scholarly journals Xanthine Oxidoreductase Activity Is Correlated With Hepatic Steatosis

Author(s):  
Chisako Yagi ◽  
Yoshiki Kusunoki ◽  
Taku Tsunoda ◽  
Takayo Murase ◽  
Takashi Nakamura ◽  
...  

Abstract The enzyme xanthine oxidoreductase (XOR) catalyzes the formation of uric acid (UA) from hypoxanthine and xanthine, which in turn are products of purine metabolism starting from ribose-5-phosphate. Several studies suggested a relationship between hyperuricemia and hepatic steatosis; however, few previous studies have directly examined the relationship between XOR and hepatic steatosis. A total of 223 subjects with one or more cardiovascular risk factors were enrolled. Hepatic steatosis was calculated according to the liver-to-spleen (L/S) ratio on computed tomography and the hepatic steatosis index (HSI). We measured a plasma XOR activity assay using a newly established highly sensitive assay based on [13C2, 15N2] xanthine and liquid chromatography/triple quadrupole mass spectrometry. XOR activity and the UA level were increased in subjects with L/S ratio <1.1 and HSI <36. Multivariate logistic regression analysis indicated that plasma XOR activity was associated with the risk of hepatic steatosis as assessed by the L/S ratio and HSI independently of insulin resistance, whereas UA levels were not associated with risk of hepatic steatosis. The results of this study indicated that plasma XOR activity is associated with hepatic steatosis independently of insulin resistance and serum UA levels.

2015 ◽  
Vol 39 (1-3) ◽  
pp. 224-229 ◽  
Author(s):  
Sung Jin Moon ◽  
Jung Eun Lee ◽  
Jwa-Kyung Kim ◽  
Soo Young Yoon ◽  
Shin Wook Kang ◽  
...  

Background: Although various modalities of hemodialysis (HD) are presumed to have different effects on insulin resistance (IR), the relationship between hemodiafiltration (HDF) and IR has not been fully evaluated. Methods: In a cross-sectional study, 82 non-diabetic HD patients were enrolled. The patients were divided into two groups according to the median homeostasis model assessment index (HOMA-IR) value of 1.685. Clinical and biochemical data were compared, and multivariate logistic regression analysis was performed to identify the independent factors associated with higher HOMA-IR. Results: The higher HOMA-IR group had increased body mass index (BMI), decreased HDL cholesterol, and lower beta-2 microglobulin reduction rate (β2-MG RR) compared to the lower HOMA-IR group. HOMA-IR was significantly correlated with β2-MG RR. In addition, HDF patients had lower HOMA-IR levels compared with low flux hemodialysis patients. On multivariate logistic regression analysis, BMI and HDF treatment were independent factors associated with higher and lower HOMA-IR, respectively. Conclusion: This study suggests that HDF treatment may reduce IR in non-diabetic HD patients.


Hypertension ◽  
2013 ◽  
Vol 62 (suppl_1) ◽  
Author(s):  
Cheng Wang ◽  
Jun Zhang ◽  
Cuicui Li ◽  
Wenyu Gong ◽  
Tanqi Lou

Background: Neural precursor cell expressed developmentally down-regulated 4-like (NEDD4L) is a candidate gene for hypertension, and carriers of an intact NEDD4L C2-domain,encoded by the NEDD4L rs4149601 (G/A) GG genotype, together with the C-allele of the NEDD4L rs2288774 (C/T) polymorphism have been found be associated with hypertension both in African Americans and whites. However, there is no data on the relationship between polymorphism of NEDD4L rs4149601 and rs2288774 and hypertension in Chinese chronic kidney disease (CKD) patients. The purpose of the current study was to investigate the relationship between the variation of NEDD4L rs4149601, rs2288774 and hypertension in CKD patients. Methods: A total of 546 Chines Hans CKD patients were enrolled in our study. The SNPs were genotyped using PCR-based techniques. All patients underwent ambulatory blood pressure monitoring, and clinical data were also collected. Multivariate logistic regression analysis was used to identify the relationship between polymorphisms and hypertension. Results: 506 patients carried GG/GA genotype and 30 carried AA genotype. Rs4149601 AA genotype carriers had significantly higher rate of hypertension (68.3% vs 46.2%, P = 0.022) than GG/GA genotype carriers by Chi-squared test. AA genotype carriers also had a higher day-time and bedtime systolic blood pressure (142±16 vs 135±23, P=0.036; 137±18 vs 127±13, P=0.022, respectively) when compared with GG/GA genotype carriers. AA genotype [OR= 3.08, 95% CI (1.06-9.80)], lowever eGFR [OR=0.98, 95% CI (0.97-0.99)], older age [OR=1.03, 95% CI (1.01-1.05)] were independently associated with hypertension in CKD patients by multivariate logistic regression. However, No difference was found in blood pressure with rs2288774 TT/TC/CC genotypes, and no difference was found in the incidence of hypertension among patients with three genotypes. Conclusions: Our results suggested 4149601AA genotype of NEDD4L may be associated with hypertension in CKD patients, and further genetic and functional studies are required to understand its role in the manifestation of hypertension in Chinese CKD patients.


