Publications (9)38.23 Total impact
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Article: Correlates of osteoprotegerin and association with aortic pulse wave velocity in patients with chronic kidney disease.
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ABSTRACT: Osteoprotegerin (OPG), a cytokine that regulates bone resorption, has been implicated in the process of vascular calcification and stiffness. Serum OPG was measured in 351 participants with chronic kidney disease (CKD) from one site of the Chronic Renal Insufficiency Cohort Study. Cortical bone mineral content (BMC) was measured by quantitative computed tomography in the tibia. Multivariable linear regression was used to test the association between serum OPG and traditional cardiovascular risk factors, measures of abnormal bone and mineral metabolism, and pulse wave velocity. Higher serum OPG levels were associated with older age, female gender, greater systolic BP, lower estimated GFR, and lower serum albumin. OPG was not associated with measures of abnormal bone or mineral metabolism including serum phosphorus, albumin-corrected serum calcium, intact parathyroid hormone, bone-specific alkaline phosphatase, or cortical BMC. Among 226 participants with concurrent aortic pulse wave velocity measurements, increasing tertiles of serum OPG were associated with higher aortic pulse wave velocity after adjustment for demographics, traditional vascular risk factors, and nontraditional risk factors such as estimated GFR, albuminuria, serum phosphate, corrected serum calcium, presence of secondary hyperparathyroidism, serum albumin, and C-reactive protein or after additional adjustment for cortical BMC in a subset (n = 161). These data support a strong relationship between serum OPG and arterial stiffness independent of many potential confounders including traditional cardiovascular risk factors, abnormal bone and mineral metabolism, and inflammation.Clinical Journal of the American Society of Nephrology 09/2011; 6(11):2612-9. · 5.23 Impact Factor -
Article: Orthogonal, spectroscopic high throughput screening of laccase-catalyzed p-cresol oxidation.
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ABSTRACT: There is considerable interest in the oxidative fate of phenols such as p-cresol as environmental pollutants and uremic toxins. We supply a menu of spectroscopic options for the high throughput screening of laccase oxidation of p-cresol through multiple modes of detection. Laccase activity was monitored kinetically at pH 4.5 by absorption changes at 250 nm, 274 nm or 297 nm, and in endpoint mode by the bathochromic shift in absorption to 326 nm in 50 mM NaOH. Laccase oxidation of p-cresol was also detected by product fluorescence at 425 nm after excitation at 262 nm or 322 nm in 50 mM NaOH. We optimized the kinetic parameters for p-cresol oxidation (pH optimum 4.5-5.1; 37 degrees C; Km = 2.2 mM) resulting in laccase limits of detection and quantitation of 25 pg/microL and 75 pg/microL, respectively (approximately 360 pM; 25 ppb). The sensitivity for p-cresol was similar to previously reported values. The small (approximately 20%) decrease in signal strength after six cycles of excitation over a 3 h period was attributed to photobleaching or photodegradation of the emitter and not due to fluorescence decay (photoinstability). Halide inhibition was characteristic of laccases (IC(50) = 25 mM NaCl). A unique advantage of our assay is that laccase catalysis could be interrogated using multi-mode absorption or fluorescence under acidic or basic conditions, in real time or endpoint modes. Orthogonal interrogation facilitates ratiometric analysis enabling high specificity while minimizing interferences during compound library screening. The phenolic alcohol p-cresol may be a model for monolignol oxidation. Our studies might find applications in biofuels, to triage dialysis patients, or for the environmental bioremediation of phenols.Combinatorial chemistry & high throughput screening 09/2009; 12(7):678-89. · 2.46 Impact Factor -
Article: Fabrication and testing of a microneedles sensor array for p-cresol detection with potential biofuel applications.
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ABSTRACT: We present a miniaturized high-throughput sensor array that will augment biofuel technology by facilitating in situ biochemical measurements upon micrometer-scale surfaces of leaves, stems, or petals. We used semiconductor processing to photopattern Foturan glass wafers and fabricated gold-plated microscopic electrode needles (ElectroNeedles) that pierced 125-mum-thick surfaces without deformation. The 5 x 5 or 10 x 10 arrays of ElectroNeedles can analyze 25 or 100 samples simultaneously, increasing throughput. Each microneedle in the array can also be individually addressed and selectively functionalized using diazonium electrodeposition, conferring multiplexing capability. Our microfabrication is a simple, inexpensive, and rapid alternative to the time-, cost-, and protocol-intense, deep-reactive-ion-etching Bosch process. We validated the system performance by electrochemically detecting p-cresol, a phenolic substrate for laccase, an enzyme that is implicated in lignin degradation and therefore important to biofuels. Our limits of detection (LOD) and quantization (LOQ) for p-cresol were 1.8 and 16microM, respectively, rivaling fluorescence detection (LOD and LOQ = 0.4 and 3microM, respectively). ElectroNeedles are multiplexed, high-throughput, chip-based sensor arrays designed for minimally invasive penetration of plant surfaces, enabling in situ and point-of-test analyses of biofuel-related biochemicals.ACS Applied Materials & Interfaces 07/2009; 1(7):1591-8. · 4.53 Impact Factor -
Article: Genetic polymorphisms of the RAS-cytokine pathway and chronic kidney disease.
