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  1. Simvastatin ameliorates gentamicin-induced renal injury in rats

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    Mosadegh Jabbari

    2011-01-01

    Full Text Available Gentamicin nephrotoxicity is one of the most common causes of acute renal failure. Simvastatin is one of the antioxidative drugs, which has anti-inflammatory and anabolic effects and modulates the immune system. The present study was conducted to assess the effect of simvastatin on ameliorating the gentamicin-induced renal injury in 87 Sprague-Dawley rats, which were allocated randomly to 11 study groups: (A and (B groups with only gentamicin in 2 dosages; (C, (D, and (E gentamicin 50 mg/kg/day and simvastatin with different dosage; (F, (G, and (H gentamicin 80 mg/kg/day and simvastatin with different dosage; (I only simvastatin; (J Injected normal saline; (K control (no gentamicin and no simvastatin group. Our study intervention period for injection of drugs was 12 days. Serum creatinine level and clearance were measured in all groups. At the end of the study, the rats were killed and both kidneys were removed and processed for histopathologic examination using the standard methods. The 50 mg/kg/day dose was utilized because it induces a mild form of renal toxicity, whereas the 80 mg/kg/day dose cause a more severe degree of renal injury. Morphologic examination of specimens from all rats was qualitatively assessed with blindness to treatment groups and proximal tubular profiles that were presented in each file were counted. The results demonstrated amelioration of gentamicin-induced renal toxicity in rats by simvastatin due to its antioxidant drug dose-related effect.

  2. PPARα agonist, fenofibrate, ameliorates age-related renal injury.

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    Kim, Eun Nim; Lim, Ji Hee; Kim, Min Young; Kim, Hyung Wook; Park, Cheol Whee; Chang, Yoon Sik; Choi, Bum Soon

    2016-08-01

    The kidney ages quickly compared with other organs. Expression of senescence markers reflects changes in the energy metabolism in the kidney. Two important issues in aging are mitochondrial dysfunction and oxidative stress. Peroxisome proliferator-activated receptor α (PPARα) is a member of the ligand-activated nuclear receptor superfamily. PPARα plays a major role as a transcription factor that regulates the expression of genes involved in various processes. In this study, 18-month-old male C57BL/6 mice were divided into two groups, the control group (n=7) and the fenofibrate-treated group (n=7) was fed the normal chow plus fenofibrate for 6months. The PPARα agonist, fenofibrate, improved renal function, proteinuria, histological change (glomerulosclerosis and tubular interstitial fibrosis), inflammation, and apoptosis in aging mice. This protective effect against age-related renal injury occurred through the activation of AMPK and SIRT1 signaling. The activation of AMPK and SIRT1 allowed for the concurrent deacetylation and phosphorylation of their target molecules and decreased the kidney's susceptibility to age-related changes. Activation of the AMPK-FOXO3a and AMPK-PGC-1α signaling pathways ameliorated oxidative stress and mitochondrial dysfunction. Our results suggest that activation of PPARα and AMPK-SIRT1 signaling may have protective effects against age-related renal injury. Pharmacological targeting of PPARα and AMPK-SIRT1 signaling molecules may prevent or attenuate age-related pathological changes in the kidney. PMID:27130813

  3. Rivaroxaban versus enoxaparin/vitamin K antagonist therapy in patients with venous thromboembolism and renal impairment

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    Bauersachs, Rupert M.; Lensing, Anthonie WA; Prins, Martin H.; Kubitza, Dagmar; Pap, Ákos F; Decousus, Hervé; Beyer-Westendorf, Jan; Prandoni, Paolo

    2014-01-01

    Background Patients with renal impairment receiving classical anticoagulation for venous thromboembolism (VTE) are at increased risk of bleeding and possibly pulmonary embolism. We examined the efficacy and safety of oral rivaroxaban in patients with VTE with and without renal impairment. Methods Prespecified subgroup analysis of the EINSTEIN DVT and EINSTEIN PE studies comparing fixed-dose rivaroxaban with enoxaparin/a vitamin K antagonist (VKA), performed in 8246 patients enrolled from 2007...

  4. Paeoniflorin ameliorates acute necrotizing pancreatitis and pancreatitis‑induced acute renal injury.

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    Wang, Peng; Wang, Weixing; Shi, Qiao; Zhao, Liang; Mei, Fangchao; Li, Chen; Zuo, Teng; He, Xiaobo

    2016-08-01

    Acute renal injury caused by acute necrotizing pancreatitis (ANP) is a common complication that is associated with a high rate of mortality. Paeoniflorin is the active ingredient of paeonia radix and exhibits a number of pharmacological effects, such as anti‑inflammatory, anticancer, analgesic and immunomodulatory effects. The present study detected the potential treatment effects of paeoniflorin on acute renal injury induced by ANP in a rat model. The optimal dose of paeoniflorin for preventing acute renal injury induced by ANP was determined. Then, the possible protective mechanism of paeoniflorin was investigated. The serum levels of tumor necrosis factor (TNF)‑α, interleukin (IL)‑1β and IL‑6 were measured with enzyme‑linked immunosorbent assay kits. Renal inflammation and apoptosis were measured by immunohistochemistry and terminal deoxynucleotidyl transferase‑mediated dUTP nick end labeling assay. The expression of nitric oxide in kidney tissues was also evaluated. The p38 mitogen‑activated protein kinases (MAPKs) were measured by western blotting. The results shown that paeoniflorin may ameliorate acute renal injury following ANP in rats by inhibiting inflammatory responses and renal cell apoptosis. These effects may be associated with the p38MAPK and nuclear factor‑κB signal pathway. PMID:27279569

  5. 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.

  6. Fetal kidney stem cells ameliorate cisplatin induced acuterenal failure and promote renal angiogenesis

    Institute of Scientific and Technical Information of China (English)

    2015-01-01

    AIM To investigate whether fetal kidney stem cells(fKSC) ameliorate cisplatin induced acute renal failure(ARF) in rats and promote renal angiogenesis.METHODS: The fKSC were isolated from rat fetusesof gestation day 16 and expanded in vitro up to 3rdpassage. They were characterized for the expressionof mesenchymal and renal progenitor markers by flowcytometry and immunocytochemistry, respectively.The in vitro differentiation of fKSC towards epitheliallineage was evaluated by the treatment with specificinduction medium and their angiogenic potential bymatrigel induced tube formation assay. To study theeffect of fKSC in ARF, fKSC labeled with PKH26 wereinfused in rats with cisplatin induced ARF and, the bloodand renal tissues of the rats were collected at differenttime points. Blood biochemical parameters werestudied to evaluate renal function. Renal tissues wereevaluated for renal architecture, renal cell proliferationand angiogenesis by immunohistochemistry, renal cellapoptosis by terminal deoxynucleotidyl transferase nickendlabeling assay and early expression of angiogenicmolecules viz . vascular endothelial growth factor (VEGF),hypoxia-inducible factor (HIF)-1α and endothelial nitricoxide synthase (eNOS) by western blot.RESULTS: The fKSC expressed mesenchymal markersviz . CD29, CD44, CD73, CD90 and CD105 as well as renal progenitor markers viz . Wt1, Pax2 and Six2. Theyexhibited a potential to form CD31 and Von Willebrandfactor expressing capillary-like structures and could bedifferentiated into cytokeratin (CK)18 and CK19 positiveepithelial cells. Administration of fKSC in rats with ARF ascompared to administration of saline alone, resulted in asignificant improvement in renal function and histology onday 3 (2.33 ± 0.33 vs 3.50 ± 0.34, P 〈 0.05) and on day7 (0.83 ± 0.16 vs 2.00 ± 0.25, P 〈 0.05). The infusedPKH26 labeled fKSC were observed to engraft in damagedrenal tubules and showed increased proliferation andreduced

  7. 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.

  8. Reversible renal impairment induced by treatment with the angiotensin II receptor antagonist candesartan in a patient with bilateral renal artery stenosis

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    Kjaer Andreas

    2001-05-01

    Full Text Available Abstract Background It is well established that ACE-inhibitors should be avoided in patients with renal artery stenosis. In recent years it has also been recommended that caution should be demonstrated when angiotensin II blockers are used in the same type of patients but the evidence is based only on few cases. Results We describe a case where use of the angiotensin II antagonist candesartan (Atacand induced renal failure in a patient with bilateral renal artery stenosis. The course of the case is enlighted by results from sequential renography, selective renal vein catheterisation for measurement of renin, and angiographic findings. Conclusions In patients with renal artery stenosis the angiotensin II antagonist candesartan should be avoided.

  9. Erythropoietin ameliorates renal interstitial fibrosis via the inhibition of fibrocyte accumulation.

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    Geng, Xu Chang; Hu, Zhou Pang; Lian, Guo Yong

    2015-05-01

    Erythropoietin (EPO) is a hematopoietic hormone that protects against renal interstitial fibrosis in animal models; however, the mechanism underlying the anti‑fibrotic activity of EPO has remained elusive. The present study aimed to elucidate this mechanism. Twenty‑four male C57BL6 mice were randomly divided into four groups, each comprising six mice: (i) control group (Sh); (ii) unilateral ureteral obstruction (UUO) plus vehicle group (U+V); (ⅲ) UUO plus 300 U/kg body weight recombinant human (rh)EPO (U+E1) and (ⅳ) UUO plus 1,000 U/kg body weight rhEPO (U+E2). Seven days post‑surgery, the mice were sacrificed for examination. UUO induced significant deposition of extracellular matrix, detected by picro‑sirius red staining, which was decreased following rhEPO treatment. UUO also induced deposition of collagen I and fibronectin, rhEPO treatment was able to attenuate this effect at protein and mRNA levels. Compared with the control groups, UUO resulted in the accumulation of α‑smooth muscle actin‑positive cells in the interstitium, an effect which was ameliorated by rhEPO. Furthermore, rhEPO abrogated the UUO‑induced increase in the number of bone marrow‑derived myofibroblasts. Mechanistically, it was discovered that rhEPO decreased CXC chemokine ligand 16 (CXCL16) expression at protein level. However, treatment with rhEPO did not alter the protein expression of CC chemokine ligand 21 or CXCL12. These results suggested that rhEPO decreased fibrocyte accumulation via the suppression of renal CXCL16, which resulted in the attenuation of renal fibrosis. PMID:25572934

  10. A Pegylated Leptin Antagonist Ameliorates CKD-Associated Cachexia in Mice

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    Cheung, Wai W.; Ding, Wei; Gunta, Sujana S.; Gu, Yong; Tabakman, Rinat; Klapper, Leah N.; Gertler, Arieh; Mak, Robert H.

    2013-01-01

    Elevated serum leptin levels correlate with inflammation and predict changes in lean body mass in patients with CKD, and activation of the melanocortin system by leptin signaling mediates the pathophysiology of CKD-associated cachexia. We tested whether treatment with a pegylated leptin receptor antagonist (PLA) attenuates cachexia in mice with CKD. CKD and Sham mice received vehicle or PLA (2 or 7 mg/kg per day). At these doses, PLA did not influence serum leptin levels in mice. Treatment wi...

  11. Ameliorating effect of cobalt chloride on renal failure and glucose lowering effect in diabetic nephropathy induced in uninephrectomized diabetic rat

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    Aaishwarya Deshmukh

    2012-02-01

    Full Text Available Diabetic nephropathy, a progressive development of renal insufficiency in the setting of hyperglycemia, is the major single cause of chronic renal failure (CRF in which hypoxia plays a critical role. This study evaluated the efficacy of cobalt chloride, a Prolyl 4-hydroxylase (PHD inhibtor, in amelioration of renal injury, as well as its effect on hyperglycemia in uninephrectomized diabetic rat. The effect of cobalt chloride (CoCl2,10 mg/kg, i.p. OD treatment on plasma urea, creatinine, uric acid, electrolytes like sodium, potassium, chloride, as well as blood glucose levels were checked along with measurement of the dry weight of contralateral kidney in different groups. A significant rise in plasma urea, creatinine and uric acid levels was observed in uninephrectomized diabetic rat. Cobalt chloride (10 mg/kg, i.p. OD treatment for seven continuous days, followed by intermittent dosing for 30 days, showed improvement in renal injury by a significant fall in the plasma urea, creatinine and uric acid levels with restoration to partially normal values as compared to an uninephrectomized uninephrectomized diabetic group. A significant change in plasma electrolyte levels was observed which was partially normalized in the cobalt chloride group along with a reduction in the dry weight of kidney. A significant decrease in the blood glucose level was observed in the CoCl2 treated group as compared to the uninephrectomized diabetic group. Our study shows the effect of CoCl2 in amelioration of renal failure and antihyperglycemic effect.

  12. N-acetylcysteine pretreatment ameliorates mercuric chloride-induced oxidative renal damage in rats.

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    Ekor, M; Adesanoye, O A; Farombi, E O

    2010-12-01

    The effectiveness of the antioxidant thiol, N-acetylcysteine (NAC), in enhancing methylmercury (CH3HgCl) excretion and its utility as a possible antidote in CH3HgCl poisoning has been reported. NAC, however, has been reported to be ineffective in accelerating excretion of divalent toxic metals, including inorganic mercury, Hg2+. In this study, we evaluated the possible protective effect of short-term pretreatment with NAC against mercuric chloride (HgCl2) toxicity in rat model. This is aimed at determining its chemopreventive or prophylactic benefit in situations of high risk exposure (occupational/industrial) to mercury. Rats were divided into three treatment groups. Group I received saline (10 ml/kg) and served as control. Group II received HgCl2 (5mg/kg) and group III received NAC (10mg/kg) plus (5mg/kg). All administration was via intraperitoneal (i.p.) injection. Saline and NAC were administered for 5days and HgCl2 was administered to rats in groups II and III on the 5th day. Animals were sacrificed 24 hours after HgCl2 injection and samples obtained for biochemical evaluation. Results revealed that single i.p. injection of HgCl2 induced significant renal oxidative damage resulting in significant decrease in the activities of superoxide dismutase (SOD), catalase (CAT), glutathione-s-transferase (GST), depletion of reduced glutathione (GSH) and increase in malondialdehyde (MDA) levels in these rats. The activities of glucose-6-phosphatase (G6Pase) and 5'-nucleotidase (5'-NTD) (markers of microsomal damage) also decreased in these HgCl2 treated rats. The oxidative damage induced by HgCl2 led to significant alterations in renal histology and caused functional impairment (indicated by elevated blood urea nitrogen (BUN) and serum creatinine) in these rats. NAC was effective in attenuating the oxidative damage, functional impairments and histopathological changes that characterized HgCl2 intoxication in this study. Renal antioxidant defense system was re-enforced by

  13. A pegylated leptin antagonist ameliorates CKD-associated cachexia in mice.

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    Cheung, Wai W; Ding, Wei; Gunta, Sujana S; Gu, Yong; Tabakman, Rinat; Klapper, Leah N; Gertler, Arieh; Mak, Robert H

    2014-01-01

    Elevated serum leptin levels correlate with inflammation and predict changes in lean body mass in patients with CKD, and activation of the melanocortin system by leptin signaling mediates the pathophysiology of CKD-associated cachexia. We tested whether treatment with a pegylated leptin receptor antagonist (PLA) attenuates cachexia in mice with CKD. CKD and Sham mice received vehicle or PLA (2 or 7 mg/kg per day). At these doses, PLA did not influence serum leptin levels in mice. Treatment with 7 mg/kg per day PLA stimulated appetite and weight gain, improved lean mass and muscle function, reduced energy expenditure, and normalized the levels of hepatic TNF-α and IL-6 mRNA in mice with CKD. Furthermore, treatment with 7 mg/kg per day PLA attenuated the CKD-associated increase in the transcriptional and protein abundance of uncoupling proteins that mediates thermogenesis, and it normalized the molecular signatures of processes associated with muscle wasting in CKD, including proteolysis, myogenesis and muscle regeneration, and expression of proinflammatory muscle cytokines, such as IL-1α, -1β, and -6 and TNF-α. Our results suggest that leptin antagonism may represent a viable therapeutic strategy for cachexia in CKD. PMID:24115476

  14. Calcitriol ameliorates renal damage in a pre-established proteinuria model

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    MAQUIGUSSA, EDGAR; ARNONI, CARINE P; PEREIRA, LUCIANA G; BOIM, MIRIAN A

    2015-01-01

    Proteinuria is critical in the tubulointerstitial changes that ultimately lead to renal insufficiency. Increased protein filtration has direct toxic effects on tubular epithelial cells, leading to epithelial mesenchymal transition (EMT) to a myofibroblast phenotype. Angiotensin II and transforming growth factor (TGF)-β1 are the main mediators of EMT. Calcitriol may exert a potential renoprotective effect by reducing the activity of the renin angiotensin system by suppressing renin gene expression and also by inhibiting the proinflammatory nuclear factor-κB pathway. The present study investigated the benefits of calcitriol treatment in a puromycin-induced protein-uric nephropathy model. Uninephrectomized adult male Wistar rats received intraperitoneal administration of a single dose of puromycin (100 mg/kg) or vehicle. After eight weeks, the animals were divided into two groups and received vehicle or calcitriol (0.5 μg/kg) for four weeks. The vehicle-treated, proteinuric rats developed progressive proteinuria and tubulointerstitial fibrosis after 12 weeks. Increased collagen deposition and fibrosis were significantly ameliorated by calcitriol treatment. Calcitriol was effective in preventing an increase in the EMT markers, α-smooth muscle actin and fibroblast-specific protein 1, reducing macrophage infiltration as evidenced by levels of ED-1. In addition, calcitriol increased the anti-inflammatory cytokine interleukin-10 and reduced the pro-oxidant p47 phox enzyme. These effects were paralleled by a reduction in TGF-β/Smad3 expression. Calcitriol may have therapeutic potential in the proteinuric nephropathy model used in the present study by inhibiting the TGF-β1 axis. PMID:25823676

  15. Nicotine ameliorates NMDA receptor antagonist-induced deficits in contextual fear conditioning through high-affinity nicotinic acetylcholine receptors in the hippocampus.

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    André, Jessica M; Leach, Prescott T; Gould, Thomas J

    2011-03-01

    NMDA glutamate receptors (NMDARs) and nicotinic acetylcholine receptors (nAChRs) are both involved in learning and synaptic plasticity. Increasing evidence suggests processes mediated by these receptors may interact to modulate learning; however, little is known about the neural substrates involved in these interactive processes. The present studies investigated the effects of nicotine on MK-801 hydrogen maleate (MK-801) and DL-2-Amino-5-phosphonovaleric acid (APV)-induced disruption of contextual fear conditioning in male C57BL/6J mice, using direct drug infusion and selective nAChR antagonists to define the brain regions and the nAChR subtypes involved. Mice treated with MK-801 showed a deficit in contextual fear conditioning that was ameliorated by nicotine. Direct drug infusion demonstrated that the NMDAR antagonists disrupted hippocampal function and that nicotine acted in the dorsal hippocampus to ameliorate the deficit in learning. The high-affinity nAChR antagonist Dihydro-β-erythroidine hydrobromide (DhβE) blocked the effects of nicotine on MK-801-induced deficits while the α7 nAChR antagonist methyllycaconitine citrate salt hydrate (MLA) did not. These results suggest that NMDARs and nAChRs may mediate similar hippocampal processes involved in contextual fear conditioning. Furthermore, these results may have implications for developing effective therapeutics for the cognitive deficits associated with schizophrenia because a large subset of patients with schizophrenia exhibit cognitive deficits that may be related to NMDAR dysfunction and smoke at much higher rates than the healthy population, which may be an attempt to ameliorate cognitive deficits. PMID:21167848

  16. Bone marrow-derived cells can acquire renal stem cells properties and ameliorate ischemia-reperfusion induced acute renal injury

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    Jia Xiaohua

    2012-09-01

    Full Text Available Abstract Background Bone marrow (BM stem cells have been reported to contribute to tissue repair after kidney injury model. However, there is no direct evidence so far that BM cells can trans-differentiate into renal stem cells. Methods To investigate whether BM stem cells contribute to repopulate the renal stem cell pool, we transplanted BM cells from transgenic mice, expressing enhanced green fluorescent protein (EGFP into wild-type irradiated recipients. Following hematological reconstitution and ischemia-reperfusion (I/R, Sca-1 and c-Kit positive renal stem cells in kidney were evaluated by immunostaining and flow cytometry analysis. Moreover, granulocyte colony stimulating factor (G-CSF was administrated to further explore if G-CSF can mobilize BM cells and enhance trans-differentiation efficiency of BM cells into renal stem cells. Results BM-derived cells can contribute to the Sca-1+ or c-Kit+ renal progenitor cells population, although most renal stem cells came from indigenous cells. Furthermore, G-CSF administration nearly doubled the frequency of Sca-1+ BM-derived renal stem cells and increased capillary density of I/R injured kidneys. Conclusions These findings indicate that BM derived stem cells can give rise to cells that share properties of renal resident stem cell. Moreover, G-CSF mobilization can enhance this effect.

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

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    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.

  18. Identification of renal natriuretic peptide receptor subpopulations by use of the non-peptide antagonist, HS-142-1.

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    Rutherford, R A; Matsuda, Y; Wilkins, M R; Polak, J M; Wharton, J

    1994-01-01

    1. The renal actions of natriuretic peptides are dictated by the distribution of guanylyl cyclase-linked (NPRA and NPRB) and non-guanylyl cyclase-linked (NPRC) receptors. Natriuretic peptide receptors have previously been distinguished on the basis of their differential affinity for peptide fragments and analogues; however, most of the available ligands are not fully selective. We have used the specific guanylyl cyclase-linked receptor antagonist, HS-142-1, to investigate the differential dis...

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

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    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...

  20. 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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    CarineMBoustany-Kari; TristanMaurer; RenaEudy; StephenOrena

    2013-01-01

    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 ...

  1. Berberine ameliorates renal injury in streptozotocin-induced diabetic rats by suppression of both oxidative stress and aldose reductase

    Institute of Scientific and Technical Information of China (English)

    LIU Wei-hua; HUANG Wen-ge; CHEN Feng-ying; LIU Pei-qing; HEI Zi-qing; NIE Hong; TANG Fu-tian; HUANG He-qing; LI Xue-juan; DENG Yan-hui; CHEN Shao-rui; GUO Fen-fen

    2008-01-01

    Background Berberine is one of the main constituents of Coptidis rhizoma (CR) and Cortex phellodendri, In this study, we investigated the beneficial effects of berberine on renal function and its possible mechanisms in rats with diabetic nephropathy(DN). Methods Male Wistar rats were divided into three groups: normal, diabetic model, and berberine treatment groups. Rats in the diabetic model and berberine treatment groups were induced to diabetes by intraperitonal injection with streptozotocin(STZ). Glomerular area, glomerular volume, fasting blood glucose(FBG), blood urea nitrogen(BUN), serum creatinine (Cr)and urine protein for 24 hours(UP24h) were measured using commercially available kits. Meanwhile, the activity of superoxide dismutase (SOD), content of malondialdehyde (MDA) in serum, activity of aldose reductase (AR)and the expression of AR mRNA and protein in kidney were detected by different methods. Results The result showed that oral administration of berberine (200mg·kg-1·d-1) significantly ameliorated the ratio of kidney weight to body weight. Glomerular area, glomerular volume, FBG, BUN, Cr and UP24h were significantly decreased in the berberine treatment group compared with the diabetic model group(P<0.05). Berberine treatment significantly increased serum SOD activity and decreased the content of MDA compared with diabetic model group(P<0.05). AR activity as well as the expression of AR mRNA and protein in the kidney was markedly decreased in the berberine treatment group compared with diabetic model group (P<0.05). Conclusion These results suggested that berberine could ameliorate renal dysfunction in DN rats through controlling blood glucose, reduction of oxidative stress and inhibition of the activation of the polyol pathway.

  2. The Role of Urotensin Receptors in the Paracetamol-Induced Hepatotoxicity Model in Mice: Ameliorative Potential of Urotensin II Antagonist.

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    Palabiyik, Saziye S; Karakus, Emre; Akpinar, Erol; Halici, Zekai; Bayir, Yasin; Yayla, Muhammed; Kose, Duygu

    2016-02-01

    We aimed to evaluate the possible protective effect of a UTR antagonist and to determine the effect of the antagonist on ALT and AST levels in serum, the mRNA expression level of UTR, tumour necrosis factor-alpha (TNF-α) and IL-1β and SOD activity, GSH and MDA levels in liver tissues, which are important mediators or markers for the hepatotoxicity animal model in mice. Animals fasted overnight and were divided into seven equal groups (n = 12). The first group was the healthy group (administered 0.1% DMSO intraperitoneally). Group 2 received only paracetamol (PARA) (administered orally at a dosage of 300 mg/kg). Groups 3 and 4 were treated with only AGO (AC7954, UTR agonist) 15 and 30 mg/kg intraperitoneally, respectively. Groups 5 and 6 were treated with only ANTA (SB657510, UTR antagonist) 30 and 60 mg/kg intraperitoneally, respectively. Group 7 was treated with AGO 30 mg/kg and ANTA 60 mg/kg intraperitoneally. One hour after the pre-treatment drugs were administered, groups 3 through 7 were given PARA. After the experimental period, the mice were killed 6 and 24 hr after PARA was administered. Antagonist administration significantly decreased the ALT and AST levels, while agonist administration did not. In addition, SOD activity and GSH levels increased, and the MDA level decreased with the pre-treatment of two antagonist doses. The increased UTR gene expression through PARA was significantly lower in both doses of the antagonist groups at 24 hr when compared with the agonist and PARA groups. This study showed that UTR antagonists have hepatoprotective and anti-inflammatory effects on high-dose PARA-induced hepatotoxicity in mice. PMID:26176337

  3. Benincasa cerifera Ameliorates Renal Ischemia/Reperfusion Injury in Hyperlipidemic Rat

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    Y S Bhalodia

    2009-01-01

    Full Text Available To investigate protective effect of Benincasa cerifera (BC against kidney injury induced by Ischemia/Reperfusion (I/R in hyperlipidemic (HC rats. Hyperlipidemia was developed by cholesterol diet (2% cholesterol and 20 % coconut oil feeding for 3 weeks. At the end of 3rd week, renal ischemia was induced by both renal arteries occlusion for 60 min followed 24 h of reperfusion. Methanolic extract of Benincasa cerifera (500 mg/kg/day was administered orally 7 days before induction of ischemia. Benincasa cerifera treatment reversed all antioxidant parameters like superoxide dismutase (SOD, reduced glutathione (GSH and malondialdehyde (MDA contents as well serum creatinine and blood urea nitrogen (BUN levels. This data conclude the renoprotective activity of Benincasa cerifera against renal damage induced by ischemia/reperfusion injury in hyperlipidemic rat.

  4. The restrained expression of NF-kB in renal tissue ameliorates folic acid induced acute kidney injury in mice.

    Science.gov (United States)

    Kumar, Dev; Singla, Surinder K; Puri, Veena; Puri, Sanjeev

    2015-01-01

    The Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB) represent family of structurally-related eukaryotic transcription factors which regulate diverse array of cellular processes including immunological responses, inflammation, apoptosis, growth & development. Increased expression of NF-kB has often been seen in many diverse diseases, suggesting the importance of genomic deregulation to disease pathophysiology. In the present study we focused on acute kidney injury (AKI), which remains one of the major risk factor showing a high rate of mortality and morbidity. The pathology associated with it, however, remains incompletely known though inflammation has been reported to be one of the major risk factor in the disease pathophysiology. The role of NF-kB thus seemed pertinent. In the present study we show that high dose of folic acid (FA) induced acute kidney injury (AKI) characterized by elevation in levels of blood urea nitrogen & serum creatinine together with extensive tubular necrosis, loss of brush border and marked reduction in mitochondria. One of the salient observations of this study was a coupled increase in the expression of renal, relA, NF-kB2, and p53 genes and proteins during folic acid induced AKI (FA AKI). Treatment of mice with NF-kB inhibitor, pyrrolidine dithio-carbamate ammonium (PDTC) lowered the expression of these transcription factors and ameliorated the aberrant renal function by decreasing serum creatinine levels. In conclusion, our results suggested that NF-kB plays a pivotal role in maintaining renal function that also involved regulating p53 levels during FA AKI. PMID:25559736

  5. Mild systemic thermal therapy ameliorates renal dysfunction in a rodent model of chronic kidney disease.

    Science.gov (United States)

    Iwashita, Yoshihiro; Kuwabara, Takashige; Hayata, Manabu; Kakizoe, Yutaka; Izumi, Yuichiro; Iiyama, Junichi; Kitamura, Kenichiro; Mukoyama, Masashi

    2016-06-01

    Thermal therapy has become a nonpharmacological therapy in clinical settings, especially for cardiovascular diseases. However, the practical role of thermal therapy on chronic kidney disease remains elusive. We performed the present study to investigate whether a modified thermal protocol, repeated mild thermal stimulation (MTS), could affect renal damages in chronic kidney disease using a mouse renal ablation model. Mice were subjected to MTS or room temperature (RT) treatment once daily for 4 wk after subtotal nephrectomy (Nx) or sham operation (Sh). We revealed that MTS alleviated renal impairment as indicated by serum creatinine and albuminuria in Nx groups. In addition, the Nx + MTS group showed attenuated tubular histological changes and reduced urinary neutrophil gelatinase-associated lipocalin excretion approximately by half compared with the Nx + RT group. Increased apoptotic signaling, such as TUNEL-positive cell count and cleavage of caspase 3, as well as enhanced oxidative stress were significantly reduced in the Nx + MTS group compared with the Nx + RT group. These changes were accompanied with the restoration of kidney Mn-SOD levels by MTS. Heat shock protein 27, a key molecular chaperone, was phosphorylated by MTS only in Nx kidneys rather than in Sh kidneys. MTS also tended to increase the phosphorylation of p38 MAPK and Akt in Nx kidneys, possibly associated with the activation of heat shock protein 27. Taken together, these results suggest that modified MTS can protect against renal injury in a rodent model of chronic kidney disease. PMID:27029428

  6. 6-gingerol ameliorates gentamicin induced renal cortex oxidative stress and apoptosis in adult male albino rats.

    Science.gov (United States)

    Hegazy, Ahmed M S; Mosaed, Mohammed M; Elshafey, Saad H; Bayomy, Naglaa A

    2016-06-01

    Ginger or Zingiber officinale which is used in traditional medicine has been found to possess antioxidant effect that can control the generation of free radicals. Free radicals are the causes of renal cell degeneration that leads to renal failure in case of gentamicin induced toxicity. This study was done to evaluate the possible protective effects of 6-gingerol as natural antioxidant on gentamicin-induced renal cortical oxidative stress and apoptosis in adult male albino rats. Forty adult male albino rats were used in this study and were randomly divided into four groups, control group; 6-gingerol treated group; gentamicin treated group and protected group (given simultaneous 6-gingerol and gentamicin). At the end of the study, blood samples were drawn for biochemical study. Kidney sections were processed for histological, and immunohistochemical examination for caspase-3 to detect apoptosis and anti heat shock protein 47 (HSP47) to detect oxidative damage. Gentamicin treated rats revealed a highly significant increase in renal function tests, tubular dilatation with marked vacuolar degeneration and desquamation of cells, interstitial hemorrhage and cellular infiltration. Immunohistochemically, gentamicin treated rats showed a strong positive immunoreaction for caspase-3 and anti heat shock protein 47 (HSP47). Protected rats showed more or less normal biochemical, histological, and immunohistochemical pictures. In conclusion, co-administration of 6-gingerol during gentamicin 'therapy' has a significant reno-protective effect in a rat model of gentamicin-induced renal damage. It is recommended that administration of ginger with gentamicin might be beneficial in men who receive gentamicin to treat infections. PMID:27036327

  7. Calcitriol ameliorates renal damage in a pre-established proteinuria model

    OpenAIRE

    MAQUIGUSSA, EDGAR; ARNONI, CARINE P; PEREIRA, LUCIANA G; Mirian A. Boim

    2015-01-01

    Proteinuria is critical in the tubulointerstitial changes that ultimately lead to renal insufficiency. Increased protein filtration has direct toxic effects on tubular epithelial cells, leading to epithelial mesenchymal transition (EMT) to a myofibroblast phenotype. Angiotensin II and transforming growth factor (TGF)-β1 are the main mediators of EMT. Calcitriol may exert a potential renoprotective effect by reducing the activity of the renin angiotensin system by suppressing renin gene expres...

  8. CXCR4 antagonist AMD3100 ameliorates thyroid damage in autoimmune thyroiditis in NOD.H‑2h4 mice.

    Science.gov (United States)

    Liu, Xin; Mao, Jinyuan; Han, Cheng; Peng, Shiqiao; Li, Chenyan; Jin, Ting; Fan, Chenling; Shan, Zhongyan; Teng, Weiping

    2016-04-01

    CXC chemokine ligand 12 (CXCL12) and its receptor, CXC chemokine receptor 4 (CXCR4), are upregulated in mice with autoimmune thyroid diseases. However, whether this interaction is involved in the pathophysiology of autoimmune thyroiditis (AIT) remains to be elucidated. In the present study, the effects of the CXCR4 antagonist, AMD3100, in an iodine‑induced autoimmune thyroiditis model were investigated. NOD.H‑2h4 mice were randomly separated into a control, AIT and AIT+AMD3100 groups. The mice were fed with 0.05% sodium iodide water for 8 weeks to induce AIT. The AMD3100‑treated mice were administered with the CXCR4 antagonist at a dose of 10 mg/kg intraperitoneally three times a week during the experimental period. The percentages of CD19+interleukin (IL)10+ B cells and CD4+IL10+ T cells, and the mRNA expression levels of IL10 in the splenocytes were reduced in the AIT group, compared with the control group, however, they increased following AMD3100 treatment, compared with the untreated AIT group. The percentages of CD4+ T cells, CD8+ T cells, CD19+ B cells and CD8+ interferon (IFN)γ+ T cells, and the mRNA expression levels of IFNγ increased in the AIT group, compared with the control group, however, these were reduced in the AMD3100 group, compared with the AIT group. The AMD3100‑treated mice also had lower serum thyroglobulin antibody titers and reduced lymphocytic infiltration in the thyroid, compared with the untreated AIT mice. These results suggested that inhibition of this chemokine axis may offer potential as a therapeutic target for the treatment of AIT. PMID:26935473

  9. Mentha piperita in nephrotoxicity - a possible intervention to ameliorate renal derangements associated with gentamicin

    Directory of Open Access Journals (Sweden)

    Naveed Ullah

    2014-01-01

    Full Text Available Objective: Free radical generation has a strong role in the pathogenesis of renal damage associated with the use of gentamicin. Therefore, the present study was carried out to evaluate the renoprotective effect of Mentha piperita against gentamicin induced nephrotoxicity. Materials and Methods: A total of 24 male rabbits were divided into 4 groups receiving normal saline, gentamicin, M. piperita extract and co-therapy of extract and gentamicin respectively. Gentamicin was provided as 80 mg/kg/day intramuscularly and extract was given 200 mg/kg/day orally for a period of 21 days. Serum and urinary biochemical parameters and histological changes were studied for each group. The impact of the extract on the antibacterial action of gentamicin was also evaluated. Results: Animals treated with gentamicin showed derangements in serum and urinary biochemical parameters. These alterations were reversed by treatment with M. piperita extract. The histological changes showed in gentamicin group were also reverted by treatment with the extract. Further the plant did not influence the efficacy of gentamicin with respect to its antimicrobial properties. Conclusion: Co-therapy of M. piperita with gentamicin successfully attenuated biochemical kidney functioning derangements and morphological changes associated with gentamicin.

  10. Low-Density Lipoprotein Apheresis Ameliorates Renal Prognosis of Cholesterol Crystal Embolism.

    Science.gov (United States)

    Ishiyama, Katsuya; Sato, Toshinobu; Taguma, Yoshio

    2015-08-01

    Drugs such as corticosteroids and statins have been used to treat cholesterol crystal embolism (CCE), but the prognosis remains poor. This study evaluated the efficacy of low-density lipoprotein apheresis (LDL-A) in patients with CCE. Patients with CCE who showed renal deterioration after vascular interventions were studied retrospectively. Information on demographic variables, clinical measurements, and medication use was collected. The outcomes were incidence of maintenance dialysis and mortality at 24 weeks. A total of 49 patients with CCE were included, among whom 37 (76%) were diagnosed pathologically and the remainder were diagnosed clinically. The median estimated GFR at baseline and at diagnosis were 40.5 and 13.4 mL/min per 1.73 m(2) , respectively. Corticosteroids were used in 42 patients (86%), statins in 30 patients (61%), and angiotensin-converting enzyme inhibitors and angiotensin receptor blockers in 29 patients (59%). LDL-A was performed in 25 patients (LDL-A group), and not in 24 patients (control group). Smoking (100% vs. 72%, P = 0.02), white blood cell count (8900/mm(3) vs. 7000/mm(3) ) and corticosteroid use (96% vs. 75%) were higher in the LDL-A group compared with the control group, but there were no differences in other demographic and clinical parameters between the groups. Patients in the LDL-A group had a lower incidence of maintenance dialysis (2/25 (8%) vs. 8/24 (33%), P CCE patients after vascular interventions. PMID:26386224

  11. Targeting Imbalance between IL-1β and IL-1 Receptor Antagonist Ameliorates Delayed Epithelium Wound Healing in Diabetic Mouse Corneas.

    Science.gov (United States)

    Yan, Chenxi; Gao, Nan; Sun, Haijing; Yin, Jia; Lee, Patrick; Zhou, Li; Fan, Xianqun; Yu, Fu-Shin

    2016-06-01

    Patients with diabetes mellitus often develop corneal complications and delayed wound healing. How diabetes might alter acute inflammatory responses to tissue injury, leading to delayed wound healing, remains mostly elusive. Using a streptozotocin-induced type I diabetes mellitus mice and corneal epithelium-debridement wound model, we discovered that although wounding induced marked expression of IL-1β and the secreted form of IL-1 receptor antagonist (sIL-1Ra), diabetes suppressed the expressions of sIL-1Ra but not IL-1β in healing epithelia and both in whole cornea. In normoglycemic mice, IL-1β or sIL-1Ra blockade delayed wound healing and influenced each other's expression. In diabetic mice, in addition to delayed reepithelization, diabetes weakened phosphatidylinositol 3-kinase-Akt signaling, caused cell apoptosis, diminished cell proliferation, suppressed neutrophil and natural killer cell infiltrations, and impaired sensory nerve reinnervation in healing mouse corneas. Local administration of recombinant IL-1Ra partially, but significantly, reversed these pathological changes in the diabetic corneas. CXCL10 was a downstream chemokine of IL-1β-IL-1Ra, and exogenous CXCL10 alleviated delayed wound healing in the diabetic, but attenuated it in the normal corneas. In conclusion, the suppressed early innate/inflammatory responses instigated by the imbalance between IL-1β and IL-1Ra is an underlying cause for delayed wound healing in the diabetic corneas. Local application of IL-1Ra accelerates reepithelialization and may be used to treat chronic corneal and potential skin wounds of diabetic patients. PMID:27109611

  12. Quercetin and allopurinol ameliorate kidney injury in STZ-treated rats with regulation of renal NLRP3 inflammasome activation and lipid accumulation.

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    Chuang Wang

    Full Text Available Hyperuricemia, hyperlipidemia and inflammation are associated with diabetic nephropathy. The NLRP3 inflammasome-mediated inflammation is recently recognized in the development of kidney injury. Urate and lipid are considered as danger signals in the NLRP3 inflammasome activation. Although dietary flavonoid quercetin and allopurinol alleviate hyperuricemia, dyslipidmia and inflammation, their nephroprotective effects are currently unknown. In this study, we used streptozotocin (STZ-induced diabetic nephropathy model with hyperuricemia and dyslipidemia in rats, and found over-expression of renal inflammasome components NLRP3, apoptosis-associated speck-like protein and Caspase-1, resulting in elevation of IL-1β and IL-18, with subsequently deteriorated renal injury. These findings demonstrated the possible association between renal NLRP3 inflammasome activation and lipid accumulation to superimpose causes of nephrotoxicity in STZ-treated rats. The treatment of quercetin and allopurinol regulated renal urate transport-related proteins to reduce hyperuricemia, and lipid metabolism-related genes to alleviate kidney lipid accumulation in STZ-treated rats. Furthermore, quercetin and allopurinol were found to suppress renal NLRP3 inflammasome activation, at least partly, via their anti-hyperuricemic and anti-dyslipidemic effects, resulting in the amelioration of STZ-induced the superimposed nephrotoxicity in rats. These results may provide a basis for the prevention of diabetes-associated nephrotoxicity with urate-lowering agents such as quercetin and allopurinol.

  13. Pre-conditioned mesenchymal stem cells ameliorate renal ischemic injury in rats by augmented survival and engraftment

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    Masoud Muhammad

    2012-12-01

    Full Text Available Abstract Background Ischemia is the major cause of acute kidney injury (AKI, associated with high mortality and morbidity. Mesenchymal stem cells (MSCs have multilineage differentiation potential and can be a potent therapeutic option for the cure of AKI. Methods MSCs were cultured in four groups SNAP (S-nitroso N-acetyl penicillamine, SNAP + Methylene Blue (MB, MB and a control for in vitro analysis. Cultured MSCs were pre-conditioned with either SNAP (100 μM or MB (1 μM or both for 6 hours. Renal ischemia was induced in four groups (as in in vitro study of rats by clamping the left renal padicle for 45 minutes and then different pre-conditioned stem cells were transplanted. Results We report that pre-conditioning of MSCs with SNAP enhances their proliferation, survival and engraftment in ischemic kidney. Rat MSCs pre-conditioned with SNAP decreased cell apoptosis and increased proliferation and cytoprotective genes’ expression in vitro. Our in vivo data showed enhanced survival and engraftment, proliferation, reduction in fibrosis, significant improvement in renal function and higher expression of pro-survival and pro-angiogenic factors in ischemic renal tissue in SNAP pre-conditioned group of animals. Cytoprotective effects of SNAP pre-conditioning were abrogated by MB, an inhibitor of nitric oxide synthase (NOS and guanylate cyclase. Conclusion The results of these studies demonstrate that SNAP pre-conditioning might be useful to enhance therapeutic potential of MSCs in attenuating renal ischemia reperfusion injury.

  14. Hydroxysafflor Yellow A Ameliorates Renal Fibrosis by Suppressing TGF-β1-Induced Epithelial-to-Mesenchymal Transition.

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    Naping Hu

    Full Text Available Renal fibrosis is the common pathological foundation of many chronic kidney diseases (CKDs. The aim of this study was to investigate whether Hydroxysafflor yellow A (HSYA can preserve renal function by inhibiting the progression of renal fibrosis and the potential mechanisms.Renal fibrosis was induced by unilateral ureteral obstruction (UUO performed on 7-week-old C57BL/6 mice. HSYA (10, 50 and 100 mg/kg were intragastrically administered. Sham group and model group were administered with the same volume of vehicle. Serum and kidney samples were collected 14 days after the UUO surgery. Serum biochemical indicators were measured by automatic biochemical analyzer. Histological changes were evaluated by HE and Masson staining. In vitro, the anti-fibrotic effect of HSYA was tested on human recombinant transforming growth factor-β1 (TGF-β1 stimulated HK-2 cells. The protein levels of α-SMA, collagen-I and fibronectin in kidney tissue andHK-2 cells were measured by immunohistochemistry and immunofluorescence. The protein levels of apoptosis-relative and TGF-β1/Smad3 signaling were detected by western blot.HSYA slowed the development of renal fibrosis both in vivo and in vitro. In UUO rats, renal function index suggested that HSYA treatment decreased the level of serum creatinine (Scr and blood urea nitrogen (BUN rose by UUO (P<0.05. HE staining and Masson staining demonstrated that kidney interstitial fibrosis, tubular atrophy, and inflammatory cell infiltration were notably attenuated in the high-dose HSYA group compared with the model group. The expressions of α-SMA, collagen-I and fibronectin were decreased in the UUO kidney and HK-2 cells of the HSYA-treatment group. Moreover, HSYA reduced the apoptotic rate of HK-2 cells stimulated by TGF-β1. Further study revealed that HSYA regulated the TGF-β1/Smads signaling pathway both in kidney tissue and HK-2 cells.These results suggested that HSYA had a protective effect against fibrosis in renal

  15. Hydroxysafflor Yellow A Ameliorates Renal Fibrosis by Suppressing TGF-β1-Induced Epithelial-to-Mesenchymal Transition

    Science.gov (United States)

    Chu, Jianjie; Sun, Jin; Liu, Meiyou; Wang, Chao; Lu, Chengtao; Wen, Aidong

    2016-01-01

    Objective Renal fibrosis is the common pathological foundation of many chronic kidney diseases (CKDs). The aim of this study was to investigate whether Hydroxysafflor yellow A (HSYA) can preserve renal function by inhibiting the progression of renal fibrosis and the potential mechanisms. Methods Renal fibrosis was induced by unilateral ureteral obstruction (UUO) performed on 7-week-old C57BL/6 mice. HSYA (10, 50 and 100 mg/kg) were intragastrically administered. Sham group and model group were administered with the same volume of vehicle. Serum and kidney samples were collected 14 days after the UUO surgery. Serum biochemical indicators were measured by automatic biochemical analyzer. Histological changes were evaluated by HE and Masson staining. In vitro, the anti-fibrotic effect of HSYA was tested on human recombinant transforming growth factor-β1 (TGF-β1) stimulated HK-2 cells. The protein levels of α-SMA, collagen-I and fibronectin in kidney tissue andHK-2 cells were measured by immunohistochemistry and immunofluorescence. The protein levels of apoptosis-relative and TGF-β1/Smad3 signaling were detected by western blot. Results HSYA slowed the development of renal fibrosis both in vivo and in vitro. In UUO rats, renal function index suggested that HSYA treatment decreased the level of serum creatinine (Scr) and blood urea nitrogen (BUN) rose by UUO (P<0.05). HE staining and Masson staining demonstrated that kidney interstitial fibrosis, tubular atrophy, and inflammatory cell infiltration were notably attenuated in the high-dose HSYA group compared with the model group. The expressions of α-SMA, collagen-I and fibronectin were decreased in the UUO kidney and HK-2 cells of the HSYA-treatment group. Moreover, HSYA reduced the apoptotic rate of HK-2 cells stimulated by TGF-β1. Further study revealed that HSYA regulated the TGF-β1/Smads signaling pathway both in kidney tissue and HK-2 cells. Conclusions These results suggested that HSYA had a protective

  16. Aqueous extract of Annona squamosa (L.) ameliorates renal failure induced by 5/6 nephrectomy in rat

    OpenAIRE

    Aaishwarya B Deshmukh; Patel, Jayvadan K.

    2011-01-01

    Objective : To assess the renoprotective activity of the water extract of Annona squamosa in 5/6 nephrectomized animals. Materials and Methods : For evaluating the renoprotective effects of Annona squamosa, 5/6 nephrectomized rats were used as a model for renal failure. The effects of hot-water extract of leaves of Annona squamosa L. (A. squamosa) at a dose 300 mg/kg bw on biochemical and urinary parameters like plasma urea, plasma creatinine, and urine creatinine were analyzed. For eluc...

  17. Endothelin A receptor antagonist, atrasentan, attenuates renal and cardiac dysfunction in Dahl salt-hypertensive rats in a blood pressure independent manner.

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    Mohammed A Samad

    Full Text Available Proteinuria is a hallmark of chronic kidney disease (CKD and cardiovascular disease (CVD, and a good predictor of clinical outcome. Selective endothelin A (ETA receptor antagonist used with renin-angiotensin system (RAS inhibitors prevents development of proteinuria in CKD. However, whether the improvement in proteinuria would have beneficial effects on CVD, independent of RAS inhibition, is not well understood. In this study, we investigated whether atrasentan, an ETA receptor antagonist, has renal and cardiovascular effects independent of RAS inhibition. Male Dahl salt sensitive (DSS rats, at six weeks of age, received water with or without different doses of atrasentan and/or enalapril under high salt (HS diet or normal diet (ND for 6 weeks. At the end of 12th week, atrasentan at a moderate dose significantly attenuated proteinuria and serum creatinine without reducing mean arterial pressure (MAP, thereby preventing cardiac hypertrophy and improving cardiac function. ACE inhibitor enalapril at a dose that did not significantly lowered BP, attenuated cardiac hypertrophy while moderately improving cardiac function without reducing proteinuria and serum creatinine level. Nonetheless, combined therapy of atrasentan and enalapril that does not altering BP exerted additional cardioprotective effect. Based on these findings, we conclude that BP independent monotherapy of ETA receptor antagonist attenuates the progression of CKD and significantly mitigates CVD independent of RAS inhibition.

  18. Endothelin A receptor antagonist, atrasentan, attenuates renal and cardiac dysfunction in Dahl salt-hypertensive rats in a blood pressure independent manner.

    Science.gov (United States)

    Samad, Mohammed A; Kim, Ui Kyoung; Kang, Joshua J; Ke, Qingen; Kang, Peter M

    2015-01-01

    Proteinuria is a hallmark of chronic kidney disease (CKD) and cardiovascular disease (CVD), and a good predictor of clinical outcome. Selective endothelin A (ETA) receptor antagonist used with renin-angiotensin system (RAS) inhibitors prevents development of proteinuria in CKD. However, whether the improvement in proteinuria would have beneficial effects on CVD, independent of RAS inhibition, is not well understood. In this study, we investigated whether atrasentan, an ETA receptor antagonist, has renal and cardiovascular effects independent of RAS inhibition. Male Dahl salt sensitive (DSS) rats, at six weeks of age, received water with or without different doses of atrasentan and/or enalapril under high salt (HS) diet or normal diet (ND) for 6 weeks. At the end of 12th week, atrasentan at a moderate dose significantly attenuated proteinuria and serum creatinine without reducing mean arterial pressure (MAP), thereby preventing cardiac hypertrophy and improving cardiac function. ACE inhibitor enalapril at a dose that did not significantly lowered BP, attenuated cardiac hypertrophy while moderately improving cardiac function without reducing proteinuria and serum creatinine level. Nonetheless, combined therapy of atrasentan and enalapril that does not altering BP exerted additional cardioprotective effect. Based on these findings, we conclude that BP independent monotherapy of ETA receptor antagonist attenuates the progression of CKD and significantly mitigates CVD independent of RAS inhibition. PMID:25775254

  19. Ameliorative potentials of cocoyam (Colocasia esculenta L.) and unripe plantain (Musa paradisiacal L.) on renal and liver growth in streptozotocin induced diabetic rats

    Institute of Scientific and Technical Information of China (English)

    Eleazu CO; Iroaganachi M; Eleazu KC

    2013-01-01

    Objective:To investigate the ameliorating potentials of cocoyam(Colocasia esculenta(C. esculenta)L.) and unripe plantain(Musa paradisiacae(M. paradisiacae)L.) incorporated feeds on renal and liver growth ofSTZ induced rats.Method:The blood glucose level of all the rats was measured with a glucometer, the protein and glucose levels in the urine samples of the rats were determined using urine assay strips while the specific gravity of the urine samples of all the rats was determined with a urinometer.The assay of the proximate, phytochemical, mineral composition as well as screening for antioxidant activity of the test feeds was carried out using standard techniques.Results:The administration of the test feeds to the diabetic rats in58.75% and38.13% decreases in their hyperglycemia with a corresponding amelioration of their elevated urinary protein, glucose, specific gravity as well as renal and kidney growths.Administration of the cocoyam incorporated feeds to the diabetic rats of group4, resulted in2.71% increase in body weight with a corresponding19.52% increase in growth rate unlike the diabetic rats of group 5, administered unripe plantain feed that had5.12% decrease in weight with a corresponding 29.52% decrease in growth rate but higher than the diabetic control rats that recorded28.69% and 29.46% decreases in body weights with a corresponding248.9% and250.14% decreases in growth rates.Analysis revealed that the test feeds contained low quantities of moisture but significant quantities of crude fibre, proteins, lipids, carbohydrates, ash, alkaloids, flavonoids, saponins, tannins, calcium, magnesium, potassium, iron, zinc, phosphorous as well as considerable amount of energy.In addition, the cocoyam incorporated feeds contained higher quantities of flavonoids, saponin, tannin,Ca,Mg,Fe,Zn,K,P, crude fibre as well as antioxidant activity but lower quantities of alkaloids than the unripe plantain feed.Conclusion:The use of cocoyam and unripe plantain flours in the

  20. Interstitial renal fibrosis due to multiple cisplatin treatments is ameliorated by semicarbazide-sensitive amine oxidase inhibition.

