Perceptions and use of phenylbutyrate metabolite testing in urea cycle disorders: Results of a clinician survey and analysis of a centralized testing database.

The nitrogen scavengers sodium and glycerol phenylbutyrate (PB), approved for chronic treatment of urea cycle disorders (UCDs), undergo hepatic conversion to phenylacetate (PAA), which conjugates glutamine to form phenylacetylglutamine for urinary nitrogen excretion. Elevated PAA has been associated with reversible neurological toxicity, with symptoms similar to hyperammonemia. Plasma PB metabolite analysis can assess for toxicity and therapeutic drug levels.

Glycerol phenylbutyrate efficacy and safety from an open label study in pediatric patients under 2 months of age with urea cycle disorders.

Background/aims: Neonatal onset Urea cycle disorders (UCDs) can be life threatening with severe hyperammonemia and poor neurological outcomes. Glycerol phenylbutyrate (GPB) is safe and effective in reducing ammonia levels in patients with UCD above 2 months of age. This study assesses safety, ammonia control and pharmacokinetics (PK) of GPB in UCD patients below 2 months of age.

Perspectives on urea cycle disorder management: Results of a clinician survey.

Background/aims: Urea cycle disorders (UCDs) are rare inborn errors of urea synthesis. US and European consensus statements on the diagnosis and treatment of UCDs were last published in 2001 and 2019, respectively. Recommendations are based primarily on case reports and expert opinion and there is limited agreement or consistency related to long-term management approaches.

Protein and calorie intakes in adult and pediatric subjects with urea cycle disorders participating in clinical trials of glycerol phenylbutyrate.

Background: Little prospectively collected data are available comparing the dietary intake of urea cycle disorder (UCD) patients to UCD treatment guidelines or to healthy individuals.

Objective: To examine the protein and calorie intakes of UCD subjects who participated in clinical trials of glycerol phenylbutyrate (GPB) and compare these data to published UCD dietary guidelines and nutritional surveys.

Design: Dietary data were recorded for 45 adult and 49 pediatric UCD subjects in metabolic control during participation in clinical trials of GPB.

Relationships of obesity and fat distribution with atherothrombotic risk factors: baseline results from the Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D) trial.

The impact of obesity on cardiovascular disease (CVD) outcomes in patients with type 2 diabetes mellitus (T2DM) and established coronary artery disease (CAD) is controversial; whether BMI and/or waist circumference correlate with atherothrombotic risk factors in such patients is uncertain. We sought to evaluate whether higher BMI or waist circumference are associated with specific risk factors among 2,273 Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D) study participants with T2DM and documented CAD (baseline data, mean age 62 years, 66% non-Hispanic white, 71% men). Multiple linear regression models were constructed after adjusting for sex, age, race/ethnicity, US vs.

Hepatic insulin gene therapy normalizes diurnal fluctuation of oxidative metabolism in diabetic BB/Wor rats.

Previous studies of hepatic insulin gene therapy (HIGT) focused on glycemic effects of insulin produced from hepatocytes. In this study, we extend the observations of glycemic control with metabolically regulated HIGT to include systemic responses and whole-body metabolism. An insulin transgene was administered with an adenoviral vector [Ad/(GlRE)(3)BP1-2xfur] to livers of BB/Wor rats made diabetic with polyinosinic polycytidilic acid (poly-I:C) (HIGT group), and results compared with nondiabetic controls (non-DM), and diabetic rats receiving different doses of continuous-release insulin implants (DM-low BG and DM-high BG).

Host cells reduce glucose uptake and glycogen deposition in response to hepatic insulin gene therapy.

Background: Hepatic insulin gene therapy (HIGT) restores weight gain and near-normal glycemia in rodent models of insulin-deficient diabetes mellitus. However, the effect of transgenic insulin on endogenous genes and recipient cell function is relatively unexplored. To investigate hepatocellular effects of transgenic insulin expression, we evaluated intermediary glucose metabolism in primary cultured hepatocytes treated with HIGT.

Sexual dimorphism in the response of adipose mass and cellularity to graded caloric restriction.

Objective: To investigate the effects of mild to moderate caloric restriction on parameters of body growth, fat mass, and adipose tissue cellularity in female and male Wistar rats.

Research Methods And Procedures: Three-month-old female and male Wistar rats were subjected to a chronic, mild to moderate caloric restriction paradigm (5%, 10%, or 20% reduction in caloric intake from ad libitum values) for 6 months. This was accomplished using a unique automated feeder system tailored to the food consumption levels of individual rats.

Glucose-responsive hepatic insulin gene therapy of spontaneously diabetic BB/Wor rats.

Hepatic insulin gene therapy (HIGT) ameliorates hyperglycemia in multiple rodent models of diabetes mellitus, with variable degrees of glucose control. We demonstrate here that adenoviral delivery of a glucose-regulated transgene into rat hepatocytes produces near-normal glycemia in spontaneously diabetic BB/Wor rats without administration of exogenous insulin. We compared growth, glycemia, counterregulatory hormones, and lipids in HIGT-treated diabetic rats to nondiabetic rats and diabetic rats treated with either insulin injections or sustained-release insulin pellets.

Effects of TNF-alpha on glucose metabolism and lipolysis in adipose tissue and isolated fat-cell preparations.

We hypothesized that exposure to tumor necrosis factor-alpha (TNF-alpha) would significantly increase lactate production by adipose-tissue (AT) fragments and isolated adipocytes. We therefore examined the effects of TNF-alpha on the metabolism of epididymal AT explants during 24-hour tissue incubation. We also studied the effects of this 24-hour TNF-alpha tissue exposure on subsequent glucose metabolism and lipolysis by isolated adipocytes.