adrenergic antagonist has an anxiolytic effect. Further investigations are essential for better understanding of anxiolytic and anxiogenic properties and neurobiological mechanisms of action and probable interactions of the two systems.

  13. Interaction between Antagonist of Cannabinoid Receptor and Antagonist of Adrenergic Receptor on Anxiety in Male Rat.

    Science.gov (United States)

    Komaki, Alireza; Abdollahzadeh, Fatemeh; Sarihi, Abdolrahman; Shahidi, Siamak; Salehi, Iraj

    2014-01-01

    Anxiety is among the most common and treatable mental disorders. Adrenergic and cannabinoid systems have an important role in the neurobiology of anxiety. The elevated plus-maze (EPM) has broadly been used to investigate anxiolytic and anxiogenic compounds. The present study investigated the effects of intraperitoneal (IP) injection of cannabinoid CB1 receptor antagonist (AM251) in the presence of alpha-1 adrenergic antagonist (Prazosin) on rat behavior in the EPM. In this study, the data were obtained from male Wistar rat, which weighing 200- 250 g. Animal behavior in EPM were videotaped and saved in computer for 10 min after IP injection of saline, AM251 (0.3 mg/kg), Prazosin (0.3 mg/kg) and AM251 + Prazosin, subsequently scored for conventional indices of anxiety. During the test period, the number of open and closed arms entries, the percentage of entries into the open arms of the EPM, and the spent time in open and closed arms were recorded. Diazepam was considered as a positive control drug with anxiolytic effect (0.3, 0.6, 1.2 mg/kg). Diazepam increased the number of open arm entries and the percentage of spent time on the open arms. IP injection of AM251 before EPM trial decreased open arms exploration and open arm entry. Whereas, Prazosin increased open arms exploration and open arm entry. This study showed that both substances in simultaneous injection have conflicting effects on the responses of each of these two compounds in a single injection. Injection of CB1 receptor antagonist may have an anxiogenic profile in rat, whereas adrenergic antagonist has an anxiolytic effect. Further investigations are essential for better understanding of anxiolytic and anxiogenic properties and neurobiological mechanisms of action and probable interactions of the two systems.

  14. Renal angiomyoadenomatous tumour: Imaging features

    Science.gov (United States)

    Sahni, V. Anik; Hirsch, Michelle S.; Silverman, Stuart G.

    2012-01-01

    Renal angiomyoadenomatous tumour is a rare, recently described neoplasm with a distinctive histological appearance. Although reported in the pathology literature, to our knowledge, no prior reports have described its imaging appearance. We describe the computed tomography and magnetic resonance imaging features of an incidentally detected renal angiomyoadenomatous tumour that appeared as a well-marginated, solid T2-hypointense enhancing mass, in a 50-year-old woman. It is indistinguishable from a variety of benign and malignant renal neoplasms. PMID:23093565

  15. Multiple oncocytomas and renal carcinoma

    International Nuclear Information System (INIS)

    Velasquez, G.; Glass, T.A.; D'Souza, V.J.; Formanek, A.G.

    1984-01-01

    Renal oncocytoma, although rare, is being diagnosed more frequently, and criteria to differentiate it from other tumors have been described. Multiple oncocytomas have been reported, but an association between multiple oncocytomas and renal carcinoma in the same kidney has not been described. The authors report a case with two oncocytomas and a renal carcinoma in the right kidney as well as a right adrenal adenoma

  16. Stimulant effects of adenosine antagonists on operant behavior: differential actions of selective A2A and A1 antagonists

    Science.gov (United States)

    Randall, Patrick A.; Nunes, Eric J.; Janniere, Simone L.; Stopper, Colin M.; Farrar, Andrew M.; Sager, Thomas N.; Baqi, Younis; Hockemeyer, Jörg; Müller, Christa E.

    2012-01-01

    Rationale Adenosine A2A antagonists can reverse many of the behavioral effects of dopamine antagonists, including actions on instrumental behavior. However, little is known about the effects of selective adenosine antagonists on operant behavior when these drugs are administered alone. Objective The present studies were undertaken to investigate the potential for rate-dependent stimulant effects of both selective and nonselective adenosine antagonists. Methods Six drugs were tested: two nonselective adenosine antagonists (caffeine and theophylline), two adenosine A1 antagonists (DPCPX and CPT), and two adenosine A2A antagonists (istradefylline (KW6002) and MSX-3). Two schedules of reinforcement were employed; a fixed interval 240-s (FI-240 sec) schedule was used to generate low baseline rates of responding and a fixed ratio 20 (FR20) schedule generated high rates. Results Caffeine and theophylline produced rate-dependent effects on lever pressing, increasing responding on the FI-240 sec schedule but decreasing responding on the FR20 schedule. The A2A antagonists MSX-3 and istradefylline increased FI-240 sec lever pressing but did not suppress FR20 lever pressing in the dose range tested. In fact, there was a tendency for istradefylline to increase FR20 responding at a moderate dose. A1 antagonists failed to increase lever pressing rate, but DPCPX decreased FR20 responding at higher doses. Conclusions These results suggest that adenosine A2A antagonists enhance operant response rates, but A1 antagonists do not. The involvement of adenosine A2A receptors in regulating aspects of instrumental response output and behavioral activation may have implications for the treatment of effort-related psychiatric dysfunctions, such as psychomotor slowing and anergia in depression. PMID:21347642

  17. Insulin-Producing Cells Differentiated from Human Bone Marrow Mesenchymal Stem Cells In Vitro Ameliorate Streptozotocin-Induced Diabetic Hyperglycemia.

    Directory of Open Access Journals (Sweden)

    Ying Xin

    Full Text Available The two major obstacles in the successful transplantation of islets for diabetes treatment are inadequate supply of insulin-producing tissue and immune rejection. Induction of the differentiation of human bone marrow-derived mesenchymal stem cells (hMSCs into insulin-producing cells (IPCs for autologous transplantation may alleviate those limitations.hMSCs were isolated and induced to differentiate into IPCs through a three-stage differentiation protocol in a defined media with high glucose, nicotinamide, and exendin-4. The physiological characteristics and functions of IPCs were then evaluated. Next, about 3 × 10(6 differentiated cells were transplanted into the renal sub-capsular space of streptozotocin (STZ-induced diabetic nude mice. Graft survival and function were assessed by immunohistochemistry, TUNEL staining and measurements of blood glucose levels in the mice.The differentiated IPCs were characterized by Dithizone (DTZ positive staining, expression of pancreatic β-cell markers, and human insulin secretion in response to glucose stimulation. Moreover, 43% of the IPCs showed L-type Ca2+ channel activity and similar changes in intracellular Ca2+ in response to glucose stimulation as that seen in pancreatic β-cells in the process of glucose-stimulated insulin secretion. Transplantation of functional IPCs into the renal subcapsular space of STZ-induced diabetic nude mice ameliorated the hyperglycemia. Immunofluorescence staining revealed that transplanted IPCs sustainably expressed insulin, c-peptide, and PDX-1 without apparent apoptosis in vivo.IPCs derived from hMSCs in vitro can ameliorate STZ-induced diabetic hyperglycemia, which indicates that these hMSCs may be a promising approach to overcome the limitations of islet transplantation.

  18. Central Methysergide Prevents Renal Sympathoinhibition and Bradycardia during Hypotensive Hemorrhage

    Science.gov (United States)

    Veelken, Roland; Johnson, Kim; Scrogin, Karie E.

    1998-01-01

    Central methysergide prevents renal sympathoinhibition and bradycardia during hypotensive hemorrhage. Mean arterial pressure (MAP), heart rate (HR), and renal sympathetic nerve activity (RSNA) were measured in conscious rats during either hemorrhage or cardiopulmonary receptor stimulation with phenylbiguanide (PBG) after intracerebroventricular injection of the 5-HT1/5-HT2-receptor antagonist, methysergide (40 microg). Progressive hemorrhage caused an initial rise (109 +/- 33%) followed by a fall in RSNA (-60 +/- 7%) and a fall in HR (-126 +/- 7 beats/min). Methysergide delayed the hypotension and prevented both the sympathoinhibitory and bradycardic responses to hemorrhage. Systemic 5-HT3-receptor blockade did not influence responses to hemorrhage. The PBG infusion caused transient depressor(-25 +/- 6 mmHg), bradycardic (-176 +/- 40 beats/min), and renal sympathostimulatory (182 +/-47% baseline) responses that were not affected by central methysergide (-20 +/- 6 mmHg, -162 +/- 18 beats/min, 227 +/- 46% baseline). These data indicate that a central serotonergic receptor-mediated component contributes to the sympathoinhibitory and bradycardic responses to hypotensive hemorrhage in conscious rats. Furthermore, the same central 5-HT-receptor populations involved in reflex responses to hypotensive hemorrhage probably do not mediate the sympathoinhibitory response to cardiopulmonary chemosensitive 5-HT3 receptors.

  19. CT features of renal infarction

    International Nuclear Information System (INIS)

    Suzer, Okan; Shirkhoda, Ali; Jafri, S. Zafar; Madrazo, Beatrice L.; Bis, Kostaki G.; Mastromatteo, James F.

    2002-01-01

    Purpose: To demonstrate the different patterns of renal infarction to avoid pitfalls. To present 'flip-flop enhancement' pattern in renal infarction. Materials and methods: Retrospective review of a total of 41 renal infarction in 37 patients were done. These patients underwent initial CT and the diagnosis of renal infarction was confirmed with either follow up CT or at surgery. Results: Twenty-three patients had wedge-shaped focal infarcts, nine patients had global and five patients had multifocal infarcts of the kidneys. Cortical rim sign was seen predominantly with global infarcts. In five patients, a 'flip-flop enhancement' pattern was observed. In two patients, planned renal biopsies due to tumefactive renal lesions were cancelled because of 'flip-flop enhancement' pattern on follow up CTs. Conclusion: Although most of our cases were straightforward for the diagnosis of renal infarction, cases with tumefactive lesions and global infarctions without the well-known cortical rim sign were particularly challenging. We describe a new sign, flip-flop enhancement pattern, which we believe solidified the diagnosis of renal infarction in five of our cases. The authors recommend further investigations for association of flip-flop enhancement and renal infarction

  20. Sporotrichosis in Renal Transplant Patients

    Directory of Open Access Journals (Sweden)

    Paulo Gewehr

    2013-01-01

    Full Text Available The current report describes two renal transplant recipients who presented with sporotrichosis. In addition, the authors review the general aspects of sporotrichosis in renal transplant recipients reported in the literature. Sporotrichosis is a rare fungal infection in transplant patients and has been reported primarily in renal transplant recipients not treated with antifungal prophylaxis. Extracutaneous forms of sporotrichosis without skin manifestations and no previous history of traumatic injuries have been described in such patients and are difficult to diagnose. Renal transplant recipients with sporotrichosis described in the present report were successfully treated with antifungal therapy including amphotericin B deoxycholate, lipid amphotericin B formulations, fluconazole and itraconazole.

  1. Renal myxoma: a case report

    Directory of Open Access Journals (Sweden)

    Carlos Henrique C Souza

    2015-04-01

    Full Text Available Myxomas are rare tumors that can appear in many anatomical locations. There are only 14 cases of renal involvement documented in the literature. This article reports a case of renal myxoma in an elderly woman with recurrent cystitis. After five years of follow-up, the computed tomography (CT revealed a large solid tumor mass in the left kidney. Tumor resection was performed preserving the affected kidney with histopathological diagnosis of renal myxoma. The objective of this study is to report a rare case of renal myxoma, emphasizing the importance of the differential diagnosis from other benign and malignant mesenchymal tumors.

  2. Effects of astrogaloside on the inflammation and immunity of renal failure patients receiving maintenance dialysis.

    Science.gov (United States)

    Sun, Renlian; Ren, Haiwei; Wei, Jianxin

    2018-03-01

    Chronic renal failure is a type of clinical syndrome originating from chronic renal diseases. The aim of the study was to investigate the effect of astrogaloside on the inflammation and immunity of renal failure patients receiving maintenance dialysis. We randomly selected 92 renal failure patients receiving maintenance dialysis who were admitted to hospital for treatment between May, 2015 and April, 2016. Patients were randomly divided into the control (n=46) and observation (n=46) groups. Patients in the control group received the regular dialysis plus the basic treatment in Western medicine, while in the observation group, patients additionally received astrogaloside via intravenous injection as treatment. We compared the clinical efficacy of patients between the two groups, residual renal function (RRF), changes in urine volume, variations in inflammatory indicators [C-reaction protein (CRP), interleukin-6 (IL-6), IL-17, and tumor necrosis factor-α (TNF-α)] before and after treatment, and the levels of the thymus-dependent lymphocyte (T cells) subgroup (CD3 + , CD4 + , CD8 + and CD4 + /CD8 + ) in the immune system of patients after treatment. In the observation group, the total effective rate was significantly higher than that in the control group (Prenal failure patients receiving the maintenance dialysis, ameliorate the inflammatory responses, and enhance the immune function, thereby increasing the disease resistance of patients and improving the clinical symptoms.

  3. Serelaxin as a potential treatment for renal dysfunction in cirrhosis: Preclinical evaluation and results of a randomized phase 2 trial.

    Directory of Open Access Journals (Sweden)

    Victoria K Snowdon

    2017-02-01

    Full Text Available Chronic liver scarring from any cause leads to cirrhosis, portal hypertension, and a progressive decline in renal blood flow and renal function. Extreme renal vasoconstriction characterizes hepatorenal syndrome, a functional and potentially reversible form of acute kidney injury in patients with advanced cirrhosis, but current therapy with systemic vasoconstrictors is ineffective in a substantial proportion of patients and is limited by ischemic adverse events. Serelaxin (recombinant human relaxin-2 is a peptide molecule with anti-fibrotic and vasoprotective properties that binds to relaxin family peptide receptor-1 (RXFP1 and has been shown to increase renal perfusion in healthy human volunteers. We hypothesized that serelaxin could ameliorate renal vasoconstriction and renal dysfunction in patients with cirrhosis and portal hypertension.To establish preclinical proof of concept, we developed two independent rat models of cirrhosis that were characterized by progressive reduction in renal blood flow and glomerular filtration rate and showed evidence of renal endothelial dysfunction. We then set out to further explore and validate our hypothesis in a phase 2 randomized open-label parallel-group study in male and female patients with alcohol-related cirrhosis and portal hypertension. Forty patients were randomized 1:1 to treatment with serelaxin intravenous (i.v. infusion (for 60 min at 80 μg/kg/d and then 60 min at 30 μg/kg/d or terlipressin (single 2-mg i.v. bolus, and the regional hemodynamic effects were quantified by phase contrast magnetic resonance angiography at baseline and after 120 min. The primary endpoint was the change from baseline in total renal artery blood flow. Therapeutic targeting of renal vasoconstriction with serelaxin in the rat models increased kidney perfusion, oxygenation, and function through reduction in renal vascular resistance, reversal of endothelial dysfunction, and increased activation of the AKT

  4. Yokukansan and Yokukansankachimpihange Ameliorate Aggressive Behaviors in Rats with Cholinergic Degeneration in the Nucleus Basalis of Meynert

    Directory of Open Access Journals (Sweden)

    Masahiro Tabuchi

    2017-04-01

    Full Text Available Yokukansan (YKS and yokukansankachimpihange (YKSCH are traditional Japanese Kampo medicines. The latter comprises YKS along with the medicinal herbs Citrus unshiu peel and Pinellia tuber. Both of these Kampo medicines are indicated for the treatment of night crying and irritability in children and for neurosis and insomnia in adults. In recent clinical trials, YKS exhibited ameliorative effects on the behavioral and psychological symptoms of dementia, such as aggressiveness, excitement, and irritability. In the present study, we aimed to clarify the involvement of cholinergic degeneration in the nucleus basalis of Meynert (NBM in the development of aggressiveness in rats. Subsequently, using this animal model, the effects of YKS and YKSCH on aggressiveness were compared and the mechanisms underlying these effects were investigated. L-Glutamic acid (Glu was injected into the right NBM of rats to induce deterioration of cholinergic neurons. On day 8 after Glu injection, aggressive behaviors were evaluated using resident–intruder tests. After the evaluation, YKS or YKSCH was administered to rats with aggressive behaviors daily for 7 days. In some groups, the 5-HT1A receptor antagonist WAY-100635 was coadministered with YKS or YKSCH over the same period. In other groups, locomotor activity was measured on days 12–14 after Glu injection. On day 15, immunohistochemistry was then performed to examine choline acetyltransferase (ChAT activities in the NBM. Aggressive behaviors had developed on day 8 after Glu injection and were maintained until day 15. YKS and YKSCH significantly ameliorated the aggressive behaviors. These suppressive effects were entirely abolished following coadministration of WAY-100635. Finally, the number of ChAT-positive cells in the right NBM was significantly reduced on day 15 after Glu injection, and treatment with YKS or YKSCH did not ameliorate these reduced cell numbers. Our results show that unilateral Glu injections

  5. Renal computed angiography. Part I: Renal CT phlebography. Renal veins variants

    International Nuclear Information System (INIS)

    Al-Amin, M.; Krupev, M.; Hadjidekov, V.; Plachkov, I.

    2012-01-01

    The changing trend in renal surgery, transplantation and minimal invasive urology implies preprocedure evaluation of renal veins. Development of imaging methods offers new possibilities for venographic visualization. The goal of this study is to present authors experience in visualization of renal veins using 64 MDCT and to evaluate the utility in assessments of their variants. 128 patients (68 females and 60 males, mean age 53,3) with urological complaints underwent 64MDCT examination including CT angiography. Contrast enhancement includes 3-4ml/sec injection flow of 90 ml contrast medium followed by 20 ml saline at the same rate. In 23 out of 128 examined patients some of the common variants of the renal vein is found. 64 MDCT angiography visualize very well renal veins and becomes method of choice in preoperative assessment of renal vein anatomy. (authors)

  6. General Information about Renal Cell Cancer

    Science.gov (United States)

    ... Tumors Treatment Genetics of Kidney Cancer Research Renal Cell Cancer Treatment (PDQ®)–Patient Version General Information About Renal Cell Cancer Go to Health Professional Version Key Points Renal ...

  7. Treatment Option Overview (Renal Cell Cancer)

    Science.gov (United States)

    ... Tumors Treatment Genetics of Kidney Cancer Research Renal Cell Cancer Treatment (PDQ®)–Patient Version General Information About Renal Cell Cancer Go to Health Professional Version Key Points Renal ...

  8. The Role of Vasodilator Receptors of Renin-angiotensin System on Nitric Oxide Formation and Kidney Circulation after Angiotensin II Infusion in Renal Ischemia/Reperfusion Rats.

    Science.gov (United States)

    Maleki, Maryam; Hasanshahi, Jalal; Moslemi, Fatemeh

    2018-01-01

    Nitric oxide (NO) as a vasodilator factor has renoprotective effect against renal ischemia. The balance between angiotensin II (Ang II) and NO can affect kidney homeostasis. The aim of this study was to determine NO alteration in response to renin-Ang system vasodilator receptors antagonists (PD123319; Ang II type 2 receptor antagonist and A779; Mas receptor antagonist) in renal ischemia/reperfusion injury (IRI) in rats. Sixty-three Wistar male and female rats were used. Animals from each gender were divided into four groups received saline, Ang II, PD123319 + Ang II, and A779 + Ang II after renal IRI. Renal IRI induced with an adjustable hook. Blood pressure and renal blood flow (RBF) measured continuously. The nitrite levels were measured in serum, kidney, and urine samples. In female rats, the serum and kidney nitrite levels increased significantly by Ang II ( P < 0.05) and decreased significantly ( P < 0.05) when PD123319 was accompanied with Ang II. Such observation was not seen in male. Ang II decreased RBF significantly in all groups ( P < 0.05), while PD + Ang II group showed significant decrease in RBF in comparison with the other groups in female rats ( P < 0.05). Males show more sensibility to Ang II infusion; in fact, it is suggested that there is gender dimorphism in the Ang II and NO production associated with vasodilator receptors.

  9. Current position of 5HT3 antagonists and the additional value of NK1 antagonists; a new class of antiemetics

    NARCIS (Netherlands)

    R. de Wit (Ronald)

    2003-01-01

    textabstractThe advent of the 5HT3 receptor antagonists (5HT3 antagonists) in the 1990s and the combination with dexamethasone has resulted in acute emesis protection in 70% of patients receiving highly emetogenic chemotherapy. Despite complete protection in the acute phase, however, 40% of patients

  10. The renal scan in pregnant renal transplant patients

    International Nuclear Information System (INIS)

    Goldstein, H.A.; Ziessman, H.A.; Fahey, F.H.; Collea, J.V.; Alijani, M.R.; Helfrich, G.B.

    1985-01-01

    With the greater frequency of renal transplant surgery, more female pts are becoming pregnant and carrying to term. In the renal allograft blood vessels and ureter may be compressed resulting in impaired renal function and/or, hypertension. Toxemia of pregnancy is seen more frequently than normal. Radionuclide renal scan monitoring may be of significant value in this high risk obstetrical pt. After being maintained during the pregnancy, renal function may also deteriorate in the post partum period. 5 pregnant renal transplant pts who delivered live babies had renal studies with Tc-99m DTPA to assess allograft perfusion and function. No transplanted kidney was lost during or after pregnancy as a result of pregnancy. No congenital anomalies were associated with transplant management. 7 studies were performed on these 5 pts. The 7 scans all showed the uterus/placenta. The bladder was always distorted. The transplanted kidney was rotated to a more vertical position in 3 pts. The radiation dose to the fetus is calculated at 0.024 rad/mCi administered. This study demonstrates the anatomic and physiologic alterations expected in the transplanted kidney during pregnancy when evaluated by renal scan and that the radiation burden may be acceptable in management of these pts

  11. Ameliorative Effect of Gallic Acid on Cyclophosphamide-Induced Oxidative Injury and Hepatic Dysfunction in Rats

    Science.gov (United States)

    Olayinka, Ebenezer Tunde; Ore, Ayokanmi; Ola, Olaniyi Solomon; Adeyemo, Oluwatobi Adewumi

    2015-01-01

    Cyclophosphamide (CP), a bifunctional alkylating agent used in chemotherapy has been reported to induce organ toxicity mediated by generation of reactive oxygen species and oxidative stress. Gallic acid (GA), a phenolic substance, is a natural antioxidant with proven free radical scavenging activity and offers protection against oxidative damage. This research study was designed to investigate the ameliorative effect of GA against CP-induced toxicity in rats. Twenty-five male Wistar rats (180–200 g) were randomized into five treatment groups: (A) control, (B) CP, 2 mg/kg body weight (b.w.), (C) pre-treatment with GA (20 mg/kg b.w.) for seven days followed by CP (2 mg/kg b.w.) for seven days, (D) co-treatment with GA (20 mg/kg b.w) and CP (2 mg/kg b.w.) for seven days, and (E) GA (20 mg/kg b.w.) for seven days. CP induced marked renal and hepatic damages as plasma levels of urea, creatinine, bilirubin and activities of AST, ALT, ALP and GGT were significantly elevated (p acid. PMID:29083393

  12. Cobrotoxin from Naja naja atra Venom Ameliorates Adriamycin Nephropathy in Rats

    Directory of Open Access Journals (Sweden)

    Shu-Zhi Wang

    2015-01-01

    Full Text Available Chronic kidney disease (CKD becomes a global health problem with high morbidity and mortality. Adriamycin- (ADR- induced rodent chronic nephropathy is a classic experimental model of human minimal lesion nephrotic syndrome. The present study investigated the effect of cobrotoxin (CTX on ADR-induced nephropathy. Rats were given 6 mg/kg ADR once through the tail vein to replicate ADR nephropathy model. CTX was administered to rats daily by placing a fast dissolving CTX membrane strip under the tongue starting from 5 days prior to ADR administration until the end of experiment. The results showed that CTX ameliorated the symptoms of ADR nephropathy syndrome with reduced body weight loss, proteinuria, hypoalbuminemia, dyslipidemia, serum electrolyte imbalance, oxidative stress, renal function abnormities, and kidney pathological lesions. Anti-inflammatory cytokine IL-10 expression was elevated after CTX administration in ADR nephropathy model. CTX inhibited the phosphorylation of IκB-α and NF-κB p65 nuclear translocation. Meanwhile, CTX upregulated the protein level of podocyte-specific nephrin and downregulated the level of fibrosis-related TGF-β. These findings suggest that CTX may be a potential drug for chronic kidney diseases.

  13. Ameliorative effects of pine bark extract on cisplatin-induced acute kidney injury in rats.

    Science.gov (United States)

    Lee, In-Chul; Ko, Je-Won; Park, Sung-Hyeuk; Shin, Na-Rae; Shin, In-Sik; Kim, Yun-Bae; Kim, Jong-Choon

    2017-11-01

    This study investigated the dose-response effects of pine bark extract (PBE, pycnogenol ® ) on oxidative stress-mediated apoptotic changes induced by cisplatin (Csp) in rats. The ameliorating potential of PBE was evaluated after orally administering PBE at doses of 10 or 20 mg/kg for 10 days. Acute kidney injury was induced by a single intraperitoneal injection of Csp at 7 mg/kg on test day 5. Csp treatment caused acute kidney injury manifested by elevated levels of serum blood urea nitrogen (BUN) and creatinine (CRE) with corresponding histopathological changes, including degeneration of tubular epithelial cells, hyaline casts in the tubular lumen, and inflammatory cell infiltration (interstitial nephritis). Csp also induced significant apoptotic changes in renal tubular cells. In addition, Csp treatment induced high levels of oxidative stress, as evidenced by an increased level of malondialdehyde, depletion of the reduced glutathione (GSH) content, and decreased activities of glutathione S-transferase, superoxide dismutase, and catalase in kidney tissues. On the contrary, PBE treatment lowered BUN and CRE levels and effectively attenuated histopathological alterations and apoptotic changes induced by Csp. Additionally, treatment with PBE suppressed lipid peroxidation, prevented depletion of GSH, and enhanced activities of the antioxidant enzymes in kidney tissue. These results indicate that PBE has a cytoprotective effect against oxidative stress-mediated apoptotic changes caused by Csp in the rat kidney, which may be attributed to both increase of antioxidant enzyme activities and inhibition of lipid peroxidation.