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ABSTRACT: Chronic kidney disease (CKD) in children is irreversible. It is associated with renal failure progression and atherosclerotic cardiovascular (CV) abnormalities. Nearly 60% of children with CKD are affected since birth with congenital or inherited kidney disorders. Preliminary evidence primarily from adult CKD studies indicates common genetic risk factors for CKD and atherosclerotic CV disease. Although multiple physiologic pathways share common genes for CKD and CV disease, substantial evidence supports our attention to the renin angiotensin system (RAS) and the interlinked inflammatory cascade because they modulate the progressions of renal and CV disease. Gene polymorphisms in the RAS-cytokine pathway, through altered gene expression of inflammatory cytokines, are potential factors that modulate the rate of CKD progression and CV abnormalities in patients with CKD. For studying such hypotheses, the cooperative efforts among scientific groups and the availability of robust and affordable technologies to genotype thousands of single nucleotide polymorphisms (SNPs) across the genome make genome-wide association studies an attractive paradigm for studying polygenic diseases such as CKD. Although attractive, such studies should be interpreted carefully, with a fundamental understanding of their potential weaknesses. Nevertheless, whole-genome association studies for diabetic nephropathy and future studies pertaining to other types of CKD will offer further insight for the development of targeted interventions to treat CKD and associated atherosclerotic CV abnormalities in the pediatric CKD population.Pediatric Nephrology 08/2008; 23(7):1037-51. · 2.52 Impact Factor -
Article: Effect of intravenous iron supplementation on hepatic cytochrome P450 3A4 activity in hemodialysis patients: a prospective, open-label study.
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ABSTRACT: Cytochrome P450 (CYP) 3A4 is an enzyme with activity dependent on the reduction of heme iron that is responsible for the metabolism of many drugs. CYP3A4 activity is reduced in hemodialysis (HD) patients and thus may be related to functional iron deficiency. The purpose of this study was to investigate the effect of IV iron supplementation on hepatic is CYP3A4 activity in HD patients. This prospective, open-label study was conducted in 12 iron-deficient (transferrin saturation <20% or ferritin <100 ng/L) HD patients on stable medication regimens. To probe for hepatic CYP3A4 activity, an erythromycin breath test (ERMBT) was administered before and after 1 g IV iron sucrose (administered as a 100-mg dose [20 mg/mL]), at each of 10 consecutive HD sessions). CYP3A4 activity was estimated by the percentage of administered (14)C exhaled in a single-breath collection after the test dose of erythromycin underwent demethylation by CYP3A4. The ERMBT was also administered to 7 age-, sex-, and race-matched healthy controls. Twelve HD patients (6 Hispanic, 3 white, 3 Native American; 8 men, 4 women; mean [SEM] age, 56.2 [5.0] years; mean [SEM] weight, 77.0 [5.6] kg; and 7 controls (4 men, 3 women; mean [SEM] age, 51.3 [5.0] years; mean [SEM] weight, 77.5 [7.4] kg) were enrolled in the study. In the total HD population studied, mean (SEM) CYP3A4 activity did not change significantly after IV iron replacement (1.46 [0.27] vs 1.57 [0.24] (14)C exhaled/h). A subgroup of 7 HD patients had significantly lower CYP3A4 activity before IV iron replacement compared with the other 5 HD patients and controls (mean [SEM] 0.86 [0.24] vs 2.30 [0.26] and 2.10 [0.26] (14)C exhaled/h; P < 0.01). After IV iron replacement, mean (SEM) CYP3A4 activity increased in these 7 HD patients (120.1% [67.1%]); P = 0.04) and it was not statistically different from that of controls (1.50 [0.36] vs 2.10 [0.26]). Overall, IV iron administration had no significant effect on hepatic CYP3A4 activity. However, in a subset of HD patients with low baseline CYP3A4 activity indicated by low ERMBT values, IV iron supplementation was associated with a potentially clinically relevant increase in hepatic CYP3A4 activity. Further studies are needed to clarify mechanisms and clinical implications of this interaction.Clinical Therapeutics 12/2007; 29(12):2699-705. · 2.32 Impact Factor -
Article: Renin-angiotensin polymorphisms and QTc interval prolongation in end-stage renal disease.
