7-Tetrahydrobiopterin is an uncoupled cofactor for rat hepatic phenylalanine hydroxylase

AbstractRat hepatic phenylalanine hydroxylase requires both a tetrahydropterin cofactor and molecular oxygen to convert phenylalanine to tyrosine. During the physiological hydroxylation, a single mol of the natural cofactor, tetrahydrobiopterin, is oxidized for each mol of phenylalanine converted to tyrosine. Artificial conditions have been devised in which the oxidation of the tetrahydropterin is uncoupled from the hydroxylation of the aromatic amino acid substrate. Recently, an isomer of tetrahydrobiopterin, 7-tetrahydrobiopterin, has been isolated from the urine of certain mildly hyperphenylalaninemic children. We report in this communication that 7-tetrahydrobiopterin may be an inefficient cofactor for phenylalanine hydroxylase because, in vitro, the phenylalanine-dependent oxidation of 7-tetrahydrobiopterin is accompanied by the hydroxylation of the aromatic amino acid substrate only about 15% of the time, i.e. the enzymatic oxidation of 7-tetrahydrobiopterin is about 85% uncoupled from the hydroxylation of the amino acid substrate

The Age Structure of Occupations and Jobs

Age segmentation in the labor force can be analyzed in terms of the age distributions of occupations. In this paper we show that the majority of detailed census occupations conform to one of five basic age profiles. Further, these age profiles have meaning as they derive from the operation of well-defined institutional forces. We discuss the relevance of industry for a refined understanding of occupational-age patterns and conclude with some observations about the likely consequence of a change in the age of compulsory retirement for the age distributions of different occupations

Urinary neopterin concentrations vs total neopterins for clinical utility

Fuchs D, Milstien S, Krämer A, et al. Urinary neopterin concentrations vs total neopterins for clinical utility. Clinical Chemistry. 1989;35(12):2305-2307.Neopterin measurements are especially useful as an early marker in (e.g.) allograft rejections and in patients infected with human immunodeficiency virus type 1 (HIV-1). An increased concentration of total neopterins (neopterin + dihydroneopterin) is also a significant marker in patients with HIV-1 infection. In this study we compared concentrations of neopterin and total neopterins in urine samples from 77 homosexual men with and 73 without established HIV-1 infection. HIV- 1-seropositive homosexual men had higher concentrations of neopterin and total neopterins (and 7,8-dihydroneopterin) in their urine than did those who were HIV-1-seronegative, and there was a close correlation between neopterin and total neopterins. Both neopterin variables correlated inversely with CD4 + T-cell counts and CD4 +/CD8 + T-cell ratios but not with CD8+ T-cell counts in the HIV-1-seropositive men. Our data indicate that measurements of neopterin and total neopterins are of almost equal potential for clinical diagnosis. However, when measuring total neopterins, which includes oxidation of 7,8- dihydroneopterin to neopterin, more strict requirements of sample collection and handling are necessary to avoid degradation of the 7,8- dihydro derivative

Altered Hyperlipidemia, Hepatic Steatosis, and Hepatic Peroxisome Proliferator-Activated Receptors in Rats with Intake of Tart Cherry

ABSTRACT Elevated plasma lipids, glucose, insulin, and fatty liver are among components of metabolic syndrome, a phenotypic pattern that typically precedes the development of Type 2 diabetes. Animal studies show that intake of anthocyanins reduces hyperlipidemia, obesity, and atherosclerosis and that anthocyanin-rich extracts may exert these effects in association with altered activity of tissue peroxisome proliferator-activated receptors (PPARs). However, studies are lacking to test this correlation using physiologically relevant, whole food sources of anthocyanins. Tart cherries are a rich source of anthocyanins, and whole cherry fruit intake may also affect hyperlipidemia and/or affect tissue PPARs. This hypothesis was tested in the Dahl Salt-Sensitive rat having insulin resistance and hyperlipidemia. For 90 days, Dahl rats were pair-fed AIN-76a-based diets supplemented with either 1% (wt:wt) freeze-dried whole tart cherry or with 0.85% additional carbohydrate to match macronutrient and calorie provision. After 90 days, the cherry-enriched diet was associated with reduced fasting blood glucose, hyperlipidemia, hyperinsulinemia, and reduced fatty liver. The cherry diet was also associated with significantly enhanced hepatic PPAR-α mRNA, enhanced hepatic PPAR-α target acyl-coenzyme A oxidase mRNA and activity, and increased plasma antioxidant capacity. In conclusion, physiologically relevant tart cherry consumption reduced several phenotypic risk factors that are associated with risk for metabolic syndrome and Type 2 diabetes. Tart cherries may represent a whole food research model of the health effects of anthocyanin-rich foods and may possess nutraceutical value against risk factors for metabolic syndrome and its clinical sequelae.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/63187/1/jmf.2007.658.pd