  14. Renal posttransplant's vascular complications

    Directory of Open Access Journals (Sweden)

    Bašić Dragoslav

    2003-01-01

    Full Text Available INTRODUCTION Despite high graft and recipient survival figures worldwide today, a variety of technical complications can threaten the transplant in the postoperative period. Vascular complications are commonly related to technical problems in establishing vascular continuity or to damage that occurs during donor nephrectomy or preservation [13]. AIM The aim of the presenting study is to evaluate counts and rates of vascular complications after renal transplantation and to compare the outcome by donor type. MATERIAL AND METHODS A total of 463 kidneys (319 from living related donor LD and 144 from cadaveric donor - CD were transplanted during the period between June 1975 and December 1998 at the Urology & Nephrology Institute of Clinical Centre of Serbia in Belgrade. Average recipients' age was 33.7 years (15-54 in LD group and 39.8 (19-62 in CD group. Retrospectively, we analyzed medical records of all recipients. Statistical analysis is estimated using Hi-squared test and Fischer's test of exact probability. RESULTS Major vascular complications including vascular anastomosis thrombosis, internal iliac artery stenosis, internal iliac artery rupture obliterant vasculitis and external iliac vein rupture were analyzed. In 25 recipients (5.4% some of major vascular complications were detected. Among these cases, 22 of them were from CD group vs. three from LD group. Relative rate of these complications was higher in CD group vs. LD group (p<0.0001. Among these complications dominant one was vascular anastomosis thrombosis which occurred in 18 recipients (17 from CD vs. one from LD. Of these recipients 16 from CD lost the graft, while the rest of two (one from each group had lethal outcome. DISCUSSION Thrombosis of renal allograft vascular anastomosis site is the most severe complication following renal transplantation. In the literature, renal allograft thrombosis is reported with different incidence rates, from 0.5-4% [14, 15, 16]. Data from the

  15. Citrato y litiasis renal

    Directory of Open Access Journals (Sweden)

    Elisa E. Del Valle

    2013-08-01

    Full Text Available El citrato es un potente inhibidor de la cristalización de sales de calcio. La hipocitraturia es una alteración bioquímica frecuente en la formación de cálculos de calcio en adultos y especialmente en niños. El pH ácido (sistémico, tubular e intracelular es el principal determinante de la excreción de citrato en la orina. Si bien la mayoría de los pacientes con litiasis renal presentan hipocitraturia idiopática, hay un número de causas para esta anormalidad que incluyen acidosis tubular renal distal, hipokalemia, dietas ricas en proteínas de origen animal y/o dietas bajas en álcalis y ciertas drogas, como la acetazolamida, topiramato, IECA y tiazidas. Las modificaciones dietéticas que benefician a estos pacientes incluyen: alta ingesta de líquidos y frutas, especialmente cítricos, restricción de sodio y proteínas, con consumo normal de calcio. El tratamiento con citrato de potasio es efectivo en pacientes con hipocitraturia primaria o secundaria y en aquellos desordenes en la acidificación, que provocan un pH urinario persistentemente ácido. Los efectos adversos son bajos y están referidos al tracto gastrointestinal. Si bien hay diferentes preparaciones de citrato (citrato de potasio, citrato de sodio, citrato de potasio-magnesio en nuestro país solo está disponible el citrato de potasio en polvo que es muy útil para corregir la hipocitraturia y el pH urinario bajo, y reducir marcadamente la recurrencia de la litiasis renal.

  16. The Effect of Vitamin E on Ameliorating Primary Dysmenorrhea: A ...

    African Journals Online (AJOL)

    Dysmenorrhea or painful menstruation is one of the most common problems of women. Using systematic review and meta‑analysis, this study aimed to determine the effect of vitamin E on ameliorating the intensity of pain of primary dysmenorrhea. Available databases comprising PubMed, Google Scholar, ISI, Science ...

  17. Designing urban parks that ameliorate the effects of climate change

    NARCIS (Netherlands)

    Brown, R.D.; Vanos, J.; Kenny, N.; Lenzholzer, S.

    2015-01-01

    Many inhabitants of cities throughout the world suffer from health problems and discomfort that are caused by overheating of urban areas, and there is compelling evidence that these problems will be exacerbated by global climate change. Most cities are not designed to ameliorate these effects

  18. Oral Metformin-Ascorbic Acid Co-Administration Ameliorates Alcohol ...

    African Journals Online (AJOL)

    Oral Metformin-Ascorbic Acid Co-Administration Ameliorates Alcohol-Induced Hepatotoxicity In Rats. ... Nigerian Quarterly Journal of Hospital Medicine ... the present in vivo animal study was to determine whether metformin-ascorbic acid co-administration also prevents alcoholic hepatotoxicity in chronic alcohol exposure.

  19. Antibiotics can ameliorate circulatory complications of liver cirrhosis

    DEFF Research Database (Denmark)

    Madsen, Bjørn Stæhr; Schaffalitzky de Muckadell, Ove B

    2011-01-01

    . This review focuses on how broad spectrum antibiotics can ameliorate the haemodynamic consequences of bacterial translocation. It is possible that the use of broad spectrum antibiotics in the future may be used to prevent other complications of liver cirrhosis than spontaneous bacterial peritonitis...

  20. Ameliorative effect of the hydroethanolic whole plant extract of ...

    African Journals Online (AJOL)

    At the end of the study, biochemical markers of nitrosative and oxidative stress status were determined. Results: DH (12.5, 50 and 100 mg/kg) significantly ameliorated haloperidol-induced catalepsy (bar test), spontaneous motor and working memory deficits (open field and elevated plus maze tests, respectively), ...

  1. Ameliorative effects of Cnidoscolus aconitifolius on anaemia and ...

    African Journals Online (AJOL)

    STORAGESEVER

    2008-06-03

    Jun 3, 2008 ... This study was designed to evaluate the ameliorative effect of ... The group fed with 20% C. aconitifolius in place of 20% soya protein also ... to cholesterol enrichment of the erythrocytes membrane, ... rabbit and horse erythrocytes membrane with 1,2- .... various substances such as iron, vitamins and protein.

  2. Ameliorative effects of Cnidoscolus aconitifolius on anaemia and ...

    African Journals Online (AJOL)

    This study was designed to evaluate the ameliorative effect of dietary supplementation of Cnidoscolus aconitifolius leaf on anaemia and changes in erythrocyte osmotic fragility in protein energy malnourished rats. Protein energy malnutrition has been associated with anaemia and changes in osmotic fragility, deformability ...

  3. Automatic quantitative renal scintigraphy

    International Nuclear Information System (INIS)

    Valeyre, J.; Deltour, G.; Delisle, M.J.; Bouchard, A.

    1976-01-01

    Renal scintigraphy data may be analyzed automatically by the use of a processing system coupled to an Anger camera (TRIDAC-MULTI 8 or CINE 200). The computing sequence is as follows: normalization of the images; background noise subtraction on both images; evaluation of mercury 197 uptake by the liver and spleen; calculation of the activity fractions on each kidney with respect to the injected dose, taking into account the kidney depth and the results referred to normal values; edition of the results. Automation minimizes the scattering parameters and by its simplification is a great asset in routine work [fr

  4. Imaging of renal metastases

    International Nuclear Information System (INIS)

    Bruneton, J.N.; Normand, F.; Balu-Maestro, C.; Rogopoulos, A.; Drouillard, J.; Laurent, F.

    1988-01-01

    Metastases are the most frequent malignant tumors of the kidney, but these lesions are of late onset in neoplastic disease. The 19 cases reported here were all investigated with various imaging techniques (CT 12 cases, ultrasonography 12 cases, urography 8 cases, angiography 2 cases, MRI 1 case). The most common primary malignancies were lung cancer, melanoma and cancer of the controlateral kidney. In this series, 8 of the lesions were solitary, and 9 were unilateral. Tumor vascularity was evaluated in 15 cases: 14 of these lesions were hypovascular. The differential diagnosis includes small cysts, lymphoma, bilateral renal cancer, multiple small abscesses and multiple small infarcts [fr

  5. Ameliorating effects of goby fish protein hydrolysates on high-fat-high-fructose diet-induced hyperglycemia, oxidative stress and deterioration of kidney function in rats.

    Science.gov (United States)

    Nasri, Rim; Abdelhedi, Ola; Jemil, Ines; Daoued, Ines; Hamden, Khaled; Kallel, Choumous; Elfeki, Abdelfattah; Lamri-Senhadji, Myriem; Boualga, Ahmed; Nasri, Moncef; Karra-Châabouni, Maha

    2015-12-05

    This study investigated the therapeutic potential of undigested goby fish (Zosterisessor ophiocephalus) muscle proteins (UGP) and their hydrolysates on high-fat-high-fructose diet (HFFD)-fed rats. HFFD induced hyperglycemia, manifested by a significant increase in the levels of glucose and glycogen as well as α-amylase activity when compared to normal rats. The administration of GPHs to HFFD-fed rats significantly decreased α-amylase activity and the contents of blood glucose and hepatic glycogen. By contrast, the UGP increased the glucose metabolic disorders in HFFD-fed rats. Furthermore, HFFD-fed rats showed oxidative stress, as evidenced by decreased antioxidant enzyme activities and glutathione (GSH) levels and increased concentration of the lipid peroxidation product malondialdehyde in liver and kidney. Interestingly, the daily gavage of UGP and GPHs improved the redox status in liver and kidney of HFFD-rats by ameliorating or reversing the above-mentioned changes. Moreover, GPHs exhibited a renal protective role by reversing the HFFD-induced decease of uric acid and increase of creatinine levels in serum and preventing some HFFD-induced changes in kidney architecture. The results demonstrate that GPHs contain bioactive peptides that possess significant hypoglycemic and antioxidant properties, and ameliorate renal damage in rats fed hypercaloric diet. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  6. The antagonistic effect of Banana bunchy top virus multifunctional protein B4 against Fusarium oxysporum.

    Science.gov (United States)

    Zhuang, Jun; Coates, Christopher J; Mao, Qianzhuo; Wu, Zujian; Xie, Lianhui

    2016-06-01

    The viral-induced banana bunchy top disease and the fungal-induced banana blight are two major causes of concern for industrial scale production of bananas. Banana blight is particularly troublesome, affecting ∼80% of crops worldwide. Strict guidelines and protocols are in place in order to ameliorate the effects of this devastating disease, yet little success has been achieved. From the data presented here, we have found that Banana bunchy top virus (BBTV)-infected bananas are more resistant to Fusarium oxysporum f. sp. cubense (Foc). BBTV appears to be antagonistic towards Foc, thus improving the survivability of plants against blight. The BBTV suppressor of RNA silencing, namely protein B4, displays fungicidal properties in vitro. Furthermore, transgenic tomatoes expressing green fluorescent protein (GFP)-tagged protein B4 demonstrate enhanced resistance to F. oxysporum f. sp. lycopersici (Fol). Differential gene expression analysis indicates that increased numbers of photogenesis-related gene transcripts are present in dark-green leaves of B4-GFP-modified tomato plants relative to those found in WT plants. Conversely, the transcript abundance of immunity-related genes is substantially lower in transgenic tomatoes compared with WT plants, suggesting that plant defences may be influenced by protein B4. This viral-fungal interaction provides new insights into microbial community dynamics within a single host and has potential commercial value for the breeding of transgenic resistance to Fusarium-related blight/wilt. © 2016 BSPP AND JOHN WILEY & SONS LTD.

  7. [Effect of the estrogen antagonist tamoxifen in the treatment of advanced mastocarcinoma (author's transl)].

    Science.gov (United States)

    Szepesi, T; Kärcher, K H

    1977-12-01

    Today the endocrin therapy of the advanced mastocarcinoma is in common use. Besides the already known therapy by estrogens, androgens, gestagens, and steroids, Tamoxifen, and estrogen antagonist, is a very promising therapeutic drug. In the presented study, Tamoxifen was submitted to a critical clinical control during a period of one year from 1st October 1975 until 1st October 1976. After a three months' treatment, a rate of 41% of objective remissions could be obtained. The criteria of success were estimated according to the scheme of Karnofsky. The average remission time is 5,5 months. By a determination of the estrogen receptors it would be possible to realize a therapeutic selection and to achieve a higher remission rate. The authors made an interesting observation, i.e. a probably immuno-stimulating effect which, however, still has to be submitted to further examinations. The side effects are described in detail and the indications are established. Its is astonishing that the subjective ameliorations, i.e. cessation of pains in case of generalized formation of metastases in the bones are much more frequent than the objective remissions. We came to the conclusion that the treatment by Tamoxifen is a valuable alternative in the therapy of the mastocarcinoma, above all in the postmenopausal period if the disease is advanced and incurable.

  8. Renal involvement in behcet's disease

    International Nuclear Information System (INIS)

    Ardalan, Mohammad Reza; Noshad, Hamid; Sadreddini, Shahram; Ebrahimi, Aliasghar; Molaeefard, Mahsheed; Somi, Mohammad Hossein; Shoja, Mohammadali Mohajel

    2009-01-01

    There are conflicting reports about the renal involvement in Behcet's disease (BD). In this study we aimed to study the frequency and type of renal involvement in a group of patients with BD in Azerbaijan province that is one of the prevalent areas of BD in Iran. All cases of BD were prospectively followed between June 2004 and January 2007, and evaluated for renal dys-function (serum creatinine > 1.7 mg/dL), glomerular hematuria and proteinuria. Those patients with proteinuria > 500 mg/day and serum creatinine level > 2 mg/dL, underwent renal biopsy. From a total number of 100 patients, six patients (6%) had obvious renal involvements. Four patients had glomerular hematuria and proteinuria. Renal biopsy in two of them revealed measangial proliferative glumerulonephritis with IgA deposit in one of them and membranoproliferative glumerolonephritis in another one. Two remaining patients had serum creatinine > 2 mg/dL without any hematuria or proteinuria. Serologic study for viral agents and collagen vascular disease were negative in all patients with renal involvements. In conclusion, renal involvement in BD is not infrequent, although in most cases it is mild in nature and may be missed. (author)

  9. Leiomyosarcoma of the renal vein

    Directory of Open Access Journals (Sweden)

    Lemos Gustavo C.

    2003-01-01

    Full Text Available Leiomyosarcoma of the renal vein is a rare tumor of complex diagnosis. We presented a case of renal vein leiomyosarcoma detected in a routine study. The primary treatment was complete surgical removal of the mass. In cases where surgical removal is not possible the prognosis is poor, with high rates of local recurrence and distant spread.

  10. Ultrasonography in chronic renal failure

    International Nuclear Information System (INIS)

    Buturovic-Ponikvar, Jadranka; Visnar-Perovic, Alenka

    2003-01-01

    Many chronic renal diseases lead to the final common state of decrease in renal size, parenchymal atrophy, sclerosis and fibrosis. The ultrasound image show a smaller kidney, thinning of the parenchyma and its hyperechogenicity (reflecting sclerosis and fibrosis). The frequency of renal cysts increases with the progression of the disease. Ultrasound generally does not allow for the exact diagnosis of an underlying chronic disease (renal biopsy is usually required), but it can help to determine an irreversible disease, assess prognosis and avoid unnecessary diagnostic or therapeutic procedures. The main exception in which the ultrasound image does not show a smaller kidney with parenchymal atrophy is diabetic nephropathy, the leading cause of chronic and end-stage renal failure in developed countries in recent years. In this case, both renal size and parenchymal thickness are preserved until end-stage renal failure. Doppler study of intrarenal vessels can provide additional information about microvascular and parenchymal lesions, which is helpful in deciding for or against therapeutic intervention and timely planning for optimal renal replacement therapy option

  11. Modulatory effect of fenugreek seed mucilage and spent turmeric on intestinal and renal disaccharidases in streptozotocin induced diabetic rats.

    Science.gov (United States)

    Kumar, G Suresh; Shetty, A K; Salimath, P V

    2005-06-01

    To elucidate the effect of feeding fenugreek seed mucilage and spent turmeric (10%) on disaccharidases activities, the specific activities of intestinal and renal disaccharidases viz., sucrase, maltase and lactase were measured in streptozotocin induced diabetic rats. Specific activities of intestinal disaccharidases were increased significantly during diabetes and amelioration of these activities during diabetes was clearly visible by supplementing fenugreek seed mucilage and spent turmeric in the diet. However during diabetes renal disaccharidases activities were significantly lower than those in the control rats. Fenugreek seed mucilage and spent turmeric supplementations were beneficial in alleviating the reduction in maltase activity during diabetes, however not much change in the activities of sucrase and lactase was observed upon feeding. This positive influence of feeding fenugreek seed mucilage and spent turmeric on intestinal and renal disaccharidases clearly indicates their beneficial role in the management of diabetes.

  12. Antagonistic neural networks underlying differentiated leadership roles

    Science.gov (United States)

    Boyatzis, Richard E.; Rochford, Kylie; Jack, Anthony I.

    2014-01-01

    The emergence of two distinct leadership roles, the task leader and the socio-emotional leader, has been documented in the leadership literature since the 1950s. Recent research in neuroscience suggests that the division between task-oriented and socio-emotional-oriented roles derives from a fundamental feature of our neurobiology: an antagonistic relationship between two large-scale cortical networks – the task-positive network (TPN) and the default mode network (DMN). Neural activity in TPN tends to inhibit activity in the DMN, and vice versa. The TPN is important for problem solving, focusing of attention, making decisions, and control of action. The DMN plays a central role in emotional self-awareness, social cognition, and ethical decision making. It is also strongly linked to creativity and openness to new ideas. Because activation of the TPN tends to suppress activity in the DMN, an over-emphasis on task-oriented leadership may prove deleterious to social and emotional aspects of leadership. Similarly, an overemphasis on the DMN would result in difficulty focusing attention, making decisions, and solving known problems. In this paper, we will review major streams of theory and research on leadership roles in the context of recent findings from neuroscience and psychology. We conclude by suggesting that emerging research challenges the assumption that role differentiation is both natural and necessary, in particular when openness to new ideas, people, emotions, and ethical concerns are important to success. PMID:24624074

  13. Antagonistic Neural Networks Underlying Differentiated Leadership Roles

    Directory of Open Access Journals (Sweden)

    Richard Eleftherios Boyatzis

    2014-03-01

    Full Text Available The emergence of two distinct leadership roles, the task leader and the socio-emotional leader, has been documented in the leadership literature since the 1950’s. Recent research in neuroscience suggests that the division between task oriented and socio-emotional oriented roles derives from a fundamental feature of our neurobiology: an antagonistic relationship between two large-scale cortical networks -- the Task Positive Network (TPN and the Default Mode Network (DMN. Neural activity in TPN tends to inhibit activity in the DMN, and vice versa. The TPN is important for problem solving, focusing of attention, making decisions, and control of action. The DMN plays a central role in emotional self-awareness, social cognition, and ethical decision making. It is also strongly linked to creativity and openness to new ideas. Because activation of the TPN tends to suppress activity in the DMN, an over-emphasis on task oriented leadership may prove deleterious to social and emotional aspects of leadership. Similarly, an overemphasis on the DMN would result in difficulty focusing attention, making decisions and solving known problems. In this paper, we will review major streams of theory and research on leadership roles in the context of recent findings from neuroscience and psychology. We conclude by suggesting that emerging research challenges the assumption that role differentiation is both natural and necessary, in particular when openness to new ideas, people, emotions, and ethical concerns are important to success.

  14. Antagonistic neural networks underlying differentiated leadership roles.

    Science.gov (United States)

    Boyatzis, Richard E; Rochford, Kylie; Jack, Anthony I

    2014-01-01

    The emergence of two distinct leadership roles, the task leader and the socio-emotional leader, has been documented in the leadership literature since the 1950s. Recent research in neuroscience suggests that the division between task-oriented and socio-emotional-oriented roles derives from a fundamental feature of our neurobiology: an antagonistic relationship between two large-scale cortical networks - the task-positive network (TPN) and the default mode network (DMN). Neural activity in TPN tends to inhibit activity in the DMN, and vice versa. The TPN is important for problem solving, focusing of attention, making decisions, and control of action. The DMN plays a central role in emotional self-awareness, social cognition, and ethical decision making. It is also strongly linked to creativity and openness to new ideas. Because activation of the TPN tends to suppress activity in the DMN, an over-emphasis on task-oriented leadership may prove deleterious to social and emotional aspects of leadership. Similarly, an overemphasis on the DMN would result in difficulty focusing attention, making decisions, and solving known problems. In this paper, we will review major streams of theory and research on leadership roles in the context of recent findings from neuroscience and psychology. We conclude by suggesting that emerging research challenges the assumption that role differentiation is both natural and necessary, in particular when openness to new ideas, people, emotions, and ethical concerns are important to success.

  15. Exercise training normalizes renal blood flow responses to acute hypoxia in experimental heart failure: role of the α1-adrenergic receptor.

    Science.gov (United States)

    Pügge, Carolin; Mediratta, Jai; Marcus, Noah J; Schultz, Harold D; Schiller, Alicia M; Zucker, Irving H

    2016-02-01

    Recent data suggest that exercise training (ExT) is beneficial in chronic heart failure (CHF) because it improves autonomic and peripheral vascular function. In this study, we hypothesized that ExT in the CHF state ameliorates the renal vasoconstrictor responses to hypoxia and that this beneficial effect is mediated by changes in α1-adrenergic receptor activation. CHF was induced in rabbits. Renal blood flow (RBF) and renal vascular conductance (RVC) responses to 6 min of 5% isocapnic hypoxia were assessed in the conscious state in sedentary (SED) and ExT rabbits with CHF with and without α1-adrenergic blockade. α1-adrenergic receptor expression in the kidney cortex was also evaluated. A significant decline in baseline RBF and RVC and an exaggerated renal vasoconstriction during acute hypoxia occurred in CHF-SED rabbits compared with the prepaced state (P renal denervation (DnX) blocked the hypoxia-induced renal vasoconstriction in CHF-SED rabbits. α1-adrenergic protein in the renal cortex of animals with CHF was increased in SED animals and normalized after ExT. These data provide evidence that the acute decline in RBF during hypoxia is caused entirely by the renal nerves but is only partially mediated by α1-adrenergic receptors. Nonetheless, α1-adrenergic receptors play an important role in the beneficial effects of ExT in the kidney. Copyright © 2016 the American Physiological Society.

  16. A high-fat diet increases oxidative renal injury and protein glycation in D-galactose-induced aging rats and its prevention by Korea red ginseng.

    Science.gov (United States)

    Park, Sok; Kim, Chan-Sik; Min, Jinah; Lee, Soo Hwan; Jung, Yi-Sook

    2014-01-01

    Declining renal function is commonly observed with age. Obesity induced by a high-fat diet (HFD) may reduce renal function. Korean red ginseng (KRG) has been reported to ameliorate oxidative tissue injury and have an anti-aging effect. This study was designed to investigate whether HFD would accelerate the D-galactose-induced aging process in the rat kidney and to examine the preventive effect of KRG on HFD and D-galactose-induced aging-related renal injury. When rats with D-galactose-induced aging were fed an HFD for 9 wk, enhanced oxidative DNA damage, renal cell apoptosis, protein glycation, and extracellular high mobility group box 1 protein (HMGB1), a signal of tissue damage, were observed in renal glomerular cells and tubular epithelial cells. However, treatment of rats with HFD- plus D-galactose-induced aging with KRG restored all of these renal changes. Our data suggested that a long-term HFD may enhance D-galactose-induced oxidative renal injury in rats and that this age-related renal injury could be suppressed by KRG through the repression of oxidative injury.

  17. Acute renal failure after rifampicin

    Directory of Open Access Journals (Sweden)

    Adriana Weinberg

    1984-12-01

    Full Text Available A patient with miliary tuberculosis and a chronic urogenital focus is described, who had a borderline renal function at diagnosis and developed overt renal failure upon daily treatment with rifampin (RMP, isoniazid (INH and ethambutol (EMB. This is the first Brazilian report of BMP induced renal damage. A renal biopsy taken on the third day of oliguria showed recent tubular necrosis with acute interstitial inflammation and granuloma formation. The aspect of the granulomatous lesion hightly suggested drug etiology because of the lack of palisading, high incidence of neutrophils and absence of facid-fast bacilli. This is the first presentation of an acute granulomatous interstitial nephritis probably due to RMP. Furthermore the pathogenesis of the renal damage caused by tuberculosis and RMP are discussed.

  18. Fetal programming of renal function.

    Science.gov (United States)

    Dötsch, Jörg; Plank, Christian; Amann, Kerstin

    2012-04-01

    Results from large epidemiological studies suggest a clear relation between low birth weight and adverse renal outcome evident as early as during childhood. Such adverse outcomes may include glomerular disease, hypertension, and renal failure and contribute to a phenomenon called fetal programming. Other factors potentially leading to an adverse renal outcome following fetal programming are maternal diabetes mellitus, smoking, salt overload, and use of glucocorticoids during pregnancy. However, clinical data on the latter are scarce. Here, we discuss potential underlying mechanisms of fetal programming, including reduced nephron number via diminished nephrogenesis and other renal (e.g., via the intrarenal renin-angiotensin-aldosterone system) and non-renal (e.g., changes in endothelial function) alterations. It appears likely that the outcomes of fetal programming may be influenced or modified postnatally, for example, by the amount of nutrients given at critical times.