    Science.gov (United States)

    Katagiri, Daisuke; Hamasaki, Yoshifumi; Doi, Kent; Negishi, Kousuke; Sugaya, Takeshi; Nangaku, Masaomi; Noiri, Eisei

    2016-02-01

    Elucidation of acute kidney diseases and disorders (AKD), including acute kidney injury (AKI), is important to prevent their progression to chronic kidney disease. Current animal AKI models are often too severe for use in evaluating human AKI. Therefore, new animal models of mild kidney injury are needed. Here a new clinically relevant animal model using multiple low doses of cisplatin (CP) was used to evaluate AKD. When 10 mg/kg CP was administered intraperitoneally once weekly for three times to L-type fatty acid-binding protein (L-FABP) transgenic mice, moderate renal interstitial fibrosis and tubule dilatation occurred, accompanied by brush-border loss. Urinary L-FABP, a promising biomarker of AKI, changed more drastically than blood urea nitrogen or creatinine. Preventing fibrosis in organs was also studied. Oral administration of a recently reported selective semicarbazide-sensitive amine oxidase inhibitor, PXS-4728A, for 1 week attenuated kidney injury and interstitial fibrosis compared with vehicle. Inhibition of renal lipid accumulation in semicarbazide-sensitive amine oxidase inhibitor-treated mice, together with reduced oxidative stress and L-FABP suppression in proximal tubules, suggested an antifibrotic effect of semicarbazide-sensitive amine oxidase inhibition in this CP-AKD model, a representative onco-nephrology. Thus, semicarbazide-sensitive amine oxidase inhibitors may be promising candidates for the prevention of chronic kidney disease in patients using CP to treat malignancy. PMID:26535996

  1. 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...... describes a case of acute renal graft dysfunction following the addition of an ARB to existing ACE inhibition. This unmasked an unknown iliac artery stenosis. The case indicates a possible important role of Ang II generated by non-ACE pathways in this situation....

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

    Directory of Open Access Journals (Sweden)

    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.

  3. 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.

  4. A RETROSPECTIVE STUDY ON THE POTENTIAL DRUG INTERACTION BETWEEN ANGIOTENSIN CONVERTING ENZYME INHIBITOR OR ANGIOTENSIN RECEPTOR ANTAGONIST AND OTHER DRUGS IN END-STAGE CHRONIC RENAL FAILURE PATIENTS

    Directory of Open Access Journals (Sweden)

    Honey Iskandar

    2012-10-01

    Full Text Available Increasing number of chronic renal failure (CRF patients had reflected an increase in the number of patients with diabetes and hypertension. Therefore, health practitioners would be faced with management of complicated medical problems for the patients of chronic renal disease. In this way, various complications of chronic renal failure would lead to polypharmacy, where the patients receive three to five drugs in a dose. Development of polypharmacy had made the potential of drug interaction greater. The objective was to determine whether CRF patients admitted to hospital with specific adverse drug reactions were likely to have been prescribed with interacting drugs. Retrospective study was designed. The study was conducted at the General Practice Rooms Floor 1 – Floor VI of Central Army Hospital Gatot Soebroto Jakarta. The study was conducted from December 2011 – February 2012. The data were collected in a retrospective way for a year (January – December 2011. End-stage CRF patients who were having hemodialysis therapy and receiving ACE Inhibitor drugs or Angiotensin II Receptor Antagonist (AIIRA and receiving treatment at the General Practice Rooms at Central Army Hospital Gatot Soebroto Jakarta. During the period of January – December 2011, 84 patients were treated with end-stage CRF at the Central Army Hospital and having routine hemodialysis and 44 patients were receiving therapy with ACE Inhibitor and AIIRA. Other drugs simultaneously given with ACE Inhibitor and AIIRA were captopril-spironolactone, captopril-aspirin, captopril-allopurinol, captopril-KSR, captopril-furosemide, lisinopril-furosemide and valsartan-mefenemic acid. An increase in adverse effects of the drugs was found based on the clinical evaluation and laboratory examination. The adverse effects included hyperkalemia (9,09%, decrease in anti-hypertension effect (6,8%, acute hypotension (40%, and declining renal function (11,36%. The study identifies drug interaction

  5. 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. PMID:26463157

  6. 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

    International Nuclear Information System (INIS)

    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

  7. 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

  8. Aldosterone antagonists in monotherapy are protective against streptozotocin-induced diabetic nephropathy in rats.

    Science.gov (United States)

    Banki, Nora F; Ver, Agota; Wagner, Laszlo J; Vannay, Adam; Degrell, Peter; Prokai, Agnes; Gellai, Renata; Lenart, Lilla; Szakal, Dorottya-Nagy; Kenesei, Eva; Rosta, Klara; Reusz, Gyorgy; Szabo, Attila J; Tulassay, Tivadar; Baylis, Chris; Fekete, Andrea

    2012-01-01

    Angiotensin converting enzyme inhibitors (ACEi) and angiotensin II receptor blockers (ARB) are the standard clinical therapy of diabetic nephropathy (DN), while aldosterone antagonists are only used as adjuncts. Previously in experimental DN we showed that Na/K ATPase (NKA) is mislocated and angiotensin II leads to superimposed renal progression. Here we investigated the monotherapeutic effect of aldosterone blockers on the progression of DN and renal NKA alteration in comparison to ACEi and ARBs. Streptozotocin-diabetic rats developing DN were treated with aldosterone antagonists; ACEi and ARB. Renal function, morphology, protein level and tubular localization of NKA were analyzed. To evaluate the effect of high glucose per se; HK-2 proximal tubular cells were cultured in normal or high concentration of glucose and treated with the same agents. Aldosterone antagonists were the most effective in ameliorating functional and structural kidney damage and they normalized diabetes induced bradycardia and weight loss. Aldosterone blockers also prevented hyperglycemia and diabetes induced increase in NKA protein level and enzyme mislocation. A monotherapy with aldosterone antagonists might be as, or more effective than ACEi or ARBs in the prevention of STZ-induced DN. Furthermore the alteration of the NKA could represent a novel pathophysiological feature of DN and might serve as an additional target of aldosterone blockers. PMID:22761931

  9. Aldosterone antagonists in monotherapy are protective against streptozotocin-induced diabetic nephropathy in rats.

    Directory of Open Access Journals (Sweden)

    Nora F Banki

    Full Text Available Angiotensin converting enzyme inhibitors (ACEi and angiotensin II receptor blockers (ARB are the standard clinical therapy of diabetic nephropathy (DN, while aldosterone antagonists are only used as adjuncts. Previously in experimental DN we showed that Na/K ATPase (NKA is mislocated and angiotensin II leads to superimposed renal progression. Here we investigated the monotherapeutic effect of aldosterone blockers on the progression of DN and renal NKA alteration in comparison to ACEi and ARBs. Streptozotocin-diabetic rats developing DN were treated with aldosterone antagonists; ACEi and ARB. Renal function, morphology, protein level and tubular localization of NKA were analyzed. To evaluate the effect of high glucose per se; HK-2 proximal tubular cells were cultured in normal or high concentration of glucose and treated with the same agents. Aldosterone antagonists were the most effective in ameliorating functional and structural kidney damage and they normalized diabetes induced bradycardia and weight loss. Aldosterone blockers also prevented hyperglycemia and diabetes induced increase in NKA protein level and enzyme mislocation. A monotherapy with aldosterone antagonists might be as, or more effective than ACEi or ARBs in the prevention of STZ-induced DN. Furthermore the alteration of the NKA could represent a novel pathophysiological feature of DN and might serve as an additional target of aldosterone blockers.

  10. Beneficial effects montelukast, cysteinyl-leukotriene receptor antagonist, on renal damage after unilateral ureteral obstruction in rats

    Directory of Open Access Journals (Sweden)

    Alper Otunctemur

    2015-04-01

    Full Text Available Introductıon Ureteral obstruction is a common pathology and caused kidney fibrosis and dysfunction at late period. In this present, we investigated the antifibrotic and antiinflammatory effects of montelukast which is cysteinyl leukotriene receptor antagonist, on kidney damage after unilateral ureteral obstruction(UUO in rats. Mateirıals and Methods 32 rats divided four groups. Group 1 was control, group 2 was sham, group 3 was rats with UUO and group 4 was rats with UUO which were given montelukast sodium (oral 10 mg/kg/day. After 14 days, rats were killed and their kidneys were taken and blood analysis was performed. Tubular necrosis, mononuclear cell infiltration and interstitial fibrosis scoring were determined histopathologically in a part of kidneys; nitric oxide(NO, malondialdehyde(MDA and reduced glutathione(GSH levels were determined in the other part of kidneys. Urea-creatinine levels were investigated at blood analysis. Statistical analyses were made by the Chi-square test and one-way analysis of variance (ANOVA. Results There was no difference significantly for urea-creatinine levels between groups. Pathologically, there was serious tubular necrosis and fibrosis in group 3 and there was significantly decreasing for tubular necrosis and fibrosis in group 4(p<0.005. Also, there was significantly increasing for NO and MDA levels; decreasing for GSH levels in group 3 compared the other groups(p<0.005. Conclusıon We can say that montelukast prevent kidney damage with antioxidant effect, independently of NO.

  11. Multiple human isoforms of drug transporters contribute to the hepatic and renal transport of olmesartan, a selective antagonist of the angiotensin II AT1-receptor.

    Science.gov (United States)

    Yamada, Akihiro; Maeda, Kazuya; Kamiyama, Emi; Sugiyama, Daisuke; Kondo, Tsunenori; Shiroyanagi, Yoshiyuki; Nakazawa, Hayakazu; Okano, Teruo; Adachi, Masashi; Schuetz, John D; Adachi, Yasuhisa; Hu, Zhuohan; Kusuhara, Hiroyuki; Sugiyama, Yuichi

    2007-12-01

    Olmesartan, a novel angiotensin II AT1-receptor antagonist, is excreted into both bile and urine, with minimal metabolism. Because olmesartan is a hydrophilic anionic compound, some transporters could be involved in its hepatic and renal clearance. In this study, we characterized the role of human drug transporters in the pharmacokinetics of olmesartan and determined the contribution of each transporter to the overall clearance of olmesartan. Olmesartan was significantly taken up into human embryonic kidney 293 cells expressing organic anion-transporting polypeptide (OATP) 1B1, OATP1B3, organic anion transporter (OAT) 1, and OAT3. We also observed its saturable uptake into human hepatocytes and kidney slices. Estimated from the relative activity factor method and application of specific inhibitors, the relative contributions of OATP1B1 and OATP1B3 to the uptake of olmesartan in human hepatocytes were almost the same, whereas OAT3 was predominantly involved in its uptake in kidney slices. The vectorial transport of olmesartan was observed in OATP1B1/multidrug resistance-associated protein (MRP) 2 double transfectants, but not in OATP1B1/multidrug resistance (MDR) 1 and OATP1B1/breast cancer resistance protein (BCRP) transfectants. ATP-dependent transport into membrane vesicles expressing human MRP2 and MRP4 was clearly observed, with K(m) values of 14.9 and 26.2 microM, respectively, whereas the urinary excretion of olmesartan in Mrp4-knockout mice was not different from that of control mice. We also investigated the transcellular transport of olmesartan medoxomil, a prodrug of olmesartan. Vectorial basal-to-apical transport was observed in OATP1B1/MRP2, OATP1B1/MDR1 double, and OATP1B1/BCRP double transfectants, suggesting the possible involvement of MRP2, MDR1, and BCRP in the limit of intestinal absorption of olmesartan medoxomil. From these results, we suggest that multiple transporters make a significant contribution to the pharmacokinetics of olmesartan and

  12. 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

    Science.gov (United States)

    Ju, Sung Min; Kang, Jun Gue; Bae, Jun Sang; Pae, Hyun Ock; Lyu, Yeoung Su; Jeon, Byung Hun

    2015-01-01

    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. PMID:26089934

  13. 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.

  14. Endothelin A Receptor Antagonist, Atrasentan, Attenuates Renal and Cardiac Dysfunction in Dahl Salt-Hypertensive Rats in a Blood Pressure Independent Manner

    OpenAIRE

    Samad, Mohammed A.; Kim, Ui Kyoung; Kang, Joshua J.; Ke, Qingen; Kang, Peter M.

    2015-01-01

    Proteinuria is a hallmark of chronic kidney disease (CKD) and cardiovascular disease (CVD), and a good predictor of clinical outcome. Selective endothelin A (ETA) receptor antagonist used with renin-angiotensin system (RAS) inhibitors prevents development of proteinuria in CKD. However, whether the improvement in proteinuria would have beneficial effects on CVD, independent of RAS inhibition, is not well understood. In this study, we investigated whether atrasentan, an ETA receptor antagonist...

  15. Fructus Gardenia Extract Ameliorates Oxonate-Induced Hyperuricemia with Renal Dysfunction in Mice by Regulating Organic Ion Transporters and mOIT3

    Directory of Open Access Journals (Sweden)

    Hui Ji

    2013-07-01

    Full Text Available The potent anti-hyperuricemia activities of Fructus Gardenia Extract (FGE have been well reported. The aim of this study was to evaluate the uricosuric and nephro-protective effects of FGE and explore its possible mechanisms of action in oxonate-induced hyperuricemic mice. FGE was orally administered to hyperuricemic and normal mice for 1 week. Serum and urinary levels of uric acid, creatinine and blood urea nitrogen (BUN, and fractional excretion of uric acid (FEUA were measured. The mRNA and protein levels of mouse urate transporter 1 (mURAT1, glucose transporter 9 (mGLUT9, ATP-binding cassette, subfamily G, 2 (mABCG2, organic anion transporter 1 (mOAT1, mOAT3, oncoprotein induced transcript 3 (mOIT3, organic cation/carnitine transporters in the kidney were analyzed. Simultaneously, Tamm-Horsfall glycoprotein (THP levels in urine and kidney were detected. FGE significantly reduced serum urate levels and increased urinary urate levels and FEUA in hyperuricemic mice. It could also effectively reverse oxonate-induced alterations in renal mURAT1, mGLUT9, mOAT1 and mOIT3 expressions, as well as THP levels, resulting in the enhancement of renal uric acid excretion. Moreover, FGE decreased serum creatinine and BUN levels, and up-regulated expression of organic cation/carnitine transporters, improving renal dysfunction in this model. Furthermore, FGE decreased renal mABCG2 expressions in hyperuricemic mice, contributing to its beneficial actions. However, further investigation is needed in clinical trials of FGE and its bioactive components.

  16. Naringenin ameliorates renal and platelet purinergic signalling alterations in high-cholesterol fed rats through the suppression of ROS and NF-κB signaling pathways.

    Science.gov (United States)

    Chtourou, Yassine; Kamoun, Zeineb; Zarrouk, Wissem; Kebieche, Mohammed; Kallel, Choumous; Gdoura, Radhouane; Fetoui, Hamadi

    2016-01-01

    Naringenin (NGEN) is a natural flavonoid aglycone of naringin that has been reported to have a wide range of pharmacological properties, such as antioxidant activity and free radical scavenging capacity. The aim of this study was to investigate the protective effect of NGEN on oxidative and inflammatory parameters, as well as to evaluate the hydrolysis of adenine nucleotides in kidney and platelet membranes of rats exposed to a hypercholesterolemic diet (HCD) for 90 days. Kidney oxidative stress and mRNA expression of the ectonucleoside triphosphate diphosphohydrolases (NTPDases), ecto-5'-nucleotidase (CD73), inducible NO synthase (iNOS), tumor necrosis factor-α (TNF-α), interleukin 6 (IL-6) and the nuclear factor kappa B (NF-κB) genes were evaluated by real time RT-PCR. The co-administration of NGEN (50 mg kg(-1)) for 90 days significantly prevented renal failure in HCD rats as indicated by an improvement of renal markers. Histopathological observation findings are also consistent with these effects. Moreover, NGEN (50 mg kg(-1)) significantly decreased the lipid profile and inhibited pro-oxidant and inflammation marker levels in the kidney of HCD rats. Furthermore, the NTPDase activities were significantly decreased in platelets and kidney membranes of HCD-treated rats and these alterations were improved by NGEN. In conclusion, this study suggests that naringenin can potentially improve the renal failure and platelet alterations observed in rats fed a hypercholesterolemic diet probably through its antioxidant effects. PMID:26565065

  17. 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)

    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

  18. 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.

  19. Betulinic acid ameliorates experimental diabetic-induced renal inflammation and fibrosis via inhibiting the activation of NF-κB signaling pathway.

    Science.gov (United States)

    Wang, Shaogui; Yang, Zhiying; Xiong, Fengxiao; Chen, Cheng; Chao, Xiaojuan; Huang, Junying; Huang, Heqing

    2016-10-15

    Diabetic nephropathy (DN) is the leading cause of end-stage renal failure and is characterized by excessive deposition of extracellular matrix (ECM) proteins such as fibronectin (FN), in the glomerular mesangium and tubulointerstitium. Betulinic acid (BA), a pentacyclic triterpene derived from the bark of the white birch tree, has been demonstrated to have many pharmacological activities. However, the effect of BA on DN has not been fully elucidated. To explore the possible anti-inflammatory effects of BA and their underlying mechanisms, we used streptozotocin-induced diabetic rat kidneys and high glucose-treated glomerular mesangial cells. Our study showed BA could inhibit the degradation of IκBα and the activity of NF-κB in diabetic rat kidneys and high glucose-induced mesangial cells, resulting in reduction of FN expression. In addition, BA suppressed the DNA binding activity and transcriptional activity of NF-κB in high glucose-induced glomerular mesangial cells (GMCs). Furthermore, BA enhanced the interaction between IκBα and β-arrestin2 in mesangial cells. Taken together, our data suggest BA inhibits NF-κB activation through stabilizing NF-κB inhibitory protein IκBα, thereby preventing diabetic renal fibrosis. PMID:27364889

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

    Directory of Open Access Journals (Sweden)

    Amrit Pal Singh

    2011-01-01

    Full Text Available Objective : 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. Materials and Methods : 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. Results : 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. Conclusion : 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.

  1. 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)

    Pan, Hao; Chen, Jun; Shen, Kezhen; 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

  2. A low toxicity synthetic cinnamaldehyde derivative ameliorates renal inflammation in mice by inhibiting NLRP3 inflammasome and its related signaling pathways.

    Science.gov (United States)

    Ka, Shuk-Man; Kuoping Chao, Louis; Lin, Jung-Chen; Chen, Shui-Tein; Li, Wen-Tai; Lin, Chien-Nan; Cheng, Jen-Che; Jheng, Huei-Ling; Chen, Ann; Hua, Kuo-Feng

    2016-02-01

    Uncontrolled inflammation is a leading cause of various chronic diseases. Cinnamaldehyde (CA) is a major bioactive compound isolated from the essential oil of the leaves of Cinnamomum osmophloeum kaneh that exhibits anti-inflammatory activity; however, the use of CA is limited by its cytotoxicity. Here, we synthesized three CA derivatives and identified 4-hydroxycinnamaldehyde-galactosamine (HCAG) as a low toxicity anti-inflammatory compound in vitro (HCAG IC50 ≫ 1600 µM; CA IC50=40 µM) and in vivo. HCAG reduced pro-inflammatory mediator expression in LPS-activated macrophages by inhibiting MAPK and PKC-α/δ phosphorylation, decreasing ROS generation and reducing NF-κB activation. HCAG also reduced NLRP3 inflammasome-derived IL-1β secretion by inhibiting the ATP-mediated phosphorylation of AKT and PKC-α/δ. In a mouse model of LPS-induced renal inflammation, we observed reduced albuminuria and a mild degree of glomerular proliferation, glomerular sclerosis and periglomerular inflammation in the HCAG-treated mice compared with the vehicle-treated mice. The underlying mechanisms for these renoprotective effects involved: (1) inhibited NLRP3 inflammasome activation; (2) decreased superoxide anion levels and apoptosis; and (3) suppressed activation of NF-κB and related downstream inflammatory mediators. PMID:26675345

  3. Cordyceps militaris fruit body extract ameliorates membranous glomerulonephritis by attenuating oxidative stress and renal inflammation via the NF-κB pathway.

    Science.gov (United States)

    Song, Jingjing; Wang, Yingwu; Liu, Chungang; Huang, Yan; He, Liying; Cai, Xueying; Lu, Jiahui; Liu, Yan; Wang, Di

    2016-04-01

    Membranous glomerulonephritis (MGN) is a common pathogenesis of nephritic syndrome in adult patients. Nuclear factor kappa B (NF-κB) serves as the main transcription factor for the inflammatory response mediated nephropathy. Cordyceps militaris, containing various pharmacological components, has been used as a kind of crude drug and folk tonic food for improving immunity and reducing inflammation. The current study aims to investigate the renoprotective activity of Cordyceps militaris aqueous extract (CM) in the cationic bovine serum albumin (C-BSA)-induced rat model of membranous glomerulonephritis. Significant renal dysfunction was observed in MGN rats; comparatively, 4-week CM administration strongly decreased the levels of 24 h urine protein, total cholesterol, triglyceride, blood urea nitrogen and serum creatinine, and increased the levels of serum albumin and total serum protein. Strikingly, recovery of the kidney histological architecture was noted in CM-treated MGN rats. A significant improvement in the glutathione peroxidase and superoxide dismutase levels, and a reduced malondialdehyde concentration were observed in the serum and kidney of CM-treated rats. Altered levels of inflammatory cytokines including interleukins, monocyte chemoattractant protein-1, intercellular adhesion molecule 1, vascular adhesion molecule 1, tumor necrosis factor-α, 6-keto-prostaglandin F1α, and nuclear transcriptional factor subunit NF-κB p65 reverted to normal levels upon treatment with CM. The present data suggest that CM protects rats against membranous glomerulonephritis via the normalization of NF-κB activity, thereby inhibiting oxidative damage and reducing inflammatory cytokine levels, which further provide experimental evidence in support of the clinical use of CM as an effective renoprotective agent. PMID:27008597

  4. Effects of silica exposure on the cardiac and renal inflammatory and fibrotic response and the antagonistic role of interleukin-1 beta in C57BL/6 mice.

    Science.gov (United States)

    Guo, Jiali; Shi, Tingming; Cui, Xiuqing; Rong, Yi; Zhou, Ting; Zhang, Zhihong; Liu, Yuewei; Shen, Yan; Chen, Weihong

    2016-02-01

    Current epidemiological studies suggest that crystalline silica exposure is associated with an increased risk of cardiovascular and renal disease; however, the potential pathological damage of the heart and kidney and its underlying mechanisms have not been completely elucidated. This study tried to investigate the silica-induced inflammatory and fibrotic changes in the heart and kidney and evaluate the role of interleukin (IL)-1 beta (β) in silica-induced cardiac and renal damage. In this study, a silica-exposed model was generated by intratracheally instilling silica dust in mice. The anti-IL-1β monoclonal antibody (mAb) was used to neutralise IL-1β in the pulmonary alveolus and serum. The real-time PCR studies showed that (1) inhalational silica induced inflammatory responses in the heart and kidney by elevated mRNA levels of TNF-α, IL-6 and MCP-1; (2) early fibrotic responses in the heart were observed as elevated mRNA levels of collagen I and fibronectin. What is more, fibrosis of the kidney was demonstrated by pathological results and significantly increased mRNA levels of TGF-β, collagen I, collagen III and fibronectin. Further studies showed that usage of anti-IL-1β mAb decreased the inflammatory response of the heart and kidney induced by inhalational silica and also attenuated fibrosis in the mouse kidney. In conclusion, this study found that inhaled silica induced inflammatory and early fibrotic responses in the mouse heart and inflammatory response and fibrosis in the mouse kidney. Neutralisation of IL-1β attenuated the silica-induced inflammatory response of the heart and kidney and decreased fibrosis in the mouse kidney. PMID:25388157

  5. Renoprotective Effects of a Highly Selective A3 Adenosine Receptor Antagonist in a Mouse Model of Adriamycin-induced Nephropathy.

    Science.gov (United States)

    Min, Hye Sook; Cha, Jin Joo; Kim, Kitae; Kim, Jung Eun; Ghee, Jung Yeon; Kim, Hyunwook; Lee, Ji Eun; Han, Jee Young; Jeong, Lak Shin; Cha, Dae Ryong; Kang, Young Sun

    2016-09-01

    The concentration of adenosine in the normal kidney increases markedly during renal hypoxia, ischemia, and inflammation. A recent study reported that an A3 adenosine receptor (A3AR) antagonist attenuated the progression of renal fibrosis. The adriamycin (ADX)-induced nephropathy model induces podocyte injury, which results in severe proteinuria and progressive glomerulosclerosis. In this study, we investigated the preventive effect of a highly selective A3AR antagonist (LJ1888) in ADX-induced nephropathy. Three groups of six-week-old Balb/c mice were treated with ADX (11 mg/kg) for four weeks and LJ1888 (10 mg/kg) for two weeks as following: 1) control; 2) ADX; and 3) ADX + LJ1888. ADX treatment decreased body weight without a change in water and food intake, but this was ameliorated by LJ1888 treatment. Interestingly, LJ1888 lowered plasma creatinine level, proteinuria, and albuminuria, which had increased during ADX treatment. Furthermore, LJ1888 inhibited urinary nephrin excretion as a podocyte injury marker, and urine 8-isoprostane and kidney lipid peroxide concentration, which are markers of oxidative stress, increased after injection of ADX. ADX also induced the activation of proinflammatory and profibrotic molecules such as TGF-β1, MCP-1, PAI-1, type IV collagen, NF-κB, NOX4, TLR4, TNFα, IL-1β, and IFN-γ, but they were remarkably suppressed after LJ1888 treatment. In conclusion, our results suggest that LJ1888 has a renoprotective effect in ADX-induced nephropathy, which might be associated with podocyte injury through oxidative stress. Therefore, LJ1888, a selective A3AR antagonist, could be considered as a potential therapeutic agent in renal glomerular diseases which include podocyte injury and proteinuria. PMID:27510383

  6. GABAB antagonists

    DEFF Research Database (Denmark)

    Frydenvang, Karla Andrea; Hansen, J J; Krogsgaard-Larsen, P;

    1994-01-01

    Phaclofen, which is the phosphonic acid analogue of the GABAB agonist (RS)-3-(4-chlorophenyl)-4-aminobutyric acid (baclofen), is a GABAB antagonist. As part of our studies on the structural requirements for activation and blockade of GABAB receptors, we have resolved phaclofen using chiral...... chromatographic techniques. The absolute stereochemistry of (-)-(R)-phaclofen was established by X-ray crystallographic analysis. (-)-(R)-Phaclofen was shown to inhibit the binding of [3H]-(R)-baclofen to GABAB receptor sites on rat cerebellar membranes (IC50 = 76 +/- 13 microM), whereas (+)-(S)-phaclofen was...... inactive in this binding assay (IC50 > 1000 microM). (-)-(R)-Phaclofen (200 microM) was equipotent with (RS)-phaclofen (400 microM) in antagonizing the action of baclofen in rat cerebral cortical slices, while (+)-(S)-phaclofen (200 microM) was inactive. The structural similarity of the agonist (R)-baclofen...

  7. ACTH Antagonists

    Science.gov (United States)

    Clark, Adrian John; Forfar, Rachel; Hussain, Mashal; Jerman, Jeff; McIver, Ed; Taylor, Debra; Chan, Li

    2016-01-01

    Adrenocorticotropin (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 while preparing for definitive treatment of a causative tumor, 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. PMID:27547198

  8. Immunosuppressive Treatment Protects Against Angiotensin II-Induced Renal Damage

    OpenAIRE

    Muller, Dominik N.; Shagdarsuren, Erdenechimeg; Park, Joon-Keun; Dechend, Ralf; Mervaala, Eero; Hampich, Franziska; Fiebeler, Anette; Ju, Xinsheng; Finckenberg, Piet; Theuer, Jürgen; Viedt, Christiane; Kreuzer, Joerg; Heidecke, Harald; Haller, Hermann; Zenke, Martin

    2002-01-01

    Angiotensin (Ang) II promotes renal infiltration by immunocompetent cells in double-transgenic rats (dTGRs) harboring both human renin and angiotensinogen genes. To elucidate disease mechanisms, we investigated whether or not dexamethasone (DEXA) immunosuppression ameliorates renal damage. Untreated dTGRs developed hypertension, renal damage, and 50% mortality at 7 weeks. DEXA reduced albuminuria, renal fibrosis, vascular reactive oxygen stress, and prevented mortality, independent of blood p...

  9. Endothelin receptors and their antagonists.

    Science.gov (United States)

    Maguire, Janet J; Davenport, Anthony P

    2015-03-01

    All three members of the endothelin (ET) family of peptides, ET-1, ET-2, and ET-3, are expressed in the human kidney, with ET-1 being the predominant isoform. ET-1 and ET-2 bind to two G-protein-coupled receptors, ETA and ETB, whereas at physiological concentrations ET-3 has little affinity for the ET(A) receptor. The human kidney is unusual among the peripheral organs in expressing a high density of ET(B). The renal vascular endothelium only expresses the ET(B) subtype and ET-1 acts in an autocrine or paracrine manner to release vasodilators. Endothelial ETB in kidney, as well as liver and lungs, also has a critical role in scavenging ET-1 from the plasma. The third major function is ET-1 activation of ET(B) in in the nephron to reduce salt and water re-absorption. In contrast, ET(A) predominate on smooth muscle, causing vasoconstriction and mediating many of the pathophysiological actions of ET-1. The role of the two receptors has been delineated using highly selective ET(A) (BQ123, TAK-044) and ET(B) (BQ788) peptide antagonists. Nonpeptide antagonists, bosentan, macitentan, and ambrisentan, that are either mixed ET(A)/ET(B) antagonists or display ET(A) selectivity, have been approved for clinical use but to date are limited to pulmonary hypertension. Ambrisentan is in clinical trials in patients with type 2 diabetic nephropathy. This review summarizes ET-receptor antagonism in the human kidney, and considers the relative merits of selective versus nonselective antagonism in renal disease. PMID:25966344

  10. Trauma renal Renal trauma

    Directory of Open Access Journals (Sweden)

    Gerson Alves Pereira Júnior

    1999-02-01

    Full Text Available Apresentamos uma revisão sobre trauma renal, com ênfase na avaliação radiológica, particularmente com o uso da tomografia computadorizada, que tem se tornado o exame de eleição, ao invés da urografia excretora e arteriografia. O sucesso no tratamento conservador dos pacientes com trauma renal depende de um acurado estadiamento da extensão da lesão, classificado de acordo com a Organ Injury Scaling do Colégio Americano de Cirurgiões. O tratamento conservador não-operatório é seguro e consiste de observação contínua, repouso no leito, hidratação endovenosa adequada e antibioti- coterapia profilática, evitando-se uma exploração cirúrgica desnecessária e possível perda renal. As indicações para exploração cirúrgica imediata são abdome agudo, rápida queda do hematócrito ou lesões associadas determinadas na avaliação radiológica. Quando indicada, a exploração renal após controle vascular prévio é segura, permitindo cuidadosa inspeção do rim e sua reconstrução com sucesso, reduzindo a probabilidade de nefrectomia.We present a revision of the renal trauma with emphasis in the radiographic evaluation, particularly CT scan that it has largely replaced the excretory urogram and arteriogram in the diagnostic worh-up and management of the patient with renal trauma. The successful management of renal injuries depends upon the accurate assessment of their extent in agreement with Organ Injury Scaling classification. The conservative therapy managed by careful continuous observation, bed rest, appropriate fluid ressuscitation and prophylactic antibiotic coverage after radiographic staging for severely injured kidneys can yield favorable results and save patients from unnecessary exploration and possible renal loss. The indications for immediate exploratory laparotomy were acute abdomen, rapidly dropping hematocrit or associated injuries as determinated from radiologic evaluation. When indicated, renal exploration

  11. Effects of angiotensin Ⅱ receptor antagonist on expression of plasminogen activator inhibitor-1 in the renal biopsy of patients with chronic kidney disease%血管紧张素Ⅱ受体拮抗剂对慢性肾脏病患者肾组织中纤溶酶原激活物抑制物-1表达的影响

    Institute of Scientific and Technical Information of China (English)

    王文革; 李侠

    2010-01-01

    Objective To evaluate the effects of angiotensin Ⅱreceptor antagonist (ARB) on expression of plasminogen activator inhibitor(PAI)-1 in the human renal biopsy of patients with chronic kidney disease(CKD)and analyse its clinical significance.Methods PAI-1 expression of 63 specimens with CKD was detected by immunohistochemistry and quantitative analysis was achieved by image analysis system. meanwhile, the patients'clinical data were collected,and PAI-1 expression of 63 specimens with CKD was compared with that of normal renal tissue(19 cases).Results Compared with the normal renal tissue,the expression of PAI-1 in CKD 1,2 and 3 stage wag respectively drastically increased(P<0.05).The expression of PAI-1 in CKD 3 stage was higher than that in CKD 1 and 2 stage(P<0.05).The expression of PAI-1 in the patients treated by valsartan[renal corpuscle(4.73±1.18)%,renal tubule(37.16±6.81)%]was lower than that with no treatment[renal corpuscle(5.81±1.95)%,renal tubule(43.22 ±10.25)%](P<0.05).Conclusions It suggests that the abnormal expression of PAI-1 in CKD play an important role in the progression of glomerular and tubulointerstitiai sclerosis in patients with CKD.ARB may prevent the development of renal inflammation and sclerosis by inhibiting the production of PAI-1.ARB may contribute to the prevention and therapy of CKD.%目的 探讨血管紧张索Ⅱ受体拮抗剂(ARB)对慢性肾脏病(CKD)患者肾组织中纤溶酶原激活物抑制物(PAI)-1表达的影响及临床意义.方法 采用免疫组化法检测63例CKD患者肾穿刺标本中PAI-1的表达水平,用图像分析法对PAI-1进行定量测定,同时收集患者的相关临床资料,并与因肾肿瘤切除肾脏的远离肿瘤部分的正常肾组织19例比较.结果 CKD 1、2、3期患者PAI-1在肾组织中的表达均较正常肾组织显著增多(P<0.05);而CKD 3期患者PAI-1在肾组织中的表达明显高于CKDI期和2期患者(P<0.05).应用缬沙坦治疗的CKD 16例患者肾组织中PAI-1

  12. Ondansetron, a 5-HT3 antagonist, improves cerebellar tremor.

    OpenAIRE

    Rice, G P; Lesaux, J; Vandervoort, P.; Macewan, L; Ebers, G C

    1997-01-01

    It has been previously shown that ondansetron, a 5-HT3 antagonist, can ameliorate vertigo in patients with acute brainstem disorders. A coincidental benefit was the improvement of cerebellar tremor in some patients with both vertigo and tremor. To further evaluate this effect, a placebo controlled, double blind, crossover study was conducted of a single dose of intravenous ondansetron in 20 patients with cerebellar tremor caused by multiple sclerosis, cerebellar degeneration, or drug toxicity...

  13. ACE Inhibition in Anti-Thy1 Glomerulonephritis Limits Proteinuria but Does Not Improve Renal Function and Structural Remodeling

    Directory of Open Access Journals (Sweden)

    Peter E. Westerweel

    2012-01-01

    Full Text Available Background/Aims: ACE inhibitor (ACE-I treatment effectively inhibits proteinuria and ameliorates the course of various renal diseases. In experimental glomerulonephritis, however, angiotensin II (AngII infusion has also been shown to be renoprotective. We evaluated the long-term (28 days course of anti-Thy1 glomerulonephritis in animals with suppressed AngII formation by ACE-I treatment. Methods: Brown Norway rats received perindopril (2.8 mg/kg/day, n = 12, dihydropyridine calcium-antagonist amlodipine (Ca-A; 13 mg/kg/day, n = 6 or were left untreated (n = 14. All animals were monitored for blood pressure, proteinuria, and creatinine clearance after anti-Thy1 injection. Renal histology was assessed at day 7 and 28. Results: Systolic blood pressure was equally reduced by ACE-I and Ca-A treatment. AngII suppression prevented development of proteinuria, but did not protect against glomerular microaneurysm formation or reduction in creatinine clearance. After resolution of the microaneurysms, animals with suppressed AngII production showed a modest increase in glomerulosclerosis and vasculopathic thickening of intrarenal vessels. Conclusions: In anti-Thy1 glomerulonephritis, suppression of AngII formation does not protect against the induction of glomerular damage and is associated with mild aggravation of adverse renal fibrotic remodeling. Proteinuria, however, is effectively prevented by ACE-I treatment. Ca-A treatment did not affect the course of glomerulonephritis, indicating that ACE-I effects are blood pressure independent.

  14. Renal angiomyolipoma

    DEFF Research Database (Denmark)

    Holm-Nielsen, P; Sørensen, Flemming Brandt

    1988-01-01

    Renal angiomyolipoma is a rare lesion composed of smooth muscle cells, adipose tissue and abnormal vessels. It is currently classified as a benign, non-epithelial renal tumor. It has a high incidence in patients suffering from tuberous sclerosis but is more frequently found as an isolated renal...

  15. A Foldable Antagonistic Actuator

    OpenAIRE

    Shintake, Jun; Rosset, Samuel; Schubert, Bryan Edward; Floreano, Dario; Shea, Herbert

    2015-01-01

    We report on an actuator based on dielectric elastomers that is capable of antagonistic actuation and passive folding. This actuator enables foldability in robots with simple structures. Unlike other antagonistic dielectric elastomer devices, our concept uses elastic hinges to allow the folding of the structure, which also provides an additional design parameter. To validate the actuator concept through a specific application test, a foldable elevon actuator with outline size of 70 mm × 130 m...

  16. RENAL CRYOABLATION

    Directory of Open Access Journals (Sweden)

    A. V. Govorov

    2014-08-01

    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.

  17. Renal liposarcoma

    Directory of Open Access Journals (Sweden)

    Diogo A.L. Bader

    2004-06-01

    Full Text Available INTRODUCTION: Liposarcoma is a malignant mesenchymal tumor frequently located in retroperitoneum, and rarely presenting an isolated lesion in kidney. CASE REPORT: Female, Caucasian, 49-year old patient, with family history of renal polycystic disease, was selected for organ donation. During preoperative examinations a renal pleomorphic liposarcoma was detected. She was treated with radical nephrectomy and remains asymptomatic, without evidences of recurrence in control ecographic examinations after a 4-year follow-up. COMMENTS: Renal liposarcoma is a rare tumor. We report one case incidentally diagnosed during a routine pre-transplantation assessment in renal donor.

  18. 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. PMID:25855780

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

    International Nuclear Information System (INIS)

    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, [3H]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

  20. [Renal elastography].

    Science.gov (United States)

    Correas, Jean-Michel; Anglicheau, Dany; Gennisson, Jean-Luc; Tanter, Mickael

    2016-04-01

    Renal elastography has become available with the development of noninvasive quantitative techniques (including shear-wave elastography), following the rapidly growing field of diagnosis and quantification of liver fibrosis, which has a demonstrated major clinical impact. Ultrasound or even magnetic resonance techniques are leaving the pure research area to reach the routine clinical use. With the increased incidence of chronic kidney disease and its specific morbidity and mortality, the noninvasive diagnosis of renal fibrosis can be of critical value. However, it is difficult to simply extend the application from one organ to the other due to a large number of anatomical and technical issues. Indeed, the kidney exhibits various features that make stiffness assessment more complex, such as the presence of various tissue types (cortex, medulla), high spatial orientation (anisotropy), local blood flow, fatty sinus with variable volume and echotexture, perirenal space with variable fatty content, and the variable depth of the organ. Furthermore, the stiffness changes of the renal parenchyma are not exclusively related to fibrosis, as renal perfusion or hydronephrosis will impact the local elasticity. Renal elastography might be able to diagnose acute or chronic obstruction, or to renal tumor or pseudotumor characterization. Today, renal elastography appears as a promising application that still requires optimization and validation, which is the contrary for liver stiffness assessment. PMID:26976058

  1. 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.

  2. Osteodistrofia renal

    OpenAIRE

    Teles, Tobias José Freitas Trindade

    2014-01-01

    A doença renal crónica é um problema de saúde mundial, com incidência e prevalência crescentes. Apesar dos avanços científicos na compreensão da patogénese e o desenvolvimento de terapêuticas mais eficazes, a osteodistrofia renal continua a ser uma complicação importante nos doentes renais crónicos. A osteodistrofia renal abrange um espectro diverso de alterações ósseas nos doentes com doença renal crónica, classificada histologicamente por lesões de elevada ou baixa taxa de remodelação ó...

  3. Renal failure

    Institute of Scientific and Technical Information of China (English)

    1993-01-01

    930150 Epidermal growth factor and its recep-tor in the renal tissue of patients with acute re-nal failure and normal persons.LIU Zhihong(刘志红),et al.Jinling Hosp,Nanjing,210002.Natl Med J China 1992;72(10):593-595.Epidermal growth factor(EGF)and its receptor(EGF-R)were identified by immunohis-tochemical method(4 layer PAP)in the renaltissue specimens obtained from 11 normal kid-neys and 17 cases of acute renal failure(ARF).The quantitative EGF and EGF-R in the tissuewere expressed as positive tubules per mm~2.The amount of EGF and EGF-R in renal tissue

  4. Renal failure

    Institute of Scientific and Technical Information of China (English)

    2005-01-01

    2005234 Association between serum fetuin-A and clinical outcome in end-stage renal disease patients. WANG Kai(王开), Dept Renal Dis, Renji Hosp Shanghai, 2nd Med Univ, Shanghai 200001. Chin J Nephrol, 2005;21(2):72-75. Objective: To investigate the change of serum fetuin-A level before and after dialysis, and the association of serum fetuin-A level with clinical parameters

  5. Renal failure

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    2008463 Protective effect of recombination rat augmenter of liver regeneration on kidney in acute renal failure rats. TANG Xiaopeng(唐晓鹏), et al. Dept Nephrol, 2nd Affili Hosp Chongqing Med Univ, Chongqing 400010.Chin J Nephrol 2008;24(6):417-421. Objective To investigate the protective effects of recombination rat augmenter of liver regeneration (rrALR) on tubular cell injury and renal dysfunction

  6. Renal failure

    Institute of Scientific and Technical Information of China (English)

    1995-01-01

    950351 Serum erythropoietin levels in chronic renalinsufficiency.ZHAI Depei(翟德佩),et al.DeptNephrol.General Hosp,Tianjin Med Univ,Tianjin,300000.Tianjin Med J 1995;23(1):19-21.Patients with chronic renal insufficiency(CRI) areoften associated with anemia.The deficiency of EPOproduction in the kidney is thought to be a key factorin the pathogenesis of renal anemia.Serum erythropoi-

  7. Renal liposarcoma

    OpenAIRE

    Diogo A.L. Bader; Luis A.B. Peres; Sérgio L. Bader

    2004-01-01

    INTRODUCTION: Liposarcoma is a malignant mesenchymal tumor frequently located in retroperitoneum, and rarely presenting an isolated lesion in kidney. CASE REPORT: Female, Caucasian, 49-year old patient, with family history of renal polycystic disease, was selected for organ donation. During preoperative examinations a renal pleomorphic liposarcoma was detected. She was treated with radical nephrectomy and remains asymptomatic, without evidences of recurrence in control ecographic examinations...

  8. Dexmedetomidine preconditioning ameliorates kidney ischemia-reperfusion injury

    Science.gov (United States)

    Lempiäinen, Juha; Finckenberg, Piet; Mervaala, Elina E; Storvik, Markus; Kaivola, Juha; Lindstedt, Ken; Levijoki, Jouko; Mervaala, Eero M

    2014-01-01

    Kidney ischemia-reperfusion (I/R) injury is a common cause of acute kidney injury. We tested whether dexmedetomidine (Dex), an alpha2 adrenoceptor (α2-AR) agonist, protects against kidney I/R injury. Sprague–Dawley rats were divided into four groups: (1) Sham-operated group; (2) I/R group (40 min ischemia followed by 24 h reperfusion); (3) I/R group + Dex (1 μg/kg i.v. 60 min before the surgery), (4) I/R group + Dex (10 μg/kg). The effects of Dex postconditiong (Dex 1 or 10 μg/kg i.v. after reperfusion) as well as the effects of peripheral α2-AR agonism with fadolmidine were also examined. Hemodynamic effects were monitored, renal function measured, and acute tubular damage along with monocyte/macrophage infiltration scored. Kidney protein kinase B, toll like receptor 4, light chain 3B, p38 mitogen-activated protein kinase (p38 MAPK), sirtuin 1, adenosine monophosphate kinase (AMPK), and endothelial nitric oxide synthase (eNOS) expressions were measured, and kidney transciptome profiles analyzed. Dex preconditioning, but not postconditioning, attenuated I/R injury-induced renal dysfunction, acute tubular necrosis and inflammatory response. Neither pre- nor postconditioning with fadolmidine protected kidneys. Dex decreased blood pressure more than fadolmidine, ameliorated I/R-induced impairment of autophagy and increased renal p38 and eNOS expressions. Dex downregulated 245 and upregulated 61 genes representing 17 enriched Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, in particular, integrin pathway and CD44. Ingenuity analysis revealed inhibition of Rac and nuclear factor (erythroid-derived 2)-like 2 pathways, whereas aryl hydrocarbon receptor (AHR) pathway was activated. Dex preconditioning ameliorates kidney I/R injury and inflammatory response, at least in part, through p38-CD44-pathway and possibly also through ischemic preconditioning. PMID:25505591

  9. [Renal disease].

    Science.gov (United States)

    Espinosa-Cuevas, María de Los Ángeles

    2016-09-01

    Chronic renal failure in its various stages, requires certain nutritional restrictions associated with the accumulation of minerals and waste products that cannot be easily eliminated by the kidneys. Some of these restrictions modify the intake of proteins, sodium, and phosphorus. Milk and dairy products are sources of these nutrients. This article aims to inform the reader about the benefits including milk and dairy products relying on a scientific and critical view according to the clinical conditions and the stage of renal disease in which the patient is. PMID:27603894

  10. Selective orexin receptor antagonists.

    Science.gov (United States)

    Lebold, Terry P; Bonaventure, Pascal; Shireman, Brock T

    2013-09-01

    The orexin, or hypocretin, neuropeptides (orexin-A and orexin-B) are produced on neurons in the hypothalamus which project to key areas of the brain that control sleep-wake states, modulation of food intake, panic, anxiety, emotion, reward and addictive behaviors. These neuropeptides exert their effects on a pair of G-protein coupled receptors termed the orexin-1 (OX1) and orexin-2 (OX2) receptors. Emerging biology suggests the involvement of these receptors in psychiatric disorders as they are thought to play a key role in the regulation of multiple systems. This review is intended to highlight key selective OX1 or OX2 small-molecule antagonists. PMID:23891187

  11. Renal (Kidney) Manifestations in TSC

    Medline Plus

    Full Text Available ... in TSC: renal cysts, renal angiomyolipoma and renal cell carcinoma . Renal angiomyolipomata, or angiomyolipomas, are usually the ... kidney failure, requiring dialysis or transplantation. Lastly, renal cell carcinoma, the least common renal association with TSC, ...

  12. Renal failure

    Institute of Scientific and Technical Information of China (English)

    1997-01-01

    970363 Effect on serum PTH and 1, 25(OH)2 D3levels of rapid correction of metabolic acidosis in CRFpatients with secondary hyperparathyroidism. YUANQunsheng(袁群生), et al. Renal Div, PUMC Hosp,Beijing, 100730. Chin J Nephrol 1996; 12(6): 328-331.

  13. Renal failure (chronic)

    OpenAIRE

    Clase, Catherine

    2009-01-01

    Chronic renal failure is characterised by a gradual and sustained decline in renal clearance or glomerular filtration rate (GFR). Continued progression of renal failure will lead to renal function too low to sustain healthy life. In developed countries, such people will be offered renal replacement therapy in the form of dialysis or renal transplantation. Requirement for dialysis or transplantation is termed end-stage renal disease (ESRD).Diabetes, glomerulonephritis, hypertension, pyelone...

  14. Sesamin Ameliorates High-Fat Diet–Induced Dyslipidemia and Kidney Injury by Reducing Oxidative Stress

    Science.gov (United States)

    Zhang, Ruijuan; Yu, Yan; Deng, Jianjun; Zhang, Chao; Zhang, Jinghua; Cheng, Yue; Luo, Xiaoqin; Han, Bei; Yang, Haixia

    2016-01-01

    The study explored the protective effect of sesamin against lipid-induced renal injury and hyperlipidemia in a rat model. An animal model of hyperlipidemia was established in Sprague-Dawley rats. Fifty-five adult Sprague-Dawley rats were divided into five groups. The control group was fed a standard diet, while the other four groups were fed a high-fat diet for 5 weeks to induce hyperlipidemia. Three groups received oral sesamin in doses of 40, 80, or 160 mg/(kg·day). Seven weeks later, the blood lipids, renal function, antioxidant enzyme activities, and hyperoxide levels in kidney tissues were measured. The renal pathological changes and expression levels of collagen type IV (Col-IV) and α-smooth muscle actin (α-SMA) were analyzed. The administration of sesamin improved the serum total cholesterol, triglyceride, low-density lipoprotein cholesterol, apolipoprotein-B, oxidized-low-density lipoprotein, and serum creatinine levels in hyperlipidemic rats, while it increased the high-density lipoprotein cholesterol and apolipoprotein-A levels. Sesamin reduced the excretion of 24-h urinary protein and urinary albumin and downregulated α-SMA and Col-IV expression. Moreover, sesamin ameliorated the superoxide dismutase activity and reduced malondialdehyde levels in kidney tissue. Sesamin could mediate lipid metabolism and ameliorate renal injury caused by lipid metabolism disorders in a rat model of hyperlipidemia. PMID:27171111

  15. Sesamin Ameliorates High-Fat Diet–Induced Dyslipidemia and Kidney Injury by Reducing Oxidative Stress

    Directory of Open Access Journals (Sweden)

    Ruijuan Zhang

    2016-05-01

    Full Text Available The study explored the protective effect of sesamin against lipid-induced renal injury and hyperlipidemia in a rat model. An animal model of hyperlipidemia was established in Sprague-Dawley rats. Fifty-five adult Sprague-Dawley rats were divided into five groups. The control group was fed a standard diet, while the other four groups were fed a high-fat diet for 5 weeks to induce hyperlipidemia. Three groups received oral sesamin in doses of 40, 80, or 160 mg/(kg·day. Seven weeks later, the blood lipids, renal function, antioxidant enzyme activities, and hyperoxide levels in kidney tissues were measured. The renal pathological changes and expression levels of collagen type IV (Col-IV and α-smooth muscle actin (α-SMA were analyzed. The administration of sesamin improved the serum total cholesterol, triglyceride, low-density lipoprotein cholesterol, apolipoprotein-B, oxidized-low-density lipoprotein, and serum creatinine levels in hyperlipidemic rats, while it increased the high-density lipoprotein cholesterol and apolipoprotein-A levels. Sesamin reduced the excretion of 24-h urinary protein and urinary albumin and downregulated α-SMA and Col-IV expression. Moreover, sesamin ameliorated the superoxide dismutase activity and reduced malondialdehyde levels in kidney tissue. Sesamin could mediate lipid metabolism and ameliorate renal injury caused by lipid metabolism disorders in a rat model of hyperlipidemia.

  16. Sesamin Ameliorates High-Fat Diet-Induced Dyslipidemia and Kidney Injury by Reducing Oxidative Stress.

    Science.gov (United States)

    Zhang, Ruijuan; Yu, Yan; Deng, Jianjun; Zhang, Chao; Zhang, Jinghua; Cheng, Yue; Luo, Xiaoqin; Han, Bei; Yang, Haixia

    2016-01-01

    The study explored the protective effect of sesamin against lipid-induced renal injury and hyperlipidemia in a rat model. An animal model of hyperlipidemia was established in Sprague-Dawley rats. Fifty-five adult Sprague-Dawley rats were divided into five groups. The control group was fed a standard diet, while the other four groups were fed a high-fat diet for 5 weeks to induce hyperlipidemia. Three groups received oral sesamin in doses of 40, 80, or 160 mg/(kg·day). Seven weeks later, the blood lipids, renal function, antioxidant enzyme activities, and hyperoxide levels in kidney tissues were measured. The renal pathological changes and expression levels of collagen type IV (Col-IV) and α-smooth muscle actin (α-SMA) were analyzed. The administration of sesamin improved the serum total cholesterol, triglyceride, low-density lipoprotein cholesterol, apolipoprotein-B, oxidized-low-density lipoprotein, and serum creatinine levels in hyperlipidemic rats, while it increased the high-density lipoprotein cholesterol and apolipoprotein-A levels. Sesamin reduced the excretion of 24-h urinary protein and urinary albumin and downregulated α-SMA and Col-IV expression. Moreover, sesamin ameliorated the superoxide dismutase activity and reduced malondialdehyde levels in kidney tissue. Sesamin could mediate lipid metabolism and ameliorate renal injury caused by lipid metabolism disorders in a rat model of hyperlipidemia. PMID:27171111

  17. 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; Holstein-Rathlou, Niels-Henrik; Deacon, Carolyn F; Jensen, Boye L; Holst, Jens J; Sorensen, Charlotte Mehlin

    2015-01-01

    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 (125)I-GLP-1......, (125)I-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...

