Metabolic abnormalities in acute renal failure, influence on nutritional management

No abstract available

Taxation of Oil and Gas in the United States 1970-1997

This article provides an extensive examination of all major types of taxes and royalties levied on the oil and gas industry by federal, state, and local governments in the United States during the 1970-1997 period. Important taxes levied on the oil and gas industry can be grouped into three broad categories based on their effects on resource extraction: (1) production, (2) property, and (3) income. Reliance on these three types of taxes differs substantially among the eight key states responsible for about 73 percent of U.S. oil and 83 percent of U.S. gas production (Alaska, California, Kansas, Louisiana, New Mexico, Oklahoma, Texas, and Wyoming). A detailed comparison of differences in institutional structure and effective tax rates for the eight major oil and gas producing states is presented

Signal regulatory protein alpha initiates cachexia through muscle to adipose tissue crosstalk

BACKGROUND: Muscle wasting from chronic kidney disease (CKD) or from defective insulin signalling results in morbidity and, ultimately, mortality. We have identified an endogenous mediator of insulin resistance, signal regulatory protein alpha (SIRPα), which leads to cachexia in mice and is associated with cachexia in patients with CKD. METHODS: We assessed insulin signalling and mechanisms causing muscle atrophy plus white adipose tissue (WAT) metabolism in mouse models of CKD or acute diabetes (streptozotocin treatment). We then examined these factors in mice with global knockout (KO) of SIRPα and sought mediators of metabolic responses in muscle and adipose tissues of mice with either muscle-specific or adipose tissue-specific KO of SIRPα. Metabolic responses were confirmed in primary cultures of adipose cells. RESULTS: In mice with CKD, SIRPα expression was increased in WAT (three-fold, P \u3c 0.05), and this was associated with precursors of cachexia: \u27pathologic browning\u27, thermogenesis, and a two-fold activation of protein kinase A (P \u3c 0.05 vs. control mice) plus loss of adipose tissue mass. In contrast, mice with SIRPα global KO and CKD or acute diabetes experienced improved insulin signalling and activation of pAkt plus \u27physiologic browning\u27 of WAT. These mice avoided losses of muscle and adipose tissues and experienced a 31% improvement in survival (P \u3c 0.05) than did wild-type mice with CKD. In muscle-specific SIRPα KO mice with CKD, we uncovered that serum SIRPα levels (P \u3c 0.05) were suppressed and were associated with improved insulin signalling both in skeletal muscles and in WAT. These changes were accompanied by physiologic WAT browning. However, in adipose-specific SIRPα KO mice with CKD, levels of serum SIRPα were increased over two-fold (P \u3c 0.05), while muscle losses were minimally inhibited. Clinical implications of SIRPα signalling are suggested by our findings that include increased SIRPα expression in muscle and adipose tissues (P \u3c 0.05 vs. healthy controls) plus higher SIRPα levels in the serum of patients with CKD (2.4-fold, P=0.000017 vs. healthy controls). CONCLUSIONS: Our results show that SIRPα plays an important role as an anti-insulin mediator regulating pathways to cachexia. In muscle-specific SIRPα KO, changes in SIRPα serum levels seem to improve insulin signalling in muscle and WAT, suggesting crosstalk between muscle and adipose tissue. Therefore, targeting SIRPα may prevent cachexia in patients with CKD or acute diabetes

Toxicology and Biodistribution Studies for MGH2.1, an Oncolytic Virus that Expresses Two Prodrug-activating Genes, in Combination with Prodrugs

MGH2.1 is a herpes simplex virus type 1 (HSV1) oncolytic virus that expresses two prodrug-activating transgenes: the cyclophosphamide (CPA)-activating cytochrome P4502B1 (CYP2B1) and the CPT11-activating secreted human intestinal carboxylesterase (shiCE). Toxicology and biodistribution of MGH2.1 in the presence/absence of prodrugs was evaluated in mice. MGH2.1 ± prodrugs was cytotoxic to human glioma cells, but not to normal cells. Pharmacokinetically, intracranial MGH2.1 did not significantly alter the metabolism of intraperitoneally (i.p.) administered prodrugs in mouse plasma, brain, or liver. MGH2.1 did not induce an acute inflammatory reaction. MGH2.1 DNA was detected in brains of mice inoculated with 108 pfus for up to 60 days. However, only one animal showed evidence of viral gene expression at this time. Expression of virally encoded genes was restricted to brain. Intracranial inoculation of MGH2.1 did not induce lethality at 108 pfus in the absence of prodrugs and at 106 pfus in the presence of prodrugs. This study provides safety and toxicology data justifying a possible clinical trial of intratumoral injection of MGH2.1 with peripheral administration of CPA and/or CPT11 prodrugs in humans with malignant gliomas