  19. Renal manifestations of primary hyperparathyroidism

    Directory of Open Access Journals (Sweden)

    Anurag Ranjan Lila

    2012-01-01

    Full Text Available Primary hyperparathyroidism (PHPT is associated with nephrolithiasis and nephrocalcinosis. Hypercalciuria is one of the multiple factors that is implicated in the complex pathophysiology of stone formation. The presence of a renal stone (symptomatic or asymptomatic categorizes PHPT as symptomatic and is an indication for parathyroid adenomectomy. Progression of nephrocalcinosis is largely reversible after successful surgery, but the residual risk persists. PHPT is also associated with declining renal function. In case of asymptomatic mild PHPT, annual renal functional assessment is advised. Guidelines suggest that an estimated glomerular filtration rate (eGFR < 60 ml / minute / 1.73 m 2 is an indication for parathyroid adenomectomy. This article discusses how to monitor and manage renal stones and other related renal parameters in case of PHPT.

  20. Renal replacement therapy in Europe

    DEFF Research Database (Denmark)

    Pippias, Maria; Stel, Vianda S; Abad Diez, José Maria

    2015-01-01

    BACKGROUND: This article summarizes the 2012 European Renal Association-European Dialysis and Transplant Association Registry Annual Report (available at www.era-edta-reg.org) with a specific focus on older patients (defined as ≥65 years). METHODS: Data provided by 45 national or regional renal...... disease (ESRD) receiving renal replacement therapy (RRT) and renal transplantation rates for 2012 are presented. RESULTS: In 2012, the overall unadjusted incidence rate of patients with ESRD receiving RRT was 109.6 per million population (pmp) (n = 69 035), ranging from 219.9 pmp in Portugal to 24.2 pmp...... to 32% between countries. The overall renal transplantation rate in 2012 was 28.3 pmp (n = 15 673), with the highest rate seen in the Spanish region of Catalonia. The proportion of patients ≥65 years receiving a transplant ranged from 0 to 35%. Five-year adjusted survival for all RRT patients was 59...

  1. PA21, a novel phosphate binder, improves renal osteodystrophy in rats with chronic renal failure.

    Science.gov (United States)

    Yaguchi, Atsushi; Tatemichi, Satoshi; Takeda, Hiroo; Kobayashi, Mamoru

    2017-01-01

    The effects of PA21, a novel iron-based and non-calcium-based phosphate binder, on hyperphosphatemia and its accompanying bone abnormality in chronic kidney disease-mineral and bone disorder (CKD-MBD) were evaluated. Rats with adenine-induced chronic renal failure (CRF) were prepared by feeding them an adenine-containing diet for four weeks. They were also freely fed a diet that contained PA21 (0.5, 1.5, and 5%), sevelamer hydrochloride (0.6 and 2%) or lanthanum carbonate hydrate (0.6 and 2%) for four weeks. Blood biochemical parameters were measured and bone histomorphometry was performed for femurs, which were isolated after drug treatment. Serum phosphorus and parathyroid hormone (PTH) levels were higher in the CRF rats. Administration of phosphate binders for four weeks decreased serum phosphorus and PTH levels in a dose-dependent manner and there were significant decreases in the AUC0-28 day of these parameters in 5% PA21, 2% sevelamer hydrochloride, and 2% lanthanum carbonate hydrate groups compared with that in the CRF control group. Moreover, osteoid volume improved significantly in 5% of the PA21 group, and fibrosis volume and cortical porosity were ameliorated in 5% PA21, 2% sevelamer hydrochloride, and 2% lanthanum carbonate hydrate groups. These results suggest that PA21 is effective against hyperphosphatemia, secondary hyperparathyroidism, and bone abnormalities in CKD-MBD as sevelamer hydrochloride and lanthanum carbonate hydrate are, and that PA21 is a new potential alternative to phosphate binders.

  2. Magnification renal arteriography

    International Nuclear Information System (INIS)

    Carr, D.; Davidson, J.K.; McMillan, M.; Davison, M.

    1979-01-01

    Magnification selective renal arteriograms were performed on 24 patients, 12 of whom were hypertensive, and compared with non-magnification arteriograms by two observers independently. The magnification angiograms were performed on a Siemens Microfocus Bi 125/3/50 RG tube with a 0.1 mm focal spot. Of the 24 patients examined, information crucial to the diagnosis was found only on the magnification films in three patients (12.5%). Extra information compared with the non-magnification films was found in the magnification films in 12 patients (50%). No additional information was discovered in the remaining nine patients (37.5%). The magnification angiograms enabled the interlobular vessels to be visualised - this was not possible on the non-magnification films. Against the additional information gained must be weighed the disadvantages of magnification arteriography which include increased radiation dose and lengthening of procedure time plus additional injections of contrast. In conclusion, there is a place for magnification renal arteriography and the advantages seem to outweigh the disadvantages. (author)

  3. Angiography in renal tuberculosis

    Energy Technology Data Exchange (ETDEWEB)

    Choi, Doo Suk [Seoul National University College of Medicine, Seoul (Korea, Republic of)

    1974-10-15

    Angiographies on forty cases of renal tuberculosis performed at the National Medical Center during a period 1960 through 1970 were reviewed. Abdominal angiography was performed via the femoral route. Some were followed by selective nephroangiography. All patients were subjected to urographyior to angiography. The results of X-ray findings in the forty cases with renal tuberculosis were follows. 1. The age varied 18 to 57 years, average 30.5 years. Twenty one patients were male, and nineteen were female. 2. The right kidney was involved in 17 cases and the left in 15 cases. Both kidneys were involved in 8 cases. 3. Urographic examination revealed pathologic changes in all patients. 4. Focal destruction in the collecting system was the most common finding in the urography of 16 patients. 5. A varying degree of hydronephrosis was present in 15 patients, of whom nine had complained of palpable mass due to hydronephrosis. 6. In the 7 patients with extensive destruction there was no observable excretion contrast medium from the diseased kidney. 7. Angiographic examination was normal in 6 of the 40 patients. 8. Decreased vascularity in the subsegmental or smaller arteries of the affected kidney was the most frequent finding, being found in 34 patients. 9. Occlusion or abrupt termination of the subsegmental arteries was present in 4 patients. 10. Eighteen of the patients had signs of an expansive process within the cavity, the vessels being displaced and stretched around the lesions.

  4. Prenatal Exposure to LPS Alters The Intrarenal RAS in Offspring, Which Is Ameliorated by Adipose Tissue-Derived Mesenchymal Stem Cells.

    Science.gov (United States)

    Ding, Xian-Fei; Sun, Mou; Guan, Fang-Xia; Guo, Li-Na; Zhang, Yan-Yan; Wan, You-Dong; Zhang, Xiao-Juan; Yu, Yan-Wu; Ma, Shan-Shan; Yao, Hai-Mu; Yao, Rui; Zhang, Rui-Fang; Sun, Tong-Wen; Kan, Quan-Cheng

    2017-11-06

    Prenatal lipopolysaccharide (LPS) exposure causes hypertension in rat offspring through an unknown mechanism. Here, we investigated the role of the intrarenal renin-angiotensin system (RAS) in hypertension induced by prenatal LPS exposure and also explored whether adipose tissue-derived mesenchymal stem cells (ADSCs) can ameliorate the effects of prenatal LPS exposure in rat offspring. Sixty-four pregnant rats were randomly divided into 4 groups (n = 16 in each), namely, a control group and an LPS group, which were intraperitoneally injected with vehicle and 0.79 mg/kg LPS, respectively, on the 8th, 10th, and 12th days of gestation; an ADSCs group, which was intravenously injected with 1.8 × 107 ADSCs on the 8th, 10th, and 12th days of gestation; and an LPS + ADSCs group, which received a combination of the treatments administered to the LPS and ADSCs groups. Prenatal LPS exposure increased blood pressure, Ang II expression, Ang II-positive, monocyte and lymphocyte, apoptotic cells in the kidney, and induced renal histological changes in offspring; however, the LPS and control groups did not differ significantly with respect to plasma renin activity levels, Ang II levels, or renal function. ADSCs treatment attenuated the blood pressure and also ameliorated the other effects of LPS-treated adult offspring. Prenatal exposure to LPS activates the intrarenal RAS but not the circulating RAS and thus induces increases in blood pressure in adult offspring; however, ADSCs treatment attenuates the blood pressure increases resulting from LPS exposure and also ameliorates the other phenotypic changes induced by LPS treatment by inhibiting intrarenal RAS activation. © American Journal of Hypertension, Ltd 2017. All rights reserved. For Permissions, please email: journals.permissions@oup.com

  5. Multiple Targeting Approaches on Histamine H3 Receptor Antagonists

    Directory of Open Access Journals (Sweden)

    Mohammad eKhanfar

    2016-05-01

    Full Text Available With the very recent market approval of pitolisant (Wakix®, the interest in clinical applications of novel multifunctional histamine H3 receptor antagonists has clearly increased. Since histamine H3 receptor antagonists in clinical development have been tested for a variety of different indications, the combination of pharmacological properties in one molecule for improved pharmacological effects and reduced unwanted side-effects is rationally based on the increasing knowledge on the complex neurotransmitter regulations. The polypharmacological approaches on histamine H3 receptor antagonists on different G-protein coupled receptors, transporters, enzymes as well as on NO-signaling mechanism are described, supported with some lead structures.

  6. Galectin-9 ameliorates anti-GBM glomerulonephritis by inhibiting Th1 and Th17 immune responses in mice.

    Science.gov (United States)

    Zhang, Qian; Luan, Hong; Wang, Le; He, Fan; Zhou, Huan; Xu, Xiaoli; Li, Xingai; Xu, Qing; Niki, Toshiro; Hirashima, Mitsuomi; Xu, Gang; Lv, Yongman; Yuan, Jin

    2014-04-15

    Antiglomerular basement membrane glomerulonephritis (anti-GBM GN) is a Th1- and Th17-predominant autoimmune disease. Galectin-9 (Gal-9), identified as the ligand of Tim-3, functions in diverse biological processes and leads to the apoptosis of CD4(+)Tim-3(+) T cells. It is still unclear how Gal-9 regulates the functions of Th1 and Th17 cells and prevents renal injury in anti-GBM GN. In this study, Gal-9 was administered to anti-GBM GN mice for 7 days. We found that Gal-9 retarded the increase of Scr, ameliorated renal tubular injury, and reduced the formation of crescents. The infiltration of Th1 and Th17 cells into the spleen and kidneys significantly decreased in Gal-9-treated nephritic mice. The reduced infiltration of Th1 and Th17 cells might be associated with the downregulation of CCL-20, CXCL-9, and CXCL-10 mRNAs in the kidney. In parallel, the blood levels of IFN-γ and IL-17A declined in Gal-9-treated nephritic mice at days 21 and 28. In addition, an enhanced Th2 cell-mediated immune response was observed in the kidneys of nephritic mice after a 7-day injection of Gal-9. In conclusion, the protective role of Gal-9 in anti-GBM GN is associated with the inhibition of Th1 and Th17 cell-mediated immune responses and enhanced Th2 immunity in the kidney.

  7. Luteolin ameliorates cisplatin-induced nephrotoxicity in mice through inhibition of platinum accumulation, inflammation and apoptosis in the kidney

    International Nuclear Information System (INIS)

    Domitrović, Robert; Cvijanović, Olga; Pugel, Ester Pernjak; Zagorac, Gordana Blagojević; Mahmutefendić, Hana; Škoda, Marko

    2013-01-01

    The aim of this study was to investigate the effects of flavone luteolin against cisplatin (CP)-induced kidney injury in mice. Luteolin at doses of 10 mg/kg was administered intraperitoneally (ip) once daily for 3 days following single CP (10 or 20 mg/kg) ip injection. Mice were sacrificed 24 h after the last dose of luteolin. The CP treatment significantly increased serum creatinine and blood urea nitrogen and induced pathohistological changes in the kidneys. Renal oxidative/nitrosative stress was evidenced by decreased glutathione (GSH) levels and increased 3-nitrotyrosine (3-NT) and 4-hydroxynonenal (4-HNE) formation as well as cytochrome P450 2E1 (CYP2E1) expression. The CP administration triggered inflammatory response in mice kidneys through activation of nuclear factor-kappaB (NF-κB) and overexpression of tumor necrosis factor-alpha (TNF-α) and cyclooxygenase-2 (COX-2). Simultaneously, the increase in renal p53 and caspase-3 expression indicated apoptosis of tubular cells. The administration of luteolin significantly reduced histological and biochemical changes induced by CP, decreased platinum (Pt) levels and suppressed oxidative/nitrosative stress, inflammation and apoptosis in the kidneys. These results suggest that luteolin is an effective nephroprotective agent, with potential to reduce Pt accumulation in the kidneys and ameliorate CP-induced nephrotoxicity

  8. The Protective Role of Tempol Against Oxidative Stress-Related Renal Impairment Induced by Gamma Rays in Rats

    International Nuclear Information System (INIS)

    Mekawy, H.M.S.; Elkhouly, W.A.; Tawfik, S.S.

    2015-01-01

    Tempol (4-hydroxy-2,2,6,6-tetramethyl-piperidine-1 oxyl) is a naturally occurring substance that counteracts the harmful and damaging effects of oxidation in animal tissues and has been reported to permeate the biological membranes. In this study, tempol with dose of 18 mg/kg/day for 2 weeks has been shown to be effective in preventing several of the adverse consequences of oxidative stress and inflammation that underlie radiation damage. Adult rats were exposed to a total dose of 6 Gy gamma rays to determine the protective role of tempol on the biochemistry of the injured kidney because gamma rays displayed significant augmentation in renal oxidative modifications markers.The results indicated that plasma renal function tests; urea (Ur), creatinine (Cr), uric acid (UA) and sodium (Na), and plasma renal tubular injury markers; γ -glutamyltransferase ( γ -GT), aspartate aminotransferase (AST), creatine phosphokinase (CPK) and lactate dehydrogenase (LDH), were increased significantly in gamma rays group. In addition, the renal oxidative stress parameters; malondialdehyde (MDA), total cholesterol (TC) and protein carbonyl (PC), were increased significantly, and reduced glutathione (GSH) was decreased significantly in gamma rays group. Moreover, the levels of renal antioxidant enzymes; superoxide dismutase (SOD) and catalase (CAT), were decreased significantly, and myeloperoxidase (MPO) was in creased significantly in gamma rays group.The antioxidant treatment with tempol ameliorates gamma rays-induced biochemical alterations and dysfunction of kidney.Tempol, at levels within tolerable nutritional strategy, reduced the oxidative modification-related renal impairment induced by gamma radiation in rats.

  9. Renal acidification responses to respiratory acid-base disorders.

    Science.gov (United States)

    Madias, Nicolaos E

    2010-01-01

    Respiratory acid-base disorders are those abnormalities in acid-base equilibrium that are expressed as primary changes in the arterial carbon dioxide tension (PaCO2). An increase in PaCO2 (hypercapnia) acidifies body fluids and initiates the acid-base disturbance known as respiratory acidosis. By contrast, a decrease in PaCO2 (hypocapnia) alkalinizes body fluids and initiates the acid-base disturbance known as respiratory alkalosis. The impact on systemic acidity of these primary changes in PaCO2 is ameliorated by secondary, directional changes in plasma [HCO3¯] that occur in 2 stages. Acutely, hypercapnia or hypocapnia yields relatively small changes in plasma [HCO3¯] that originate virtually exclusively from titration of the body's nonbicarbonate buffers. During sustained hypercapnia or hypocapnia, much larger changes in plasma [HCO3¯] occur that reflect adjustments in renal acidification mechanisms. Consequently, the deviation of systemic acidity from normal is smaller in the chronic forms of these disorders. Here we provide an overview of the renal acidification responses to respiratory acid-base disorders. We also identify gaps in knowledge that require further research.

  10. Safety and tolerability of the novel non-steroidal mineralocorticoid receptor antagonist BAY 94-8862 in patients with chronic heart failure and mild or moderate chronic kidney disease

    DEFF Research Database (Denmark)

    Pitt, Bertram; Kober, Lars; Ponikowski, Piotr

    2013-01-01

    Mineralocorticoid receptor antagonists (MRAs) improve outcomes in patients with heart failure and reduced left ventricular ejection fraction (HFrEF), but their use is limited by hyperkalaemia and/or worsening renal function (WRF). BAY 94-8862 is a highly selective and strongly potent non-steroida......Mineralocorticoid receptor antagonists (MRAs) improve outcomes in patients with heart failure and reduced left ventricular ejection fraction (HFrEF), but their use is limited by hyperkalaemia and/or worsening renal function (WRF). BAY 94-8862 is a highly selective and strongly potent non......-steroidal MRA. We investigated its safety and tolerability in patients with HFrEF associated with mild or moderate chronic kidney disease (CKD)....

  11. A SELECTIVE ANTAGONIST OF MINERALOCORTICOID RECEPTOR EPLERENONE IN CARDIOLOGY PRACTICE

    Directory of Open Access Journals (Sweden)

    B. B. Gegenava

    2015-01-01

    Full Text Available The role of aldosterone in pathophysiological processes is considered. The effects of the selective antagonist of mineralocorticoid receptor eplerenone are analyzed. The advantages of eplerenone compared with spironolactone are discussed.

  12. Characterization and design of antagonistic shape memory alloy actuators

    International Nuclear Information System (INIS)

    Georges, T; Brailovski, V; Terriault, P

    2012-01-01

    Antagonistic shape memory actuators use opposing shape memory alloy (SMA) elements to create devices capable of producing differential motion paths and two-way mechanical work in a very efficient manner. There is no requirement for additional bias elements to ‘re-arm’ the actuators and allow repetitive actuation. The work generation potential of antagonistic shape memory actuators is determined by specific SMA element characteristics and their assembly conditions. In this study, the selected SMA wires are assembled in antagonistic configuration and characterized using a dedicated test bench to evaluate their stress–strain characteristics as a function of the number of cycles. Using these functional characteristics, a so-called ‘working envelope’ is built to assist in the design of such an actuator. Finally, the test bench is used to simulate a real application of an antagonistic actuator (case study). (paper)

  13. Gender Difference in Renal Blood Flow Response to Angiotensin II Administration after Ischemia/Reperfusion in Rats: The Role of AT2 Receptor.

    Science.gov (United States)

    Maleki, Maryam; Nematbakhsh, Mehdi

    2016-01-01

    Background. Renal ischemia/reperfusion (I/R) is one of the major causes of kidney failure, and it may interact with renin angiotensin system while angiotensin II (Ang II) type 2 receptor (AT2R) expression is gender dependent. We examined the role of AT2R blockade on vascular response to Ang II after I/R in rats. Methods. Male and female rats were subjected to 30 min renal ischemia followed by reperfusion. Two groups of rats received either vehicle or AT2R antagonist, PD123319. Mean arterial pressure (MAP), and renal blood flow (RBF) responses were assessed during graded Ang II (100, 300, and 1000 ng/kg/min, i.v.) infusion at controlled renal perfusion pressure (RPP). Results. Vehicle or antagonist did not alter MAP, RPP, and RBF levels significantly; however, 30 min after reperfusion, RBF decreased insignificantly in female treated with PD123319 (P = 0.07). Ang II reduced RBF and increased renal vascular resistance (RVR) in a dose-related fashion (P dose renal I/R injury appears to be sexually dimorphic. PD123319 infusion promotes these hemodynamic responses in female more than in male rats.

  14. FUROSEMIDE TEST: ITS PATTERN IN NOT SEVERE CHRONIC RENAL DISEASE

    Directory of Open Access Journals (Sweden)

    Carlos G. Musso

    2008-01-01

    Full Text Available Furosemide test is a simple and useful test of renal physiology used to evaluate the capability of the collecting tubules to secrete potassium under the effect of serum aldosterone. Its behaviour pattern has already been established in children and young adults but not described in chronic renal disease patients yet, which we explored in this study.Material & Method: Twenty-six young volunteers (between 20 and 40 years old, chronically on a low potassium diet (40 mmol of K day were studied: twenty of them were healthy young ( they were neither suffering form diseases nor on any medication, and the rest were young patients suffering from stage II / III chronic renal disease (damaged kidney with GFR between 83.1 ml-min to 39.2 ml-min secondary to glomerular diseases documented by kidney biopsy. None of the studied chronic renal disease patients were suffering from diabetes mellitus, urinary obstruction, nor treated with dyskalemia generating drugs, such as: diuretics, angiotensin converting enzyme inhibitors, angiotensin receptor antagonists, etc. Before, while the test was being carried out and after 180 minutes of a single dose of intravenous furosemide (1 mg/kg, urine and blood samples were obtained, for creatinine and potassium levels. From these data we calculated fractional excretion (FE of potassium. Statistical analysis was performed applying Student´s t-test.Results: There was no significant difference neither in pre-furosemide (basal and post-furosemide average FE of potassium between the healthy and chronic renal disease (CRD group: 16.4 ± 8.6% (CRD vs 11.5 ± 4.6% (healthy (p = NS ; 40.8 ± 3.2 % (CRD vs 35.4 ± 8.9% (healthy (p = NS respectively. Conversely, there was a significant difference in post-furosemide peak FE of potassium value, which was higher and delayed in the CRD group compared to the healthy one: 49.5 ± 8.2 % at 118 mins (CRD vs 31.6 ± 11% at 30 mins (healthy (p = 0.001.Conclusion: Furosemide test showed a

  15. The effects of N-methyl D-aspartate and B-adrenergic receptor antagonists on the reconsolidation of reward memory: a meta-analysis.

    Science.gov (United States)

    Das, Ravi K; Freeman, Tom P; Kamboj, Sunjeev K

    2013-03-01

    Pharmacological memory reconsolidation blockade provides a potential mechanism for ameliorating the maladaptive reward memories underlying relapse in addiction. Two of the most promising classes of drug that interfere with reconsolidation and have translational potential for human use are N-methyl-D-aspartate receptor (NMDAR) and B-Adrenergic receptor (B-AR) antagonists. We used meta-analysis and meta-regression to assess the effects of these drugs on the reconsolidation of reward memory in preclinical models of addiction. Pharmacokinetic, mnemonic and methodological factors were assessed for their moderating impact on effect sizes. An analysis of 52 independent effect sizes (NMDAR=30, B-AR=22) found robust effects of both classes of drug on memory reconsolidation, but a far greater overall effect of NMDAR antagonism than B-AR antagonism. Significant moderating effects of drug dose, relapse process and primary reinforcer were found. The findings suggest that reward memory reconsolidation can be robustly targeted by NMDAR antagonists and to a lesser extent, by B-AR antagonists. Implications for future clinical work are discussed. Copyright © 2012 Elsevier Ltd. All rights reserved.

  16. RENAL DAMAGE WITH MALIGNANT NEOPLASMS

    Directory of Open Access Journals (Sweden)

    I. B. Kolina

    2015-01-01

    Full Text Available The relationship between renal damage and malignant neoplasms is one of the most actual problems of the medicine of internal diseases. Very often, exactly availability of renal damage determines the forecast of cancer patients. The range of renal pathologies associated with tumors is unusually wide: from the mechanical effect of the tumor or metastases on the kidneys and/or the urinary tract and paraneoplastic manifestations in the form of nephritis or amyloidosis to nephropathies induced with drugs or tumor lysis, etc. Thrombotic complications that develop as a result of exposure to tumor effects, side effects of certain drugs or irradiation also play an important role in the development of the kidney damage. The most frequent variants of renal damage observed in the practice of medical internists (therapists, urologists, surgeons, etc., as well as methods of diagnosis and treatment approaches are described in the article. Timely and successful prevention and treatment of tumor-associated nephropathies give hope for retaining renal functions, therefore, a higher life standard after completion of anti-tumor therapy. Even a shortterm episode of acute renal damage suffered by a cancer patient must be accompanied with relevant examination and treatment. In the caseof transformation of acute renal damage into the chronic kidney disease, such patients need systematic and weighted renoprotective therapy and correct dosing of nephrotoxic drugs.

  17. 5-HT7 Receptor Antagonists with an Unprecedented Selectivity Profile.

    Science.gov (United States)

    Ates, Ali; Burssens, Pierre; Lorthioir, Olivier; Lo Brutto, Patrick; Dehon, Gwenael; Keyaerts, Jean; Coloretti, Francis; Lallemand, Bénédicte; Verbois, Valérie; Gillard, Michel; Vermeiren, Céline

    2018-04-23

    Selective leads: In this study, we generated a new series of serotonin 5-HT 7 receptor antagonists. Their synthesis, structure-activity relationships, and selectivity profiles are reported. This series includes 5-HT 7 antagonists with unprecedented high selectivity for the 5-HT 7 receptor, setting the stage for lead optimization of drugs acting on a range of neurological targets. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  18. Renal acidification defects in medullary sponge kidney

    DEFF Research Database (Denmark)

    Osther, P J; Hansen, A B; Røhl, H F

    1988-01-01

    Thirteen patients with medullary sponge kidney underwent a short ammonium chloride loading test to investigate their renal acidification capacity. All but 1 presented with a history of recurrent renal calculi and showed bilateral widespread renal medullary calcification on X-ray examination. Nine...... of renal calculi in medullary sponge kidney, have considerable therapeutic implications....

  19. Cólica renal

    OpenAIRE

    Pinheiro, JC

    1999-01-01

    Os aspectos práticos de actuação na cólica renal são abordados nesta apresentação, que o médico de família, a quem os doentes primeiro recorrem, deve conhecer em pormenor.É referida a incidência da afecção num serviço de urgência dum grande hospital e descreve-se, ainda que sumariamente, a fisiopatologia da dor, o quadro clínico mais frequente e a conveniente actuação terapêutica para o imediato alívio da dor intensa que estes doentes apresentam. Nas conclusões sublinha-se que a cólica ...