  18. 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 inde

  19. Sulphasalazine induced renal failure.

    OpenAIRE

    Dwarakanath, A D; Michael, J.; Allan, R. N.

    1992-01-01

    Two men with longstanding ulcerative colitis who were treated with sulphasalazine for several years and who developed chronic renal failure are reported. Renal biopsy specimens showed histological changes consistent with drug induced chronic intestinal nephritis. Extensive investigation made other causes of chronic renal failure unlikely. One of these patients underwent renal transplantation, the other has impaired but stable renal function.

  20. Renal candidiasis

    International Nuclear Information System (INIS)

    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

  1. Nebivolol Ameliorates Nitric Oxide–Deficient Hypertension

    Directory of Open Access Journals (Sweden)

    L.A. Fortepiani

    2002-01-01

    Full Text Available Nebivolol is a new selective beta 1-adrenoceptor antagonist with nitric oxide (NO–releasing properties. In the present study we have analyzed whether nebivolol affects the development of the arterial hypertension that follows the chronic inhibition of nitric oxide synthesis. Nebivolol (1 mg/kg/day, 14 days was given concurrently with the NO synthesis inhibitor Nw-nitro-L-arginine methyl ester (L-NAME, 0.1, 1, and 10 mg/kg/day, 14 days to several groups of rats. Blood pressure, renal function, plasma renin activity (PRA, and NO activity and metabolites were measured at the end of the treatment period. L-NAME treatment alone increased mean arterial pressure dose dependently (103.5 ± 2.4, 110.9 ± 2.0, and 125.8 ± 2.2 mmHg, respectively. Nebivolol completely prevented the development of arterial hypertension in the groups treated with L-NAME at the doses of 0.1 and 1 mg/kg/day and reduced the increase achieved with the L-NAME dose of 10 mg/kg/day (110.3 ± 2.7. There were no differences in glomerular filtration rate or natriuresis between nebivolol-treated and -untreated rats. Plasma nitrates+nitrites and calcium-dependent NO synthase activity in the kidney also decreased dose dependently with L-NAME treatment and nebivolol did not significantly modify it. However, PRA was lower in all groups treated with nebivolol and L-NAME as compared to the rats receiving only L-NAME. These data indicate that nebivolol prevents the development of the arterial hypertension associated with chronic NO deficit and this effect seems to be dependent on the inhibition of renin-angiotensin system.

  2. Renal artery embolization in severe nephrotic syndrome.

    Science.gov (United States)

    Solak, Yalcin; Koc, Osman; Ucar, Ramazan; Ozbek, Orhan; Ergenc, Hasan; Gaipov, Abduzhappar; Turk, Suleyman

    2016-07-01

    Introduction Severe nephrotic syndrome is associated with increased morbidity and mortality. Renal artery embolization (RAE) has been used in a number of renal diseases such as renal tumors, arteriovenous fistulas etc. However, data regarding benefits of RAE in patients with symptomatic severe proteinuria is limited. We decided to evaluate role of RAE in the setting of severe symptomatic nephrotic syndrome. Methods Eight patients who had undergone transcatheter renal artery embolization with polyvinyl alcohol (PVA) were included. Clinico-demographic characteristics as well as baseline laboratory data including level of proteinuria, serum albumin, C-reactive protein and LDL cholesterol levels were recorded for each patient. After RAE, outpatient clinic control laboratory values were also assessed. Findings All patients except one underwent bilateral RAE (four simultaneous or three sequential). Two patients experienced postembolization syndrome characterized by flank pain, fever, and leukocytosis, which was self-limited and responded to analgesics in all patients. There was no technical complications associated with RAE procedure. All patients became anuric except one. Serum albumin levels increased and serum LDL-cholesterol levels decreased considerably in treated patients. Discussion Renal artery embolization with the purpose of amelioration in nephrotic syndrome complications was effective and free of major technical complications in our patients. PMID:26833695

  3. Pharmacological management of renal colic in the older patient.

    Science.gov (United States)

    Welk, Blayne K; Teichman, Joel M H

    2007-01-01

    Renal colic affects up to 12% of the population. Initial management of most patients is expectant. Acute symptom management of renal colic is best accomplished with a combination of parenteral opioids and NSAIDs. The elderly patient with a kidney stone should be screened for contraindications to NSAID therapy, such as renal failure or previous peptic ulcer disease. Use of parenteral opioids is often necessary during the acute setting, and downward-adjusted doses and monitoring are necessary to prevent associated confusion and respiratory depression. Novel therapy with desmopressin may also be effective for symptom control at the initial presentation, without the adverse effects of opioids or NSAIDs. However, use of desmopressin in the elderly must be undertaken cautiously, given the potential adverse effects of this agent. Many small, distal ureteral stones are treated initially with watchful waiting for the first 2-4 weeks after presentation. The patient should have effective, non-parenteral analgesics for use at home. Included in these agents are oral or suppository NSAIDs and oral opioids. Medical expulsion therapy with alpha-adrenoceptor antagonists or calcium channel antagonists is efficacious. alpha-Adrenoceptor antagonists such as the alpha(1A/)(1)(D)-selective tamsulosin are well tolerated in the elderly and increase the rate of spontaneous stone passage by approximately 50% for small distal stones. These agents also appear to decrease the severity of renal colic. Corticosteroids and calcium channel antagonists are also effective but their use in the elderly is not recommended as first-line therapy. PMID:17953457

  4. Rationale and design of MinerAlocorticoid Receptor antagonist Tolerability Study-Heart Failure (ARTS-HF)

    DEFF Research Database (Denmark)

    Pitt, Bertram; Anker, Stefan D; Böhm, Michael;

    2015-01-01

    AIMS: To investigate the safety and potential efficacy of the novel non-steroidal mineralocorticoid receptor antagonist finerenone in patients with worsening chronic heart failure and reduced left ventricular ejection fraction (HFrEF) and at high risk of hyperkalaemia and worsening renal dysfunct......AIMS: To investigate the safety and potential efficacy of the novel non-steroidal mineralocorticoid receptor antagonist finerenone in patients with worsening chronic heart failure and reduced left ventricular ejection fraction (HFrEF) and at high risk of hyperkalaemia and worsening renal...

  5. Computerized technique for evaluating renal transplant function

    International Nuclear Information System (INIS)

    This investigation was undertaken to improve the assessment of renal transplant function in the early post-operative period when the usual measures of renal function afford little useful information. A simplified mathematical model of I-131 hippurate transport allows separation of renal uptake and excretion. Uptake (U) is defined as the fraction of I-131 hippurate in the plasma picked up by the kidney per minute, and excretion (E), the fraction of I-131 hippurate in the kidney excreted into the bladder per minute. Scintillation camera data from the region of the renal allograft are framed at 4/min by a computer system for up to 30 minutes post injection. After regions of interest are flagged over the kidney, bladder and background regions, the activity-time curves are analyzed, and values for U and E are output in a report updated through punched paper tape for any values from previous studies. The entire analysis of a patient study requires about 5 minutes of technologist time. Over 150 studies on 24 patients have been analyzed using the above technique. In the immediate post-operative state when anuria or severe oliguria is often present, sequential estimation of U was found to be a sensitive measure of renal transplant viability. In the period beyond one week reductions in U and E appeared to be sensitive measures of rejection, while increases in U and E heralded amelioration of the rejection episode. Changes in U and E appeared to be more sensitive measures of changes in renal function than routine qualitative scintiphotographic analysis. This technique has proven useful in following the renal function status of the kidney transplant recipient through acute tubular necrosis and rejection episodes and has been a significant adjunct to routine scintigraphy

  6. Celecoxib offsets the negative renal influences of cyclosporine via modulation of the TGF-β1/IL-2/COX-2/endothelin ET{sub B} receptor cascade

    Energy Technology Data Exchange (ETDEWEB)

    El-Gowelli, Hanan M. [Pharmacology and Toxicology, Faculty of Pharmacy, Alexandria University, Alexandria (Egypt); Helmy, Maged W.; Ali, Rabab M. [Pharmacology and Toxicology, Faculty of Pharmacy, Pharos University, Alexandria (Egypt); El-Mas, Mahmoud M., E-mail: mahelm@hotmail.com [Pharmacology and Toxicology, Faculty of Pharmacy, Alexandria University, Alexandria (Egypt)

    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{sub 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-β{sub 1}, TGF-β{sub 1}). 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{sub B} receptors were reduced by CSA and restored to near-control values in rats treated simultaneously with celecoxib. The importance of ET{sub 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 ET{sub B} 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{sub B} receptors constitutes the cellular mechanism by which celecoxib ameliorates the nephrotoxic manifestations of CSA in rats. - Highlights: • Celecoxib abolishes nephrotoxic manifestations of CSA in rats. • Blockade of ETB receptors by BQ788 mimicked the nephrotoxic effects of CSA. • CSA or BQ788 reduces renal protein expression of COX-2 and endothelin ETB receptors. • Enhanced TGFβ1/IL-2/COX2/ETB

  7. Renal denervation mitigates cardiac remodeling and renal damage in Dahl rats: a comparison with β-receptor blockade.

    Science.gov (United States)

    Watanabe, Heitaro; Iwanaga, Yoshitaka; Miyaji, Yuki; Yamamoto, Hiromi; Miyazaki, Shunichi

    2016-04-01

    Chronic activation of the sympathetic nervous system (SNS) contributes to cardiac remodeling and the transition to heart failure (HF). Renal sympathetic denervation (RDN) may ameliorate this damage by improving renal function and sympathetic cardioregulation in hypertensive HF patients with renal injury. The efficacy may be comparable to that of chronic β-blocker treatment. Dahl salt-sensitive hypertensive rats were subjected to RDN in the hypertrophic stage. Another group of Dahl rats were subjected to sham operations and treated chronically with vehicle (CONT) or β-blocker bisoprolol (BISO). Neither RDN nor BISO altered the blood pressure; however, BISO significantly reduced the heart rate (HR). Both RDN and BISO significantly prolonged survival (22.2 and 22.4 weeks, respectively) compared with CONT (18.3 weeks). Echocardiography revealed reduced left ventricular (LV) hypertrophy and improved LV function, and histological analysis demonstrated the amelioration of LV myocyte hypertrophy and fibrosis in the RDN and BISO rats at the HF stage. Tyrosine hydroxylase and β1-adrenergic receptor (ADR) expression levels in the LV myocardium significantly increased only in the RDN rats, whereas the α1b-, α1d- and α2c-ADR expression levels increased only in the BISO rats. In both groups, renal damage and dysfunction were also reduced, and this reduction was accompanied by the suppression of endothelin-1, renin and angiotensin-converting enzyme mRNAs. RDN ameliorated the progression of both myocardial and renal damage in the hypertensive rats independent of blood pressure changes. The overall effects were similar to those of β-receptor blockade with favorable effects on HR and α-ADR expression. These findings may be associated with the restoration of the myocardial SNS and renal protection. PMID:26631854

  8. CTGF Promotes Inflammatory Cell Infiltration of the Renal Interstitium by Activating NF-κB

    OpenAIRE

    Sánchez-López, Elsa; Rayego, Sandra; Rodrigues-Díez, Raquel; Rodriguez, Javier Sánchez; Rodrigues-Díez, Raúl; Rodríguez-Vita, Juan; Carvajal, Gisselle; Aroeira, Luiz Stark; Selgas, Rafael; Mezzano, Sergio A.; Ortiz, Alberto; Egido, Jesús; Ruiz-Ortega, Marta

    2009-01-01

    Connective tissue growth factor (CTGF) is an important profibrotic factor in kidney diseases. Blockade of endogenous CTGF ameliorates experimental renal damage and inhibits synthesis of extracellular matrix in cultured renal cells. CTGF regulates several cellular responses, including adhesion, migration, proliferation, and synthesis of proinflammatory factors. Here, we investigated whether CTGF participates in the inflammatory process in the kidney by evaluating the nuclear factor-kappa B (NF...

  9. 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...

  10. 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

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

    International Nuclear Information System (INIS)

    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

  12. Determinants and consequences of renal function variations with aldosterone blocker therapy in heart failure patients after myocardial infarction

    DEFF Research Database (Denmark)

    Rossignol, Patrick; Cleland, John G F; Bhandari, Sunil; Tala, Stéphane; Gustafsson, Finn; Fay, Renaud; Lamiral, Zohra; Dobre, Daniela; Pitt, Bertram; Zannad, Faiez

    2012-01-01

    We evaluated the effect of the selective mineralocorticoid receptor antagonist eplerenone on renal function and the interaction between changes in renal function and subsequent cardiovascular outcomes in patients with heart failure and left ventricular systolic dysfunction after an acute myocardial...... infarction in the Eplerenone Post-Acute Myocardial Infarction Heart Failure Efficacy and Survival Study (EPHESUS)....

  13. BMP antagonists enhance myogenic differentiation and ameliorate the dystrophic phenotype in a DMD mouse model.

    Science.gov (United States)

    Shi, SongTing; Hoogaars, Willem M H; de Gorter, David J J; van Heiningen, Sandra H; Lin, Herbert Y; Hong, Charles C; Kemaladewi, Dwi U; Aartsma-Rus, Annemieke; ten Dijke, Peter; 't Hoen, Peter A C

    2011-02-01

    Duchenne Muscular Dystrophy (DMD) is an X-linked lethal muscle wasting disease characterized by muscle fiber degeneration and necrosis. The progressive pathology of DMD can be explained by an insufficient regenerative response resulting in fibrosis and adipose tissue formation. BMPs are known to inhibit myogenic differentiation and in a previous study we found an increased expression of a BMP family member BMP4 in DMD myoblasts. The aim of the current study was therefore to investigate whether inhibition of BMP signaling could be beneficial for myoblast differentiation and muscle regeneration processes in a DMD context. All tested BMP inhibitors, Noggin, dorsomorphin and LDN-193189, were able to accelerate and enhance myogenic differentiation. However, dorsomorphin repressed both BMP and TGFβ signaling and was found to be toxic to primary myoblast cell cultures. In contrast, Noggin was found to be a potent and selective BMP inhibitor and was therefore tested in vivo in a DMD mouse model. Local adenoviral-mediated overexpression of Noggin in muscle resulted in an increased expression of the myogenic regulatory genes Myog and Myod1 and improved muscle histology. In conclusion, our results suggest that repression of BMP signaling may constitute an attractive adjunctive therapy for DMD patients. PMID:20940052

  14. 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.

  15. Renal failure

    Institute of Scientific and Technical Information of China (English)

    1993-01-01

    930564 Dwell times affect the local host de-fence mechanism of peritoneal dialysis patients.WANG Tao(汪涛),et al.Renal Instit,SunYatsen Med Univ,Guangzhou,510080.Chin JNephrol 1993;9(2):75—77.The effect of different intraperitoneal awelltimes on the local host defence in 6 peritonealdialysis patients was studied.A significant de-crease in the number of peritoneal cells,IgG con-centration and the phagoeytosis and bactericidalactivity of macrophages was determined when thedwell time decreased from 12 to 4 hs or form 4 to0.5hs,but the peroxidase activity in macrophagesincreased significantly.All variables,except theperoxidase activity in macrophages,showed nosignificant difference between patients of high or

  16. CRF receptor 1 antagonism and brain distribution of active components contribute to the ameliorative effect of rikkunshito on stress-induced anorexia.

    Science.gov (United States)

    Mogami, Sachiko; Sadakane, Chiharu; Nahata, Miwa; Mizuhara, Yasuharu; Yamada, Chihiro; Hattori, Tomohisa; Takeda, Hiroshi

    2016-01-01

    Rikkunshito (RKT), a Kampo medicine, has been reported to show an ameliorative effect on sustained hypophagia after novelty stress exposure in aged mice through serotonin 2C receptor (5-HT2CR) antagonism. We aimed to determine (1) whether the activation of anorexigenic neurons, corticotropin-releasing factor (CRF), and pro-opiomelanocortin (POMC) neurons, is involved in the initiation of hypophagia induced by novelty stress in aged mice; (2) whether the ameliorative effect of RKT is associated with CRF and POMC neurons and downstream signal transduction; and (3) the plasma and brain distribution of the active components of RKT. The administration of RKT or 5-HT2CR, CRF receptor 1 (CRFR1), and melanocortin-4 receptor antagonists significantly restored the decreased food intake observed in aged male C57BL/6 mice in the early stage after novelty stress exposure. Seven components of RKT exhibited antagonistic activity against CRFR1. Hesperetin and isoliquiritigenin, which showed antagonistic effects against both CRFR1 and 5-HT2CR, were distributed in the plasma and brain of male Sprague-Dawley rats after a single oral administration of RKT. In conclusion, the ameliorative effect of RKT in this model is assumed to be at least partly due to brain-distributed active components possessing 5-HT2CR and CRFR1 antagonistic activities. PMID:27273195

  17. CRF receptor 1 antagonism and brain distribution of active components contribute to the ameliorative effect of rikkunshito on stress-induced anorexia

    Science.gov (United States)

    Mogami, Sachiko; Sadakane, Chiharu; Nahata, Miwa; Mizuhara, Yasuharu; Yamada, Chihiro; Hattori, Tomohisa; Takeda, Hiroshi

    2016-01-01

    Rikkunshito (RKT), a Kampo medicine, has been reported to show an ameliorative effect on sustained hypophagia after novelty stress exposure in aged mice through serotonin 2C receptor (5-HT2CR) antagonism. We aimed to determine (1) whether the activation of anorexigenic neurons, corticotropin-releasing factor (CRF), and pro-opiomelanocortin (POMC) neurons, is involved in the initiation of hypophagia induced by novelty stress in aged mice; (2) whether the ameliorative effect of RKT is associated with CRF and POMC neurons and downstream signal transduction; and (3) the plasma and brain distribution of the active components of RKT. The administration of RKT or 5-HT2CR, CRF receptor 1 (CRFR1), and melanocortin-4 receptor antagonists significantly restored the decreased food intake observed in aged male C57BL/6 mice in the early stage after novelty stress exposure. Seven components of RKT exhibited antagonistic activity against CRFR1. Hesperetin and isoliquiritigenin, which showed antagonistic effects against both CRFR1 and 5-HT2CR, were distributed in the plasma and brain of male Sprague-Dawley rats after a single oral administration of RKT. In conclusion, the ameliorative effect of RKT in this model is assumed to be at least partly due to brain-distributed active components possessing 5-HT2CR and CRFR1 antagonistic activities. PMID:27273195

  18. Chromophobe Renal Cell Carcinoma

    OpenAIRE

    Jyotsna Vijaykumar Wader; Sujata S Kumbhar; Huddedar AD; Wasim GM Khatib

    2013-01-01

    Renal cell carcinoma is the most common neoplasm of the kidney comprised of different histological variants. Chromophobe renal cell carcinoma (ChRCC) is a rare subtype of renal cell carcinoma (RCC) mainly diagnosed in the sixth decade of life. It is important to identify this entity because it has significantly better prognosis than the clear cell (conventional) and papillary renal cell carcinomas. The chromophobe renal cell carcinoma should be differentiated from oncocytoma and clear cell ca...

  19. Berberine Improves Kidney Injury Following Renal Ischemia Reperfusion in Rats

    Directory of Open Access Journals (Sweden)

    Firouzeh Gholampour

    2015-01-01

    Full Text Available This study investigated the effect of berberine on the renal dysfunction and histological damage induced by renal ischaemia/reperfusion at an early stage. There were four groups (n = 7. In Ber+I/R group, rats received berberine (Ber; 15 mg kg-1 day-1 orally for 7 days before induction of ischemia. The I/R group received distilled water orally for 7 days. In sham and Ber+sham groups, that renal arteries were not occluded, distilled water and berberin (15 mg kg-1 day-1, respectively were administered orally for 7 days before surgery. Renal ischemia was induced by occlusion of both renal arteries for 45 min followed by 24 h of reperfusion. Blood samples were collected for biochemical analysis and finally the left kidney was preserved for future histological examination. The renal ischaemic challenge resulted in major histological damages of the kidney which were associated with increased levels of creatinine and Blood Urea Nitrogen (BUN at the end of reperfusion period. In Ber+I/R group, the histological damage to the kidney was improved along with increased in plasma creatinine and BUN being smaller than those of the non-treated rats. Berberine exhibited an ameliorative effect against renal ischemia/reperfusion-induced lesions.

  20. Nebivolol Ameliorates Cisplatin-Induced Nephrotoxicity in Rats.

    Science.gov (United States)

    Morsy, Mohamed A; Heeba, Gehan H

    2016-06-01

    Treatment with cisplatin is associated with dose-limiting side effects, mainly nephrotoxicity. On the other hand, nebivolol, a β1 -adrenoceptor antagonist, exhibits vasodilatory and antioxidative properties. This study aimed to determine whether nebivolol possesses a protective effect against cisplatin nephrotoxicity and explore many mechanisms underlying this potential effect. Nephrotoxicity was induced in Wistar rats by a single intraperitoneal injection of cisplatin (6 mg/kg) on day 2. Nebivolol (10 mg/kg) was administered orally for 7 consecutive days. Nebivolol showed a nephroprotective effect as demonstrated by the significant reduction in the elevated levels of serum creatinine and urea as well as renal levels of malondialdehyde, nitric oxide products (nitrite/nitrate), inducible nitric oxide synthase, tumour necrosis factor-alpha, caspase-3, angiotensin II and endothelin-1 with a concurrent increase in renal levels of reduced glutathione and endothelial nitric oxide synthase compared to untreated rats. Histopathological examination confirmed the nephroprotective effect of nebivolol. Pre-treatment with Nω -nitro-L-arginine methyl ester, the non-specific nitric oxide synthase inhibitor, partially altered the protection afforded by nebivolol. In conclusion, nebivolol protects rats against cisplatin-induced nephrotoxicity that is most likely through its antioxidant, anti-inflammatory and antiapoptotic effects as well as by abrogation of the augmented angiotensin II and endothelin-1 levels. PMID:26617394

  1. 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...

  2. Small-molecule nociceptin receptor agonist ameliorates mast cell activation and pain in sickle mice.

    Science.gov (United States)

    Vang, Derek; Paul, Jinny A; Nguyen, Julia; Tran, Huy; Vincent, Lucile; Yasuda, Dennis; Zaveri, Nurulain T; Gupta, Kalpna

    2015-12-01

    Treatment of pain with morphine and its congeners in sickle cell anemia is suboptimal, warranting the need for analgesics devoid of side effects, addiction and tolerance liability. Small-molecule nociceptin opioid receptor ligands show analgesic efficacy in acute and chronic pain models. We show that AT-200, a high affinity nociceptin opioid receptor agonist with low efficacy at the mu opioid receptor, ameliorated chronic and hypoxia/reoxygenation-induced mechanical, thermal and deep tissue/musculoskeletal hyperalgesia in HbSS-BERK sickle mice. The antinociceptive effect of AT-200 was antagonized by SB-612111, a nociceptin opioid receptor antagonist, but not naloxone, a non-selective mu opioid receptor antagonist. Daily 7-day treatment with AT-200 did not develop tolerance and showed a sustained anti-nociceptive effect, which improved over time and led to reduced plasma serum amyloid protein, neuropeptides, inflammatory cytokines and mast cell activation in the periphery. These data suggest that AT-200 ameliorates pain in sickle mice via the nociceptin opioid receptor by reducing inflammation and mast cell activation without causing tolerance. Thus, nociceptin opioid receptor agonists are promising drugs for treating pain in sickle cell anemia. PMID:26294734

  3. Angiotensin antagonists in the dog with chronic pericardial tamponade

    International Nuclear Information System (INIS)

    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)

  4. Two Cases of Hypophosphatemia with Increased Renal Phosphate Excretion in Legionella Pneumonia

    Science.gov (United States)

    Watanabe, Shuhei; Kono, Keiji; Fujii, Hideki; Nakai, Kentaro; Goto, Shunsuke; Nishi, Shinichi

    2016-01-01

    We encountered 2 cases of hypophosphatemia due to Legionella pneumonia. Both cases showed increased urinary phosphate excretion and renal tubular dysfunction, which ameliorated with recovery from Legionella pneumonia. Serum fibroblast growth factor-23 level was suppressed, whereas serum 1,25(OH)2 vitamin D and parathyroid hormone levels were normal. Delayed elevation of serum 1,25(OH)2 vitamin D levels was observed with improvement in renal tubular function. These findings suggested hypophosphatemia might be mediated by renal tubular dysfunction. PMID:27066493

  5. Renal cell cancer without a renal primary

    OpenAIRE

    Cumani B; Bratcher J; Wang W.; Wayne M.; Kasmin F; Cooperman A

    2010-01-01

    Abstract Renal cell carcinoma has been increasing in incidence over the past two decades. Men are affected more than women and metastatic disease at presentation occurs in up to one third of patients. Metastasis can occur to virtually any organ, and involvement of multiple organs is not uncommon. To date, no reports have been found of metastatic disease without a renal primary. We present a case of renal cell cancer initially presenting as a subcutaneous mass with subsequent pancreatic and pa...

  6. Renal (Kidney) Manifestations in TSC

    Medline Plus

    Full Text Available ... renal (kidney) disease during their lifetime. There are three particular renal disorders in TSC: renal cysts, renal ... at the time of diagnosis, and at 2-3 year intervals if no cysts or angiomyolipomas are ...

  7. Renal (Kidney) Manifestations in TSC

    Medline Plus

    Full Text Available ... during their lifetime. There are three particular renal disorders in TSC: renal cysts, renal angiomyolipoma and renal ... Government Action Team TS Alliance Online Support Community Facebook Twitter YouTube How to Make a Donation Research ...

  8. Effective use of TNF antagonists

    OpenAIRE

    Yocum, David

    2004-01-01

    Tumor necrosis factor (TNF) antagonists are biologic response modifiers that have significantly improved functional outcomes in patients with rheumatoid arthritis (RA). RA is a progressive disease in which structural joint damage can continue to develop even in the face of symptomatic relief. Before the introduction of biologic agents, the management of RA involved the use of disease-modifying antirheumatic drugs (DMARDs) early in the course of disease. This focus on early treatment, combined...

  9. Cardio Renal Syndrome

    Directory of Open Access Journals (Sweden)

    KV Sahasranam

    2014-10-01

    Full Text Available For a long time, physicians have recognized that the kidney and the heart are related especially when there is severe dysfunction of either of them. Dysfunction of one of these organs seldom occurs in isolation. Of late the cardio renal syndrome is assuming significance because of its increasing incidence, awareness and complications. There is no definite definition of the cardio renal syndrome. However, an attempted definition states that it is a "decline in renal function in the setting of advanced heart failure". This definition does not cover the whole gamut of the cardio renal syndrome. Cardiac diseases are associated independently with a decrease in renal function and progression of existing renal disease. Chronic Kidney disease (CKD is an independent risk factor for cardiovascular events and outcome. This bidirectional nature of cardiac and renal interaction is called Cardio Renal Syndrome (CRS.

  10. Renal papillary necrosis

    Science.gov (United States)

    ... your provider. Alternative Names Necrosis - renal papillae; Renal medullary necrosis Images Kidney anatomy Kidney - blood and urine flow References Ruggenenti P, Cravedi P, Remuzzi G. Microvascular and macrovascular diseases of the kidney. In: Taal MW, Chertow GM, ...

  11. Kidney (Renal) Failure

    Science.gov (United States)

    ... How is kidney failure treated? What is kidney (renal) failure? The kidneys are designed to maintain proper fluid ... marrow and strengthen the bones. The term kidney (renal) failure describes a situation in which the kidneys have ...

  12. Renal cell carcinoma

    Science.gov (United States)

    Renal cell carcinoma is a type of kidney cancer that starts in the lining of very small tubes (tubules) in the kidney. ... cancer; Kidney cancer; Hypernephroma; Adenocarcinoma of renal cells; Cancer - kidney

  13. On Renal Artery Stenosis

    OpenAIRE

    Eklöf, Hampus

    2005-01-01

    Renal artery stenosis (RAS) is a potentially curable cause of hypertension and azotemia. Besides intra-arterial renal angiography there are several non-invasive techniques utilized to diagnose patients with suspicion of renal artery stenosis. Removing the stenosis by revascularization to restore unobstructed blood flow to the kidney is known to improve and even cure hypertension/azotemia, but is associated with a significant complication rate. To visualize renal arteries with x-ray technique...

  14. RENAL INVOLVEMENT IN LEPTOSPIROSIS

    OpenAIRE

    Galya I. Gancheva

    2012-01-01

    Renal involvement is a common feature of leptospirosis. It is variable from mild to severe acute renal failure. Materials and methods: We performed analysis of 100 consecutive leptospirosis cases treated in Clinic of Infectious Diseases at University Hospital – Pleven (1976-2012) (90 male, age 37±18 years, lethal outcome in 13%), followed by comparative analysis of group with renal involvement (n1=59) versus group without renal involvement (controls: n2=41). Results: Fever (100%), hepatomegal...

  15. Recurrent acute renal failure

    OpenAIRE

    Satish, S.; Rajesh, R.; Kurian, G.; Seethalekshmi, N. V.; Unni, M.; Unni, V. N.

    2010-01-01

    While acute renal failure secondary to intravascular hemolysis is well described in hemolytic anemias, recurrent acute renal failure as the presenting manifestation of a hemolytic anemia is rare. We report a patient with recurrent acute renal failure who was found to have paroxysmal nocturnal hemoglobinuria (PNH), on evaluation.

  16. 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 ...

  17. 黄连素调节鞘氨醇激酶-1-磷酸鞘氨醇信号通路抗糖尿病小鼠肾损伤的研究%Berberine ameliorates diabetic mouse renal injury through inhibition of SphK1-S1P signaling pathway

    Institute of Scientific and Technical Information of China (English)

    彭晶; 兰天; 黄凯鹏; 黄娟; 谢曦; 黄河清

    2011-01-01

    Aim To evaluate the protective effects of berberine on alloxan-induced diabetic renal injury in mice and the inhibitory effects of berberine on the Sphingosine kinase Sphingosine 1-phosphate ( SphK SIP) signaling pathway in mouse kidney. Methods Diabetic mice in berberine treatment group were treated orally with berberine (300 mg ? Kg"1 ? D~* ) or vehicle for 12 weeks. Mice in control or diabetic group were administrated with the equal volume of vehicle. Western blot method was applied to detect the protein expression of SphKl, FN, Col IV and RT-PCR was used to detect the mRNA expression of SphKl, TGF-(31, FN, Col IV. Results Berberine significantly attenuated the abnormal increases in fasting blood glu-cose , kidney/body weight, blood urea nitrogen, serum creatinine and 24 h urine protein. In addition, berberine prevented renal hypertrophy, TGF-pl synthesis, FN and Col IV accumulation in kidney of diabetic mouse. Moreover, berberine down-regulated the elevated stainining, activity and levels of mRNA and protein of SphKl, and SI P production as well. Conclusion The protective effects of berberine on the diabetic renal injury in mice are relevant to the inhibition of activation of SphK-Sl P pathway in diabetic mouse kidney.%目的 研究黄连素对四氧嘧啶诱导的糖尿病小鼠肾损伤的保护作用及其对糖尿病小鼠肾脏鞘氨醇激酶-1-磷酸鞘氨醇(SphK-S1P)信号通路的抑制效应.方法 四氧嘧啶诱导的糖尿病小鼠采用黄连素(300 mg·kg-1·d-1)灌胃给药12周,正常组和糖尿病组小鼠给予同体积的溶媒.采用Real-time PCR技术检测肾组织中SphK1、TGF-β1、FN、Col Ⅳ的基因;Western blot法检测肾脏组织中SphK1、FN、Col Ⅳ的蛋白表达;LC-MS/MS检测肾脏组织中SphK1活性和S1P含量.结果 黄连素明显抑制糖尿病小鼠血糖,肾重/体重比、血尿素氮、血肌酐和24 h尿蛋白异常增高;抑制肾脏肥大、纤维连接蛋白和Ⅳ型胶原积聚.此外,黄

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

    OpenAIRE

    Ozgur Cakmak; Cemal Selcuk Isoglu; Ercument Aziz Peker; Huseyin Tarhan; Ulku Kucuk; Orcun Celik; Ferruh Zorlu; Yusuf Ozlem Ilbey

    2016-01-01

    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 vascu...

  19. [Hypertension and renal disease

    DEFF Research Database (Denmark)

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

    2009-01-01

    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......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...

  20. Inhibition of Acetylcholinesterase Modulates NMDA Receptor Antagonist Mediated Alterations in the Developing Brain

    Directory of Open Access Journals (Sweden)

    Ivo Bendix

    2014-03-01

    Full Text Available Exposure to N-methyl-d-aspartate (NMDA receptor antagonists has been demonstrated to induce neurodegeneration in newborn rats. However, in clinical practice the use of NMDA receptor antagonists as anesthetics and sedatives cannot always be avoided. The present study investigated the effect of the indirect cholinergic agonist physostigmine on neurotrophin expression and the extracellular matrix during NMDA receptor antagonist induced injury to the immature rat brain. The aim was to investigate matrix metalloproteinase (MMP-2 activity, as well as expression of tissue inhibitor of metalloproteinase (TIMP-2 and brain-derived neurotrophic factor (BDNF after co-administration of the non-competitive NMDA receptor antagonist MK801 (dizocilpine and the acetylcholinesterase (AChE inhibitor physostigmine. The AChE inhibitor physostigmine ameliorated the MK801-induced reduction of BDNF mRNA and protein levels, reduced MK801-triggered MMP-2 activity and prevented decreased TIMP-2 mRNA expression. Our results indicate that AChE inhibition may prevent newborn rats from MK801-mediated brain damage by enhancing neurotrophin-associated signaling pathways and by modulating the extracellular matrix.

  1. Effect of TGF-β1 antisense oligodeoxynucleotide on renal function in chronic renal failure rats

    Institute of Scientific and Technical Information of China (English)

    Law Chung HIONG; Kiew Lik VOON; Nor Azizan ABDULLAH; Munavvar A SATTAR; Nazarina AbduRAHMAN; Abdul Hye KHAN; Edward James JOHNS

    2008-01-01

    Aim:The aim of the present study was to investigate the effectiveness of trans-forming growth factor (TGF)-β1 antisense oligodeoxynucleotides (ODN) in ame-liorating deteriorated kidney function in rats with puromycin-induced chronic renal failure (CRF). Methods:Saline, puromycin, puromycin+TGF-β1 antisense ODN or puromycin+scrambled ODN were administered to unilaterally nephrecto-mized rats. Renal hemodynamic and excretory measurements were taken in the anaesthetized rats that had undergone surgical procedure. Results:It was ob-served that in the CRF rats, there was a marked reduction in the renal blood flow (RBF), glomerular filtration rate (GFR), severe proteinuria, and almost 6-fold in-creased fractional excretion of sodium (FE Na+) as compared to that in the control rats (all P<0.05). It was further observed that in the CRF rats, the treatment with TGF-β1 antisense, but not scrambled ODN, markedly attenuated the reduction of RBF, GFR, and proteinuria and markedly prevented the increase of the FE Na+ (all P<0.05). In addition, the renal hypertrophy in the CRF group (P<0.05 vs non-renal failure control) was markedly attenuated after treatment with TGF-1 antisense ODN (P<0.05). Focal segmental glomerulosclerosis was evident only in the un-treated and scrambled ODN-treated CRF groups. An interesting observation of this study was that in the CRF rats, although there was marked attenuating and preventive effects of the TGF-β1 antisense ODN on the deteriorated renal functions, the antisense treatment did not cause any marked change in the renal expression of TGF-β1 at the protein level. Conclusion:Collectively, the data obtained sug-gests that TGF-β1 antisense ODN possesses beneficial effects in puromycin-induced chronic renal failure and that the deterioration in morphology and im-paired renal function in this pathological state is in part dependent upon the action of TGF-β1 within the kidney.

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

    Science.gov (United States)

    Amaral, Nathalia O; de Oliveira, Thiago S; Naves, Lara M; Filgueira, Fernando P; Ferreira-Neto, Marcos L; Schoorlemmer, Gerard H M; de Castro, Carlos H; Freiria-Oliveira, André H; Xavier, Carlos H; Colugnati, Diego B; Rosa, Daniel A; Blanch, Graziela T; Borges, Clayton L; Soares, Célia M A; Reis, Angela A S; Cravo, Sergio L; Pedrino, Gustavo R

    2014-01-01

    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. PMID:25279805

  3. 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.

  4. Antianginal Actions of Beta-Adrenoceptor Antagonists

    OpenAIRE

    O'Rourke, Stephen T.

    2007-01-01

    Angina pectoris is usually the first clinical sign of underlying myocardial ischemia, which results from an imbalance between oxygen supply and oxygen demand in the heart. This report describes the pharmacology of β-adrenoceptor antagonists as it relates to the treatment of angina. The β-adrenoceptor antagonists are widely used in long-term maintenance therapy to prevent acute ischemic episodes in patients with chronic stable angina. Beta-adrenoceptor antagonists competitively inhibit the bin...

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

    International Nuclear Information System (INIS)

    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)

  6. Effect of paricalcitol and enalapril on renal inflammation/oxidative stress in atherosclerosis

    Institute of Scientific and Technical Information of China (English)

    Kazim; Husain; Edu; Suarez; Angel; Isidro; Wilfredo; Hernandez; Leon; Ferder

    2015-01-01

    AIM: To investigate the protective effect of paricalcitol and enalapril on renal inflammation and oxidative stress in Apo E-knock out mice. METHODS: Animals treated for 4 mo as group(1) Apo E-knock out plus vehicle, group(2) Apo E-knock out plus paricalcitol(200 ng thrice a week),(3) Apo Eknock out plus enalapril(30 mg/L),(4) Apo E-knock out plus paricalcitol plus enalapril and(5) normal. Blood pressure(BP) was recorded using tail cuff method. The kidneys were isolated for biochemical assays using spectrophotometer and Western blot analyses. RESULTS: Apo E-deficient mice developed high BP(127 ± 3 mm Hg) and it was ameliorated by enalapril and enalapril plus paricalcitol treatments but not with paricalcitol alone. Renal malondialdehyde concentrations, p22 phox, manganese-superoxide dismutase, inducible nitric oxide synthase(NOS), monocyte chemoattractant protein-1, tumor necrosis factor-alpha and transforming growth factor-β1 levels significantly elevated but reduced glutathione, Cu Zn-SOD and e NOS levels significantly depleted in Apo E-knock out animals compared to normal. Administration of paricalcitol, enalapril and combined together ameliorated the renal inflammation and oxidative stress in Apo E-knock out animals. CONCLUSION: Paricalcitol and enalapril combo treatment ameliorates renal inflammation as well as oxidative stress in atherosclerotic animals.

  7. Renal Preservation Therapy for Renal Cell Carcinoma

    OpenAIRE

    Yichun Chiu; Allen W. Chiu

    2012-01-01

    Renal preservation therapy has been a promising concept for the treatment of localized renal cell carcinoma (RCC) for 20 years. Nowadays partial nephrectomy (PN) is well accepted to treat the localized RCC and the oncological control is proved to be the same as the radical nephrectomy (RN). Under the result of well oncological control, minimal invasive method gains more popularity than the open PN, like laparoscopic partial nephrectomy (LPN) and robot assisted laparoscopic partial nephrectomy...

  8. Renal function after renal artery stenting

    Institute of Scientific and Technical Information of China (English)

    George S. Hanzel; Mark Downes; Peter A. McCullough

    2005-01-01

    @@ Atherosclerotic renal artery stenosis (ARAS), a common clinical finding, is increasing in prevalence as the population ages. ARAS is seen in ~ 7% of persons over 65 years of age1 and in ~ 20% of patients at the time of coronary angiography.2 It is an important cause of chronic kidney disease and may result in 11-14% of cases of end stage renal disease.3

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

    International Nuclear Information System (INIS)

    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) (5 mg/kg/day) for 5 days to produce acute AA nephropathy (AAN) model. BARD (10 mg/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

  10. LMWH in cancer patients with renal impairment - better than warfarin?

    Science.gov (United States)

    Bauersachs, Rupert M

    2016-04-01

    Venous thromboembolism (VTE) is one of the leading causes of death in cancer patients, which are known to have a 5- to 7-fold increased risk for VTE. The anticoagulant treatment of VTE in cancer patients is less effective with a three-fold increased risk of VTE recurrence compared to non-cancer patients, and it is less safe with more than double rates of major bleeding. Compared to vitamin-K antagonists (VKA), long-term secondary prevention with low molecular weight heparin (LMWH) has been shown to reduce the risk of recurrent VTE in cancer-associated thrombosis (CAT), and therefore, current international guidelines recommend the use of LMWH over VKA. With increasing age, cancer prevalence and VTE incidence increase while renal function decreases. Anti-cancer treatment may impair renal function additionally. Therefore, renal insufficiency is a frequent challenge in CAT patients, which is associated with a higher risk of both bleeding and recurrent VTE. Both VKA and LMWH may be associated with less efficacy and higher bleeding risk in renal insufficiency. Unfortunately, there is a lack of prospective data on renal insufficiency and CAT. A recent sub-analysis from a large randomized controlled trial shows that the bleeding risk in patients with severe renal insufficiency in CAT is not elevated with the use of LMWH compared to VKA while efficacy is maintained. In addition, LMWH treatment has several practical advantages over VKA, particularly in patients with CAT while they are receiving anti-cancer treatment. PMID:27067971

  11. Mesenchymal stromal cells in renal ischemia/reperfusion injury

    Directory of Open Access Journals (Sweden)

    Dorottya K. De Vries

    2012-07-01

    Full Text Available Ischemia/reperfusion (I/R injury is an inevitable consequence of organ transplantation and a major determinant of patient and graft survival in kidney transplantation. Renal I/R injury can lead to fibrosis and graft failure. Although the exact sequence of events in the pathophysiology of I/R injury remains unknown, the role of inflammation has become increasingly clear. In this perspective, mesenchymal stromal cells (MSCs are under extensive investigation as potential therapy for I/R injury, since MSCs are able to exert immune regulatory and reparative effects. Various preclinical studies indicate the beneficial effects of MSCs in ameliorating renal injury and accelerating tissue repair. These versatile cells have been shown to migrate to sites of injury and to enhance repair by paracrine mechanisms instead of by differentiating and replacing the injured cells. The first phase I studies of MSCs in human renal I/R injury and kidney transplantation have been started, and results are awaited soon. In this review, preliminary results and opportunities of MSCs in human renal I/R injury are summarized. We might be heading towards a cell-based paradigm shift in the treatment of renal I/R injury.

  12. Neuronal dysfunction with aging and its amelioration

    OpenAIRE

    Ando, Susumu

    2012-01-01

    The author focused on the functional decline of synapses in the brain with aging to understand the underlying mechanisms and to ameliorate the deficits. The first attempt was to unravel the neuronal functions of gangliosides so that gangliosides could be used for enhancing synaptic activity. The second attempt was to elicit the neuronal plasticity in aged animals through enriched environmental stimulation and nutritional intervention. Environmental stimuli were revealed neurochemically and mo...

  13. Calcium ameliorates diarrhea in immune compromised children

    OpenAIRE

    Cheng, Sam X.; Bai, Harrison X; Gonzalez-Peralta, Regino; Mistry, Pramod K.; Gorelick, Fred S.

    2013-01-01

    Treatment of infectious diarrheas remains a challenge, particularly in immunocompromised patients in whom infections usually persist and resultant diarrhea is often severe and protracted. Children with infectious diarrhea who become dehydrated are normally treated with oral or intravenous rehydration therapy. Although rehydration therapy can replace the loss of fluid, it does not ameliorate diarrhea. Thus, over the past decades, there has been continuous effort to search for ways to safely st...

  14. Renal cystic disease

    Energy Technology Data Exchange (ETDEWEB)

    Hartman, D.S.

    1988-01-01

    The book begins with an overview of renal cystic disease and a presentation of simple renal cysts. Subsequent chapters cover cystic disease in association with renal neoplasms and medullary sponge kidney. The chapters addressing autosomal-dominant and autosomal-recessive polycystic kidney disease discuss and differentiate the infantile and adult forms of the disease. There are also separate discussions of medullary cystic disease, multicystic dysplastic kidney, and cysts of the renarenal sinus.

  15. Rupture of Renal Transplant

    OpenAIRE

    Shona Baker; Maria Popescu; Jacob A Akoh

    2015-01-01

    Background. Rupture of renal allograft is a rare and serious complication of transplantation that is usually attributed to acute rejection, acute tubular necrosis, or renal vein thrombosis. Case Presentation. LD, a 26-year-old male with established renal failure, underwent deceased donor transplantation using kidney from a 50-year-old donor with acute kidney injury (Cr 430 mmol/L). LD had a stormy posttransplant recovery and required exploration immediately for significant bleeding. On day th...

  16. 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

    metabolic disturbances in renal stone formers. Distal renal tubular acidosis (dRTA) was relatively more common in female stone formers and most often found in patients with bilateral stone disease (36%). Since prophylactic treatment in renal stone formers with renal acidification defects is available, this...... (1.1%) had complete distal renal tubular acidosis and 14 (15.5%) incomplete distal renal tubular acidosis. Our results confirm that distal renal tubular acidification defects are associated with a more severe form of stone disease and make distal renal tubular acidosis one of the most frequent...

  17. Renal (Kidney) Manifestations in TSC

    Medline Plus

    Full Text Available ... methods to diagnosis these renal abnormalities include renal ultrasonography, CT scanning and magnetic resonance imaging (MRI). These ... in almost every major medical center. The renal ultrasound provides the least detailed image of the kidney, ...

  18. Renal (Kidney) Manifestations in TSC

    Medline Plus

    Full Text Available ... the kidneys are filled with cysts. If kidney failure occurs, renal replacement therapy such as dialysis or transplantation is ... can develop in infancy or early childhood and renal failure most often occurs in early adulthood. Renal Angiomyolipomas ...

  19. Client Perceptions of Two Antagonist Programs.

    Science.gov (United States)

    Capone, Thomas A.; And Others

    1980-01-01

    Reports results of a questionnaire administered to participants in an antagonist drug outpatient clinic and an antagonist drug work-release program to obtain awareness of acceptance of the program participants. Naltrexone patients recommended an alternative method of administering the drug and changing the money system to award deserving inmates…

  20. The protective effects of beta-casomorphin-7 against glucose -induced renal oxidative stress in vivo and vitro.

    Directory of Open Access Journals (Sweden)

    Wei Zhang

    Full Text Available Oxidative stress is implicated in the pathogenesis of diabetic nephropathy. The present study aimed to investigate the effect of β-casomorphin-7 (BCM7 on the oxidative stress occurring in kidney tissue in streptozotocin (STZ-induced diabetic rats and proximal tubular epithelial cells (NRK-52E exposure to high glucose (HG by using biochemical methods. There is a significant decrease in plasma insulin and a significant increase in plasma glucagon in the rats of diabetic group. Oral administration of BCM7 for 30 days to rats with STZ-induced diabetes resulted in a significant increase in serum level of insulin, and a decrease in the level of glucagon. Moreover, rats with STZ-induced diabetes had lower levels of superoxide dismutase (SOD, glutathione peroxidase (GPx and total antioxidative capacity (T-AOC, higher levels of malondialdehyde (MDA and hydrogen peroxide (H2O2 in the kidney than that in the control rats. The administration of BCM7 altered the changes of SOD, GPx, T-AOC, MDA and H2O2 in the kidney of diabetic rats. Furthermore, BCM7 alleviated high glucose-induced decreasement in SOD and GPx activity, increasement in MDA contents in the NRK-52E cells. BCM7 ameliorated the changes of angiotensin converting enzyme (ACE and ACE2 levels in the kidney of diabetic rats and BCM7 lowered the levels of angiotensin (AngII in the kidney of diabetic rats and culture medium for cells. Moreover losartan (antagonist of angiotensin II type I receptor lowered the high glucose-induced oxidative stress in the NRK-52E cells. Our results suggest that administration of BCM7 would alleviate high glucose-induced renal oxidative stress in vivo and in vitro, which may be associated with down regulation of the concentration of Ang II partly.

  1. Normalizing renal reducing ability prevents adriamycin-induced proteinuria

    International Nuclear Information System (INIS)

    Reactive oxygen species play an important role in adriamycin (ADR) nephropathy. We showed by in vivo electron paramagnetic resonance (EPR) that renal reducing ability (RRA) declined on the 7th day after ADR administration. Proteinuria appeared after the decline in RRA. The aim of this study was to prove by in vivo EPR whether the decline in RRA is altered by scavengers such as dimethyl sulfoxide (DMSO) and dimethylthiourea (DMTU) and that it is this change which is responsible for the proteinuria in ADR nephropathy. By showing that DMSO and DMTU ameliorate the RRA, we demonstrate that the decline in RRA is related to ADR-induced proteinuria

  2. Ameliorating antipsychotic-induced weight gain by betahistine: Mechanisms and clinical implications.

    Science.gov (United States)

    Lian, Jiamei; Huang, Xu-Feng; Pai, Nagesh; Deng, Chao

    2016-04-01

    Second generation antipsychotic drugs (SGAs) cause substantial body weight gain/obesity and other metabolic side-effects such as dyslipidaemia. Their antagonistic affinity to the histaminergic H1 receptor (H1R) has been identified as one of the main contributors to weight gain/obesity side-effects. The effects and mechanisms of betahistine (a histaminergic H1R agonist and H3 receptor antagonist) have been investigated for ameliorating SGA-induced weight gain/obesity in both animal models and clinical trials. It has been demonstrated that co-treatment with betahistine is effective in reducing weight gain, associated with olanzapine in drug-naïve patients with schizophrenia, as well as in the animal models of both drug-naïve rats and rats with chronic, repeated exposure to olanzapine. Betahistine co-treatment can reduce food intake and increase the effect of thermogenesis in brown adipose tissue by modulating hypothalamic H1R-NPY-AMPKα (NPY: neuropeptide Y; AMPKα: AMP-activated protein kinase α) pathways, and ameliorate olanzapine-induced dyslipidaemia through modulation of AMPKα-SREBP-1-PPARα-dependent pathways (SREBP-1: Sterol regulatory element binding protein 1; PPARα: Peroxisome proliferator-activated receptor-α) in the liver. Although reduced locomotor activity was observed from antipsychotic treatment in rats, betahistine did not affect locomotor activity. Importantly, betahistine co-treatment did not influence the effects of antipsychotics on serotonergic receptors in the key brain regions for antipsychotic therapeutic efficacy. However, betahistine co-treatment reverses the upregulated dopamine D2 binding caused by chronic olanzapine administration, which may be beneficial in reducing D2 supersensitivity often observed in chronic antipsychotic treatment. Therefore, these results provide solid evidence supporting further clinical trials in treating antipsychotics-induced weight gain using betahistine in patients with schizophrenia and other mental

  3. 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.

  4. Upregulation of miR-21 by Ghrelin Ameliorates Ischemia/Reperfusion-Induced Acute Kidney Injury by Inhibiting Inflammation and Cell Apoptosis.

    Science.gov (United States)

    Zhang, Wanzhe; Shu, Liliang

    2016-08-01

    Renal ischemia-reperfusion (I/R) injury can be caused by cardiac surgery, renal vascular obstruction, and kidney transplantation, mainly leading to acute kidney injury (AKI), which is complicated by lack of effective preventative and therapeutic strategies. Ghrelin has recently been reported to possess anti-inflammatory properties in several types of cells; however, little attention has been given to the role of ghrelin in I/R-induced AKI. The aim of this study is to explore the role of ghrelin in I/R-induced AKI. In this study, an I/R-induced rat AKI model and a hypoxia-induced NRK-52E cell I/R model were successfully constructed. Ghrelin expression was increased significantly in these rat and cell models. After enhancing ghrelin level by injecting exogenous ghrelin into rats or transfecting a ghrelin-pcDNA3.1 vector into renal tubular epithelial cells, we observed that I/R-induced AKI can be ameliorated by ghrelin, as shown by alterations in histology, as well as changes in serum creatinine (SCr) level, cell apoptosis, and the levels of inflammatory factors. Based on the importance of microRNA-21 (miR-21) in renal disease and the modulation effect of ghrelin on miR-21 in gastric epithelial cells, we tested whether miR-21 participates in the protective effect of ghrelin on I/R-induced AKI. Ghrelin could upregulate the PI3K/AKT signaling pathway by increasing the miR-21 level, which led to the protective effect of ghrelin on I/R-induced AKI by inhibiting the inflammatory response and renal tubular epithelial cell apoptosis. Our research identifies that ghrelin can ameliorate I/R-induced AKI by upregulating miR-21, which advances the understanding of mechanisms by which ghrelin ameliorates I/R-induced AKI. PMID:27152763

  5. Loss of Renal Tubular PGC-1α Exacerbates Diet-Induced Renal Steatosis and Age-Related Urinary Sodium Excretion in Mice.