Regular Tart Cherry Intake Alters Abdominal Adiposity, Adipose Gene Transcription, and Inflammation in Obesity-Prone Rats Fed a High Fat Diet

Abstract Obesity, systemic inflammation, and hyperlipidemia are among the components of metabolic syndrome, a spectrum of phenotypes that can precede the development of type 2 diabetes and cardiovascular disease. Animal studies show that intake of anthocyanin-rich extracts can affect these phenotypes. Anthocyanins can alter the activity of tissue peroxisome proliferator-activated receptors (PPARs), which affect energy substrate metabolism and inflammation. However, it is unknown if physiologically relevant, anthocyanin-containing whole foods confer similar effects to concentrated, anthocyanin extracts. The effect of anthocyanin-rich tart cherries was tested in the Zucker fatty rat model of obesity and metabolic syndrome. For 90 days, rats were pair-fed a higher fat diet supplemented with either 1% (wt/wt) freeze-dried, whole tart cherry powder or with a calorie- and macronutrient-matched control diet. Tart cherry intake was associated with reduced hyperlipidemia, percentage fat mass, abdominal fat (retroperitoneal) weight, retroperitoneal interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) expression, and plasma IL-6 and TNF-α. Tart cherry diet also increased retroperitoneal fat PPAR-α and PPAR-γ mRNA (P=.12), decreased IL-6 and TNF-α mRNA, and decreased nuclear factor κB activity. In conclusion, in at-risk obese rats fed a high fat diet, physiologically relevant tart cherry consumption reduced several phenotypes of metabolic syndrome and reduced both systemic and local inflammation. Tart cherries may reduce the degree or trajectory of metabolic syndrome, thereby reducing risk for the development of type 2 diabetes and heart disease.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/78120/1/jmf.2008.0270.pd

Blueberry Intake Alters Skeletal Muscle and Adipose Tissue Peroxisome Proliferator-Activated Receptor Activity and Reduces Insulin Resistance in Obese Rats

Metabolic syndrome can precede the development of type 2 diabetes and cardiovascular disease and includes phenotypes such as obesity, systemic inflammation, insulin resistance, and hyperlipidemia. A recent epidemiological study indicated that blueberry intake reduced cardiovascular mortality in humans, but the possible genetic mechanisms of this effect are unknown. Blueberries are a rich source of anthocyanins, and anthocyanins can alter the activity of peroxisome proliferator-activated receptors (PPARs), which affect energy substrate metabolism. The effect of blueberry intake was assessed in obesity-prone rats. Zucker Fatty and Zucker Lean rats were fed a higher-fat diet (45% of kcal) or a lower-fat diet (10% of kcal) containing 2% (wt/wt) freeze-dried whole highbush blueberry powder or added sugars to match macronutrient and calorie content. In Zucker Fatty rats fed a high-fat diet, the addition of blueberry reduced triglycerides, fasting insulin, homeostasis model index of insulin resistance, and glucose area under the curve. Blueberry intake also reduced abdominal fat mass, increased adipose and skeletal muscle PPAR activity, and affected PPAR transcripts involved in fat oxidation and glucose uptake/oxidation. In Zucker Fatty rats fed a low-fat diet, the addition of blueberry also significantly reduced liver weight, body weight, and total fat mass. Finally, Zucker Lean rats fed blueberry had higher body weight and reduced triglycerides, but all other measures were unaffected. In conclusion, whole blueberry intake reduced phenotypes of metabolic syndrome in obesity-prone rats and affected PPAR gene transcripts in adipose and muscle tissue involved in fat and glucose metabolism.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/90448/1/jmf-2E2010-2E0292.pd