  20. Mature Cystic Renal Teratoma

    International Nuclear Information System (INIS)

    Yavuz, Alpaslan; Ceken, Kagan; Alimoglu, Emel; Akkaya, Bahar

    2014-01-01

    Teratomas are rare germline tumors that originate from one or more embryonic germ cell layers. Teratoma of the kidney is extremely rare, and less than 30 cases of primary intrarenal teratomas have been published to date. We report the main radiologic features of an unusual case of mature cystic teratoma arising from the left kidney in a two-year-old boy. A left-sided abdominal mass was detected on physical examination and B-Mod Ultrasound (US) examination revealed a heterogeneous mass with central cystic component. Computed tomography (CT) demonstrated a lobulated, heterogeneous, hypodense mass extending craniocaudally from the splenic hilum to the level of the left iliac fossa. Nephrectomy was performed and a large, fatty mass arising from the left kidney was excised. The final pathologic diagnosis was confirmed as cystic renal teratoma

  1. Hyperparathyroidism of Renal Disease.

    Science.gov (United States)

    Yuen, Noah K; Ananthakrishnan, Shubha; Campbell, Michael J

    2016-01-01

    Renal hyperparathyroidism (rHPT) is a common complication of chronic kidney disease characterized by elevated parathyroid hormone levels secondary to derangements in the homeostasis of calcium, phosphate, and vitamin D. Patients with rHPT experience increased rates of cardiovascular problems and bone disease. The Kidney Disease: Improving Global Outcomes guidelines recommend that screening and management of rHPT be initiated for all patients with chronic kidney disease stage 3 (estimated glomerular filtration rate, < 60 mL/min/1.73 m(2)). Since the 1990s, improving medical management with vitamin D analogs, phosphate binders, and calcimimetic drugs has expanded the treatment options for patients with rHPT, but some patients still require a parathyroidectomy to mitigate the sequelae of this challenging disease.

  2. Lung and renal transplantation

    Directory of Open Access Journals (Sweden)

    Patrícia Caetano Mota

    2009-11-01

    Full Text Available Renal transplantation is the most common type of solid organ transplantation and kidney transplant recipients are susceptible to pulmonary complications of immunosuppressive therapy, which are a diagnostic and therapeutic challenge. Aim: To evaluate patients admitted to the Renal Transplant Unit (RTU of Hospital de S. João with respiratory disease. Subject and methods: We performed a retrospective study of all patients admitted to RTU with respiratory disease during a period of 12 months. Results: Thirty-six patients were included. Mean age 55.2 ( ± 13.4 years; 61.1% male. Immunosuppressive agents most frequently used were prednisolone and mycophenolate mofetil associated with ciclosporin (38.9% or tacrolimus (22.2% or rapamycin (13.9%. Thirty-one patients (86.1% presented infectious respiratory disease. In this group the main diagnoses were 23 (74.2% pneumonias, 5 (16.1% opportunistic infections, 2 (6.5% tracheobronchitis, and 1 case (3.2% of lung abscesses. Microbiological agent was identified in 7 cases (22.6%. Five patients (13.9% presented rapamycin-induced lung disease. Fibreoptic bronchoscopy was performed in 15 patients (41.7%, diagnostic in 10 cases (66.7%. Mean hospital stay was 17.1 ( ± 18.5 days and no related death was observed. Conclusion: Respiratory infections were the main complications in these patients. Drug-induced lung disease implies recognition of its features and a rigorous monitoring of drug serum levels. A more invasive diagnostic approach was determinant in the choice of an early and more specific therapy. Resumo: O transplante renal é o transplante de órgãos sólidos mais frequente, sendo os transplantados renais alvo de complicações pulmonares inerentes à própria terapêutica imunossupressora, as quais constituem, por vezes, um desafio diagnóstico e terapêutico. Objectivo: Avaliar os doentes admitidos na Unidade de Transplante Renal (UTR do Hospital de S. João com o diagnóstico de patologia respirat

  3. Characterization of complex renal cysts

    DEFF Research Database (Denmark)

    Graumann, Ole; Osther, Susanne Sloth; Osther, Palle Jörn Sloth

    2010-01-01

    Abstract Objective. Complex renal cysts represent a major clinical problem, since it is often difficult to exclude malignancy. The Bosniak classification system, based on computed tomography (CT), is widely used to categorize cystic renal lesions. The aim of this study was to evaluate critically...... available data on the Bosniak classification. Material and methods. All publications from an Entrez Pubmed search were reviewed, focusing on clinical applicability and the use of imaging modalities other than CT to categorize complex renal cysts. Results. Fifteen retrospective studies were found. Most...

  4. Renal rickets-practical approach

    Science.gov (United States)

    Sahay, Manisha; Sahay, Rakesh

    2013-01-01

    Rickets/osteomalacia is an important problem in a tropical country. Many cases are due to poor vitamin D intake or calcium deficient diets and can be corrected by administration of calcium and vitamin D. However, some cases are refractory to vitamin D therapy and are related to renal defects. These include rickets of renal tubular acidosis (RTA), hypophosphatemic rickets, and vitamin D dependent rickets (VDDR). The latter is due to impaired action of 1α-hydroxylase in renal tubule. These varieties need proper diagnosis and specific treatment. PMID:24251212

  5. Renal epithelioid angiomyolipoma presenting clinically as renal cell ...

    African Journals Online (AJOL)

    M.S. Johnson

    a Detroit Medical Center, Michigan State University School of Osteopathic Medicine, Detroit, MI, USA .... Immunohistochemically, the tumor cells stained strongly positive .... [10] Cao Q, Liu F, Xiao P, Tian X, Li B, Li Z. Coexistence of renal.

  6. Diagnosis of renal disease in rabbits.

    Science.gov (United States)

    Harcourt-Brown, Frances Margaret

    2013-01-01

    There are differences in renal anatomy and physiology between rabbits and other domestic species. Neurogenic renal ischemia occurs readily. Reversible prerenal azotemia may be seen in conjunction with gut stasis. Potentially fatal acute renal failure may be due to structural kidney damage or post-renal disease. Chronic renal failure is often associated with encephalitozoonosis. Affected rabbits cannot vomit and often eat well. Weight loss, lethargy, and cachexia are common clinical signs. Polydypsia/polyuria may be present. Derangements in calcium and phosphorus metabolism are features of renal disease. Radiography is always indicated. Urolithiasis, osteosclerosis, aortic and renal calcification are easily seen on radiographs. Copyright © 2013 Elsevier Inc. All rights reserved.

  7. Na+-K+ pump in chronic renal failure

    International Nuclear Information System (INIS)

    Deepak, K.; Kahn, T.

    1987-01-01

    This review summarizes the evidence for the defect in Na + -K + pump in chronic renal failure, considers the role of various factors in causing this defect, and discusses the clinical implications thereof. Intracellular Na is elevated in erythrocytes, leukocytes, and muscle cells from some patients with chronic renal failure (CRF). Recent evidence suggest that this elevation of cell Na may be, in large part, a consequence of decreased number of Na + -K + pump units per cell. Maintenance dialysis over a period of weeks ameliorates the defect in intracellular Na + , and this improvement is contemporaneous with an increase in the number of Na + -K + pump sites per cell. In erythrocytes with normal cell Na + , acute hemodialysis increases the rate of 22 Na + and 42 K + transport. Many factors such as the presence of retained toxic metabolite or circulating inhibitor in the uremic plasma, or biochemical changes produced by acute hemodialysis, may explain this finding. In cells with high cell Na + , the pump-mediated 42 K + transport is normalized at the expense of a raised cell Na + . The decreased muscle membrane potential in uremic subjects has been attributed to a decreased activity of Na + -K + pump. The authors discuss the role of hormonal abnormalities and circulating inhibitors, which may cause an acute inhibition of the pump and of other factors such as K + depletion, which may cause more chronic alterations. The implications of alteration of Na + and K + pump transport and raised cell Na + on other non-pump-mediated transport pathways are discussed. Raised cell Na + may be a marker for the adequacy of maintenance dialysis in patients with end-stage renal failure

  8. Valsartan ameliorates podocyte loss in diabetic mice through the Notch pathway.

    Science.gov (United States)

    Gao, Feng; Yao, Min; Cao, Yanping; Liu, Shuxia; Liu, Qingjuan; Duan, Huijun

    2016-05-01

    The Notch pathway is known to be linked to diabetic nephropathy (DN); however, its underlying mechanism was poorly understood. In the present study, we examined the effect of Valsartan, an angiotensin II type 1 receptor antagonist, on the Notch pathway and podocyte loss in DN. Diabetes was induced in mice by an intraperitoneal injection of streptozotocin and and this was followed by treatment with Valsartan. Levels of blood glucose, kidney weight and body weight, as well as proteinuria were measured. Samples of the kidneys were also histologically examined. The relative levels of Jagged1, Notch1, Notch intracellular domain 1 (NICD1), Hes family BHLH transcription factor 1 (Hes1) and Hes-related family BHLH transcription factor with YRPW motif 1 expression (Hey1) in the glomeruli were determined by immunohistochemical analysis, western blot analysis and RT-qPCR. The B-Cell CLL/Lymphoma 2 (Bcl-2) and p53 pathways were examined by western blot analysis. Apoptosis and detachment of podocytes from the glomerular basement membrane were examined using a TUNEL assay, flow cytometric analysis and ELISA. The number of podocytes was quantified by measuring Wilms tumor-1 (WT-1) staining. We noted that the expression of Jagged1, Notch1, NICD1, Hes1 and Hey1 was increased in a time-dependent manner in the glomeruli of mice with streptozotocin (STZ)-induced diabetes. Moreover, in diabetic mice, Valsartan significantly reduced kidney weight and proteinuria, and mitigated the pathogenic processes in the kidneys. Valsartan also inhibited the activation of Notch, Bcl-2 and p53 pathways and ameliorated podocyte loss in the glomeruli of mice with STZ-induced diabetes. Taken together, these findings indicated that Valsartan exerted a beneficial effect on reducing podocyte loss, which is associated with inhibition of Notch pathway activation in the glomeruli of diabetic mice.

  9. Cannabinoids ameliorate impairments induced by chronic stress to synaptic plasticity and short-term memory.

    Science.gov (United States)

    Abush, Hila; Akirav, Irit

    2013-07-01

    Repeated stress is one of the environmental factors that precipitates and exacerbates mental illnesses like depression and anxiety as well as cognitive impairments. We have previously shown that cannabinoids can prevent the effects of acute stress on learning and memory. Here we aimed to find whether chronic cannabinoid treatment would alleviate the long-term effects of exposure to chronic restraint stress on memory and plasticity as well as on behavioral and neuroendocrine measures of anxiety and depression. Late adolescent rats were exposed to chronic restraint stress for 2 weeks followed each day by systemic treatment with vehicle or with the CB1/2 receptor agonist WIN55,212-2 (1.2 mg/kg). Thirty days after the last exposure to stress, rats demonstrated impaired long-term potentiation (LTP) in the ventral subiculum-nucleus accumbens (NAc) pathway, impaired performance in the prefrontal cortex (PFC)-dependent object-recognition task and the hippocampal-dependent spatial version of this task, increased anxiety levels, and significantly reduced expression of glucocorticoid receptors (GRs) in the amygdala, hippocampus, PFC, and NAc. Chronic WIN55,212-2 administration prevented the stress-induced impairment in LTP levels and in the spatial task, with no effect on stress-induced alterations in unconditioned anxiety levels or GR levels. The CB1 antagonist AM251 (0.3 mg/kg) prevented the ameliorating effects of WIN55,212-2 on LTP and short-term memory. Hence, the beneficial effects of WIN55,212-2 on memory and plasticity are mediated by CB1 receptors and are not mediated by alterations in GR levels in the brain areas tested. Our findings suggest that cannabinoid receptor activation could represent a novel approach to the treatment of cognitive deficits that accompany a variety of stress-related neuropsychiatric disorders.

  10. Renal vein oxygen saturation in renal artery stenosis

    DEFF Research Database (Denmark)

    Nielsen, K; Rehling, M; Henriksen, Jens Henrik Sahl

    1992-01-01

    Renal vein oxygen-saturation was measured in 56 patients with arterial hypertension and unilateral stenosis or occlusion of the renal artery. Oxygen-saturation in blood from the ischaemic kidney (84.4%, range 73-93%) was significantly higher than that from the 'normal' contralateral kidney (81...... than its blood flow. This is probably due to decreased filtration fraction and filtered sodium with subsequent reduction in absolute tubular re-absorption of sodium ions....

  11. CUTANEOUS MANIFESTATIONS OF CHRONIC RENAL FAILURE AND RENAL TRANSPLANTATION

    OpenAIRE

    R. Suganya Gnanadeepam; S. Kayalvizhi Money

    2017-01-01

    BACKGROUND The kidney and the skin are the two large networks of the body with abundant blood supply associated with various cutaneous manifestations. This study aims to detect the various cutaneous manifestations and its incidence in patients with chronic renal failure and renal transplantation. MATERIALS AND METHODS This study was done for a period of 1 year from January 2016 to December 2016 at Nephrology OPD ward and Medicine wards, Government KAPV Medical College Hos...

  12. Lactobacillus plantarum MYS6 Ameliorates Fumonisin B1-Induced Hepatorenal Damage in Broilers

    Directory of Open Access Journals (Sweden)

    B. V. Deepthi

    2017-11-01

    Full Text Available Fumonisin B1 (FB1, a mycotoxin produced by Fusarium species is a predominant Group 2B carcinogen occurring in maize and maize-based poultry feeds. It is shown to be nephrotoxic, hepatotoxic, neurotoxic, and immunosuppressing in animals. In this study, we report the ameliorating effects of a probiotic strain, Lactobacillus plantarum MYS6 on FB1-induced toxicity and oxidative damage in broilers. A 6-week dietary experiment consisting of 48 broilers was performed in six treatment groups. Probiotic treatment (109 cells/mL involved pre-colonization of broilers with L. plantarum MYS6 while co-administration treatment involved supplementation of probiotic and FB1-contaminated diet (200 mg/Kg feed simultaneously. At the end of the treatment period, growth performance, hematology, serum biochemistry, and markers of oxidative stress in serum and tissue homogenates were evaluated in all the broilers. The histopathological changes in hepatic and renal tissues were further studied. The results demonstrated that administration of L. plantarum MYS6 efficiently improved the feed intake, body weight and feed conversion ratio in broilers. It mitigated the altered levels of hematological indices such as complete blood count, hemoglobin, and hematocrit. Serum parameters such as serum glutamic oxaloacetic transaminase, serum glutamic pyruvic transaminase, creatinine, cholesterol, triglycerides, and albumin were significantly restored after administering the probiotic in FB1-intoxicated broilers. Additionally, L. plantarum MYS6 alleviated the levels of oxidative stress markers in serum and tissue homogenate of liver. The histopathological data of liver and kidney further substantiated the overall protection offered by L. plantarum MYS6 against FB1-induced cellular toxicity and organ damage in broilers. Our results indicated that co-administration of probiotic along with the toxin had better effect in detoxification compared to its pre-colonization in broilers

  13. Biochar from commercially cultivated seaweed for soil amelioration

    OpenAIRE

    Roberts, David A.; Paul, Nicholas A.; Dworjanyn, Symon A.; Bird, Michael I.; de Nys, Rocky

    2015-01-01

    Seaweed cultivation is a high growth industry that is primarily targeted at human food and hydrocolloid markets. However, seaweed biomass also offers a feedstock for the production of nutrient-rich biochar for soil amelioration. We provide the first data of biochar yield and characteristics from intensively cultivated seaweeds (Saccharina, Undaria and Sargassum ? brown seaweeds, and Gracilaria, Kappaphycus and Eucheuma ? red seaweeds). While there is some variability in biochar properties as ...

  14. Pyrolysis temperature influences ameliorating effects of biochars on acidic soil.

    Science.gov (United States)

    Wan, Qing; Yuan, Jin-Hua; Xu, Ren-Kou; Li, Xing-Hui

    2014-02-01

    The biochars were prepared from straws of canola, corn, soybean, and peanut at different temperatures of 300, 500, and 700 °C by means of oxygen-limited pyrolysis.Amelioration effects of these biochars on an acidic Ultisol were investigated with incubation experiments, and application rate of biochars was 10 g/kg. The incorporation of these biochars induced the increase in soil pH, soil exchangeable base cations, base saturation, and cation exchange capacity and the decrease in soil exchangeable acidity and exchangeable Al. The ameliorating effects of biochars on acidic soil increased with increase in their pyrolysis temperature. The contribution of oxygen-containing functional groups on the biochars to their ameliorating effects on the acidic soil decreased with the rise in pyrolysis temperature, while the contribution from carbonates in the biochars changed oppositely. The incorporation of the biochars led to the decrease in soil reactive Al extracted by 0.5mol/L CuCl2, and the content of reactive Al was decreased with the increase in pyrolysis temperature of incorporated biochars. The biochars generated at 300 °C increased soil organically complexed Al due to ample quantity of oxygen-containing functional groups such as carboxylic and phenolic groups on the biochars, while the biochars generated at 500 and 700 °C accelerated the transformation of soil exchangeable Al to hydroxyl-Al polymers due to hydrolysis of Al at higher pH. Therefore, the crop straw-derived biochars can be used as amendments for acidic soils and the biochars generated at relatively high temperature have great ameliorating effects on the soils.

  15. Infiltration in reclaimed mined land ameliorated with deep tillage treatments

    International Nuclear Information System (INIS)

    Chong, S.K.; Cowsert, P.T.

    1997-01-01

    Reclamation of mined land with heavy machinery can result in soil compaction, which increases soil bulk density and reduces porosity, water infiltrability, root elongation and crop productivity. This paper examines the effect on infiltration in reclaimed surface mined land of a deep tillage treatment, and the subsequent changes in infiltration after the amelioration. The experiment was conducted at the Horse Creek Mine near Conant, Ferry County, IL, USA

  16. Biochar from commercially cultivated seaweed for soil amelioration

    Science.gov (United States)

    Roberts, David A.; Paul, Nicholas A.; Dworjanyn, Symon A.; Bird, Michael I.; de Nys, Rocky

    2015-01-01

    Seaweed cultivation is a high growth industry that is primarily targeted at human food and hydrocolloid markets. However, seaweed biomass also offers a feedstock for the production of nutrient-rich biochar for soil amelioration. We provide the first data of biochar yield and characteristics from intensively cultivated seaweeds (Saccharina, Undaria and Sargassum – brown seaweeds, and Gracilaria, Kappaphycus and Eucheuma – red seaweeds). While there is some variability in biochar properties as a function of the origin of seaweed, there are several defining and consistent characteristics of seaweed biochar, in particular a relatively low C content and surface area but high yield, essential trace elements (N, P and K) and exchangeable cations (particularly K). The pH of seaweed biochar ranges from neutral (7) to alkaline (11), allowing for broad-spectrum applications in diverse soil types. We find that seaweed biochar is a unique material for soil amelioration that is consistently different to biochar derived from ligno-cellulosic feedstock. Blending of seaweed and ligno-cellulosic biochar could provide a soil ameliorant that combines a high fixed C content with a mineral-rich substrate to enhance crop productivity. PMID:25856799

  17. Biochar from commercially cultivated seaweed for soil amelioration

    Science.gov (United States)

    Roberts, David A.; Paul, Nicholas A.; Dworjanyn, Symon A.; Bird, Michael I.; de Nys, Rocky

    2015-04-01

    Seaweed cultivation is a high growth industry that is primarily targeted at human food and hydrocolloid markets. However, seaweed biomass also offers a feedstock for the production of nutrient-rich biochar for soil amelioration. We provide the first data of biochar yield and characteristics from intensively cultivated seaweeds (Saccharina, Undaria and Sargassum - brown seaweeds, and Gracilaria, Kappaphycus and Eucheuma - red seaweeds). While there is some variability in biochar properties as a function of the origin of seaweed, there are several defining and consistent characteristics of seaweed biochar, in particular a relatively low C content and surface area but high yield, essential trace elements (N, P and K) and exchangeable cations (particularly K). The pH of seaweed biochar ranges from neutral (7) to alkaline (11), allowing for broad-spectrum applications in diverse soil types. We find that seaweed biochar is a unique material for soil amelioration that is consistently different to biochar derived from ligno-cellulosic feedstock. Blending of seaweed and ligno-cellulosic biochar could provide a soil ameliorant that combines a high fixed C content with a mineral-rich substrate to enhance crop productivity.

  18. Ghrelin Ameliorates Asthma by Inhibiting Endoplasmic Reticulum Stress.

    Science.gov (United States)

    Fu, Tian; Wang, Lei; Zeng, Qingdi; Zhang, Yan; Sheng, Baowei; Han, Liping

    2017-12-01

    This study aimed to confirm the ameliorative effect of ghrelin on asthma and investigate its mechanism. The murine model of asthma was induced by ovalbumin (OVA) treatment and assessed by histological pathology and airway responsiveness to methacholine. The total and differential leukocytes were counted. Tumor necrosis factor α, interferon γ, interleukin-5 and interleukin-13 levels in bronchoalveolar lavage fluid were quantified by commercial kits. The protein levels in pulmonary tissues were measured by Western blot analysis. Ghrelin ameliorated the histological pathology and airway hyperresponsiveness in the OVA-induced asthmatic mouse model. Consistently, OVA-increased total and differential leukocytes and levels of tumor necrosis factor α, interferon γ, interleukin-5 and interleukin-13 in bronchoalveolar lavage fluid were significantly attenuated by ghrelin. Ghrelin prevented the increased protein levels of the endoplasmic reticulum stress markers glucose regulated protein 78 and CCAAT/enhancer binding protein homologous protein and reversed the reduced levels of p-Akt in asthmatic mice. Ghrelin might prevent endoplasmic reticulum stress activation by stimulating the Akt signaling pathway, which attenuated inflammation and ameliorated asthma in mice. Ghrelin might be a new target for asthma therapy. Copyright © 2017. Published by Elsevier Inc.

  19. Administration of red ginseng ameliorates memory decline in aged mice.

    Science.gov (United States)

    Lee, Yeonju; Oh, Seikwan

    2015-07-01

    It has been known that ginseng can be applied as a potential nutraceutical for memory impairment; however, experiments with animals of old age are few. To determine the memory enhancing effect of red ginseng, C57BL/6 mice (21 mo old) were given experimental diet pellets containing 0.12% red ginseng extract (approximately 200 mg/kg/d) for 3 mo. Young and old mice (4 mo and 21 mo old, respectively) were used as the control group. The effect of red ginseng, which ameliorated memory impairment in aged mice, was quantified using Y-maze test, novel objective test, and Morris water maze. Red ginseng ameliorated age-related declines in learning and memory in older mice. In addition, red ginseng's effect on the induction of inducible nitric oxide synthase and proinflammatory cytokines was investigated in the hippocampus of aged mice. Red ginseng treatment suppressed the production of age-processed inducible nitric oxide synthase, cyclooxygenase-2, tumor necrosis factor-α, and interleukin-1β expressions. Moreover, it was observed that red ginseng had an antioxidative effect on aged mice. The suppressed glutathione level in aged mice was restored with red ginseng treatment. The antioxidative-related enzymes Nrf2 and HO-1 were increased with red ginseng treatment. The results revealed that when red ginseng is administered over long periods, age-related decline of learning and memory is ameliorated through anti-inflammatory activity.

  20. Relationship between renal cortex and parenchyma thickness and renal function: study with CT measurement

    International Nuclear Information System (INIS)

    Xu Yufeng; Tang Guangjian; Jiang Xuexiang

    2006-01-01

    Objective: To study the relationship between renal morphology and renal function, and to assess the value of CT as a criterion to grade renal function. Methods: Enhancement CT were performed in 89 patients with no local renal disease whose split renal glomerular filtration rates (GFR) were measured by renal dynamic imaging with 99 Tc m -DTPA. The 178 kidneys were divided into normal renal function, mild and severe renal impairment groups according to renal function. Differences between three groups respect to the mean thickness of renal cortex and parenchyma were assessed by ANOVA. Using Pearson's correlation test, the correlation between the renal cortex, parenchyma thicknesses and renal GFR were examined. The value of CT in predicting renal function was assessed by using ROC analysis. Results: The renal cortex thicknesses of normal renal function, mild and severe renal impairment groups were (5.9±1.1), (4.6± 1.1), and (3.3±1.0) mm respectively, and the renal parenchyma thicknesses were (26.3±4.2), (21.3±4.6), (16.2±4.6) mm. There were significant differences of renal cortex, parenchyma thicknesses between 3 groups (cortex F=54.78, P<0.01; parenehyma F=43.90, P<0.01). The thicknesses of renal cortex (r=0.752, P<0.01), parenchyma (r=0.738, P<0.01) had positive linear correlation with renal function. ROC analysis of the renal cortex thicknesses measured by CT in predicting mild and severe renal impairment showed that the Az was 0.860 and 0.905 respectively, whereas that of parenchyma was 0.868 and 0.884. Conclusion: The thicknesses of renal cortex, parenchyma measured by CT can reflect renal function. CT was a supplementary method to assess renal function. (authors)

  1. The Effects of Renal Denervation on Renal Hemodynamics and Renal Vasculature in a Porcine Model.

    Directory of Open Access Journals (Sweden)

    Willemien L Verloop

    Full Text Available Recently, the efficacy of renal denervation (RDN has been debated. It is discussed whether RDN is able to adequately target the renal nerves.We aimed to investigate how effective RDN was by means of functional hemodynamic measurements and nerve damage on histology.We performed hemodynamic measurements in both renal arteries of healthy pigs using a Doppler flow and pressure wire. Subsequently unilateral denervation was performed, followed by repeated bilateral hemodynamic measurements. Pigs were terminated directly after RDN or were followed for 3 weeks or 3 months after the procedure. After termination, both treated and control arteries were prepared for histology to evaluate vascular damage and nerve damage. Directly after RDN, resting renal blood flow tended to increase by 29±67% (P = 0.01. In contrast, renal resistance reserve increased from 1.74 (1.28 to 1.88 (1.17 (P = 0.02 during follow-up. Vascular histopathology showed that most nerves around the treated arteries were located outside the lesion areas (8±7 out of 55±25 (14% nerves per pig were observed within a lesion area. Subsequently, a correlation was noted between a more impaired adventitia and a reduction in renal resistance reserve (β: -0.33; P = 0.05 at three weeks of follow-up.Only a small minority of renal nerves was targeted after RDN. Furthermore, more severe adventitial damage was related to a reduction in renal resistance in the treated arteries at follow-up. These hemodynamic and histological observations may indicate that RDN did not sufficiently target the renal nerves. Potentially, this may explain the significant spread in the response after RDN.