    Science.gov (United States)

    Svensson, Kristoffer; Schnyder, Svenia; Cardel, Bettina; Handschin, Christoph

    2016-01-01

    The kidney has a high energy demand and is dependent on oxidative metabolism for ATP production. Accordingly, the kidney is rich in mitochondria, and mitochondrial dysfunction is a common denominator for several renal diseases. While the mitochondrial master regulator peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α) is highly expressed in kidney, its role in renal physiology is so far unclear. Here we show that PGC-1α is a transcriptional regulator of mitochondrial metabolic pathways in the kidney. Moreover, we demonstrate that mice with an inducible nephron-specific inactivation of PGC-1α in the kidney display elevated urinary sodium excretion, exacerbated renal steatosis during metabolic stress but normal blood pressure regulation. Overall, PGC-1α seems largely dispensable for basal renal physiology. However, the role of PGC-1α in renal mitochondrial biogenesis indicates that activation of PGC-1α in the context of renal disorders could be a valid therapeutic strategy to ameliorate renal mitochondrial dysfunction. PMID:27463191

  6. FARMACOFISIOLOGÍA RENAL

    Directory of Open Access Journals (Sweden)

    Musso CG

    2014-03-01

    Full Text Available Renal physiology plays a key role in the pharmacokinetics of many drugs. Knowledge of the particularities of each nephron function (filtration, secretion, reabsorption and excretion and each of renal tubular transport mechanisms (simple diffusion, facilitated diffusion, facilitated transport, active transport, endocytosis and pinocytosis is fundamental to achieve better management of drug prescriptions.

  7. Renal Function in Hypothyroidism

    International Nuclear Information System (INIS)

    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)

  8. Renal Function in Hypothyroidism

    International Nuclear Information System (INIS)

    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).

  9. Eligibility for renal denervation

    DEFF Research Database (Denmark)

    Persu, Alexandre; Jin, Yu; Baelen, Marie;

    2014-01-01

    Based on the SYMPLICITY studies and CE (Conformité Européenne) certification, renal denervation is currently applied as a novel treatment of resistant hypertension in Europe. However, information on the proportion of patients with resistant hypertension qualifying for renal denervation after a th...

  10. 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.

  11. Tetracycline in uranyl nitrate intoxication: Its action on renal damage and U retention in bone

    International Nuclear Information System (INIS)

    In acute intoxication, uranium (U) not only inhibits bone formation but its excretion in urine also causes renal damage. The former effect is ameliorated by tetracycline (TC), probably due to its chelation property, which might also prevent U deposition in bone. Chemical determination of U incorporated in bone and a histological study of the kidneys were performed on animals injected with U and then treated with TC. The results showed that TC was unable to prevent the binding of U to bone while it exacerbated U-induced renal damage

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

    International Nuclear Information System (INIS)

    Objective: To study the value of 99Tcm-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 99Tcm-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 99Tcm-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: 99Tcm-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

  13. Renal replacement therapy after cardiac surgery; renal function recovers

    DEFF Research Database (Denmark)

    Steinthorsdottir, Kristin Julia; Kandler, Kristian; Agerlin Windeløv, Nis;

    2013-01-01

    To assess renal outcome in patients discharged from hospital following cardiac surgery-associated acute kidney injury (CSA-AKI) with need for renal replacement therapy.......To assess renal outcome in patients discharged from hospital following cardiac surgery-associated acute kidney injury (CSA-AKI) with need for renal replacement therapy....

  14. Antagonistic formation motion of cooperative agents

    Institute of Scientific and Technical Information of China (English)

    卢婉婷; 代明香; 薛方正

    2015-01-01

    This paper investigates a new formation motion problem of a class of first-order multi-agent systems with antagonis-tic interactions. A distributed formation control algorithm is proposed for each agent to realize the antagonistic formation motion. A sufficient condition is derived to ensure that all agents make an antagonistic formation motion in a distributed manner. It is shown that all agents can be spontaneously divided into several groups, and agents in the same group collab-orate while agents in different groups compete. Finally, a numerical simulation is included to demonstrate our theoretical results.

  15. Angiotensin receptor blocker telmisartan suppresses renal gluconeogenesis during starvation

    Directory of Open Access Journals (Sweden)

    Tojo A

    2015-02-01

    Full Text Available Akihiro Tojo, Saaya Hatakeyama, Satoshi Kinugasa, Masaomi Nangaku Division of Nephrology and Endocrinology, The University of Tokyo, Tokyo, Japan Abstract: The kidney plays an important role in gluconeogenesis during starvation. To clarify the anti-diabetic action of angiotensin receptor blockers, we examined the effects of telmisartan on the sodium-glucose co-transporters (SGLT and the pathways of renal gluconeogenesis in streptozotocin-induced diabetes mellitus (DM rats. At 4 weeks, the DM rats treated with/without telmisartan for 2 weeks and normal control rats were used for the study after a 24-hour fast. SGLT2 expressed on the brush border membrane of the proximal convoluted tubules increased in the DM rats, but decreased in the rats treated with telmisartan. The expression of restriction enzymes of gluconeogenesis, glucose-6-phosphatase, and phosphoenolpyruvate carboxykinase increased in the proximal tubules in the DM rats, whereas these enzymes decreased in the kidneys of the rats treated with telmisartan. The elevated cytoplasmic glucose-6-phosphate and glucose levels in the kidney of DM rats significantly decreased in those treated with telmisartan, whereas those levels in the liver did not show significant change. Meanwhile, the high plasma glucose levels in the DM rats during the intravenous insulin tolerance tests were ameliorated by telmisartan. The increased fasting plasma glucose levels after 24 hours of starvation in the DM rats thus returned to the control levels by telmisartan treatment. In conclusion, the increased renal SGLT2 expression, elevated renal gluconeogenesis enzymes and extent of insulin-resistance in the DM rats were ameliorated by telmisartan therapy, thus resulting in decreased plasma glucose levels after 24 hours of fasting. Keywords: SGLT2, renal gluconeogenesis, diabetes, angiotensin II

  16. Strategies for Reducing Respiratory Motion Artifacts in Renal Perfusion Imaging with Arterial Spin Labeling

    OpenAIRE

    Robson, Philip M.; Madhuranthakam, Ananth J.; Dai, Weiying; Pedrosa, Ivan; Rofsky, Neil M.; Alsop, David C.

    2009-01-01

    Arterial Spin Labeling (ASL) perfusion measurements may have many applications outside the brain. In the abdomen, severe image-artifacts can arise from motions between acquisitions of multiple signal averages in ASL, even with single-shot image-acquisition. Background suppression and respiratory motion synchronization techniques can be used to ameliorate these artifacts. Two separate in-vivo studies of renal perfusion imaging using pulsed-continuous ASL were performed. The first study assesse...

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

    OpenAIRE

    Amrit Pal Singh; Amteshwar Jaggi Singh; Nirmal Singh

    2011-01-01

    Objective : 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. Materials and Methods : 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, ...

  18. Effects of Sodium Citrate on Salt Sensitivity and Kidney Injury in Chronic Renal Failure

    OpenAIRE

    Kim, Sejoong; Yang, Jin Young; Jung, Eun Sook; Lee, Jeonghwan; Heo, Nam Ju; Lee, Jae Wook; Na, Ki Young; Han, Jin Suk

    2014-01-01

    Metabolic acidosis, which is observed in salt-sensitive hypertension, is also associated with kidney injury. Alkali therapy in chronic renal failure (CRF) may ameliorate the progression of kidney disease; however, few studies have examined the effects of alkali therapy on salt sensitivity and kidney injury in CRF. We randomly administered standard diet (SD), sodium chloride with 20% casein diet (NACL), or sodium citrate with 20% casein diet (NACT) to Sprague-Dawley rats after a CRF or a sham ...

  19. A novel NF-κB inhibitor, DHMEQ, ameliorates pristane-induced lupus in mice.

    Science.gov (United States)

    Qu, Huiqing; Bian, Weihua; Xu, Yanyan

    2014-07-01

    Nuclear factor (NF)-κB is strongly associated with the development of immune regulation and inflammation. The aim of the present study was to identify whether a NF-κB inhibitor, dehydroxymethylepoxyquinomicin (DHMEQ), ameliorates systemic lupus erythematosus (SLE) in a pristane-induced mouse model. SLE was induced in 8-week-old female BALB/c mice by the injection of 0.5 ml pristane. The therapeutic effect of 12 mg/kg DHMEQ on the pristane-induced BALB/c mouse model of lupus was investigated to elucidate the effects on SLE. The intraperitoneal administration of DHMEQ three times per week was initiated when the mice were 16 weeks-old (8 weeks following the pristane injection) and the treatment was continued for 16 weeks. Serum IgG autoantibodies against nucleosomes, dsDNA and histones were detected at weeks 8, 16 and 32. In addition, the expression levels of interleukin (IL)-1β, 6 and 17, as well as tumor necrosis factor (TNF)-α, were analyzed at week 32. Renal lesions were also observed. DHMEQ was shown to antagonize the increasing levels of anti-nucleosome, anti-dsDNA and anti-histone autoantibodies, as well as the increasing levels of IL-1β, 6 and 17 and TNF-α. In addition, DHMEQ reduced the number of renal lesions caused by pristane, as reflected by milder proteinuria and reduced renal pathology. The renal expression levels of phosphorylated-p38 mitogen-activated protein kinase (MAPK), phosphorylated-c-Jun N-terminal kinase (JNK) and NF-κB p65 were significantly downregulated. Therefore, the results of the present study indicate that DHMEQ has a beneficial effect on pristane-induced lupus through regulating cytokine levels and the MAPK/JNK/NF-κB signaling pathway. PMID:24944605

  20. Amelioration of radiation nephropathy in rats by postirradiation treatment with dexamethasone and/or captopril

    International Nuclear Information System (INIS)

    Dexamethasone (DEX) and captopril are effective drugs in the treatment of radiation nephropathy in experimental animals. The aim of the present study was to determine the relative effectiveness of the two drugs and to see if their combination is more effective than either drug alone. For this purpose both kidneys of 143 rats were exposed surgically and irradiated with 13-20 Gy γ rays. The surrounding tissues, with the exception of a segment of lumbar cord, were shielded. Each group had free access to acidified drinking water containing either DEX (94 μg/l), captopril (500 mg/l), DEX (94μg/l) + captopril (500 mg/l) or drug-free water. Dexamethasone treatment was stopped after 90 days, but animals continued to receive captopril until death. At approximately monthly intervals the animals were weighed and renal function (PUN, hematocrit, 51Cr-EDTA retention) was measured. A side effect of treatment with DEX and DEX + captopril was a reduced increase in body weight. Paralysis of the hind limbs developed in nine animals that received captopril and/or DEX treatment. The classical histological lesions associated with radiation myelopathy were not evident in these paretic rats. It is therefore suggested that paralysis may be attributed in part to drug-induced neurotoxicity in animals with impaired renal clearance. Macroscopically and histologically, nearly all the animals that survived more than 400 days had evidence of renal tumor development. dexamethasone and/or captopril appear to selectively ameliorate glomerular compared to tubular damage, based on histological findings. All three experimental treatments delayed but did not stop the progression of lethal renal injury as measured by kidney function tests and survival time. Median survival times for nontreated and captopril-DEX- and DEX + captopril-treated animals exposed to 14.5 to 19.0 Gy kidney irradiation were 175,242,261 and 395 days, respectively. 33 refs., 8 figs., 4 tabs

  1. Renal Preservation Therapy for Renal Cell Carcinoma

    Directory of Open Access Journals (Sweden)

    Yichun Chiu

    2012-01-01

    Full Text Available Renal preservation therapy has been a promising concept for the treatment of localized renal cell carcinoma (RCC for 20 years. Nowadays partial nephrectomy (PN is well accepted to treat the localized RCC and the oncological control is proved to be the same as the radical nephrectomy (RN. Under the result of well oncological control, minimal invasive method gains more popularity than the open PN, like laparoscopic partial nephrectomy (LPN and robot assisted laparoscopic partial nephrectomy (RPN. On the other hand, thermoablative therapy and cryoablation also play an important role in the renal preservation therapy to improve the patient procedural tolerance. Novel modalities, but limited to small number of patients, include high-intensity ultrasound (HIFU, radiosurgery, microwave therapy (MWT, laser interstitial thermal therapy (LITT, and pulsed cavitational ultrasound (PCU. Although initial results are encouraging, their real clinical roles are still under evaluation. On the other hand, active surveillance (AS has also been advocated by some for patients who are unfit for surgery. It is reasonable to choose the best therapeutic method among varieties of treatment modalities according to patients' age, physical status, and financial aid to maximize the treatment effect among cancer control, patient morbidity, and preservation of renal function.

  2. Renal infarction in patients presenting with suspected renal colic *

    OpenAIRE

    Seetho, Ian W.; Bungay, Peter M.; Taal, Maarten W.; Fluck, Richard J.; Leung, Janson C. H.

    2009-01-01

    Acute renal infarction is a serious medical emergency. The diagnosis is often delayed or missed as it is not common. Hence, the exact incidence of acute renal infarction is not known. Failure to consider renal infarction in the initial differential diagnosis results in a delay in diagnosis and treatment, which in turn leads to permanent loss of renal function. We present two cases of acute kidney infarction that were initially treated as renal colic. In addition, we present a third case when ...

  3. Renal (Kidney) Manifestations in TSC

    Medline Plus

    Full Text Available ... in TSC: renal cysts, renal angiomyolipoma and renal cell carcinoma . Renal angiomyolipomata, or angiomyolipomas, are usually the greatest concern in TSC. The blood vessels within angiomyolipomas are abnormal and can develop weak spots in their wall, called aneurysms, that can burst and lead to ...

  4. 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.

  5. Renal imaging in paediatrics

    International Nuclear Information System (INIS)

    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.)

  6. Synergism of irbesartan and amlodipine on hemodynamic amelioration and organ protection in spontaneously hypertensive rats

    Institute of Scientific and Technical Information of China (English)

    Wen SHANG; Ping HAN; Cheng-bing YANG; Xiao-wen GU; Wei ZHANG; Li-ping XU; Shou-ting FU; Ding-feng SU; He-hui XlE

    2011-01-01

    To investigate the synergism of low-doses of amlodipine and irbesartan on reduction of blood pressure variability (BPV),amelioration of baroreflex sensitivity (BRS) and organ protection in spontaneously hypertensive rats (SHR).Methods:The rats were administered amlodipine (1 mg-kgl.dl) alone,irbesartan (10 mg·kg-1·d-1) alone,or the combination of the two drugs for 4 months.The drugs were mixed into the rat chow.Blood pressure (BP) was continuously monitored in conscious animals.After the determination of BRS,the rats were killed for morphological evaluation of organ damages.Results:The combination of low-dose irbesartan and amlodipine had statistically significant synergism on reduction of BP and BPV,amelioration of BRS and organ protection in SHR.Multiple regression analysis showed that the decrease in left ventricular hypertrophy was associated with the decrease in systolic BPV (r=0.665,P<0.01); the decrease in aortic hypertrophy was associated with the increase in BRS (r=0.656,P<0.01); and the amelioration in renal lesion was associated with the increase in BRS (r=0.763,P<0.01)and the decrease in systolic BPV (r=0.706,P<0.01).Conclusion:Long-term treatment with a combination of low-doses of amlodipine and irbesartan showed significant synergism on reduction of BP and BPV,restoration of BRS and organ protection in SHR.Besides BP reduction,the enhancement of BRS and reduction of BPV might contribute to the organ protection.

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

    International Nuclear Information System (INIS)

    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

  8. Salvianolic acid A as a multifunctional agent ameliorates doxorubicin-induced nephropathy in rats.

    Science.gov (United States)

    Fan, Hua-Ying; Yang, Ming-Yan; Qi, Dong; Zhang, Zuo-Kai; Zhu, Lin; Shang-Guan, Xiu-Xin; Liu, Ke; Xu, Hui; Che, Xin

    2015-01-01

    Nephrotic syndrome (NS) is still a therapeutic challenge. To date there is no ideal treatment. Evidence suggest that multidrug therapy has more effect than monotherapy in amelioration of renal injury. Salvianolic acid A (SAA) is the major active component of Salviae Miltiorrhizae Bunge. Previous studies have demonstrated that SAA is a multi-target agent and has various pharmacological activities. The pleiotropic properties of SAA predict its potential in the treatment of NS. The study investigated the effect of SAA on doxorubicin-induced nephropathy. The kidney function related-biochemical changes, hemorheological parameters and oxidative stress status were determined, and histological examination using light and transmission electron microcopies and western blot analysis were also performed. Results revealed that treatment with SAA alleviated histological damages, relieved proteinuria, hypoalbuminemia and hyperlipidemia, reduced oxidative stress, as well as improving hemorheology. Furthermore, SAA restored podocin expression, down-regulated the expression of NF-κB p65 and p-IκBα while up-regulating IκBα protein expression. Overall, as a multifunctional agent, SAA has a favorable renoprotection in doxorubicin-induced nephropathy. The anti-inflammation, antioxidant, amelioration of podocyte injury, improvement of hemorheology and hypolipidemic properties may constituent an important part of its therapeutic effects. All these indicate that SAA is likely to be a promising agent for NS. PMID:26194431

  9. Cytokine antagonists and their potential therapeutic use

    OpenAIRE

    Debets, Reno; Savelkoul, Huub

    1994-01-01

    textabstractNew and exciting developments in the understanding of the interaction between cytokines and their receptors, and the clinical application of cytokine antagonists, were discussed at a recent meeting. Here, Reno Debets and Huub Savelkoul revisit this progress.

  10. Cacao polyphenols ameliorate autoimmune myocarditis in mice.

    Science.gov (United States)

    Zempo, Hirofumi; Suzuki, Jun-Ichi; Watanabe, Ryo; Wakayama, Kouji; Kumagai, Hidetoshi; Ikeda, Yuichi; Akazawa, Hiroshi; Komuro, Issei; Isobe, Mitsuaki

    2016-04-01

    Myocarditis is a clinically severe disease; however, no effective treatment has been established. The aim of this study was to determine whether cacao bean (Theobroma cacao) polyphenols ameliorate autoimmune myocarditis. We used an experimental autoimmune myocarditis (EAM) model in Balb/c mice. Mice with induced EAM were treated with a cacao polyphenol extract (CPE, n=12) or vehicle (n=12). On day 21, hearts were harvested and analyzed. Elevated heart weight to body weight and fibrotic area ratios as well as high cardiac cell infiltration were observed in the vehicle-treated EAM mice. However, these increases were significantly suppressed in the CPE-treated mice. Reverse transcriptase-PCR revealed that mRNA expressions of interleukin (Il)-1β, Il-6, E-selectin, vascular cell adhesion molecule-1 and collagen type 1 were lower in the CPE group compared with the vehicle group. The mRNA expressions of nicotinamide adenine dinucleotide phosphate-oxidase (Nox)2 and Nox4 were increased in the vehicle-treated EAM hearts, although CPE treatment did not significantly suppress the transcription levels. However, compared with vehicle treatment of EAM hearts, CPE treatment significantly suppressed hydrogen peroxide concentrations. Cardiac myeloperoxidase activity, the intensity of dihydroethidium staining and the phosphorylation of nuclear factor-κB p65 were also lower in the CPE group compared with the vehicle group. Our data suggest that CPE ameliorates EAM in mice. CPE is a promising dietary supplement to suppress cardiovascular inflammation and oxidative stress. PMID:26657007

  11. Means for limiting and ameliorating electrode shorting

    Energy Technology Data Exchange (ETDEWEB)

    Konynenburg, R.A. van; Farmer, J.C.

    1999-11-09

    A fuse and filter arrangement is described for limiting and ameliorating electrode shorting in capacitive deionization water purification systems utilizing carbon aerogel, for example. This arrangement limits and ameliorates the effects of conducting particles or debonded carbon aerogel in shorting the electrodes of a system such as a capacitive deionization water purification system. This is important because of the small interelectrode spacing and the finite possibility of debonding or fragmentation of carbon aerogel in a large system. The fuse and filter arrangement electrically protect the entire system from shutting down if a single pair of electrodes is shorted and mechanically prevents a conducting particle from migrating through the electrode stack, shorting a series of electrode pairs in sequence. It also limits the amount of energy released in a shorting event. The arrangement consists of a set of circuit breakers or fuses with one fuse or breaker in the power line connected to one electrode of each electrode pair and a set of screens of filters in the water flow channels between each set of electrode pairs.

  12. Means for limiting and ameliorating electrode shorting

    Energy Technology Data Exchange (ETDEWEB)

    Van Konynenburg, Richard A. (Livermore, CA); Farmer, Joseph C. (Tracy, CA)

    1999-01-01

    A fuse and filter arrangement for limiting and ameliorating electrode shorting in capacitive deionization water purification systems utilizing carbon aerogel, for example. This arrangement limits and ameliorates the effects of conducting particles or debonded carbon aerogel in shorting the electrodes of a system such as a capacitive deionization water purification system. This is important because of the small interelectrode spacing and the finite possibility of debonding or fragmentation of carbon aerogel in a large system. The fuse and filter arrangement electrically protect the entire system from shutting down if a single pair of electrodes is shorted and mechanically prevents a conducting particle from migrating through the electrode stack, shorting a series of electrode pairs in sequence. It also limits the amount of energy released in a shorting event. The arrangement consists of a set of circuit breakers or fuses with one fuse or breaker in the power line connected to one electrode of each electrode pair and a set of screens of filters in the water flow channels between each set of electrode pairs.

  13. 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.

  14. Acute renal failure in children

    International Nuclear Information System (INIS)

    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.)

  15. Insuficiencia renal aguda.

    OpenAIRE

    Carlos Hernán Mejía

    2009-01-01

    La insuficiencia renal aguda se diagnostica aproximadamente en 5% de los pacientes hospitalizados. Sus principales causas se relacionan con la alteración del flujo sanguíneo renal, sea por depleción de volumen, baja perfusión renal o por distribución intrarrenal inadecuada y obstrucción del árbol urinario. El diagnóstico parte de la historia clínica y un buen examen físico que corrobore el estado de volemia del paciente y se complementa con el uso adecuado de los índices urinarios (excreción ...

  16. Insuficiencia renal aguda

    OpenAIRE

    Carlos Hernán Mejía

    1985-01-01

    La insuficiencia renal aguda se diagnostica aproximadamente en 5% de los pacientes hospitalizados. Sus principales causas se relacionan con la alteración del flujo sanguíneo renal, sea por depleción de volumen, baja perfusión renal o por distribución intrarrenal inadecuada y obstrucción del árbol urinario. El diagnóstico parte de la historia clínica y un buen examen físico que corrobore el estado de volemia del paciente y se complementa con el uso adecuado de los índices urinarios (excreción ...

  17. Diphenyl diselenide, a simple organoselenium compound, decreases methylmercury-induced cerebral, hepatic and renal oxidative stress and mercury deposition in adult mice.

    Science.gov (United States)

    de Freitas, Andressa Sausen; Funck, Vinícius Rafael; Rotta, Mariana dos Santos; Bohrer, Denise; Mörschbächer, Vanessa; Puntel, Robson Luís; Nogueira, Cristina Wayne; Farina, Marcelo; Aschner, Michael; Rocha, João Batista Teixeira

    2009-04-01

    Oxidative stress has been pointed out as an important molecular mechanism in methylmercury (MeHg) intoxication. At low doses, diphenyl diselenide ((PhSe)2), a structurally simple organoselenium compound, has been shown to possess antioxidant and neuroprotective properties. Here we have examined the possible in vivo protective effect of diphenyl diselenide against the potential pro-oxidative effects of MeHg in mouse liver, kidney, cerebrum and cerebellum. The effects of MeHg exposure (2 mg/(kg day) of methylmercury chloride 10 ml/kg, p.o.), as well as the possible antagonist effect of diphenyl diselenide (1 and 0.4 mg/(kg day); s.c.) on body weight gain and on hepatic, cerebellar, cerebral and renal levels of thiobarbituric acid reactive substances (TBARS), non-protein thiols (NPSH), ascorbic acid content, mercury concentrations and activities of antioxidant enzymes (glutathione peroxidase (GPx), catalase (CAT) and superoxide dismutase (SOD)) were evaluated after 35 days of treatment. MeHg caused an increase in TBARS and decreased NPSH levels in all tissues. MeHg also induced a decrease in hepatic ascorbic acid content and in renal GPx and CAT activities. Diphenyl diselenide (1 mg/kg) conferred protection against MeHg-induced hepatic and renal lipid peroxidation and at both doses prevented the reduction in hepatic NPSH levels. Diphenyl diselenide also conferred a partial protection against MeHg-induced oxidative stress (TBARS and NPSH) in liver and cerebellum. Of particular importance, diphenyl diselenide decreased the deposition of Hg in cerebrum, cerebellum, kidney and liver. The present results indicate that diphenyl diselenide can protect against some toxic effects of MeHg in mice. This protection may be related to its antioxidant properties and its ability to reduce Hg body burden. We posit that formation of a selenol intermediate, which possesses high nucleophilicity and high affinity for MeHg, accounts for the ability of diphenyl diselenide to ameliorate Me

  18. High-affinity neuropeptide Y receptor antagonists.

    OpenAIRE

    Daniels, A J; Matthews, J. E.; Slepetis, R J; Jansen, M; Viveros, O. H.; Tadepalli, A.; Harrington, W; Heyer, D; Landavazo, A; Leban, J J

    1995-01-01

    Neuropeptide Y (NPY) is one of the most abundant peptide transmitters in the mammalian brain. In the periphery it is costored and coreleased with norepinephrine from sympathetic nerve terminals. However, the physiological functions of this peptide remain unclear because of the absence of specific high-affinity receptor antagonists. Three potent NPY receptor antagonists were synthesized and tested for their biological activity in in vitro, ex vivo, and in vivo functional assays. We describe he...

  19. 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....

  20. GABAA receptor partial agonists and antagonists

    DEFF Research Database (Denmark)

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

    2015-01-01

    A high degree of structural heterogeneity of the GABAA receptors (GABAARs) has been revealed and is reflected in multiple receptor subtypes. The subunit composition of GABAAR subtypes is believed to determine their localization relative to the synapses and adapt their functional properties to the...... 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....

  1. Role of Cystathionine Gamma-Lyase in Immediate Renal Impairment and Inflammatory Response in Acute Ischemic Kidney Injury.

    Science.gov (United States)

    Markó, Lajos; Szijártó, István A; Filipovic, Milos R; Kaßmann, Mario; Balogh, András; Park, Joon-Keun; Przybyl, Lukasz; N'diaye, Gabriele; Krämer, Stephanie; Anders, Juliane; Ishii, Isao; Müller, Dominik N; Gollasch, Maik

    2016-01-01

    Hydrogen sulfide (H2S) is known to act protectively during renal ischemia/reperfusion injury (IRI). However, the role of the endogenous H2S in acute kidney injury (AKI) is largely unclear. Here, we analyzed the role of cystathionine gamma-lyase (CTH) in acute renal IRI using CTH-deficient (Cth(-/-)) mice whose renal H2S levels were approximately 50% of control (wild-type) mice. Although levels of serum creatinine and renal expression of AKI marker proteins were equivalent between Cth(-/-) and control mice, histological analysis revealed that IRI caused less renal tubular damage in Cth(-/-) mice. Flow cytometric analysis revealed that renal population of infiltrated granulocytes/macrophages was equivalent in these mice. However, renal expression levels of certain inflammatory cytokines/adhesion molecules believed to play a role in IRI were found to be lower after IRI only in Cth(-/-) mice. Our results indicate that the systemic CTH loss does not deteriorate but rather ameliorates the immediate AKI outcome probably due to reduced inflammatory responses in the kidney. The renal expression of CTH and other H2S-producing enzymes was markedly suppressed after IRI, which could be an integrated adaptive response for renal cell protection. PMID:27273292

  2. 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

  3. Renal tumors in infancy

    International Nuclear Information System (INIS)

    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

  4. Dopamins renale virkninger

    DEFF Research Database (Denmark)

    Olsen, Niels Vidiendal

    1990-01-01

    which are possible not exclusively secondary to alterations in the renal haemodynamics but may also be due to specific tubular effects. Recent investigations have revealed that dopamine does not increase RBF and GFR in patients with chronic renal failure if GFR is less than 60 ml/minute. Dopamine in low...... doses 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......Dopamine is an endogenic catecholamine which, in addition to being the direct precursor of noradrenaline, has also an effect on peripheral dopaminergic receptors. These are localized mainly in the heart, splanchnic nerves and the kidneys. Dopamine is produced in the kidneys and the renal metabolism...

  5. 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.

  6. 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

  7. 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

  8. Primary Renal Synovial Sarcoma

    OpenAIRE

    Halil Ciftci; Adem Altunkol; Ismail Ozdemir; Dilek Mil; Ilyas Ozardali; Murat Savas; Ercan Yeni; Mehmet Gulum

    2011-01-01

    Synovial sarcomas are generally deep-seated tumors that most often occur in the proximity of large joints of adolescents and young adults. We describe two cases of primary renal synovial sarcoma that were treated successfully by radical nephrectomy. Synovial sarcoma originating from the kidney is extremely rare and the histogenesis is uncertain. Surgical resection and ifosfamide based chemotherapy are the mainstay for the management of renal synovial sarcoma. Fewer than 40 patients have been ...

  9. Renal failure in malaria

    OpenAIRE

    B.S. Das

    2008-01-01

    Acute renal failure (ARF) is seen mostly in Plasmodium falciparum infection, but P. vivax and P. malariae can occasionally contribute for renal impairment. Malarial ARF is commonly found in non-immune adults and older children with falciparum malaria. Occurance of ARF in severe falciparum malaria is quite common in southeast Asia and Indian subcontinent where intensity of malaria transmission is usually low with occasional microfoci of intense transmission. Since precise mechanism of malaria...

  10. Renal clearance of melatonin

    OpenAIRE

    Editorial Office

    1996-01-01

    Only two publications exist in which actual values for the renal clearance of intact melatonin in man is described. The melatonin clearance values were, however, obtained either after the oral intake of melatonin, or by applying different techniques for the determination of melatonin in urine and plasma. In this study, renal clearance of melatonin was determined during the hours where melatonin concentrations are relatively constant. Melatonin levels in plasma and urine respectively were e...

  11. Disappearing renal calculus

    OpenAIRE

    Cui, Helen; Thomas, Johanna; Kumar, Sunil

    2013-01-01

    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.

  12. Renal dysplasia: US findings

    International Nuclear Information System (INIS)

    Renal dysplasia is a congenital anomaly with abnormal development of nephrotic and ductal structure and untreatable disease with absent renal function. To determine whether any consistent sonographic patterns exists,the sonograms of 27 pediatric patients with mastocytosis despotically kidney were reviewed. The diagnosis was proved by pathology in 16 cases and other radiologic imaging in 11 cases. In the classical multicystic despotically kidney(pelvoinfundibular atresia type, 10 cases), there were typical findings, such as absent communication between peripherally located variable sized cysts and presence of the largest cyst away from the renal hilum. One case was associated contralateral renal hydronephrosis. There cases were hydro nephrotic type which had medial location of the largest cyst with non communicating peripheral cysts. Segmental dysplasia with double collecting system and ureterocele (5 cases) and dysplasia due to parasite urethral valve (2 cases) showed hydronephrosis without identifiable peripheral cysts. Among the hypoplastic dysplastic kidney (7 cases) including ectopic kidneys (3cases), corticomedullary differentiation were hard to be identified in 2 cases. In conclusion, diagnosis of the renal dysplasia can be obtained by US only or US with other functional studies such as radionuclide scan(99mTc-DMSA or renogram) and IVP. US detection of renal dysplasia is easy, and US findings provide valuable information in the subsequent management

  13. Renal dysplasia: US findings

    Energy Technology Data Exchange (ETDEWEB)

    Ha, Doo Hoe; Oh, Ki Keun; Jung, Woo Hee; Yoon, Choon Sik; Ahn, Chang Soo; Kim, Myung Joon [Yonsei University College of Medicine, Seoul (Korea, Republic of)

    1993-12-15

    Renal dysplasia is a congenital anomaly with abnormal development of nephrotic and ductal structure and untreatable disease with absent renal function. To determine whether any consistent sonographic patterns exists,the sonograms of 27 pediatric patients with mastocytosis despotically kidney were reviewed. The diagnosis was proved by pathology in 16 cases and other radiologic imaging in 11 cases. In the classical multicystic despotically kidney(pelvoinfundibular atresia type, 10 cases), there were typical findings, such as absent communication between peripherally located variable sized cysts and presence of the largest cyst away from the renal hilum. One case was associated contralateral renal hydronephrosis. There cases were hydro nephrotic type which had medial location of the largest cyst with non communicating peripheral cysts. Segmental dysplasia with double collecting system and ureterocele (5 cases) and dysplasia due to parasite urethral valve (2 cases) showed hydronephrosis without identifiable peripheral cysts. Among the hypoplastic dysplastic kidney (7 cases) including ectopic kidneys (3cases), corticomedullary differentiation were hard to be identified in 2 cases. In conclusion, diagnosis of the renal dysplasia can be obtained by US only or US with other functional studies such as radionuclide scan(99mTc-DMSA or renogram) and IVP. US detection of renal dysplasia is easy, and US findings provide valuable information in the subsequent management

  14. Adenosine A1 receptors in contrast media-induced renal dysfunction in the normal rat

    International Nuclear Information System (INIS)

    Renal vasoconstriction with resultant tissue hypoxia, especially in the renal medulla, has been suggested to play a role in contrast media (CM)-induced nephropathy. In this study we investigated the effects of injection of the non-ionic low-osmolar CM iopromide with and without pretreatment with the selective adenosine A1-receptor antagonist DPCPX. The effects were evaluated on regional renal blood flow, outer medullary oxygen tension (PO2) and urine output in normal anaesthetised rats. A laser-Doppler technique was used for recording haemodynamic changes while oxygen microelectrodes were used for oxygen measurements. The A1-receptor antagonist per se elevated glomerular filtration rate (+44%), cortical blood flow (+15%) and urine output (threefold) while reducing outer medullary PO2 (-24%). Administration of CM reduced outer medullary blood flow (OMBF; -26%) and PO2 (-80%) but did not affect cortical blood flow. Urine output increased 28-fold by CM while arterial blood pressure was reduced. The CM-mediated effect on haemodynamics, PO2, urine output and blood pressure was unaffected by the A1-receptor antagonist. Adenosine A1-receptors are not important mediators of the depression of outer medullary blood flow and PO2 caused by the CM iopromide in the normal rat; however, A1-receptors are tonically active to regulate renal haemodynamics, PO2 and urine production during normal physiological conditions. (orig.)

  15. Telmisartan Ameliorates Fibrocystic Liver Disease in an Orthologous Rat Model of Human Autosomal Recessive Polycystic Kidney Disease

    Science.gov (United States)

    Yoshihara, Daisuke; Kugita, Masanori; Sasaki, Mai; Horie, Shigeo; Nakanishi, Koichi; Abe, Takaaki; Aukema, Harold M.; Yamaguchi, Tamio; Nagao, Shizuko

    2013-01-01

    Human autosomal recessive polycystic kidney disease (ARPKD) produces kidneys which are massively enlarged due to multiple cysts, hypertension, and congenital hepatic fibrosis characterized by dilated bile ducts and portal hypertension. The PCK rat is an orthologous model of human ARPKD with numerous fluid-filled cysts caused by stimulated cellular proliferation in the renal tubules and hepatic bile duct epithelia, with interstitial fibrosis developed in the liver. We previously reported that a peroxisome proliferator activated receptor (PPAR)-γ full agonist ameliorated kidney and liver disease in PCK rats. Telmisartan is an angiotensin receptor blocker (ARB) used widely as an antihypertensive drug and shows partial PPAR-γ agonist activity. It also has nephroprotective activity in diabetes and renal injury and prevents the effects of drug-induced hepatotoxicity and hepatic fibrosis. In the present study, we determined whether telmisartan ameliorates progression of polycystic kidney and fibrocystic liver disease in PCK rats. Five male and 5 female PCK and normal control (+/+) rats were orally administered 3 mg/kg telmisartan or vehicle every day from 4 to 20 weeks of age. Treatment with telmisartan decreased blood pressure in both PCK and +/+ rats. Blood levels of aspartate amino transferase, alanine amino transferase and urea nitrogen were unaffected by telmisartan treatment. There was no effect on kidney disease progression, but liver weight relative to body weight, liver cystic area, hepatic fibrosis index, expression levels of Ki67 and TGF-β, and the number of Ki67- and TGF-β-positive interstitial cells in the liver were significantly decreased in telmisartan-treated PCK rats. Therefore, telmisartan ameliorates congenital hepatic fibrosis in ARPKD, possibly through the inhibition of signaling cascades responsible for cellular proliferation and interstitial fibrosis in PCK rats. The present results support the potential therapeutic use of ARBs for the

  16. Amelioration of cisplatin induced nephrotoxicity in Swiss albino mice by Rubia cordifolia extract

    Directory of Open Access Journals (Sweden)

    Joy Jisha

    2008-01-01

    Full Text Available Background: Cisplatin is one of the most effective chemotherapeutics against a wide range of cancers including head, neck, ovarian and lung cancers. But its usefulness is limited by its toxicity to normal tissues, including cells of the kidney proximal tubule. The purpose of the present study is to investigate whether the hydro-alcoholic extract of Rubia cordifolia could decrease the intensity of toxicity in Swiss albino mice. Materials and Methods: Cisplatin at a dose of 12 mg/kg body wt was administered intraperitoneally to Swiss albino mice. Another set of animals was given hydro-alcoholic extract of Rubia cordifolia at different doses along with cisplatin treatment. The antioxidant levels, serum creatinine, serum urea etc. were analyzed. Results: The extract could significantly decrease the cisplatin induced nephrotoxicity as inferred from the tissue antioxidant status in the drug administered animals. Remarkable change was observed in serum creatinine and urea levels. Lipid peroxidation in the kidney and liver tissues was also considerably reduced in Rubia cordifolia extract treated animals. Conclusion: Hydro-alcoholic extracts of Rubia cordifolia are effective in reducing the renal damage caused by the cancer chemotherapeutic drug cisplatin. Since Rubia cordifolia has been in use as an important ingredient in the traditional Ayurvedic system of medicine, it could be safe and beneficial to use this herbal extract as an adjuvant to ameliorate renal damage in patients undergoing cancer chemotherapy with cisplatin.

  17. PPARγ Antagonist Gleevec Improves Insulin Sensitivity and Promotes the Browning of White Adipose Tissue.

    Science.gov (United States)

    Choi, Sun-Sil; Kim, Eun-Sun; Jung, Ji-Eun; Marciano, David P; Jo, Ala; Koo, Ja Young; Choi, Soo Youn; Yang, Yong Ryoul; Jang, Hyun-Jun; Kim, Eung-Kyun; Park, Jiyoung; Kwon, Hyug Moo; Lee, In Hee; Park, Seung Bum; Myung, Kyung-Jae; Suh, Pann-Ghill; Griffin, Patrick R; Choi, Jang Hyun

    2016-04-01

    Blocking phosphorylation of peroxisome proliferator-activated receptor (PPAR)γ at Ser(273) is one of the key mechanisms for antidiabetes drugs to target PPARγ. Using high-throughput phosphorylation screening, we here describe that Gleevec blocks cyclin-dependent kinase 5-mediated PPARγ phosphorylation devoid of classical agonism as a PPARγ antagonist ligand. In high fat-fed mice, Gleevec improved insulin sensitivity without causing severe side effects associated with other PPARγ-targeting drugs. Furthermore, Gleevec reduces lipogenic and gluconeogenic gene expression in liver and ameliorates inflammation in adipose tissues. Interestingly, Gleevec increases browning of white adipose tissue and energy expenditure. Taken together, the results indicate that Gleevec exhibits greater beneficial effects on both glucose/lipid metabolism and energy homeostasis by blocking PPARγ phosphorylation. These data illustrate that Gleevec could be a novel therapeutic agent for use in insulin resistance and type 2 diabetes. PMID:26740599

  18. Anti-Angiogenic Drugs in the Treatment of Metastatic Renal Cell Carcinoma:Advances in Clinical Application

    DEFF Research Database (Denmark)

    Nielsen, Ole H; Grimm, Daniela; Wehland, Markus;

    2014-01-01

    The current paradigm in attempting to treat metastatic renal cell carcinoma (mRCC) is a first line treatment with a vascular endothelial growth factor (VEGF) antagonist and second and subsequent treatments with either a vascular endothelial growth factor receptor (VEGFR) or a mTOR (mammalian Targ...

  19. Malignant renal tumors in children

    Directory of Open Access Journals (Sweden)

    Justin Scott Lee

    2015-05-01

    Full Text Available Renal malignancies are common in children. While the majority of malignant renal masses are secondary to Wilms tumor, it can be challenging to distinguish from more aggressive renal masses. For suspicious renal lesions, it is crucial to ensure prompt diagnosis in order to select the appropriate surgical procedure and treatment. This review article will discuss the common differential diagnosis that can be encountered when evaluating a suspicious renal mass in the pediatric population. This includes clear cell sarcoma of the kidney, malignant rhabdoid tumor, renal medullary carcinoma and lymphoma. 

  20. 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...

  1. [Management of vitamin K antagonists in the elderly].

    Science.gov (United States)

    Belleville, Tiphaine; Pautas, Éric; Gaussem, Pascale; Siguret, Virginie

    2014-01-01

    Elderly patients of 80 years and above are commonly frail, due to substantial comorbid conditions and numerous medications. Managing elderly patients receiving vitamin K antagonists (VKA) is challenging because those patients are at high risk of both thrombosis and bleeding. Special considerations on the choice of the VKA drug, dosing and monitoring have to be taken into account in the elderly in order to avoid over-anticoagulation and to minimize the haemorrhagic risk which consequences may be dramatic or fatal in this age group. In these patients, INR monitoring is crucial, especially at the start of treatment. The use of dosing algorithms specifically developed for elderly patients allows to decrease over-anticoagulation during the initiation period. INR has to be monitored more frequently in case of acute illness or in case of modification of the associated drugs. Patient information and education are of great importance, even in geriatric patients and has been shown to improve the quality of anticoagulation. Even though the use of direct oral anticoagulants is currently expanding, prescribing VKA in elderly patients in whom the prevalence of severe renal insufficiency remains up to date. PMID:24736138

  2. CT diagnosis of renal and extrarenal complications after renal transplantation

    International Nuclear Information System (INIS)

    Methods and results of static and dynamic CT of renal transplants are presented. Validity of the method concerning morphologic and functional lesions of the organ and of extrarenal structures are outlined. Special attention is paid to functional changes and differential diagnosis of the most frequent complications after renal transplantation. Whereas CT diagnosis of renal and pararenal morphology is unquestioned, the problem of differentiating between acute tubular necrosis and acute rejection is not yet solved. Nevertheless description of renal function is possible. (orig.)

  3. Management of renal cell carcinoma presenting as inflammatory renal mass

    OpenAIRE

    Ehab Eltahawy; Mohamed Kamel; Mahmoud Ezzet

    2015-01-01

    Introduction: Renal cell carcinoma (RCC) can have a wide spectrum of clinical presentations. In the immunocompromised patient fever and an inflammatory renal mass can harbor RCC. Materials and Methods: We reviewed the charts of patients who were managed at our department during 1998-2008 as renal abscess or perinephric collection. Renal ultrasound and subsequently abdominal CT was done. Medical treatment in the form of antibiotics, control of diabetes and drainage was done. Percutaneous ...

  4. Renal consequences of obesity.

    Science.gov (United States)

    Naumnik, Beata; Myśliwiec, Michał

    2010-08-01

    The worldwide prevalence of obesity and its associated metabolic and cardiovascular disorders has risen dramatically within the past 2 decades. Our objective is to review the mechanisms that link obesity with altered kidney function. Current evidence suggests that excess weight gain may be responsible for 65-75% of the risk for arterial hypertension. Impaired renal pressure natriuresis, initially due to increased renal tubular sodium reabsorption, is a key factor linking obesity with hypertension. Obesity increases renal sodium reabsorption by activating the renin-angiotensin and sympathetic nervous systems, and by altering intrarenal physical forces. Adipose tissue functions as an endocrine organ, secreting hormones/cytokines (e.g., leptin) which may trigger sodium retention and hypertension. Additionally, excess visceral adipose tissue may physically compress the kidneys, increasing intrarenal pressures and tubular reabsorption. Eventually, sustained obesity via hyperinsulinemia, due to resistance to insulin, causes hyperfiltration, resulting in structural changes in the kidneys--glomerular hyperthrophy and occasionally focal segmental glomerulosclerosis. The consequences of kidney injury are continuous loss of glomerular filtration rate, further increase of arterial pressure and escalation of cardiovascular morbidity and mortality. There is a growing awareness of the renal consequences of obesity, and considerable progress is being made in understanding its pathophysiology. Weight reduction results in lowered proteinuria. Aside from low sodium diet and exercises, more widespread use of renoprotective therapy (e.g., ACE inhibitors and statins) in treatment of hypertension in obese subjects should be advocated. Renal protection should result in reducing the cardiovascular complications of obesity. PMID:20671624

  5. Histamine-2 Receptor Antagonists and Semen Quality.

    Science.gov (United States)

    Banihani, Saleem A

    2016-01-01

    Histamine-2 receptor antagonists are a class of drugs used to treat the acid-related gastrointestinal diseases such as ulcer and gastro-oesophageal reflux disease. Although such drugs, especially ranitidine and famotidine, are still widely used, their effects on semen quality, and hence on male infertility, is still unclear. This MiniReview systematically addresses and summarizes the effect of histamine-2 receptor antagonists (cimetidine, ranitidine, nizatidine and famotidine) on semen quality, particularly, on sperm function. Cimetidine appears to have adverse effects on semen quality. While the effects of ranitidine and nizatidine on semen quality are still controversial, famotidine does not appear to change semen quality. Therefore, additional studies will be required to clarify whether histamine-2 receptor-independent effects of these drugs play a role in semen quality as well as further clinical studies including direct comparison of the histamine-2 receptor antagonists. PMID:26176290

  6. Auxin-Oxylipin Crosstalk: Relationship of Antagonists

    Institute of Scientific and Technical Information of China (English)

    Maik Hoffmann; Mathias Hentrich; Stephan Pollmann

    2011-01-01

    Phytohormones regulate a wide array of developmental processes throughout the life cycle of plants. Herein, the various plant hormones may interact additively, synergistically, or antagonistically. By their cooperation they create a delicate regulatory network whose net output largely depends on the action of specific phytohormone combinations rather than on the independent activities of separate hormones. While most classical studies of plant hormonal control have focused mainly on the action of single hormones or on the synergistic interaction of hormones in regulating various developmental processes, recent work is beginning to shed light on the crosstalk of nominally antagonistic plant hormones, such as gibberellins and auxins with oxylipins or abscisic acid. In this review, we summarize our current understanding of how two of the first sight antagonistic plant hormones, i.e. auxins and oxylipins,interact in controlling plant responses and development.

  7. 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.

  8. Influence of the CB1 receptor antagonist, AM 251, on the regional haemodynamic effects of WIN-55212-2 or HU 210 in conscious rats

    OpenAIRE

    Gardiner, S. M.; March, J. E.; Kemp, P. A.; Bennett, T.

    2002-01-01

    In conscious, freely-moving, male, Sprague-Dawley rats, the regional haemodynamic responses to the synthetic cannabinoids, WIN-55212-2 and HU 210, were compared. The possible involvement of cannabinoid, CB1-receptors, or β2-adrenoceptors in the responses to WIN-55212-2 and HU 210 were investigated using the CB1-receptor antagonist, AM 251, or the β2-adrenoceptor antagonist, ICI 118551, respectively.Both WIN-55212-2 (150 μg kg−1) and HU 210 (100 μg kg−1) had pressor, renal, and mesenteric vaso...

  9. 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. PMID:26616141

  10. Renal (Kidney) Manifestations in TSC

    Medline Plus

    Full Text Available ... severe kidney disease can develop in infancy or early childhood and renal failure most often occurs in early adulthood. Renal Angiomyolipomas Angiomyolipomas are named because they ...

  11. 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.

  12. Renal (Kidney) Manifestations in TSC

    Medline Plus

    Full Text Available ... must be kept in mind. Diagnosis The current methods to diagnosis these renal abnormalities include renal ultrasonography, ... cells, which surround a fluid-filled cavity. Some children and adults with TSC and severe cystic kidneys ...

  13. Renal (Kidney) Manifestations in TSC

    Medline Plus

    Full Text Available ... in about 50 percent of individuals with TSC. These cysts, even if they are not very common, ... in mind. Diagnosis The current methods to diagnosis these renal abnormalities include renal ultrasonography, CT scanning and ...

  14. Renal (Kidney) Manifestations in TSC

    Medline Plus

    Full Text Available ... to kidney impairment and even kidney failure, requiring dialysis or transplantation. Lastly, renal cell carcinoma, the least ... kidney failure occurs, renal replacement therapy such as dialysis or transplantation is necessary. How kidney cysts develop ...

  15. Renal (Kidney) Manifestations in TSC

    Medline Plus

    Full Text Available ... Get Involved RENAL (KIDNEY) MANIFESTATIONS IN TSC Download a PDF of this information. The majority of individuals ( ... the least common renal association with TSC, is a cancerous growth of the kidney. Although it is ...

  16. Polyhydramnios and acute renal failure

    OpenAIRE

    Hamilton, D. V.; Kelly, Moira B.; Pryor, J. S.

    1980-01-01

    Acute renal failure secondary to ureteric obstruction is described in a primigravida with twin gestation and polyhydramnios. Relief of the obstruction occurred on drainage of the liquor and return to normal renal function following delivery.

  17. Renal (Kidney) Manifestations in TSC

    Medline Plus

    Full Text Available ... lesion must be kept in mind. Diagnosis The current methods to diagnosis these renal abnormalities include renal ... about clinical trials and see a list of current trials/studies related to TSC. Enroll now in ...

  18. Renal (Kidney) Manifestations in TSC

    Medline Plus

    Full Text Available ... For Individuals & Families For Healthcare Professionals For Researchers & Scientists For School Issues What Is TSC? How Is ... must be kept in mind. Diagnosis The current methods to diagnosis these renal abnormalities include renal ultrasonography, ...

  19. Role of angiotensin AT2 receptors and nitric oxide in the cardiopulmonary baroreflex control of renal sympathetic nerve activity in anaesthetised rats

    OpenAIRE

    Abdulla, Mohammed H.; Johns, Edward J.

    2013-01-01

    This study investigated the role of AT2 receptor activation and the possible interaction with nitric oxide (NO) in low-pressure baroreceptor regulation of renal sympathetic nerve activity (RSNA). Renal sympatho-inhibition to a saline volume expansion (VEP, 0.25% bwt/min I.V. for 30 min) was studied following intracerebroventricular (i.c.v.) saline, CGP42112 (CGP, AT2 agonist), PD123319 (PD, AT2 antagonist) and losartan (AT1 antagonist), and then in combination with L-NAME (NO synthase inhibit...

  20. Renal Tumor Biopsy Technique

    Institute of Scientific and Technical Information of China (English)

    Lei Zhang; Xue-Song Li; Li-Qun Zhou

    2016-01-01

    Objective:To review hot issues and future direction of renal tumor biopsy (RTB) technique.Data Sources:The literature concerning or including RTB technique in English was collected from PubMed published from 1990 to 2015.Study Selection:We included all the relevant articles on RTB technique in English,with no limitation of study design.Results:Computed tomography and ultrasound were usually used for guiding RTB with respective advantages.Core biopsy is more preferred over fine needle aspiration because of superior accuracy.A minimum of two good-quality cores for a single renal tumor is generally accepted.The use of coaxial guide is recommended.For biopsy location,sampling different regions including central and peripheral biopsies are recommended.Conclusion:In spite of some limitations,RTB technique is relatively mature to help optimize the treatment of renal tumors.

  1. Embolic renal infarction mimicking renal colic

    OpenAIRE

    Mahamid M; Francis A.; Abid A; Awawde M; Abu-Elhija O

    2014-01-01

    Mahmud Mahamid,1,3 Adi Francis,2 Ali Abid,1 Mohammed Awawde,1 Omar Abu-Elhija11Department of Internal Medicine, 2Cardiac Care Unit, Holy Family Hospital, Bar-Ilan University, Nazareth, Israel; 3Digestive Disease Institute, Liver Unit, Shaare Zedek Medical Center, Jerusalem, IsraelAbstract: Atrial fibrillation is a major health problem with risk of systemic arterial embolism. Acute embolic renal infarction is a rare condition with symptoms that are often nonspecific. We present a 36-year-old p...

  2. 5-HT2 Receptor Regulation of Mitochondrial Genes: Unexpected Pharmacological Effects of Agonists and Antagonists.

