Protective effect of hypoxylonol C and 4,5,4',5'-tetrahydroxy-1,1'-binaphthyl isolated from Annulohypoxylon annulatum against streptozotocin-induced damage in INS-1 cells.

We evaluated the protective effects of hypoxylonol C and 4,5,4',5'-tetrahydroxy-1,1'-binaphthyl (BNT) isolated from Annulohypoxylon annulatum on pancreatic ß-cell apoptosis, using the ß-cell toxin streptozotocin (STZ). Hypoxylonol C and BNT restored the STZ-induced decrease in INS-1 cell viability in a dose-dependent manner. In addition, treatment of INS-1 cells with 50 µM STZ resulted in an increase in apoptotic cell death, which was observed as annexin V fluorescence intensity. Apoptotic cell death was decreased by co-treatment with 100 µM hypoxylonol C and 100 µM BNT. Similarly, STZ caused a marked increase in the expression of cleaved caspase-8, caspase-3, Bax, and poly (ADP-ribose) polymerase (PARP), as well as a decrease in the expression of B-cell lymphoma 2 (Bcl-2), which was reversed by co-treatment with 100 µM hypoxylonol C and 100 µM BNT. These findings suggest that hypoxylonol C and BNT play an important role in protecting pancreatic ß-cells against apoptotic damage.

Isoniazid treatment to prevent TB in kidney and pancreas transplant recipients based on an interferon-γ-releasing assay: an exploratory randomized controlled trial.

BACKGROUND: We performed a randomized trial of isoniazid treatment based on interferon-γ-releasing assay (IGRA) in kidney transplant (KT) recipients in an intermediate-TB-burden country. METHODS: All adult patients admitted to a KT institute between June 2010 and May 2013 were enrolled. The IGRA (T-SPOT.TB assay) was performed on all patients, and isoniazid treatment was given to those with clinical risk factors for latent TB infection (LTBI). Patients with positive IGRA who had no clinical risk factors for LTBI were randomly assigned to isoniazid treatment or a control group. The development of TB after KT was monitored between June 2010 and November 2013. The primary endpoint was the development of TB. RESULTS: Of the 784 patients who had no clinical risk factors for LTBI, 445 (57%) gave negative results in the IGRA, 76 (10%) indeterminate results and 263 (33%) positive results. Of the latter, 131 were allocated to isoniazid treatment and 132 to the control group. Three (2%) of the control group developed TB, whereas none of the isoniazid treatment group developed TB (rate difference 1.22 per 100 person-years, P = 0.09). Of the 521 patients with negative or indeterminate IGRA results, 4 [0.8%, 0.43 per 100 person-years (95% CI 0.12-1.09)] developed TB after KT. CONCLUSIONS: IGRA-based isoniazid treatment has a trend towards reducing TB development in KT recipients without clinical risk factors, but careful monitoring of TB development is needed in negative-IGRA KT recipients.

The optimal therapy of calcineurin inhibitors for pregnancy in kidney transplantation.

We investigated the effects of pregnancy and delivery on renal function in transplant recipients and the relationship between doses of immunosuppressants and blood drug levels during pregnancy in 75 women with 88 deliveries. Significant serum creatinine elevation (> 0.5 mg/dL) was found in eight deliveries. In the remaining 80 cases, serum creatinine was reduced by an average of 0.14 mg/dL and returned to pre-pregnant levels after delivery. Tacrolimus was used in 28 deliveries and cyclosporine in others. Tacrolimus blood trough level declined from 5.8 ± 2.8 ng/mL 12 months before delivery to 4.2 ± 1.8 ng/mL at second trimester; therefore, drug dose was increased from 4.1 ± 1.9 mg/d at first trimester to 5.5 ± 2.5 mg/d at delivery. Similarly, cyclosporine levels were 125.1 ± 65.1 ng/mL 12 months before delivery and 75.4 ± 35.0 ng/mL at second trimester resulting in dose elevation from 183.0 ± 71.8 mg/d at first trimester to 225.4 ± 85.1 mg/d at delivery. Renal function in female kidney transplant recipients improved slightly during pregnancy and returned to pre-pregnant level after delivery. The dose elevation of calcineurin inhibitor by approximately 20-25% should be considered during gestational period to maintain optimal blood drug level.