  2. The Effects of Renal Denervation on Renal Hemodynamics and Renal Vasculature in a Porcine Model

    Science.gov (United States)

    Verloop, Willemien L.; Hubens, Lisette E. G.; Spiering, Wilko; Doevendans, Pieter A.; Goldschmeding, Roel; Bleys, Ronald L. A. W.; Voskuil, Michiel

    2015-01-01

    Rationale Recently, the efficacy of renal denervation (RDN) has been debated. It is discussed whether RDN is able to adequately target the renal nerves. Objective We aimed to investigate how effective RDN was by means of functional hemodynamic measurements and nerve damage on histology. Methods and Results We performed hemodynamic measurements in both renal arteries of healthy pigs using a Doppler flow and pressure wire. Subsequently unilateral denervation was performed, followed by repeated bilateral hemodynamic measurements. Pigs were terminated directly after RDN or were followed for 3 weeks or 3 months after the procedure. After termination, both treated and control arteries were prepared for histology to evaluate vascular damage and nerve damage. Directly after RDN, resting renal blood flow tended to increase by 29±67% (P = 0.01). In contrast, renal resistance reserve increased from 1.74 (1.28) to 1.88 (1.17) (P = 0.02) during follow-up. Vascular histopathology showed that most nerves around the treated arteries were located outside the lesion areas (8±7 out of 55±25 (14%) nerves per pig were observed within a lesion area). Subsequently, a correlation was noted between a more impaired adventitia and a reduction in renal resistance reserve (β: -0.33; P = 0.05) at three weeks of follow-up. Conclusion Only a small minority of renal nerves was targeted after RDN. Furthermore, more severe adventitial damage was related to a reduction in renal resistance in the treated arteries at follow-up. These hemodynamic and histological observations may indicate that RDN did not sufficiently target the renal nerves. Potentially, this may explain the significant spread in the response after RDN. PMID:26587981

  3. Abatacept Treatment Does Not Preserve Renal Function in the Streptozocin-Induced Model of Diabetic Nephropathy.

    Directory of Open Access Journals (Sweden)

    Jenny Norlin

    Full Text Available Diabetic nephropathy (DN is one of the most severe complications of diabetes and remains the largest cause of end-stage renal disease in the Western world. Treatment options are limited and novel therapies that effectively slow disease progression are warranted. Previous work suggested that treatment with CTLA4-Ig (abatacept, a molecule that binds and blocks B7-1 and is licensed for the treatment of rheumatoid arthritis, could ameliorate DN. This study was designed to assess whether B7-1 signalling constitutes a promising therapeutic pathway for DN. Mice injected with streptozotocin (STZ were treated with abatacept and glycemia and renal function were assessed. No differences were found in diabetes progression, albumin excretion rates or albumin/creatine ratios, while mesangial expansion was unaltered at endpoint. Except for increased renal CCL5, treatment did not affect a panel of gene expression endpoints reflecting early fibrotic changes, inflammation and kidney injury. Finally, abatacept treatment effectively reduced the accumulation of activated CD4+ T cells in the kidney, suggesting that renal T cell inflammation is not a driving factor in the pathology of the STZ model. In conjunction with the recent data discounting the expression of B7-1 on podocytes, our present data do not support a role for abatacept in DN treatment.

  4. Serum metabonomic analysis of protective effects of Curcuma aromatica oil on renal fibrosis rats.

    Science.gov (United States)

    Zhao, Liangcai; Zhang, Haiyan; Yang, Yunjun; Zheng, Yongquan; Dong, Minjian; Wang, Yaqiang; Bai, Guanghui; Ye, Xinjian; Yan, Zhihan; Gao, Hongchang

    2014-01-01

    Curcuma aromatica oil is a traditional herbal medicine demonstrating protective and anti-fibrosis activities in renal fibrosis patients. However, study of its mechanism of action is challenged by its multiple components and multiple targets that its active agent acts on. Nuclear magnetic resonance (NMR)-based metabonomics combined with clinical chemistry and histopathology examination were performed to evaluate intervening effects of Curcuma aromatica oil on renal interstitial fibrosis rats induced by unilateral ureteral obstruction. The metabolite levels were compared based on integral values of serum 1H NMR spectra from rats on 3, 7, 14, and 28 days after the medicine administration. Time trajectory analysis demonstrated that metabolic profiles of the agent-treated rats were restored to control levels after 7 days of dosage. The results confirmed that the agent would be an effective anti-fibrosis medicine in a time-dependent manner, especially in early renal fibrosis stage. Targeted metabolite analysis showed that the medicine could lower levels of lipid, acetoacetate, glucose, phosphorylcholine/choline, trimethylamine oxide and raise levels of pyruvate, glycine in the serum of the rats. Serum clinical chemistry and kidney histopathology examination dovetailed well with the metabonomics data. The results substantiated that Curcuma aromatica oil administration can ameliorate renal fibrosis symptoms by inhibiting some metabolic pathways, including lipids metabolism, glycolysis and methylamine metabolism, which are dominating targets of the agent working in vivo. This study further strengthens the novel analytical approach for evaluating the effect of traditional herbal medicine and elucidating its molecular mechanism.

  5. Agmatine improves renal function in gentamicin-induced nephrotoxicity in rats.

    Science.gov (United States)

    El-Kashef, Dalia H; El-Kenawi, Asmaa E; Abdel Rahim, Mona; Suddek, Ghada M; Salem, Hatem A

    2016-03-01

    The present study was designed to explore the possible protective effects of agmatine, a known nitric oxide (NO) synthase inhibitor, against gentamicin-induced nephrotoxicity in rats. For this purpose, we quantitatively evaluated gentamicin-induced renal structural and functional alterations using histopathological and biochemical approaches. Furthermore, the effect of agmatine on gentamicin-induced hypersensitivity of urinary bladder rings to acetylcholine (ACh) was evaluated. Twenty-four male Wistar albino rats were randomly divided into 3 groups, namely control, gentamicin (100 mg/kg, i.p.), and gentamicin plus agmatine (40 mg/kg, orally). At the end of the study, all rats were sacrificed and then blood and urine samples and kidneys were taken. Administration of agmatine significantly decreased kidney/body mass ratio, serum creatinine, lactate dehydrogenase (LDH), renal malondialdehyde (MDA), myeloperoxidase (MPO), NO, and tumor necrosis factor-alpha (TNF-α) while it significantly increased creatinine clearance and renal superoxide dismutase (SOD) activity when compared with the gentamicin-treated group. Additionally, agmatine ameliorated tissue morphology as evidenced by histological evaluation and reduced the responses of isolated bladder rings to ACh. Our study indicates that agmatine administration with gentamicin attenuates oxidative-stress associated renal injury by reducing oxygen free radicals and lipid peroxidation, restoring NO level and inhibiting inflammatory mediators such as TNF-α.

  6. [Use of non-vitamin K antagonist oral anticoagulants in Primary Care: ACTUA study].

    Science.gov (United States)

    Barrios, V; Escobar, C; Lobos, J M; Polo, J; Vargas, D

    2017-10-01

    Approximately 40% of patients with non-valvular auricular fibrillation (NVAF) who receive vitamin K antagonists (VKA) in Primary Care in Spain have poor anticoagulation control. The objective of the study Actuación en antiCoagulación, Tratamiento y Uso de anticoagulantes orales de acción directa (ACOD) en Atención primaria (ACTUA) (Action in Coagulation, Treatment and Use of direct oral anticoagulants [DOACs]) in Primary Care) was to analyse the current situation regarding the use of VKA and non-vitamin K antagonist oral anticoagulants (NOACs) in patients with NVAF in Primary Care in Spain and the possible issues arising from it. An online survey was created covering various aspects of the use of oral anticoagulants in NAFV. A two-round modified Delphi approach was used. Results were compiled as a set of practical guidelines. Forty-four experts responded to the survey. Consensus was reached in 62% (37/60) of the items. Experts concluded that a considerable number of patients with NVAF who receive VKA do not have a well-controlled INR and that a substantial group of patients who could benefit from being treated with NOACs do not receive them. The use of NOACs increases the probability of having good anticoagulation control and decreases the risk of severe and intracranial haemorrhage. Current limitations to the use of NOACs include administrative barriers, insufficient knowledge about the benefits and risks of NOACs, limited experience of doctors in using them, and their price. Renal insufficiency influences the choice of a particular anticoagulant. The ACTUA study highlights the existing controversies about the use of oral anticoagulants for the treatment of NVAF in Primary Care in Spain, and provides consensus recommendations that may help to improve the use of these medications. Copyright © 2016 Sociedad Española de Médicos de Atención Primaria (SEMERGEN). Publicado por Elsevier España, S.L.U. All rights reserved.

  7. Transcatheter embolisation of renal angiomyolipoma.

    LENUS (Irish Health Repository)

    Leong, S

    2010-06-01

    Angiomyolipomas (AML) are rare benign renal tumours which are associated with aneurysms that can cause haemorrhage. Embolisation of AML greater than 4 cm with a variety of embolic agents is now the first-line treatment in these cases.

  8. Renal cell carcinoma in childhood

    International Nuclear Information System (INIS)

    Zanier, J.F.C.; Ramos, C.O.P.; Pereira, A.A.

    1990-01-01

    The authors present five cases of renal cell carcinoma in children, describing its aspects on excretory urography, ultra-sonography and computerized tomography. The clinical, pathological and radiological features are compared with those of the literature. (author)

  9. Antibiotic managment in renal failure.

    Science.gov (United States)

    Winter, R E

    1976-06-01

    This is a brief compilation of the work of many investigators. It includes facts about toxicity and recommendations about antibiotic management in patients with renal failure. As new data are accrued, changes in these recommendations will be necessary.

  10. Bone scintigraphy in renal osteodystrophy

    International Nuclear Information System (INIS)

    de Graaf, P.; Schicht, I.M.; Pauwels, E.K.J.; te Velde, J.; de Graeff, J.

    1978-01-01

    Bone scintigraphy with Tc-99m HEDP was performed in 30 patients on maintenance hemodialysis, and the results of quantitative analysis were compared wth those of a normal group. To permit this comparison, elevated background activity due to the absence of renal radiotracer excretion was reduced by hemodialysis to levels found in the normals. Histologic proof of renal osteodystrophy had been obtained in all patients. the incidence of radiographic abnormalities was 46%, whereas abnormal scans were found in 25 patients (83%); skeletal lesions were also more pronounced and detected earlier. However, even when the scans appeared normal, the quantitative analysis showed increased skeletal activity in all patients. The total skeletal activity proved to be a good index of the severity of renal osteodystrophy and appeared dependent on both osteomalacia and hyperparathyroidism. These findings show that bone scintigraphy is a sensitive method to detect skeletal involvement in renal osteodystrophy

  11. Prolonged Intermittent Renal Replacement Therapy.

    Science.gov (United States)

    Edrees, Fahad; Li, Tingting; Vijayan, Anitha

    2016-05-01

    Prolonged intermittent renal replacement therapy (PIRRT) is becoming an increasingly popular alternative to continuous renal replacement therapy in critically ill patients with acute kidney injury. There are significant practice variations in the provision of PIRRT across institutions, with respect to prescription, technology, and delivery of therapy. Clinical trials have generally demonstrated that PIRRT is non-inferior to continuous renal replacement therapy regarding patient outcomes. PIRRT offers cost-effective renal replacement therapy along with other advantages such as early patient mobilization and decreased nursing time. However, due to lack of standardization of the procedure, PIRRT still poses significant challenges, especially pertaining to appropriate drug dosing. Future guidelines and clinical trials should work toward developing consensus definitions for PIRRT and ensure optimal delivery of therapy. Copyright © 2016 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

  12. Mucormycosis (zygomycosis) of renal allograft

    Science.gov (United States)

    Gupta, Krishan L.; Joshi, Kusum; Kohli, Harbir S.; Jha, Vivekanand; Sakhuja, Vinay

    2012-01-01

    Fungal infection is relatively common among renal transplant recipients from developing countries. Mucormycosis, also known as zygomycosis, is one of the most serious fungal infections in these patients. The most common of presentation is rhino-cerebral. Isolated involvement of a renal allograft is very rare. A thorough search of literature and our medical records yielded a total of 24 cases with mucormycosis of the transplanted kidney. There was an association with cytomegalovirus (CMV) infection and anti-rejection treatment in these patients and most of these transplants were performed in the developing countries from unrelated donors. The outcome was very poor with an early mortality in 13 (54.5%) patients. Renal allograft mucormycosis is a relatively rare and potentially fatal complication following renal transplantation. Early diagnosis, graft nephrectomy and appropriate antifungal therapy may result in an improved prognosis for these patients. PMID:26069793

  13. Fibromuscular dysplasia of renal arteries

    International Nuclear Information System (INIS)

    Akhtar, N.; Ahmed, T.M.

    2007-01-01

    This case reports a young child having uncontrolled hypertension, resulting from bilateral renal artery stenosis due to fibromuscular dysplasia presenting with abdominal pain, headache and visual disturbance. Diagnostic features and management is discussed. (author)

  14. Cancer - renal pelvis or ureter

    Science.gov (United States)

    ... ureter; Kidney cancer - renal pelvis; Ureter cancer Images Kidney anatomy References National Cancer Institute website. Transitional cell cancer (kidney/ureter) treatment (PDQ) - health professional version. www.cancer. ...

  15. Radiological evaluation of renal transplantation

    Energy Technology Data Exchange (ETDEWEB)

    Dorph, S [Herlev University Hospital, Copenhagen (Denmark). Dept. of Radiology

    1996-12-31

    Briefly discussed the nephrologic complications, episodes of rejection, acute tubular necrosis, cyclosporine, urologic complications, perirenal fluid collections, small asymptomatic hematomas, urinomas, abscesses, lymphocele, ureteral obstruction, cascular complications, imaging of the renal allograft, radionuclide imaging, ultrasonography, conventional radiography, cystograhy (8 refs.).

  16. Radiological evaluation of renal transplantation

    International Nuclear Information System (INIS)

    Dorph, S.

    1995-01-01

    Briefly discussed the nephrologic complications, episodes of rejection, acute tubular necrosis, cyclosporine, urologic complications, perirenal fluid collections, small asymptomatic hematomas, urinomas, abscesses, lymphocele, ureteral obstruction, cascular complications, imaging of the renal allograft, radionuclide imaging, ultrasonography, conventional radiography, cystograhy (8 refs.)

  17. Inflammation in renal atherosclerotic disease.

    Science.gov (United States)

    Udani, Suneel M; Dieter, Robert S

    2008-07-01

    The study of renal atherosclerotic disease has conventionally focused on the diagnosis and management of renal artery stenosis. With the increased understanding of atherosclerosis as a systemic inflammatory process, there has been increased interest in vascular biology at the microvasculature level. While different organ beds share some features, the inflammation and injury in the microvasculature of the kidney has unique elements as well. Understanding of the pathogenesis yields a better understanding of the clinical manifestations of renal atherosclerotic disease, which can be very subtle. Furthermore, identifying the molecular mechanisms responsible for the progression of kidney damage can also direct clinicians and scientists toward targeted therapies. Existing therapies used to treat atherosclerotic disease in other vascular beds may also play a role in the treatment of renal atherosclerotic disease.

  18. Renal Ammonia Metabolism and Transport

    Science.gov (United States)

    Weiner, I. David; Verlander, Jill W.

    2015-01-01

    Renal ammonia metabolism and transport mediates a central role in acid-base homeostasis. In contrast to most renal solutes, the majority of renal ammonia excretion derives from intrarenal production, not from glomerular filtration. Renal ammoniagenesis predominantly results from glutamine metabolism, which produces 2 NH4+ and 2 HCO3− for each glutamine metabolized. The proximal tubule is the primary site for ammoniagenesis, but there is evidence for ammoniagenesis by most renal epithelial cells. Ammonia produced in the kidney is either excreted into the urine or returned to the systemic circulation through the renal veins. Ammonia excreted in the urine promotes acid excretion; ammonia returned to the systemic circulation is metabolized in the liver in a HCO3−-consuming process, resulting in no net benefit to acid-base homeostasis. Highly regulated ammonia transport by renal epithelial cells determines the proportion of ammonia excreted in the urine versus returned to the systemic circulation. The traditional paradigm of ammonia transport involving passive NH3 diffusion, protonation in the lumen and NH4+ trapping due to an inability to cross plasma membranes is being replaced by the recognition of limited plasma membrane NH3 permeability in combination with the presence of specific NH3-transporting and NH4+-transporting proteins in specific renal epithelial cells. Ammonia production and transport are regulated by a variety of factors, including extracellular pH and K+, and by several hormones, such as mineralocorticoids, glucocorticoids and angiotensin II. This coordinated process of regulated ammonia production and transport is critical for the effective maintenance of acid-base homeostasis. PMID:23720285

  19. Novel genes in renal aging

    OpenAIRE

    Noordmans, Gerda Anke

    2015-01-01

    Renal aging is characterized by structural changes and functional decline. These changes make the elderly more vulnerable to chronic kidney disease, hypertension, and cardiovascular disease. Furthermore, they also make it more difficult to cope with stress factors, such as dehydration, toxicity, and obstruction. These stress factors can lead to acute kidney injury and reduced recovery from acute kidney injury and may result in chronic kidney disease or even end-stage renal disease. The rate o...

  20. Parasites and chronic renal failure

    OpenAIRE

    Mohammadi Manesh, Reza; Hosseini Safa, Ahmad; Sharafi, Seyedeh Maryam; Jafari, Rasool; Bahadoran, Mehran; Yousefi, Morteza; Nasri, Hamid; Yousofi Darani, Hossein

    2014-01-01

    Suppression of the human immune system results in an increase in susceptibility to infection by various infectious agents. Conditions such as AIDS, organ transplantation and chronic renal insufficiency (CRI) are the most important cause of insufficient immune response against infections. Long term renal disorders result in uremia, which can suppress human immune system. Parasitic infections are one of the most important factors indicating the public health problems of the societies. These inf...

  1. MR Imaging of renal transplants

    International Nuclear Information System (INIS)

    Gremo, L.; Avataneo, T.; Potenzoni, F.; Colla, L.; Segoloni, G.

    1988-01-01

    The authors report their experience in the study of renal transplant recipients by MR, in order to determine its clinical potentials. The main purpose of this work is to focus on MR patterns in relation to clinical findings of rejector or normally fuctioning kidney. Twenty-four patients were examined with a 0.5 T superconductive magnete, body coil, spin-echo pulse sequence (SE) and inversion-recovery (IR). MRI patterns could be seen in normally functioning kidneys and transplant rejections, while variable MRI findings were observed in transplants with acute tubular necrosis (ATN). In the normally functioning transplanted kidney there is a clear corticomedullary differentiation (CMD), and the extent of vascular penetration into the renal parenchyma is clearly seen. In transplant rejection, CMD is either diminished or absent, and there is no vascular penetration into the parenchyma; to differentiate acute from chronic rejections, the increase/decrease in renal size and the change in renal shape (spherical shape in acute transplant rejection) respectively must be observed. MRI proves thus to be useful in the study of renal transplants, even in case of questionable clinical findings, and in patients in whom renal biopsy is contraindicated

  2. Renal transplant scintigraphy (Part 1)

    International Nuclear Information System (INIS)

    Chew, Ghee

    2005-01-01

    Renal transplantation is the most effective mode of renal replacement therapy for correction of renal failure. Renal donors can either be: a. a deceased person - the kidneys being removed when brain death or absence of cerebral cortical function / perfusion is confirmed - the cadaveric kidney is packed in ice and nutrient solution and transplanted within 24 hours of removal ('cold ischemia') ob. a living donor - the donor may or may not be related to the recipient. Due to the limited length of the renal vessels and ureter of the donor kidney, it is implanted close to the bladder of the recipient. The donor vessels are anastomosed to the iliac artery and vein of the recipient. Transplant variants: a. 2 kidneys maybe transplanted because: - an old donor with less kidney reserve from atrophy due to age or disease (e.g. hypertension) - an infant donor when both kidneys are removed en bloc, b. Donor kidneys with more than 1 artery, vein or ureter. c. Donor horse shoe kidney d. Combined renal and pancreas transplant for type I diabetics -a short segment of duodenum transplanted with the pancreas maybe implanted into the bladder. Copyright (2005) The Australian and New Zealand Society of Nuclear Medicine

  3. Early Illustrations of Geste Antagoniste in Cervical and Generalized Dystonia

    Science.gov (United States)

    Broussolle, Emmanuel; Laurencin, Chloé; Bernard, Emilien; Thobois, Stéphane; Danaila, Teodor; Krack, Paul

    2015-01-01

    Background Geste antagoniste, or sensory trick, is a voluntary maneuver that temporarily reduces the severity of dystonic postures or movements. We present a historical review of early reports and illustrations of geste antagoniste. Results In 1894, Brissaud described this phenomenon in Paris in patients with torticollis. He noted that a violent muscular contraction could be reversed by a minor voluntary action. He considered the improvement obtained by what he called “simple mannerisms, childish behaviour or fake pathological movements” was proof of the psychogenic origin of what he named mental torticollis. This concept was supported by photographical illustrations of the patients. The term geste antagoniste was used by Brissaud’s pupils, Meige and Feindel, in their 1902 monograph on movement disorders. Other reports and illustrations of this sign were published in Europe between 1894 and 1906. Although not mentioned explicitly, geste antagoniste was also illustrated in a case report of generalized dystonia in Oppenheim’s 1911 seminal description of dystonia musculorum deformans in Berlin. Discussion Brissaud-Meige’s misinterpretation of the geste antagoniste unfortunately anchored the psychogenic origin of dystonia for decades. In New York, Herz brought dystonia back into the realm of organic neurology in 1944. Thereafter, it was given prominence by other authors, notably Fahn and Marsden in the 1970–1980s. Nowadays, neurologists routinely investigate for geste antagoniste when a dystonic syndrome is suspected, because it provides a further argument in favor of dystonia. The term alleviating maneuver was proposed in 2014 to replace sensory trick or geste antagoniste. This major sign is now part of the motor phenomenology of the 2013 Movement Disorder Society’s classification of dystonia. PMID:26417535

  4. Lactobacillus plantarum (VR1 isolated from an Ayurvedic medicine (Kutajarista ameliorates in vitro cellular damage caused by Aeromonas veronii

    Directory of Open Access Journals (Sweden)

    Patole Milind S

    2011-06-01

    Full Text Available Abstract Background Lactobacillus plantarum is considered as a safe and effective probiotic microorganism. Among various sources of isolation, traditionally fermented foods are considered to be rich in Lactobacillus spp., which can be exploited for their probiotic attribute. Antibacterial property of L. plantarum has been demonstrated against various enteric pathogens in both in vitro and in vivo systems. This study was aimed at characterizing L. plantarum isolated from Kutajarista, an ayurvedic fermented biomedicine, and assessing its antagonistic property against a common enteropathogen Aeromonas veronii. Results We report the isolation of L. plantarum (VR1 from Kutajarista, and efficacy of its cell free supernatant (CFS in amelioration of cytotoxicity caused by Aeromonas veronii. On the part of probiotic attributes, VR1 was tolerant to pH 2, 0.3% bile salts and simulated gastric juice. Additionally, VR1 also exhibited adhesive property to human intestinal HT-29 cell line. Furthermore, CFS of VR1 was antibacterial to enteric pathogens like Pseudomonas aeruginosa, Staphylococcus aureus, Escherichia coli, Aeromonas veronii and clinical isolates of P. aeruginosa and E. coli. Detailed study regarding the effect of VR1 CFS on A. veronii cytotoxicity showed a significant decrease in vacuole formation and detrimental cellular changes in Vero cells. On the other hand, A. veronii CFS caused disruption of tight junction proteins ZO-1 and actin in MDCK cell line, which was prevented by pre-incubation with CFS of VR1. Conclusions This is the first study to report isolation of L. plantarum (VR1 from Kutajarista and characterisation for its probiotic attributes. Our study demonstrates the antagonistic property of VR1 to A. veronii and effect of VR1 CFS in reduction of cellular damage caused by A. veronii in both Vero and MDCK cell lines.