1999 ◽  
Vol 276 (5) ◽  
pp. E990-E994 ◽  
Author(s):  
Jack F. Youngren ◽  
Ira D. Goldfine ◽  
Richard E. Pratley

In a previous study [Youngren, J. F., I. D. Goldfire, and R. E. Pratley. Am. J. Physiol. 273 ( Endocrinol. Metab. 36): E276–E283, 1997] of skeletal muscle biopsies from insulin-resistant, nondiabetic Pima Indians, we demonstrated that diminished insulin receptor (IR) autophosphorylation correlated with in vivo insulin resistance. In the present study, to determine whether decreased IR function is a primary trait of muscle, and not secondary to an altered in vivo environment, we cultured myoblasts from 17 nondiabetic Pima Indians in whom insulin-stimulated glucose disposal (M) was measured during hyperinsulinemic-euglycemic glucose clamps. Myoblast IR autophosphorylation was determined by a highly sensitive ELISA. IR autophosphorylation directly correlated with M ( r = 0.56, P = 0.02) and inversely correlated with the fasting plasma insulin ( r = −0.58, P < 0.05). The relationship between M and IR autophosphorylation remained significant after M was adjusted for the effects of percent body fat (partial r = 0.53, P < 0.04). The relationship between insulin resistance and the capacity for myoblast IR autophosphorylation in nondiabetic Pima Indians suggests that variations in IR-signaling capacity may be intrinsic characteristics of muscle that contribute to the genetic component determining insulin action in this population.


Medicina ◽  
2020 ◽  
Vol 56 (10) ◽  
pp. 501
Author(s):  
Yeonghee Eun ◽  
Kyung-Do Han ◽  
Da Hye Kim ◽  
In Young Kim ◽  
Eun-Jung Park ◽  
...  

Background and objectives: Hyperuricemia is one of the well-known cardiovascular risk factors. There is a growing interest in the association between hyperuricemia and arrhythmia. We used the representative sample data of Korean population to study the association between hyperuricemia and heart rate irregularity (HRI) that reflects total arrhythmia. Materials and Methods: We performed weighted multivariate logistic regression analysis to assess the association between hyperuricemia and HRI. Results: Of the 10,827 subjects, 1308 (13.2%) had hyperuricemia and 130 (1%) had HRI. In the presence of hyperuricemia, HRI was three times higher than that in the absence of hyperuricemia (OR 2.98, 95% CI 1.71–5.18). The risk of HRI was highest in subjects with both hypertension and hyperuricemia. In the subgroup analysis, the association of hyperuricemia with HRI was most pronounced in the smoker group. Conclusions: Hyperuricemia was highly correlated with HRI in adult Korean representative sample data. Hyperuricemia was associated with a nearly tripled risk for HRI. Hypertension has a synergistic effect with hyperuricemia on HRI. Further research is warranted to clarify the relationship between hyperuricemia and arrhythmia and its mechanism.


Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 2209-2209
Author(s):  
Dick Chung ◽  
Lily Ding ◽  
Isabelle Amigues ◽  
Katuna Kadeishvili ◽  
Theresa Lo ◽  
...  