AMP-activated protein kinase inhibits TGF-ß-, angiotensin II-, aldosterone-, high glucose-, and albumin-induced epithelial-mesenchymal transition.

The epithelial-mesenchymal transition (EMT) is a novel mechanism that promotes renal fibrosis. Transforming growth factor-ß (TGF-ß), angiotensin II, aldosterone, high glucose, and urinary albumin are well-known causes of EMT and renal fibrosis. We examined whether and how activation of AMP-activated protein kinase (AMPK) suppressed EMT induced by the above agents in tubular epithelial cells. All experiments were performed using HK-2 cells. Protein expression was measured by Western blot analysis. Intracellular reactive oxygen species (ROS) were analyzed by flow cytometry. Exposure of tubular cells to TGF-ß (10 ng/ml), angiotensin II (1 µM), aldosterone (100 nM), high glucose (30 mM), and albumin (5 mg/ml) for 5 days induced EMT, as shown by upregulation of α-smooth muscle actin and downregulation of E-cadherin. ROS and NADPH oxidase 4 (Nox4) expression were increased, and antioxidants such as tiron and N-acetylcysteine inhibited EMT induction. Metformin (the best known clinical activator of AMPK) suppressed EMT induction through inhibition of ROS via induction of heme oxygenase-1 and endogenous antioxidant thioredoxin. An AMPK inhibitor (compound C) and AMPK small interfering RNA blocked the effect of metformin, and another AMPK activator [5-aminoimidazole-4-carboxamide-1ß riboside (AICAR)] exerted the same effects as metformin. In conclusion, AMPK activation might be beneficial in attenuating the tubulointerstitial fibrosis induced by TGF-ß, angiotensin II, aldosterone, high glucose, and urinary albumin.

Mycophenolic acid regulates spleen tyrosine kinase to repress tumour necrosis factor-alpha-induced monocyte chemotatic protein-1 production in cultured human aortic endothelial cells.

Atherosclerosis develops from cascades of inflammatory processes. Spleen tyrosine kinase (Syk) and monocyte chemotatic protein-1 (MCP-1) play important roles in the pathogenesis of atherosclerosis. Mycophenolic acid (MPA) has an anti-inflammatory effect. We have investigated whether MPA regulates Syk to repress tumour necrosis factor-α (TNF-α)-induced MCP-1 production in cultured human aortic endothelial cells. Expression of MCP-1 mRNA and its protein were measured by real time RT-PCR and ELISA, respectively. Reactive oxygen species (ROS) production were measured using 2'7'-dichlorofluorescein diacetate. Activation of AP-1 and NF-κB were assessed by electrophoretic mobility shift assay. Tyrosine phosphorylation of Syk was examined by Western blot analysis. TNF-α increased MCP-1 at both mRNA and protein levels. TNF-α-induced MCP-1 mRNA expression was inhibited by N-acetylcysteine (NAC), Syk inhibitor, Syk-siRNA and MPA. TNF-α-induced MCP-1 protein production was also inhibited by Syk inhibitor and MPA. TNF-α increased DNA binding activity of AP-1 and NF-κB, whereas both AP-1 and NF-κB decoy oligodeoxynucleotides downregulated TNF-α-induced MCP-1 mRNA expression. TNF-α increased ROS generation, which was inhibited by NAC and MPA, but not by Syk inhibitor. TNF-α increased tyrosine phosphorylation of Syk, which was attenuated by NAC and MPA. MPA and Syk inhibitor attenuated TNF-α-induced DNA binding activity of NF-κB and AP-1. TNF-α induced MCP-1 expression via activation of AP-1 and NF-κB. AP-1 and NF-κB were mediated through ROS, followed by Syk. MPA exerts anti-inflammatory effect by inhibiting MCP-1 expression via suppression of ROS and Syk.