Temporal spatial and metabolic measures of walking in highly functional individuals with lower limb amputations

OBJECTIVE: The aim of this descriptive exploratory study is to record the temporal spatial parameters and metabolic energy expenditure during walking of individuals with amputation, walking with advanced prostheses and following completion of comprehensive rehabilitation, to able-bodied controls. DESIGN: Cross-sectional SETTING: Multi-disciplinary comprehensive rehabilitation centre PARTICIPANTS: Thirty severely injured United Kingdom military personnel with amputation and subsequent completion of their rehabilitation programme (10 unilateral trans-tibial, 10 unilateral trans-femoral, and 10 bilateral trans-femoral) were compared to (and of similar age, height and mass (p < 0.537) as) 10 able-bodied controls. INTERVENTIONS: Not applicable Main Outcomes and Measures: Temporal spatial and metabolic energy expenditure data were captured during walking on level ground at self-selected speed. RESULTS: The individuals with amputation were all male, with a mean age 29 years (SD = 4) and mean New Injury Severity Score of 31 (SD = 16). Walking speed, stride length, step length and cadence of individuals with a unilateral trans-tibial or trans-femoral amputation was comparable to controls, and only for individuals with a bilateral trans-femoral amputation was walking speed significantly slower (1·12m/s, p = 0.025) and cadence reduced (96 steps/min, p = 0.026). Oxygen cost for individuals with a unilateral trans-tibial amputation (0·15 ml/kg/m) was the same as for controls (0·15 ml/kg/m), and significantly increased by 20% (0·18ml/kg/m, p = 0.023) for unilateral trans-femoral and by 60% (0·24 ml/kg/m, p < 0.001) for bilateral trans-femoral individuals with amputation. CONCLUSION: The scientific literature reports a wide range of gait and metabolic energy expenditure across individuals with amputation. The results of this study indicate that the individuals with amputation have a gait pattern which is highly functional and efficient. This is comparable to a small number of studies reporting similar outcomes for individuals with a unilateral trans-tibial amputation, but the results from this study are better than those on individuals with trans-femoral amputations reported elsewhere, despite comparison with populations wearing similar prosthetic componentry. Those studies that do report similar outcomes have included individuals who have been provided with a comprehensive rehabilitation programme. This suggests that such a programme may be as important as, or even more important than, prosthetic component selection in improving metabolic energy expenditure. The data are made available as a benchmark for what is achievable in the rehabilitation of some individuals with amputations, but agreeably may not be possible for all amputees to achieve

Organ donation, ethnicity and the negotiation of death: ethnographic insights from the UK

The introduction of end-of-life care criteria in the UK aims at standardising the processes of care at the end of life, including how medical decisions on death are communicated to the families of dying and (brain) dead patients. In the setting of the intensive care unit, these activities are routinely complicated by the imperative to secure donor organs for transplantation: where recent changes to donation services have seen the accommodation of organ donation procedures into end-of-life care routines. This has ramifications for understanding how medical decisions around death and dying are brokered with the families of potential organ donors. Drawing on an ethnographic study in England, this paper will document how communications around death get turned into a particular matter of concern for the practice of requesting organ donation from minority ethnic families. It shows how attempts to resolve differences of opinion between health professionals and families about a diagnosis of brain stem death or dying are mediated by sets of brokering practices: specifically, those termed technological, authoritative and religious brokering. These practices, we argue, not only facilitate a family’s acceptance of their relative’s death, but also serve to make possible a decision on organ donation

Private Sector Union Density and the Wage Premium: Past, Present, and Future

The rise and decline of private sector unionization were among the more important features of the U.S. labor market during the twentieth century. Following a dramatic spurt in unionization after passage of the depression-era National Labor Relations Act (NLRA) of 1935, union density peaked in the mid-1950s, and then began a continuous decline. At the end of the century, the percentage of private wage and salary workers who were union members was less than 10 percent, not greatly different from union density prior to the NLRA