    Science.gov (United States)

    Harmon, Jennifer L; Wills, Lauren P; McOmish, Caitlin E; Demireva, Elena Y; Gingrich, Jay A; Beeson, Craig C; Schnellmann, Rick G

    2016-04-01

    In acute organ injuries, mitochondria are often dysfunctional, and recent research has revealed that recovery of mitochondrial and renal functions is accelerated by induction of mitochondrial biogenesis (MB). We previously reported that the nonselective 5-HT2 receptor agonist DOI [1-(4-iodo-2,5-dimethoxyphenyl)propan-2-amine] induced MB in renal proximal tubular cells (RPTCs). The goal of this study was to determine the role of 5-HT2 receptors in the regulation of mitochondrial genes and oxidative metabolism in the kidney. The 5-HT2C receptor agonist CP-809,101 [2-[(3-chlorophenyl)methoxy]-6-(1-piperazinyl)pyrazine] and antagonist SB-242,084 [6-chloro-2,3-dihydro-5-methyl-N-[6-[(2-methyl-3-pyridinyl)oxy]-3-pyridinyl]-1H-indole-1-carboxyamide dihydrochloride] were used to examine the induction of renal mitochondrial genes and oxidative metabolism in RPTCs and in mouse kidneys in the presence and absence of the 5-HT2C receptor. Unexpectedly, both CP-809,101 and SB-242,084 increased RPTC respiration and peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α) mRNA expression in RPTCs at 1-10 nM. In addition, CP-809,101 and SB-242,084 increased mRNA expression of PGC-1α and the mitochondrial proteins NADH dehydrogenase subunit 1 and NADH dehydrogenase (ubiquinone) β subcomplex 8 in mice. These compounds increased mitochondrial genes in RPTCs in which the 5-HT2C receptor was downregulated with small interfering RNA and in the renal cortex of mice lacking the 5-HT2C receptor. By contrast, the ability of these compounds to increase PGC-1α mRNA and respiration was blocked in RPTCs treated with 5-HT2A receptor small interfering RNA or the 5-HT2A receptor antagonist eplivanserin. In addition, the 5-HT2A receptor agonist NBOH-2C-CN [4-[2-[[(2-hydroxyphenyl)methyl]amino]ethyl]-2,5-dimethoxybenzonitrile] increased RPTC respiration at 1-100 nM. These results suggest that agonism of the 5-HT2A receptor induces MB and that the classic 5-HT2C receptor agonist CP

  3. Contemporary Management of Renal Trauma

    Science.gov (United States)

    Shoobridge, Jennifer J; Corcoran, Niall M; Martin, Katherine A; Koukounaras, Jim; Royce, Peter L; Bultitude, Matthew F

    2011-01-01

    In the management of renal trauma, surgical exploration inevitably leads to nephrectomy in all but a few specialized centers. With current management options, the majority of hemodynamically stable patients with renal injuries can be successfully managed nonoperatively. Improved radiographic techniques and the development of a validated renal injury scoring system have led to improved staging of injury severity that is relatively easy to monitor. This article reviews a multidisciplinary approach to facilitate the care of patients with renal injury. PMID:21941463

  4. 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

  5. Primary renal synovial sarcoma

    OpenAIRE

    Bakhshi, Girish D.; Arshad S. Khan; Shaikh, Aftab S; Khan, Mohammad Ashraf A.; Mohammad Adil A. Khan; Jamadar, Nilofar M.

    2012-01-01

    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 u...

  6. 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.

  7. Sarcomatoid renal cell carcinoma

    OpenAIRE

    Kafil Akhtar; Ahmad Shamshad; Zaheer Sufian; Mansoor Tariq

    2011-01-01

    Sarcomatoid renal cell carcinoma (SRCC) is an aggressive tumor variant thought to arise predominantly from differentiation of clear cell carcinoma. A few reports of SRCC asso-ciated with non-clear cell tumors led to the presumption that SRCC may arise from any renal cell carcinoma, although direct evidence of this is lacking. We report a case of a 70-year-old male patient, who presented with acute left upper quadrant abdominal pain and was diagnosed to have SRCC after pathological examination...

  8. Renal Failure in Pregnancy.

    Science.gov (United States)

    Balofsky, Ari; Fedarau, Maksim

    2016-01-01

    Renal failure during pregnancy affects both mother and fetus, and may be related to preexisting disease or develop secondary to diseases of pregnancy. Causes include hypovolemia, sepsis, shock, preeclampsia, thrombotic microangiopathies, and renal obstruction. Treatment focuses on supportive measures, while pharmacologic treatment is viewed as second-line therapy, and is more useful in mitigating harmful effects than treating the underlying cause. When supportive measures and pharmacotherapy prove inadequate, dialysis may be required, with the goal being to prolong pregnancy until delivery is feasible. Outcomes and recommendations depend primarily on the underlying cause. PMID:26600445

  9. Potential benefits of renal diets on cardiovascular risk factors in chronic kidney disease patients.

    Science.gov (United States)

    Cupisti, Adamasco; Aparicio, Michel; Barsotti, Giuliano

    2007-01-01

    Dietary manipulation, including protein, phosphorus, and sodium restriction, when coupled with the vegetarian nature of the renal diet and ketoacid supplementation can potentially exert a cardiovascular protective effect in chronic renal failure patients by acting on both traditional and nontraditional cardiovascular risk factors. Blood pressure control may be favored by the reduction of sodium intake and by the vegetarian nature of the diet, which is very important also for lowering serum cholesterol and improving plasma lipid profile. The low protein and phosphorus intake has a crucial role for reducing proteinuria and preventing and reversing hyperphosphatemia and secondary hyperparathyroidism, which are major causes of the vascular calcifications, cardiac damage, and mortality risk of uremic patients. The reduction of nitrogenous waste products and lowering of serum PTH levels may also help ameliorate insulin sensitivity and metabolic control in diabetic patients, as well as increase the responsiveness to erythropoietin therapy, thus allowing greater control of anemia. Protein-restricted diets may have also anti-inflammatory and anti-oxidant properties. Thus, putting aside the still debatable effects on the progression of renal disease and the more admitted effects on uremic signs and symptoms, it is possible that a proper nutritional treatment early in the course of renal disease may be useful also to reduce the cardiovascular risk in the renal patient. However, conclusive data cannot yet be drawn because quality studies are lacking in this field; future studies should be planned to assess the effect of renal diets on hard outcomes, as cardiovascular events or mortality. PMID:17654313

  10. CTGF promotes inflammatory cell infiltration of the renal interstitium by activating NF-kappaB.

    Science.gov (United States)

    Sánchez-López, Elsa; Rayego, Sandra; Rodrigues-Díez, Raquel; Rodriguez, Javier Sánchez; Rodrigues-Díez, Raúl; Rodríguez-Vita, Juan; Carvajal, Gisselle; Aroeira, Luiz Stark; Selgas, Rafael; Mezzano, Sergio A; Ortiz, Alberto; Egido, Jesús; Ruiz-Ortega, Marta

    2009-07-01

    Connective tissue growth factor (CTGF) is an important profibrotic factor in kidney diseases. Blockade of endogenous CTGF ameliorates experimental renal damage and inhibits synthesis of extracellular matrix in cultured renal cells. CTGF regulates several cellular responses, including adhesion, migration, proliferation, and synthesis of proinflammatory factors. Here, we investigated whether CTGF participates in the inflammatory process in the kidney by evaluating the nuclear factor-kappa B (NF-kappaB) pathway, a key signaling system that controls inflammation and immune responses. Systemic administration of CTGF to mice for 24 h induced marked infiltration of inflammatory cells in the renal interstitium (T lymphocytes and monocytes/macrophages) and led to elevated renal NF-kappaB activity. Administration of CTGF increased renal expression of chemokines (MCP-1 and RANTES) and cytokines (INF-gamma, IL-6, and IL-4) that recruit immune cells and promote inflammation. Treatment with a NF-kappaB inhibitor, parthenolide, inhibited CTGF-induced renal inflammatory responses, including the up-regulation of chemokines and cytokines. In cultured murine tubuloepithelial cells, CTGF rapidly activated the NF-kappaB pathway and the cascade of mitogen-activated protein kinases, demonstrating crosstalk between these signaling pathways. CTGF, via mitogen-activated protein kinase and NF-kappaB activation, increased proinflammatory gene expression. These data show that in addition to its profibrotic properties, CTGF contributes to the recruitment of inflammatory cells in the kidney by activating the NF-kappaB pathway. PMID:19423687

  11. Novel benzo[1,4]diazepin-2-one derivatives as endothelin receptor antagonists.

    Science.gov (United States)

    Bolli, Martin H; Marfurt, Judith; Grisostomi, Corinna; Boss, Christoph; Binkert, Christoph; Hess, Patrick; Treiber, Alexander; Thorin, Eric; Morrison, Keith; Buchmann, Stephan; Bur, Daniel; Ramuz, Henri; Clozel, Martine; Fischli, Walter; Weller, Thomas

    2004-05-20

    Since its discovery in 1988 by Yanagisawa et al., endothelin (ET), a potent vasoconstrictor, has been widely implicated in the pathophysiology of cardiovascular, cerebrovascular, and renal diseases. Many research groups have embarked on the discovery and development of ET receptor antagonists for the treatment of such diseases. While several compounds, e.g., ambrisentan 2, are in late clinical trials for various indications, one compound (bosentan, Tracleer) is being marketed to treat pulmonary arterial hypertension. Inspired by the structure of ambrisentan 2, we designed a novel class of ET receptor antagonists based on a 1,3,4,5-tetrahydro-1H-benzo[e][1,4]diazepin-2-one scaffold. Here, we report on the preparation as well as the in vitro and in vivo structure-activity relationships of these derivatives. Potent dual ET(A)/ET(B) receptor antagonists with affinities in the low nanomolar range have been identified. In addition, several compounds efficiently reduced arterial blood pressure after oral administration to Dahl salt sensitive rats. In this animal model, the efficacy of the benzo[e][1,4]diazepin-2-one derivative rac-39au was superior to that of racemic ambrisentan, rac-2. PMID:15139756

  12. Anemia of renal failure. Use of erythropoietin.

    Science.gov (United States)

    Humphries, J E

    1992-05-01

    Chronic renal failure is almost invariably accompanied by symptomatic anemia. It has been demonstrated that the primary cause of this anemia is inadequate production of erythropoietin by the diseased kidneys. The isolation of erythropoietin, followed by the cloning and expression of the human erythropoietin gene, made possible clinical trials of rHuEPO in uremic patients. rHuEPO produced dramatic increases in the hematocrit in almost all patients treated and also ameliorated many symptoms, such as lethargy, dizziness, and poor appetite, that had long been attributed to the effect of uremic toxins. Adverse effects of treatment with rHuEPO noted in the early clinical trials included hypertension, seizures, arteriovenous fistula or shunt thrombosis, and hyperkalemia. Further study of rHuEPO has shown that many of these side effects may be no more frequent in patients receiving rHuEPO than in other uremic patients not receiving rHuEPO. Reduction of the rHuEPO dosage and subcutaneous administration produce less rapid increases in the hematocrit and may lessen the incidence and severity of these side effects. rHuEPO therapy places great demands on both the body's iron stores and the capacity to rapidly transfer iron from storage sites to the erythroid progenitor cells. Thus, almost all patients treated with rHuEPO become iron deficient and require oral or parenteral iron replacement. Response to rHuEPO in uremic patients is diminished if the anemia is complicated by iron deficiency, inflammatory disorders, aluminum overload, or deficiency of folate or vitamin B12. rHuEPO therapy is safe and effective in the treatment of the anemia of chronic renal failure. The use of rHuEPO leads to enhanced quality of life and eliminates the need for red cell transfusions. In addition to hemodialysis patients, predialysis patients and those on CAPD benefit from and are candidates for rHuEPO therapy. PMID:1578966

  13. Amelioration of glomerulosclerosis with all-trans retinoic acid is linked to decreased plasminogen activator inhibitor-1 and α-smooth muscle actin

    Institute of Scientific and Technical Information of China (English)

    Xia LIU; Lei L(U); Bei-bei TAO; Ai-ling ZHOU; Yi-chun ZHU

    2011-01-01

    Aim:To examine the effects of all-trans retinoic acid (atRA) on renal morphology and function as well as on renal plasminogen activator inhibitor-1 (PAI-1) expression and plasmin activity in rats with 5/6 nephrectomy.Methods:Adult male Sprague Dawley rats were given 5/6 nephrectomy or sham operation. Renal function was measured 2 weeks later. The nephrectomized rats were assigned to groups matched for proteinuria and treated with vehicle or atRA (5 or 10 mg/kg by gastric gavage once daily) for the next 12 weeks. Rats with sham operation were treated with vehicle. At the end of the treatments,kidneys were collected for histological examination, Western blot analysis, and enzymatic activity measurements.Results:The 5/6 nephrectomy promoted hypertension, renal dysfunction, and glomerulosclerosis. These changes were significantly reduced in the atRA-treated group. The expressions of PAI-1 and α-smooth muscle actin (α-SMA) were significantly increased in the vehicle-treated nephrectomized rats. Treatment with atRA significantly reduced the expressions of PAI-1 and α-SMA. However, piasmin activity remained unchanged following atRA treatment.Conclusion:Treatment with atRA ameliorates glomerulosclerosis and improves renal function in rats with 5/6 nephrectomy. This is associated with a decrease in PAI-1 and α-SMA, but not with a change in plasmin activity.

  14. Dopamine-1 and dopamine-2 mechanisms in the control of renal function.

    Science.gov (United States)

    Carey, R M; Siragy, H M; Ragsdale, N V; Howell, N L; Felder, R A; Peach, M J; Chevalier, R L

    1990-06-01

    Dopamine (DA), a catecholamine produced in the kidney, is a renal vasodilator and natriuretic substance, but its action at dopamine-1 (DA-1), dopamine-2 (DA-2) and alpha- and beta-adrenergic receptors limits its effectiveness as a heuristic tool and pharmacologic agent. We have studied the effects of highly selective DA-1 and DA-2 receptor agonists and antagonists in normal human subjects and experimental animals to determine the precise physiological role of renal dopamine at DA-1 and DA-2 receptors within the kidney. We studied fenoldopam, a selective DA-1 agonist, in normal human subjects in metabolic balances at high (300 mEq/day) and low (10 mEq/day) sodium (Na) intake. Selective DA-1 receptor stimulation during high Na intake resulted in renal vasodilation, natriuresis and diuresis in a sustained manner for 3 hours. The natriuresis was mediated by a reduction in Na reabsorption at both proximal and distal tubular sites. In contrast, during low Na intake, DA-1 receptor stimulation did not engender a natriuretic or diuretic response. Thus, sodium depletion may inhibit the function of renal tubular cells in response to DA-1 stimulation. DA-1 receptors are present in the medial layer of the renal vasculature, proximal tubule and cortical collecting duct; DA-2 receptors are localized to the glomerulus, the renal nerves surrounding renal blood vessels and possibly the renal vascular endothelium. We have performed studies in conscious dogs with indwelling renal arterial catheters to identify the physiological role of renal DA to DA-1 and DA-2 receptors.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:1974444

  15. Amelioration of safety management in infrastructure projects

    Directory of Open Access Journals (Sweden)

    Mr. Gopinath S.Mohite

    2014-11-01

    Full Text Available Accidents are a major public health concern, resulting in an estimated 1.2 million deaths and 50 million injuries worldwide each year specifically, the relationships between drivers' characteristics and road accidents are not fully understood. Many factors are involved in the accident occurrence at construction site. Some important elements that create a significant portion of accidents include: safety management error, poor training programs, human element, act of god, outdated procedure and no clear monitoring policy. Although some of these items are inevitable, but the occurrence of the largest part can be prevented. Therefore, for ameliorating the safety in a project each of these items should be analyzed and a practical approach introduced. In general, near miss, incident and accident are three dependent levels that mainly lead to injury. Risk and hazard are allocated in first level which means near miss, therefore, no on-time identification of hazard and risk causes to create incident and preventing accident in incident stage is unavoidable.

  16. 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.

  17. Oxazolidinones as novel human CCR8 antagonists.

    Science.gov (United States)

    Jin, Jian; Wang, Yonghui; Wang, Feng; Kerns, Jeffery K; Vinader, Victoria M; Hancock, Ashley P; Lindon, Matthew J; Stevenson, Graeme I; Morrow, Dwight M; Rao, Parvathi; Nguyen, Cuc; Barrett, Victoria J; Browning, Chris; Hartmann, Guido; Andrew, David P; Sarau, Henry M; Foley, James J; Jurewicz, Anthony J; Fornwald, James A; Harker, Andy J; Moore, Michael L; Rivero, Ralph A; Belmonte, Kristen E; Connor, Helen E

    2007-03-15

    High-throughput screening of the corporate compound collection led to the discovery of a novel series of N-substituted-5-aryl-oxazolidinones as potent human CCR8 antagonists. The synthesis, structure-activity relationships, and optimization of the series that led to the identification of SB-649701 (1a), are described. PMID:17267215

  18. Azines as histamine H4 receptor antagonists.

    Science.gov (United States)

    Lazewska, Dorota; Kiec-Kononowicz, Katarzyna

    2012-01-01

    Since 2000, when the histamine H4 receptor (H4R) was cloned, it has constituted an interesting target for drug development. Pharmacological studies suggest the potential utility of histamine H4R antagonists/inverse agonists in the treatment of inflammatory diseases, e.g. allergic rhinitis, asthma, atopic dermatitis, colitis, or pruritus. The first H4R ligands were non-selective compounds, but intensive chemical and pharmacological work has led to the discovery of highly potent and selective H4R antagonists (e.g. JNJ7777120, CZC-13788, PF-2988403, A-940894, A-987306). The first compound (UR-63325) has finally entered into clinical studies for the treatment of allergic respiratory diseases (completing the phase I ascending dose trial) and has been found to be safe and well tolerated. The number of scientific publications and patent applications in the H4 field is increasing annually. Among the diverse chemical structures of the H4R antagonists described a 2-aminopyrimidine scaffold is repeatedly found. This review looked at recent advances in the search for H4R antagonists as reflected in patent applications/patents and peer-reviewed publications over the last two years. The work concerns azines (mono-, di-, triazines) and their fused analogues. The chemistry and pharmacology has been described. PMID:22202103

  19. Genetic factors influencing pyrimidine-antagonist chemotherapy

    NARCIS (Netherlands)

    Maring, JG; Groen, HJM; Wachters, FM; Uges, DRA; de Vries, EGE

    2005-01-01

    Pyrimidine antagonists, for example, 5-fluorouracil (5-FU), cytarabine (ara-C) and gemcitabine (dFdC), are widely used in chemotherapy regimes for colorectal, breast, head and neck, non-small-cell lung cancer, pancreatic cancer and leukaemias. Extensive metabolism is a prerequisite for conversion of

  20. 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...

  1. Stem cells and progenitor cells in renal disease.

    Science.gov (United States)

    Haller, Hermann; de Groot, Kirsten; Bahlmann, Ferdinand; Elger, Marlies; Fliser, Danilo

    2005-11-01

    Stem cells and progenitor cells are necessary for repair and regeneration of injured renal tissue. Infiltrating or resident stem cells can contribute to the replacement of lost or damaged tissue. However, the regulation of circulating progenitor cells is not well understood. We have analyzed the effects of erythropoietin on circulating progenitor cells and found that low levels of erythropoietin induce mobilization and differentiation of endothelial progenitor cells. In an animal model of 5/6 nephrectomy we could demonstrate that erythropoietin ameliorates tissue injury. Full regeneration of renal tissue demands the existence of stem cells and an adequate local "milieu," a so-called stem cell niche. We have previously described a stem cell niche in the kidneys of the dogfish, Squalus acanthus. Further analysis revealed that in the regenerating zone of the shark kidney, stem cells exist that can be induced by loss of renal tissue to form new glomeruli. Such animal models improve our understanding of stem cell behavior in the kidney and may eventually contribute to novel therapies. PMID:16221168

  2. 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

  3. Epidemiological characteristics of renal stone patients age (21-60) and barriers in their dietary modification in Saurashtra Region

    OpenAIRE

    Arpan Chandubhai Patel; Nishank Harris Mehta

    2014-01-01

    Background: Dietary factors remain an entity attributed to a kidney stone and thus renal stone becomes more of a \\'lifestyle\\' disease relying more on prevention for its amelioration than advanced and specific treatment modalities. Although there are various studies conducted in past to show importance of dietary modification in patient with kidney stone , no single study was conducted to identify perceived barriers in dietary modification by patient. Methods: Through this population base...

  4. Renal trapping of cadmium

    International Nuclear Information System (INIS)

    Renal Cd retention is well known; its mechanism was here studied in rabbits. 109CdCl2 or 65ZnCl2 were injected IA, together with SH-ethanol (ME) to prevent isotope binding to plasma protein; the bolus was trapped in the kidney for 40 s by aortic occlusion as described previously. Total uptake (TU, in % of renal load) = the sum of (A) reabsorbed metal, calculated on the basis of free filtrn. of ME complexes, their insignificant urinary excretion, and av. filtrn. fraction of 20%; and (B) basolateral (BL) extraction, determined from recoveries of metal compared to that of inulin in renal venous samples collected over 3 min after release of occlusion. TU averaged 32% for Cd (n=6), and 42% for Zn (n=4). Three ± 10% (SD) of TU Cd but 86 ± 37% of TU Zn returned to blood. These findings recall the positive correlation between relative affinities of Cd, Zn and Ni for metallothionein (MT), and their retention by jejunal mucosa (AJP 253:G134,1987); endogenous MT has been directly implicated in Cd retention by that tissue (Tox. 38:285,1986). Present results similarly support the commonly postulated role of MT in renal Cd retention, and reemphasize the contribution BL uptake of nonMT Cd can make to total Cd accumulation

  5. Insuficiencia renal aguda.

    Directory of Open Access Journals (Sweden)

    Carlos Hernán Mejía

    2009-10-01

    Full Text Available La insuficiencia renal aguda se diagnostica aproximadamente en 5% de los pacientes hospitalizados. Sus principales causas se relacionan con la alteración del flujo sanguíneo renal, sea por depleción de volumen, baja perfusión renal o por distribución intrarrenal inadecuada y obstrucción del árbol urinario. El diagnóstico parte de la historia clínica y un buen examen físico que corrobore el estado de volemia del paciente y se complementa con el uso adecuado de los índices urinarios (excreción de sodio y osmolaridad, el uroanálisis y la ecografía renal. Su tratamiento consiste en una adecuada recuperación del volumen, manejo de los diuréticos, soporte nutricional, conservación del equilibrio hidroelectrolítico y brindar terapia de diálisis si hay toxicidad urémica, hipercaliemia severa (>6.5 mEq/l, acidosis metabólica o sobrecarga severa de volumen.

  6. Effect of two human growth hormone receptor antagonists on glomerulosclerosis in streptozotocin-induced diabetic rats

    Institute of Scientific and Technical Information of China (English)

    Wei LI; Shui-xian SHEN; Li-hua ZHU; En-bi WANG; Zeng-can YE; Jun LIN; Li-he GUO; Fei-hong LUO; Xi-hong LIU; Xin FANG

    2004-01-01

    AIM: To explore the feasibility of human growth hormone (hGH) receptor antagonist in the treatment of end-stage diabetic renal complications. METHODS: Two hGH mutants, hGHA1 (Cys-hGH-dell-4, G120R, K168A, E174A,C182S, de1186-191) and hGHA2 (hGH-H21A, G120R, E174A) were expressed in E coli. The IC50 (Mean±SD)values for the mutants for inhibiting 125I-hGH binding to rabbit growth hormone receptor were (65±10) ng for hGHA1, (27±5.6) ng for hGHA2, and (10±0.6) ng for wild type hGH, respectively. RESULTS: After treatment for 12 weeks, the renal histology analysis showed that treatment with hGHA2 at 4 mg/kg body weight daily markedly suppressed glomerulosclerosis in streptozotocin-induced diabetic Sprague-Dawley (SD) rats; hGHA1 at the same dosage slightly increased the renal damage compared with saline; while wild type hGH at 1 U/kg body weight daily severely worsened the glomerulo-sclerosis in diabetic SD rats. CONCLUSION: The data indicated that hGHA2 inhibited the end-stage glomerulosclerosis in diabetic rats, but hGHA1 mildly increased the glomerulosclerosis.

  7. ''Aggressive'' renal angiomyolipoma

    International Nuclear Information System (INIS)

    We describe the US and CT examinations of 4 patients with renal angiomyolipoma with an 'aggressive' appearance, and review the literature. The imaging findings in 4 patients with benign renal angiomyolipomas associated with thrombosis of the renal vein and/or inferior vena cava are presented. CT demonstrated fat densities within both tumor and thrombus. In one patient, small lymph nodes with low density internal areas were detected in the para-aortic region. When considering our patients together with those reported in the literature, we found that most angiomyolipomas with venous invasion were large and centrally located within the kidney. Venous thrombosis was observed in 9 lesions of the right kidney, and in only 4 of the left one. One patient only had symptoms due to the thrombus; 10 had problems due to the tumor; and 3 were asymptomatic. Only 4 patients with pararenal enlarged lymph nodes have been reported on in the imaging literature. Fat-containing nodes were detected by CT in one case only; the others had enlarged nodes of soft-tissue density. In one patient the diagnosis of hamartomatous lymph node invasion was established by angiography. In patients with renal angiomyolipoma, demonstration of both fatty thrombus and the fatty infiltration of lymph nodes of the renal hilum cannot be regarded as an indication of malignancy, but only of local aggessive behavior. Conservative treatment seems possible. Detection of enlarged lymph nodes of soft tissue density may cause difficult diagnostic problems, with the diagnosis addressed only by the presence of associated lesions. (orig./MG)

  8. ``Aggressive`` renal angiomyolipoma

    Energy Technology Data Exchange (ETDEWEB)

    Cittadini, G. Jr. [Univ. of Genoa (Italy). Dept. of Radiology; Pozzi Mucelli, F. [Univ. of Trieste (Italy). Dept. of Radiology; Danza, F.M. [Catholic Sacro Cuore Univ., Rome (Italy). Dept. of Radiology; Derchi, L.E. [Univ. of Genoa (Italy). Dept. of Radiology; Pozzi Mucelli, R.S. [Univ. of Trieste (Italy). Dept. of Radiology

    1996-11-01

    We describe the US and CT examinations of 4 patients with renal angiomyolipoma with an `aggressive` appearance, and review the literature. The imaging findings in 4 patients with benign renal angiomyolipomas associated with thrombosis of the renal vein and/or inferior vena cava are presented. CT demonstrated fat densities within both tumor and thrombus. In one patient, small lymph nodes with low density internal areas were detected in the para-aortic region. When considering our patients together with those reported in the literature, we found that most angiomyolipomas with venous invasion were large and centrally located within the kidney. Venous thrombosis was observed in 9 lesions of the right kidney, and in only 4 of the left one. One patient only had symptoms due to the thrombus; 10 had problems due to the tumor; and 3 were asymptomatic. Only 4 patients with pararenal enlarged lymph nodes have been reported on in the imaging literature. Fat-containing nodes were detected by CT in one case only; the others had enlarged nodes of soft-tissue density. In one patient the diagnosis of hamartomatous lymph node invasion was established by angiography. In patients with renal angiomyolipoma, demonstration of both fatty thrombus and the fatty infiltration of lymph nodes of the renal hilum cannot be regarded as an indication of malignancy, but only of local aggessive behavior. Conservative treatment seems possible. Detection of enlarged lymph nodes of soft tissue density may cause difficult diagnostic problems, with the diagnosis addressed only by the presence of associated lesions. (orig./MG).

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

    International Nuclear Information System (INIS)

    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.)

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1983-05-01

    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.

  11. Combination of telmisartan with sildenafil ameliorate progression of diabetic nephropathy in streptozotocin-induced diabetic model.

    Science.gov (United States)

    El-Mahdy, Nageh Ahmed; El-Sayad, Magda El-Sayed; El-Kadem, Aya Hassan

    2016-07-01

    Diabetic nephropathy (DN) is a leading cause of end-stage renal disease in the world. Several signaling pathways are involved in the pathogenesis of DN including elevation in level of angiotensin II, formation of advanced glycation end products (AGE), activation of protein kinase c (PKC), and lipid accumulation. These pathways activate one another mutually leading to oxidative stress, increasing expression of transforming growth factor beta-1(TGF-β 1) and release of interleukins and adhesion molecules, so the aim of this study is to interrupt more than pathogenic pathway to ameliorate the progression of DN. In the present study, white male rats (N=48) were divided into six groups (8 rats each), the first two groups served as normal control and a control vehicle group while the remaining four groups were rendered diabetic by a single intraperitoneal injection of Streptozotocin (STZ) and being left for 4 weeks to develop DN. Thereafter, the rats were divided into DN group, DN group receiving Telmisartan or Sildenafil or Telmisartan Sildenafil combination. After the specified treatment period, urine samples were collected (using metabolic cages) to measure proteinuria, animals were then euthanized, blood and tissue samples were collected for measurement of Blood glucose,BUN, S.Cr, LDL, NO, TGF-β1, IL-1β, AGEPs, and SOD. The combination therapy showed significant decrease in BUN, S.Cr,LDL, TGF-β1, IL-1β, Proteinuria and AGEPs and significant increase in SOD and NO. The findings showed that combination therapy was able to ameliorate DN and that the effects were superior to the single drugs alone. PMID:27261587

  12. 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

  13. Effects of the angiotensin type I receptor antagonist, losartan, on systemic and regional vascular responses to lower body negative pressure in healthy volunteers.

    OpenAIRE

    Duranteau, J; Pussard, E; Berdeaux, A; Giudicelli, J. F.

    1995-01-01

    1. The effects of a single oral dose (50 mg) of the angiotensin II AT1-receptor antagonist, losartan, on the systemic and regional vascular responses to simulated orthostatic stress by the lower body negative pressure (LBNP) technique were investigated in nine healthy volunteers, in a double-blind, placebo-controlled crossover study. 2. Arterial blood pressure remained unchanged throughout the study. Three hours after its administration and before LBNP, losartan selectively increased renal bl...

  14. The effects of dopamine D3 agonists and antagonists in a nonhuman primate model of tardive dyskinesia.

    Science.gov (United States)

    Malik, Peter; Andersen, Maibritt B; Peacock, Linda

    2004-08-01

    Tardive dyskinesia (TD), a serious complication of antipsychotic dopamine (DA) antagonist treatment, has been hypothesised to develop due to a dominant DA D1 relative to DA D2 receptor function. Recent genetic and pharmacological studies implicate the DA D3 receptor in TD. The present study examined the role of the DA D3 receptor in relation to the DA D1/D2 imbalance hypothesis of TD in nonhuman primates. Eight Cebus monkeys displaying mild to severe TD due to previous chronic exposure to DA D2 antagonists were acutely injected with SKF 81297 (DA D1 agonist) 0.3 and 0.6 mg/kg, pramipexole (DA D3>D2 agonist) 0.025-0.1 mg/kg, CIS-8-OH-PBZI (DA D3 agonist) 5-10 mg/kg and SB-27701-A (DA D3 antagonist) 1-5 mg/kg and rated for oral dyskinesia. SKF 81297, 0.3 and 0.6 mg/kg, exacerbated TD. Pramipexole and CIS-8-OH-PBZI reduced SKF 81297-induced TD, while SB-27701-A had no effect. When administered alone, SB-27701-A increased TD relative to placebo, while pramipexole and CIS-8-OH-PBZI had no significant effect. Pramipexole did, however, ameliorate TD in those monkeys with severe TD. These results point towards a role of the DA D3 receptor in TD, but indicate that the DA D2 receptor may also play an essential role. PMID:15301939

  15. Epigallocatechin-3-gallate attenuates cadmium-induced chronic renal injury and fibrosis.

    Science.gov (United States)

    Chen, Jinglou; Du, Lifen; Li, Jingjing; Song, Hongping

    2016-10-01

    Cadmium (Cd) pollution is a serious environmental problem. Kidney is a main target organ of Cd toxicity. This study was undertaken to investigate the potential protective effects of epigallocatechin-3-gallate (EGCG) against chronic renal injury and fibrosis induced by CdCl2. Rat model was induced by exposing to 250 mg/L CdCl2 through drinking water. The renal function was evaluated by detecting the levels of blood urea nitrogen (BUN) and serum creatinine (SCR). The oxidative stress was measured by detecting the levels of malondialdehyde (MDA), nitric oxide (NO), reduced glutathione/oxidized glutathione (GSH/GSSG) and renal enzymatic antioxidant status. Additionally, the renal levels of transforming growth factor-β1 (TGF-β1), Smad3, phosphorylation-Smad3 (pp-Smad3), α-smooth muscle actin (α-SMA), vimentin and E-cadherin were measured by western blot assay. Renal levels of microRNA-21 (miR-21), miR-29a/b/c and miR-192 were measured by quantitative RT-PCR. It was found that EGCG ameliorated the CdCl2-induced renal injury, inhibited the level of oxidative stress, normalized renal enzymatic antioxidant status and E-cadherin level, as well as attenuated the over generation of TGF-β1, pp-Smad3, vimentin and α-SMA. EGCG also decreased the production of miR-21 and miR-192, and enhanced the levels of miR-29a/b/c. These results showed that EGCG could attenuate Cd induced chronic renal injury. PMID:27474435

  16. 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......; 13 had incomplete and 1 had complete distal RTA. Distal RTA was found particularly in recurrent stone formers (17%), and especially in those with bilateral stone disease, where a distal renal tubular acidification defect was found in 50%. We have been unable to differentiate primary from secondary...... 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 in...

  17. Vasopressin receptor antagonists: Characteristics and clinical role.

    Science.gov (United States)

    Rondon-Berrios, Helbert; Berl, Tomas

    2016-03-01

    Hyponatremia, the most common electrolyte disorder in hospitalized patients is associated with increased risk of mortality even when mild and apparently asymptomatic. Likewise morbidity manifested as attention deficits, gait disturbances, falls, fractures, and osteoporosis is more prevalent in hyponatremic subjects. Hyponatremia also generates a significant financial burden. Therefore, it is important to explore approaches that effectively and safely treat hyponatremia. Currently available strategies are physiologically sound and affordable but lack evidence from clinical trials and are limited by variable efficacy, slow response, and/or poor compliance. The recent emergence of vasopressin receptor antagonists provides a class of drugs that target the primary pathophysiological mechanism, namely vasopressin mediated impairment of free water excretion. This review summarizes the historical development, pharmacology, clinical trials supporting efficacy and safety, shortcomings, as well as practical suggestions for the use of vasopressin receptor antagonists. PMID:27156765

  18. 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. PMID:26872270

  19. Improvement of renal function after opening occluded atherosclerotic renal arteries.

    Science.gov (United States)

    Kanamori, Hiroshi; Toma, Masanao; Fukatsu, Atsushi

    2009-09-01

    Percutaneous transluminal renal angioplasty (PTRA) with stenting has been effective in the control of hypertension, renal function and pulmonary edema caused by atherosclerotic renal artery stenosis (ARAS). However, concerning the viability of renal function, this procedure has not been fully established, especially in the presence of renal atrophy or severe renal parenchymal disease. We report a dramatically improved case of acute renal failure caused by acute worsening ARAS treated by stenting. A 72-year-old female was admitted for accelerated renal dysfunction (serum ceatinine; 1.2-2.3 mg/dl) and hypertension (190/100 mmHg). At 10 days after admission, the patient's serum ceatinine increased to 6.7 mg/dl, her pulmonary edema was exaggerated and hemodialysis was required. Ultrasonography showed bilateral high-echoic kidneys, but no apparent finding of renal artery stenosis (RAS). At day 15, computed tomographic angiography indicated bilateral ostial RAS. Renal angiography demonstrated total occlusion of the right and severe (90%) disease in the left. ARAS was diagnosed by intravascular ultrasonography. The guidewire was inserted in both renal arteries, PTRA with stenting was performed in the right and a stent was directly implanted in the left. Immediately, each kidney enlarged to almost normal size, leading to satisfactory urination. She was released from hemodialysis the next day since her serum creatinine was normal and the pulmonary edema was improved. Although there is still no reliable prognostic factor including resistive index or kidney size, it is important that PTRA with stenting in ARAS should be considered in a case of accelerated renal dysfunction because of the possible improvement. PMID:19726830

  20. Renal aspergillosis secondary to renal intrumentation in immunocompetent patient

    OpenAIRE

    Paul, Sagorika; Singh, Viswajeet; Sankhwar, Satyanarayan; Garg, Manish

    2013-01-01

    Primary renal aspergillosis is a rare urological entity and immune-compromised persons are commonly prone to it. The clinical presentation resembles that of usual bacterial pyelonephritis. We report a case of localised unilateral renal aspergillosis with obstructive uropathy (hypoplastic contralateral kidney) in a young man, occurring after the endoscopic removal of impacted right upper ureteric calculus in a non-immunocompromised patient. In view of deranged renal function, he was initially ...

  1. Bicycloorthocarboxylate convulsants. Potent GABAA receptor antagonists

    International Nuclear Information System (INIS)

    4-t-Butyl-1-(4-bromophenyl)-bicycloorthocarboxylate antagonizes gamma-aminobutyric acid (GABA)-mediated relaxation at a functional insect nerve-muscle synapse, mimicking the action of picrotoxinin, suggesting that it causes GABA antagonism through blockade of the chloride ionophore. It is also a potent GABAA receptor antagonist, inhibiting the binding of [35S]t-butyl-bicyclophosphorothionate ([35S]TBPS) to EDTA/water-dialyzed human brain P2 membranes. Structure-activity relationships of 74 1,4-bis-substituted bicycloorthocarboxylates, mostly new compounds, reveal that for high potency as a GABAA receptor antagonist the optimal 4-substituent is a C4 to C6 branched chain alkyl or cycloalkyl group (e.g., t-butyl, s-butyl, or cyclohexyl) and the optimal 1-substituent is a phenyl moiety with one or more electron-withdrawing groups (e.g., 4-cyano, 4-bromo, 4-chloro, 3,4-dichloro, or pentafluoro). Bicycloorthocarboxylate inhibitors of [35S]TBPS binding with IC50 values of 5-10 nM exceed by several-fold the potency of any GABAA receptor antagonist previously reported. The 4-t-butyl-1-(4-azidophenyl) analog, synthesized as a candidate photoaffinity label, gives an IC50 of 315 nM. The potency of bicycloorthocarboxylates for decreasing [35S]TBPS binding generally correlates with their toxicity, i.e., compounds without inhibitory activity in this brain receptor assay are of low toxicity on intraperitoneal administration to mice, and the analogs most potent as inhibitors are generally those most toxic to mice (e.g., IC50 of 5 nM and LD50 of 0.06 mg/kg for 4-t-butyl-1-(4-cyanophenyl)-bicycloorthocarboxylate). The effects of phenyl substituents on the potency of the orthobenzoates as GABAA receptor antagonists are similar to those on toxicity

  2. Antagonistic parent-offspring co-adaptation.

    Directory of Open Access Journals (Sweden)

    Mathias Kölliker

    Full Text Available BACKGROUND: 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. METHODOLOGY/PRINCIPAL FINDINGS: 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. CONCLUSIONS/SIGNIFICANCE: 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.

  3. Aminopyrimidine derivatives as adenosine antagonists / Janke Kleynhans

    OpenAIRE

    Kleynhans, Janke

    2013-01-01

    Aims of this project - The aim of this study was to design and synthesise novel 2-aminopyrimidine derivatives as potential adenosine A1 and A2A receptor antagonists. Background and rationale - Parkinson’s disease is the second most common neurodegenerative disorder (after Alzheimer’s disease) and is characterised by the selective death of the dopaminergic neurons of the nigro-striatal pathway. Distinctive motor symptoms include bradykinesia, muscle rigidity and tremor, while non-m...

  4. Antagonistic neural networks underlying differentiated leadership roles

    OpenAIRE

    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...

  5. Primary renal synovial sarcoma

    Directory of Open Access Journals (Sweden)

    Vandana U Grampurohit

    2011-01-01

    Full Text Available Primary synovial sarcoma (SS of kidney is very rare and difficult to diagnose. Here, we present a case of a 21-year-old female clinically diagnosed as renal cell carcinoma. Right nephrectomy specimen showed a cystic tumor in the upper pole of kidney with areas of hemorrhage and solid growth. Histologically, it showed poorly differentiated cells with hemangiopericytoma-like vascular pattern. Morphologic and immunohistochemical features were compatible with the diagnosis of poorly differentiated SS of kidney. Primary renal SS is a recently described entity. To the best of our knowledge, approximately 34 cases have been reported till date and this is the eighth documented case of poorly differentiated variant. Most of the time, poorly differentiated SS of kidney exhibits hemangiopericytoma like histology. Reverse transcriptase-polymerase chain reaction analysis to demonstrate SYT-SSX fusion gene transcript helps to confirm the diagnosis.

  6. Papillary renal cell carcinoma

    International Nuclear Information System (INIS)

    Between 1976 and 1987, 395 patients with kidney tumors were studied with radiological techniques and sonography. In 37 cases (9.4%) histopathology diagnosed pure papillary renal cell carcinoma. Analyzing the radiographic patterns of these neoplasms, the authors observed constantly diminished vascularity (100%) frequent calcifications (35.1%) and necrotic areas (51.3%). Such X-ray features are not specific: nevertheless, their coexistence is strongly suggestive of papillary renal cell cancer. No consistent US pattern was found; however, necrotic areas were easily demonstrated in most cases. It must be stressed how patients with papillary carcinoma experienced a longer post-operative survival; it has not yet been established whether such favorable behavior is due to low biological aggressiveness or to earlier diagnosis

  7. Renal Medullary Interstitial Cells

    Science.gov (United States)

    Rao, Reena; Hao, Chuan-Ming; Breyer, Matthew D.

    2007-04-01

    Renal medullary interstitial cells (RMICs) are specialized fibroblast-like cells that reside in the renal medulla among the vasa recta, the thin limbs of Henle's loop, and medullary collecting ducts. These cells are characterized by abundant lipid droplets in the cytoplasm. The lipid droplets are composed of triglycerides, cholesterol esters and free long-chain fatty acids, including arachidonic acid. RMICs are also a major site of cyclooxygenase2 (COX-2) expression, and thus a major site of COX-2 derived prostanoid biosynthesis. RMICs are also a potential target of hormones such as angiotensin II and endothelin. The RMIC COX-2 expression and the abundance of lipid droplets change with salt and water intake. These properties of RMICs are consistent with an important role of these cells in modulating physiologic and pathologic processes of the kidney.

  8. Medicinal chemistry of competitive kainate receptor antagonists.

    Science.gov (United States)

    Larsen, Ann M; Bunch, Lennart

    2011-02-16

    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

  9. Renal lithiasis and nutrition

    OpenAIRE

    Prieto Rafel M; Costa-Bauza Antonia; Grases Felix

    2006-01-01

    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...

  10. Renal Clearance of Nanoparticles

    OpenAIRE

    Choi, Hak Soo; Liu, Wenhao; Misra, Preeti; Tanaka, Eiichi; Zimmer, John P.; Ipe, Binil Itty; Bawendi, Moungi G.; Frangioni, John V.

    2007-01-01

    The field of nanotechnology holds great promise for the diagnosis and treatment of human disease. However, the size and charge of most nanoparticles preclude their efficient clearance from the body as intact nanoparticles. Without such clearance or their biodegradation into biologically benign components, toxicity is potentially amplified and radiological imaging is hindered. Using quantum dots (QDs) as a model system, we have precisely defined the requirements for renal filtration and urinar...

  11. Renal Replacement Therapy

    OpenAIRE

    Zaccaria Ricci; Stefano Romagnoli; Claudio Ronco

    2016-01-01

    During the last few years, due to medical and surgical evolution, patients with increasingly severe diseases causing multiorgan dysfunction are frequently admitted to intensive care units. Therapeutic options, when organ failure occurs, are frequently nonspecific and mostly directed towards supporting vital function. In these scenarios, the kidneys are almost always involved and, therefore, renal replacement therapies have become a common routine practice in critically ill patients with acute...

  12. 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, disease. PMID:27479950

  13. Adenosine A{sub 1} receptors in contrast media-induced renal dysfunction in the normal rat

    Energy Technology Data Exchange (ETDEWEB)

    Liss, Per; Palm, Fredrik [Department of Diagnostic Radiology, University Hospital, 75185, Uppsala (Sweden); Department of Medical Cell Biology, University Hospital, 75185, Uppsala (Sweden); Carlsson, Per-Ola [Department of Medical Cell Biology, University Hospital, 75185, Uppsala (Sweden); Department of Medical Sciences, University Hospital, 75185, Uppsala (Sweden); Hansell, Peter [Department of Medical Cell Biology, University Hospital, 75185, Uppsala (Sweden)

    2004-07-01

    Renal vasoconstriction with resultant tissue hypoxia, especially in the renal medulla, has been suggested to play a role in contrast media (CM)-induced nephropathy. In this study we investigated the effects of injection of the non-ionic low-osmolar CM iopromide with and without pretreatment with the selective adenosine A{sub 1}-receptor antagonist DPCPX. The effects were evaluated on regional renal blood flow, outer medullary oxygen tension (PO{sub 2}) and urine output in normal anaesthetised rats. A laser-Doppler technique was used for recording haemodynamic changes while oxygen microelectrodes were used for oxygen measurements. The A{sub 1}-receptor antagonist per se elevated glomerular filtration rate (+44%), cortical blood flow (+15%) and urine output (threefold) while reducing outer medullary PO{sub 2} (-24%). Administration of CM reduced outer medullary blood flow (OMBF; -26%) and PO{sub 2} (-80%) but did not affect cortical blood flow. Urine output increased 28-fold by CM while arterial blood pressure was reduced. The CM-mediated effect on haemodynamics, PO{sub 2}, urine output and blood pressure was unaffected by the A{sub 1}-receptor antagonist. Adenosine A{sub 1}-receptors are not important mediators of the depression of outer medullary blood flow and PO{sub 2} caused by the CM iopromide in the normal rat; however, A{sub 1}-receptors are tonically active to regulate renal haemodynamics, PO{sub 2} and urine production during normal physiological conditions. (orig.)

  14. Renal scintigraphy in infants with antenatally diagnosed renal pelvis dilatation

    Directory of Open Access Journals (Sweden)

    Ajdinović Boris

    2008-01-01

    Full Text Available Background/Aim. Ureteropelvic junction obstruction and vesicoureteral reflux are the most frequent entities identified on the basis of antenatal hydronephrosis. The aim of this study was to determine the incidence and pattern of abnormal renal scintigraphy findings in postnatal investigation of children with antenatal hydronephrosis. Methods. Twenty four infants (19 boys and five girls presented with antenatal hydronephrosis and mild to moderate hydronephrosis on ultrasound in newborn period were referred for renal scintigraphy. Ten patients with vesicoureteral reflux documented on micturating cystoureterography underwent 99mTc-DMSA renal scintigraphy and 14 patients were subjected to 99mTc-DTPA scintigraphy. Results. Anteroposterior pelvic diameter on ultrasound ranged from 11 to 24 mm. Renal DMSA scans identified congenital scars in two boys with bilateral reflux of grade V and unilateral reflux of grade III. Relative kidney uptake (RKU less than 40% was found in three, and poor kidney function (RKU less than 10% in two patients. Significant obstruction was shown on DTPA diuretic renal scintigraphy in 6/14 patients. Some slowing in dranaige (T1/2 greater than 10 minutes with no reduction in differential renal function was identified in three patients. Differential renal function less than 10% was obtained in one case. Conclusion. A high percent of abnormal renal scintigraphy findings was obtained. Renal scintigraphy was useful in determination of underlying cause of antenatally detected hydronephrosis.

  15. Renal Replacement Therapy.

    Science.gov (United States)

    Ricci, Zaccaria; Romagnoli, Stefano; Ronco, Claudio

    2016-01-01

    During the last few years, due to medical and surgical evolution, patients with increasingly severe diseases causing multiorgan dysfunction are frequently admitted to intensive care units. Therapeutic options, when organ failure occurs, are frequently nonspecific and mostly directed towards supporting vital function. In these scenarios, the kidneys are almost always involved and, therefore, renal replacement therapies have become a common routine practice in critically ill patients with acute kidney injury. Recent technological improvement has led to the production of safe, versatile and efficient dialysis machines. In addition, emerging evidence may allow better individualization of treatment with tailored prescription depending on the patients' clinical picture (e.g. sepsis, fluid overload, pediatric). The aim of the present review is to give a general overview of current practice in renal replacement therapies for critically ill patients. The main clinical aspects, including dose prescription, modality of dialysis delivery, anticoagulation strategies and timing will be addressed. In addition, some technical issues on physical principles governing blood purification, filters characteristics, and vascular access, will be covered. Finally, a section on current standard nomenclature of renal replacement therapy is devoted to clarify the "Tower of Babel" of critical care nephrology. PMID:26918174

  16. 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.

  17. Zinc Deficiency in Humans and its Amelioration

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    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

  18. From the Cover: Glutamate antagonists limit tumor growth

    Science.gov (United States)

    Rzeski, Wojciech; Turski, Lechoslaw; Ikonomidou, Chrysanthy

    2001-05-01

    Neuronal progenitors and tumor cells possess propensity to proliferate and to migrate. Glutamate regulates proliferation and migration of neurons during development, but it is not known whether it influences proliferation and migration of tumor cells. We demonstrate that glutamate antagonists inhibit proliferation of human tumor cells. Colon adenocarcinoma, astrocytoma, and breast and lung carcinoma cells were most sensitive to the antiproliferative effect of the N-methyl-D-aspartate antagonist dizocilpine, whereas breast and lung carcinoma, colon adenocarcinoma, and neuroblastoma cells responded most favorably to the -amino-3-hydroxy-5-methyl-4-isoxazole-propionate antagonist GYKI52466. The antiproliferative effect of glutamate antagonists was Ca2+ dependent and resulted from decreased cell division and increased cell death. Morphological alterations induced by glutamate antagonists in tumor cells consisted of reduced membrane ruffling and pseudopodial protrusions. Furthermore, glutamate antagonists decreased motility and invasive growth of tumor cells. These findings suggest anticancer potential of glutamate antagonists.

  19. 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.

  20. Drug-induced renal disorders.

    Science.gov (United States)

    Ghane Shahrbaf, Fatemeh; Assadi, Farahnak

    2015-01-01

    Drug-induced nephrotoxicity are more common among infants and young children and in certain clinical situations such as underlying renal dysfunction and cardiovascular disease. Drugs can cause acute renal injury, intrarenal obstruction, interstitial nephritis, nephrotic syndrome, and acid-base and fluid electrolytes disorders. Certain drugs can cause alteration in intraglomerular hemodynamics, inflammatory changes in renal tubular cells, leading to acute kidney injury (AKI), tubulointerstitial disease and renal scarring. Drug-induced nephrotoxicity tends to occur more frequently in patients with intravascular volume depletion, diabetes, congestive heart failure, chronic kidney disease, and sepsis. Therefore, early detection of drugs adverse effects is important to prevent progression to end-stage renal disease. Preventive measures requires knowledge of mechanisms of drug-induced nephrotoxicity, understanding patients and drug-related risk factors coupled with therapeutic intervention by correcting risk factors, assessing baseline renal function before initiation of therapy, adjusting the drug dosage and avoiding use of nephrotoxic drug combinations. PMID:26468475

  1. Effects of olmesartan on arterial stiffness in rats with chronic renal failure

    Directory of Open Access Journals (Sweden)

    Chuang Yao-Chen

    2012-06-01

    Full Text Available Abstract Background It has been suggested that the antioxidant properties of olmesartan (OLM, an angiotensin II type 1 receptor (AT1R blocker, contribute to renal protection rather than blood pressure lowering effects despite the fact that causal relationships between hypertension and renal artery disease exist. This study aimed to examine the hypothesis whether the antioxidative activities of OLM were correlated to arterial stiffness, reactive oxygen species and advanced glycation end products (AGEs formation in rats with chronic renal failure (CRF. Methods CRF rats were induced by 5/6 nephrectomy and randomly assigned to an OLM (10 mg/day group or a control group. Hemodynamic states, oxidative stress, renal function and AGEs were measured after 8 weeks of OLM treatment. Results All the hemodynamic derangements associated with renal and cardiovascular dysfunctions were abrogated in CRF rats receiving OLM. Decreased cardiac output was normalized compared to control (p p p p p p p  Conclusion OLM treatment could ameliorate arterial stiffness in CRF rats with concomitant inhibition of MDA and AGEs levels through the reduction of oxidative stress in aortic wall.

  2. Renal and cardiovascular role of the neuropeptide Y Y1 receptor in ischaemic heart failure rats

    DEFF Research Database (Denmark)

    Zhao, Xin; Sun, X Y; Bergdahl, A;

    1999-01-01

    pressor response to preganglionic sympathetic nerve stimulation in ischaemic heart failure rats as well as on the contractile response to noradrenaline in renal arteries in sham-operated animals were also inhibited by the neuropeptide Y Y1 antagonist. In conscious ischaemic heart failure rats, incremental...... doses of BIBP 3226 (0.125-1 mg kg(-1)) significantly reduced basal blood pressure and heart rate. Compared with sham-operated rats, neuropeptide Y by itself induced no contraction and no potentiation on noradrenaline elicited contraction in renal artery of the ischaemic heart failure rat. Furthermore......, under in-vivo conditions, BIBP 3226 did not influence basal renal function or the response to exogenous neuropeptide Y on urinary volume, urinary sodium and urinary potassium. Our results demonstrate that although there is a downregulation of the Y1 receptors by ischaemic heart failure, Y1 receptors are...