Examination of the Structural Response of the Orion European Service Module to Reverberant and Direct Field Acoustic Testing

The NASA Orion Multi-Purpose Crew Vehicle (MPCV), comprised of the Service Module, the Crew Module, and the Launch Abort System, is the next generation human spacecraft designed and built for deep space exploration. Orion will launch on NASAs new heavy-lift rocket, the Space Launch System. The European Space Agency (ESA) is responsible for providing the propulsion sub-assembly of the Service Module to NASA, called the European Service Module (ESM). The ESM is being designed and built by Airbus Safran Launchers for ESA. Traditionally, NASA has utilized reverberant acoustic testing for qualification of spaceflight hardware. The ESM Structural Test Article (E-STA) was tested at the NASA Plum Brook Stations (PBS) Reverberant Acoustic Test Facility in April-May 2016. However, Orion is evaluating an alternative acoustic test method, using direct field acoustic excitation, for the MPCVs Service Module and Crew Module. Lockheed Martin is responsible for the Orion proof-of-concept direct field acoustic test program. The E-STA was exposed to direct field acoustic testing at NASA PBS in February 2017. This paper compares the dynamic response of the E-STA structure and its components to both the reverberant and direct field acoustic test excitations. Advantages and disadvantages of direct field acoustic test excitation method are discussed

Etiology of the Protein-Energy Wasting Syndrome in Chronic Kidney Disease: A Consensus Statement From the International Society of Renal Nutrition andMetabolism (ISRNM)

Protein-energy wasting (PEW), a term proposed by the International Society of Renal Nutrition and Metabolism (ISRNM), refers to the multiple nutritional and catabolic alterations that occur in chronic kidney disease (CKD) and associate with morbidity and mortality. To increase awareness, identify research needs, and provide the basis for future work to understand therapies and consequences of PEW, ISRNM provides this consensus statement of current knowledge on the etiology of PEW syndrome in CKD. Although insufficient food intake (true undernutrition) due to poor appetite and dietary restrictions contribute, other highly prevalent factors are required for the full syndrome to develop. These include uremia-induced alterations such as increased energy expenditure, persistent inflammation, acidosis, and multiple endocrine disorders that render a state of hypermetabolism leading to excess catabolism of muscle and fat. in addition, comorbid conditions associated with CKD, poor physical activity, frailty, and the dialysis procedure per se further contribute to PEW. Published by Elsevier Inc. on behalf of the National Kidney Foundation, Inc.Abbott NutritionShireAbbot Renal NutritionBaxter HealthcareKarolinska Inst, Div Renal Med, Dept Clin Sci Intervent & Technol, Solna, SwedenUniversidade Federal de São Paulo, Div Nephrol, Dept Med, São Paulo, BrazilVanderbilt Univ, Sch Med, Dept Med, Div Nephrol, Nashville, TN 37212 USAUniv Calif Irvine, Med Ctr, Harold Simmons Ctr, Div Nephrol & Hypertens, Orange, CA USAUniv Calif Davis, Dept Internal Med, Davis, CA 95616 USAUniv Calif Davis, Dept Biochem & Mol Med, Davis, CA 95616 USABaylor Coll Med, Dept Med, Div Nephrol, Houston, TX 77030 USAEmory Univ, Sch Med, Div Renal, Dept Med, Atlanta, GA 30306 USAAtlanta Dept Vet Affairs Med Ctr, Res Serv, Decatur, GA 30033 USAUniv Wurzburg, Div Nephrol, Dept Internal Med, D-97070 Wurzburg, GermanyUniv Hong Kong, Dept Med, Queen Mary Hosp, Hong Kong, Hong Kong, Peoples R ChinaVrije Univ Amsterdam Med Ctr, Dept Nephrol, Amsterdam, NetherlandsUniversidade Federal de São Paulo, Div Nephrol, Dept Med, São Paulo, BrazilWeb of Scienc

Human skeletal muscle nitrate and nitrite in individuals with peripheral arterial disease: effect of inorganic nitrate supplementation and exercise