Comparison of the MDRD study and CKD-EPI equations for the estimation of the glomerular filtration rate in the Korean general population: the fifth Korea National Health and Nutrition Examination Survey (KNHANES V-1), 2010.

BACKGROUND: We compared the accuracy of the Modification of Diet in Renal Disease (MDRD) study and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations in Korean patients and evaluated the difference in CKD prevalence determined using the two equations in the Korean general population. METHODS: The accuracy of the two equations was evaluated in 607 patients who underwent a chromium-51-ethylenediaminetetraacetic acid GFR measurement. Additionally, we compared the difference in CKD prevalence determined by the two equations among 5,822 participants in the fifth Korea National Health and Nutrition Examination Survey, 2010. RESULTS: Among the 607 subjects, the median bias of the CKD-EPI equation was significantly lower than that of the MDRD study equation (0.9 vs. 2.2, p=0.020). The accuracy of the two equations was not significantly different in patients with mGFR <60 mL/min/1.73m(2); however, the accuracy of the CKD-EPI equation was significantly higher than that of the MDRD study equation in patients with GFR ≥60 mL/min/1.73m(2). The prevalences of the CKD stages 1, 2 and 3 in the Korean general population were 47.56, 49.23, and 3.07%, respectively, for the MDRD study equation; and were 68.48, 28.89, and 2.49%, respectively, for the CKD-EPI equation. CONCLUSIONS: These data suggest that the CKD-EPI equation might be more useful in clinical practice than the MDRD study equation in Koreans.

Living donor and recipient screening for latent tuberculosis infection by tuberculin skin test and interferon-gamma releasing assay in a country with an intermediate burden of tuberculosis.

There are few data on donor screening for latent tuberculosis infection (LTBI) using the tuberculin skin test (TST) and interferon-gamma releasing assay (IGRA). In South Korea, most renal allografts involve living donors (average, 80%). Hence, we have an opportunity to evaluate donor and recipient screening for LTBI by TST and IGRA. All donors and recipients admitted for kidney transplantation during a 20-month period were evaluated prospectively by using TST and Mycobacterium tuberculosis-specific enzyme-linked immunosorbent spot (ELISPOT) assay. The study population consisted of 205 living donor-recipient pairs (≥16 years) including 15 (7%) who yielded indeterminate donor or recipient ELISPOT results. Of the 205 donors, 63 (31%) gave a positive TST ≥5 mm, 33 (16%) a positive TST ≥10 mm, and 96 (47%) a positive ELISPOT. Of the 205 recipients, 9 (5%) gave a positive TST ≥5 mm, 3 (2%) a positive TST ≥10 mm, and 79 (39%) had a positive ELISPOT. Of the 205 donor-recipient pairs, only 59 (29%) gave negative donor and recipient ELISPOT results and 139 (68%) negative donor and recipient TSTs (<5 mm) (P < 0.001). One third of donor-recipient pairs tends to be positive in the TST, and two thirds of the donor-recipient pairs tends to be positive in the ELISPOT. Given the high positive rate of LTBI obtained by screening donors, further studies on the clinical value of solid organ transplant donors with positive TST or ELISPOT and health economics analysis in countries with intermediate burden of TB are needed for policy decisions on isoniazid (INH) prophylaxis.

Activation of AMP-activated protein kinase inhibits albumin-induced endoplasmic reticulum stress and apoptosis through inhibition of reactive oxygen species.