  5. Augmenter of liver regeneration inhibits TGF-β1-induced renal tubular epithelial-to-mesenchymal transition via suppressing TβR II expression in vitro

    International Nuclear Information System (INIS)

    Liao, Xiao-hui; Zhang, Ling; Chen, Guo-tao; Yan, Ru-yu; Sun, Hang; Guo, Hui; Liu, Qi

    2014-01-01

    Tubular epithelial-to-mesenchymal transition (EMT) plays a crucial role in the progression of renal tubular interstitial fibrosis (TIF), which subsequently leads to chronic kidney disease (CKD) and eventually, end-stage renal disease (ESRD). We propose that augmenter of liver regeneration (ALR), a member of the newly discovered ALR/Erv1 protein family shown to ameliorate hepatic fibrosis, plays a similar protective role in renal tubular cells and has potential as a new treatment option for CKD. Here, we showed that recombinant human ALR (rhALR) inhibits EMT in renal tubular cells by antagonizing activation of the transforming growth factor-β1 (TGF-β1) signaling pathway. Further investigation revealed that rhALR suppresses the expression of TGF-β receptor type II (TβR II) and significantly alleviates TGF-β1-induced phosphorylation of Smad2 and nuclear factor-κB (NF-κB). No apparent adverse effects were observed upon the addition of rhALR alone to cells. These findings collectively suggest that ALR plays a role in inhibiting progression of renal tubular EMT, supporting its potential utility as an effective antifibrotic strategy to reverse TIF in CKD. - Highlights: • ALR is involved in the pathological progression of renal EMT in NRK-52E cells. • ALR suppresses the expression of TβRII and the phosphorylation of Smad2 and NF-κB. • ALR plays a role in inhibiting progression of renal tubular EMT

  6. Angiotensin-(1-7 relieved renal injury induced by chronic intermittent hypoxia in rats by reducing inflammation, oxidative stress and fibrosis

    Directory of Open Access Journals (Sweden)

    W. Lu

    Full Text Available We aimed to study the renal injury and hypertension induced by chronic intermittent hypoxia (CIH and the protective effects mediated by angiotensin 1-7 [Ang(1-7]. We randomly assigned 32 male Sprague-Dawley rats (body weight 180-200 g to normoxia control, CIH, Ang(1-7-treated normoxia, and Ang(1-7-treated CIH groups. Systolic blood pressure (SBP was monitored at the start and end of each week. Renal sympathetic nerve activity (RSNA was recorded. CTGF and TGF-β were detected by immunohistochemistry and western blotting. Tissue parameters of oxidative stress were also determined. In addition, renal levels of interleukin-6, tumor necrosis factor-α, nitrotyrosine, and hypoxia-inducible factor-1α were determined by immunohistochemistry, immunoblotting, and ELISA. TUNEL assay results and cleaved caspase 3 and 12 were also determined. Ang(1-7 induced a reduction in SBP together with a restoration of RSNA in the rat model of CIH. Ang(1-7 treatment also suppressed the production of reactive oxygen species, reduced renal tissue inflammation, ameliorated mesangial expansion, and decreased renal fibrosis. Thus, Ang(1-7 treatment exerted renoprotective effects on CIH-induced renal injury and was associated with a reduction of oxidative stress, inflammation and fibrosis. Ang(1-7 might therefore represent a promising therapy for obstructive sleep apnea-related hypertension and renal injury.

  7. Augmenter of liver regeneration inhibits TGF-β1-induced renal tubular epithelial-to-mesenchymal transition via suppressing TβR II expression in vitro

    Energy Technology Data Exchange (ETDEWEB)

    Liao, Xiao-hui [Department of Nephrology, The Second Affiliated Hospital, Chongqing Medical University, Chongqing 400010 (China); Zhang, Ling, E-mail: lindazhang8508@hotmail.com [Department of Nephrology, The Second Affiliated Hospital, Chongqing Medical University, Chongqing 400010 (China); Chen, Guo-tao; Yan, Ru-yu [Department of Nephrology, The Second Affiliated Hospital, Chongqing Medical University, Chongqing 400010 (China); Sun, Hang; Guo, Hui [Institute for Viral Hepatitis, Key Laboratory of Molecular Biology for Infectious Diseases, The Second Affiliated Hospital, Chongqing Medical University, Chongqing 400010 (China); Liu, Qi, E-mail: txzzliuqi@163.com [Institute for Viral Hepatitis, Key Laboratory of Molecular Biology for Infectious Diseases, The Second Affiliated Hospital, Chongqing Medical University, Chongqing 400010 (China)

    2014-10-01

    Tubular epithelial-to-mesenchymal transition (EMT) plays a crucial role in the progression of renal tubular interstitial fibrosis (TIF), which subsequently leads to chronic kidney disease (CKD) and eventually, end-stage renal disease (ESRD). We propose that augmenter of liver regeneration (ALR), a member of the newly discovered ALR/Erv1 protein family shown to ameliorate hepatic fibrosis, plays a similar protective role in renal tubular cells and has potential as a new treatment option for CKD. Here, we showed that recombinant human ALR (rhALR) inhibits EMT in renal tubular cells by antagonizing activation of the transforming growth factor-β1 (TGF-β1) signaling pathway. Further investigation revealed that rhALR suppresses the expression of TGF-β receptor type II (TβR II) and significantly alleviates TGF-β1-induced phosphorylation of Smad2 and nuclear factor-κB (NF-κB). No apparent adverse effects were observed upon the addition of rhALR alone to cells. These findings collectively suggest that ALR plays a role in inhibiting progression of renal tubular EMT, supporting its potential utility as an effective antifibrotic strategy to reverse TIF in CKD. - Highlights: • ALR is involved in the pathological progression of renal EMT in NRK-52E cells. • ALR suppresses the expression of TβRII and the phosphorylation of Smad2 and NF-κB. • ALR plays a role in inhibiting progression of renal tubular EMT.

  8. Recommendations for the use of tolvaptan in autosomal dominant polycystic kidney disease : a position statement on behalf of the ERA-EDTA Working Groups on Inherited Kidney Disorders and European Renal Best Practice

    NARCIS (Netherlands)

    Gansevoort, Ron T; Arici, Mustafa; Benzing, Thomas; Birn, Henrik; Capasso, Giovambattista; Covic, Adrian; Devuyst, Olivier; Drechsler, Christiane; Eckardt, Kai-Uwe; Emma, Francesco; Knebelmann, Bertrand; Le Meur, Yannick; Massy, Ziad A; Ong, Albert C M; Ortiz, Alberto; Schaefer, Franz; Torra, Roser; Vanholder, Raymond; Więcek, Andrzej; Zoccali, Carmine; Van Biesen, Wim

    Recently, the European Medicines Agency approved the use of the vasopressin V2 receptor antagonist tolvaptan to slow the progression of cyst development and renal insufficiency of autosomal dominant polycystic kidney disease (ADPKD) in adult patients with chronic kidney disease stages 1-3 at

  9. Technical aspects of renal denervation in end-stage renal disease patients with challenging anatomy.

    Science.gov (United States)

    Spinelli, Alessio; Da Ros, Valerio; Morosetti, Daniele; Onofrio, Silvia D; Rovella, Valentina; Di Daniele, Nicola; Simonetti, Giovanni

    2014-01-01

    We describe our preliminary experience with percutaneous renal denervation in end-stage renal disease patients with resistant hypertension and challenging anatomy, in terms of the feasibility, safety, and efficacy of this procedure. Four patients with end-stage renal disease patients with resistant hypertension (mean hemodialysis time, 2.3 years) who had been taking at least four antihypertensive medications underwent percutaneous renal denervation. Renal artery eligibility included the absence of prior renal artery interventions, vessel stenosis renal denervation is a feasible approach for end-stage renal disease patients with resistant hypertension with encouraging short-term preliminary results in terms of procedural efficacy and safety.

  10. Preclinical development of a novel class of CXCR4 antagonist impairing solid tumors growth and metastases.

    Directory of Open Access Journals (Sweden)

    Luigi Portella

    Full Text Available The CXCR4/CXCL12 axis plays a role in cancer metastases, stem cell mobilization and chemosensitization. Proof of concept for efficient CXCR4 inhibition has been demonstrated in stem cell mobilization prior to autologous transplantation in hematological malignancies. Nevertheless CXCR4 inhibitors suitable for prolonged use as required for anticancer therapy are not available. To develop new CXCR4 antagonists a rational, ligand-based approach was taken, distinct from the more commonly used development strategy. A three amino acid motif (Ar-Ar-X in CXCL12, also found in the reverse orientation (X-Ar-Ar in the vMIP-II inhibitory chemokine formed the core of nineteen cyclic peptides evaluated for inhibition of CXCR4-dependent migration, binding, P-ERK1/2-induction and calcium efflux. Peptides R, S and I were chosen for evaluation in in vivo models of lung metastases (B16-CXCR4 and KTM2 murine osteosarcoma cells and growth of a renal cells xenograft. Peptides R, S, and T significantly reduced the association of the 12G5-CXCR4 antibody to the receptor and inhibited CXCL12-induced calcium efflux. The four peptides efficiently inhibited CXCL12-dependent migration at concentrations as low as 10 nM and delayed CXCL12-mediated wound healing in PES43 human melanoma cells. Intraperitoneal treatment with peptides R, I or S drastically reduced the number of B16-CXCR4-derived lung metastases in C57/BL mice. KTM2 osteosarcoma lung metastases were also reduced in Balb/C mice following CXCR4 inhibition. All three peptides significantly inhibited subcutaneous growth of SN12C-EGFP renal cancer cells. A novel class of CXCR4 inhibitory peptides was discovered. Three peptides, R, I and S inhibited lung metastases and primary tumor growth and will be evaluated as anticancer agents.

  11. Treatment of renal anemia: Erythropoiesis stimulating agents and beyond

    Directory of Open Access Journals (Sweden)

    Patrick Biggar

    2017-09-01

    Full Text Available Anemia, complicating the course of chronic kidney disease, is a significant parameter, whether interpreted as subjective impairment or an objective prognostic marker. Renal anemia is predominantly due to relative erythropoietin (EPO deficiency. EPO inhibits apoptosis of erythrocyte precursors. Studies using EPO substitution have shown that increasing hemoglobin (Hb levels up to 10-11 g/dL is associated with clinical improvement. However, it has not been unequivocally proven that further intensification of erythropoiesis stimulating agent (ESA therapy actually leads to a comprehensive benefit for the patient, especially as ESAs are potentially associated with increased cerebro-cardiovascular events. Recently, new developments offer interesting options not only via stimulating erythropoeisis but also by employing additional mechanisms. The inhibition of activin, a member of the transforming growth factor superfamily, has the potential to correct anemia by stimulating liberation of mature erythrocyte forms and also to mitigate disturbed mineral and bone metabolism as well. Hypoxia-inducible factor prolyl hydroxylase inhibitors also show pleiotropic effects, which are at the focus of present research and have the potential of reducing mortality. However, conventional ESAs offer an extensive body of safety evidence, against which the newer substances should be measured. Carbamylated EPO is devoid of Hb augmenting effects whilst exerting promising tissue protective properties. Additionally, the role of hepcidin antagonists is discussed. An innovative new hemodialysis blood tube system, reducing blood contact with air, conveys a totally different and innocuous option to improve renal anemia by reducing mechanical hemolysis.

  12. Continuous renal replacement therapy improves renal recovery from acute renal failure.

    Science.gov (United States)

    Jacka, Michael J; Ivancinova, Xenia; Gibney, R T Noel

    2005-03-01

    Acute renal failure (ARF) occurs in up to 10% of critically ill patients, with significant associated morbidity and mortality. The optimal mode of renal replacement therapy (RRT) remains controversial. This retrospective study compared continuous renal replacement therapy (CRRT) and intermittent hemodialysis (IHD) for RRT in terms of intensive care unit (ICU) and hospital mortality, and renal recovery. We reviewed the records of all patients undergoing RRT for the treatment of ARF over a 12-month period. Patients were compared according to mode of RRT, demographics, physiologic characteristics, and outcomes of ICU and hospital mortality and renal recovery using the Chi square, Student's t test, and multiple logistic regression as appropriate. 116 patients with renal insufficiency underwent RRT during the study period. Of these, 93 had ARF. The severity of illness of CRRT patients was similar to that of IHD patients using APACHE II (25.1 vs 23.5, P = 0.37), but they required significantly more intensive nursing (therapeutic intervention scale 47.8 vs 37.6, P = 0.0001). Mortality was associated with lower pH at presentation (P = 0.003) and increasing age (P = 0.03). Renal recovery was significantly more frequent among patients initially treated with CRRT (21/24 vs 5/14, P = 0.0003). Further investigation to define optimal timing, dose, and duration of RRT may be beneficial. Although further study is needed, this study suggests that renal recovery may be better after CRRT than IHD for ARF. Mortality was not affected significantly by RRT mode.

  13. Renal manifestations in children with Alagille syndrome.

    Science.gov (United States)

    Di Pinto, Diana; Adragna, Marta

    2018-04-01

    Alagille syndrome (AS) is a cholestatic disease secondary to scarcity of interlobular bile ducts. It is associated with extrahepatic manifestations, and renal involvement is frequent. To describe the prevalence, type and outcome of renal pathology in children with AS. The presence and outcome of renal pathology was retrospectively studied in 21 children who met AS criteria. Renal pathology was observed in 18 patients (85.7%): (1) ultrasound variations in 7 patients (6 cases of bilateral renal dysplasia and 1 case of renal agenesis); (2) distal renal tubular acidosis in 2 patients; (3) a drop in glomerular filtration and/or proteinuria in 16 patients. The frequency of a drop in glomerular filtration was similar between patients with and without pathological kidney ultrasound findings. Our study confirms a high prevalence of renal involvement, which enhances the importance of diagnosis and renal function follow-up in children with AS. Sociedad Argentina de Pediatría.

  14. Renal failure in patients with multiple myeloma.

    Science.gov (United States)

    Almueilo, Samir H

    2015-01-01

    Renal dysfunction is encountered in 20-25% of patients with multiple myeloma (MM) at the time of diagnosis. There is often a precipitating event. Several biochemical and clinical correlations with renal failure in MM have been reported. Renal failure in MM is associated with worse outcome of the disease. We retrospectively analyzed the medical records of 64 patients with MM admitted to our institution during the period January 1992 to December 2012. Abnormal renal function was observed in 24 (37.5%) patients and 17 (26.6%) of them had renal failure; 14 of the 17 (82.4%) of patients with renal failure had Stage III MM. Urine Bence- Jones protein was positive in ten (58.8%) patients with renal failure versus ten (21.3%) patients without renal failure (P = 0.004). Potential precipitating factors of renal failure were determined in nine patients. Renal function normalized in 11 patients with simple measures, while six patients required hemodialysis; one remained dialysis dependent till time of death. Early mortality occurred in five (29.4%) patients with renal failure as compared with two (4.3%) patients in the group without renal failure (P = 0.005). In conclusion, renal failure is associated with a higher tumor burden and Bence-Jones proteinuria in patients with MM. It is reversible in the majority of patients; however, early mortality tends to be higher in patients with persistent renal failure.

  15. Renal vasculitis presenting with acute kidney injury.

    Science.gov (United States)

    Villacorta, Javier; Diaz-Crespo, Francisco; Acevedo, Mercedes; Cavero, Teresa; Guerrero, Carmen; Praga, Manuel; Fernandez-Juarez, Gema

    2017-06-01

    Renal failure secondary to ANCA-associated vasculitis represents a clinical and therapeutic challenge. In this study, we aimed to assess the treatment response rates and long-term outcomes of vasculitis patients presenting with renal failure. This retrospective study included 151 patients with renal vasculitis from three hospitals who underwent a renal biopsy between 1997 and 2014. Patients with renal failure which required dialysis at the onset were compared to those presenting with more preserved renal function. The primary end point was treatment response and patient surivival. Patients with severe renal involvement had a lower response to treatment compared to those having preserved renal function (26.6 versus 93.4%; p renal recovery (41.6 versus 12.5%; p = 0.05). A higher incidence of severe infections was observed among patients with severe renal involvement (38.4 versus 18.1%, p = 0.01). The mortality rate was significantly higher among vasculitis patients presenting with renal failure (53.8 versus 22.2%, p = 0.001). Global survival at 1 and 5 years was 60 and 47% in patients requiring dialysis compared with 90 and 80% among those with more preserved renal function (p renal dysfunction represents an independent risk factor for patient survival in renal vasculitis. Patients requiring dialysis associate a lower response rate to immunosuppressive therapy and a higher incidence of severe infections.

  16. MDM2 Antagonists Counteract Drug-Induced DNA Damage

    Directory of Open Access Journals (Sweden)

    Anna E. Vilgelm

    2017-10-01

    Full Text Available Antagonists of MDM2-p53 interaction are emerging anti-cancer drugs utilized in clinical trials for malignancies that rarely mutate p53, including melanoma. We discovered that MDM2-p53 antagonists protect DNA from drug-induced damage in melanoma cells and patient-derived xenografts. Among the tested DNA damaging drugs were various inhibitors of Aurora and Polo-like mitotic kinases, as well as traditional chemotherapy. Mitotic kinase inhibition causes mitotic slippage, DNA re-replication, and polyploidy. Here we show that re-replication of the polyploid genome generates replicative stress which leads to DNA damage. MDM2-p53 antagonists relieve replicative stress via the p53-dependent activation of p21 which inhibits DNA replication. Loss of p21 promoted drug-induced DNA damage in melanoma cells and enhanced anti-tumor activity of therapy combining MDM2 antagonist with mitotic kinase inhibitor in mice. In summary, MDM2 antagonists may reduce DNA damaging effects of anti-cancer drugs if they are administered together, while targeting p21 can improve the efficacy of such combinations.

  17. Gonadotrophin releasing hormone antagonist in IVF/ICSI

    Directory of Open Access Journals (Sweden)

    M S Kamath

    2008-01-01

    Full Text Available Objective : To study the efficacy of gonadotrophin releasing hormone (GnRH antagonist in In-vitro-fertilization/Intracytoplasmic sperm injection (IVF/ICSI cycles. Type of Study : Observational study. Setting: Reproductive Medicine Unit, Christian Medical College Hospital, Vellore, Tamil Nadu. Materials and Methods: GnRH antagonists were introduced into our practice in November 2005. Fifty-two women undergoing the antagonist protocol were studied and information gathered regarding patient profile, treatment parameters (total gonadotrophin dosage, duration of treatment, and oocyte yield, and outcomes in terms of embryological parameters (cleavage rates, implantation rates and clinical pregnancy. These parameters were compared with 121 women undergoing the standard long protocol. The costs between the two groups were also compared. Main Outcome : Clinical pregnancy rate. Results : The clinical pregnancy rate per embryo transfer in the antagonist group was 31.7% which was comparable to the clinical pregnancy rate in women undergoing the standard long protocol (30.63%. The costs between the two groups were comparable. Conclusions : GnRH antagonist protocol was found to be effective and comparable to the standard long protocol regimen. In addition it was simple, convenient, and patient friendly.

  18. Novel Peripherally Restricted Cannabinoid 1 Receptor Selective Antagonist TXX-522 with Prominent Weight-Loss Efficacy in Diet Induced Obese Mice

    Directory of Open Access Journals (Sweden)

    Wei Chen

    2017-10-01

    Full Text Available The clinical development of the first generation of globally active cannabinoid 1 receptor (CB1R antagonists was suspended because of their adverse neuropsychiatric effects. Selective blockade of peripheral CB1Rs has the potential to provide a viable strategy for the treatment of severe obesity while avoiding these central nervous system side effects. In the current study, a novel compound (TXX-522 was rationally designed based on the parent nucleus of a classical CB1R-selective antagonist/inverse agonist, rimonabant (SR141716A. Docking assays indicate that TXX-522 was bound with the CB1R in a mode similar to that of SR141716A. TXX-522 showed good binding, CB1R-selectivity (over the CB2R, and functional antagonist activities in a range of in vitro molecular and cellular assays. In vivo analysis of the steady state distribution of TXX-522 in the rat brain and blood tissues and the assay of its functional effects on CB1R activity collectively showed that TXX-522 showed minimal brain penetration. Moreover, the in vivo pharmacodynamic study further revealed that TXX-522 had good oral bioavailability and a potent anti-obesity effect, and ameliorated insulin resistance in high-fat diet-induced obese mice. No impact on food intake was observed in this model, confirming the limited brain penetration of this compound. Thus, the current study indicates that TXX-522 is a novel and potent peripherally acting selective CB1R antagonist with the potential to control obesity and related metabolic disorders.

  19. Moringa oleifera from Cambodia Ameliorates Oxidative Stress, Hyperglycemia, and Kidney Dysfunction in Type 2 Diabetic Mice.

    Science.gov (United States)

    Tang, Yujiao; Choi, Eun-Ju; Han, Weon Cheol; Oh, Mirae; Kim, Jin; Hwang, Ji-Young; Park, Pyo-Jam; Moon, Sang-Ho; Kim, Yon-Suk; Kim, Eun-Kyung

    2017-05-01

    Recent reports have shown the antidiabetic effect of Moringa oleifera from various parts of the world. However, M. oleifera from Cambodia has never determined. Therefore, the aim of this study was to assess the antidiabetic effect of M. oleifera extract from Cambodia. The leaf ethanolic extract contained flavonoids (31.90 mg/mL), polyphenols (53.03 mg/mL), lycopene (0.042 mg/mL), and ß-carotene (0.170 mg/mL), and possessed 2,2-diphenyl-1-picrylhydrazyl, hydrogen peroxide, and hydroxyl radical scavenging activities of 92.40, 99.25, and 83.57 TE/μM at 1 mg/mL, respectively. Db/db mice were orally administered the leaf extract (150 mg/kg/day) for 5 weeks. M. oleifera treatment significantly ameliorated the altered fasting plasma glucose (from 483 to 312 mg/dL), triglyceride (from 42.12 to 23.00 mg/dL), and low-density lipoprotein cholesterol (from 107.21 to 64.25 mg/dL) compared to control group, and increased the insulin levels from 946 ± 92 to 1678 ± 268 pg/mL. The histopathological damage and expression levels of tumor necrosis factor-alpha, interleukin (IL)-1β, IL-6, cyclooxygenase-2, and inducible nitric oxide synthase in renal tissue decreased. These results indicate the potential antidiabetic benefits of M. oleifera ethanolic leaf extract.

  20. Ameliorative Effect of Arctium lappa Against Cadmium Genotoxicity and Histopathology in Kidney of Wistar Rat.

    Science.gov (United States)

    Suliman Al-Gebaly, Asma

    2017-01-01

    Cadmium (Cd) is a non-essential metal whose dispersion in the environment has increased recently, Cd may enhance cell oxidative stress that leads to DNA damage and apoptotic cell death. The study aimed to evaluate the antioxidative capability of Burdock root 'Arctium lappa' on cadmium-induced oxidative stress and histopathology of the kidney of Wistar rats. Cadmium was applied in a form of cadmium chloride to three groups (15 mg Cd kg-1) for five weeks with two groups pre-treated with 'Arctium lappa' administration, 100 and 200 mg kg-1 b.wt. Data were analyzed using one way analysis of variance (ANOVA) followed by Least Significant Difference (LSD) test to determine the difference among means using the JMP version 12. Results revealed that cadmium induced a significant disorganization (pArctium lappa kg-1 b.wt., showed a slightly less hypercellularity of glomerulus and reduction in the cell tail (59 μm). Furthermore, histological sections of kidney of rats pre-treated with 200 mg Arctium lappa kg-1 b.wt., showed high improvement of renal tubules and glomerulus with a prominent urinary space beside tail length of cells was recorded as 39 μm which was lower in comparison to other groups. Moreover, cadmium induced cellular destruction of the kidney was resumed with the pre-treatment of the secondary metabolites as an antioxidant compounds that produced from plant extracts. Arctium lappa leaf extract was efficient at both applied doses while 200 mg Arctium lappa kg-1 b.wt., had the most ameliorative effect.

  1. The Role of Calcium in Ameliorating the Oxidative Stress of Fluoride in Rats.

    Science.gov (United States)

    Mohamed, N E

    2016-03-01

    The present study was carried out to investigate the effects of fluoride toxicity on some biochemical, hormonal, and histological parameters of female rats and the protective role of calcium against such effects. Adult female albino rats were divided into five groups; control group received distilled water for 60 days, calcium group received calcium carbonate with dose of 50 mg/kg three times per week for 60 days, fluoride group received sodium fluoride with dose of 20 mg/kg three times per week for 60 days, calcium + fluoride group received calcium carbonate (50 mg/kg) then after 2 h received sodium fluoride (20 mg/kg) three times per week for 60 days, and fluoride + calcium group received sodium fluoride (20 mg/kg) three times per week for 30 days then received calcium carbonate (50 mg/kg) three times per week for another 30 days. The results showed that the levels of thiobarbituric acid reactive substances, urea, creatinine, alkaline phosphatase, triiodothyronine, thyroxine, parathormone, phosphorous, magnesium, alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, and gamma glutamyl transferase were significantly increased in rats treated with fluoride while serum estradiol, calcium, and organ glutathione were significantly decreased. The histological examination of the femur bone revealed that fluoride treatment induced thinning of bone trabeculae with wilding of marrow space, demineralization, and loss of trabeculae interconnections. Also, the histological examination of hepatic and renal tissues of fluoride-treated rats showed some damages in these tissues while administration of calcium carbonate for 30 or 60 days during fluoride treatment minimized such damages. It could be concluded that administration of calcium to female rats can ameliorate the hazardous effects of fluoride observed in the biochemical, hormonal, and histological parameters.

  2. Activation of GLP-1 receptors on vascular smooth muscle cells reduces the autoregulatory response in afferent arterioles and increases renal blood flow.