  3. Trasplante renal Kidney transplant

    Directory of Open Access Journals (Sweden)

    P. Martín

    2006-08-01

    Full Text Available El trasplante renal es la terapia de elección para la mayoría de las causas de insuficiencia renal crónica terminal porque mejora la calidad de vida y la supervivencia frente a la diálisis. El trasplante renal de donante vivo es una excelente alternativa para el paciente joven en situación de prediálisis porque ofrece mejores resultados. El tratamiento inmunosupresor debe ser individualizado buscando la sinergia inmunosupresora y el mejor perfil de seguridad, y debe adaptarse a las diferentes etapas del trasplante renal. En el seguimiento del trasplante renal hay que tener muy en cuenta los factores de riesgo cardiovascular y los tumores puesto que la muerte del paciente con injerto funcionante es la segunda causa de pérdida del injerto tras el primer año del trasplante. La función alterada del injerto es un factor de mortalidad cardiovascular independiente que requerirá seguimiento y control de todas sus complicaciones para retrasar la entrada en diálisis.The kidney transplant is the therapy of choice for the majority of the causes of chronic terminal kidney insufficiency, because it improves the quality of life and survival in comparison with dialysis. A kidney transplant from a live donor is an excellent alternative for the young patient in a state of pre-dialysis because it offers the best results. Immunosuppressive treatment must be individualised, seeking immunosuppressive synergy and the best safety profile, and must be adapted to the different stages of the kidney transplant. In the follow-up to the kidney transplant, cardiovascular risk factors and tumours must be especially taken into account, given that the death of the patient with a working graft is the second cause of loss of the graft following the first year of the transplant. The altered function of the graft is a factor of independent cardiovascular mortality that will require follow-up and the control of all its complications to postpone the entrance in dialysis.

  4. The epidemiology of renal trauma

    OpenAIRE

    Voelzke, Bryan B.; Leddy, Laura

    2014-01-01

    Introduction Nonoperative and minimally invasive management techniques for both blunt and penetrating renal trauma have become standard of care over the past decades. We sought to examine the modern epidemiology of renal trauma over the past decade. Methods A systematic review of PubMed from the past decade was conducted to examine adult and pediatric renal trauma. A total of 605 articles were identified. Of these, 15 adult and 5 pediatric articles met our a priori search criteria. Results Th...

  5. Renal Dysfunction and Cardiovascular Disease

    OpenAIRE

    Soveri, Inga

    2006-01-01

    Kidney dysfunction increases cardiovascular disease (CVD) risk. The mechanisms for the risk increase seem to involve a combination of traditional and non-traditional CVD risk factors. We studied renal dysfunction as CVD and mortality risk factor in middle-aged men free from diabetes and CVD. The risk for myocardial infarction (MI) and CVD mortality was increased by ~40% in the 16.5% of men with worse renal function, independent of other CVD risk factors. Renal transplant dysfunction as CVD an...

  6. Taurine and the renal system

    OpenAIRE

    Chesney Russell W; Han Xiaobin; Patters Andrea B

    2010-01-01

    Abstract Taurine participates in a number of different physiologic and biologic processes in the kidney, often reflected by urinary excretion patterns. The kidney is key to aspects of taurine body pool size and homeostasis. This review will examine the renal-taurine interactions relative to ion reabsorption; renal blood flow and renal vascular endothelial function; antioxidant properties, especially in the glomerulus; and the role of taurine in ischemia and reperfusion injury. In addition, ta...

  7. Renal replacement therapy in ICU

    Directory of Open Access Journals (Sweden)

    C Deepa

    2012-01-01

    Full Text Available Diagnosing and managing critically ill patients with renal dysfunction is a part of the daily routine of an intensivist. Acute kidney insufficiency substantially contributes to the morbidity and mortality of critically ill patients. Renal replacement therapy (RRT not only does play a significant role in the treatment of patients with renal failure, acute as well as chronic, but also has spread its domains to the treatment of many other disease conditions such as myaesthenia gravis, septic shock and acute on chronic liver failure. This article briefly outlines the role of renal replacement therapy in ICU.

  8. Renal Carcinogenesis After Uninephrectomy1

    OpenAIRE

    Sui, Yi; ZHAO, HAI-LU; Lee, Heung Man; Guan, Jing; He, Lan; Lai, Fernand MM; Tong, Peter CY; Chan, Juliana CN

    2009-01-01

    Nephrectomized rats have widely been used to study chronic renal failure. Interestingly, renal cell carcinoma occurred in the remnant kidney after uninephrectomy (UNX). In this study, we probed insulin-like growth factor (IGF)-1 signaling pathway in UNX-induced renal cancer. Adult male Sprague-Dawley rats were randomized into two groups: UNX rats (n = 22) and sham-operated rats (n = 12). Rats were killed at 3, 7, and 10 months. After 7 months after nephrectomy, the UNX rats developed renal ce...

  9. Effects of bulbus Fritillaria water extract on blood pressure and renal functions in the L-NAME-induced hypertensive rats.

    Science.gov (United States)

    Kang, Dae Gill; Sohn, Eun Jin; Lee, Yun Mi; Lee, An Sook; Han, Jong Hyun; Kim, Tai Yo; Lee, Ho Sub

    2004-03-01

    A pharmacological inhibition of nitric oxide synthase (NOS) in rats produces renal vasoconstriction, renal dysfunction, and hypertension. The present study was aimed at investigating whether Bulbus Fritillaria water extract (BFWE) ameliorates NG-nitro-L-arginine methylester (L-NAME)-induced hypertension. Treatment of rats with L-NAME (60 mg/l drinking water, 4 weeks) caused a sustained increase in systolic blood pressure (SBP). The NO concentration in plasma and NO productions in the vascular tissues of the L-NAME-treated group were significantly reduced as compared with those in the control, whereas the expressions of NOS proteins were not altered. BFWE restored SBP to normal level in the L-NAME-treated hypertensive rats. Moreover, BFWE was able to preserve the vascular NO production and plasma NO metabolites concentration without changes of the expression NOS proteins. The renal functional parameters including urinary volume, sodium excretion, and creatinine clearance (Ccr) were significantly restored in rats co-treated with BFWE and L-NAME compared to the L-NAME-treated group. Taken together, these results suggest that BFWE prevents the increase of SBP in the L-NAME-induced hypertension that may have been caused by enhanced generation of vascular NO and amelioration of renal functions. PMID:15036467

  10. Segmental renal dysplasia--a case report.

    OpenAIRE

    Gupta S; Chumber S; Sharma L

    1995-01-01

    A case of segmental renal dysplasia presenting with loin pain, a renal mass and hypertension in a young girl of 16 years is being reported. Clinical and histological features of this rare renal anomaly are discussed.

  11. Genetics Home Reference: renal coloboma syndrome

    Science.gov (United States)

    ... syndrome include backflow of urine from the bladder (vesicoureteral reflux), multiple kidney cysts, loose joints, and mild hearing ... disease coloboma-ureteral-renal syndrome ONCR optic coloboma, vesicoureteral reflux, and renal anomalies optic nerve coloboma renal syndrome ...

  12. Direct oral anticoagulants in real practice: which doses for which patients. Limitations and bleeding risk compared to vitamin K antagonists

    Directory of Open Access Journals (Sweden)

    Giancarlo Landini

    2013-12-01

    Full Text Available The new oral direct anticoagulants (DOACs could represent a new frontier for management of thromboembolic diseases. However, the new drugs have limitations that need to be considered. Despite the fact that their efficacy and safety profile are at least not inferior to comparators, bleeding risk represents the most feared complication, as for all the antithrombotic drugs. Bleeding risk increases with conditions that interfere with pharmacokinetics, in addition to the risk strictly linked to patients or their co-morbidities. Since all DOACs are excreted from kidneys (even though at different percentages according to the different molecules, renal impairment represents one of the leading causes of DOACs accumulation and bleeding risk. Moderate renal failure is the main condition in which dose adjustment of DOACs could be required, while severe renal impairment represents an absolute contraindication for their use. Renal function must, therefore, be carefully monitored before prescription and during assumption. The older population is at higher bleeding risk, and dose adjustment of DOACs could be required. Although to a lesser degree than oral anticoagulant vitamin K antagonists, DOACs can have drug interactions, especially with P-glycoprotein and cytochrome P3A4 inducers or inhibitors, and these interactions must be taken into account in real practice to avoid accumulation or under dosage. The concomitant use of other drugs, especially antithrombotics, may expose the patients to bleeding risk by reducing the hemostatic properties.

  13. The renal scan in pregnant renal transplant patients

    International Nuclear Information System (INIS)

    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

  14. Leptin and the Regulation of Renal Sodium Handling and Renal Na-Transporting ATPases: Role in the Pathogenesis of Arterial Hypertension.

    Science.gov (United States)

    Bełtowski, Jerzy

    2010-02-01

    Leptin, an adipose tissue hormone which regulates food intake, is also involved in the pathogenesis of arterial hypertension. Plasma leptin concentration is increased in obese individuals. Chronic leptin administration or transgenic overexpression increases blood pressure in experimental animals, and some studies indicate that plasma leptin is elevated in hypertensive subjects independently of body weight. Leptin has a dose- and time-dependent effect on urinary sodium excretion. High doses of leptin increase Na(+) excretion in the short run; partially by decreasing renal Na(+),K(+)-ATPase (sodium pump) activity. This effect is mediated by phosphatidylinositol 3-kinase (PI3K) and is impaired in animals with dietary-induced obesity. In contrast to acute, chronic elevation of plasma leptin to the level observed in patients with the metabolic syndrome impairs renal Na(+) excretion, which is associated with the increase in renal Na(+),K(+)-ATPase activity. This effect results from oxidative stress-induced deficiency of nitric oxide and/or transactivation of epidermal growth factor receptor and subsequent stimulation of extracellular signal-regulated kinases. Ameliorating "renal leptin resistance" or reducing leptin level and/or leptin signaling in states of chronic hyperleptinemia may be a novel strategy for the treatment of arterial hypertension associated with the metabolic syndrome. PMID:21286276

  15. Early diagnosis of renal disease and renal failure.

    Science.gov (United States)

    Lees, George E

    2004-07-01

    The main goal of early diagnosis of renal disease and renal failure in dogs and cats is to enable timely application of therapeutic interventions that may slow or halt disease progression. Strategies for early diagnosis of renal disease use urine tests that detect proteinuria that is a manifestation of altered glomerular permselectivity or impaired urine-concentrating ability as well blood tests to evaluate plasma creatinine concentration. Animals with progressive renal disease should be carefully investigated and treated appropriately. Animals with mild, possibly nonprogressive, renal disease should be monitored adequately to detect any worsening trends,which should lead to further investigation and treatment even if the increments of change are small. PMID:15223206

  16. Renal posttransplant's vascular complications

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    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

  17. Unexpected recovery from longterm renal failure in severe diffuse proliferative lupus nephritis

    Directory of Open Access Journals (Sweden)

    Ross Sophia

    2012-08-01

    Full Text Available Abstract Background Severe renal manifestation of systemic lupus erythematosus (SLE is not uncommon and is associated with an indeterminate prognosis. Complete remission can be obtained, however, at least in the young when chronic lesions are absent and adequate anti-inflammatory therapy is immediately initiated. Case presentation We report the unusual case of a 12-year-old girl who presented with severe oliguric renal failure, macrohematuria and skin rash. Renal biopsy revealed the diagnosis of severe diffuse proliferative glomerulonephritis (GN with cellular crescents in 15 out of 18 glomeruli and full-house pattern in immunofluorescence indicating lupus nephritis IVB according to WHO, IV-G(A according to ISN/RPS classification. The serological parameters confirmed the diagnosis of SLE and the patient was immediately treated with methylprednisolone, cyclophosphamide and immunoadsorption. Initially, despite rapid amelioration of her general condition, no substantial improvement of renal function could be achieved and the patient needed hemodialysis treatment for 12 weeks. Unexpectedly, in the further follow-up at first diuresis increased and thereafter also creatinine levels substantially declined so that hemodialysis could be discontinued. Today, 6 years after the initial presentation, the patient has normal renal function and a SLEDAI score of 0 under a continuous immunosuppressive therapy with Mycophenolate mofetil (MMF and low dose steroid. Conclusion Despite the severity of the initial renal injury and the unfavourable renal prognosis the kidney apparently has a tremendous capacity to recover in young patients when the damage is acute and adequate anti-inflammatory therapy is initiated without delay.

  18. Citrato y litiasis renal

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    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.

  19. Renal metabolism of calcitonin

    International Nuclear Information System (INIS)

    The kidneys account for approximately two-thirds of the metabolism of calcitonin, but relatively little is known regarding the details thereof. To further characterize this process, we examined the renal handling and metabolism of human calcitonin (hCT) by the isolated perfused rat kidney. We also studied the degradation of radiolabeled salmon calcitonin (sCT) by subcellular fractions prepared from isolated rabbit proximal tubules. The total renal (organ) clearance of immunoreactive hCT by the isolated kidney was 1.96 +/- 0.18 ml/min. This was independent of the perfusate total calcium concentration from 5.5 to 10.2 mg/dl. Total renal clearance exceeded the glomerular filtration rate (GFR, 0.68 +/- 0.05 ml/min), indicating filtration-independent removal. Urinary calcitonin clearance as a fraction of GFR averaged 2.6%. Gel filtration chromatography of medium from isolated kidneys perfused with 125I-labeled sCT showed the principal degradation products to be low molecular weight forms eluting with monoiodotyrosine. Intermediate size products were not detected. In the subcellular fractionation experiments, when carried out at pH 5.0, calcitonin hydrolysis exclusively followed the activities of the lysosomal enzyme N-acetyl-beta-glucosaminidase. Typically, at pH 7.5, 42% of total degradation occurred in the region of the brush-border enzyme alanyl aminopeptidase and 29% occurred in the region of the cytosolic enzyme phosphoglucomutase. Although 9% of the calcitonin-degrading activity was associated with basolateral membrane fractions, most of this activity could be accounted for by the presence of brush-border membranes

  20. Hesperidin ameliorates streptozotocin and high fat diet induced diabetic nephropathy in rats

    Directory of Open Access Journals (Sweden)

    Dilpesh P. Jain

    2014-12-01

    Full Text Available Objective: The present study investigates protective effect of hesperidin on streptozotocin and high fat diet induced diabetic nephropathy in experimental type 2 diabetic rats. Methods: Sprague Dawley rats were fed with high fat emulsion and high fat diet for 2 weeks to induce glucose intolerance and then injected with streptozotocin (35 mg/kg, i.p.. Following 48 h of streptozotocin injection blood glucose level was estimated to confirm hyperglycemia. After 4 weeks of diabetes induction diabetic rats were orally treated with hesperidin (50, 100 and 200 mg/kg body weight for 4 weeks. At the end of the treatment kidney functions, oxidative stress indices, biochemical estimations and histopathological examination were carried out to assess the efficacy of the treatment. Results: Diabetic rats exhibited significant rise in blood glucose level, altered kidney functions, oxidative stress and histological abnormalities compared to control rats. Hesperidin treatment significantly reduced the elevated levels of blood glucose, creatinine, urea nitrogen, total cholesterol and triglyceride when compared with diabetic control rats. Significant rise in renal hypertrophy, hyperfiltration, microalbuminuria as well as oxidative stress in the diabetic rats were effectively attenuated with hesperidin treatment, dose dependently. Moreover, basement membrane thickening and mesangial expansion observed in the kidney of diabetic rats restored near to normal structure. Conclusion: Results of the present study suggest that hesperidin ameliorate early diabetic nephropathy. [J Exp Integr Med 2014; 4(4.000: 261-267

  1. Platycodin D, a triterpenoid sapoinin from Platycodon grandiflorum, ameliorates cisplatin-induced nephrotoxicity in mice.

    Science.gov (United States)

    Kim, Tae-Won; Song, In-Bae; Lee, Hong-Ki; Lim, Jong-Hwan; Cho, Eun-Sang; Son, Hwa-Young; Park, Sang-Jin; Kim, Jong-Woo; Yun, Hyo-In

    2012-12-01

    Platycodin D (PD) is well known as a potent triterpenoid saponin having various pharmacological activities isolated from the root of Platycodon grandiflorum (Jacq.) A. DC. (Campanulaceae). We aimed to evaluate protective effect of PD on cisplatin (CDDP)-induced nephrotoxicity. Male ICR mice were allocated into five groups as follows: Negative control, CDDP alone and CDDP with PD (0.1, 1 and 5 mg/kg) treated group. PD was given for three consecutive days before CDDP injection. Increased blood urea nitrogen (BUN) and creatinine (CRE) levels in CDDP alone treated mice were decreased to normal range by pretreatment with PD. It also decreased nitric oxide (NO) and lipid peroxidation with increased antioxidant enzymes such as glutathione (GSH), glutathione peroxidase (GPx) and superoxide dismutase (SOD) in PD pretreated mice. In histopathological examination, pretreatment with PD showed ameliorated renal injury such as intraluminal cast formation and epithelial desquamation. Furthermore, over-expression of nuclear factor-kappa B p65 and apoptotic cells were suppressed by PD pretreatment. Taken together, PD pretreatment might be beneficial to CDDP-induced nephrotoxicity. PMID:22617354

  2. Rhubarb extract ameliorates some biochemical disorders induced by gamma irradiation in male rats

    International Nuclear Information System (INIS)

    The current study was conducted to evaluate the possible modulating efficacy of prolonged oral administration of rhubarb extract against gamma irradiation induced some biochemical disorders in male rats. Rhubarb extract was orally administrated at a concentration of 100 mg/kg body wt daily for 21 days before irradiation at a single dose of 7 Gy and for 7 days post exposure. Transaminases (AST and ALT), urea, creatinine, alkaline phosphatase (ALP), lipid profile; cholesterol, triglycerides (T.G.) and low density lipoprotein (LDL) as well as serum glucose level were determined. Also, liver reduced glutathione (GSH) content and lipid peroxidation were estimated. Rats exposed to ionizing radiation revealed transaminases disorders, lipid abnormalities, elevation in serum glucose, ALP activity as well as liver TBARS. Whereas a sharp drop in glutathione was recorded. The obtained data showed that rats treated with rhubarb extract before and after whole body gamma irradiation exhibited a significant amelioration in liver and renal marker enzymes, serum glucose and lipids as well as noticeable improvement in liver glutathione contents. Rhubarb extract was also effective in minimizing lipid peroxidation induced by irradiation. It could be concluded that rhubarb extract exerts a beneficial protective role against gamma irradiation

  3. Amelioration of Endothelial Dysfunction Associated with Diabetes Mellitus and Hypertension by Etoricoxib, Lornoxicam and Allopurinol

    Directory of Open Access Journals (Sweden)

    V. S. Nade

    2014-04-01

    Full Text Available Endothelial dysfunction is associated with diabetes mellitus and hypertension. Oxidative stress and augmented activity of associated enzymes like cyclooxygenase (COX and xanthine oxidase (XO is a major culprit. In this study, diabetes mellitus (DM was induced by alloxan (75 mg/kg, i.v and hypertension was induced by left renal artery (LRA ligation in male Wistar rats. Treatment with COX inhibitors, etoricoxib (10 mg/kg, p.o, lornoxicam (4.5 mg/kg, i.p and XO inhibitor, allopurinol (50 mg/kg, p.o was initiated after confirming induction of diabetes and hypertension and continued for 6 weeks. Vascular reactivity to catecholamines like adrenaline (1 µg/kg, noradrenaline (1 µg/kg, and phenylephrine (1 µg/kg, was evaluated in both models wherein treated rats expressed better responses than untreated groups. In an in vitro study, relaxant response to acetylcholine (ACh and sodium nitroprusside (SNP was observed on isolated aortas. Relaxation to ACh was impaired in untreated groups but treated groups produced near to normal relaxant responses. In case of SNP, no significant results were obtained. Diabetes and hypertension induced significant oxidative stress reflected by increase in lipid peroxidation level and decrease in antioxidant enzymes like catalase and superoxide dismutase. Drugs treatment reversed these effects on oxidative stress indices and ameliorated endothelial dysfunction.

  4. 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

    2015-12-01

    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. PMID:26327248

  5. Implementation of a fluorescence-based screening assay identifies histamine H3 receptor antagonists clobenpropit and iodophenpropit as subunit-selective N-methyl-D-aspartate receptor antagonists

    DEFF Research Database (Denmark)

    Hansen, Kasper Bø; Mullasseril, Praseeda; Dawit, Sara; Kurtkaya, Natalie L; Yuan, Hongjie; Vance, Katie M; Orr, Anna G; Kvist, Trine; Ogden, Kevin K; Le, Phuong; Vellano, Kimberly M; Lewis, Iestyn; Kurtkaya, Serdar; Du, Yuhong; Qui, Min; Murphy, T J; Snyder, James P; Bräuner-Osborne, Hans; Traynelis, Stephen F

    2010-01-01

    NMDA receptor function, including the histamine H3 receptor antagonists clobenpropit and iodophenpropit, as well as the vanilloid receptor transient receptor potential cation channel, subfamily V, member 1 (TRPV1) antagonist capsazepine. These compounds are noncompetitive antagonists and the histamine...

  6. Imaging of renal metastases

    International Nuclear Information System (INIS)

    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

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

    International Nuclear Information System (INIS)

    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 [125I][Sar1-Ile8]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. (author)

  8. 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.

  9. Future aspects of renal transplantation*

    OpenAIRE

    Makowka, L.; Lopatin, W.B.; Shapiro, R.; Tzakis, A.G.; Starzl, T.E.

    1988-01-01

    New and exciting advances in renal transplantation are continuously being made, and the horizons for organ transplantation are bright and open. This article reviews only a few of the newer advances that will allow renal transplantation to become even more widespread and successful. The important and exciting implications for extrarenal organ transplantation are immediately evident.

  10. Renal involvement in behcet's disease

    International Nuclear Information System (INIS)

    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)

  11. 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 r...

  12. Renal (Kidney) Manifestations in TSC

    Medline Plus

    Full Text Available ... renal abnormalities include renal ultrasonography, CT scanning and magnetic resonance imaging (MRI). These are all non-invasive procedures that are ... least detailed image of the kidney, while the MRI provides the most detailed. In general, the ultrasound ...

  13. Renal Heme Oxygenase-1 Induction with Hemin Augments Renal Hemodynamics, Renal Autoregulation, and Excretory Function

    Science.gov (United States)

    Botros, Fady T.; Dobrowolski, Leszek; Navar, L. Gabriel

    2012-01-01

    Heme oxygenases (HO-1; HO-2) catalyze conversion of heme to free iron, carbon monoxide, and biliverdin/bilirubin. To determine the effects of renal HO-1 induction on blood pressure and renal function, normal control rats (n = 7) and hemin-treated rats (n = 6) were studied. Renal clearance studies were performed on anesthetized rats to assess renal function; renal blood flow (RBF) was measured using a transonic flow probe placed around the left renal artery. Hemin treatment significantly induced renal HO-1. Mean arterial pressure and heart rate were not different (115 ± 5 mmHg versus 112 ± 4 mmHg and 331 ± 16 versus 346 ± 10 bpm). However, RBF was significantly higher (9.1 ± 0.8 versus 7.0 ± 0.5 mL/min/g, P < 0.05), and renal vascular resistance was significantly lower (13.0 ± 0.9 versus 16.6 ± 1.4 [mmHg/(mL/min/g)], P < 0.05). Likewise, glomerular filtration rate was significantly elevated (1.4 ± 0.2 versus 1.0 ± 0.1 mL/min/g, P < 0.05), and urine flow and sodium excretion were also higher (18.9 ± 3.9 versus 8.2 ± 1.0 μL/min/g, P < 0.05 and 1.9 ± 0.6 versus 0.2 ± 0.1 μmol/min/g, P < 0.05, resp.). The plateau of the autoregulation relationship was elevated, and renal vascular responses to acute angiotensin II infusion were attenuated in hemin-treated rats reflecting the vasodilatory effect of HO-1 induction. We conclude that renal HO-1 induction augments renal function which may contribute to the antihypertensive effects of HO-1 induction observed in hypertension models. PMID:22518281

  14. Glycine preconditioning to ameliorate pulmonary ischemia reperfusion injury in rats

    NARCIS (Netherlands)

    Sommer, Sebastian-Patrick; Sommer, Stefanie; Sinha, Bhanu; Leyh, Rainer G.

    2012-01-01

    This study examines the impact of glycine (Gly) preconditioning on ischemia reperfusion (IR)-induced pulmonary mitochondrial injury to research the previously, in pig lungs, demonstrated Gly-dependent amelioration of pulmonary IR injury. IR injury was induced in rat lungs by 30 min pulmonary hilum c

  15. 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 althou

  16. Renal biopsy: methods and interpretation.

    Science.gov (United States)

    Vaden, Shelly L

    2004-07-01

    Renal biopsy most often is indicated in the management of dogs and cats with glomerular disease or acute renal failure. Renal biopsy can readily be performed in dogs and cats via either percutaneous or surgical methods. Care should be taken to ensure that proper technique is used. When proper technique is employed and patient factors are properly addressed, renal biopsy is a relatively safe procedure that minimally affects renal function. Patients should be monitored during the post biopsy period for severe hemorrhage, the most common complication. Accurate diagnosis of glomerular disease, and therefore, accurate treatment planning,requires that the biopsy specimens not only be evaluated by light microscopy using special stains but by electron and immunofluorescent microscopy. PMID:15223207

  17. Low molecular weight fucoidan against renal ischemia-reperfusion injury via inhibition of the MAPK signaling pathway.

    Directory of Open Access Journals (Sweden)

    Jihui Chen

    Full Text Available BACKGROUND: Ischemia reperfusion injury (IRI is a leading cause of acute kidney injury (AKI in both native and transplanted kidneys. The objective of the present study was to evaluate whether low-molecular-weight fucoidan (LMWF could attenuate renal IRI in an animal model and in vitro cell models and study the mechanisms in which LMWF protected from IRI. METHODOLOGY/PRINCIPAL FINDINGS: Male mice were subjected to right renal ischemia for 30 min and reperfusion for 24 h, or to a sham operation with left kidney removed. Kidneys undergone IR showed characteristic morphological changes, such as tubular dilatation, and brush border loss. However, LMWF significantly corrected the renal dysfunction and the abnormal levels of MPO, MDA and SOD induced by IR. LMWF also inhibited the activation of MAPK pathways, which consequently resulted in a significant decrease in the release of cytochrome c from mitochondria, ratios of Bax/Bcl-2 and cleaved caspase-3/caspase-3, and phosphorylation of p53. LMWF alleviated hypoxia-reoxygenation or CoCl(2 induced cell viability loss and ΔΨm dissipation in HK2 renal tubular epithelial cells, which indicates LMWF may result in an inhibition of the apoptosis pathway through reducing activity of MAPK pathways in a dose-dependent manner. CONCLUSIONS/SIGNIFICANCE: Our in vivo and in vitro studies show that LMWF ameliorates acute renal IRI via inhibiting MAPK signaling pathways. The data provide evidence that LMWF may serve as a potential therapeutic agent for acute renal IRI.

  18. Renal transplantation in infants.

    Science.gov (United States)

    Jalanko, Hannu; Mattila, Ilkka; Holmberg, Christer

    2016-05-01

    Renal transplantation (RTx) has become an accepted mode of therapy in infants with severe renal failure. The major indications are structural abnormalities of the urinary tract, congenital nephrotic syndrome, polycystic diseases, and neonatal kidney injury. Assessment of these infants needs expertise and time as well as active treatment before RTx to ensure optimal growth and development, and to avoid complications that could lead to permanent neurological defects. RTx can be performed already in infants weighing around 5 kg, but most operations occur in infants with a weight of 10 kg or more. Perioperative management focuses on adequate perfusion of the allograft and avoidance of thrombotic and other surgical complications. Important long-term issues include rejections, infections, graft function, growth, bone health, metabolic problems, neurocognitive development, adherence to medication, pubertal maturation, and quality of life. The overall outcome of infant RTx has dramatically improved, with long-term patient and graft survivals of over 90 and 80 %, respectively. PMID:26115617

  19. Ultrasound of renal transplantation

    Energy Technology Data Exchange (ETDEWEB)

    Baxter, G.M

    2001-10-01

    The most effective primary treatment of chronic renal failure is renal transplantation. A significant improvement in lifestyle and family life in conjunction with it being an extremely cost-effective procedure has resulted in an intense monitoring and imaging programme to help ensure a successful outcome. Ultrasound, both grey-scale and colour-flow Doppler, are useful monitoring techniques when interpreted in the clinical context, and in the delineation of peri-transplant collections, some of which can be drained under ultrasound guidance. After the early post-operative period it can also be utilized in the diagnosis of chronic vascular complications including transplant artery stenosis and arteriovenous fistula, although it is of limited use in the diagnosis of chronic rejection. This article will discuss the role of ultrasound in all its guises and how its efficacy in both the early transplant period in the monitoring of graft dysfunction and in the detection of the more chronic conditions including transplant artery stenosis and arteriovenous fistulae. A more limited role for ultrasound also exists in the long-term follow-up of patients and to aid the detection of complications including susceptibility to malignancy. Baxter, G.M. (2001)

  20. Antagonistic coevolution between quantitative and Mendelian traits.

    Science.gov (United States)

    Yamamichi, Masato; Ellner, Stephen P

    2016-03-30

    Coevolution is relentlessly creating and maintaining biodiversity and therefore has been a central topic in evolutionary biology. Previous theoretical studies have mostly considered coevolution between genetically symmetric traits (i.e. coevolution between two continuous quantitative traits or two discrete Mendelian traits). However, recent empirical evidence indicates that coevolution can occur between genetically asymmetric traits (e.g. between quantitative and Mendelian traits). We examine consequences of antagonistic coevolution mediated by a quantitative predator trait and a Mendelian prey trait, such that predation is more intense with decreased phenotypic distance between their traits (phenotype matching). This antagonistic coevolution produces a complex pattern of bifurcations with bistability (initial state dependence) in a two-dimensional model for trait coevolution. Furthermore, with eco-evolutionary dynamics (so that the trait evolution affects predator-prey population dynamics), we find that coevolution can cause rich dynamics including anti-phase cycles, in-phase cycles, chaotic dynamics and deterministic predator extinction. Predator extinction is more likely to occur when the prey trait exhibits complete dominance rather than semidominance and when the predator trait evolves very rapidly. Our study illustrates how recognizing the genetic architectures of interacting ecological traits can be essential for understanding the population and evolutionary dynamics of coevolving species. PMID:27009218

  1. Sexually antagonistic selection in human male homosexuality.

    Science.gov (United States)

    Camperio Ciani, Andrea; Cermelli, Paolo; Zanzotto, Giovanni

    2008-01-01

    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. PMID:18560521

  2. 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.

  3. Influences of renal stone surgeries on renal function

    International Nuclear Information System (INIS)

    From 1984 to 1990, 99mTc-DMSA renal scintigraphy was performed before and after nephrolithotomy (15 cases), pyelolithotomy (15 cases), percutaneous nephrolithotripsy (PNL: 15 cases) and extracorporeal shock wave lithotripsy (ESWL: 16 cases, 17 kidneys) in order to evaluate of influences of renal stone surgeries on split renal function. DMSA renal uptake change ratio of treated kidneys of nephrolithotomy (-24.94±5.60%) was significantly lower than that of PNL (-0.06±3.92%), pyelolithotomy (-4.08±4.79%) (p<0.01) and ESWL (-7.72±3.87%) (p<0.05). The average change ratios of contralateral kidneys were as follows: PNL 4.80±4.21% nephrolithotomy 4.67±4.73%, pyelolithotomy -1.46±5.39% and ESWL -2.02±4.44%. One to 3 weeks after PNL, the cold area on the renal image was found in 10 (66.7%) of 15 cases. In cases of ESWL, DMSA renal uptake decreased even 4-10 weeks (mean 7 weeks) after treatment. In conclusion, possibility of deterioration of renal function after ESWL was suggested. (author)

  4. Amelioration of Cadmium-Induced Nephropathy using Polyphenol-rich Extract of Vernonia amygdalina (Del. Leaves in Rat Model

    Directory of Open Access Journals (Sweden)

    Christian E. Imafidon

    2015-11-01

    Full Text Available AIM: To determine the effects of polyphenol-rich extract of the leaves of Vernonia amygdalina (PEVA in rats with Cd-induced nephropathy. MATERIALS AND METHODS: Sixty five male Wistar rats were divided into five groups as follows; Group 1 received distilled water throughout the period of study. Group 2 received 5 mg/kg body weight of cadmium (Cd, in the form of CdSO4, for five consecutive days via intraperitoneal route. Groups 3, 4 and 5 were pretreated with Cd as group 2 and thereafter received oral treatment of PEVA for 4 weeks at 100 mg/kg, 200 mg/kg and 400 mg/kg body weight, respectively. RESULTS: Exposure to Cd toxicity significantly induced deleterious alterations in plasma and urine levels of creatinine, urea and glucose as well as creatinine and urea clearance (p < 0.05 in the rat model. There was a significant disturbance in the antioxidant system as revealed by the levels of thiobarbituric acid reactive substance (TBARS and reduced glutathione (GSH (p < 0.05 in the kidney tissue of the rats. With marked improvements in renal histoarchitecture, PEVA treatment showed a duration and non dose-dependent ameliorative potential. CONCLUSION: PEVA treatment reversed the compromise of renal function that was induced by Cd toxicity in rat model.

  5. Functional Importance of L- and P/Q-Type Voltage-Gated Calcium Channels in Human Renal Vasculature

    DEFF Research Database (Denmark)

    Hansen, Pernille B; Poulsen, Christian B; Walter, Steen;

    2011-01-01

    revealed signals for Ca(v) 2.1 and Ca(v) 3.1 associated with smooth muscle cells of preglomerular and postglomerular vessels. In human intrarenal arteries, depolarization with potassium induced a contraction inhibited by the L-type antagonist nifedipine, EC(50) 1.2×10(-8) mol/L. The T-type antagonist...... L- and P/Q-type channels are of functional importance for the depolarization-induced vasoconstriction. The contribution of P/Q-type channels to contraction in the human vasculature is a novel mechanism for the regulation of renal blood flow and suggests that clinical treatment with calcium blockers......Calcium channel blockers are widely used for treatment of hypertension, because they decrease peripheral vascular resistance through inhibition of voltage-gated calcium channels. Animal studies of renal vasculature have shown expression of several types of calcium channels that are involved in...

  6. 99Tcm-diethylenetriaminepenta hydroxamic acid renal dynamic imaging to evaluate split renal GFR of unilateral renal function failure patient

    International Nuclear Information System (INIS)

    Objective: To explore the use of evaluating split glomerular flow rate (GFB) in patients with unilateral renal function failure by 99Tcm-diethylenetriaminepenta hydroxamic acid renal dynamic imaging. Methods: Split GFR of 82 cases with unilateral renal function failure was evaluated by 99Tcm- DTPA renal dynamic imaging, and was correlated with serum creatinine (SCr). Beside, causes of renal function failure were analyzed. Results: Split CFR were negatively correlated with SCr(r=-0.643, P99Tcm-DTPA renal dynamic imaging to treat early and reserve renal function. (authors)

  7. 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...... renal calculi in medullary sponge kidney, have considerable therapeutic implications....

  8. Integrated imaging of neonatal renal masses

    Energy Technology Data Exchange (ETDEWEB)

    Kirks, D.R.; Rosenberg, E.R.; Johnson, D.G.; King, L.R.

    1985-02-01

    Thirty-three neonatal renal masses were evaluated during a 2 year interval. The final diagnoses in these 33 patients were hydronephrosis, multicystic dysplastic kidney, renal vein thrombosis, obstructed upper pole duplication, polycystic kidney disease, nephroblastomatosis, and mesoblastic nephroma. We recommend an integrated imaging approach that utilizes sonography to clarify anatomy and renal scintigraphy or excretory urography to determine renal function.

  9. 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.

  10. Losartan renography for the detection of renal artery stenosis: comparison with captopril renography and evaluation of dose and timing

    Energy Technology Data Exchange (ETDEWEB)

    Guenay, Emel Ceylan; Erguen, Eser Lay; Salanci, Bilge Volkan; Ugur, Oemer; Caner, Biray [Hacettepe University Faculty of Medicine, Department of Nuclear Medicine, Ankara (Turkey); Oeztuerk, M. Halil; Hekimoglu, Baki [Social Security Hospital Clinic of Radiology, Ankara (Turkey); Altun, Buelent [Hacettepe University Faculty of Medicine, Department of Nephrology, Ankara (Turkey); Cil, Barbaros [Hacettepe University Faculty of Medicine, Department of Radiology, Ankara (Turkey)

    2005-09-01

    Radionuclide renography with angiotensin converting enzyme (ACE) inhibition plays an important role in the diagnosis of haemodynamically significant renal artery stenosis. Angiotensin receptor antagonists inhibit the renin angiotensin system at different levels from ACE inhibitors by selectively blocking the binding of angiotensin II to AT1 receptors. The AT1 angiotensin receptor antagonist losartan has recently been used clinically in the treatment of hypertension. However, the available data on the use of losartan with renography for the detection of renovascular hypertension are limited and contradictory. The purpose of this prospective study was to compare the effectiveness of losartan renography and captopril scintigraphy in revealing renal artery stenosis. A total of 61 renal units in 32 patients with hypertension were studied in two groups based on the losartan dosage (50 mg in group A and 100 mg in group B). Group A consisted of 17 patients, in whom 19 renal units had angiographically proven renal artery stenosis ({>=}50%). In group B, there were 15 patients, in whom 20 renal arteries were stenotic. All of the patients underwent three renographies (baseline, captopril renography and early losartan renography). Early losartan renography was performed at 1 h after oral losartan administration in both groups. In group B, seven patients underwent additional losartan renography (late losartan) performed 3 h after oral losartan administration; these patients composed group B1. The sensitivities of captopril and losartan studies were 63.2% and 42% in group A, 65% and 65% in group B and 55.6% and 66.6% in group B1, respectively. From our preliminary results, we conclude that losartan is not superior to captopril renography for the detection of haemodynamically significant renal artery stenosis. However, a high dose (100 mg) of losartan provided higher sensitivity than the lower dose (50 mg). Late losartan scintigraphy provided similar diagnostic efficacy to early

  11. Na+-K+ pump in chronic renal failure

    International Nuclear Information System (INIS)

    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 22Na+ and 42K+ 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 42K+ 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

  12. 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

  13. Corticospinal control of antagonistic muscles in the cat.

    Science.gov (United States)

    Ethier, Christian; Brizzi, Laurent; Giguère, Dominic; Capaday, Charles

    2007-09-01

    We recently suggested that movement-related inter-joint muscle synergies are recruited by selected excitation and selected release from inhibition of cortical points. Here we asked whether a similar cortical mechanism operates in the functional linking of antagonistic muscles. To this end experiments were done on ketamine-anesthetized cats. Intracortical microstimulation (ICMS) and intramuscular electromyographic recordings were used to find and characterize wrist, elbow and shoulder antagonistic motor cortical points. Simultaneous ICMS applied at two cortical points, each evoking activity in one of a pair of antagonistic muscles, produced co-contraction of antagonistic muscle pairs. However, we found an obvious asymmetry in the strength of reciprocal inhibition; it was always significantly stronger on physiological extensors than flexors. Following intravenous injection of a single bolus of strychnine, a cortical point at which only a physiological flexor was previously activated also elicited simultaneous activation of its antagonist. This demonstrates that antagonistic corticospinal neurons are closely grouped, or intermingled. To test whether releasing a cortical point from inhibition allows it to be functionally linked with an antagonistic cortical point, one of three GABA(A) receptor antagonists, bicuculline, gabazine or picrotoxin, was injected iontophoretically at one cortical point while stimulation was applied to an antagonistic cortical point. This coupling always resulted in co-contraction of the represented antagonistic muscles. Thus, antagonistic motor cortical points are linked by excitatory intracortical connections held in check by local GABAergic inhibition, with reciprocal inhibition occurring at the spinal level. Importantly, the asymmetry of cortically mediated reciprocal inhibition would appear significantly to bias muscle maps obtained by ICMS in favor of physiological flexors. PMID:17880397

  14. Cardiac and Renal Effects of Atrasentan in Combination with Enalapril and Paricalcitol in Uremic Rats

    Directory of Open Access Journals (Sweden)

    Cynthia Ritter

    2014-09-01

    Full Text Available Background/Aims: The search for new therapies providing cardiorenal protection in chronic kidney disease (CKD has led to treatments that combine conventional renin-angiotensin-aldosterone-system inhibitors with other drugs that exhibit potential in disease management. Methods: In rats made uremic by renal ablation, we examined the effects of addition of the endothelin-A receptor antagonist atrasentan to a previously examined combination of enalapril (angiotensin converting enzyme inhibitor and paricalcitol (vitamin D receptor activator on cardiac and renal parameters. The effects of the individual and combined drugs were examined after a 3-month treatment. Results: A decrease in systolic blood pressure, serum creatinine and proteinuria, and improvement of renal histology in uremic rats were attributed to enalapril and/or paricalcitol treatment; atrasentan alone had no effect. In heart tissue, individual treatment with the drugs blunted the increase in cardiomyocyte size, and combined treatment additively decreased cardiomyocyte size to normal levels. Perivascular fibrosis was blunted in uremic control rats with atrasentan or enalapril treatment. Conclusions: We found distinct cardiac and renal effects of atrasentan. Combination treatment with atrasentan, enalapril and paricalcitol provided positive effects on cardiac remodeling in uremic rats, whereas combination treatment did not offer further protective effects on blood pressure, proteinuria or renal histology.

  15. 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

    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 (Pdose < 0.0001), and PD123319 intensified the reduction of RBF response in female (Pgroup < 0.005), but not in male rats. Conclusion. The impact of the AT2R on vascular responses to Ang II in renal I/R injury appears to be sexually dimorphic. PD123319 infusion promotes these hemodynamic responses in female more than in male rats. PMID:27034657

  16. Complement C5a-C5aR interaction enhances MAPK signaling pathway activities to mediate renal injury in trichloroethylene sensitized BALB/c mice.

    Science.gov (United States)

    Zhang, Jia-xiang; Zha, Wan-sheng; Ye, Liang-ping; Wang, Feng; Wang, Hui; Shen, Tong; Wu, Chang-hao; Zhu, Qi-xing

    2016-02-01

    We have previously shown complement activation as a possible mechanism for trichloroethylene (TCE) sensitization, leading to multi-organ damage including the kidneys. In particular, excessive deposition of C5 and C5b-9-the membrane attack complex, which can generate significant tissue damage, was observed in the kidney tissue after TCE sensitization. The present study tested the hypothesis that anaphylatoxin C5a binding to its receptor C5aR mediates renal injury in TCE-sensitized BALB/c mice. BALB/c mice were sensitized through skin challenge with TCE, with or without pretreatment by the C5aR antagonist W54011. Kidney histopathology and the renal functional test were performed to assess renal injury, and immunohistochemistry and fluorescent labeling were carried out to assess C5a and C5aR expressions. TCE sensitization up-regulated C5a and C5aR expressions in kidney tissue, generated inflammatory infiltration, renal tubule damage, glomerular hypercellularity and impaired renal function. Antagonist pretreatment blocked C5a binding to C5aR and attenuated TCE-induced tissue damage and renal dysfunction. TCE sensitization also caused the deposition of major pro-inflammatory cytokines IL-2, TNF-α and IFN-γ in the kidney tissue (P TCE sensitization-induced increase of IL-2, TNF-α and IFN-γ (P TCE or other environmental chemicals. PMID:26095957

  17. Mature Cystic Renal Teratoma

    International Nuclear Information System (INIS)

    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

  18. [Cystic renal pathology].

    Science.gov (United States)

    Rosi, P; Cesaroni, M; Bracarda, S; Rociola, W; Virgili, G

    1993-08-01

    Ultrasonography has a great interest in diagnosis of cystic kidney disorders for typical eco-pattern of this pathology. In this work we show the eco-pattern of the most common cystic kidney disorders. Particularly we examine simple cysts (typical, atypical, complicated), multicystic kidney dysplasia, autosomal recessive polycystic kidney disease (infantile) autosomal dominant polycystic kidney disease (adult age). The so-called neoplastic cysts (multiloculated cysts, multiloculated cysts nephroma, cystic nephroblastoma), medullar cysts (medullary sponge kidney, medullary cystic disease), parapyelic cysts, acquired cystic kidney disease in renal failure patients, parasitic cysts, epidermoid cysts. About this disorders we present the more typical and expressive ultrasonographic appearance and we define the role and the opportunity of diagnostic setting by echography, moreover ultrasonography allows us to make a differential diagnosis between cystic kidney disorders and other kidney disease. PMID:8353538

  19. Genetic Counseling in Renal Masses

    OpenAIRE

    José Antonio López-Guerrero; Zaida García-Casado; Antonio Fernández-Serra; José Rubio-Briones

    2008-01-01

    All urologists have faced patients suffering a renal cancer asking for the occurrence of the disease in their offspring and very often the answer to this question has not been well founded from the scientific point of view, and only in few cases a familial segregation tree is performed. The grate shift seen in the detection of small renal masses and renal cancer in the last decades will prompt us to know the indications for familial studies, which and when are necessary, and probably to refer...

  20. Non-renal urological lymphomas

    International Nuclear Information System (INIS)

    IVP, US and CT findings for 5 rare cases of non-renal lymphomas of the urinary tract are discussed. The 4 non-Hodgkin lymphomas (NHL) and 1 Hodgkin's disease (HD) involved the ureter (2 cases), bladder (2 cases) and renal pelvis (1 case). US and CT visualised the pyelic lesion (undetected by urography) as wall thickening and detected the two ureteral lesions (which were also revealed by antegrade pyelography for the 1 HD and by retrograde pyelography for an ureteral NHL). One bladder lesion was associated with a renal lesion (CT demonstrated retroperitoneal lymph nodes); the other was a multinodular form infiltrating the entire bladder. (orig.)

  1. 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.

  2. Mutually-antagonistic interactions in baseball networks

    Science.gov (United States)

    Saavedra, Serguei; Powers, Scott; McCotter, Trent; Porter, Mason A.; Mucha, Peter J.

    2010-03-01

    We formulate the head-to-head matchups between Major League Baseball pitchers and batters from 1954 to 2008 as a bipartite network of mutually-antagonistic interactions. We consider both the full network and single-season networks, which exhibit structural changes over time. We find interesting structure in the networks and examine their sensitivity to baseball’s rule changes. We then study a biased random walk on the matchup networks as a simple and transparent way to (1) compare the performance of players who competed under different conditions and (2) include information about which particular players a given player has faced. We find that a player’s position in the network does not correlate with his placement in the random walker ranking. However, network position does have a substantial effect on the robustness of ranking placement to changes in head-to-head matchups.

  3. Mutually-Antagonistic Interactions in Baseball Networks

    CERN Document Server

    Saavedra, Serguei; McCotter, Trent; Porter, Mason A; Mucha, Peter J

    2009-01-01

    We formulate the head-to-head matchups between Major League Baseball pitchers and batters from 1954 to 2008 as a bipartite network of mutually-antagonistic interactions. We consider both the full network and single-season networks, which exhibit interesting structural changes over time. We also find that these networks exhibit a significant network structure that is sensitive to baseball's rule changes. We then study a biased random walk on the matchup networks as a simple and transparent way to compare the performance of players who competed under different conditions. We find that a player's position in the network does not correlate with his success in the random walker ranking but instead has a substantial effect on its sensitivity to changes in his own aggregate performance.

  4. The protective effects of pomegranate extracts against renal ischemia-reperfusion injury in male rats

    Directory of Open Access Journals (Sweden)

    Ahmet A Sancaktutar

    2014-01-01

    Full Text Available Aim: To evaluate the possible protective effect of pomegranate extract (PE on rats following renal ischemia-reperfusion (I/R injury. Materials and Methods: Twenty-four Wistar rats were divided into three groups. Sham group underwent laparotomy then waited for 45 minutes without ischemia. I/R group were subjected to left renal ischemia for 45 minutes followed by 60 minutes of reperfusion. I/R + PE group were subjected to the same renal I/R as the I/R group were also given 225 mg/kg PE peroral 30 minutes prior to the ischemia. Malondialdehyde (MDA, total antioxidant capacity (TAC, total oxidant status (TOS, and oxidative stress index (OSI were determined on the blood samples and kidney tissues. Histopathological analyses were conducted on the kidney tissues. Results: Serum TAC levels were significantly decreased in I/R group when compared with S group (P = 0.001. Serum MDA levels were increased in I/R group; however, it was not statistically significant. In rat kidney tissues, TOS levels and OSI index were significantly increased after I/R injury, while TAC levels were decreased. In I/R + PE group, PE reversed the negative effects of I/R injury. PE pretreatment was effective in decreasing tubular necrosis score. Conclusion: PE pretreatment ameliorated the oxidative damage and histopathological changes occurring following renal I/R injury.

  5. Downregulation of miR-30c promotes renal fibrosis by target CTGF in diabetic nephropathy.

    Science.gov (United States)

    Wang, Jinyang; Duan, Lijun; Guo, Tiankang; Gao, Yanbin; Tian, Limin; Liu, Jing; Wang, Shaocheng; Yang, Jinkui

    2016-04-01

    MicroRNAs (miRs) play important roles in initiation and progression of many pathologic processes. However, the role of miR-30c in diabetic nephropathy (DN) remains unclear. This study was to determine whether miR-30c was involved in the mechanism of renal fibrosis by inhibiting target CTGF expression in DN. In this study, In Situ Hybridization(ISH), RT-PCR, cell transfection, western blotting and laser confocal telescope were used, respectively. ISH showed that miR-30c, concentrated in cytoplasmic foci in the proximity of the nucleus, was mainly localized in glomerular and renal tubular epithelial cells within the cortex. RT-PCR showed that miR-30c expression was significantly decreased in DN (p0.05). More importantly, miR-30c mimics significantly decreased col-IV, FN, GSI, GBM, GA, MRA/CLA and ACR (p<0.05) and, in contrast, slightly but significantly increased Ccr (p<0.05). In conclusion, our results suggested that loss of miR-30c may contribute to the pathogenesis of DN by inhibiting target CTGF expression; replenishing miR-30c may ameliorate renal structure and function by reducing renal fibrosis in DN. PMID:26775556

  6. Protective Effects of Berberine on Renal Injury in Streptozotocin (STZ)-Induced Diabetic Mice

    Science.gov (United States)

    Zhang, Xiuli; He, Hui; Liang, Dan; Jiang, Yan; Liang, Wei; Chi, Zhi-Hong; Ma, Jianfei

    2016-01-01

    Diabetic nephropathy (DN) is a serious diabetic complication with renal hypertrophy and expansion of extracellular matrices in renal fibrosis. Epithelial-to-mesenchymal transition (EMT) of renal tubular epithelial cells may be involved in the main mechanism. Berberine (BBR) has been shown to have antifibrotic effects in liver, kidney and lung. However, the mechanism of cytoprotective effects of BBR in DN is still unclear. In this study, we investigated the curative effects of BBR on tubulointerstitial fibrosis in streptozotocin (STZ)-induced diabetic mice and the high glucose (HG)-induced EMT in NRK 52E cells. We found that BBR treatment attenuated renal fibrosis by activating the nuclear factor-erythroid 2-related factor 2 (Nrf2) signaling pathway in the diabetic kidneys. Further revealed that BBR abrogated HG-induced EMT and oxidative stress in relation not only with the activation of Nrf2 and two Nrf2-targeted antioxidative genes (NQO-1 and HO-1), but also with the suppressing the activation of TGF-β/Smad signaling pathway. Importantly, knockdown Nrf2 with siRNA not only abolished the BBR-induced expression of HO-1 and NQO-1 but also removed the inhibitory effect of BBR on HG-induced activation of TGF-β/Smad signaling as well as the anti-fibrosis effects. The data from present study suggest that BBR can ameliorate tubulointerstitial fibrosis in DN by activating Nrf2 pathway and inhibiting TGF-β/Smad/EMT signaling activity. PMID:27529235

  7. Sodium-Glucose Cotransporter Inhibitors: Effects on Renal and Intestinal Glucose Transport: From Bench to Bedside.

    Science.gov (United States)

    Mudaliar, Sunder; Polidori, David; Zambrowicz, Brian; Henry, Robert R

    2015-12-01

    Type 2 diabetes is a chronic disease with disabling micro- and macrovascular complications that lead to excessive morbidity and premature mortality. It affects hundreds of millions of people and imposes an undue economic burden on populations across the world. Although insulin resistance and insulin secretory defects play a major role in the pathogenesis of hyperglycemia, several other metabolic defects contribute to the initiation/worsening of the diabetic state. Prominent among these is increased renal glucose reabsorption, which is maladaptive in patients with diabetes. Instead of an increase in renal glucose excretion, which could ameliorate hyperglycemia, there is an increase in renal glucose reabsorption, which helps sustain hyperglycemia in patients with diabetes. The sodium-glucose cotransporter (SGLT) 2 inhibitors are novel antidiabetes agents that inhibit renal glucose reabsorption and promote glucosuria, thereby leading to reductions in plasma glucose concentrations. In this article, we review the long journey from the discovery of the glucosuric agent phlorizin in the bark of the apple tree through the animal and human studies that led to the development of the current generation of SGLT2 inhibitors. PMID:26604280

  8. 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. PMID:26641937

  9. Antagonistic activity of marine sponges associated Actinobacteria

    Institute of Scientific and Technical Information of China (English)

    Selvakumar Dharmaraj; Dhevendaran Kandasamy

    2016-01-01

    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 universally well

  10. Hypertension Caused by Renal Arteriovenous Fistula

    OpenAIRE

    An, Hye-Sung; Kang, Tae-Gon; Yun, Hyun-Jin; Kim, Myo-Jing; Jung, Jin-A; Yoo, Jae-Ho; Lee, Young-Seok

    2009-01-01

    We describe a case of secondary hypertension caused by renal arteriovenous fistula. An 8-year old girl was hospitalized with a severe headache, vomiting, and seizure. Renal angiography demonstrated multiple renal arteriovenous fistula and increased blood renin concentration in the left renal vein. Thus, left renal arteriovenous fistula and renin induced secondary hypertension were diagnosed. Her blood pressure was well controlled by medication with angiotensin converting enzyme inhibitor.