BACKGROUND: Endoplasmic reticulum (ER) stress induced by urinary albumin plays an important role in tubulointerstitial injury. We have shown that albumin-induced ER stress is regulated through reactive oxygen species (ROS)-c-Src kinase-mTOR signaling pathways. We postulated that peroxisome proliferator-activated receptor-γ (PPAR-γ) might also act as an upstream signaling molecule between c-Src kinase and mTOR. It has been suggested that AMP-activated protein kinase (AMPK) is involved in attenuation of ER stress. We examined whether and how activation of AMPK suppressed the albumin-induced ER stress and apoptosis in tubular epithelial cells. METHOD: HK-2 cells, a proximal tubular cell line, were used. Protein expressions were measured by Western blot analysis. Intracellular ROS and apoptosis were analyzed by flow cytometry. RESULTS: Albumin-induced PPAR-γ expression and PPAR-γ inhibitor (GW9662) suppressed the albumin-induced ER stress. c-Src kinase inhibitor and GW9662 reduced the albumin-induced PPAR-γ and mTOR, respectively. Metformin (the best known clinical activator of AMPK) and another AMPK activator (AICAR) suppressed the albumin-induced ER stress via inhibition of ROS through induction of endogenous antioxidant thioredoxin. AMPK inhibitor blocked the effect of metformin and AICAR. Our in vivo animal study showed that metformin reduced the renal cortical expression of ER stress protein (GRP78) in protein-overload proteinuria rats. Metformin also reduced the caspase 3-dependent apoptosis induced by albumin. CONCLUSION: PPAR-γ was involved in albumin-induced ER stress as an upstream signaling molecule between c-Src kinase and mTOR. AMPK activation might be beneficial in attenuating the tubulointerstitial injury induced by albumin.

Long-term outcome of Hepatitis B-positive renal allograft recipients after development of antiviral treatment.

BACKGROUND/AIMS: Hepatitis B virus (HBV) infection can adversely affect the clinical outcome of kidney transplantation (KT). Short-term efficacy of lamivudine has been demonstrated for chronic hepatitis B in KT recipients (KTR). METHODS: To clarify the long-term impact of antiviral treatment for HBV-positive KTR, we retrospectively reviewed 94 HBV-positive (male 73%) and 282 age/sex-matched HBV-negative patients who underwent KT from February 1997 to November 2009, after lamivudine had come into wide use. RESULTS: Mean follow-up was 75.7 months. 56 patients received antiviral agent for prophylaxis, and other 18 for HBV reactivation. During follow-up, 15 died, with 5 deaths being HBV related. Although the patient survival rate was lower for HBVpositive than HBV-negative KTRs (89% vs. 94% at 5 years, 78% vs. 88% at 10 years, p = 0.031), graft survival was comparable (86% vs. 92% at 5 years, 73% vs. 81% at 10 years, p = 0.113). In multivariate analysis, HBsAg positivity was a significant risk factor for patient death (OR 2.19, 95% CI 1.14 - 4.20, p = 0.019), but not significant for graft loss (OR 1.64, 95% CI 0.94 - 2.86, p = 0.079). Of the 26 hepatitis B e antigen (HBeAg)-positive patients, 14 experienced HBV reactivations, but all survived with stable liver chemistry, except for one who died of hepatocellular carcinoma. Among 57 HBeAg-negative patients, 12 died, whereas the remaining 45 survived without hepatic dysfunction. CONCLUSION: Long-term outcomes of HBV-positive KTRs may be favorable after antiviral agents have been introduced.

Long-term impact of prophylactic antiviral treatment in Hepatitis B surface antigen positive renal allograft recipients.

BACKGROUND: Antiviral prophylaxis has been shown to prevent hepatic dysfunction in Hepatitis B virus (HBV)-positive kidney transplantation recipients (KTRs). However the long-term effects of antiviral prophylaxis on the patient death, graft loss, or hepatic decompensation have not been determined. METHOD: We therefore retrospectively analyzed outcomes in 94 HBV-positive patients, who underwent KT between February 1997 and November 2009 and were followed-up for a mean 75.7 months. Of the 94 KTRs, 56 received antiviral prophylaxis (Group 1), 51 with lamivudine and 5 with entecavir, and 38 did not (Group 2). RESULT: Of the latter group, 20 experienced HBV reactivation and 18 did not (mean 85 months); of those with reactivation, 16 received lamivudine, 2 received entecavir and 2 received no antiviral treatment. Cox-regression analysis showed that antiviral prophylaxis had no benefit on patient death (OR 1.29, 95% CI 0.37 - 4.49, p = 0.693), graft failure (OR 1.25, 0.45 - 3.46, p = 0.666) or hepatic decompensation (OR 2.01, 0.35 - 11.57, p = 0.434). Lamivudine resistance occurred in 21 lamivudine-treated Group 1 and 4 lamivudine-treated Group 2 patients (p = 0.243), with mean times of resistance after KT of 82 and 132 months, respectively (p = 0.001). CONCLUSION: These findings indicate that lamivudine-based antiviral prophylaxis for HBV-positive renal recipients has no long-term clinical benefits.