Abstract Background: Low MBL2 concentration and MBL2 genotype variants have been associated with an increased risk of infection in various clinical settings. Pulmonary infection is a major complication of HSCT. We examined the relationship of MBL genotypes with post-engraftment bacterial (B-PNA) and fungal (F-PNA) pneumonia Methods: Retrospective review of 236 non-consecutive, non-selected patients who underwent HSCT at MSKCC from 1/1/2000–4/30/2007. Microbiologically confirmed infections and pneumonias were recorded. Antifungal prophylaxis consisted of fluconazole 400 mg daily. Patients at high risk for mold infection received mold-active prophylaxis. After 1/1/2006 voriconazole was the first line anti-mold prophylaxis. Genotype was determined by PR-Melting Curve Analysis on blood or buccal swab specimens. MBL genotype was classified as wild-type: A/A (MBL-sufficient, MBL-S) or variant-type: A/O, O/O (MBL deficient, MBL-D). Patients were followed for up to 2 years. Statistical analysis: Fisher’s Exact test was used to compare the incidence rate between MBL-S and MBL-D patients. Multivariate logistical regression models were used to investigate the relationship between bacterial or fungal pneumonia and MBL genotype, matched related donor (MRD), myeloablative conditioning (MC) peripheral blood as stem cell source (PBSC), acute GVHD grade 2–4 (aGVHD). The results from Maximum Likelihood Estimates were summarized. Results: Transplant characteristics: 80% MC, 76% PBSC, 48.6% MRD. Incidence of aGVHD: 22.4%. MBL genotypes: One-hundred and forty-two (60%) patients were homozygous for wild-type MBL2 (AA), 85(36%) were heterozygous (A/0) and 9 (3.8%) were homozygous for variant genotypes (OO). Transplant characteristics, rates of GVHD, relapse-free and overall survival were similar between MBL-D and MBL-S. There was higher incidence of overall bacterial infections in MBL-D compared to MBL-S pts (47.87% vs 36.62%, p=0.1049). MBL-D had a higher incidence of B-PNA (12.7% vs 4.9%, p=0.048). In multivariate logistic regression analysis, MBL-D(p=0.04) and aGVHD(p=0.06) were likely associated with B-PNA. Rates of overall fungal infections and F-PNA were similar [among MBL-D and MBL-S pts (12.77% vs 9.86%, p=0.5277) and (8.51% vs 7.75%, p=0.1049) respectively]. In multivariate logistic regression analysis only aGVHD was statistically significantly associated with F-PNA p=0.0002. Conclusions: 1) MBL-D genotype was likely associated with increased risk of bacterial pneumonia. 2) MBL-D and aGVHD were risk factors for B-PNA. 3) Further analyses are in progress to evaluate the effect of MBL-D on fungal pneumonia in patients who received mold prophylaxis versus patients who did not receive mold prophylaxis. 4) Prospective studies are needed to assess the relative contribution of MBL-D genotype on the risk of pulmonary infection in HSCT.


2002 ◽  
Vol 283 (3) ◽  
pp. L563-L572 ◽  
Author(s):  
Andrew J. Ghio ◽  
Thomas P. Kennedy ◽  
Jacqueline Stonehuerner ◽  
Jacqueline D. Carter ◽  
Kelly A. Skinner ◽  
...  

The iron chelator deferoxamine has been reported to inhibit both xanthine oxidase (XO) and xanthine dehydrogenase activity, but the relationship of this effect to the availability of iron in the cellular and tissue environment remains unexplored. XO and total xanthine oxidoreductase activity in cultured V79 cells was increased with exposure to ferric ammonium sulfate and inhibited by deferoxamine. Lung XO and total xanthine oxidoreductase activities were reduced in rats fed an iron-depleted diet and increased in rats supplemented with iron, without change in the ratio of XO to total oxidoreductase. Intratracheal injection of an iron salt or silica-iron, but not aluminum salts or silica-zinc, significantly increased rat lung XO and total xanthine oxidoreductase activities, immunoreactive xanthine oxidoreductase, and the concentration of urate in bronchoalveolar fluid. These results suggest the possibility that the production of uric acid, a major chelator of iron in extracellular fluid, is directly influenced by iron-mediated regulation of the expression and/or activity of its enzymatic source, xanthine oxidase.