Skeletal muscle may act as a reservoir for N-oxides following inorganic nitrate supplementation. This idea is most intriguing in individuals with peripheral artery disease (PAD) who are unable to endogenously upregulate nitric oxide. This study analyzed plasma and skeletal muscle nitrate and nitrite concentrations along with exercise performance, prior to and following 12-weeks of exercise training combined with oral inorganic nitrate supplementation (EX+BR) or placebo (EX+PL) in participants with PAD. Non-supplemented, at baseline, there were no differences in plasma and muscle nitrate. For nitrite, muscle concentration was higher than plasma (+0.10 nmol.g−1). After 12 -weeks, acute oral nitrate increased both plasma and muscle nitrate (455.04 and 121.14 nmol.g−1, p < 0.01), which were correlated (r = 0.63, p < 0.01), plasma nitrate increase was greater than in muscle (p < 0.01). Nitrite increased in the plasma (1.01 nmol.g−1, p < 0.05) but not in the muscle (0.22 nmol.g−1) (p < 0.05 between compartments). Peak walk time (PWT) increased in both groups (PL + 257.6 s;BR + 315.0 s). Six-minute walk (6 MW) distance increased only in the (EX+BR) group (BR + 75.4 m). We report no substantial gradient of nitrate (or nitrite) from skeletal muscle to plasma, suggesting a lack of reservoir-like function in participants with PAD. Oral nitrate supplementation produced increases in skeletal muscle nitrate, but not skeletal muscle nitrite. The related changes in nitrate concentration between plasma and muscle suggests a potential for inter-compartmental nitrate “communication”. Skeletal muscle did not appear to play a role in within compartment nitrate reduction. Muscle nitrate and nitrite concentrations did not appear to contribute to exercise performance in patients with PAD

Effects of Losartan on renal and cardiovascular outcomes in patients with type 2 diabetes and nephropathy

Background: Diabetic nephropathy is the leading cause of end-stage renal disease. Interruption of the renin-angiotensin system slows the progression of renal disease in patients with type 1 diabetes, but similar data are not available for patients with type 2, the most common form of diabetes. We assessed the role of the angiotensin-II-receptor antagonist losartan in patients with type 2 diabetes and nephropathy. Methods: A total of 1513 patients were enrolled in this randomized, double-blind study comparing losartan (50 to 100 mg once daily) with placebo, both taken in addition to conventional antihypertensive treatment (calcium-channel antagonists, diuretics, alpha-blockers, beta-blockers, and centrally acting agents), for a mean of 3.4 years. The primary outcome was the composite of a doubling of the base-line serum creatinine concentration, end-stage renal disease, or death. Secondary end points included a composite of morbidity and mortality from cardiovascular causes, proteinuria, and the rate of progression of renal disease. Results: A total of 327 patients in the losartan group reached the primary end point, as compared with 359 in the placebo group (risk reduction, 16 percent; P=0.02). Losartan reduced the incidence of a doubling of the serum creatinine concentration (risk reduction, 25 percent; P=0.006) and end-stage renal disease (risk reduction, 28 percent; P=0.002) but had no effect on the rate of death. The benefit exceeded that attributable to changes in blood pressure. The composite of morbidity and mortality from cardiovascular causes was similar in the two groups, although the rate of first hospitalization for heart failure was significantly lower with losartan (risk reduction, 32 percent; P=0.005). The level of proteinuria declined by 35 percent with losartan (P<0.001 for the comparison with placebo). Conclusions: Losartan conferred significant renal benefits in patients with type 2 diabetes and nephropathy, and it was generally well tolerated

Muscle wasting in chronic kidney disease: the role of the ubiquitin proteasome system and its clinical impact

Muscle wasting in chronic kidney disease (CKD) and other catabolic diseases (e.g. sepsis, diabetes, cancer) can occur despite adequate nutritional intake. It is now known that complications of these various disorders, including acidosis, insulin resistance, inflammation, and increased glucocorticoid and angiotensin II production, all activate the ubiquitin–proteasome system (UPS) to degrade muscle proteins. The initial step in this process is activation of caspase-3 to cleave the myofibril into its components (actin, myosin, troponin, and tropomyosin). Caspase-3 is required because the UPS minimally degrades the myofibril but rapidly degrades its component proteins. Caspase-3 activity is easily detected because it leaves a characteristic 14kD actin fragment in muscle samples. Preliminary evidence from several experimental models of catabolic diseases, as well as from studies in patients, indicates that this fragment could be a useful biomarker because it correlates well with the degree of muscle degradation in dialysis patients and in other catabolic conditions