Assessment of the influence of severe renal impairment on the pharmacokinetics of mirodenafil in Korean male volunteers.

OBJECTIVE: To evaluate and compare the pharmacokinetics and tolerability of a single oral dose of mirodenafil in volunteer patients with severe renal impairment and healthy volunteers. METHODS AND MATERIALS: This open-label, single-dose, parallel group clinical study enrolled a total 12 volunteers (6 healthy volunteers and 6 volunteer patients with severe renal impairment). Each volunteer was orally administered 50 mg mirodenafil and serial blood samples were obtained after drug administration to determine the plasma concentration of mirodenafil using LC-MS/MS. The measured individual plasma concentrations were used to calculate the pharmacokinetic parameters using noncompartmental methods. Tolerability was also assessed using measurements of vital signs, clinical chemistry tests, and interviews. RESULTS: All of the volunteers completed the study with no serious adverse events (AEs). A total of 4 AEs were reported, but all were of mild or moderate intensity and not considered to be related to the study drug. The geometric mean (95% CI) of the terminal half-life (t1/2ß) and the apparent clearance (CL/F) values of mirodenafil were 2.2 (1.4 - 3.4) h and 127.2 (95.1 - 170.2) l/h in the volunteer patients, and 3.0 (2.1 - 4.4) h and 136.1 (74.4 - 249.2) l/h in the healthy volunteers, respectively. The geometric mean of the AUC0-t of the volunteer patients was 8% higher and the geometric mean for clearance was 7% lower compared with the healthy volunteers. However, the geometric mean of the Cmax of the volunteer patients was 38% higher than that of the healthy volunteers. CONCLUSIONS: A single oral 50-mg dose of mirodenafil was well tolerated. Exposure (AUC0-t) to mirodenafil was similar in both healthy volunteers and volunteer patients with severe renal impairment and healthy volunteers.

Albumin-induced epithelial-mesenchymal transition and ER stress are regulated through a common ROS-c-Src kinase-mTOR pathway: effect of imatinib mesylate.

The epithelial-mesenchymal transition (EMT) and endoplasmic reticulum (ER) stress induced by urinary protein, particularly albumin, play an important role in tubulointerstitial injury. However, signaling pathways regulating both albumin-induced EMT and ER stress are not precisely known. We postulated that reactive oxygen species (ROS), c-Src kinase, and mammalian target of rapamysin (mTOR) would act as upstream signaling molecules. We further examined the effect of imatinib mesylate on these processes. All experiments were performed using HK-2 cells, a human proximal tubular cell line. Protein and mRNA expression were measured by Western blot analysis and real-time PCR, respectively. Exposure of tubular cells to albumin (5 mg/ml) for up to 5 days induced EMT in a time-dependent manner, as shown by conversion to the spindle-like morphology, loss of E-cadherin protein, and upregulation of α-smooth muscle actin mRNA and protein. Albumin also induced ER stress as evidenced by phosphorylation of eukaryotic translation initiation factor-2α and increased expression of GRP78 mRNA and protein. Albumin induced ROS, c-Src kinase, and mTOR as well. Antioxidants, c-Src kinase inhibitor (PP2), and mTOR inhibitor (rapamycin) suppressed the albumin-induced EMT and ER stress. Antioxidants and PP2 inhibited the albumin-induced c-Src kinase and mTOR, respectively. Imatinib suppressed the albumin-induced EMT and ER stress via inhibition of ROS and c-Src kinase. Imatinib also inhibited the albumin-induced mRNA expression of MCP-1, VCAM-1, transforming growth factor (TGF)-ß1, and collagen I (α1). In conclusion, the ROS-c-Src kinase-mTOR pathway played a central role in the signaling pathway that linked albumin to EMT and ER stress. Imatinib might be beneficial in attenuating the albumin-induced tubular injury.