2015 ◽  
Vol 123 (5) ◽  
pp. 1145-1150 ◽  
Author(s):  
Keisuke Takanari ◽  
Yoshio Araki ◽  
Sho Okamoto ◽  
Hideyoshi Sato ◽  
Shunjiro Yagi ◽  
...  

OBJECT Intracranial revascularization surgeries are an effective treatment for moyamoya disease and other intracranial vascular obliterative diseases. However, in some cases, wound-related complications develop after surgery. Although the incidence of wound complication is supposed to be higher than that with a usual craniotomy, this complication has rarely been the focus of studies in the literature that report the outcomes of revascularization surgeries. Here, the relationship between intracranial revascularization surgeries and their complications is statistically assessed. METHODS Between October 2004 and February 2010, 71 patients were treated using cerebral revascularization surgeries on 98 sides of the head. The relationship between wound complications and operative technique was retrospectively assessed. Multivariate logistic regression analysis was performed to identify the risk factors of wound complication, including operative technique, age, sex, diabetes mellitus (DM), hypertension, hyperlipidemia, and smoking history. RESULTS In total, there were 21 (21.4%) operative wound complications. Of these 21 complications, there were 14 (66.7%) minor complications and 7 (33.3%) major complications. No statistically significant relationship was found between wound complications and any surgical procedure. A trend toward severer complications was demonstrated for the procedures that used both STA branches (“double” procedures) in comparison with the procedures that used only 1 STA branch (“single” procedures, p = 0.016, Cochran-Armitage trend test). Multivariate logistic regression analysis also revealed that double procedures demonstrated a significantly higher incidence of wound complications than single procedures (OR 3.087, p = 0.048). DM was found to be a risk factor for wound complication (OR 9.42, p = 0.02), but age, sex, hypertension, and hyperlipidemia were not associated with the incidence of complications. Even though the blood supply to the scalp is abundant due to 5 arteriovenous systems, sometimes cutaneous necrosis develops after intracranial revascularization surgeries. The galeal blood supply is thought to be crucial for preventing wound-related complications. Special care is also thought to be required for DM patients. CONCLUSIONS Revascularization surgeries seemed to demonstrate a higher risk of wound-related complications. Double-type procedures, which use both branches of the STA, and a history of DM were found to be risk factors for wound-related complications. Attention should be paid to the design of the galeal incision and vessel harvest line. Also, special attention should be paid to patients with DM.


2018 ◽  
Vol 2018 ◽  
pp. 1-7 ◽  
Author(s):  
Alessandro Ciresi ◽  
Valentina Guarnotta ◽  
Daniela Campo ◽  
Carla Giordano

Objective. In acromegaly, both lipotoxicity secondary to GH excess and insulin resistance have a significant impact on the liver. Ultrasonography has shown poor sensitivity in detecting hepatic steatosis and noninvasive methods have been proposed. We evaluated the hepatic steatosis index (HSI), a validated surrogate index of hepatic steatosis, and we correlated it with disease activity and insulin resistance. Design. Thirty-one patients with newly diagnosed acromegaly were studied at diagnosis and after 12 months of treatment with somatostatin receptor ligands. Methods. Glucose and insulin levels, surrogate estimates of insulin sensitivity, and hepatic steatosis through ultrasonography and HSI were evaluated. Results. At diagnosis, ultrasonography documented steatosis in 19 patients (61.2%) while 26 (83.8%) showed high HSI. After 12 months, both GH (p=0.033) and IGF-1 (p<0.001) significantly decreased and, overall, 58% of patients were classified as controlled. Ultrasonography documented steatosis in all the same initial 19 patients, while only 14 patients (45.1%) showed high HSI (p<0.001). A significant reduction in HOMA-IR (p=0.002) and HSI (p<0.001) and increased ISI Matsuda (p<0.001), was documented. The change of HSI from baseline to 12 months was found to be directly correlated with the change of ISI (Rho -0.611; p=0.004) while no correlation was found with the change of GH or IGF-1 levels and other parameters. Conclusions. In acromegaly, HSI is mainly related with insulin resistance and the reduction of GH and IGF-1 levels, and above all the improvement in insulin sensitivity leads to an improvement of this surrogate index of hepatic steatosis.


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