    Science.gov (United States)

    Jensen, Elisa P; Poulsen, Steen S; Kissow, Hannelouise; Holstein-Rathlou, Niels-Henrik; Deacon, Carolyn F; Jensen, Boye L; Holst, Jens J; Sorensen, Charlotte M

    2015-04-15

    Glucagon-like peptide (GLP)-1 has a range of extrapancreatic effects, including renal effects. The mechanisms are poorly understood, but GLP-1 receptors have been identified in the kidney. However, the exact cellular localization of the renal receptors is poorly described. The aim of the present study was to localize renal GLP-1 receptors and describe GLP-1-mediated effects on the renal vasculature. We hypothesized that renal GLP-1 receptors are located in the renal microcirculation and that activation of these affects renal autoregulation and increases renal blood flow. In vivo autoradiography using (125)I-labeled GLP-1, (125)I-labeled exendin-4 (GLP-1 analog), and (125)I-labeled exendin 9-39 (GLP-1 receptor antagonist) was performed in rodents to localize specific GLP-1 receptor binding. GLP-1-mediated effects on blood pressure, renal blood flow (RBF), heart rate, renin secretion, urinary flow rate, and Na(+) and K(+) excretion were investigated in anesthetized rats. Effects of GLP-1 on afferent arterioles were investigated in isolated mouse kidneys. Specific binding of (125)I-labeled GLP-1, (125)I-labeled exendin-4, and (125)I-labeled exendin 9-39 was observed in the renal vasculature, including afferent arterioles. Infusion of GLP-1 increased blood pressure, RBF, and urinary flow rate significantly in rats. Heart rate and plasma renin concentrations were unchanged. Exendin 9-39 inhibited the increase in RBF. In isolated murine kidneys, GLP-1 and exendin-4 significantly reduced the autoregulatory response of afferent arterioles in response to stepwise increases in pressure. We conclude that GLP-1 receptors are located in the renal vasculature, including afferent arterioles. Activation of these receptors reduces the autoregulatory response of afferent arterioles to acute pressure increases and increases RBF in normotensive rats. Copyright © 2015 the American Physiological Society.

  3. Crisis de esclerodermia renal normotensiva

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    M. Villaverde

    2003-01-01

    Full Text Available Paciente de sexo masculino de 60 años con esclerosis sistémica que evolucionó con crisis de esclerodermia renal normotensiva. Tenía compromiso poliarticular, esofágico, pulmonar y cutáneo. Antes de internarse en nuestro hospital recibió tratamiento con altas dosis de corticoides, lo que probablemente precipitó el daño renal que presentó en su evolución, caracterizado por falla renal, anemia hemolítica microangiopática sin elevación de la presión arterial. La ausencia de hipertensión se observa sólo en el 10% de los casos de esclerodermia renal. Recibió tratamiento con enalapril y hemodiálisis. Evolucionó en forma desfavorable, sin respuesta a la terapeútica y falleció a los siete días de internado.A 60 year old male patient having systemic scleroderma and normotensive scleroderma renal crisis was admitted in our hospital. He presented polyarticular, esophagic, lung and skin compromise. Before admission he had been treated with high doses of corticosteroids. We believe corticosteroids led to the worsening of renal damage with renal failure, microangiopathic hemolytic anemia without high blood pressure. The 10% of these cases have normal blood pressure. The patient was treated with enalapril and hemodyalisis. There was no favourable response to this treatment and he died seven days after admission.

  4. Icariin combined with human umbilical cord mesenchymal stem cells significantly improve the impaired kidney function in chronic renal failure.

    Science.gov (United States)

    Li, Wen; Wang, Li; Chu, Xiaoqian; Cui, Huantian; Bian, Yuhong

    2017-04-01

    At present, the main therapy for chronic renal failure (CRF) is dialysis and renal transplantation, but neither obtains satisfactory results. Human umbilical cord mesenchymal stem cells (huMSCs) are isolated from the fetal umbilical cord which has a high self-renewal and multi-directional differentiation potential. Icariin (ICA), a kidney-tonifying Chinese Medicine can enhance the multipotency of huMSCs. Therefore, this work seeks to employ the use of ICA-treated huMSCs for the treatment of chronic renal failure. Blood urea nitrogen and creatinine (Cr) analyses showed amelioration of functional parameters in ICA-treated huMSCs for the treatment of CRF rats at 3, 7, and 14 days after transplantation. ICA-treated huMSCs can obviously increase the number of cells in injured renal tissues at 3, 7, and 14 days after transplantation by optical molecular imaging system. Hematoxylin-eosin staining demonstrated that ICA-treated huMSCs reduced the levels of fibrosis in CRF rats at 14 days after transplantation. Superoxide dismutase and Malondialdehyde analyses showed that ICA-treated huMSCs reduced the oxidative damage in CRF rats. Moreover, transplantation with ICA-treated huMSCs decreased inflammatory responses, promoted the expression of growth factors, and protected injured renal tissues. Taken together, our findings suggest that ICA-treated huMSCs could improve the kidney function in CRF rats.

  5. Dynamic CT of the renal parenchyma

    International Nuclear Information System (INIS)

    Ohyama, Yukio; Imanishi, Yoshimasa; Ishikawa, Tohru; Fujii, Masamichi; Uji, Teruyuki

    1985-01-01

    Normal renal dynamic CT findings of 57 cases were analysed in termes of sequential change of renal parenchymal CT image. Cortex, outer medulla and inner medulla were delineated and their sequential CT image was well correlated with the anatomicophysiological character of the kidney. Dynamic CT of 32 abnormal cases showed abnormal sequential CT findings explaining the mechanism of the abnormalities. Especially, delayed enhancement of renal cortex was noted in 17 of 19 kidneys with arterial obstruction and delayed enhancement of renal medulla in 22 of 25 cases with renal dysfunction. Compaired with excretory urography in 11 cases with renal dysfunction, advantage of dynamic CT were noted. (author)

  6. CT imaging spectrum of infiltrative renal diseases.

    Science.gov (United States)

    Ballard, David H; De Alba, Luis; Migliaro, Matias; Previgliano, Carlos H; Sangster, Guillermo P

    2017-11-01

    Most renal lesions replace the renal parenchyma as a focal space-occupying mass with borders distinguishing the mass from normal parenchyma. However, some renal lesions exhibit interstitial infiltration-a process that permeates the renal parenchyma by using the normal renal architecture for growth. These infiltrative lesions frequently show nonspecific patterns that lead to little or no contour deformity and have ill-defined borders on CT, making detection and diagnosis challenging. The purpose of this pictorial essay is to describe the CT imaging findings of various conditions that may manifest as infiltrative renal lesions.

  7. CT differentiation of infiltrating renal cell carcinoma and renal urothelial tumor

    International Nuclear Information System (INIS)

    Choi, Hyo Kyeong; Goo, Dong Erk; Bang, Sun Woo; Lee, Moon Gyu; Cho, Kyoung Sik; Auh, Yong Ho

    1994-01-01

    It may be difficult to differentiate renal cell carcinoma involving collecting system from renal urothelial tumor invading into renal parenchyma. The purpose of this study was to assess the differences of CT findings between two conditions. CT findings of 5 cases of renal cell carcinoma involving the renal collecting systems and 10 cases of renal urothelial tumors invading the renal parenchyma were compared, and analyzed about the presence or absence of hydronephrosis, normal or abnormal CT nephrogram, renal contour changes due to mass and tentative diagnosis. The diagnoses were confirmed at surgery. Renal cell carcinoma showed hydronephrosis in only 20% and normal CT nephrogram and outward contour bulging in all cases. In contrast, renal urothelial tumor showed hydronephrosis(70%), abnormal CT nephrogram(60%), and preservation of reinform shape(100%). Renal contour changes and CT nephrogram may be useful in distinguishing both disease entities

  8. Inhibition of CPU0213, a Dual Endothelin Receptor Antagonist, on Apoptosis via Nox4-Dependent ROS in HK-2 Cells

    Directory of Open Access Journals (Sweden)

    Qing Li

    2016-06-01

    Full Text Available Background/Aims: Our previous studies have indicated that a novel endothelin receptor antagonist CPU0213 effectively normalized renal function in diabetic nephropathy. However, the molecular mechanisms mediating the nephroprotective role of CPU0213 remain unknown. Methods and Results: In the present study, we first detected the role of CPU0213 on apoptosis in human renal tubular epithelial cell (HK-2. It was shown that high glucose significantly increased the protein expression of Bax and decreased Bcl-2 protein in HK-2 cells, which was reversed by CPU0213. The percentage of HK-2 cells that showed Annexin V-FITC binding was markedly suppressed by CPU0213, which confirmed the inhibitory role of CPU0213 on apoptosis. Given the regulation of endothelin (ET system to oxidative stress, we determined the role of redox signaling in the regulation of CPU0213 on apoptosis. It was demonstrated that the production of superoxide (O2-. was substantially attenuated by CPU0213 treatment in HK-2 cells. We further found that CPU0213 dramatically inhibited expression of Nox4 protein, which gene silencing mimicked the role of CPU0213 on the apoptosis under high glucose stimulation. We finally examined the role of CPU0213 on ET-1 receptors and found that high glucose-induced protein expression of endothelin A and B receptors was dramatically inhibited by CPU0213. Conclusion: Taken together, these results suggest that this Nox4-dependenet O2- production is critical for the apoptosis of HK-2 cells in high glucose. Endothelin receptor antagonist CPU0213 has an anti-apoptosis role through Nox4-dependent O2-.production, which address the nephroprotective role of CPU0213 in diabetic nephropathy.

  9. First Irish birth following IVF therapy using antagonist protocol.

    LENUS (Irish Health Repository)

    Mocanu, E V

    2012-02-01

    BACKGROUND: During in vitro fertilization (IVF), the prevention of a premature LH surge was traditionally achieved using a gonadotrophin releasing hormone agonist (GnRH-a), and more recently, a GnRH antagonist. AIMS: We report a case of a 37 year old treated using the GnRH antagonist in a second completed cycle of IVF. METHODS: IVF was performed for primary infertility of 5-year duration due to frozen pelvis secondary to endometriosis. RESULTS: Following controlled ovarian hyperstimulation, oocyte recovery and fertilization, cleavage and transfer of two zygotes, a pregnancy established. A twin gestation was diagnosed at 7-weeks scan and pregnancy ended with the delivery of twin girls by emergency caesarean section. CONCLUSION: This is a first report of a delivery following IVF using the antagonist protocol in Ireland. Such therapy is patient friendly and its use should be introduced on a larger scale in clinical practice.

  10. ANTAGONISTIC BACTERIA AGAINST SCHIZOPHYLLUM COMMUNE FR. IN PENINSULAR MALAYSIA

    Directory of Open Access Journals (Sweden)

    ANTARJO DIKIN

    2006-01-01

    Full Text Available Schizophyllum commune Fr., is one of the important fungi, causes brown germ and seed rot of oil palm. Biodiversity of antagonistic bacteria from oil palm plantations in Peninsular Malaysia is expected to support in development of biopesticide. Isolation with liquid assay and screening antagonistic bacteria using dual culture assay were carried out in the bioexploration. A total of 265 bacterial isolates from plant parts of oil palm screened 52 antagonistic bacterial isolates against 5. commune. Bacterial isolates were identified by using Biolog* Identification System i.e. Bacillus macroccanus, B. thermoglucosidasius, Burkholderia cepacia, B. gladioli, B. multivorans, B pyrrocinia, B. spinosa, Corynebacterium agropyri, C. misitidis, Enterobacter aerogenes, Microbacterium testaceum, Pseudomonas aeruginosa, P. citronellolis, Rhodococcus rhodochrous, Serratia ficaria, Serratia sp., S. marcescens, Staphylococcus sciuri, Sternotrophomonas maltophilia.

  11. Ocean acidification ameliorates harmful effects of warming in primary consumer.

    Science.gov (United States)

    Pedersen, Sindre Andre; Hanssen, Anja Elise

    2018-01-01

    Climate change-induced warming and ocean acidification are considered two imminent threats to marine biodiversity and current ecosystem structures. Here, we have for the first time examined an animal's response to a complete life cycle of exposure to co-occurring warming (+3°C) and ocean acidification (+1,600 μatm CO 2 ), using the key subarctic planktonic copepod, Calanus finmarchicus , as a model species. The animals were generally negatively affected by warming, which significantly reduced the females' energy status and reproductive parameters (respectively, 95% and 69%-87% vs. control). Unexpectedly, simultaneous acidification partially offset the negative effect of warming in an antagonistic manner, significantly improving reproductive parameters and hatching success (233%-340% improvement vs. single warming exposure). The results provide proof of concept that ocean acidification may partially offset negative effects caused by warming in some species. Possible explanations and ecological implications for the observed antagonistic effect are discussed.

  12. Mesenchymal stem cells ameliorate rhabdomyolysis-induced acute kidney injury via the activation of M2 macrophages

    Science.gov (United States)

    2014-01-01

    Introduction The mortality of rhabdomyolysis-induced acute kidney injury (AKI) is still high, as there is no effective therapy. It has been shown that bone marrow-derived mesenchymal stem cells (MSCs) can induce M2 macrophages, which mediate MSC protection in other experimental inflammation-related organ injury. This study was designed to investigate the protective effects of macrophage activation in MSC therapy of rhabdomyolysis-induced AKI. Methods MSCs were injected into glycerol-induced rhabdomyolysis mice. Renal injury was evaluated using the serum creatinine, urea nitrogen, renal pathology and acute tubular necrosis score. The distribution of MSCs was detected using two-photon fluorescence confocal imaging. Immunofluorescence of anti-F4/80 and anti-CD206 was performed to determine macrophages and M2 macrophages in the tissues of the kidney, and M2 macrophage infiltration was also evaluated using western blotting analyses. After depletion of macrophages using clodronate liposomes at the phase of kidney repair, renal injury was re-evaluated. RAW 264.7 macrophages were incubated with lipopolysaccharide and co-cultured with MSCs and subsequently visualised using immunofluorescence staining and flow cytometry analysis. Finally, disparate phenotype macrophages, including normal macrophages (M0), lipopolysaccharide-stimulated macrophages (M1), and MSC-co-cultured macrophages (M2), were infused into mice with AKI, which were pre-treated with liposomal clodronate. Results In vivo infusion of MSCs protected AKI mice from renal function impairment and severe tubular injury, which was accompanied by a time-dependent increase in CD206-positive M2 macrophage infiltration. In addition, depleting macrophages with clodronate delayed restoration of AKI. In vitro, macrophages co-cultured with MSCs acquired an anti-inflammatory M2 phenotype, which was characterised by an increased expression of CD206 and the secretory cytokine interleukin (IL)-10. The concentrations of IL-10, IL

  13. Hyperdense renal masses: a CT manifestation of hemorrhagic renal cysts

    International Nuclear Information System (INIS)

    Sussman, S.; Cochran, S.T.; Pagani, J.J.; McArdle, C.; Wong, W.; Austin, R.; Curry, N.; Kelly, K.M.

    1984-01-01

    Eleven patients with sharply circumscribed round to ovoid renal cysts measuring 70-90 H on CT are reported. The cysts were hyperdense on unenhanced scans, measuring 30-60 H greater than the adjacent parenchyma, and either hypodense, isodense, or hyperdense on enhanced scans. Four patients had polycystic kidney disease; of the other 7 patients, the cysts were cortical in 6 and parapelvic in 1. Eight patients had a solitary cyst and 3 had multiple cysts. Sonography demonstrated internal echoes and/or lack of increased through-transmission in 6 patients. Pathological analysis was available in 6 cases and indicated a benign, hemorrhagic renal cyst. This hyperdense CT appearance is characteristic of some hemorrhagic renal cysts, though differentiation between benign and malignant cysts requires cyst puncture and/or surgery

  14. [Renal hemorrhage after ESWL: From small hematoma to renal blowout].

    Science.gov (United States)

    Panach-Navarrete, Jorge; Palmero Martí, Jose Luis; Ganau Ituren, Amparo; Pastor Lence, Juan Carlos; Benedicto Redón, Antonio

    2016-04-01

    To report two cases of renal hemorrhage after extracorporeal shock wave lithotripsy (ESWL) and their therapeutic management. Description of the clinical cases, together with the diagnosis and therapeutic management of these complications. We present two cases of patients with renal hemorrhage after ESWL, which were performed without immediate complications. One of the cases, after detecting an important laceration of the renal parenchyma, needed two embolization sessions for its short-term resolution; however, the patient finally passed away due to the complications derived from hemorrhage. The other case was solved through conservative management. Even though hemorrhage is an infrequent complication after ESWL, it should be suspected when the patient presents compatible clinical symptoms, since even though most cases are resolved in a conservative manner, on some occasions specific treatments for the hemorrhage are necessary. Old age and the presence of vascular comorbidities seem to be related to a higher risk of hemorrhage after ESWL.

  15. Renal Blood Flow, Glomerular Filtration Rate, and Renal Oxygenation in Early Clinical Septic Shock.

    Science.gov (United States)

    Skytte Larsson, Jenny; Krumbholz, Vitus; Enskog, Anders; Bragadottir, Gudrun; Redfors, Bengt; Ricksten, Sven-Erik

    2018-06-01

    Data on renal hemodynamics, function, and oxygenation in early clinical septic shock are lacking. We therefore measured renal blood flow, glomerular filtration rate, renal oxygen consumption, and oxygenation in patients with early septic shock. Prospective comparative study. General and cardiothoracic ICUs. Patients with norepinephrine-dependent early septic shock (n = 8) were studied within 24 hours after arrival in the ICU and compared with postcardiac surgery patients without acute kidney injury (comparator group, n = 58). None. Data on systemic hemodynamics and renal variables were obtained during two 30-minute periods. Renal blood flow was measured by the infusion clearance of para-aminohippuric acid, corrected for renal extraction of para-aminohippuric acid. Renal filtration fraction was measured by renal extraction of chromium-51 labeled EDTA. Renal oxygenation was estimated from renal oxygen extraction. Renal oxygen delivery (-24%; p = 0.037) and the renal blood flow-to-cardiac index ratio (-21%; p = 0.018) were lower, renal vascular resistance was higher (26%; p = 0.027), whereas renal blood flow tended to be lower (-19%; p = 0.068) in the septic group. Glomerular filtration rate (-32%; p = 0.006) and renal sodium reabsorption (-29%; p = 0.014) were both lower in the septic group. Neither renal filtration fraction nor renal oxygen consumption differed significantly between groups. Renal oxygen extraction was significantly higher in the septic group (28%; p = 0.022). In the septic group, markers of tubular injury were elevated. In early clinical septic shock, renal function was lower, which was accompanied by renal vasoconstriction, a lower renal oxygen delivery, impaired renal oxygenation, and tubular sodium reabsorption at a high oxygen cost compared with controls.

  16. Nasal Colivelin treatment ameliorates memory impairment related to Alzheimer's disease.

    Science.gov (United States)

    Yamada, Marina; Chiba, Tomohiro; Sasabe, Jumpei; Terashita, Kenzo; Aiso, Sadakazu; Matsuoka, Masaaki

    2008-07-01

    Humanin (HN) and its derivatives, such as Colivelin (CLN), suppress neuronal death induced by insults related to Alzheimer's disease (AD) by activating STAT3 in vitro. They also ameliorate functional memory impairment of mice induced by anticholinergic drugs or soluble toxic amyloid-beta (Abeta) in vivo when either is directly administered into the cerebral ventricle or intraperitoneally injected. However, the mechanism underlying the in vivo effect remains uncharacterized. In addition, from the standpoint of clinical application, drug delivery methods that are less invasive and specific to the central nervous system (CNS) should be developed. In this study, we show that intranasally (i.n.) administered CLN can be successfully transferred to CNS via the olfactory bulb. Using several behavioral tests, we have demonstrated that i.n. administered CLN ameliorates memory impairment of AD models in a dose-responsive manner. Attenuation of AD-related memory impairment by HN derivatives such as CLN appears to be correlated with an increase in STAT3 phosphorylation levels in the septohippocampal region, suggesting that anti-AD activities of HN derivatives may be mediated by activation of STAT3 in vivo as they are in vitro. We further demonstrate that CLN treatment inhibits an Abeta induced decrease in the number of choline acetyltransferase (ChAT)-positive neurons in the medial septum. Combined with the finding that HN derivatives upregulate mRNA expression of neuronal ChAT and vesicular acetylcholine transporter (VAChT) in vitro, it is assumed that CLN may ameliorate memory impairment of AD models by supporting cholinergic neurotransmission, which is at least partly mediated by STAT3-mediated transcriptional upregulation of ChAT and VAChT.

  17. Acute renal failure in rats

    International Nuclear Information System (INIS)

    Cederholm, C.; Almen, T.; Bergquist, D.; Golman, K.; Takolander, R.; Malmoe Allmaenna Sjukhus

    1989-01-01

    It was demonstrated in rats that renal injury which follows transient renal hypoxia is potentiated by the contrast media metrizoate, ioxaglate, iopamidol and iohexol. Intravenous injection of 1 g I/kg of all four media alone to 82 rats caused no significant increase in serum urea 1, 3 and 7 days later. The percentage increase of serum urea is given in median values and interquartile range (in parentheses). Bilateral renal arterial occlusion alone for 40 minutes in 42 rats increased serum urea one day later by 40% (20-130). Intravenous injection of the media followed in one hour by bilateral renal arterial occlusion for 40 minutes in 104 rats caused serum urea to increase one day later by 130% (70-350) after metrizoate, by 220% (50-380) after ioxaglate, by 290 % (60-420) after iopamidol and by 160% (50-330) after iohexol. There were no significant differences between the potentiating effects of the various media on ischemic renal failure. (orig.)

  18. A note on inventory model for ameliorating items with time dependent second order demand rate

    Directory of Open Access Journals (Sweden)

    Gobinda Chandra Panda

    2013-03-01

    Full Text Available Background: This paper is concerned with the development of ameliorating inventory models. The ameliorating inventory is the inventory of goods whose utility increases over the time by ameliorating activation. Material and Methods: This study is performed according to two areas: one is an economic order quantity (EOQ model for the items whose utility is ameliorating in accordance with Weibull distribution, and the other is a partial selling quantity (PSQ model developed for selling the surplus inventory accumulated by ameliorating activation with linear demand. The aim of this paper was to develop a mathematical model for inventory type concerned in the paper. Numerical examples were presented show the effect of ameliorating rate on inventory polices.  Results and Conclusions:  The inventory model for items with Weibull ameliorating is developed. For the case of small ameliorating rate (less than linear demand rate, EOQ model is developed, and for the case where ameliorating rate is greater than linear demand rate, PSQ model is developed.  .  

  19. Shared epitope-antagonistic ligands: a new therapeutic strategy in mice with erosive arthritis.

    Science.gov (United States)

    Ling, Song; Liu, Ying; Fu, Jiaqi; Colletta, Alessandro; Gilon, Chaim; Holoshitz, Joseph

    2015-05-01

    The mechanisms underlying bone damage in rheumatoid arthritis (RA) are incompletely understood. We recently identified the shared epitope (SE), an HLA-DRB1-coded 5-amino acid sequence motif carried by the majority of RA patients as a signal transduction ligand that interacts with cell surface calreticulin and accelerates osteoclast (OC)-mediated bone damage in collagen-induced arthritis (CIA). Given the role of the SE/calreticulin pathway in arthritis-associated bone damage, we sought to determine the therapeutic targetability of calreticulin. A library of backbone-cyclized peptidomimetic compounds, all carrying an identical core DKCLA sequence, was synthesized. The ability of these compounds to inhibit SE-activated signaling and OC differentiation was tested in vitro. The effect on disease severity and OC-mediated bone damage was studied by weekly intraperitoneal administration of the compounds to DBA/1 mice with CIA. Two members of the peptidomimetics library were found to have SE-antagonistic effects and antiosteoclast differentiation effects at picomolar concentrations in vitro. The lead mimetic compound, designated HS(4-4)c Trp, potently ameliorated arthritis and bone damage in vivo when administered in picogram doses to mice with CIA. Another mimetic analog, designated HS(3-4)c Trp, was found to lack activity, both in vitro and in vivo. The differential activity of the 2 analogs depended on minor differences in their respective ring sizes and correlated with distinctive geometry when computationally docked to the SE binding site on calreticulin. These findings identify calreticulin as a novel therapeutic target in erosive arthritis and provide sound rationale and early structure/activity relationships for future drug design. © 2015, American College of Rheumatology.

  20. Discovery of tertiary sulfonamides as potent liver X receptor antagonists.

    Science.gov (United States)

    Zuercher, William J; Buckholz, Richard G; Campobasso, Nino; Collins, Jon L; Galardi, Cristin M; Gampe, Robert T; Hyatt, Stephen M; Merrihew, Susan L; Moore, John T; Oplinger, Jeffrey A; Reid, Paul R; Spearing, Paul K; Stanley, Thomas B; Stewart, Eugene L; Willson, Timothy M

    2010-04-22

    Tertiary sulfonamides were identified in a HTS as dual liver X receptor (LXR, NR1H2, and NR1H3) ligands, and the binding affinity of the series was increased through iterative analogue synthesis. A ligand-bound cocrystal structure was determined which elucidated key interactions for high binding affinity. Further characterization of the tertiary sulfonamide series led to the identification of high affinity LXR antagonists. GSK2033 (17) is the first potent cell-active LXR antagonist described to date. 17 may be a useful chemical probe to explore the cell biology of this orphan nuclear receptor.

  1. Hyperglycemia of Diabetic Rats Decreased by a Glucagon Receptor Antagonist

    Science.gov (United States)

    Johnson, David G.; Ulichny Goebel, Camy; Hruby, Victor J.; Bregman, Marvin D.; Trivedi, Dev

    1982-02-01

    The glucagon analog [l-Nα-trinitrophenylhistidine, 12-homoarginine]-glucagon (THG) was examined for its ability to lower blood glucose concentrations in rats made diabetic with streptozotocin. In vitro, THG is a potent antagonist of glucagon activation of the hepatic adenylate cyclase assay system. Intravenous bolus injections of THG caused rapid decreases (20 to 35 percent) of short duration in blood glucose. Continuous infusion of low concentrations of the inhibitor led to larger sustained decreases in blood glucose (30 to 65 percent). These studies demonstrate that a glucagon receptor antagonist can substantially reduce blood glucose levels in diabetic animals without addition of exogenous insulin.