Uric acid contributes to glomerular filtration rate deterioration in renal transplantation.

BACKGROUND: Many studies have been performed in kidney transplant recipients to test whether hyperuricemia plays a role in decreased kidney function, but the results have been controversial. We conducted a retrospective cohort study to assess the predictors of hyperuricemia and how uric acid (UA) influences glomerular filtration rate (GFR) changes. METHODS: 556 patients who underwent kidney transplantation between January 1, 1990 and February 24, 2009, were included. Serum UA levels were routinely recorded every 3 months after transplantation. Hyperuricemia was defined as serum UA ≥ 6.0 mg/dl for women, and ≥ 7.0 mg/dl for men. A time-dependent covariate Cox model was used to assess the association of serial changes of estimated GFR (eGFR) and UA. RESULTS: Multivariate analysis indicated that male gender, eGFR, and transplant duration were associated with higher mean UA levels. A time-dependent covariate Cox model indicated that initial eGFR level (hazard ratio: 1.001; p = 0.035) and previous UA level (hazard ratio: 1.454; p < 0.001) affected the subsequent eGFR level. CONCLUSIONS: Our results indicated a predictive relationship between UA and eGFR based on the results of a time-dependent covariate Cox model that elevated serum UA precedes a graft dysfunction in kidney transplant recipients.

TEM sample preparation of microsized LiMn2O4 powder using an ion slicer.

The main purpose of this paper is the preparation of transmission electron microscopy (TEM) samples from the microsized powders of lithium-ion secondary batteries. To avoid artefacts during TEM sample preparation, the use of ion slicer milling for thinning and maintaining the intrinsic structure is described. Argon-ion milling techniques have been widely examined to make optimal specimens, thereby making TEM analysis more reliable. In the past few years, the correction of spherical aberration (Cs) in scanning transmission electron microscopy (STEM) has been developing rapidly, which results in direct observation at an atomic level resolution not only at a high acceleration voltage but also at a deaccelerated voltage. In particular, low-kV application has markedly increased, which requires a sufficiently transparent specimen without structural distortion during the sample preparation process. In this study, sample preparation for high-resolution STEM observation is accomplished, and investigations on the crystal integrity are carried out by Cs-corrected STEM.

Myoglobin induces vascular cell adhesion molecule-1 expression through c-Src kinase-activator protein-1/nuclear factor-kappaB pathways.

BACKGROUND/AIMS: It is not clear whether a sublethal dose of myoglobin induces some pathophysiological changes in tubular cells, potentially affecting tubular injury or tubular regeneration. We investigated the effect of a low dose of myoglobin on vascular cell adhesion molecule-1 (VCAM-1) expression and elucidated the underlying signaling pathways. We further examined the effect of losartan and simvastatin on myoglobin-induced VCAM-1 expression and the signaling pathways. METHODS: Activation of nuclear factor (NF)-kappaB and activator protein (AP)-1 was assessed by electrophoretic mobility shift assay. Phosphorylation of protein kinases was examined by Western blot analysis. VCAM-1 mRNA and protein were measured by Northern blot analysis and cell ELISA. RESULTS: A sublethal dose of myoglobin (100 microg/ml) induced VCAM-1 expression via activation of AP-1 and NF-kappaB, which was mediated through activation of c-Src kinase, followed by mitogen-activated protein kinases (p38, ERK 1/2, JNK-1) and the I kappaB kinase - I kappaB-alpha. Inhibitors of protein kinase C and tyrosine kinase, antioxidants and intracellular calcium chelator suppressed myoglobin-induced activation of c-Src kinase. Losartan and simvastatin suppressed myoglobin-induced VCAM-1 expression via inhibition of c-Src kinase. CONCLUSION: VCAM-1 expression via c-Src kinase-AP-1/NF-kappaB pathways might be one of the possible mechanisms linking myoglobin to tubular injury. Losartan and simvastatin might be beneficial in attenuating myoglobin-induced tubular injury.