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ABSTRACT: Polymorphisms of renin-angiotensin system (RAS) genes in patients with end-stage renal disease (ESRD) on chronic hemodialysis may be associated with QTc interval prolongation, leading to fatal arrhythmias. The objective of this study was to determine (1) the prevalence of QTc prolongation in hemodialysis patients, and (2) the association of a prolonged QTc in these patients with RAS polymorphisms [angiotensin-converting enzyme-insertion/deletion (ACE-I/D), angiotensin type 1 receptor-A1166C (AT1R-A1166C), and angiotensinogen-M235T (AGT-M235T)]. Twelve-lead electrocardiograms (ECGs), serum electrolytes (sodium, potassium, and calcium), and ACE and angiotensin II levels were obtained 10 to 12 hours after a hemodialysis session in 43 patients with ESRD on chronic hemodialysis [mean age (+/-SD), 55 +/- 14 years]. Using polymerase chain reaction (PCR), the presence of polymorphisms of the ACE-I/D, AT1R-A1166C, and AGT-M235T genes was determined from the buccal cells. A maximum QT interval in patients with sinus rhythm and normal QRS duration was corrected for heart rate using Hodges' formula. Fifty-eight percent of the patients had QTc interval prolongation (>440 msec). The ACE-DD genotype (P = 0.002) and the C allele of the AT1R-A1166C gene (P = 0.004), but not the AGT-M235T gene, contributed to QTc prolongation. Polymorphisms of ACE and AT1R genes additively contribute to QTc prolongation found in a great majority of ESRD patients. Therefore, ESRD patients with both or one of these polymorphisms may be at a higher risk for sudden cardiac death.Kidney International 10/2005; 68(3):1186-9. · 6.61 Impact Factor -
Article: Renin-angiotensin polymorphisms and QTc interval prolongation in end-stage renal disease
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ABSTRACT: Renin-angiotensin polymorphisms and QTc interval prolongation in end- stage renal disease.Background Polymorphisms of renin-angiotensin system (RAS) genes in patients with end-stage renal disease (ESRD) on chronic hemodialysis may be associated with QTc interval prolongation, leading to fatal arrhythmias. The objective of this study was to determine (1) the prevalence of QTc prolongation in hemodialysis patients, and (2) the association of a prolonged QTc in these patients with RAS polymorphisms [angiotensin-converting enzyme-insertion/deletion (ACE-I/D), angiotensin type 1 receptor-A1166C (AT1R-A1166C), and angiotensinogen-M235T (AGT-M235T)].Kidney International 08/2005; 68(3):1186-1189. · 6.61 Impact Factor -
Article: Amino acid control of muscle protein turnover in renal disease.
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ABSTRACT: This review discusses the concept that skeletal muscle intracellular amino acids (ICAAs), in particular the essential amino acids, are regulated throughout a wide range of physiologic circumstances. Whether in critical illness, severe injury, or healthy states, ICAAs are closely regulated by a coordinated response in 1 or more of the processes of synthesis, breakdown, and tissue transport. For a given metabolic signal (hormonal, change in plasma amino acid concentrations), the regulation of ICAAs entails appropriate and corresponding changes in amino acid kinetics. These changes vary according to the strength of the metabolic signal and the existing requirement to maintain the ICAA pool. For the patient with end-stage renal disease (ESRD), frequent dialysis induces an abrupt removal of half of the circulating amino acids, which in turn results in a substantial efflux of amino acids from skeletal muscle. ICAAs are maintained through the increase in protein breakdown, and similar to other stress states, there is a concomitant increase in protein synthesis. Thus, the regulation of ICAAs often pushes subsequent adaptations in amino acid kinetics to maintain the existing homeostasis. This regulatory mechanism is evident in circumstances ranging from increased amino acid availability in healthy volunteers to a change in anabolic signal in severe injury. Despite the substantial evidence of ICAA regulation, its physiologic significance is not evident. However, the regulation of ICAAs represents a method by which skeletal muscle ensures its capacity for anabolism.Journal of Renal Nutrition 02/2005; 15(1):34-8. · 1.57 Impact Factor -
Article: Metabolic alkalosis after orthotopic liver transplantation.
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ABSTRACT: To ascertain the etiology of metabolic alkalosis (MA) following orthotopic liver transplantation (OLT) the records of patients with 123 consecutive OLTs from 1995 to 2000 were reviewed. Metabolic alkalosis occurred in 51.2% of patients. Patients with MA had a larger fluid deficit (-3991 +/- 4324 vs. -1018 +/- 4863, p < 0.05), cumulative furosemide dose (406 +/- 356 vs. 243 +/- 189, p < 0.02), and citrate load from blood transfusions (9164 +/- 4870 vs. 7809 +/- 3967, p < 0.05). There was no difference in serum lactate concentration (3.15 +/- 1.63 vs. 3.11 +/- 1.91) in patients with and without MA. The duration of ICU stay was longer in patients with MA (14.9 +/- 15.3 vs. 5.3 +/- 3.9 days, p < 0.004). Treatment of severe MA in 19 (15.4%) patients consisted of 0.1 N hydrochloric acid and/or acetazolamide. Hypokalemia and hypomagnesemia occurred in 37.4% and 59.3% of patients, respectively. In conclusion, MA is a common post-OLT complication that is associated with a longer ICU stay. Diuretic-induced volume depletion, the citrate load from blood transfusions, hypokalemia, and hypomagnesemia contribute to the pathogenesis of MA in OLT.American Journal of Transplantation 01/2004; 3(12):1566-9. · 6.39 Impact Factor
Top co-authors
Top Journals
Institutions
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2009
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Sandia National Laboratories
Albuquerque, NM, USA
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2008
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University of New Mexico
- Department of Pediatrics
Albuquerque, NM, USA
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