  2. ELM pace making and amelioration at ASDEX upgrade

    Energy Technology Data Exchange (ETDEWEB)

    Lang, P.T.; Gruber, O.; Haas, G.; Horton, L.D.; Kaufmann, M.; Mertens, V.; Neu, R.; Neuhauser, J.; Puetterich, T.; Schneider, W.; Sihler, C.; Sips, A.C.C.; Suttrop, W.; Treutterer, W. [Max-Planck-Institut fuer Plasmaphysik, Euratom Association, Garching (Germany); Bucalossi, J. [Association Euratom-Confederation Suisse, CRPP-EPFL, Lausanne (Switzerland); Kalvin, S.; Kocsis, G. [Association Euratom, KFKI-RMKI, Budapest (Hungary); Mc Carthy, P.J. [University College Cork, Physics Dept., Association Euratom-DCu, Cork (Ireland)

    2004-07-01

    Different techniques were tried to trigger ELMs (edge localized mode): injection of cryogenic solid pellets or a super-sonic molecular gas jet composed of deuterium or magnetic triggering, relying on a fast motion of the plasma column in a spatially asymmetric flux configuration. Our investigations prove externally imposed control techniques can change the ELM frequency. Frequency enhancement can result in amelioration of the single ELMs. Moreover, the approach can maintain plasma operation at a high performance level. Both pellet injection and magnetic triggering have been shown their potential to act as useful control tools. This yields the option to choose eventually the most appropriate technique for a given scenario.

  3. Albumin stimulates renal tubular inflammation through an HSP70-TLR4 axis in mice with early diabetic nephropathy

    Science.gov (United States)

    Jheng, Huei-Fen; Tsai, Pei-Jane; Chuang, Yi-Lun; Shen, Yi-Ting; Tai, Ting-An; Chen, Wen-Chung; Chou, Chuan-Kai; Ho, Li-Chun; Tang, Ming-Jer; Lai, Kuei-Tai A.; Sung, Junne-Ming; Tsai, Yau-Sheng

    2015-01-01

    ABSTRACT Increased urinary albumin excretion is not simply an aftermath of glomerular injury, but is also involved in the progression of diabetic nephropathy (DN). Whereas Toll-like receptors (TLRs) are incriminated in the renal inflammation of DN, whether and how albumin is involved in the TLR-related renal inflammatory response remains to be clarified. Here, we showed that both TLR2 and TLR4, one of their putative endogenous ligands [heat shock protein 70 (HSP70)] and nuclear factor-κB promoter activity were markedly elevated in the kidneys of diabetic mice. A deficiency of TLR4 but not of TLR2 alleviated albuminuria, tubulointerstitial fibrosis and inflammation induced by diabetes. The protection against renal injury in diabetic Tlr4−/− mice was associated with reduced tubular injuries and preserved cubilin levels, rather than amelioration of glomerular lesions. In vitro studies revealed that albumin, a stronger inducer than high glucose (HG), induced the release of HSP70 from proximal tubular cells. HSP70 blockade ameliorated albumin-induced inflammatory mediators. HSP70 triggered the production of inflammatory mediators in a TLR4-dependent manner. Moreover, HSP70 inhibition in vivo ameliorated diabetes-induced albuminuria, inflammatory response and tubular injury. Finally, we found that individuals with DN had higher levels of TLR4 and HSP70 in the dilated tubules than non-diabetic controls. Thus, activation of the HSP70-TLR4 axis, stimulated at least in part by albumin, in the tubular cell is a newly identified mechanism associated with induction of tubulointerstitial inflammation and aggravation of pre-existing microalbuminuria in the progression of DN. PMID:26398934

  4. Apelin ameliorates TNF-α-induced reduction of glycogen synthesis in the hepatocytes through G protein-coupled receptor APJ.

    Directory of Open Access Journals (Sweden)

    Jiaojiao Chu

    Full Text Available Apelin, a novel adipokine, is the specific endogenous ligand of G protein-coupled receptor APJ. Consistent with its putative role as an adipokine, apelin has been linked to states of insulin resistance. However, the function of apelin in hepatic insulin resistance, a vital part of insulin resistance, and its underlying mechanisms still remains unclear. Here we define the impacts of apelin on TNF-α-induced reduction of glycogen synthesis in the hepatocytes. Our studies indicate that apelin reversed TNF-α-induced reduction of glycogen synthesis in HepG2 cells, mouse primary hepatocytes and liver tissues of C57BL/6J mice by improving JNK-IRS1-AKT-GSK pathway. Moreover, Western blot revealed that APJ, but not apelin, expressed in the hepatocytes and liver tissues of mice. We found that F13A, a competitive antagonist for G protein-coupled receptor APJ, suppressed the effects of apelin on TNF-α-induced reduction of glycogen synthesis in the hepatocytes, suggesting APJ is involved in the function of apelin. In conclusion, we show novel evidence suggesting that apelin ameliorates TNF-α-induced reduction of glycogen synthesis in the hepatocytes through G protein-coupled receptor APJ. Apelin appears as a beneficial adipokine with anti-insulin resistance properties, and thus as a promising therapeutic target in metabolic disorders.

  5. Genistein ameliorates learning and memory deficits in amyloid β(1-40) rat model of Alzheimer's disease.

    Science.gov (United States)

    Bagheri, Maryam; Joghataei, Mohammad-Taghi; Mohseni, Simin; Roghani, Mehrdad

    2011-03-01

    Alzheimer's disease (AD) is a debilitating neurodegenerative disorder characterized by increased β-amyloid (Aβ) deposition and neuronal dysfunction leading to impaired learning and recall. Ageing, heredity, and induced oxidative stress are among proposed risk factors. The increased frequency of the disease in women also suggests a role for estrogen in development of AD. In the present study, effects of the phytoestrogen genistein (10mg/kg) on learning and memory impairments was assessed in intrahippocampal Aβ(1-40)-injected rats. The estrogen receptor antagonist fulvestrant was injected intracerebroventricularly in a group of Aβ-lesioned rats. The Aβ-injected animals exhibited the following: lower spontaneous alternation score in Y-maze tasks, impaired retention and recall capability in the passive avoidance test, and fewer correct choices and more errors in the RAM task. Genistein, but not genistein and fulvestrant, significantly improved most of these parameters. Measurements of oxidative stress markers in hippocampal tissue of Aβ-injected rats showed an elevation of malondialdehyde (MDA) and nitrite content, and a reduction of superoxide dismutase (SOD) activity. Genistein significantly attenuated the increased MDA content but did not affect the nitrite content or SOD activity. These results indicate that genistein pretreatment ameliorates Aβ-induced impairment of short-term spatial memory in rats through an estrogenic pathway and by inducing attenuation of oxidative stress. Copyright © 2010 Elsevier Inc. All rights reserved.

  6. The influence of certain molecular descriptors of fecal elimination of angiotensin II receptor antagonists

    Directory of Open Access Journals (Sweden)

    Trbojević-Stanković Jasna B.

    2015-01-01

    Full Text Available Angiotensin II receptor antagonists (ARBs modulate the function of the renin-angiotensin-aldosterone system and are commonly prescribed antihypertensive drugs, especially in patients with renal failure. In this study, the relationship between several molecular properties of seven ARBs (candesartan, eprosartan, irbesartan, losartan, olmesartan, telmisartan, valsartan and their fecal elimination data obtained from the literature were investigated. The ARB molecular descriptors were calculated using three software packages. Simple linear regression analysis showed the best 2 correlation between fecal elimination data and lipophilicity descriptor, ClogP values (R2 = 0.725. Multiple linear regression was applied to examine the correlation of ARBs’ fecal elimination data with their lipophilicity and one additional, calculated descriptor. The best correlation (R2 = 0.909 with an acceptable probability value, P <0.05 was established between the ARB fecal elimination data and their lipophilicity and aqueous solubility data. Applying computed molecular descriptors for evaluating drug elimination is of great importance in drug research.

  7. Pharmacological profile of CS-3150, a novel, highly potent and selective non-steroidal mineralocorticoid receptor antagonist.

    Science.gov (United States)

    Arai, Kiyoshi; Homma, Tsuyoshi; Morikawa, Yuka; Ubukata, Naoko; Tsuruoka, Hiyoyuki; Aoki, Kazumasa; Ishikawa, Hirokazu; Mizuno, Makoto; Sada, Toshio

    2015-08-15

    The present study was designed to characterize the pharmacological profile of CS-3150, a novel non-steroidal mineralocorticoid receptor antagonist. In the radioligand-binding assay, CS-3150 inhibited (3)H-aldosterone binding to mineralocorticoid receptor with an IC50 value of 9.4nM, and its potency was superior to that of spironolactone and eplerenone, whose IC50s were 36 and 713nM, respectively. CS-3150 also showed at least 1000-fold higher selectivity for mineralocorticoid receptor over other steroid hormone receptors, glucocorticoid receptor, androgen receptor and progesterone receptor. In the reporter gene assay, CS-3150 inhibited aldosterone-induced transcriptional activation of human mineralocorticoid receptor with an IC50 value of 3.7nM, and its potency was superior to that of spironolactone and eplerenone, whose IC50s were 66 and 970nM, respectively. CS-3150 had no agonistic effect on mineralocorticoid receptor and did not show any antagonistic or agonistic effect on glucocorticoid receptor, androgen receptor and progesterone receptor even at the high concentration of 5μM. In adrenalectomized rats, single oral administration of CS-3150 suppressed aldosterone-induced decrease in urinary Na(+)/K(+) ratio, an index of in vivo mineralocorticoid receptor activation, and this suppressive effect was more potent and longer-lasting than that of spironolactone and eplerenone. Chronic treatment with CS-3150 inhibited blood pressure elevation induced by deoxycorticosterone acetate (DOCA)/salt-loading to rats, and this antihypertensive effect was more potent than that of spironolactone and eplerenone. These findings indicate that CS-3150 is a selective and highly potent mineralocorticoid receptor antagonist with long-lasting oral activity. This agent could be useful for the treatment of hypertension, cardiovascular and renal disorders. Copyright © 2015 Elsevier B.V. All rights reserved.

  8. Evidence of active transport of cadmium complexing dithiocarbamates into renal and hepatic cells in vivo

    International Nuclear Information System (INIS)

    Gale, G.R.; Smith, A.B.; Jones, M.M.; Singh, P.K.

    1992-01-01

    A study was made of the effects of certain inhibitors of transport systems on the actions of four cadmium (Cd) complexing N,N-disubstituted dithiocarbamates (DTCs) in mobilizing murine renal and hepatic Cd in vivo. Probenecid, the prototypical antagonist of organic anion transport in the kidney, when given 1 hr prior to each DTC, sharply suppressed the DTC-induced reduction of renal Cd but was virtually without effect on mobilization of Cd from liver. Sulfinpyrazone, which blocks tubular reabsorption of uric acid and also inhibits transport of a variety of organic acids, inhibited markedly the mobilization of both renal and hepatic Cd by DTCs. Phlorizin, an inhibitor of tubular sugar reabsorption, did not affect the Cd mobilizing actions of DTCs in any consistent fashion. We propose that the high degree of selectivity of DTCs in mobilizing renal hepatic Cd is dependent, at lest in part, upon active transport of DTCs into these tissues via the organic anion transport systems. This report presents the first evidence that compounds of the (R) 2 NCSS - class may gain access to intracellular space by an active, carrier-mediated process. (au)

  9. Cannabinoid receptor-2 (CB2) agonist ameliorates colitis in IL-10−/− mice by attenuating the activation of T cells and promoting their apoptosis

    International Nuclear Information System (INIS)

    Singh, Udai P.; Singh, Narendra P.; Singh, Balwan; Price, Robert L.; Nagarkatti, Mitzi; Nagarkatti, Prakash S.

    2012-01-01

    Inflammatory bowel disease (IBD) is a chronic intestinal inflammation caused by hyperactivated effector immune cells that produce pro-inflammatory cytokines. Recent studies have shown that the cannabinoid system may play a critical role in mediating protection against intestinal inflammation. However, the effect of cannabinoid receptor induction after chronic colitis progression has not been investigated. Here, we investigate the effect of cannabinoid receptor-2 (CB2) agonist, JWH-133, after chronic colitis in IL-10 −/− mice. JWH-133 effectively attenuated the overall clinical score, and reversed colitis-associated pathogenesis and decrease in body weight in IL-10 −/− mice. After JWH-133 treatment, the percentage of CD4 + T cells, neutrophils, mast cells, natural killer (NK1.1) cells, and activated T cells declined in the intestinal lamina propria (LP) and mesenteric lymph nodes (MLN) of mice with chronic colitis. JWH-133 was also effective in ameliorating dextran sodium sulfate (DSS)-induced colitis. In this model, JWH-133 reduced the number and percentage of macrophages and IFN-γ expressing cells that were induced during colitis progression. Treatment with aminoalkylindole 6-iodo-pravadoline (AM630), a CB2 receptor antagonist, reversed the colitis protection provided by JWH-133 treatment. Also, activated T cells were found to undergo apoptosis following JWH-133 treatment both in-vivo and in-vitro. These findings suggest that JWH-133 mediates its effect through CB2 receptors, and ameliorates chronic colitis by inducing apoptosis in activated T cells, reducing the numbers of activated T cells, and suppressing induction of mast cells, NK cells, and neutrophils at sites of inflammation in the LP. These results support the idea that the CB2 receptor agonists may serve as a therapeutic modality against IBD. -- Highlights: ► JWH-133, a cannnabinoid receptor-2 agonist ameliorates experimental colitis. ► JWH-133 suppressed inflammation and toxicity to colon

  10. Cannabinoid receptor-2 (CB2) agonist ameliorates colitis in IL-10{sup −/−} mice by attenuating the activation of T cells and promoting their apoptosis

    Energy Technology Data Exchange (ETDEWEB)

    Singh, Udai P.; Singh, Narendra P. [Pathology, Microbiology and Immunology, School of Medicine, University of South Carolina, Columbia, SC 29208 (United States); Singh, Balwan [National Primate Research Center, Emory University, Atlanta GA 30329 (United States); Price, Robert L. [Department of Cell and Developmental Biology, University of South Carolina, Columbia, SC 29208 (United States); Nagarkatti, Mitzi [Pathology, Microbiology and Immunology, School of Medicine, University of South Carolina, Columbia, SC 29208 (United States); Nagarkatti, Prakash S., E-mail: Prakash.Nagarkatti@uscmed.sc.edu [Pathology, Microbiology and Immunology, School of Medicine, University of South Carolina, Columbia, SC 29208 (United States)

    2012-01-15

    Inflammatory bowel disease (IBD) is a chronic intestinal inflammation caused by hyperactivated effector immune cells that produce pro-inflammatory cytokines. Recent studies have shown that the cannabinoid system may play a critical role in mediating protection against intestinal inflammation. However, the effect of cannabinoid receptor induction after chronic colitis progression has not been investigated. Here, we investigate the effect of cannabinoid receptor-2 (CB2) agonist, JWH-133, after chronic colitis in IL-10{sup −/−} mice. JWH-133 effectively attenuated the overall clinical score, and reversed colitis-associated pathogenesis and decrease in body weight in IL-10{sup −/−} mice. After JWH-133 treatment, the percentage of CD4{sup +} T cells, neutrophils, mast cells, natural killer (NK1.1) cells, and activated T cells declined in the intestinal lamina propria (LP) and mesenteric lymph nodes (MLN) of mice with chronic colitis. JWH-133 was also effective in ameliorating dextran sodium sulfate (DSS)-induced colitis. In this model, JWH-133 reduced the number and percentage of macrophages and IFN-γ expressing cells that were induced during colitis progression. Treatment with aminoalkylindole 6-iodo-pravadoline (AM630), a CB2 receptor antagonist, reversed the colitis protection provided by JWH-133 treatment. Also, activated T cells were found to undergo apoptosis following JWH-133 treatment both in-vivo and in-vitro. These findings suggest that JWH-133 mediates its effect through CB2 receptors, and ameliorates chronic colitis by inducing apoptosis in activated T cells, reducing the numbers of activated T cells, and suppressing induction of mast cells, NK cells, and neutrophils at sites of inflammation in the LP. These results support the idea that the CB2 receptor agonists may serve as a therapeutic modality against IBD. -- Highlights: ► JWH-133, a cannnabinoid receptor-2 agonist ameliorates experimental colitis. ► JWH-133 suppressed inflammation and

  11. Massive postpartum right renal hemorrhage.

    Science.gov (United States)

    Kiracofe, H L; Peterson, N

    1975-06-01

    All reported cases of massive postpartum right renal hemorrhage have involved healthy young primigravidas and blacks have predominated (4 of 7 women). Coagulopathies and underlying renal disease have been absent. Hematuria was painless in 5 of 8 cases. Hemorrhage began within 24 hours in 1 case, within 48 hours in 4 cases and 4 days post partum in 3 cases. Our first case is the only report in which hemorrhage has occurred in a primipara. Failure of closure or reopening of pyelovenous channels is suggested as the pathogenesis. The hemorrhage has been self-limiting, requiring no more than 1,500 cc whole blood replacement. Bleeding should stop spontaneously, and rapid renal pelvic clot lysis should follow with maintenance of adequate urine output and Foley catheter bladder decompression. To date surgical intervention has not been necessary.

  12. Renal Myxoma, an Incidental Finding

    Directory of Open Access Journals (Sweden)

    Parth Thakker

    2017-07-01

    Full Text Available Myxomas are mesenchymal tumors commonly found in the heart and skin. Renal myxomas are rare, having only been documented 14 times. Our case is a 55-year-old woman who presented to our clinic after a right renal mass was incidentally found on CT. Evaluation with MRI showed a mass that appeared to arise from the supero-medial cortex of the right kidney. As the imaging was concerning for renal cell carcinoma, the patient underwent a partial nephrectomy. Microscopic examination showed a well-circumscribed mass with polygonal to spindle-shaped cells in a granular eosinophilic cytoplasm. Immunohistochemical staining for CD-10, Desmin, HMB-45, and Pankeratin were negative.

  13. Renal diseases in AIDS patients

    OpenAIRE

    Álvarez Escobar, María del Carmen; Alfonso de León, José Alberto; Lima Gutiérrez, Héctor; Torres Álvarez, Armella; Torres Álvarez, Arling Yuliett

    2009-01-01

    La afectación renal en el SIDA es un tema poco abordado a pesar de su frecuencia, la misma depende de la acción directa e indirecta del virus, así como de las complicaciones y del tratamiento. La más frecuente de las complicaciones es la Insuficiencia Renal Aguda. La forma más típica de nefropatía asociada al VIH (NAVIH) se caracteriza por alto grado de proteinuria con progresión rápida a Insuficiencia Renal Terminal. En el SIDA se presentan diversas formas de glomerulopatías cuya expresión c...

  14. CT of the renal infarction

    International Nuclear Information System (INIS)

    Tazawa, Satoru; Ito, Hisao; Tange, Isamu

    1984-01-01

    We have five cases of the global renal infarction, four of which resulted from post-transarterial embolization(TAE) of the hypernephroma, the remaining one was probably caused by the cardiac disease. Generally speaking, CE-CT is useful for the diagnosis of the acute renal infarction, because the ''rim sign'' which represents viable subcapsular parenchyma is helpful for the diagnosis. It seems that band-like enhancement from the renal sinus to the periphery in the low-attenuation-parenchyma on CE-CT, named as ''band sign'', is useful for the diagnosis. ''Band sign'' may also be valuable for distinguishing the neoplastic area from the non-neoplastic one after TAE of the hypernephroma. (author)

  15. Radiologic observation of renal tuberculosis

    International Nuclear Information System (INIS)

    Kim, S. W.; Ra, Y. W.; Kim, Y. J.

    1981-01-01

    Radiographic findings of thirty eight cases of renal tuberculosis treated at this hospital during last 4 years were analysed with following results. The cases examined were 24 male and 14 female patients. Age distribution was broad and evenly distributed ranging from 2nd decades to 5th decades. Main symptoms complained were urinary frequency, hematuria, dysuria and flank pain. Findings of physical examination revealed tenderness of costovertebral angle, palpable mass on flank area and epididymal indutration. The simple chest films showed pulmonary tuberculosis in 22 cases including 6 cases of active military type. Thirty one cases showed increased ESR, 8 cases showed AFB positive in urine and 12 cases showed bilateral renal tuberculosis. Through urographic findings nonvisualization, cyceopelviectasis, motheaten appearance of minor calyx, contracted bladder, delayed visualization, ureteral stricture and beading were observed in order of frequency. Five cases with miliary tuberculosis showed advanced renal lesion on urogram

  16. Renal replacement therapy in Europe

    DEFF Research Database (Denmark)

    Noordzij, Marlies; Kramer, Anneke; Abad Diez, José M

    2014-01-01

    the Mediterranean Sea were used. From 27 registries, individual patient data were received, whereas 17 registries contributed data in aggregated form. We present the incidence and prevalence of RRT, and renal transplant rates in 2011. In addition, survival probabilities and expected remaining lifetimes were....... The overall unadjusted prevalence of RRT for ESRD on 31 December 2011 was 692 pmp (n = 425 824). The highest prevalence was reported by Portugal (1662 pmp) and the lowest by Ukraine (131 pmp). Among all registries, a total of 22 814 renal transplantations were performed (37 pmp). The highest overall.......6-47.0], and on dialysis 39.3% (95% CI 39.2-39.4). The unadjusted 5-year patient survival after the first renal transplantation performed between 2002 and 2006 was 86.7% (95% CI 86.2-87.2) for kidneys from deceased donors and 94.3% (95% CI 93.6-95.0) for kidneys from living donors....

  17. CT diagnosis of simple renal cysts

    International Nuclear Information System (INIS)

    Nanakawa, Seito; Yasunaga, Tadamasa; Tsuchigame, Tadatoshi; Kawano, Shoji; Takahashi, Mutsumasa; Fukui, Koutaro.

    1987-01-01

    CT is indispensable in the evaluation of renal masses, providing noninvasive and clear transverse images. With wider clinical application of CT, renal cysts have been found more frequently. CT examinations on 500 patients, who underwent CT for the diagnosis of renal diseases except for renal cysts, have been reviewed and analysed. The incidence of renal cysts was 9.6 % without prediction for sexes, but the incidence and sizes of the cysts increased with the advancing age. The upper portion of the kidneys was more frequently involved, but there was no relationship between number, sex and age of the patients. Since renal cysts produce mass effect in the kidneys, understanding of the nature and incidence of the renal cysts is important in diagnosing renal mass lesions. (author)

  18. Drugs Approved for Kidney (Renal Cell) Cancer

    Science.gov (United States)

    ... Your Treatment Research Drugs Approved for Kidney (Renal Cell) Cancer This page lists cancer drugs approved by the ... not listed here. Drugs Approved for Kidney (Renal Cell) Cancer Afinitor (Everolimus) Aldesleukin Avastin (Bevacizumab) Axitinib Bevacizumab Cabometyx ( ...

  19. Radionuclide renal dynamic and function study

    International Nuclear Information System (INIS)

    Guan Liang

    1991-01-01

    The radionuclide dynamic and function study, glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) were reported in 14 cases of renal and ureteral calculi patients before and after extracorporeal shock wave lithotripsy (ESWL). In 12 cases with normal renal blood flow, within 3 months after ESWL, the GFR of shock and non-shock side decreased with different extent, while the individual ERPF had little change. In 5 cases followed up 1 year after ESWL, the individual GFR and ERPF were normal. In 2 cases of severe renal function insufficiency, there was no improvement in renal function in shock side, after 5 months and 1 year, the renal function was still at low level. Thereby it is considered that ESWL is not suitable for the renal calculi patients with severe renal function insufficiency

  20. Longitudinal prospective observational type study about determinants of renal resistive index variations in chronic renal failure patients treated with conventional medical and dietetic therapy

    Directory of Open Access Journals (Sweden)

    Simone Brardi

    2017-12-01

    Full Text Available Objective: This longitudinal prospective observational type study was conceived with the aim to examine the impact on renal resistive index (RRI of the variables that we can manipulate with therapeutic and or dietetic interventions in a chronic kidney disease population in order to known which of these variables was statistically related to changes in RRI and therefore could become the object of the greatest therapeutic effort. Material and methods: This study was undertaken between May 2016 to May 2017 in the outpatient nephrology and urology clinic of San Donato Hospital in Arezzo. The study population (84 patients: 47 males and 37 females was randomly selected among the chronic kidney patients (with various degrees of renal impairment affected by hypertension and or diabetes mellitus. After a comprehensive medical examination these patients were submitted to determination of serum creatinine, glycated hemoglobin, 24-hour urinary albumin excretion and finally renal Doppler ultrasonography. Then the patients were submitted to a full therapeutic and dietetic intervention to ameliorate the renal impairment by a wide range of actions and after on average a one-year interval were submitted again to a new medical examination and a second determination of serum creatinine, glycated hemoglobin, 24-hour urinary albumin excretion and a new renal Doppler ultrasonography too. Results: The comparison between basal and final data revealed a slight reduction in the mean of bilateral renal resistance indices (Delta RRI: -0.0182 ± 0.08, associated to a slight increase in the mean glomerular filtration rate (Delta GFR: 0.8738 ± 10.95 ml/min/1.73 m2, a reduction in mean body weight (Delta weight: -1.9548 ± 5.26 Kg and mean BMI (Delta BMI: -0.7643 ± 2.10 Kg/m2 as well as a reduction in the mean systolic blood pressure (Delta systolic blood pressure: -8.8333 ± 25.19 mmHg. Statistical analysis showed statistically significant correlations (p < 0.05 between