Fatty acid-bearing albumin induces VCAM-1 expression through c-Src kinase-AP-1/NF-kB pathways: effect of L-carnitine.

BACKGROUND: Fatty acid-bearing albumin [FA(+) albumin] exerts more deleterious effects in tubular cells than albumin alone. We investigated the effect of FA(+) albumin on the vascular cell adhesion molecule-1 (VCAM-1) expression and elucidated the underlying signaling pathways. We further examined the effect of L-carnitine, since it was known to modulate intracellular fatty acid concentration. METHODS: Activation of AP-1 and NF-kappaB was assessed by electrophoretic mobility shift assay. Phosphorylation of protein kinase was examined by Western blot analysis. VCAM-1 mRNA and protein expression were measured by Northern blot analysis and cell ELISA. RESULTS: FA(+) albumin induced VCAM-1 expression via activation of AP-1 and NF-kappaB, which was mediated through activation of c-Src kinase, followed by MAP kinases (p38, ERK 1/2, JNK-1) and IkappaB kinase and IkappaB-alpha, respectively. Inhibitors of protein kinase C and tyrosine kinase, anti-oxidants and intracellular calcium chelator suppressed the FA(+) albumin-induced activation of c-Src kinase. L-Carnitine suppressed the FA(+) albumin-induced VCAM-1 expression via inhibition of c-Src kinase. CONCLUSIONS: VCAM-1 expression with activation of c-Src kinase-AP-1/NFkappaB pathways might be one of the possible mechanisms that linked FA(+) albumin to tubulointerstitial injury. L-Carnitine might be beneficial in attenuating FA(+) albumin-induced tubular injury.

Desmopressin improves platelet dysfunction measured by in vitro closure time in uremic patients.

BACKGROUND/AIMS: Desmopressin decreases bleeding time in uremic patients. Although bleeding time is the most frequently used measure of global platelet function, this test has important disadvantages. In vitro closure time (CT) is a relatively new and efficient test of primary hemostasis. We designed a prospective randomized study to evaluate the effect of desmopressin on platelet function, as measured by in vitro CT, in uremic patients. METHODS: Forty-eight uremic patients, about to commence hemodialysis and with prolonged CT, were randomized to infusion with desmopressin (n = 24) or saline alone (n = 24). Complete blood count, prothrombin time, activated partial thrombin time, levels of plasma fibrinogen, von Willebrand factor (VWF), factor VIII (FVIII) and CT were measured before and 1 h after desmopressin or saline infusion. RESULTS: Following desmopressin infusion, collagen/epinephrine and collagen/adenosine diphosphate CT were significantly shortened from 212 +/- 58 to 152 +/- 45 s (p = 0.01) and from 189 +/- 78 to 147 +/- 58 s (p = 0.012), respectively; levels of FVIII and VWF were significantly increased from 188 +/- 66 to 252 +/- 93% (p = 0.017) and from 113 +/- 9 to 121 +/- 9% (p = 0.043), respectively. There were no significant changes in the control group. CONCLUSIONS: Desmopressin improved platelet dysfunction and increased the plasma concentrations of VWF and FVIII, suggesting that desmopressin may play a role in improving the bleeding tendency in uremic patients.

Suitability of the IDMS-traceable MDRD equation method to estimate GFR in early postoperative renal transplant recipients.