  11. Renal vein thrombosis in transitional cell carcinoma

    International Nuclear Information System (INIS)

    Full text: A rare case of renal transitional cell carcinoma (TCC) associated with bland thrombus of the renal vein extending into the inferior vena cava is described. Tumour thrombus in renal cell carcinoma is frequently encountered, but only very rarely occurs with TCC. Bland renal vein thrombosis occurring with renal TCC has not been described before. Contrast enhanced computed tomography assisted in distinguishing between bland and tumour thrombosis and aided in surgical management

  12. Case of hereditary papillary renal cell carcinoma

    OpenAIRE

    Mustafa, Sadaf; Jadidi, Nima; Faraj, Sheila F.; Rodriquez, Ronald

    2012-01-01

    Renal cell carcinoma is the most common type of renal malignancy and it originates from the renal tubular epithelium. Due to the diversity in the histopathological and molecular characteristics, it is typically subclassified into five different categories. Papillary renal cell carcinoma is one subclassification and it includes two variants: sporadic and hereditary. Although the hereditary form comprises a smaller number of cases of papillary renal cell carcinoma, an understanding of the molec...

  13. Serotonin 2A receptor antagonists for treatment of schizophrenia

    DEFF Research Database (Denmark)

    Ebdrup, Bjørn Hylsebeck; Rasmussen, Hans; Arnt, Jørn; Glenthøj, Birte Yding

    2011-01-01

    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...

  14. DEFICIENCY OF INTERLEUKIN-1 RECEPTOR ANTAGONIST RESPONSIVE TO ANAKINRA

    OpenAIRE

    SCHNELLBACHER, CHARLOTTE; CIOCCA, GIOVANNA; MENENDEZ, ROXANNA; Aksentijevich, Ivona; Goldbach-Mansky, Raphaela; DUARTE, ANAM.; RIVAS-CHACON, RAFAEL

    2012-01-01

    We describe a 3-month-old infant who presented to our institution with interleukin (IL)-1 receptor antagonist deficiency (DIRA), which consists of neutrophilic pustular dermatosis, periostitis, aseptic multifocal osteomyelitis, and persistently high acutephase reactants. Skin findings promptly improved upon initiation of treatment with anakinra (recombinant human IL-1 receptor antagonist), and the bony lesions and systemic inflammation resolved with continued therapy.

  15. 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…

  16. Pros and cons of vitamin K antagonists and non-vitamin K antagonist oral anticoagulants.

    Science.gov (United States)

    Riva, Nicoletta; Ageno, Walter

    2015-03-01

    Anticoagulant treatment can be currently instituted with two different classes of drugs: the vitamin K antagonists (VKAs) and the newer, "novel" or non-vitamin K antagonist oral anticoagulant drugs (NOACs). The NOACs have several practical advantages over VKAs, such as the rapid onset/offset of action, the lower potential for food and drug interactions, and the predictable anticoagulant response. However, the VKAs currently have a broader spectrum of indications, a standardized monitoring test, and established reversal strategies. The NOACs emerged as alternative options for the prevention and treatment of venous thromboembolism and for the prevention of stroke and systemic embolism in patients with nonvalvular atrial fibrillation. Nevertheless, there remain some populations for whom the VKAs remain the most appropriate anticoagulant drug. This article discusses the advantages and disadvantages of VKAs and NOACs. PMID:25703519

  17. Acute renal dysfunction in liver diseases

    Institute of Scientific and Technical Information of China (English)

    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 (MRS) is a unique form of renal failure associated with advanced liver disease or cirrhosis, and is characterized by functional renal impairment without significant changes in renal histology. Irrespective of the type of renal failure, renal hypoperfusion is the central pathogenetic mechanism, due either to reduced perfusion pressure or increased renal vascular resistance. Volume expansion, avoidance of precipitating factors and treatment of underlying liver disease constitute the mainstay of therapy to prevent and reverse renal impairment. Splanchnic vasoconstrictor agents, such as terlipressin, along with volume expansion, and early placement of transjugular intrahepatic portosystemic shunt (TIPS) may be effective in improving renal function in HRS. Continuous renal replacement therapy (CRRT) and molecular absorbent recirculating system (MARS) in selected patients may be life saving while awaiting liver transplantation.

  18. The AMPA receptor antagonist perampanel robustly rescues amyotrophic lateral sclerosis (ALS) pathology in sporadic ALS model mice.

    Science.gov (United States)

    Akamatsu, Megumi; Yamashita, Takenari; Hirose, Naoki; Teramoto, Sayaka; Kwak, Shin

    2016-01-01

    Both TDP-43 pathology and failure of RNA editing of AMPA receptor subunit GluA2, are etiology-linked molecular abnormalities that concomitantly occur in the motor neurons of the majority of patients with amyotrophic lateral sclerosis (ALS). AR2 mice, in which an RNA editing enzyme adenosine deaminase acting on RNA 2 (ADAR2) is conditionally knocked out in the motor neurons, exhibit a progressive ALS phenotype with TDP-43 pathology in the motor neurons through a Ca(2+)-permeable AMPA receptor-mediated mechanism. Therefore, amelioration of the increased Ca(2+) influx by AMPA receptor antagonists may be a potential ALS therapy. Here, we showed that orally administered perampanel, a selective, non-competitive AMPA receptor antagonist significantly prevented the progression of the ALS phenotype and normalized the TDP-43 pathology-associated death of motor neurons in the AR2 mice. Given that perampanel is an approved anti-epileptic drug, perampanel is a potential candidate ALS drug worthy of a clinical trial. PMID:27350567

  19. 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.

  20. Pharmacokinetic interactions with calcium channel antagonists (Part I).

    Science.gov (United States)

    Schlanz, K D; Myre, S A; Bottorff, M B

    1991-11-01

    Calcium channel antagonists are a diverse class of drugs widely used in combination with other therapeutic agents. The potential exists for many clinically significant pharmacokinetic interactions between these and other concurrently administered drugs. The mechanisms of calcium channel antagonist-induced changes in drug metabolism include altered hepatic blood flow and impaired hepatic enzyme metabolising activity. Increases in serum concentrations and/or reductions in clearance have been reported for several drugs used with a number of calcium channel antagonists. A number of reports and studies of calcium channel antagonist interactions have yielded contradictory results and the clinical significance of pharmacokinetic changes seen with these agents is ill-defined. The first part of this article deals with interactions between calcium antagonists and marker compounds, theophylline, midazolam, lithium, doxorubicin, oral hypoglycaemics and cardiac drugs. PMID:1773549

  1. Renal (Kidney) Manifestations in TSC

    Medline Plus

    Full Text Available ... transplantation would be indicated. Renal Cell Carcinoma (Kidney Cancer) Over the past 20 years, there have been at least 25 published reports of kidney cancer occurring in individuals with TSC. Drs. Bjornsson, Short, ...

  2. Renal (Kidney) Manifestations in TSC

    Medline Plus

    Full Text Available ... and lead to bleeding. About 20% of the time this bleeding is life-threatening. Approximately 80 percent ... with TSC will experience angiomyolipomas. Most of the time both kidneys are involved. Renal cysts are often ...

  3. Radiological evaluation of renal transplantation

    International Nuclear Information System (INIS)

    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.)

  4. Renal cell carcinoma in childhood

    International Nuclear Information System (INIS)

    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)

  5. Renal (Kidney) Manifestations in TSC

    Medline Plus

    Full Text Available ... abdominal or back pain, nausea and vomiting and fever. For the individual who is non-verbal, this ... significant back or abdominal pain, nausea, vomiting and fever. If these growths involve both kidneys, renal failure ...

  6. Renal (Kidney) Manifestations in TSC

    Medline Plus

    Full Text Available ... kidney disease can develop in infancy or early childhood and renal failure most often occurs in early ... should be performed by a team with TSC experience, many individuals with TSC can maintain normal kidney ...

  7. Clinical study on renal trauma

    International Nuclear Information System (INIS)

    We analyzed 26 cases of renal trauma, which occurred during the last 7 years and 6 months. Computed tomography was performed in all cases. Four cases were of type Ib, 13 cases of type II, 3 cases of type IIIa, 5 cases of type IIIb and 1 case of type IVa, according to the classification of renal injury by the Japanese association for the surgery of trauma. Conservative treatment was done in 21 cases, selective transcatheter arterial embolization (TAE) in 4 cases, and surgical treatment in 1 case. Conservative treatment was effective for type I and II renal trauma. In the cases of type IIIa and IIIb renal trauma, open surgery could be avoided and the affected kidney preserved by early TAE. (author)

  8. Renal (Kidney) Manifestations in TSC

    Medline Plus

    Full Text Available ... majority of individuals (greater than 80 percent) with tuberous sclerosis complex (TSC) will develop some form of renal ( ... Dallas, TX. November 2013. **This publication from the Tuberous Sclerosis Alliance is intended to provide basic information about ...

  9. Renal (Kidney) Manifestations in TSC

    Medline Plus

    Full Text Available ... History Database Tissue Donation Audio & Video Archives Brochures, Books, & Booklets Information Sheets Perspective Magazine Archives Life Stages ... Scientific Advisory Board 2015 International TSC Research Conference Text Size Get Involved RENAL (KIDNEY) MANIFESTATIONS IN TSC ...

  10. Renal (Kidney) Manifestations in TSC

    Medline Plus

    Full Text Available ... increased blood pressure, but usually they do not cause discomfort. However, sometimes the kidney is filled with cysts, and this can lead to kidney impairment and even kidney failure, requiring dialysis or transplantation. Lastly, renal cell carcinoma, ...

  11. Markers of renal function tests

    Directory of Open Access Journals (Sweden)

    Shivaraj Gowda

    2010-01-01

    Full Text Available Background : The markers of renal function test assess the normal functioning of kidneys. These markers may be radioactive and non radioactive. They indicate the glomerular filtration rate, concentrating and diluting capacity of kidneys (tubular function. If there is an increase or decrease in the valves of these markers it indicates dysfunction of kidney. Aim: The aim of this review is to compare and analyze the present and newer markers of renal function tests which help in diagnosis of clinical disorders. Material & Methods: An extensive literature survey was done aiming to compare and compile renal function tests makers required in diagnosis of diseases. Results: Creatinine, urea, uric acid and electrolytes are makers for routine analysis whereas several studies have confirmed and consolidated the usefulness of markers such as cystatin C and β-Trace Protein. Conclusion: We conclude that further investigation is necessary to define these biomarkers in terms of usefulness in assessing renal function.

  12. Renal (Kidney) Manifestations in TSC

    Medline Plus

    Full Text Available ... depending on the size of the involvement, further management can be recommended. Individuals with TSC and angiomyolipomas less than 4 cm would benefit from repeat renal imaging every one to two ...

  13. Renal (Kidney) Manifestations in TSC

    Medline Plus

    Full Text Available ... with cysts. If kidney failure occurs, renal replacement therapy such as dialysis or transplantation is necessary. How kidney cysts develop is not known. The TSC genes are tumor suppressor genes. Normally, tumor suppressor genes ...

  14. Renal (Kidney) Manifestations in TSC

    Medline Plus

    Full Text Available ... of individuals (greater than 80 percent) with tuberous sclerosis complex (TSC) will develop some form of renal ( ... TX. November 2013. **This publication from the Tuberous Sclerosis Alliance is intended to provide basic information about ...

  15. Renal (Kidney) Manifestations in TSC

    Medline Plus

    Full Text Available ... rare, such a lesion must be kept in mind. Diagnosis The current methods to diagnosis these renal ... nor does it, constitute medical or other advice. Readers are warned not to take any action with ...

  16. Pulmonary edema in renal failure

    International Nuclear Information System (INIS)

    Forty-nine cases of pulmonary edema in nephropatic patients were studied. The most frequent radiologic findings are discussed. The unreliability of a precise differentiation between ''cardiac'' and ''renal'' patterns of pulmonary edema in nephropatic patients is emphasized

  17. Renal (Kidney) Manifestations in TSC

    Medline Plus

    Full Text Available ... include renal ultrasonography, CT scanning and magnetic resonance imaging (MRI). These are all non-invasive procedures that ... be done to calibrate and correlate with ultrasound imaging. Repeat CT scans should be limited to reduce ...

  18. Renal (Kidney) Manifestations in TSC

    Medline Plus

    Full Text Available ... with cysts. If kidney failure occurs, renal replacement therapy such as dialysis or transplantation is necessary. How ... significant and occasionally life threatening. Therefore, diagnosis and treatment guidelines have been proposed to initially identify which ...

  19. Renal (Kidney) Manifestations in TSC

    Medline Plus

    Full Text Available ... procedures that are available in almost every major medical center. The renal ultrasound provides the least detailed ... Henske, M.D., Brigham and Women's Hospital, Harvard Medical School and Dana Farber Cancer Institute, Boston, MA, ...

  20. Stages of Renal Cell Cancer

    Science.gov (United States)

    ... cell cancer is a disease in which malignant (cancer) cells form in tubules of the kidney. Renal cell ... diagnosed, tests are done to find out if cancer cells have spread within the kidney or to other ...

  1. 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.

  2. Renal (Kidney) Manifestations in TSC

    Medline Plus

    Full Text Available ... individuals (greater than 80 percent) with tuberous sclerosis complex (TSC) will develop some form of renal (kidney) ... intended to provide basic information about tuberous sclerosis complex (TSC). It is not intended to, nor does ...

  3. Cystic renal neoplasms and renal neoplasms associated with cystic renal diseases in adults: cross-sectional imaging findings.

    Science.gov (United States)

    Katabathina, Venkata S; Garg, Deepak; Prasad, Srinivasa R; Vikram, Raghu

    2012-01-01

    Cystic renal neoplasms in adults are a heterogeneous group of tumors with characteristic histogenesis, pathological findings, and variable biological profiles. They include disparate entities that are either biologically benign (lymphangioma, cystic nephroma, and mixed epithelial and stromal tumor) or malignant (cystic renal cell carcinoma, multilocular cystic renal cell carcinoma, and primary renal synovial sarcoma). Renal cystic diseases are characterized by cystic changes of the kidneys due to hereditary, developmental, or acquired etiology. Cystic renal diseases such as acquired cystic kidney disease, von Hippel-Lindau disease, and tuberous sclerosis are associated with the development of a wide spectrum of benign and malignant renal neoplasms. Most cystic renal tumors and cystic disease-associated renal neoplasms show characteristic cross-sectional imaging findings that permit accurate diagnosis. In addition, cross-sectional imaging is pivotal in the follow-up and surveillance of adult cystic tumors of the kidney. PMID:23192202

  4. New treatments for renal carcinoma

    OpenAIRE

    Perez-Gracia, J L; Lopez-Picazo, J M; Olier, C. (Clara); ALFARO, C.; Garcia-Foncillas, J; Melero, I; Gurpide, A

    2007-01-01

    Renal cell carcinoma presents several unique features, which distinguish it from other tumours. The increase in survival that has been described in patients with renal cell carcinoma following nephrectomy breaks a classical rule of oncology, which states that surgery of the primary tumour has no role in the treatment of patients with advanced disease. Together with melanoma, it is the only tumour in which immunomodulatory treatments with drugs such as interleukin-2 produces a clinical benefit...

  5. On renal pathophysiology in preeclampsia

    OpenAIRE

    Penning, Maria Elisabeth (Marlies)

    2014-01-01

    Preeclampsia is a complication of pregnancy which can suddenly change from a relatively mild phenotype into a life-threatening situation. One of the organs that is always involved during preeclampsia is the kidney. The placenta plays an important role in the renal pathophysiology of preeclampsia. The placenta produces excessive amounts of anti-angiogenic factors which are associated with systemic endothelial dysfunction. Although the underlying mechanisms of renal injury during preeclampsia r...

  6. Chickenpox infection after renal transplantation

    OpenAIRE

    Kaul, Anupma; Sharma, Raj K.; Bhadhuria, Dharmendra; Gupta, Amit; Prasad, Narayan

    2012-01-01

    Background. Chicken pox, although a common infection among children, is rare in immunocompromised patients, particularly renal transplant recipients, and carries a very high incidence of morbidity and mortality There is little data on chickenpox in adult renal transplant recipients, although reports have suggested that it may follow a virulent course requiring frequent hospitalization, and in severe cases can cause death. Aims. To evaluate the incidence, severity and complications of a varice...

  7. The effects of a 5-HT5A receptor antagonist in a ketamine-based rat model of cognitive dysfunction and the negative symptoms of schizophrenia.

    Science.gov (United States)

    Nikiforuk, Agnieszka; Hołuj, Małgorzata; Kos, Tomasz; Popik, Piotr

    2016-06-01

    Serotonin (5-HT) receptors still represent promising targets for the development of novel multireceptor or stand-alone antipsychotic drugs with a potential to ameliorate cognitive impairments and negative symptoms in schizophrenia. The 5-HT5A receptor, one of the least known members of the serotonin receptor family, has also drawn attention in this regard. Although the antipsychotic efficacy of 5-HT5A antagonists is still equivocal, recent experimental data suggest the cognitive-enhancing activity of this strategy. The aim of the present study was to evaluate pro-cognitive and pro-social efficacies of the 5-HT5A receptor antagonist in a rat pharmacological model of schizophrenia employing the administration of the NMDA receptor antagonist, ketamine. The ability of SB-699551 to reverse ketamine-induced cognitive deficits in the attentional set-shifting task (ASST) and novel object recognition task (NORT) was examined. The compound's efficacy against ketamine-induced social withdrawal was assessed in the social interaction test (SIT) and in the social choice test (SCT). The results demonstrated the efficacy of SB-699551 in ameliorating ketamine-induced impairments on the ASST and NORT. Moreover, the tested compound also enhanced set-shifting performance in cognitively unimpaired control rats and improved object recognition memory in conditions of delay-induced natural forgetting. The pro-social activity of SB-699551 was demonstrated on both employed paradigms, the SIT and SCT. The present study suggests the preclinical efficacy of a strategy based on the blockade of 5-HT5A receptors against schizophrenia-like cognitive deficits and negative symptoms. The utility of this receptor as a target for improvement of cognitive and social dysfunctions warrants further studies. PMID:26826431

  8. AMELIORATIVE EFFECTS OF TINOSPORA CORDIFOLIA IN SCIATICA PAIN INDUCED RATS

    OpenAIRE

    Thaakur Santhrani; Yaidikar Lavanya

    2012-01-01

    The present study was aimed at investigating the ameliorative effect of Tinospora cordifolia in sciatic nerve root Ligation -induced sciatica pain in rats. Adult male albino rats weighing 130-150gm were used for the study, and were divided into seven groups and ligation was performed on left sciatic nerve in group II to group VII. Tail cold-hyperalgesia, motor co-ordination tests, foot deformity, and total calcium levels were estimated to assess the extent of sciatica. Superoxide dismutase ...

  9. Losartan ameliorates dystrophic epidermolysis bullosa and uncovers new disease mechanisms

    OpenAIRE

    Nyström, Alexander; Thriene, Kerstin; Mittapalli, Venugopal; Kern, Johannes S; Kiritsi, Dimitra; Dengjel, Jörn; Bruckner-Tuderman, Leena

    2015-01-01

    Genetic loss of collagen VII causes recessive dystrophic epidermolysis bullosa (RDEB)—a severe skin fragility disorder associated with lifelong blistering and disabling progressive soft tissue fibrosis. Causative therapies for this complex disorder face major hurdles, and clinical implementation remains elusive. Here, we report an alternative evidence-based approach to ameliorate fibrosis and relieve symptoms in RDEB. Based on the findings that TGF-β activity is elevated in injured RDEB skin,...

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

    OpenAIRE

    Pujiyanto Pujiyanto

    2007-01-01

    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 cof...

  11. Antibiotics can ameliorate circulatory complications of liver cirrhosis

    DEFF Research Database (Denmark)

    Madsen, Bjørn Stæhr; Schaffalitzky de Muckadell, Ove B

    2011-01-01

    Livercirrhosis can be complicated by a hyperdynamic circulatory syndrome. This is due to translocation of bacteria and bacterial product (bacterial DNA and endotoxins), which stimulate the splanchnic nitric oxide synthase and leads to splanchnic vasodilatation and haemodynamic derangement. 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 and...

  12. Response of Field Crops to Ameliorative Phosphorus Fertilization

    OpenAIRE

    KOVACEVIC, Vlado; Rastija, Mirta; KOMLJENOVIC, Ilija; BEGIC, Sabina; JOVIC, Jurica

    2014-01-01

    Different types of nutritional unbalances, including also low levels of plant available phosphorus (P), are often limiting factor of soil fertility in Croatia and in countries of the region, particularly in Bosnia and Herzegovina (B&H). Aim of this study was survey our recent investigations (eight stationary field experiments) of maize, soybean, wheat and barley responses to ameliorative P fertilization up to different levels (depending on the trial up to from 825 to 1580 kg P2O5 ha-1). Eithe...

  13. Renal calculus complicated with squamous cell carcinoma of renal pelvis: Report of two cases

    OpenAIRE

    Xiao, Jiantao; LEI, JUN; He, Leye; YIN, GUANGMING

    2015-01-01

    Longstanding renal calculus is a risk factor of squamous cell carcinoma (SCC) of the renal pelvis. It is highly aggressive and usually diagnosed at advanced stages with a poor prognosis. We present two cases of kidney stone complications with renal pelvic SCC. These two patients had a radical nephrectomy and the dissected tissues were renal pelvic SCC. Our cases further emphasize that renal pelvic SCC should be considered in patients with longstanding renal calculus. These cases contribute gr...

  14. MR Imaging of renal transplants

    International Nuclear Information System (INIS)

    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

  15. 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.

  16. Intranigral administration of substance P receptor antagonist attenuated levodopa-induced dyskinesia in a rat model of Parkinson's disease.

    Science.gov (United States)

    Yang, Xinxin; Zhao, Hui; Shi, Hongjuan; Wang, Xiaoying; Zhang, Shenyang; Zhang, Zunsheng; Zu, Jie; Zhang, Wei; Shen, Xia; Cui, Guiyun; Hua, Fang

    2015-09-01

    Levodopa (L-dopa) remains the most effective drug in the treatment of Parkinson's disease (PD). However, L-dopa-induced dyskinesia (LID) has hindered its use for PD patients. The mechanisms of LID are not fully understood. Substance P (SP) receptor antagonist has been shown to reduce parkinsonism in animal models of PD, and ameliorate LID in PD rats. But the concrete mechanism is not fully understood. To address this issue, we produced a rat model of PD using 6-hydroxydompamine (6-OHDA) injections, and valid PD rats were intranigrally administrated with different doses of SP receptor antagonist LY303870 (5 nmol/day, 10 nmol/day and 20 nmol/day) following L-dopa (6 mg/kg/day, i.p.) plus benserazide (12 mg/kg/day, i.p.) for 23 days. We found that nigral SP levels were increased on days 3, 7 and 14 and decreased on day 21 after 6-hydroxydompamine lesions. But nigral SP levels kept increasing after repeated L-dopa administration in PD rats. Intranigral administration of low and moderate LY303870 reduced abnormal involuntary movements (AIMs) while improving motor deficits in PD rats treated with L-dopa plus benserazide. Microdialysis revealed that LY303870 (10 nmol/day) treatment attenuated the increase of striatal dopamine and the reduction of γ-aminobutyric acid in ventromedial thalamus of PD rats primed with L-dopa. Additionally, LY303870 (10 nmol/day) treatment prior to L-dopa administration reduced the phosphorylated levels of dopamine- and cyclic adenosine monophosphate-regulated phosphoprotein of 32 kDa at Thr 34 and extracellular signal-regulated kinases 1/2 as well as the levels of activity-regulated cytoskeleton-associated protein and Penk in L-dopa-primed PD rats. Taken together, these data showed that low and moderate SP receptor antagonists LY303870 could ameliorate LID via neurokinin 1 receptor without affecting therapeutic effect of L-dopa. PMID:26001615

  17. Pathophysiology and management of progressive renal disease.

    Science.gov (United States)

    Brown, S A; Crowell, W A; Brown, C A; Barsanti, J A; Finco, D R

    1997-09-01

    Recently, the hypothesis that all renal diseases are inherently progressive and self-perpetuating has focused attention on adaptive changes in renal structure and function that occur whenever renal function is reduced. These glomerular adaptations to renal disease include increases in filtration rate, capillary pressure and size, and are referred to as glomerular hyperfiltration, glomerular hypertension and glomerular hypertrophy, respectively. Extrarenal changes, such as dietary phosphate excess, systemic hypertension, hyperlipidaemia, acidosis and hyperparathyroidism occur in animals with renal disease and may be contributors to progression of renal disease. Emphasis in the management of companion animals with renal disease has shifted to identifying, understanding and controlling those processes that play a role in the progression from early to end-stage renal failure. Advances made by veterinary nephrologists in the past 15 years permit resolution of old controversies, formulation of new hypotheses and discussion of unresolved issues about the nature of progressive renal disease in dogs and cats. PMID:9308397

  18. Renal Heme Oxygenase-1 Induction with Hemin Augments Renal Hemodynamics, Renal Autoregulation, and Excretory Function

    Directory of Open Access Journals (Sweden)

    Fady T. Botros

    2012-01-01

    Full Text Available Heme oxygenases (HO-1; HO-2 catalyze conversion of heme to free iron, carbon monoxide, and biliverdin/bilirubin. To determine the effects of renal HO-1 induction on blood pressure and renal function, normal control rats (n=7 and hemin-treated rats (n=6 were studied. Renal clearance studies were performed on anesthetized rats to assess renal function; renal blood flow (RBF was measured using a transonic flow probe placed around the left renal artery. Hemin treatment significantly induced renal HO-1. Mean arterial pressure and heart rate were not different (115±5 mmHg versus 112±4 mmHg and 331±16 versus 346±10 bpm. However, RBF was significantly higher (9.1±0.8 versus 7.0±0.5 mL/min/g, P<0.05, and renal vascular resistance was significantly lower (13.0±0.9 versus 16.6±1.4 [mmHg/(mL/min/g], P<0.05. Likewise, glomerular filtration rate was significantly elevated (1.4±0.2 versus 1.0±0.1 mL/min/g, P<0.05, and urine flow and sodium excretion were also higher (18.9±3.9 versus 8.2±1.0 μL/min/g, P<0.05 and 1.9±0.6 versus 0.2±0.1 μmol/min/g, P<0.05, resp.. The plateau of the autoregulation relationship was elevated, and renal vascular responses to acute angiotensin II infusion were attenuated in hemin-treated rats reflecting the vasodilatory effect of HO-1 induction. We conclude that renal HO-1 induction augments renal function which may contribute to the antihypertensive effects of HO-1 induction observed in hypertension models.

  19. Renal trauma in adults - a pictorial review

    International Nuclear Information System (INIS)

    Full text: This review provides a framework for understanding the classification and features of renal trauma. Computed tomography (CT) is now the modality of choice in prompt diagnosis and staging of renal trauma. A retrospective review of the CT scans of all patients with blunt abdominal trauma sustaining renal injury that presented to our hospital within the last 2 years was undertaken. The patient list was obtained from our Trauma Registry database at the Trauma Services Unit. Representative cases of each category of renal injury are displayed on a poster, accompanied by explanatory notes. We also reviewed the literature on renal trauma between 1985-2001 on Medline. The indications for radiological assessment and the management of renal trauma remain controversial. Staging of renal trauma with CT imaging, when integrated with clinical information helps to facilitate appropriate management plan. Renal injuries are classified into four grades on the basis of imaging: - Grade 1: Minor cortical contusion, minor laceration with limited perinephric hematoma, and small cortical infarct. - Grade 2: Major renal lacerations extending to the medulla with or without involvement of the collecting system and segmental renal infarct. - Grade 3: Catastrophic injury which include multiple renal lacerations and injury to the renal vascular pedicle. - Grade 4: Ureteropelvic junction injuries. Diagnostic imaging and staging plays a major role in assessing patients with renal injuries and affects clinical management decisions. Understanding the radiologic classification of traumatic renal injuries and integrating the findings with clinical information assist in developing an optimal management plan. Copyright (2002) Blackwell Science Pty Ltd

  20. Mitochondrial reactive oxygen species-mediated NLRP3 inflammasome activation contributes to aldosterone-induced renal tubular cells injury.

    Science.gov (United States)

    Ding, Wei; Guo, Honglei; Xu, Chengyan; Wang, Bin; Zhang, Minmin; Ding, Feng

    2016-04-01

    Aldosterone (Aldo) is an independent risk factor for chronic kidney disease (CKD), and although Aldo directly induces renal tubular cell injury, the underlying mechanisms remain unclear. NLRP3 inflammasome and mitochondrial reactive oxygen species (ROS) have recently been implicated in various kinds of CKD. The present study hypothesized that mitochondrial ROS and NLRP3 inflammasome mediated Aldo-induced tubular cell injury. The NLRP3 inflammasome is induced by Aldo in a dose- and time-dependent manner, as evidenced by increased NLRP3, ASC, caspase-1, and downstream cytokines, such as interleukin (IL)-1β and IL-18. The activation of the NLRP3 inflammasome was significantly prevented by the selective mineralocorticoid receptor (MR) antagonist eplerenone (EPL) (P < 0.01). Mice harboring genetic knock-out of NLRP3 (NLRP3(-/-)) showed decreased maturation of renal IL-1β and IL-18, reduced renal tubular apoptosis, and improved renal epithelial cell phenotypic alternation, and attenuated renal function in response to Aldo-infusion. In addition, mitochondrial ROS was also increased in Aldo-stimulated HK-2 cells, as assessed by MitoSOXTM red reagent. Mito-Tempo, the mitochondria-targeted antioxidant, significantly decreased HK-2 cell apoptosis, oxidative stress, and the activation of NLRP3 inflammasome. We conclude that Aldo induces renal tubular cell injury via MR dependent, mitochondrial ROS-mediated NLRP3 inflammasome activation. PMID:27014913

  1. Mitochondrial reactive oxygen species-mediated NLRP3 inflammasome activation contributes to aldosterone-induced renal tubular cells injury

    Science.gov (United States)

    Ding, Wei; Guo, Honglei; Xu, Chengyan; Wang, Bin; Zhang, Minmin; Ding, Feng

    2016-01-01

    Aldosterone (Aldo) is an independent risk factor for chronic kidney disease (CKD), and although Aldo directly induces renal tubular cell injury, the underlying mechanisms remain unclear. NLRP3 inflammasome and mitochondrial reactive oxygen species (ROS) have recently been implicated in various kinds of CKD. The present study hypothesized that mitochondrial ROS and NLRP3 inflammasome mediated Aldo–induced tubular cell injury. The NLRP3 inflammasome is induced by Aldo in a dose- and time-dependent manner, as evidenced by increased NLRP3, ASC, caspase-1, and downstream cytokines, such as interleukin (IL)-1β and IL-18. The activation of the NLRP3 inflammasome was significantly prevented by the selective mineralocorticoid receptor (MR) antagonist eplerenone (EPL) (P < 0.01). Mice harboring genetic knock-out of NLRP3 (NLRP3−/−) showed decreased maturation of renal IL-1β and IL-18, reduced renal tubular apoptosis, and improved renal epithelial cell phenotypic alternation, and attenuated renal function in response to Aldo-infusion. In addition, mitochondrial ROS was also increased in Aldo-stimulated HK-2 cells, as assessed by MitoSOXTM red reagent. Mito-Tempo, the mitochondria-targeted antioxidant, significantly decreased HK-2 cell apoptosis, oxidative stress, and the activation of NLRP3 inflammasome. We conclude that Aldo induces renal tubular cell injury via MR dependent, mitochondrial ROS-mediated NLRP3 inflammasome activation. PMID:27014913

  2. Functional importance of T-type voltage-gated calcium channels in the cardiovascular and renal system

    DEFF Research Database (Denmark)

    Hansen, Pernille B L

    2015-01-01

    lack of highly specific blockers cast doubt on the conclusions. As new T-type channel antagonists are being designed, the roles of T-type channels in cardiovascular and renal pathology need to be elucidated before T-type blockers can be clinically useful. Two types of T-type channels, Cav3.1 and Cav3...... several cardiovascular pathologies, but the use of T-type blockers should be specifically directed to the disease and to the channel subtype.......Over the years, it has been discussed whether T-type calcium channels Cav3 play a role in the cardiovascular and renal system. T-type channels have been reported to play an important role in renal hemodynamics, contractility of resistance vessels, and pacemaker activity in the heart. However, the...

  3. [Renal transplantation: ethical issues].

    Science.gov (United States)

    Mamzer-Bruneel, Marie-France; Laforêt, Emmanuelle Grand; Kreis, Henri; Thervet, Éric; Martinez, Frank; Snanoudj, Renaud; Hervé, Christian; Legendre, Christophe

    2012-12-01

    One of the most significant advances in medicine during the last 50 years is the development of organ transplantation. In the context of chronic kidney diseases, renal transplantation offers patients a better clinical outcome than other treatment options. However, the benefits of organ transplantation have not been maximized due to an inadequate supply of organs for transplantation. Despite the establishment of elaborate legal rules for organs procurement, both on deceased and living donors in numerous countries, ethical concerns remain. Most of them are consequences of the strategies implemented or proposed to address the so-called organ shortage. The involvement of society in these complex problems is crucial as numerous questions emerge: could actual state of organ procurement change? Is it possible and/or realistic to increase the number of organs, with respects to living donors or deceased persons? Is the shortage an indicator to limit the use of kidney transplantation? How do we maintain efficiency and justice, in this context. PMID:23168353

  4. Renal transplant NMR

    International Nuclear Information System (INIS)

    The preliminary results of NMR evaluation of renal transplants (Txs) are reported including correlation with nuclear medicine (NM) and ultrasound (US). Thirteen Txs (8 cadaver (Cd), 5 living related doner (LRD) in 13 patients (6M, 7F) ranging in age from 25-47 (x 35) were evaluated by NM (32), NMR (15) and US (5). Clinical diagnoses included: rejection (8), ATN (2), infarction (1), and normal (2). Of the 8 patients with rejection (5) Cd; 3 LRD) pathologic proof was obtained in 3. An experimental 0.12 T resistive magnet (GE) was used with a partial saturation technique with repetition time (TR) of 143 and 286 msec to provide T1 weighting. T2 weighted information was obtained with a spin echo technique with echo times (TE) of 20, 40, 60 and 80 msec. The NMR appearance of normal Txs consisted of a uniform signal intensity (Tx> pelvic musculature), well-defined internal architecture with good cortical medullary differentiation and normal appearing vessels. The NMR appearance of abnormal transplants consisted of a heterogeneous or overall decrease in signal intensity (kidney muscle) with poor cortical medullary differentiation with or without a halo of decreased signal intensity. Although NMR was able to differentiate normal from abnormal, it was unable to clearly discriminate between ATN and rejection. Advantages of NMR included the ability to demonstrate regional anatomy, vasculature, post operative fluid collections and hematomas, and associated avascular necrosis of the hips

  5. Differential effect of T-type voltage-gated calcium channel disruption on renal plasma flow and glomerular filtration rate in vivo

    DEFF Research Database (Denmark)

    Thuesen, Anne D; Andersen, Henrik; Cardel, Majken;

    2014-01-01

    Voltage-gated calcium channels (Cav) play an essential role in regulation of renal blood flow and GFR. Because T-type Cavs are differentially expressed in pre- and postglomerular vessels it was hypothesized that they impact renal blood flow and GFR differentially. The question was addressed by use...... in Cav 3.1 KO compared to Wt with no difference in blood pressure. T-type antagonists significantly inhibited the constriction of human intra-renal arteries in response to a small depolarization. In conclusion, Cav 3.2 channels support dilatation of efferent arterioles and affect GFR while Cav 3.......1 channels in vivo contribute to renal vascular resistance. It is suggested that endothelial and nerve localization of Cav 3.2 and Cav 3.1, respectively, may account for the observed effects....

  6. 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: a randomized, double-blind trial

    OpenAIRE

    Pitt, Bertram; Kober, Lars; Ponikowski, Piotr; Gheorghiade, Mihai; Filippatos, Gerasimos; Krum, Henry; Nowack, Christina; Kolkhof, Peter; Kim, So-Young; Zannad, Faiez

    2013-01-01

    Aims 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). Methods and results This randomized, controlled, phase II ...

  7. Differential regulation of renal phospholipase C isoforms by catecholamines.

    Science.gov (United States)

    Yu, P Y; Asico, L D; Eisner, G M; Jose, P A

    1995-01-01

    Dopamine and D1 agonists and NE all increase phosphatidyl inositol-specific phospholipase C (PLC) activity, but whereas dopamine produces a natriuresis, NE has an antinatriuretic effect. To determine if catecholamines differentially regulate the expression of PLC isoforms, we infused fenoldopam, a D1 agonist, or pramipexole, a D1/D2 agonist, intravenously or infused fenoldopam or NE into the renal artery of anesthetized rats. After 3-4 h of infusion, when the expected natriuresis (fenoldopam or pramipexole) or antinatriuresis (NE) occurred, the kidneys were removed for analysis of PLC isoform protein expression activity. Western blot analysis revealed that in renal cortical membranes, fenoldopam and pramipexole increased expression of PLC beta 1 and decreased expression of PLC gamma 1; PLC delta was unchanged. In the cytosol, pramipexole and fenoldopam increased expression of both PLC beta 1 and PLC gamma 1. No effects were noted in the medulla. A preferential D1 antagonist, SKF 83742, which by itself had no effect, blocked the effects of pramipexole, thus confirming the involvement of the D1 receptor. In contrast, NE also increased PLC beta 1 but did not affect PLC gamma 1 protein expression in membranes. The changes in PLC isoform expression were accompanied by similar changes in PLC isoform activity. These studies demonstrate for the first time differential regulation of PLC isoforms by catecholamines. PMID:7814630

  8. 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 and...... 10 women, median age 47 years (range, 25-63 years), were studied in an open randomized crossover trial, comparing a 2-week control period with a 2-week period of once-daily administration of 50 mg of losartan. The main outcome measurements were fractional excretion of uric acid (FE(uric acid)) based...... on 24-hr urine collections and plasma uric acid. RESULTS: The median FE(uric acid) was 5.7% (range, 2.4-10.4%) in the control period with a median change of +0.84% (range, -1.15% to +2.77%) in the losartan period (P<0.0002). Plasma uric acid was 0.47 mM (0.29-0.69 mM) in the control period with a...

  9. Erythropoietin ameliorates podocyte injury in advanced diabetic nephropathy in the db/db mouse.

    Science.gov (United States)

    Loeffler, Ivonne; Rüster, Christiane; Franke, Sybille; Liebisch, Marita; Wolf, Gunter

    2013-09-15

    Podocyte damage and accumulation of advanced glycation end products (AGEs) are characteristics of diabetic nephropathy (DN). The pathophysiology of AGE-challenged podocytes, such as hypertrophy, apoptosis, and reduced cell migration, is closely related to the induction of the cell cycle inhibitor p27(Kip1) and to the inhibition of neuropilin 1 (NRP1). We have previously demonstrated that treatment with erythropoietin is associated with protective effects for podocytes in vitro. db/db mice with overt DN aged 15-16 wk were treated with either placebo, epoetin-β, or continuous erythropoietin receptor activator (CERA) for 2 wk. db/db mice compared with nondiabetic db/m control mice revealed the expected increases in body weight, blood glucose, albumin-to-creatinine ratio, and AGE accumulation. Whereas there were no differences in body weight, hyperglycemia and AGEs were observed among diabetic mice that received epoetin-β compared with CERA and placebo treatment, indicating that epoetin-β/CERA treatment does not interfere with the development of diabetes in this model. However, the albumin-to-creatinine ratio was significantly lower in db/db mice treated with epoetin-β or CERA. Furthermore, kidney weights in db/db mice were increased compared with db/m control mice, indicating renal hypertrophy, whereas the increase in renal weight in epoetin-β- or CERA-treated db/db mice was significantly lower than in placebo-treated control mice. Induction of p27(Kip1) and suppression of NRP1 were significantly reduced in the epoetin-β treatment group versus the CERA treatment group. Furthermore, erythropoietin treatment diminished the diabetes-induced podocyte loss. Together, independently from hematopoetic effects, epoetin-β or CERA treatment was associated with protective changes in DN, especially that NRP1 and p27(Kip1) expressions as well as numbers of podocytes returned to normal levels. Our data show, for the first time, that medication of overt DN with erythropoietin

  10. 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

  11. 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.

  12. Endothelin receptor antagonists in pulmonary arterial hypertension.

    Science.gov (United States)

    Dupuis, J; Hoeper, M M

    2008-02-01

    The endothelin (ET) system, especially ET-1 and the ET(A) and ET(B) receptors, has been implicated in the pathogenesis of pulmonary arterial hypertension (PAH). Together with prostanoids and phosphodiesterase 5 inhibitors, ET receptor antagonists have become mainstays in the current treatment of PAH. Three substances are currently available for the treatment of PAH. One of these substances, bosentan, blocks both ET(A) and ET(B) receptors, whereas the two other compounds, sitaxsentan and ambrisentan, are more selective blockers of the ET(A) receptor. There is ongoing debate as to whether selective or nonselective ET receptor blockade is advantageous in the setting of PAH, although there is no clear evidence that receptor selectivity is relevant with regard to the clinical effects of these drugs. For the time being, other features, such as safety profiles and the potential for pharmacokinetic interactions with other drugs used in the treatment of PAH, may be more important than selectivity or nonselectivity when selecting treatments for individual patients. PMID:18238950

  13. 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.

  14. Barium can replace calcium in calmodulin-dependent contractions of skinned renal arteries of the rabbit.

    Science.gov (United States)

    Kreye, V A; Hofmann, F; Mühleisen, M

    1986-03-01

    Renal arteries of the rabbit were chemically skinned using Triton X-100. In EGTA-buffered solutions containing calmodulin and ATP, small strips of the skinned preparations were found to develop contractile force which was dependent on the concentrations of either free calcium or of free barium. However, a 220 times greater concentration of barium than of calcium was necessary for comparable effects. Quantitatively, the response to barium was dependent on the concentration of calmodulin added to the test solutions. The contractile effect of barium was partly antagonized by the calmodulin antagonist, trifluoperazine. PMID:3960707

  15. The muscarinic antagonists scopolamine and atropine are competitive antagonists at 5-HT3 receptors.

    Science.gov (United States)

    Lochner, Martin; Thompson, Andrew J

    2016-09-01

    Scopolamine is a high affinity muscarinic antagonist that is used for the prevention of post-operative nausea and vomiting. 5-HT3 receptor antagonists are used for the same purpose and are structurally related to scopolamine. To examine whether 5-HT3 receptors are affected by scopolamine we examined the effects of this drug on the electrophysiological and ligand binding properties of 5-HT3A receptors expressed in Xenopus oocytes and HEK293 cells, respectively. 5-HT3 receptor-responses were reversibly inhibited by scopolamine with an IC50 of 2.09 μM. Competitive antagonism was shown by Schild plot (pA2 = 5.02) and by competition with the 5-HT3 receptor antagonists [(3)H]granisetron (Ki = 6.76 μM) and G-FL (Ki = 4.90 μM). The related molecule, atropine, similarly inhibited 5-HT evoked responses in oocytes with an IC50 of 1.74 μM, and competed with G-FL with a Ki of 7.94 μM. The reverse experiment revealed that granisetron also competitively bound to muscarinic receptors (Ki = 6.5 μM). In behavioural studies scopolamine is used to block muscarinic receptors and induce a cognitive deficit, and centrally administered concentrations can exceed the IC50 values found here. It is therefore possible that 5-HT3 receptors are also inhibited. Studies that utilise higher concentrations of scopolamine should be mindful of these potential off-target effects. PMID:27108935

  16. HYPERTENSION IN RENAL ALLOGRAFT RECIPIENTS

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    Objective To further evaluate the effect of hypertension on renal graft function, and the relationship between hypertension, hyperlipoidemia and ischemic heart disease. Methods 102 renal transplant recipients with a functioning renal graft for more than 1 year were enrolled in this study. Renal function was followed for the further 24 months. Results The overall prevalence of hypertension was 89.2%(91/102) and 36.2%(33/91) hypertensive patients had uncontrolled blood pressure. After 24 months those with high blood pressure had significantly higher Scr levels than normotensive patients (P<0.05). The number of different antihypertensive classes required was related to Scr (P<0.05). Plasma cholesterol levels in hypertension patients especially in blood pressure uncontrolled group were significantly elevated (P<0.01). Ischemic heart disease was more common in hypertensive patients (P<0.05). Cyclosporine A was associated with hypertension more frequently than azathioprine and FK506, whereas low-dose prednisolone did not appear to influence blood pressure. Conclusion The data further confirmed that hypertension was associated with hyperlipidemia and ischemic heart disease, and emerged as a predictor of renal graft dysfunction. Whether cyclosporine A should be converted to new immunosuppressive agents and which class of antihypertensive medication is more effective in this population remain open questions.

  17. Acute renal failure in rats

    International Nuclear Information System (INIS)

    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. Protocol biopsies for renal transplantation

    Directory of Open Access Journals (Sweden)

    Rush David

    2010-01-01

    Full Text Available Protocol biopsies in renal transplantation are those that are procured at predetermined times post renal transplantation, regardless of renal function. These biopsies have been useful to study the natural history of the transplanted kidney as they have detected unexpected - i.e. "subclinical" pathology. The most significant subclinical pathologies that have been detected with protocol biopsies have been acute lesions, such as cellular and antibody mediated rejection, and chronic lesions, such as interstitial fibrosis and tubular atrophy, and transplant glomerulopathy. The potential benefit of early recognition of the above lesions is that their early treatment may result in improved long-term outcomes. Conversely, the identification of normal histology on a protocol biopsy, may inform us about the safety of reduction in overall immunosuppression. Our centre, as well as others, is attempting to develop non-invasive methods of immune monitoring of renal transplant patients. However, we believe that until such methods have been developed and validated, the protocol biopsy will remain an indispensable tool for the complete care of renal transplant patients.

  19. Exercise-induced acute renal failure and patchy renal vasoconstriction

    International Nuclear Information System (INIS)

    This paper evaluates the CT and MR findings and to understand the pathophysiology of kidneys in patients with acute renal failure accompanied by loin pain after participation in a track event. The authors obtained CT scan of the kidney enhanced by contrast material and 24- to 72-hour delayed scans without further use of contrast media were performed in all six patients with acute renal failure accompanied by severe loin pain after participation in a track event. MR imaging of the kidney was also performed in one patient. Five patients received analygensics

  20. Damaged renal parenchyma as a sign of renal tuberculosis

    International Nuclear Information System (INIS)

    Findings of urogenital tuberculosis in computed tomography have been reported seldom although this manifestation of the tuberculous disease is on the second place following pulmonary tuberculosis. We report on a 52 year old women suffering by culturally proven urogenital tuberculosis. The enhanced computed tomography showed hypodense lesions clearly decipted on the cortex border of the kidney. Other findings of renal tuberculosis reported in the current literature as hydrocalices or hydronephrosis were not seen at all. We postulate that the described finding is characteristic for an early stage of renal tuberculosis. (orig.)

  1. The effect of renal diet in association with enalapril or benazepril on proteinuria in dogs with proteinuric chronic kidney disease.

    Science.gov (United States)

    Zatelli, A; Roura, X; D'Ippolito, P; Berlanda, M; Zini, E

    2016-01-01

    Treating proteinuria in dogs reduces the progression of chronic kidney disease (CKD); renal diets and angiotensin-converting enzyme (ACE)-inhibitors are cornerstones of treatment. Whether different ACE-inhibitors have distinct kidney protective effects is unknown; it is therefore hypothesized that renal diets and enalapril or benazepril have different beneficial effects in proteinuric CKD dogs. Forty-four dogs with proteinuric CKD (IRIS stages 1-4) were enrolled in the study and were fed renal diet for 30 days. Thereafter, they were randomly assigned to one of 2 groups. Dogs in group A (n=22) received enalapril (0.5 mg/kg, q12h) and in group B (n=22) benazepril (0.5 mg/kg, q24h); in both groups, dogs were fed the same renal diet. After randomization, dogs were monitored for 120 days. Body weight and body condition score (BCS), serum concentrations of creatinine, blood urea nitrogen (BUN), albumin and total proteins, and urine protein-to-creatinine (UPC) ratio were compared at different time-points. After 30 days of renal diet, creatinine, BUN and UPC ratio decreased significantly (p<0.0001). Compared to randomization, body weight, BCS, albumin, total proteins, creatinine and BUN did not vary during follow-up in the 44 dogs and differences between group A and B were not observed. However, the UPC ratio of group A at day 60, 90 and 150 was significantly lower than in group B and compared to randomization (p<0.05). In group B it did not vary overtime. It is concluded that the renal diet is beneficial to decrease creatinine, BUN and UPC ratio in proteinuric CKD dogs. Enalapril further ameliorates proteinuria if administered along with renal diet. PMID:27540513

  2. Ischemic conditioning by short periods of reperfusion attenuates renal ischemia/reperfusion induced apoptosis and autophagy in the rat

    Directory of Open Access Journals (Sweden)

    Chien Chiang-Ting

    2009-02-01

    Full Text Available Abstract Prolonged ischemia amplified iscehemia/reperfusion (IR induced renal apoptosis and autophagy. We hypothesize that ischemic conditioning (IC by a briefly intermittent reperfusion during a prolonged ischemic phase may ameliorate IR induced renal dysfunction. We evaluated the antioxidant/oxidant mechanism, autophagy and apoptosis in the uninephrectomized Wistar rats subjected to sham control, 4 stages of 15-min IC (I15 × 4, 2 stages of 30-min IC (I30 × 2, and total 60-min ischema (I60 in the kidney followed by 4 or 24 hours of reperfusion. By use of ATP assay, monitoring O2-. amounts, autophagy and apoptosis analysis of rat kidneys, I60 followed by 4 hours of reperfusion decreased renal ATP and enhanced reactive oxygen species (ROS level and proapoptotic and autophagic mechanisms, including enhanced Bax/Bcl-2 ratio, cytochrome C release, active caspase 3, poly-(ADP-ribose-polymerase (PARP degradation fragments, microtubule-associated protein light chain 3 (LC3 and Beclin-1 expression and subsequently tubular apoptosis and autophagy associated with elevated blood urea nitrogen and creatinine level. I30 × 2, not I15 × 4 decreased ROS production and cytochrome C release, increased Manganese superoxide dismutase (MnSOD, Copper-Zn superoxide dismutase (CuZnSOD and catalase expression and provided a more efficient protection than I60 against IR induced tubular apoptosis and autophagy and blood urea nitrogen and creatinine level. We conclude that 60-min renal ischemia enhanced renal tubular oxidative stress, proapoptosis and autophagy in the rat kidneys. Two stages of 30-min ischemia with 3-min reperfusion significantly preserved renal ATP content, increased antioxidant defense mechanisms and decreased ischemia/reperfusion enhanced renal tubular oxidative stress, cytosolic cytochrome C release, proapoptosis and autophagy in rat kidneys.

  3. 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.  .  