BACKGROUND/AIMS: Accurate measurement of glomerular filtration rate (GFR) is critical for the management of kidney transplant recipients. Comparison of creatinine and cystatin C in renal transplant recipients gave conflicting results. We aimed to compare the performance of creatinine- and cystatin C-based equations and creatinine clearance in 102 early postoperative Korean renal transplant patients. METHODS: We measured (51)Cr-EDTA clearance using a 2-compartment model and considered this the reference GFR. Then, we estimated GFR using 13 creatinine- and 7 cystatin C-based equations. Serum creatinine value was calibrated to isotope-dilution mass spectrometry (IDMS). RESULTS: The mean reference GFR was 76.77 +/- 17.01 ml/min/1.73 m(2). The IDMS-traceable MDRD (IDMS-MDRD) equation had the highest accuracy (94.12 within 30% of the reference; 99.02 within 50% of the reference) with a bias of 0.33 ml/min/1.73 m(2) and a precision of 12.57 ml/min/1.73 m(2). The Mayo Clinic equation also performed well (92.16% within 30% of the reference; 99.02% within 50% of the reference; bias: -0.19 ml/min/1.73 m(2)). As for cystatin C-based equations, the Filler equation had the least bias (0.03 ml/min/1.73 m(2)) but low accuracy (78.43% within 30% of the reference). CONCLUSIONS: We conclude that the IDMS-MDRD equation provided the best estimate of GFR in our early postoperative Korean renal transplant patients.

Minipterional craniotomy for surgical clipping of anterior circulation aneurysms: compatibility between the feasibility, safety and efficiency.

OBJECTIVE: The aim of this study was to assess the feasibility, safety and efficiency of minipterional craniotomy (MPT) for surgical clipping of anterior circulation aneurysms. METHODS: A retrospective study was conducted to compare the MPT from Jan 2015 to Dec 2018 and conventional pterional craniotomy (CPT) from Jan 2012 to Dec 2013 in unruptured intracranial aneurysms (UIA) and ruptured intracranial aneurysms (RIA). The feasibility and safety of MPT and CPT were assessed by analyzing medical records, radiologic imaging, and clinical outcomes. The efficiency of MPT and CPT were based on a survey research of temporomandibular dysfunction, facial nerve paralysis, and facial asymmetry. RESULTS: Total 628 patients who underwent 458 MPT (UIA:313, RIA:145) and 170 CPT (UIA: 106, RIA: 64) with anterior circulation aneurysms were included in this study. The baseline characteristics between MPT and CPT had no difference (p>0.05). There was no difference in the incidence of postoperative hemorrhage or ischemic lesions between MPT and CPT (p>0.05). The incidence of surgical wound infection was lower in MPT (0.4%) than CPT (3.5%) (p=0.002). More than 90% of postoperative pain disappeared faster in MPT (14.25±4.83 days) than CPT (27.59±10.35 days), and the feeling of facial asymmetry in surgical side was also lower for MPT (1.7%) than CPT (7.6%) (p<0.001). In the MPT, no patients presented with progress to chronic pain, masticatory disability, discomfort of maximal mouth opening or permanent facial palsy. CONCLUSIONS: We suggest that MPT and CPT had similar clinical outcomes, and MPT showed better functional and cosmetic outcomes than CPT in terms of temporomandibular dysfunction, facial nerve paralysis, and facial asymmetry. Therefore, MPT for surgical clipping of anterior circulation aneurysms can be a compatible technique that satisfies the feasibility, safety and efficiency.

Cervical spinal extradural arteriovenous fistula successfully treated using transarterial balloon-assisted coil embolization.

We present the case of a patient who developed compressive radiculopathy that was found to be associated with a spinal extradural arteriovenous fistula. The fistula was successfully obliterated with transarteiral balloon-assisted coiling, after which the patient was symptom-free. Although spinal extradural arteriovenous fistula is rare, this pathology should be considered in the differential diagnosis of spinal radiculopathy or myelopathy. Endovascular treatment appears to have been successful in resolving the symptoms associated with this pathology.