  4. Renal artery stenosis due to neurofibromatosis

    OpenAIRE

    Malav Ishwar; Kothari S

    2009-01-01

    A 4-year-old boy with hypertension due to renal artery stenosis and neurofibromatosis type 1 is presented for its rarity. Renal artery stenosis due to neurofibromatosis is underrecognized and may masquerade Takayasu′s arteritis in Asian children.

  5. Treatment Option Overview (Renal Cell Cancer)

    Science.gov (United States)

    ... Genetics of Kidney Cancer Research Renal Cell Cancer Treatment (PDQ®)–Patient Version General Information About Renal Cell ... Certain factors affect prognosis (chance of recovery) and treatment options. The prognosis (chance of recovery ) and treatment ...

  6. Treatment Options for Renal Cell Cancer

    Science.gov (United States)

    ... Genetics of Kidney Cancer Research Renal Cell Cancer Treatment (PDQ®)–Patient Version General Information About Renal Cell ... Certain factors affect prognosis (chance of recovery) and treatment options. The prognosis (chance of recovery ) and treatment ...

  7. Radionuclide renal dynamic and function study

    International Nuclear Information System (INIS)

    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

  8. The renal arterial resistive index and stage of chronic kidney disease in patients with renal allograft

    DEFF Research Database (Denmark)

    Winther, Stine O; Thiesson, Helle C; Poulsen, Lene N;

    2012-01-01

    The study investigated the optimal threshold value of renal arterial resistive index as assessed by Doppler ultrasonography determining chronic kidney disease stage 4 or higher in patients with renal allograft.......The study investigated the optimal threshold value of renal arterial resistive index as assessed by Doppler ultrasonography determining chronic kidney disease stage 4 or higher in patients with renal allograft....

  9. Secondary prevention with calcium antagonists after acute myocardial infarction

    DEFF Research Database (Denmark)

    Hansen, J F

    1992-01-01

    Experimental studies have demonstrated that the 3 calcium antagonists nifedipine, diltiazem, and verapamil have a comparable effect in the prevention of myocardial damage during ischaemia. Secondary prevention trials after acute myocardial infarction, which aimed at improving survival and...

  10. Future challenges in renal transplantation.

    Science.gov (United States)

    Whalen, H; Clancy, M; Jardine, A

    2012-02-01

    There is a worldwide increase in the incidence of end-stage renal disease. Renal transplantation has been shown to be cost effective, prolong survival and provide a better quality of life in comparison to dialysis. Consequently, there has been a steady increase in demand for organs leading to a shortage of available kidneys, and an increase in transplant waiting lists. Renal transplantation is therefore an expanding field with a number of unique future challenges to address. This article outlines strategies that may be employed to expand organ supply in order to meet increased demand. The ethical issues surrounding this are also summarized. Furthermore, we highlight techniques with the potential to minimize peri-transplant injury to the kidney on its journey from donor to recipient. Current and potential future management strategies to optimize graft and patient survival are also discussed. PMID:22361673

  11. Potential of carnuba wax in ameliorating brittle fracture during tableting.

    Science.gov (United States)

    Uhumwangho, M U; Okor, R S; Adogah, J T

    2009-01-01

    Carnuba wax (as binder) forms hard tablets even at low compression load attributable to its high plasticity. The aim of the present study is to investigate its potential in ameliorating brittle fracture (i.e., lamination and capping) a problem often encountered during tableting. Granules of paracetamol (test drug) were made by triturating the drug powder with the melted wax or starch mucilage (20%w/v). Resulting granules were separated into different size fractions which were separately compressed into tablets with and without a centre hole (as in- built defect) using different compression loads. The tablets were evaluated for tensile strength and the data used to calculate the brittle fracture index (BFI), using the expression: BFI = 0.5(T/T(0)-1) where T0 and T are the tensile strength of tablets with and without a centre hole respectively. The BFI values were significantly lower (pload further ameliorated the brittle fracture tendency of the tablets. Using granules with the larger particle size (850microm) and applying the lowest unit of load (6 arbitrary unit on the load scale of the tableting machine) the BFI values were 0.03 (carnuba wax tablets) and 0.11 (maize starch tablets). When the conditions were reversed (i.e., a highest load, 8 units and the smallest particle size, 212microm) the BFI values now became 0.17 (carnuba wax tablets) and 0.26 (maize starch tablets). The indication is that the use of large granules and low compression loads to form tablets can further enhance the potential of carnuba wax in ameliorating brittle fracture tendency of tablets during their manufacture. PMID:19168422

  12. Effects of ulinastatin on oxidative stress and renal injury in rats with severe heatstroke

    Directory of Open Access Journals (Sweden)

    Na PENG

    2015-06-01

    Full Text Available Objective To study the effects of ulinastatin on oxidative stress factors and renal function in rats with severe heatstroke. Methods Forty-two male SPF Wistar rats were randomly divided into normal control group (group C, n=6, heat stroke group (HS group, n=18 and ulinastatin treatment group (UTI group, n=18. Rats in the HS group and UT group were placed in an artificial climate chamber to induce HS, while rats of group C were kept at room temperature (23±0.2℃. UT rats were given by intraperitoneal injection of ulinastatin before model reproduction in a dose of 100 thousand units/kg, and it was repeated every 12h. The other in the rest two groups were injected with equal amount of normal saline. All the rats were sacrificed in batches at 0, 6 and 24h after successful modeling. Before death, blood samples were collected to determine serum creatinine and urea nitrogen with automatic biochemical analyzer. Meanwhile the concentrations of renal superoxide dismutase (SOD, glutathione peroxidase (GPx and malondialdehyde (MDA were determined with colorimetric method. Pathological changes in renal tissue of all animals were observed at 24h after model replication with light and electron microscopy. Results Compared with rats in group C, the MDA levels at 0h after onset of heatstroke increased significantly (P0.05. At the same time, compared with HS group, the elevated levels of serum Cr and BUN in the UTI group were lower at 6 and 24h after heatstroke onset (all P<0.05. The pathological damage of the kidney at 24h after heatstroke was significantly ameliorated in the UTI group. Conclusions Oxidative stress is involved in the pathogenesis of the renal injury during heatstroke, UTI may protect rats with heatstroke from renal injury by inhibiting oxidative stress in the kidney. DOI: 10.11855/j.issn.0577-7402.2015.05.04

  13. Renal Hypodysplasia Associates with a Wnt4 Variant that Causes Aberrant Canonical Wnt Signaling

    Science.gov (United States)

    Vivante, Asaf; Mark-Danieli, Michal; Davidovits, Miriam; Harari-Steinberg, Orit; Omer, Dorit; Gnatek, Yehudit; Cleper, Roxana; Landau, Daniel; Kovalski, Yael; Weissman, Irit; Eisenstein, Israel; Soudack, Michalle; Wolf, Haike Reznik; Issler, Naomi; Lotan, Danny; Anikster, Yair

    2013-01-01

    Abnormal differentiation of the renal stem/progenitor pool into kidney tissue can lead to renal hypodysplasia (RHD), but the underlying causes of RHD are not well understood. In this multicenter study, we identified 20 Israeli pedigrees with isolated familial, nonsyndromic RHD and screened for mutations in candidate genes involved in kidney development, including PAX2, HNF1B, EYA1, SIX1, SIX2, SALL1, GDNF, WNT4, and WT1. In addition to previously reported RHD-causing genes, we found that two affected brothers were heterozygous for a missense variant in the WNT4 gene. Functional analysis of this variant revealed both antagonistic and agonistic canonical WNT stimuli, dependent on cell type. In HEK293 cells, WNT4 inhibited WNT3A induced canonical activation, and the WNT4 variant significantly enhanced this inhibition of the canonical WNT pathway. In contrast, in primary cultures of human fetal kidney cells, which maintain WNT activation and more closely represent WNT signaling in renal progenitors during nephrogenesis, this mutation caused significant loss of function, resulting in diminished canonical WNT/β-catenin signaling. In conclusion, heterozygous WNT4 variants are likely to play a causative role in renal hypodysplasia. PMID:23520208

  14. Effects of ginsenosides on vascular reactivity in rat cerebral and renal arteries

    Institute of Scientific and Technical Information of China (English)

    WONG Wing-tak; LEUNG Fung-ping; YUNG Lai-hang; TIAN Xiao-yu; WONG Ricky Ngok Shun; HUANG Yu

    2008-01-01

    Objective To investigate possible mechanisms underlying the antioxidant property (1) and the in vitro vasodilator effects (2) of the two ginsenosides, Rb1 and Rg1, in isolated rat renal and cerebral arteries. Methods Arterial rings were mounted in a multi-channel myograph for recording of isometric tension. To examine the antioxidant activity, some rings were exposed to a free radical-generating reaction (hypoxan-thine and xanthine oxidase) with and without pre-treatment with ginsenosides. The calcium antagonistic effects were tested on rings contracted by membrane depolarization in elevated extracellular potassium ions, a condition that promoted Ca2+ influx in vascular smooth muscle cells. Results Ginsenosides protected endothelial function (endothelial nitric oxide-dependent relaxation) against oxidative stress; (2) ginsenoside Rb1 reduced the high K+ -induced contractions of both renal and cerebral arteries while ginsenoside Rgl relaxed the rat cerebral artery but not the renal artery. Conclusions Ginsenosides are vaso-protective via (1) the antioxidant activity which protects endothelial cell function and (2) the inhibition of Ca2+ influx through voltage-sensitive Ca2+ channels in vascular smooth muscle. The vasodilator effects may suggest the potential preventive or therapeutic values of ginsenosides against stroke and renal hypertension.

  15. TRPV1 Antagonists and Chronic Pain: Beyond Thermal Perception

    OpenAIRE

    Brandt, Michael R.; Beyer, Chad E; Stahl, Stephen M.

    2012-01-01

    In the last decade, considerable evidence as accumulated to support the development of Transient Receptor Potential Vanilloid 1 (TRPV1) antagonists for the treatment of various chronic pain conditions. Whereas there is a widely accepted rationale for the development of TRPV1 antagonists for the treatment of various inflammatory pain conditions, their development for indications of chronic pain, where conditions of tactical, mechanical and spontaneous pain predominate, is less clear. Preclinic...

  16. Bradykinin antagonists modified with dipeptide mimetic beta-turn inducers.

    Science.gov (United States)

    Alcaro, Maria C; Vinci, Valerio; D'Ursi, Anna M; Scrima, Mario; Chelli, Mario; Giuliani, Sandro; Meini, Stefania; Di Giacomo, Marcello; Colombo, Lino; Papini, Anna Maria

    2006-05-01

    Bradykinin (BK) is involved in a wide variety of pathophysiological processes. Potent BK peptide antagonists can be developed introducing constrained unnatural amino acids, necessary to force the secondary structure of the molecule. In this paper, we report a structure-activity relationship study of two peptide analogues of the potent B2 antagonist HOE 140 by replacing the D-Tic-Oic dipeptide with conformationally constrained dipeptide mimetic beta-turn inducers. PMID:16504505

  17. The Apolipoprotein E Antagonistic Pleiotropy Hypothesis: Review and Recommendations

    OpenAIRE

    Tuminello, Elizabeth R.; S Duke Han

    2011-01-01

    Research on apolipoprotein E (APOE) has consistently revealed a relationship between the gene's ε 4 allele and risk for development of Alzheimer's disease (AD). However, research with younger populations of ε 4 carriers has suggested that the APOE ε 4 allele may in fact be beneficial in earlier ages and may only confer risk of cognitive decline later in life. Accordingly, we and others have proposed that APOE may represent an example of antagonistic pleiotropy. Antagonistic pleiotropy is an e...

  18. Deficiency of interleukin-1 receptor antagonist responsive to anakinra.

    Science.gov (United States)

    Schnellbacher, Charlotte; Ciocca, Giovanna; Menendez, Roxanna; Aksentijevich, Ivona; Goldbach-Mansky, Raphaela; Duarte, Ana M; Rivas-Chacon, Rafael

    2013-01-01

    We describe a 3-month-old infant who presented to our institution with interleukin (IL)-1 receptor antagonist deficiency (DIRA), which consists of neutrophilic pustular dermatosis, periostitis, aseptic multifocal osteomyelitis, and persistently high acute-phase reactants. Skin findings promptly improved upon initiation of treatment with anakinra (recombinant human IL-1 receptor antagonist), and the bony lesions and systemic inflammation resolved with continued therapy. PMID:22471702

  19. Interleukin-2 receptor antagonists as induction therapy after heart transplantation

    DEFF Research Database (Denmark)

    Møller, Christian H; Gustafsson, Finn; Gluud, Christian;

    2008-01-01

    About half of the transplantation centers use induction therapy after heart transplantation. Interleukin-2 receptor antagonists (IL-2Ras) are used increasingly for induction therapy. We conducted a systematic review of randomized trials assessing IL-2Ras.......About half of the transplantation centers use induction therapy after heart transplantation. Interleukin-2 receptor antagonists (IL-2Ras) are used increasingly for induction therapy. We conducted a systematic review of randomized trials assessing IL-2Ras....

  20. Post-renal Transplantation de novo Renal Cell Carcinoma in a Middle-aged Man

    OpenAIRE

    Pandya, V. K.; Sutariya, H. C.

    2016-01-01

    Renal cell carcinoma is usually seen in the native kidney but may be seen in the renal allograft. We report a rare case of renal cell carcinoma in a 56-year-old renal allograft recipient who was transplanted for end-stage renal disease induced by analgesic nephropathy. This complication developed after 13 years of renal transplantation. Patient was investigated for hematuria and abdominal pain with a normal renal function. Computed tomography depicted a mass sized 9.0×7.3×6.8 cm that involved...

  1. Acute renal infarction Secondary to Atrial Fibrillation Mimicking Renal Stone Picture

    International Nuclear Information System (INIS)

    Acute renal infarction presents in a similar clinical picture to that of a renal stone. We report a 55-year-old Saudi female, known to have atrial fibrillation secondary to mitral stenosis due to rheumatic heart disease. She presented with a two day history of right flank pain that was treated initially as renal stone. Further investigations confirmed her as a case of renal infarction. Renal infarction is under-diagnosed because the similarity of its presentation to renal stone. Renal infarction should be considered in the differential diagnosis of loin pain, particularly in a patient with atrial fibrillation. (author)

  2. 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. PMID:26872270

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

    Directory of Open Access Journals (Sweden)

    María F Albertoni Borghese

    Full Text Available 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.

  4. Unusual cause of the subcapsular renal haematoma

    International Nuclear Information System (INIS)

    In 2 woman patients, the authors found subcapsular renal haematomas after paravertebral injection of a local anaesthetic as part of lumbago treatment. Clinical course and radiological findings are demonstrated. Whereas formation of subcapsular renal haematomas is a well-known phenomenon after traumas, iatrogenic and intentional punctures and a few renal and general diseases, renal lesion after paravertebral injection of a local anaesthetic is an extremely rare occurrence. (orig.)

  5. Roscovitine ameliorates endotoxin-induced uveitis through neutrophil apoptosis.

    Science.gov (United States)

    Jiang, Zhao-Xin; Qiu, Suo; Lou, Bing-Sheng; Yang, Yao; Wang, Wen-Cong; Lin, Xiao-Feng

    2016-08-01

    Neutrophils have been recognized as critical response cells during the pathogenesis of endotoxin‑induced uveitis (EIU). Apoptosis of neutrophils induced by roscovitine has previously been demonstrated to ameliorate inflammation in several in vivo models. The present study aimed to assess whether roscovitine ameliorates EIU. EIU was induced in female C57BL/6 mice by a single intravitreal injection of lipopolysaccharide (LPS; 250 ng). The mice were divided into three groups as follows: LPS alone, LPS plus vehicle, LPS plus roscovitine (50 mg/kg). The mice were euthanized 12, 24, 48 and 72 h after LPS‑induced uveitis. Accumulation of inflammatory cells in the vitreous body was confirmed by immunohistochemistry, and quantified following hematoxylin and eosin staining. Terminal deoxynucleotidyl transferase dUTP nick‑end labeling was performed to detect of apoptotic cells. The mRNA levels of inflammatory cytokines were analyzed by reverse transcription‑quantitative polymerase chain reaction and the changes in protein levels were analyzed by western blotting. Inflammatory cells accumulated in the vitreous near the optic nerve head and the quantity peaked at 24 h after LPS injection. Immunohistochemistry revealed that the majority of the inflammatory cells were neutrophils. The number of infiltrating cells was similar in the LPS and LPS plus vehicle groups, while there were significantly less in the roscovitine group at 24 h. Apoptosis of neutrophils was observed between 12 and 48 h after roscovitine injection, while no apoptosis was observed in the other groups. The mRNA expression levels of GMCSF, CINC‑1 and ICAM‑1 peaked at 12 h after LPS injection, and decreased to normal levels at 72 h. This trend in mRNA expression was similar in the LPS and LPS plus vehicle groups; however, the expression levels decreased more quickly in the roscovitine group at 24 and 48 h. Following roscovitine administration, upregulated cleaved caspase 3 expression levels

  6. Administration of red ginseng ameliorates memory decline in aged mice

    OpenAIRE

    Lee, Yeonju; Oh, Seikwan

    2015-01-01

    Background 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. Methods 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 m...

  7. Preclinical Evidence for the Efficacy of Ischemic Postconditioning against Renal Ischemia-Reperfusion Injury, a Systematic Review and Meta-Analysis.

    Directory of Open Access Journals (Sweden)

    Simone J Jonker

    Full Text Available Renal ischemia-reperfusion injury (IRI is a major cause of kidney damage after e.g. renal surgery and transplantation. Ischemic postconditioning (IPoC is a promising treatment strategy for renal IRI, but early clinical trials have not yet replicated the promising results found in animal studies.We present a systematic review, quality assessment and meta-analysis of the preclinical evidence for renal IPoC, and identify factors which modify its efficacy.We identified 39 publications studying >250 control animals undergoing renal IRI only and >290 animals undergoing renal IRI and IPoC. Healthy, male rats undergoing warm ischemia were used in the vast majority of studies. Four studies applied remote IPoC, all others used local IPoC. Meta-analysis showed that both local and remote IPoC ameliorated renal damage after IRI for the outcome measures serum creatinine, blood urea nitrogen and renal histology. Subgroup analysis indicated that IPoC efficacy increased with the duration of index ischemia. Measures to reduce bias were insufficiently reported.High efficacy of IPoC is observed in animal models, but factors pertaining to the internal and external validity of these studies may hamper the translation of IPoC to the clinical setting. The external validity of future animal studies should be increased by including females, comorbid animals, and transplantation models, in order to better inform clinical trial design. The severity of renal damage should be taken into account in the design and analysis of future clinical trials.

  8. Hyperpolarized Renal Magnetic Resonance Imaging

    DEFF Research Database (Denmark)

    Laustsen, Christoffer

    2016-01-01

    The introduction of dissolution dynamic nuclear polarization (d-DNP) technology has enabled a new paradigm for renal imaging investigations. It allows standard magnetic resonance imaging complementary renal metabolic and functional fingerprints within seconds without the use of ionizing radiation....... Increasing evidence supports its utility in preclinical research in which the real-time interrogation of metabolic turnover can aid the physiological and pathophysiological metabolic and functional effects in ex vivo and in vivo models. The method has already been translated to humans, although the clinical...

  9. Renal dendritic cells: an update

    OpenAIRE

    Velázquez, Peter; Dustin, Michael L.; Peter J Nelson

    2009-01-01

    Discovery into the role of renal dendritic cells (rDCs) in health and disease of the kidney is rapidly accelerating. Progress in deciphering DC precursors and the heterogeneity of monocyte subsets in mice and humans are providing insights into the biology of rDCs. Recent findings have extended knowledge of the origins, anatomy, and function of the rDC network at steady-state and during periods of injury to the renal parenchyma. This brief review highlights these new findings and provides an u...

  10. Emerging Entities in Renal Neoplasia.

    Science.gov (United States)

    Mehra, Rohit; Smith, Steven C; Divatia, Mukul; Amin, Mahul B

    2015-12-01

    This article reviews emerging entities in renal epithelial neoplasia, including tubulocystic carcinoma, clear-cell-papillary renal cell carcinoma (RCC), thyroid-like follicular RCC, ALK-related RCC, translocation RCC, acquired cystic disease-related RCC, succinate dehydrogenase-deficient RCC, and hereditary leiomyomatosis-RCC syndrome-associated RCC. Many of these rarer subtypes of RCC were recently studied in more depth and are included in the upcoming version of the World Health Organization classification of tumors. Emphasis is placed on common gross and morphologic features, differential diagnoses, use of ancillary studies for making accurate diagnoses, molecular alterations, and predicted biologic behavior based on previous studies. PMID:26612218

  11. Hypertensive encephalopathy complicating transplant renal artery stenosis.

    OpenAIRE

    McGonigle, R J; Bewick, M.; Trafford, J. A.; Parsons, V

    1984-01-01

    A 26-year-old female diabetic patient developed hypertensive encephalopathy with gross neurological abnormalities complicating renal artery stenosis of her transplant kidney. The elevated blood pressure was unresponsive to medical treatment. Surgical correction of the stenoses in the renal artery cured the hypertension and renal failure and led to the patient's complete recovery.

  12. Renal Cell Carcinoma Presenting as Dysphagia

    OpenAIRE

    Chauhan, Sharad; Yadav, Sher Singh; Tomar, Vinay

    2015-01-01

    Renal cell carcinoma presenting with dysphagia is rare. We report a case who presented with dysphagia as the only manifestations of renal malignancy. Biopsy from the pyriform fossa nodules revealed a clear cell neoplasm. Immuno-histochemical analysis of tissue confirmed metastasis of renal cell carcinoma.

  13. Multimodality imaging of renal inflammatory lesions

    OpenAIRE

    Das, Chandan J; Ahmad, Zohra; Sharma, Sanjay; Gupta, Arun K.

    2014-01-01

    Spectrum of acute renal infections includes acute pyelonephritis, renal and perirenal abscesses, pyonephrosis, emphysematous pyelonephritis and emphysematous cystitis. The chronic renal infections that we routinely encounter encompass chronic pyelonephritis, xanthogranulomatous pyelonephritis, and eosinophilic cystitis. Patients with diabetes, malignancy and leukaemia are frequently immunocompromised and more prone to fungal infections viz. angioinvasive aspergillus, candida and mucor. Tuberc...

  14. Secondary polycythaemia associated with bilateral renal lymphocoeles.

    OpenAIRE

    Burton, I E; Sambrook, P.; McWilliam, L J

    1994-01-01

    A patient with a 15 year history of secondary polycythaemia due to renal erythropoietin hypersecretion is presented. Subsequent spontaneous development of bilateral renal lymphocoeles, which contained high erythropoietin levels, was shown by computerized tomography. The lymphocoeles were successfully treated by bilateral peritoneal marsupialization. No cause for the persistent polycythaemia or lymphocoeles was found at laparotomy or on renal biopsy.

  15. Current treatments for renal cell carcinoma

    OpenAIRE

    Noble, Helen; Walsh, Ian

    2015-01-01

    Renal cell carcinoma (RCC), also known as kidney cancer, renal adenocarcinoma or hypernephroma, and metastatic renal cell carcinoma is a global burden. This article aims to provide a brief overview of RCC. It outlines epidemiology and presentation; invesitgation and staging; treatments and prognosis. The article also includes a focus on currently available drug treatments, and serves as an introduction to the topic.

  16. Acute Renal Failure in a Renal Center, Iraq

    International Nuclear Information System (INIS)

    We evaluated retrospectively the etiology and outcome of acute renal failure (ARF) in 84 patients in Rasheed Renal Center in Baghdad, Iraq from June 1998 through March 1999. They were 82 males and 2 females with ages that ranged between 5 and 80 years. Prerenal ARF was the commonest type found in 45 (53.6%) patients followed by renal ARF in 33 (39.3%) patients and acute obstructive uropathy six (7.1%) patients. Clinically, 74 patients presented with oligo-anuria, while 10 patients presented with non-oliguria. Of the oligo-anuria group, 61 ( 82.4%) patients required required renal replacement therapy (RRT) and 50 (67.6%) had complete recovery. The mortality rate was 25.67% in the oliguric group, while none in the non-oliguric group required RRT and the complete recvery rate was 100%. The overall survival in both groups was (77.4%). The patterns of ARF in our center were mostly compatible with the previous reports from the region. (author)

  17. Papillary adenocarcinoma of the renal pelvis with renal calculus: A rare case report

    OpenAIRE

    Li, Jianlong; Li, Qing; Yu, Yi

    2016-01-01

    Papillary adenocarcinoma of the renal pelvis is a rare clinicopathology of a kidney tumor with renal calculus. In the present case report, percutaneous renal biopsy, nephroscope lithotripsy and radical nephroureterectomy within a papillary adenocarcinoma of the renal pelvis accompanied with renal calculus was performed on a 65-year-old patient, also including a report on the patient's data and a literature review. The histopathological features confirmed the diagnosis of papillary adenocarcin...

  18. MRI appearance of massive renal replacement lipomatosis in the absence of renal calculus disease

    OpenAIRE

    Fitzgerald, E; Melamed, J.; Taneja, S. S.; Rosenkrantz, A.B.

    2011-01-01

    Renal replacement lipomatosis is a rare benign entity in which extensive fibrofatty proliferation of the renal sinus is associated with marked renal atrophy. In this report, we present a case of massive renal replacement lipomatosis demonstrated on MRI. The presentation was atypical given an absence of associated renal calculus disease, and an initial CT scan was interpreted as suspicious for a liposarcoma. The differential diagnosis and key MRI findings that served to establish this specific...

  19. 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.

  20. Pharmacokinetics of CGP 36,742, an orally active GABAB antagonist, in humans.

    Science.gov (United States)

    Gleiter, C H; Farger, G; Möbius, H J

    1996-05-01

    A study was conducted to evaluate the pharmacokinetics of CGP 36 742 (3-aminopropyl-n-butyl-phosphinic acid), an orally active gamma-aminobutyric acid B (GABAB) antagonist, in humans. Pharmacokinetic results after a single oral (600 mg) dose included maximum observed concentration (Cmax), 27 mumol/L (95% CI 22.9, 30.8); time to Cmax (tmax), 3 hours (median); half-life (t1/2), 3.6 hours (95% CI 3.24, 3.9); renal clearance (ClR), 125 mL/min (95% CI 114, 136); and absolute bioavailability (Fabs), 0.44 (95% CI 0.33, 0.47). Administration with food decreased the oral systemic availability (Frel) by 30%. The volume of distribution (285 L/kg) was in the order of magnitude of extracellular body water. The absorbed fraction of the compound was excreted completely and unchanged via the kidney, thus renal function would be the limiting factor for excretion. The rate of absorption and amount absorbed did not differ significantly between elderly and young healthy male volunteers, both after single and multiple doses. There was no gender-related difference in pharmacokinetics in healthy elderly volunteers. CGP 36 742 showed an excellent safety profile: there were no clinically relevant changes in cardiovascular variables, body temperature, or blood chemistry. In the placebo-controlled trial, adverse experiences were rare and evenly distributed among participants receiving placebo and the study drug. In addition, a newly developed high-performance liquid chromatography (HPLC) method for measurement of CGP 36 742 concentrations in plasma and urine using fluorescence detection is described. PMID:8739022

  1. Effect of Heme Oxygenase-1 Inducer Hemin on Chronic Renal Failure Rats

    Institute of Scientific and Technical Information of China (English)

    刘慎微; 石黎明; 刘晓城

    2004-01-01

    Summary: The role of HO 1 inducer, hemin, in chronic renal failure (CRF) rats and its possible mechanism of action was studied. 5/6 subtotal nephrectomy was performed to establish chronic renal failure model. Rats were randomly assigned to 4 groups: sham-operated group, CRF group,ferrous gluconate group and hemin group. At the 10th week after operation, serum creatinine,BUN, RBC, HGB and HCT were measured. Renal pathologic changes were observed. RT-PCR and immunohistochemistry were used to detect the expression and distribution of HO-1. RT-PCR and radioimmunoassay was used to determine the expression of ET-1 in the kidney and plasma. The results showed that as compared with CRF group, serum creatinine and BUN in hemin group were reduced significantly and nephrogenic anemia was improved markedly. Glomerular mesangial proliferation and interstitial lesion were also ameliorated significantly. Hemin not only increased the expression of HO-1 but also reduced the expression of ET-1 in the kidney. The level of ET-1 protein in the plasma was also reduced after hemin treatment. Most of these indexes were not obviously changed in ferrous gluconate group. It was suggested that through inducing the expression of HO-1 and reducing the level of ET-1 in the kidney and plasma, hemin plays an important protective role in 5/6 subtotal nephrectomized rats.

  2. The multifaceted role of the renal microvasculature during acute kidney injury.

    Science.gov (United States)

    Maringer, Katherine; Sims-Lucas, Sunder

    2016-08-01

    Pediatric acute kidney injury (AKI) represents a complex disease process for clinicians as it is multifactorial in cause and only limited treatment or preventatives are available. The renal microvasculature has recently been implicated in AKI as a strong therapeutic candidate involved in both injury and recovery. Significant progress has been made in the ability to study the renal microvasculature following ischemic AKI and its role in repair. Advances have also been made in elucidating cell-cell interactions and the molecular mechanisms involved in these interactions. The ability of the kidney to repair post AKI is closely linked to alterations in hypoxia, and these studies are elucidated in this review. Injury to the microvasculature following AKI plays an integral role in mediating the inflammatory response, thereby complicating potential therapeutics. However, recent work with experimental animal models suggests that the endothelium and its cellular and molecular interactions are attractive targets to prevent injury or hasten repair following AKI. Here, we review the cellular and molecular mechanisms of the renal endothelium in AKI, as well as repair and recovery, and potential therapeutics to prevent or ameliorate injury and hasten repair. PMID:26493067

  3. Variations in the lipid profile of patients with chronic renal failure treated with pyridoxine

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    Touceda Luis A

    2003-09-01

    Full Text Available Abstract Background Hyperhomocysteinemia and lipid abnormalities are commonly found in patients with chronic renal failure; both are recognized as risk factors for atherosclerosis. The homocysteine-lowering effect of pyridoxine is controversial. This study was performed to determine the effect of a high dose of pyridoxine (300 mg i.v. three times a week on plasma and red blood cell lipid profile and plasma homocysteine concentration in twelve chronic renal failure patients on regular hemodialysis. Fasting blood samples were taken at the beginning of the study (basal 1, after 30 and 60 days of treatment and 4 months after withdrawal (basal 2. Results Pyridoxine supplementation induced a significant decrease in total plasma homocysteine level and also a lowering effect in plasma total cholesterol and triglycerides. These biochemical data increased when the samples were taken at basal 2, reaching the levels obtained at the beginning of the experiment. LDL cholesterol increased whereas HDL cholesterol was reduced during the treatment. In erythrocyte membranes vitamin B6 therapy enhanced the cholesterol/phospholipid ratio as well as the fluorescence anisotropy of diphenyl-hexatriene. Conclusions We conclude that high doses of pyridoxine represent an effective strategy to ameliorate both plasma homocysteine levels and lipid profiles in chronic renal failure patients, protecting them from atherosclerosis. Further research using a long-term treatment would be necessary in an attempt to restore the fatty acid pattern and the fluidity of red cell membranes.

  4. Interventional mechanisms of herbs or herbal extracts on renal interstitial fibrosis.

    Science.gov (United States)

    Xia, Jia; He, Li-Qun; Su, Xiao

    2016-05-01

    Renal interstitial fibrosis (RIF) is a common development in chronic renal diseases that can lead to uremia and be life-threatening. The RIF pathology has complicated extracellular and intercellular mechanisms, involving many cells and cytokines, resulting in an incomplete mechanistic understanding of the disease. Finding effective herbs or herbal extracts for prevention and treatment of RIF is crucial because current medical approaches do not reliably slow or reverse RIF. In recent years, many experts have worked to identify herbs or herbal extracts to combat RIF both in vivo and in vitro, with some success. This review attempts to summarize the possible interventional mechanisms of herbs or herbal extracts involved in protecting and reversing RIF. The authors found some herbs and their extracts that may ameliorate renal impairments through anti-inflammation, anti-fibrogenesis and stabilization of extra cellular matrix. Among them, tetramethylpyrazine/ligustrazine, curcumin and polyglucoside of Tripterygium have experimentally shown good potential for improving RIF. However, conclusive evidence is still needed, especially in randomized controlled clinical trials. We expect that herbs or herbal extracts will play an important role in RIF treatment and reversal in the future. PMID:27181123

  5. Chemical Renal Denervation in the Rat

    Energy Technology Data Exchange (ETDEWEB)

    Consigny, Paul M., E-mail: paul.consigny@av.abbott.com; Davalian, Dariush, E-mail: dariush.davalian@av.abbott.com [Abbott Vascular, Innovation Incubator (United States); Donn, Rosy, E-mail: rosy.donn@av.abbott.com; Hu, Jie, E-mail: jie.hu@av.abbott.com [Abbott Vascular, Bioanalytical and Material Characterization (United States); Rieser, Matthew, E-mail: matthew.j.rieser@abbvie.com; Stolarik, DeAnne, E-mail: deanne.f.stolarik@abbvie.com [Abbvie, Analytical Pharmacology (United States)

    2013-12-03

    Introduction: The recent success of renal denervation in lowering blood pressure in drug-resistant hypertensive patients has stimulated interest in developing novel approaches to renal denervation including local drug/chemical delivery. The purpose of this study was to develop a rat model in which depletion of renal norepinephrine (NE) could be used to determine the efficacy of renal denervation after the delivery of a chemical to the periadventitial space of the renal artery. Methods: Renal denervation was performed on a single renal artery of 90 rats (n = 6 rats/group). The first study determined the time course of renal denervation after surgical stripping of a renal artery plus the topical application of phenol in alcohol. The second study determined the efficacy of periadventitial delivery of hypertonic saline, guanethidine, and salicylic acid. The final study determined the dose–response relationship for paclitaxel. In all studies, renal NE content was determined by liquid chromatography–mass spectrometry. Results: Renal NE was depleted 3 and 7 days after surgical denervation. Renal NE was also depleted by periadventitial delivery of all agents tested (hypertonic saline, salicylic acid, guanethidine, and paclitaxel). A dose response was observed after the application of 150 μL of 10{sup −5} M through 10{sup −2} M paclitaxel. Conclusion: We developed a rat model in which depletion of renal NE was used to determine the efficacy of renal denervation after perivascular renal artery drug/chemical delivery. We validated this model by demonstrating the efficacy of the neurotoxic agents hypertonic saline, salicylic acid, and guanethidine and increasing doses of paclitaxel.

  6. AMELIORATIVE EFFECTS OF TINOSPORA CORDIFOLIA IN SCIATICA PAIN INDUCED RATS

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    Thaakur Santhrani

    2012-05-01

    Full Text Available The present study was aimed at investigating the ameliorative effect of Tinospora cordifolia in sciatic nerve root Ligation -induced sciatica pain in rats. Adult male albino rats weighing 130-150gm were used for the study, and were divided into seven groups and ligation was performed on left sciatic nerve in group II to group VII. Tail cold-hyperalgesia, motor co-ordination tests, foot deformity, and total calcium levels were estimated to assess the extent of sciatica. Superoxide dismutase (SOD, catalase (CAT, and lipid peroxide (LPO levels were estimated to evaluate the extent of oxidative stress. The alcoholic and aqueous extract of Tinospora cordifolia was administered at a dose of 100 and 200 mg/kg/p.o for 15 days. Tinospora cordifolia attenuated sciatic nerve root Ligation-induced motor in-coordination, foot deformity, tail cold hyperalgesia, reversed ligation-induced alterations in lipid peroxides, total calcium, superoxide dismutase, catalase levels in a dose-dependent manner. Ameliorative effects of Tinospora cordifolia in ligation-induced sciatica may be due to its foot deformity, antioxidant, and calcium attenuating actions.

  7. Losartan ameliorates dystrophic epidermolysis bullosa and uncovers new disease mechanisms.

    Science.gov (United States)

    Nyström, Alexander; Thriene, Kerstin; Mittapalli, Venugopal; Kern, Johannes S; Kiritsi, Dimitra; Dengjel, Jörn; Bruckner-Tuderman, Leena

    2015-09-01

    Genetic loss of collagen VII causes recessive dystrophic epidermolysis bullosa (RDEB)-a severe skin fragility disorder associated with lifelong blistering and disabling progressive soft tissue fibrosis. Causative therapies for this complex disorder face major hurdles, and clinical implementation remains elusive. Here, we report an alternative evidence-based approach to ameliorate fibrosis and relieve symptoms in RDEB. Based on the findings that TGF-β activity is elevated in injured RDEB skin, we targeted TGF-β activity with losartan in a preclinical setting. Long-term treatment of RDEB mice efficiently reduced TGF-β signaling in chronically injured forepaws and halted fibrosis and subsequent fusion of the digits. In addition, proteomics analysis of losartan- vs. vehicle-treated RDEB skin uncovered changes in multiple proteins related to tissue inflammation. In line with this, losartan reduced inflammation and diminished TNF-α and IL-6 expression in injured forepaws. Collectively, the data argue that RDEB fibrosis is a consequence of a cascade encompassing tissue damage, TGF-β-mediated inflammation, and matrix remodeling. Inhibition of TGF-β activity limits these unwanted outcomes and thereby substantially ameliorates long-term symptoms. PMID:26194911

  8. Guanfacine ameliorates hypobaric hypoxia induced spatial working memory deficits.

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    Kauser, H; Sahu, S; Kumar, S; Panjwani, U

    2014-01-17

    Hypobaric hypoxia (HH) observed at high altitude causes mild cognitive impairment specifically affecting attention and working memory. Adrenergic dysregulation and neuronal damage in prefrontal cortex (PFC) has been implicated in hypoxia induced memory deficits. Optimal stimulation of alpha 2A adrenergic receptor in PFC facilitates the spatial working memory (SWM) under the conditions of adrenergic dysregulation. Therefore the present study was designed to test the efficacy of alpha 2A adrenergic agonist, Guanfacine (GFC), to restore HH induced SWM deficits and PFC neuronal damage. The rats were exposed to chronic HH equivalent to 25,000ft for 7days in an animal decompression chamber and received daily treatment of GFC at a dose of 1mg/kg body weight via the intramuscular route during the period of exposure. The cognitive performance was assessed by Delayed Alternation Task (DAT) using T-Maze and PFC neuronal damage was studied by apoptotic and neurodegenerative markers. Percentage of correct choice decreased significantly while perseverative errors showed a significant increase after 7days HH exposure, GFC significantly ameliorated the SWM deficits and perseveration. There was a marked and significant increase in chromatin condensation, DNA fragmentation, neuronal pyknosis and fluoro Jade positive cells in layer II of the medial PFC in hypoxia exposed group, administration of GFC significantly reduced the magnitude of these changes. Modulation of adrenergic mechanisms by GFC may serve as an effective countermeasure in amelioration of prefrontal deficits and neurodegenerative changes during HH. PMID:24184415

  9. Oxidative Stress in Lead and Cadmium Toxicity and Its Amelioration

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    R. C. Patra

    2011-01-01

    Full Text Available Oxidative stress has been implicated to play a role, at least in part, in pathogenesis of many disease conditions and toxicities in animals. Overproduction of reactive oxygen species and free radicals beyond the cells intrinsic capacity to neutralize following xenobiotics exposure leads to a state of oxidative stress and resultant damages of lipids, protein, and DNA. Lead and cadmium are the common environmental heavy metal pollutants and have widespread distribution. Both natural and anthropogenic sources including mining, smelting, and other industrial processes are responsible for human and animal exposure. These pollutants, many a times, are copollutants leading to concurrent exposure to living beings and resultant synergistic deleterious health effects. Several mechanisms have been explained for the damaging effects on the body system. Of late, oxidative stress has been implicated in the pathogenesis of the lead- and cadmium-induced pathotoxicity. Several ameliorative measures to counteract the oxidative damage to the body system aftermath or during exposure to these toxicants have been assessed with the use of antioxidants. The present review focuses on mechanism of lead- and cadmium-induced oxidate damages and the ameliorative measures to counteract the oxidative damage and pathotoxicity with the use of supplemented antioxidants for their beneficial effects.

  10. Phytoceramide Shows Neuroprotection and Ameliorates Scopolamine-Induced Memory Impairment

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    Seikwan Oh

    2011-10-01

    Full Text Available The function and the role phytoceramide (PCER and phytosphingosine (PSO in the central nervous system has not been well studied. This study was aimed at investigating the possible roles of PCER and PSO in glutamate-induced neurotoxicity in cultured neuronal cells and memory function in mice. Phytoceramide showed neuro-protective activity in the glutamate-induced toxicity in cultured cortical neuronal cells. Neither phytosphingosine nor tetraacetylphytosphingosine (TAPS showed neuroproective effects in neuronal cells. PCER (50 mg/kg, p.o. recovered the scopolamine-induced reduction in step-through latency in the passive avoidance test; however, PSO did not modulate memory function on this task. The ameliorating effects of PCER on spatial memory were confirmed by the Morris water maze test. In conclusion, through behavioral and neurochemical experimental results, it was demonstrated that central administration of PCER produces amelioration of memory impairment. These results suggest that PCER plays an important role in neuroprotection and memory enhancement and PCER could be a potential new therapeutic agent for the treatment of neurodegenerative diseases such as Alzheimer’s disease.

  11. Curcumin ameliorates experimental autoimmune myasthenia gravis by diverse immune cells.

    Science.gov (United States)

    Wang, Shan; Li, Heng; Zhang, Min; Yue, Long-Tao; Wang, Cong-Cong; Zhang, Peng; Liu, Ying; Duan, Rui-Sheng

    2016-07-28

    Curcumin is a traditional Asian medicine with diverse immunomodulatory properties used therapeutically in the treatment of many autoimmune diseases. However, the effects of curcumin on myasthenia gravis (MG) remain undefined. Here we investigated the effects and potential mechanisms of curcumin in experimental autoimmune myasthenia gravis (EAMG). Our results demonstrated that curcumin ameliorated the clinical scores of EAMG, suppressed the expression of T cell co-stimulatory molecules (CD80 and CD86) and MHC class II, down-regulated the levels of pro-inflammatory cytokines (IL-17, IFN-γ and TNF-α) and up-regulated the levels of the anti-inflammatory cytokine IL-10, shifted the balance from Th1/Th17 toward Th2/Treg, and increased the numbers of NKR-P1(+) cells (natural killer cell receptor protein 1 positive cells, including NK and NKT cells). Moreover, the administration of curcumin promoted the differentiation of B cells into a subset of B10 cells, increased the anti-R97-166 peptide IgG1 levels and decreased the relative affinity indexes of anti-R97-116 peptide IgG. In summary, curcumin effectively ameliorate EAMG, indicating that curcumin may be a potential candidate therapeutic agent for MG. PMID:27181511

  12. Rosuvastatin ameliorates inflammation, renal fat accumulation, and kidney injury in transgenic spontaneously hypertensive rats expressing human C-reactive protein

    Czech Academy of Sciences Publication Activity Database

    Šilhavý, Jan; Zídek, Václav; Landa, Vladimír; Šimáková, Miroslava; Mlejnek, Petr; Oliyarnyk, O.; Malínská, H.; Kazdová, L.; Mancini, M.; Pravenec, Michal

    2015-01-01

    Roč. 64, č. 3 (2015), s. 295-301. ISSN 0862-8408 R&D Projects: GA MŠk(CZ) LH11049; GA MŠk(CZ) LL1204; GA MZd(CZ) NT14325; GA ČR(CZ) GB14-36804G Institutional support: RVO:67985823 Keywords : rosuvastatin * kidney damage * CRP * transgenic * spontaneously hypertensive rat Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 1.293, year: 2014

  13. Renal function in diabetic nephropathy.

    Science.gov (United States)

    Dabla, Pradeep Kumar

    2010-05-15

    Diabetic nephropathy is the kidney disease that occurs as a result of diabetes. Cardiovascular and renal complications share common risk factors such as blood pressure, blood lipids, and glycemic control. Thus, chronic kidney disease may predict cardiovascular disease in the general population. The impact of diabetes on renal impairment changes with increasing age. Serum markers of glomerular filtration rate and microalbuminuria identify renal impairment in different segments of the diabetic population, indicating that serum markers as well as microalbuminuria tests should be used in screening for nephropathy in diabetic older people. The American Diabetes Association and the National Institutes of Health recommend Estimated glomerular filtration rate (eGFR) calculated from serum creatinine at least once a year in all people with diabetes for detection of kidney dysfunction. eGFR remains an independent and significant predictor after adjustment for conventional risk factors including age, sex, duration of diabetes, smoking, obesity, blood pressure, and glycemic and lipid control, as well as presence of diabetic retinopathy. Cystatin-C (Cys C) may in future be the preferred marker of diabetic nephropathy due differences in measurements of serum creatinine by various methods. The appropriate reference limit for Cys C in geriatric clinical practice must be defined by further research. Various studies have shown the importance of measurement of albuminuria, eGFR, serum creatinine and hemoglobin level to further enhance the prediction of end stage renal disease. PMID:21537427

  14. Genetic Counseling in Renal Masses

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    José Antonio López-Guerrero

    2008-01-01

    Full Text Available All urologists have faced patients suffering a renal cancer asking for the occurrence of the disease in their offspring and very often the answer to this question has not been well founded from the scientific point of view, and only in few cases a familial segregation tree is performed. The grate shift seen in the detection of small renal masses and renal cancer in the last decades will prompt us to know the indications for familial studies, which and when are necessary, and probably to refer those patients with a suspected familial syndrome to specialized oncological centers where the appropriate molecular and familial studies could be done. Use of molecular genetic testing for early identification of at-risk family members improves diagnostic certainty and would reduce costly screening procedures in at-risk members who have not inherited disease-causing mutations. This review will focus on the molecular bases of familial syndromes associated with small renal masses and the indications of familial studies in at-risk family members.

  15. Renal leiomyosarcoma in a cat.

    Science.gov (United States)

    Evans, Dawn; Fowlkes, Natalie

    2016-05-01

    Renal leiomyosarcoma was diagnosed in a 10-year-old Domestic Shorthair cat with a 3-year history of clinically managed, chronic renal disease. Sudden death was preceded by a brief episode of mental dullness and confusion. At postmortem examination, the gross appearance of the left kidney was suggestive of hydronephrosis, and a nephrolith was present in the contralateral kidney. However, histology revealed an infiltrative, poorly differentiated, spindle cell sarcoma bordering the grossly cavitated area. Neoplastic cells were immunoreactive for vimentin and smooth muscle actin, which led to a diagnosis of renal leiomyosarcoma; neoplastic cells were not immunoreactive for desmin. Leiomyosarcoma arising in the kidney is a rare occurrence in humans and an even rarer occurrence in veterinary medicine with no prior cases being reported in cats in the English literature. The macroscopic appearance of the tumor at postmortem examination was misleadingly suggestive of hydronephrosis as a result of the large cavitation and may be similar to particularly unusual cases of renal leiomyosarcomas in humans that have a cystic or cavitated appearance. PMID:26975352

  16. Shigella septicaemia following renal transplantation.

    OpenAIRE

    Severn, M; Michael, J

    1980-01-01

    Two patients are described who developed septicaemia with Shigella flexneri following renal transplantation. Pre-operative screening had not identified either patient as a chronic carrier of Shigella sp. The acute management and problems posed by unrecognized carriers amongst patients undergoing transplantation in areas of the world where Shigella is endemic, are discussed.

  17. Renal (Kidney) Manifestations in TSC

    Medline Plus

    Full Text Available ... of individuals (greater than 80 percent) with tuberous sclerosis complex (TSC) will develop some form of renal ( ... muscle (“myo”) and fat (“lipoma”). Usually angiomyolipomas are multiple and occur in both kidneys. The presence of ...

  18. Sequential Scintigraphy in Renal Transplantation

    International Nuclear Information System (INIS)

    Based on experience gained from more than 1600 patients with proved or suspected kidney diseases and on results on extended studies with dogs, sequential scintigraphy was performèd after renal transplantation in dogs. After intravenous injection of 500 μCi. 131I-Hippuran scintiphotos were taken during the first minute with an exposure time of 15 sec each and thereafter with an exposure of 2 min up to at least 16 min.. Several examinations were evaluated digitally. 26 examinations were performed on 11 dogs with homotransplanted kidneys. Immediately after transplantation the renal function was almost normal arid the bladder was filled in due time. At the beginning of rejection the initial uptake of radioactive Hippuran was reduced. The intrarenal transport became delayed; probably the renal extraction rate decreased. Corresponding to the development of an oedema in the transplant the uptake area increased in size. In cases of thrombosis of the main artery there was no evidence of any uptake of radioactivity in the transplant. Similar results were obtained in 41 examinations on 15 persons. Patients with postoperative anuria due to acute tubular necrosis showed still some uptake of radioactivity contrary to those with thrombosis of the renal artery, where no uptake was found. In cases of rejection the most frequent signs were a reduced initial uptake and a delayed intrarenal transport of radioactive Hippuran. Infarction could be detected by a reduced uptake in distinct areas of the transplant. (author)

  19. Neuropeptide S ameliorates olfactory spatial memory impairment induced by scopolamine and MK801 through activation of cognate receptor-expressing neurons in the subiculum complex.

    Science.gov (United States)

    Shao, Yu-Feng; Wang, Can; Xie, Jun-Fan; Kong, Xiang-Pan; Xin, Le; Dong, Chao-Yu; Li, Jing; Ren, Wen-Ting; Hou, Yi-Ping

    2016-07-01

    Our previous studies have demonstrated that neuropeptide S (NPS), via selective activation of the neurons bearing NPS receptor (NPSR) in the olfactory cortex, facilitates olfactory function. High level expression of NPSR mRNA in the subiculum complex of hippocampal formation suggests that NPS-NPSR system might be involved in the regulation of olfactory spatial memory. The present study was undertaken to investigate effects of NPS on the scopolamine- or MK801-induced impairment of olfactory spatial memory using computer-assisted 4-hole-board spatial memory test, and by monitoring Fos expression in the subiculum complex in mice. In addition, dual-immunofluorescence microscopy was employed to identify NPS-induced Fos-immunereactive (-ir) neurons that also bear NPSR. Intracerebroventricular administration of NPS (0.5 nmol) significantly increased the number of visits to switched odorants in recall trial in mice suffering from odor-discriminating inability induced by scopolamine, a selective muscarinic cholinergic receptor antagonist, or MK801, a N-methyl-D-aspartate receptor antagonist, after training trials. The improvement of olfactory spatial memory by NPS was abolished by the NPSR antagonist [D-Val(5)]NPS (40 nmol). Ex vivo c-Fos and NPSR immunohistochemistry revealed that, as compared with vehicle-treated mice, NPS markedly enhanced Fos expression in the subiculum complex encompassing the subiculum (S), presubiculum (PrS) and parasubiculum (PaS). The percentages of Fos-ir neurons that also express NPSR were 91.3, 86.5 and 90.0 % in the S, PrS and PaS, respectively. The present findings demonstrate that NPS, via selective activation of the neurons bearing NPSR in the subiculum complex, ameliorates olfactory spatial memory impairment induced by scopolamine and MK801 in mice. PMID:26323488

  20. [Renal failure and cystic kidney diseases].

    Science.gov (United States)

    Correas, J-M; Joly, D; Chauveau, D; Richard, S; Hélénon, O

    2011-04-01

    Cystic kidney diseases often are discovered at the time of initial work-up of renal failure through ultrasound or family history, or incidentally at the time of an imaging test. Hereditary diseases include autosomal dominant or recessive polycystic kidney disease (PKD), tuberous sclerosis (TS) and medullary cystic kidney disease (MCKD). Autosomal dominant PKD is characterized by large renal cysts developing in young adults. Renal failure is progressive and becomes severe around 50-60 years of age. Atypical cysts (hemorrhagic or hyperdense) are frequent on CT and MRI examinations. Imaging plays a valuable role in the management of acute complications such as cyst hemorrhage or infection. Autosomal recessive PKD is often detected in neonates, infants or young adults. It is characterized by renal enlargement due to the presence of small cysts and liver disease (fibrosis and biliary ductal dilatation). Late manifestation or slow progression of autosomal recessive PKD may be more difficult to distinguish from autosomal dominant PKD. These cystic kidney diseases should not be confused with non-hereditary incidental multiple renal cysts. In tuberous sclerosis, renal cysts are associated with angiomyolipomas and sometimes pulmonary lymphangioleiomyomatosis. Renal failure is inconstant. Other hereditary cystic kidney diseases, including MCKD and nephronophtisis, are usually associated with renal failure. Non-hereditary cystic kidney diseases include multicystic renal dysplasia (due to complete pelvi-ureteric atresia or hydronephrosis), acquired multicystic kidney disease (chronic renal failure, chronic hemodialysis) and varied cystic kidney diseases (multicystic renal disease, glomerulocystic kidney disease, microcystic kidney disease). PMID:21549887